diff --git a/data/covid/ack-preprints.csv b/data/covid/ack-preprints.csv
index ac3578e8..e7fd9eb8 100644
--- a/data/covid/ack-preprints.csv
+++ b/data/covid/ack-preprints.csv
@@ -73,8 +73,8 @@ PPR600925,https://doi.org/10.1101/2023.01.20.23284849,Comparative effectiveness
 PPR477505,https://doi.org/10.1101/2022.03.29.22273042,The new normal? Dynamics and scale of the SARS-CoV-2 variant 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.",,No Journal Info,2022,2022-04-04,Y,,,,"<h4>Summary</h4> The SARS-CoV-2 pandemic has been characterised by the regular emergence of genomic variants which have led to substantial changes in the epidemiology of the virus. 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 was first detected in late November 2021 and exhibited a high degree of immune evasion, leading to increased infection rates in many countries. However, estimates of the magnitude of the Omicron wave have relied mainly on routine testing data, which are prone to several biases. Here we infer the dynamics of the Omicron wave in England using PCR testing and genomic sequencing obtained by the REal-time Assessment of Community Transmission-1 (REACT-1) study, a series of cross-sectional surveys testing random samples of the population of England. 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 in England during February-March 2022 as the more transmissible Omicron sub-lineage, BA.2 replaced BA.1 and BA.1.1. Assuming the emergence of further distinct genomic variants, intermittent epidemics of similar magnitude as the Omicron wave may become the ‘new normal’.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/04/04/2022.03.29.22273042.full.pdf; doi:https://doi.org/10.1101/2022.03.29.22273042; html:https://europepmc.org/article/PPR/PPR477505; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR477505&type=FILE&fileName=EMS144175-pdf.pdf&mimeType=application/pdf
 PPR350007,https://doi.org/10.1101/2021.05.27.21257032,How immunity from and interaction with seasonal coronaviruses can shape SARS-CoV-2 epidemiology,"Waterlow NR, van Leeuwen E, Davies NG, Flasche S, Eggo RM, CMMID COVID-19 working group.",,No Journal Info,2021,2021-05-31,Y,,,,"We hypothesised that cross-protection from seasonal epidemics of human coronaviruses (HCoVs) could have affected SARS-CoV-2 transmission, including generating reduced susceptibility in children. To determine what the pre-pandemic distribution of immunity to HCoVs was, we fitted a mathematical model to 6 years of seasonal coronavirus surveillance data from England and Wales. We estimated a duration of immunity to seasonal HCoVs of 7.3 years (95%CI 6.8 - 7.9) and show that, while cross-protection between HCoV and SARS-CoV-2 may contribute to the age distribution, it is insufficient to explain the age pattern of SARS-CoV-2 infections in the first wave of the pandemic in England and Wales. Projections from our model illustrate how different strengths of cross-protection between circulating coronaviruses could determine the frequency and magnitude of SARS-CoV-2 epidemics over the coming decade, as well as the potential impact of cross-protection on future seasonal coronavirus transmission. <h4>Significance statement:</h4> Cross-protection from seasonal epidemics of human coronaviruses (HCoVs) has been hypothesised to contribute to the relative sparing of children during the early phase of the pandemic. Testing this relies on understanding the pre-pandemic age-distribution of recent HCoV infections, but little is known about their dynamics. Using England and Wales as a case study, we use a transmission model to estimate the duration of immunity to seasonal coronaviruses, and show how cross-protection could have affected the age distribution of susceptibility during the first wave, and alter SARS-CoV-2 transmission patterns over the coming decade.",,doi:https://doi.org/10.1073/pnas.2108395118; doi:https://doi.org/10.1101/2021.05.27.21257032; html:https://europepmc.org/article/PPR/PPR350007; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR350007&type=FILE&fileName=EMS126822-pdf.pdf&mimeType=application/pdf
 PPR525765,https://doi.org/10.1101/2022.07.28.22278152,"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, Richie L, Simpson CR, Taylor B, Fenton L, Pollock L, Gale C, Kurinczuk JJ, Robertson C, Sheikh A, Stock S, Wood R.",,No Journal Info,2022,2022-07-31,Y,,,,"<h4>Objective</h4> To examine infants in Scotland aged 0-27 days with confirmed SARS-CoV-2 infection; the risk of neonatal infection by factors including maternal infection status and gestation at birth; and the need for hospital admission among infected neonates. <h4>Design</h4> Population-based cohort study. <h4>Setting and population</h4> All live births in Scotland, 1 March 2020 to 31 January 2022. <h4>Results</h4> 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). Among infants born to women with confirmed infection around the time of birth, the infection rate was 1,811 per 100,000 live births (15/828). Nearly two-thirds (92/141, 65.2%) of babies with confirmed neonatal infection had an associated admission to neonatal or (more commonly) paediatric care. Of those admitted to hospital, 6/92 (6.5%) infants were admitted to neonatal or paediatric intensive care, however none of these six had COVID-19 recorded as the main diagnosis underlying their admission. There were no neonatal deaths among babies with confirmed infection. <h4>Implications and relevance</h4> Confirmed neonatal SARS-CoV-2 infection is uncommon. Secular trends in the neonatal infection rate broadly follow those seen in the general population, albeit at a lower level. Maternal infection at birth increases the risk of neonatal infection, but most babies with neonatal infection are born to women without confirmed infection. A high proportion of neonates with confirmed infection are admitted to hospital, with resulting implications for the baby, family, and services, although their outcomes are generally good. <h4>Key messages</h4> <h4>What is already known on this topic</h4> The incidence of SARS-CoV-2 infection in neonates is low, but some studies have suggested that age under 1 month is a risk factor for severe infection requiring admission to intensive care. Almost all the studies of neonatal SARS-CoV-2 have focused on the transmission risk from SARS-CoV-2 positive women to their offspring and data are lacking on the level of neonatal SARS-CoV-2 infection in the whole population. <h4>What this study adds</h4> This study includes all babies with confirmed SARS-CoV-2 in the neonatal period in Scotland during the first 22 months of the COVID-19 pandemic. Confirmed neonatal SARS-CoV-2 infection is uncommon, but a high proportion of neonates with confirmed infection are admitted to hospital. Confirmed maternal SARS-CoV-2 infection around the time of birth substantially increases the risk of neonatal infection, although the absolute risk of neonatal infection remains low (<2%) and most babies with neonatal infection are born to women without confirmed infection. Outcomes for neonates with confirmed SARS-CoV-2 infection are good; only 6.5% (6/92) of admitted neonates required intensive care, and COVID-19 was not the primary diagnosis recorded for these babies. There were no neonatal deaths among babies with confirmed infection.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/101466/16/367.full.pdf; doi:https://doi.org/10.1101/2022.07.28.22278152; html:https://europepmc.org/article/PPR/PPR525765; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR525765&type=FILE&fileName=EMS151967-pdf.pdf&mimeType=application/pdf
-PPR558630,https://doi.org/10.1101/2022.10.17.22281085,COVID-19 among adults living with HIV: Correlates of mortality in a general population in a resource-limited setting,"Kassanjee R, Davies M, 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.",,No Journal Info,2022,2022-10-17,Y,,,,"<h4>Introduction</h4> 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 between mortality and characteristics of HIV severity and management, and vaccination, among adult PWH. <h4>Methods</h4> 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 CD4 cell count, viral load, evidence of ART, time since first HIV evidence, and vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period. <h4>Results</h4> 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 (among those with ART evidence), and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis, chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults. <h4>Conclusions</h4> Mortality was strongly associated with suboptimal HIV control, and 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 optimised.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603837; doi:https://doi.org/10.1101/2022.10.17.22281085; html:https://europepmc.org/article/PPR/PPR558630; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR558630&type=FILE&fileName=EMS155815-pdf.pdf&mimeType=application/pdf
 PPR501811,https://doi.org/10.1101/2022.06.02.22275900,"Trends in SARS-CoV-2 infection prevalence during England’s roadmap out of lockdown, January to July 2021","Eales O, Wang H, Haw D, Ainslie KEC, Walters CE, Atchison C, Cooke G, Barclay W, Ward H, Darzi A, Ashby D, Donnelly CA, Elliott P, Riley S.",,No Journal Info,2022,2022-06-02,Y,,,,"<h4>Background</h4> Following rapidly rising COVID-19 case numbers, England entered a national lockdown on 6 January 2021, with staged relaxations of restrictions from 8 March 2021 onwards. <h4>Aim</h4> We characterise how the lockdown and subsequent easing of restrictions affected trends in SARS-CoV-2 infection prevalence. <h4>Methods</h4> On average, risk of infection is proportional to infection prevalence. The REal-time Assessment of Community Transmission-1 (REACT-1) study is a repeat cross-sectional study of over 98,000 people every round (rounds approximately monthly) that estimates infection prevalence in England. We used Bayesian P-splines to estimate prevalence and the time-varying reproduction number ( R t ) nationally, regionally and by age group from round 8 (beginning 6 January 2021) to round 13 (ending 12 July 2021) of REACT-1. As a comparator, a separate segmented-exponential model was used to quantify the impact on R t of each relaxation of restrictions. <h4>Results</h4> Following an initial plateau of 1.54% until mid-January, infection prevalence decreased until 13 May when it reached a minimum of 0.09%, before increasing until the end of the study to 0.76%. Following the first easing of restrictions, which included schools reopening, the reproduction number R t increased by 82% (55%, 108%), but then decreased by 61% (82%, 53%) at the second easing of restrictions, which was timed to match the Easter school holidays. Following further relaxations of restrictions, the observed R t increased steadily, though the increase due to these restrictions being relaxed was masked by the effects of vaccination and the rapid rise of Delta. There was a high degree of synchrony in the temporal patterns of prevalence between regions and age groups. <h4>Conclusion</h4> High-resolution prevalence data fitted to P-splines allowed us to show that the lockdown was highly effective at reducing risk of infection with school holidays/closures playing a significant part.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/100816/10/journal.pcbi.1010724.pdf; doi:https://doi.org/10.1101/2022.06.02.22275900; html:https://europepmc.org/article/PPR/PPR501811; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR501811&type=FILE&fileName=EMS145736-pdf.pdf&mimeType=application/pdf
+PPR558630,https://doi.org/10.1101/2022.10.17.22281085,COVID-19 among adults living with HIV: Correlates of mortality in a general population in a resource-limited setting,"Kassanjee R, Davies M, 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.",,No Journal Info,2022,2022-10-17,Y,,,,"<h4>Introduction</h4> 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 between mortality and characteristics of HIV severity and management, and vaccination, among adult PWH. <h4>Methods</h4> 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 CD4 cell count, viral load, evidence of ART, time since first HIV evidence, and vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period. <h4>Results</h4> 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 (among those with ART evidence), and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis, chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults. <h4>Conclusions</h4> Mortality was strongly associated with suboptimal HIV control, and 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 optimised.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603837; doi:https://doi.org/10.1101/2022.10.17.22281085; html:https://europepmc.org/article/PPR/PPR558630; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR558630&type=FILE&fileName=EMS155815-pdf.pdf&mimeType=application/pdf
 PPR342270,https://doi.org/10.2139/ssrn.3839453,Profile of Humoral and Cellular Immune Responses to Single BNT162b2 or ChAdOx1 Vaccine in Residents and Staff Within Residential Care Homes (VIVALDI Study),"Tut G, Lancaster T, Krutikov M, Sylla P, Bone D, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Butler M, Ayodele M, Bruton R, Shrotri M, Azmi B, Fuller C, Irwin-Singer A, Hayward AC, Copas A, Shallcross L, Moss P.",,No Journal Info,2021,2021-05-04,N,,,,"Background: Residents of long-term care facilities (LTCF) have experienced high mortality rates from SARS-CoV-2 infection and as such have been prioritized for Covid-19 vaccination. Several countries have implemented an extended interval of up to 12 weeks between first and second vaccine doses to increase population coverage after single administration. <br><br>Methods: Spike-specific immune responses that were induced following single administration of BNT162b2 or ChAdOx1 were studied in 89 staff and 35 residents within LTCFs. Quantitative antibody and cellular responses were determined as well as antibody inhibition of spike protein-ACE2 binding from viral variants. <br><br>Results: 20% of staff and 34% of residents were found to have serological evidence of prior SARS-CoV-2 infection and all of these donors demonstrated strong antibody responses that were independent of age. Antibody responses were detectable within 99% and 79% of ‘infection-naive’ staff and residents respectively but were 8.2-fold lower within residents. This effect resulted from slower kinetics of antibody generation within residents which reached levels comparable to staff after only 42 days. In contrast spike-specific cellular responses were equivalent between both groups. Antibody inhibition activity against the B.1.351 and P.1 viral variants of concern was low using serum from ‘infection-naive’ older donors. Prior history of natural infection thus has a marked impact on the magnitude and quality of antibody response after a single Covid-19 vaccine in care home residents. <br><br>Interpretation: Residents who are infection-naive have delayed antibody responses to the first dose of vaccine and might be considered for an early second vaccine where possible.  <br><br>Funding: UK Government Department of Health and Social Care<br><br>Declaration of Interests: LS reports grants from the Department of Health and Social Care during the conduct of the study and is a member of the Social Care Working Group, which reports to the Scientific Advisory Group for Emergencies. AH is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health.<br><br>Ethics Approval Statement: Ethical approval for this study was obtained from the South Central - Hampshire B Research Ethics Committee, REC Ref: 20/SC/023.",,doi:https://doi.org/10.2139/ssrn.3839453; html:https://europepmc.org/article/PPR/PPR342270; doi:https://doi.org/10.2139/ssrn.3839453
 PPR461923,https://doi.org/10.1101/2022.02.24.22271466,Risk of COVID-19 related deaths for SARS-CoV-2 Omicron (B.1.1.529) compared with Delta (B.1.617.2),"Ward IL, Bermingham C, Ayoubkhani D, Gethings OJ, Pouwels KB, Yates T, Khunti K, Hippisley-Cox J, Banerjee A, Walker AS, Nafilyan V.",,No Journal Info,2022,2022-02-25,Y,,,,"<h4>Objective</h4> To assess the risk of death involving COVID-19 following infection from Omicron (B.1.1.539/BA.1) relative to Delta (B.1.617.2). <h4>Design</h4> Retrospective cohort study. <h4>Setting</h4> England, UK, 1 December 2021 to 25 January 2022. <h4>Participants</h4> 1,035,163 people aged 18-100 years who tested positive for SARS-CoV-2 in the national surveillance programme, and had an infection identified as either Omicron- or Delta compatible. <h4>Main outcome measures</h4> Death involving COVID-19 as identified from death certification records. The exposure of interest was the SARS-CoV-2 variant identified from NHS Test and Trace PCR positive tests taken in the community (pillar 2) and analysed by Lighthouse laboratories. Cause-specific Cox proportional hazard regression models were adjusted for sex, age, vaccination status, previous infection, calendar time, ethnicity, Index of Multiple Deprivation rank, household deprivation, university degree, keyworker status, country of birth, main language, region, disability, and comorbidities. Additionally, we tested for interactions between variant and sex, age, vaccination status and comorbidities. <h4>Results</h4> The risk of death involving COVID-19 was 67% lower for Omicron compared to Delta and the reduction in the risk of death involving COVID-19 for Omicron compared to Delta was more pronounced in males than in females and in people under 70 years old than in people aged 70 years or over. Regardless of age, reduction of the risk of death from Omicron relative to Delta more was more pronounced in people who had received a booster than in those having received only two doses. <h4>Conclusions</h4> Our results support early work showing the relative reduction in severity of Omicron compared to Delta in terms of hospitalisation and extends this research to assess COVID-19 mortality. Our work also highlights the importance of the vaccination booster campaign, where the reduction in risk of death involving COVID-19 is most pronounced in individuals who had received a booster. <h4>What is already known on this topic</h4> The Omicron variant, which refers to the whole lineage (BA.1, BA.2, BA.3) had already been shown to be more transmissible than the Delta variant, but there is emerging evidence suggests that the risk of hospitalisation and risk of death within 28 days after a SARS-COV-2 test is lower. However, with a highly transmissible infection and high levels of population testing, definition of death within 28 days is more likely to be susceptible to misclassification bias due to asymptomatic or co-incidental infection. There is no study so far comparing the risk of COVID-19 death as identified from death certification records, with the cause of death assessed by the physician who attended the patient in the last illness. <h4>What this study adds</h4> Using data from a large cohort of COVID-19 infections that occurred in December 2021, we examined the difference in the risk COVID-19 death, as identified from death certification records, between the Delta and Omicron BA.1 variant. Our study shows that risk of death involving COVID-19 was reduced by 67% following infection with the Omicron BA.1 variant relative to the Delta variant after adjusting for a wide range of potential confounders, including vaccination status and comorbidities. Importantly, we found that the relative risk of COVID-19 mortality following Omicron versus Delta infection varied by age and sex, with lower relative risk in younger individuals and for males than females. The reduction in risk of death involving COVID-19 was also most pronounced in individuals who had received a booster.",,pdf:https://ora.ox.ac.uk/objects/uuid:f58b35e2-2a6a-44a4-ae5c-8c6df8eb041b/files/rf4752h39j; doi:https://doi.org/10.1101/2022.02.24.22271466; html:https://europepmc.org/article/PPR/PPR461923; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR461923&type=FILE&fileName=EMS148831-pdf.pdf&mimeType=application/pdf
 PPR673302,https://doi.org/10.1101/2023.06.08.544212,Towards Pandemic-Scale Ancestral Recombination Graphs of SARS-CoV-2,"Zhan SH, Ignatieva A, Wong Y, Eaton K, Jeffery B, Palmer DS, Murall CL, Otto SP, Kelleher J.",,No Journal Info,2023,2023-06-08,Y,,,,"Recombination is an ongoing and increasingly important feature of circulating lineages of SARS-CoV-2, challenging how we represent the evolutionary history of this virus and giving rise to new variants of potential public health concern by combining transmission and immune evasion properties of different lineages. Detection of new recombinant strains is challenging, with most methods looking for breaks between sets of mutations that characterise distinct lineages. In addition, many basic approaches fundamental to the study of viral evolution assume that recombination is negligible, in that a single phylogenetic tree can represent the genetic ancestry of the circulating strains. Here we present an initial version of sc2ts, a method to automatically detect recombinants in real time and to cohesively integrate them into a genealogy in the form of an ancestral recombination graph (ARG), which jointly records mutation, recombination and genetic inheritance. We infer two ARGs under different sampling strategies, and study their properties. One contains 1.27 million sequences sampled up to June 30, 2021, and the second is more sparsely sampled, consisting of 657K sequences sampled up to June 30, 2022. We find that both ARGs are highly consistent with known features of SARS-CoV-2 evolution, recovering the basic backbone phylogeny, mutational spectra, and recapitulating details on the majority of known recombinant lineages. Using the well-established and feature-rich tskit library, the ARGs can also be stored concisely and processed efficiently using standard Python tools. For example, the ARG for 1.27 million sequences—encoding the inferred reticulate ancestry, genetic variation, and extensive metadata—requires 58MB of storage, and loads in less than a second. The ability to fully integrate the effects of recombination into downstream analyses, to quickly and automatically detect new recombinants, and to utilise an efficient and convenient platform for computation based on well-engineered technologies makes sc2ts a promising approach.",,pdf:https://www.biorxiv.org/content/biorxiv/early/2023/06/08/2023.06.08.544212.full.pdf; doi:https://doi.org/10.1101/2023.06.08.544212; html:https://europepmc.org/article/PPR/PPR673302; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR673302&type=FILE&fileName=EMS177195-pdf.pdf&mimeType=application/pdf
@@ -108,8 +108,8 @@ PPR371282,https://doi.org/10.1101/2021.07.14.21260497,"Vaccine uptake and SARS-C
 PPR605877,https://doi.org/10.2139/ssrn.4065552,Impact of Dexamethasone and Remdesivir on Neurological Complications during COVID-19,"Grundmann A, Wu C, Hardwick M, Baillie JK, Openshaw P, Semple MG, Böhning D, Pett S, Michael B, Thomas RH, Galea I.",,No Journal Info,2022,2022-04-12,N,,,,"Importance: Neurological complications are common following acute COVID-19, causing significant morbidity with health economic consequences. However, no treatment studies in COVID-19 focussing on neurological complications have been published to date.<br> <br>Objective: Does treatment with either remdesivir, dexamethasone or both reduce the risk of neurological complications in adult patients hospitalised with COVID-19?<br> <br>Design and setting: COVID-19 neurological complications, and remdesivir and dexamethasone use, were studied in adults admitted to hospitals in the UK with COVID-19, using data from the International Severe Acute and emerging Respiratory Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK, study registration ISRCTN66726260). Treatment allocation was non-blinded and performed by reporting clinicians. A propensity scoring methodology was used to correct for confounding between treatment groups. <br><br>Participants: 89,297 patients aged 18 years and older with laboratory confirmed SARS-CoV-2 infection were eligible for inclusion. Patients requiring supplemental oxygen at any point during admission (n=64,088) were defined as having severe COVID-19, as per WHO criteria. Patients were excluded if they received a dose of any SARS-CoV-2 vaccine or contracted COVID-19 in hospital.<br> <br>Exposures: Treatment with remdesivir, dexamethasone or both was assessed against standard of care. <br> <br>Main outcome(s) and measure(s): A neurological complication (stroke, seizure, meningitis/encephalitis or any other neurological complication) occurring at the point of death, discharge, or resolution of the COVID-19 clinical episode. <br> <br>Results: The median age of patients was 71 (IQR, 56 to 82). 56% were identified as male and 71% were of white ethnicity. 4,408 patients (4.7%) developed neurological complications. In patients with severe COVID-19, neurological complications were associated with increased mortality (OR 1.36, 95% CI 1.25 to 1.47), intensive care admission (OR 1.54, 95% CI 1.41 to 1.6), likelihood of worse self-care on discharge (OR 3.79, 95% CI 3.36 to 4.26) and an increased time to recovery (9.65 days, 95% CI 7.12 to 12.17 days). Treatment with dexamethasone (n=21,129), remdesivir (n=1,428) and both treatments combined (n=10,846) in severe COVID-19 were associated with a reduced incidence of neurological complications; OR 0.76 (95% CI 0.69 to 0.83); OR 0.68 (95% CI 0.51 to 0.90); OR 0.54, (95% CI 0.47 to 0.61) respectively. <br> <br>Conclusions and relevance: Treatment with dexamethasone, remdesivir or both in patients hospitalised with COVID-19 was associated with reduced neurological complications in an additive manner, such that the greatest benefit was observed in patients who received both drugs together. The potential of these treatments to reduce neurological disability is of urgent importance to patients, healthcare systems and public health bodies.<br>",,doi:https://doi.org/10.2139/ssrn.4065552; html:https://europepmc.org/article/PPR/PPR605877; doi:https://doi.org/10.2139/ssrn.4065552
 PPR526793,https://doi.org/10.1101/2022.07.30.22278161,Changes in COVID-19-related mortality across key demographic and clinical subgroups: an observational cohort study using the OpenSAFELY platform on 18 million adults in England,"The OpenSAFELY Collaborative, Nab L, Parker EP, Andrews CD, Hulme WJ, Fisher L, Morley J, Mehrkar A, MacKenna B, Inglesby P, Morton CE, Bacon SC, Hickman G, Evans D, Ward T, Smith RM, Davey S, Dillingham I, Maude S, Butler-Cole BF, O’Dwyer T, Stables CL, Bridges L, Bates C, Cockburn J, Parry J, Hester F, Harper S, Zheng B, Williamson EJ, Eggo RM, Evans S, Goldacre B, Tomlinson LA, Walker AJ.",,No Journal Info,2022,2022-08-02,Y,,,,"<h4>Objectives</h4> To quantify in absolute and relative terms how population-level COVID-19 death rates have changed in demographic and clinical subgroups. <h4>Design</h4> Retrospective cohort study on behalf of NHS England. <h4>Setting</h4> Linked primary care and death registry data from the OpenSAFELY-TPP platform, covering the first three pandemic waves in England (wave 1: March 23 to May 30, 2020; wave 2: September 7, 2020 to April 24, 2021; and wave 3, delta: May 28 to December 14, 2021). <h4>Participants</h4> In total, 18.7, 18.8, and 18.7 million adults were included for waves 1, 2, and 3 respectively. <h4>Main outcome measures</h4> COVID-19-related mortality based on linked death registry records. <h4>Results</h4> The crude absolute COVID-19-related death rate per 1,000 person-years decreased from 4.48 in wave 1 (95%CI 4.41;4.55), to 2.70 in wave 2 (95%CI 2.67;2.73), to 0.64 in wave 3 (95%CI 0.63;0.66). The absolute death rate decreased by 90% between waves 1 and 3 in patients aged 80+, but by only 20% in patients aged 18-39. This higher proportional reduction in age- and sex-standardised death rates was also seen for other groups, such as neurological disease, learning disability and severe mental illness. Conversely, standardised death rates in transplant recipients stayed constant across successive waves at 10 per 1,000 person-years. There was also only a small decrease in death rates between waves in people with kidney disease, haematological malignancies or conditions associated with immunosuppression. Consequently, the relative hazard of COVID-19-related death decreased over time for some variables (e.g. age), remained similar for some (e.g. sex, ethnicity), and increased for others (e.g. transplant). <h4>Conclusions</h4> COVID-19 death rates decreased over the first three pandemic waves. An especially large decrease was seen in older age groups and people with neurological disease, learning disability or severe mental illness. Some demographic inequalities in death rates persisted over time. Groups more likely to experience impaired vaccine effectiveness did not see the same benefit in COVID-19 mortality reduction.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/08/02/2022.07.30.22278161.full.pdf; doi:https://doi.org/10.1101/2022.07.30.22278161; html:https://europepmc.org/article/PPR/PPR526793; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR526793&type=FILE&fileName=EMS152162-pdf.pdf&mimeType=application/pdf
 PPR601887,https://doi.org/10.2139/ssrn.4052647,Using National Electronic Health Records for Pandemic Preparedness: Validation of a Parsimonious Model for Predicting Excess Deaths Among Those With COVID-19,"Mizani MA, Dashtban M, Pasea L, Lai A, Thygesen JH, 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.",,No Journal Info,2022,2022-03-08,N,,,,"Background: Throughout the pandemic, research, public health, and policy emphasised prediction and surveillance of excess deaths, which have mostly occurred in older individuals with underlying conditions, highlighting importance of baseline mortality risk, infection rate (IR) and pandemic-related relative risk (RR). We now use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a model incorporating these factors for prediction of excess deaths.<br><br>Methods: In development (Clinical Practice Research Datalink) and validation (NHS Digital Trusted Research Environment) cohorts in primary and secondary care EHR in England, we included 3·8 million and 35·1 million individuals aged ≥30 years, respectively. For model development, we predicted excess deaths using baseline one-year all-cause mortality risk and assumed RR=3 and IR=10%. For model validation, we observed number of excess deaths from March 2020 to March 2021. We used baseline mortality risk, IR and RR (assumed and observed) to predict excess deaths related to COVID-19.   <br><br>Findings: Among individuals with at least one high-risk condition, baseline (pre-pandemic) 1-year mortality risk at one year was 4·46% (95% CI 4·41–4·51) and 3.55% (3.54-3.57) in development and validation cohorts, respectively. In our original published model, we predicted 73,498 COVID-19 deaths over 1 year for the population of England. From 1st March 2020 to 1st March 2021, there were 127,020 observed excess deaths. Observed RR was 4·34 (4·31-4·38, 95% CI) and IR was 6·27% (6·26-6·28, 95%CI). In the validation cohort, predicted excess deaths over one year were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79. We found that vaccination had a negligible effect on overall RR or IR between 1st December 2020 and 1st March 2021, compared to the likely effect of under-reported COVID-19 cases from the pre-vaccination period.<br><br>Interpretation: We show that a simple, parsimonious model incorporating baseline mortality risk, one-year infection rate and relative risk of the pandemic can be used to predict excess deaths. 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 prediction of morbidity and mortality, future models should take greater account of underlying conditions and their associated risks.<br><br>Funding Information: 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 Government 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. AB, MAM, MHD and LP were supported by research funding from AstraZeneca. AB has received funding from the National Institute for Health Research (NIHR), British Medical Association, and UK Research and Innovation. AB, SD and HH are part of the BigData@Heart Consortium, funded by the Innovative Medicines Initiative-2 Joint Undertaking under grant agreement No 116074. K.K. is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and NIHR Lifestyle BRC.<br><br>Declaration of Interests: JBM and TM are employees of AstraZeneca. KK is chair of the ethnicity subgroup of the Independent Scientific Advisory Group for Emergencies (SAGE) and director of the University of Leicester Centre for Black Minority Ethnic Health. KK and AB are trustees of the South Asian Health Foundation (SAHF). CS is Director of the BHF Data Science Centre. All other authors report no competing interests.<br><br>Ethics Approval Statement: Approval for the study in CPRD 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 research programme (REC No 20/NE/0161).<br>",,doi:https://doi.org/10.2139/ssrn.4052647; html:https://europepmc.org/article/PPR/PPR601887; doi:https://doi.org/10.2139/ssrn.4052647
-PPR573001,https://doi.org/10.1101/2022.11.16.22282338,Proteomic analysis of circulating immune cells identifies novel 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, Kingston N, Göttgens B, Bradley JR, Lehner PJ, Matheson NJ, Smith KG, Wills MR, Lyons PA, Weekes MP, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration.",,No Journal Info,2022,2022-11-18,Y,,,,"<h4>Summary</h4> Certain serum proteins, including CRP and D-dimer, have prognostic value in patients with SARS-CoV-2 infection. Nonetheless, these factors are non-specific, and provide limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations which drive the pathogenesis of severe COVID-19. To identify novel cellular phenotypes associated with disease progression, we here describe a comprehensive, unbiased analysis of the total and plasma membrane proteomes of PBMCs from a cohort of 40 unvaccinated individuals with SARS-CoV-2 infection, spanning the whole spectrum of disease severity. Combined with RNA-seq and flow cytometry data from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing cumulative immune cell dysregulation in progressive disease. In particular, 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 + CD177 + and CD16 + CEACAM1/6/8 + mononuclear cells. Utilisation of these markers may facilitate real-time patient assessment by flow cytometry, and identify immune cell populations that could be targeted to ameliorate immunopathology.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/11/18/2022.11.16.22282338.full.pdf; doi:https://doi.org/10.1101/2022.11.16.22282338; html:https://europepmc.org/article/PPR/PPR573001; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR573001&type=FILE&fileName=EMS157354-pdf.pdf&mimeType=application/pdf
 PPR373622,https://doi.org/10.1101/2021.07.19.21260770,Uptake of infant and pre-school immunisations in Scotland and England during the COVID-19 pandemic: an observational study of routinely collected data,"McQuaid F, Mulholland R, Rai YS, Agrawal U, Bedford H, Claire Cameron J, Gibbons C, Roy P, Sheikh A, Shi T, Simpson CR, Tait J, Tessier E, Turner S, Ortega JV, White J, Wood R.",,No Journal Info,2021,2021-07-22,N,,,,"<h4>Background</h4> In 2020, the COVID-19 pandemic and control measures such as national lockdowns threatened to disrupt routine childhood immunisation programmes. Initial reports from the early weeks of lockdown in the UK and worldwide suggested that uptake could fall putting children at risk from multiple other infectious diseases. In Scotland and England, enhanced surveillance of national data for childhood immunisations was established to inform and rapidly assess the impact of the pandemic on infant and preschool immunisation uptake rates. <h4>Methods and findings</h4> We undertook an observational study using routinely collected data for the year prior to the pandemic (2019), and immediately before, during and after the first period of the UK ‘lockdown’ in 2020. Data were obtained for Scotland from the Public Health Scotland “COVID19 wider impacts on the health care system” dashboard ( https://scotland.shinyapps.io/phs-covid-wider-impact/ ) and for England from ImmForm. Five vaccinations delivered at different ages were evaluated; three doses of the ‘6-in-1’ DTaP/IPV/Hib/HepB vaccine and two doses of MMR. Uptake in the periods in 2020 compared to that in the baseline year of 2019 using binary logistic regression analysis. For Scotland, we analysed timely uptake of immunisations, defined as uptake within four weeks of the child becoming eligible by age for each immunisation and data were also analysed by geographical region and indices of deprivation. For both Scotland and England, we assessed whether immunisations were up to date at approximately 6 months (all doses 6-in-1) and 16-18 months (first MMR) of age. We found that uptake rates within four weeks of eligibility in Scotland for all the five vaccine visits were higher during the 2020 lockdown period than in 2019. The difference ranged from 1.3% for the first dose of the 6-in-1 vaccine (95.3 vs 94%, OR 1.28, CI 1.18-1.39) to 14.3% for the second MMR dose (66.1 vs 51.8 %, OR 1.8, CI 1.74-1.87). Significant increases in uptake were seen across all deprivation levels, though, for MMR, there was evidence of greater improvement for children living in the least deprived areas. In England, fewer children who had been 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-in1 (95.8 vs 96.3%, OR 0.89, CI 0.86-0.91) to 2.1% for third 6-in-1 (86.6 vs 88.7%, OR 0.82, CI 0.81-0.83). <h4>Conclusions</h4> This study suggests that the national lockdown in Scotland was associated with a positive effect on timely childhood immunisation uptake, however in England a lower percentage of children were up to date at 6 and 18 months. Reason for the improve uptake in Scotland may include active measures taken to promote immunisation at local and national level during this period. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.",,pdf:https://discovery.ucl.ac.uk/10144866/3/Bedford_Uptake%20of%20infant%20and%20preschool%20immunisations%20in%20Scotland%20and%20England%20during%20the%20COVID-19%20pandemic_VoR.pdf; doi:https://doi.org/10.1101/2021.07.19.21260770; html:https://europepmc.org/article/PPR/PPR373622; doi:https://doi.org/10.1101/2021.07.19.21260770
+PPR573001,https://doi.org/10.1101/2022.11.16.22282338,Proteomic analysis of circulating immune cells identifies novel 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, Kingston N, Göttgens B, Bradley JR, Lehner PJ, Matheson NJ, Smith KG, Wills MR, Lyons PA, Weekes MP, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration.",,No Journal Info,2022,2022-11-18,Y,,,,"<h4>Summary</h4> Certain serum proteins, including CRP and D-dimer, have prognostic value in patients with SARS-CoV-2 infection. Nonetheless, these factors are non-specific, and provide limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations which drive the pathogenesis of severe COVID-19. To identify novel cellular phenotypes associated with disease progression, we here describe a comprehensive, unbiased analysis of the total and plasma membrane proteomes of PBMCs from a cohort of 40 unvaccinated individuals with SARS-CoV-2 infection, spanning the whole spectrum of disease severity. Combined with RNA-seq and flow cytometry data from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing cumulative immune cell dysregulation in progressive disease. In particular, 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 + CD177 + and CD16 + CEACAM1/6/8 + mononuclear cells. Utilisation of these markers may facilitate real-time patient assessment by flow cytometry, and identify immune cell populations that could be targeted to ameliorate immunopathology.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/11/18/2022.11.16.22282338.full.pdf; doi:https://doi.org/10.1101/2022.11.16.22282338; html:https://europepmc.org/article/PPR/PPR573001; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR573001&type=FILE&fileName=EMS157354-pdf.pdf&mimeType=application/pdf
 PPR579535,https://doi.org/10.1101/2022.12.02.22283049,Comparative effectiveness of sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients on kidney replacement therapy: observational cohort study using the OpenSAFELY-UKRR linked platform and SRR database,"The OpenSAFELY Collaborative, Zheng B, Campbell J, Carr EJ, Tazare J, Nab L, Mahalingasivam V, Mehrkar A, Santhakumaran S, Steenkamp R, Loud F, Lyon S, Scanlon M, Hulme WJ, Green AC, Curtis HJ, Fisher L, Parker E, Goldacre B, Douglas I, Evans S, MacKenna B, Bell S, Tomlinson LA, Nitsch D, The LH&W NCS (or CONVALESCENCE) Collaborative.",,No Journal Info,2022,2022-12-04,Y,,,,"<h4>Background</h4> Patients on kidney replacement therapy (KRT; dialysis and kidney transplantation) are at the highest risk of severe outcomes from COVID-19. Due to limited inclusion of patients on KRT in clinical trials, information is limited on the effectiveness of sotrovimab (a neutralising monoclonal antibody). We sought to address this by comparing its effectiveness against molnupiravir (an antiviral) in preventing severe COVID-19 outcomes in non-hospitalised adults with symptomatic COVID-19. <h4>Methods</h4> With the approval of NHS England we used routine clinical data from 24 million patients in England linked to the UK Renal Registry (UKRR) to identify patients on KRT, and data on antiviral treatments, COVID-19 test results, hospitalisation events and death from the OpenSAFELY-TPP data resource. Cox proportional hazards models (stratified for region) were used to estimate hazard ratios of sotrovimab vs. molnupiravir with regards to COVID-19 related hospitalisation or deaths in the subsequent 28 days (as the primary outcome). Further analyses were conducted using propensity score weighting (adjusted for region) and to investigate robustness of results with regards to different time periods, missing data, and adjustment variables. We also conducted a complementary analysis using data from patients in the Scottish Renal Registry (SRR) treated with sotrovimab or molnupiravir, following similar analytical approaches. <h4>Results</h4> Among the 2367 renal patients treated with sotrovimab (n=1852) or molnupiravir (n=515) between December 16, 2021 and August 1, 2022 in England, 38 cases (1.6%) of COVID-19 related hospitalisations/deaths were observed during the 28 days of follow-up after treatment initiation, with 21 (1.1%) in the sotrovimab group and 17 (3.3%) in the molnupiravir group. In multiple-adjusted analysis sotrovimab was associated with substantially lower risk of 28-day COVID-19 related hospitalisation/death than treatment with molnupiravir (hazard ratio, HR=0.35, 95% CI: 0.17 to 0.71; P=0.004), with results remaining robust in sensitivity analyses. In the SRR cohort, there were 19 cases (1.9%) of COVID-19 related hospitalisations/deaths during the 28 days of follow-up after treatment initiation of sotrovimab (n=723) or molnupiravir (n=270). In multiple-adjusted analysis, sotrovimab showed a trend toward lower risk of 28-day COVID-19 related hospitalisation/death than treatment with molnupiravir (HR=0.39, 95% CI: 0.13 to 1.21; P=0.106). In both datasets, sotrovimab had no evidence of association with other hospitalisation/death compared with molnupiravir (HRs ranging from 0.73-1.29; P>0.05). <h4>Conclusions</h4> In routine care of non-hospitalised patients with COVID-19 on kidney replacement therapy, those who received sotrovimab had substantially lower risk of severe COVID-19 outcomes than those receiving molnupiravir.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/12/05/2022.12.02.22283049.full.pdf; doi:https://doi.org/10.1101/2022.12.02.22283049; html:https://europepmc.org/article/PPR/PPR579535; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR579535&type=FILE&fileName=EMS158097-pdf.pdf&mimeType=application/pdf
 PPR602637,https://doi.org/10.2139/ssrn.4031570,Determinants of Antibody Responses to Two Doses of ChAdOx1 nCoV-19 or Bnt162b2 and a Subsequent Booster Dose of BNT162b2 or mRNA-1273: Population-Based Cohort Study (COVIDENCE UK),"Jolliffe D, Faustini S, Holt H, Perdek N, Maltby S, Talaei M, Greenig M, Vivaldi G, Tydeman F, Symons J, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Shaheen SO, Richter AG, Martineau AR.",,No Journal Info,2022,2022-03-03,Y,,,,"Background:  Antibody responses to SARS-CoV-2 vaccination vary for reasons that remain poorly understood. <br><br>Methods:  We tested for presence of combined IgG, IgA and IgM (IgGAM) anti-spike antibodies before and after administration of two doses of ChAdOx1 nCoV-19 (ChAdOx1, Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine from December 15, 2020 to July 10, 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacological and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Participants who were seronegative after receiving two vaccine doses were offered an additional antibody test following subsequent administration of a ‘booster’ dose of BNT162b2 or mRNA-1273 (Moderna) from September 23 to December 12, 2021. <br><br>Findings:  Serology results following two vaccine doses were available for 9,101 participants, of whom 5,770 (63.4%) received ChAdOx1 and 3,331 (36.6%) received BNT162b2. Anti-spike IgGAM was undetectable in 378 (4.2%) participants at a median of 8.6 weeks (IQR 6.4-10.7 weeks) after their second dose of vaccine. Seronegativity following two doses of SARS-CoV-2 vaccination was associated with administration of ChAdOx1  vs  BNT162b2 (aOR 7.03, 95% CI 4.39-11.24), shorter interval between first and second vaccine doses (aOR 2.37, 1.06-5.26, for <6 weeks  vs  >10 weeks; aOR 1.59, 1.18-2.13, for 6-10 weeks  vs  >10 weeks), poorer self-assessed general health (aOR 3.33, 1.49-7.46, for poor  vs  excellent), immunodeficiencies (aOR 6.75, 2.63-17.35) and prescription of systemic immunosuppressants (aOR 3.76, 2.44-5.78). By contrast, pre-vaccination SARS-CoV-2 seropositivity (aOR 0.16, 0.04-0.70, for symptomatic seropositives  vs  seronegatives) and supplemental vitamin D intake (aOR 0.73, 0.53-0.99) were associated with reduced risk of post-vaccination seronegativity. 247/378 (65.3%) of participants who were seronegative after two doses of ChAdOx1  vs  BNT162b2 provided a third sample at a median of 7.8 weeks (IQR 5.8-10.4) after receiving a booster dose of BNT162b2 or mRNA-1273: eight (3.2%) of them remained seronegative after three vaccine doses, all of whom either had a primary immunodeficiency or were taking systemic immunosuppressant drugs.<br><br>Interpretation:  We identify multiple determinants of antibody responses to two doses of ChAdOx1 or BNT162b2, many of which are potentially modifiable. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in those who failed to mount antibody responses following two doses of ChAdOx1 or BNT162b2.<br><br>Trial Registration Details:  Registered with ClinicalTrials.gov (NCT04330599).<br>		<br>Funding Information: This study was supported by a grant from Barts Charity to ARM and CJG (MGU0466) and by donations to Queen Mary University of London from the Fischer Family Trust, the Exilarch’s Foundation and DSM Nutritional Products Ltd. DAJ is supported by a Barts Charity Lectureship (MGU0459). MT is supported by a grant from the Rosetrees Trust and The Bloom Foundation (M771). The work was carried out with the support 20 of BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004) in partnership with SAIL Databank. BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK.<br>	<br>Declaration of Interests: JS declares receipt of payments from Reach plc for news stories written about recruitment to, and findings of, the COVIDENCE UK study. AS is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and its Standing Committee on Pandemics. He is also a member of the UK Government’s NERVTAG’s Risk Stratification Subgroup. ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd and Hyphens Pharma Ltd. ARM also declares support for attending meetings from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd and Abiogen Pharma Ltd. ARM also declares participation on the Data and Safety Monitoring Board for the Chair, DSMB, VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology). ARM also declares unpaid work as a Programme Committee member for the Vitamin D Workshop. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd. All other authors have nothing to declare. <br><br>Ethics Approval Statement: Approved by Leicester South Research Ethics Committee (ref 20/EM/0117). <br>",,doi:https://doi.org/10.1101/2022.02.14.22270930; doi:https://doi.org/10.2139/ssrn.4031570; html:https://europepmc.org/article/PPR/PPR602637; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR602637&type=FILE&fileName=EMS165240-pdf.pdf&mimeType=application/pdf
 PPR454901,https://doi.org/10.1101/2022.02.14.22270930,Determinants of antibody responses to two doses of ChAdOx1 nCoV-19 or BNT162b2 and a subsequent booster dose of BNT162b2 or mRNA-1273: population-based cohort study (COVIDENCE UK),"Jolliffe DA, Faustini SE, Holt H, Perdek N, Maltby S, Talaei M, Greenig M, Vivaldi G, Tydeman F, Symons J, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Shaheen SO, Richter AG, Martineau AR.",,No Journal Info,2022,2022-02-15,Y,,,,"<h4>Summary</h4> <h4>Background</h4> Antibody responses to SARS-CoV-2 vaccination vary for reasons that remain poorly understood. <h4>Methods</h4> We tested for presence of combined IgG, IgA and IgM (IgGAM) anti-spike antibodies before and after administration of two doses of ChAdOx1 nCoV-19 (ChAdOx1, Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine from December 15, 2020 to July 10, 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacological and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Participants who were seronegative after receiving two vaccine doses were offered an additional antibody test following subsequent administration of a ‘booster’ dose of BNT162b2 or mRNA-1273 (Moderna) from September 23 to December 12, 2021. <h4>Findings</h4> Serology results following two vaccine doses were available for 9,101 participants, of whom 5,770 (63.4%) received ChAdOx1 and 3,331 (36.6%) received BNT162b2. Anti-spike IgGAM was undetectable in 378 (4.2%) participants at a median of 8.6 weeks (IQR 6.4-10.7 weeks) after their second dose of vaccine. Seronegativity following two doses of SARS-CoV-2 vaccination was associated with administration of ChAdOx1 vs BNT162b2 (aOR 7.03, 95% CI 4.39-11.24), shorter interval between first and second vaccine doses (aOR 2.37, 1.06-5.26, for <6 weeks vs >10 weeks; aOR 1.59, 1.18-2.13, for 6-10 weeks vs >10 weeks), poorer self-assessed general health (aOR 3.33, 1.49-7.46, for poor vs excellent), immunodeficiencies (aOR 6.75, 2.63-17.35) and prescription of systemic immunosuppressants (aOR 3.76, 2.44-5.78). By contrast, pre-vaccination SARS-CoV-2 seropositivity (aOR 0.16, 0.04-0.70, for symptomatic seropositives vs seronegatives) and supplemental vitamin D intake (aOR 0.73, 0.53-0.99) were associated with reduced risk of post-vaccination seronegativity. 247/378 (65.3%) of participants who were seronegative after two doses of ChAdOx1 vs BNT162b2 provided a third sample at a median of 7.8 weeks (IQR 5.8-10.4) after receiving a booster dose of BNT162b2 or mRNA-1273: eight (3.2%) of them remained seronegative after three vaccine doses, all of whom either had a primary immunodeficiency or were taking systemic immunosuppressant drugs. <h4>Interpretation</h4> We identify multiple determinants of antibody responses to two doses of ChAdOx1 or BNT162b2, many of which are potentially modifiable. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in those who failed to mount antibody responses following two doses of ChAdOx1 or BNT162b2. <h4>Study registration</h4> https://clinicaltrials.gov/ct2/show/NCT04330599 <h4>Funding</h4> Barts Charity, Fischer Family Trust, The Exilarch’s Foundation, DSM Nutritional Products, Health Data Research UK <h4>Research in context</h4> <h4>Evidence before this study</h4> We searched PubMed, medRxiv, and Google Scholar for papers published from January 1, 2020, to February 1, 2022, using the search terms (antibody OR humoral OR serologic* OR immunogenic*) AND (SARS-CoV-2 vaccine OR ChAdOx1 or BNT162b2 coronavirus), with no language restrictions. Population-based studies investigating multiple potential determinants of vaccine immunogenicity in people with known pre-vaccination SARS-CoV-2 serostatus are lacking. <h4>Added value of this study</h4> This large population-based study, conducted in a population with known pre-vaccination SARS-CoV-2 serostatus, examines a comprehensive range of potential sociodemographic, behavioural, clinical, pharmacological and nutritional determinants of antibody responses to administration of two major SARS-CoV-2 vaccines (i.e., ChAdOx1 or BNT162b2), many of which have not previously been investigated. It is also the first population-based study to characterise antibody responses to booster doses of SARS-CoV-2 vaccines in adults who were seronegative after their primary course of vaccination. <h4>Implications of all the available evidence</h4> Increased risk of seronegativity following two doses of SARS-CoV-2 vaccines was associated with administration of ChAdOx1 vs BNT162b2, shorter interval between first and second vaccine doses, poorer self-assessed general health, immunocompromise and SARS-CoV-2 seronegativity pre-vaccination. Regular intake of vitamin D supplements was associated with reduced risk of post-vaccination seronegativity. Randomised controlled trials are now needed to test for causality. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in the majority of people who failed to mount antibody responses following a primary course of vaccination, the few exceptions being a subset of those with primary immunodeficiency or systemic immunosuppressant drugs.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/02/15/2022.02.14.22270930.full.pdf; doi:https://doi.org/10.1101/2022.02.14.22270930; html:https://europepmc.org/article/PPR/PPR454901; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR454901&type=FILE&fileName=EMS148745-pdf.pdf&mimeType=application/pdf
@@ -123,8 +123,8 @@ PPR546386,https://doi.org/10.1101/2022.09.16.22279985,Conventional and Bayesian
 PPR438220,https://doi.org/10.1101/2021.12.31.21268587,"The adverse impact of COVID-19 pandemic on cardiovascular disease prevention and management in England, Scotland and Wales: A population-scale analysis of trends in medication data","Dale CE, Takhar R, Carragher R, Torabi F, Katsoulis M, Duffield S, Kent S, Mueller T, Kurdi A, McTaggart S, Abbasizanjani H, Hollings S, Scourfield A, Lyons R, Griffiths R, Lyons J, Davies G, Harris D, Handy A, Mizani MA, Tomlinson C, Ashworth M, Denaxas S, Banerjee A, Sterne J, Lovibond K, Brown P, Bullard I, Priedon R, Mamas MA, Slee A, Lorgelly P, Pirmohamed M, Khunti K, Sattar N, Morris A, Sudlow C, Akbari A, Bennie M, Sofat R.",,No Journal Info,2022,2022-01-02,Y,,,,"<h4>Objectives</h4> To estimate the impact of the COVID-19 pandemic on cardiovascular disease (CVD) and CVD management using routinely collected medication data as a proxy. <h4>Design</h4> Descriptive and interrupted time series analysis using anonymised individual-level population-scale data for 1.32 billion records of dispensed CVD medications across 15.8 million individuals in England, Scotland and Wales. <h4>Setting</h4> Community dispensed CVD medications with 100% coverage from England, Scotland and Wales, plus primary care prescribed CVD medications from England (including 98% English general practices). <h4>Participants</h4> 15.8 million individuals aged 18+ years alive on 1 st April 2018 dispensed at least one CVD medicine in a year from England, Scotland and Wales. <h4>Main outcome measures</h4> Monthly counts, percent annual change (1 st April 2018 to 31 st July 2021) and annual rates (1 st March 2018 to 28 th February 2021) of medicines dispensed by CVD/ CVD risk factor; prevalent and incident use. <h4>Results</h4> Year-on-year change in dispensed CVD medicines by month were observed, with notable uplifts ahead of the first (11.8% higher in March 2020) but not subsequent national lockdowns. Using hypertension as one example of the indirect impact of the pandemic, we observed 491,203 fewer individuals initiated antihypertensive treatment across England, Scotland and Wales during the period March 2020 to end May 2021 than would have been expected compared to 2019. We estimated that this missed antihypertension treatment could result in 13,659 additional CVD events should individuals remain untreated, including 2,281 additional myocardial infarctions (MIs) and 3,474 additional strokes. Incident use of lipid-lowering medicines decreased by an average 14,793 per month in early 2021 compared with the equivalent months prior to the pandemic in 2019. In contrast, the use of incident medicines to treat type-2 diabetes (T2DM) increased by approximately 1,642 patients per month. <h4>Conclusions</h4> Management of key CVD risk factors as proxied by incident use of CVD medicines has not returned to pre-pandemic levels in the UK. Novel methods to identify and treat individuals who have missed treatment are urgently required to avoid large numbers of additional future CVD events, further adding indirect cost of the COVID-19 pandemic.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/01/07/2021.12.31.21268587.full.pdf; doi:https://doi.org/10.1101/2021.12.31.21268587; html:https://europepmc.org/article/PPR/PPR438220; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR438220&type=FILE&fileName=EMS142083-pdf.pdf&mimeType=application/pdf
 PPR393002,https://doi.org/10.1101/2021.09.02.21262979,"REACT-1 round 13 final report: exponential growth, high prevalence of SARS-CoV-2 and vaccine effectiveness associated with Delta variant in England during May to July 2021","Elliott P, Haw D, Wang H, Eales O, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, Trotter AJ, Prosolek SJ, Ashby D, Donnelly CA, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-09-10,Y,,,,"<h4>Background</h4> The prevalence of SARS-CoV-2 infection continues to drive rates of illness and hospitalisations despite high levels of vaccination, with the proportion of cases caused by the Delta lineage increasing in many populations. As vaccination programs roll out globally and social distancing is relaxed, future SARS-CoV-2 trends are uncertain. <h4>Methods</h4> We analysed prevalence trends and their drivers using reverse transcription-polymerase chain reaction (RT-PCR) swab-positivity data from round 12 (between 20 May and 7 June 2021) and round 13 (between 24 June and 12 July 2021) of the REal-time Assessment of Community Transmission-1 (REACT-1) study, with swabs sent to non-overlapping random samples of the population ages 5 years and over in England. <h4>Results</h4> We observed sustained exponential growth with an average doubling time in round 13 of 25 days (lower Credible Interval of 15 days) and an increase in average prevalence from 0.15% (0.12%, 0.18%) in round 12 to 0.63% (0.57%, 0.18%) in round 13. The rapid growth across and within rounds appears to have been driven by complete replacement of Alpha variant by Delta, and by the high prevalence in younger less-vaccinated age groups, with a nine-fold increase between rounds 12 and 13 among those aged 13 to 17 years. Prevalence among those who reported being unvaccinated was three-fold higher than those who reported being fully vaccinated. However, in round 13, 44% of infections occurred in fully vaccinated individuals, reflecting imperfect vaccine effectiveness against infection despite high overall levels of vaccination. Using self-reported vaccination status, we estimated adjusted vaccine effectiveness against infection in round 13 of 49% (22%, 67%) among participants aged 18 to 64 years, which rose to 58% (33%, 73%) when considering only strong positives (Cycle threshold [Ct] values < 27); also, we estimated adjusted vaccine effectiveness against symptomatic infection of 59% (23%, 78%), with any one of three common COVID-19 symptoms reported in the month prior to swabbing. Sex (round 13 only), ethnicity, household size and local levels of deprivation jointly contributed to the risk of higher prevalence of swab-positivity. <h4>Discussion</h4> From end May to beginning July 2021 in England, where there has been a highly successful vaccination campaign with high vaccine uptake, infections were increasing exponentially driven by the Delta variant and high infection prevalence among younger, unvaccinated individuals despite double vaccination continuing to effectively reduce transmission. Although slower growth or declining prevalence may be observed during the summer in the northern hemisphere, increased mixing during the autumn in the presence of the Delta variant may lead to renewed growth, even at high levels of vaccination.",,doi:https://doi.org/10.1101/2021.09.02.21262979; html:https://europepmc.org/article/PPR/PPR393002; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR393002&type=FILE&fileName=EMS134814-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2021/09/10/2021.09.02.21262979.full.pdf
 PPR411044,https://doi.org/10.1101/2021.10.14.21264965,REACT-1 study round 14: High and increasing prevalence of SARS-CoV-2 infection among school-aged children during September 2021 and vaccine effectiveness against infection in England,"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, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-10-22,Y,,,,"<h4>Background</h4> England experienced a third wave of the COVID-19 epidemic from end May 2021 coinciding with the rapid spread of Delta variant. Since then, the population eligible for vaccination against COVID-19 has been extended to include all 12-15-year-olds, and a booster programme has been initiated among adults aged 50 years and over, health care and care home workers, and immunocompromised people. Meanwhile, schoolchildren have returned to school often with few COVID-19-related precautions in place. <h4>Methods</h4> In the REal-time Assessment of Community Transmission-1 (REACT-1) study, throat and nose swabs were sent to non-overlapping random samples of the population aged 5 years and over in England. We analysed prevalence of SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) swab-positivity data from REACT-1 round 14 (between 9 and 27 September 2021). We combined results for round 14 with round 13 (between 24 June and 12 July 2021) and estimated vaccine effectiveness and prevalence of swab-positivity among double-vaccinated individuals. Unlike all previous rounds, in round 14, we switched from dry swabs transported by courier on a cold chain to wet swabs using saline. Also, at random, 50% of swabs (not chilled until they reached the depot) were transported by courier and 50% were sent through the priority COVID-19 postal service. <h4>Results</h4> We observed stable or rising prevalence (with an R of 1.03 (0.94, 1.14) overall) during round 14 with a weighted prevalence of 0.83% (0.76%, 0.89%). The highest weighted prevalence was found in children aged 5 to 12 years at 2.32% (1.96%, 2.73%) and 13 to 17 years at 2.55% (2.11%, 3.08%). All positive virus samples analysed correspond to the Delta variant or sub-lineages of Delta with one instance of the E484K escape mutation detected. The epidemic was growing in those aged 17 years and under with an R of 1.18 (1.03, 1.34), but decreasing in those aged 18 to 54 years with an R of 0.81 (0.68, 0.97). For all participants and all vaccines combined, at ages 18 to 64 years, vaccine effectiveness against infection (rounds 13 and 14 combined) was estimated to be 62.8% (49.3%, 72.7%) after two doses compared to unvaccinated people when adjusted for round, age, sex, index of multiple deprivation, region and ethnicity; the adjusted estimate was 44.8% (22.5%, 60.7%) for AstraZeneca and 71.3% (56.6%, 81.0%) for Pfizer-BioNTech, and for all vaccines combined it was 66.4% (49.6%, 77.6%) against symptomatic infection (one or more of 26 surveyed symptoms in month prior). Across rounds 13 and 14, at ages 18 years and over, weighted prevalence of swab-positivity was 0.55% (0.50%, 0.61%) for those who received their second dose 3-6 months before their swab compared to 0.35% (0.31%, 0.40%) for those whose second dose was within 3 months of their swab, while weighted prevalence among unvaccinated individuals was1.76% (1.60%, 1.95%). In round 14, age group, region, key worker status, and household size jointly contributed to the risk of higher prevalence of swab-positivity. <h4>Discussion</h4> In September 2021 infections were increasing exponentially in the 5-to-17-year age group coinciding with the start of the autumn school term in England. Relatively few schoolchildren aged 5 to 17 years have been vaccinated in the UK though single doses are now being offered to those aged 12 years and over. In adults, the higher prevalence of swab-positivity following two doses of vaccine from 3 to 6 months compared to within 3 months of second dose supports the use of a booster vaccine. It is important that the vaccination programme maintains high coverage and reaches children and unvaccinated or partially vaccinated adults to reduce transmission and associated disruptions to work and education.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/10/22/2021.10.14.21264965.full.pdf; doi:https://doi.org/10.1101/2021.10.14.21264965; html:https://europepmc.org/article/PPR/PPR411044; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR411044&type=FILE&fileName=EMS137524-pdf.pdf&mimeType=application/pdf
-PPR551688,https://doi.org/10.21203/rs.3.rs-2109276/v1,"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.",,No Journal Info,2022,2022-09-28,Y,,,,"<h4>Background: </h4> 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 enables 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.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-02093-0; doi:https://doi.org/10.21203/rs.3.rs-2109276/v1; html:https://europepmc.org/article/PPR/PPR551688; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR551688&type=FILE&fileName=EMS155094-pdf.pdf&mimeType=application/pdf
 PPR312488,https://doi.org/10.1101/2021.04.13.21255342,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 United Kingdom 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, Breuer J, the COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-04-15,N,,,,"<h4>Introduction</h4> Nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a significant cause of mortality in National Health Service (NHS) hospitals during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate the impact of rapid whole genome sequencing of SARS-CoV-2, supported by a novel probabilistic reporting methodology, to inform infection prevention and control (IPC) practice within NHS hospital settings. <h4>Methods and analysis</h4> COG-UK HOCI (COG-UK Consortium Hospital-Onset COVID-19 Infections study) is a multicentre, prospective, interventional, superiority study. Eligible patients must be admitted to hospital with first confirmed SARS-CoV-2 PCR positive test result >48h from time of admission, where COVID-19 diagnosis was not suspected upon admission. The projected sample size for 14 participating sites covering all study phases over winter-spring 2020/2021 in the United Kingdom is 2,380 patients. The intervention is the return of a sequence report, within 48 hours in one phase (rapid local lab) and within 5-10 days in a second phase (mimicking central lab use), comparing the viral genome from an eligible study participant with others within and outside the hospital site. The primary outcomes are the 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. A process evaluation using qualitative interviews with HCWs will be conducted alongside the study and analysis, underpinned by iterative programme theory of the sequence report. Health economic analysis will be conducted to determine cost-benefit of the intervention, and whether this leads to economic advantages within the NHS setting. <h4>Ethics and dissemination</h4> The protocol has been approved by the National Research Ethics Service Committee (Cambridge South 20/EE/0118). This manuscript is based on version 5.0 of the protocol. The study findings will be disseminated through peer-reviewed publications. <h4>Study Registration number</h4> ISRCTN50212645 <h4>Strengths and limitations of this study</h4> The COG-UK HOCI study harnesses the infrastructure of the UK’s existing national COVID-19 genome sequencing platform to evaluate the specific benefit of sequencing to hospital infection control. The evaluation is thought to be the first interventional study globally to assess effectiveness of genomic sequencing for infection control in an unbiased patient selection in secondary care settings. A range of institutional settings will participate, from specialist NHS-embedded or academic centres experienced in using pathogen genomics to district general hospitals. The findings are likely to have wider applicability in future decisions to utilise genome sequencing for infection control of other pathogens (such as influenza, respiratory syncytial virus, norovirus, clostridium difficile and antimicrobial resistant pathogens) in secondary care settings. The study has been awarded UK NIHR Urgent Public Health status, ensuring prioritised access to NIHR Clinical Research Network (CRN) research staff to recruit patients. The study does not have a randomised controlled design due to the logistics of managing this against diverse standard practice.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e052514.full.pdf; doi:https://doi.org/10.1101/2021.04.13.21255342; html:https://europepmc.org/article/PPR/PPR312488; doi:https://doi.org/10.1101/2021.04.13.21255342
+PPR551688,https://doi.org/10.21203/rs.3.rs-2109276/v1,"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.",,No Journal Info,2022,2022-09-28,Y,,,,"<h4>Background: </h4> 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 enables 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.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-02093-0; doi:https://doi.org/10.21203/rs.3.rs-2109276/v1; html:https://europepmc.org/article/PPR/PPR551688; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR551688&type=FILE&fileName=EMS155094-pdf.pdf&mimeType=application/pdf
 PPR286480,https://doi.org/10.1101/2021.02.17.21251928,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.",,No Journal Info,2021,2021-02-20,Y,,,,"<h4>Objectives</h4> To confirm the incidence of perioperative SARS-CoV-2 infection and associated mortality after surgery. <h4>Design and setting</h4> Analysis of routine electronic health record data from National Health Service (NHS) hospitals in England. <h4>Methods</h4> We extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between 1 st January 2020 and 31 st October 2020. The exposure was SARS-CoV-2 infection defined by 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 co-morbidity 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. <h4>Results</h4> We identified 1,972,153 patients undergoing surgery of whom 11,940 (0.6%) had SARS-CoV-2. In total, 19,100 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 2,618/11,940 [21.9%] vs No SARS-CoV-2: 16,482/1,960,213 [0.8%]; OR: 5.8 [5.5 – 6.1]; p<0.001). Amongst patients undergoing elective surgery 1,030/1,374,985 (0.1%) had SARS-CoV-2 of whom 83/1,030 (8.1%) died, compared with 1,092/1,373,955 (0.1%) patients without SARS-CoV-2 (OR: 29.0 [22.5 −37.3]; p<0.001). Amongst patients undergoing emergency surgery 9,742/437,891 (2.2%) patients had SARS-CoV-2, of whom 2,466/9,742 (25.3%) died compared with 14,817/428,149 (3.5%) patients without SARS-CoV-2 (OR: 5.7 [5.4 – 6.0]; p<0.001). <h4>Conclusions</h4> 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. <h4>Summary boxes</h4> <h4>What is already known on this topic</h4> High mortality rates have been reported amongst surgical patients who develop COVID-19 but we don’t know how this compares to the concurrent surgical population unaffected by COVID-19. Strict infection prevention and control procedures have substantially reduced the capacity of surgical treatment pathways in many hospitals. The very large backlog in delayed and cancelled surgical procedures is a growing public health concern. <h4>What this study adds</h4> Fewer than 1 in 100 surgical patients are affected by COVID-19 in the English National Health Service. Elective surgical patients who do develop COVID-19 are 30 times more likely to die while in hospital. Infection prevention and control procedures in NHS surgical pathways are highly effective but cannot be safely relaxed.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/02/20/2021.02.17.21251928.full.pdf; doi:https://doi.org/10.1101/2021.02.17.21251928; html:https://europepmc.org/article/PPR/PPR286480; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR286480&type=FILE&fileName=EMS117258-pdf.pdf&mimeType=application/pdf
 PPR357531,https://doi.org/10.1101/2021.06.15.21258542,"Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial","RECOVERY Collaborative Group, Horby PW, Mafham M, Peto L, Campbell M, Pessoa-Amorim G, Spata E, Staplin N, Emberson JR, Prudon B, Hine P, Brown T, Green CA, Sarkar R, Desai P, Yates B, Bewick T, Tiberi S, Felton T, 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, Weinreich DM, Haynes R, Landray MJ.",,No Journal Info,2021,2021-06-16,Y,,,,"<h4>SUMMARY</h4> <h4>Background</h4> REGEN-COV is a combination of 2 monoclonal antibodies (casirivimab and imdevimab) that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike protein. We aimed to evaluate the efficacy and safety of REGEN-COV in patients admitted to hospital with COVID-19. <h4>Methods</h4> In this randomised, controlled, open-label platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus a single dose of REGEN-COV 8g (casirivimab 4g and imdevimab 4g) by intravenous infusion (REGEN-COV group). The primary outcome was 28-day mortality assessed first among patients without detectable antibodies to SARS-CoV-2 at randomisation (seronegative) and then in the overall population. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ). <h4>Findings</h4> Between 18 September 2020 and 22 May 2021, 9785 patients were randomly allocated to receive usual care plus REGEN-COV or usual care alone, including 3153 (32%) seronegative patients, 5272 (54%) seropositive patients and 1360 (14%) patients with unknown baseline antibody status. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to REGEN-COV and 451 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio 0·80; 95% CI 0·70-0·91; p=0·0010). In an analysis involving all randomised patients (regardless of baseline antibody status), 944 (20%) of 4839 patients allocated to REGEN-COV and 1026 (21%) of 4946 patients allocated to usual care died within 28 days (rate ratio 0·94; 95% CI 0·86-1·03; p=0·17). The proportional effect of REGEN-COV on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity = 0·001). <h4>Interpretation</h4> In patients hospitalised with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) reduced 28-day mortality among patients who were seronegative at baseline. <h4>Funding</h4> UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).",,pdf:https://nottingham-repository.worktribe.com/preview/7415985/1-s2.0-S0140673622001635-main.pdf; doi:https://doi.org/10.1101/2021.06.15.21258542; html:https://europepmc.org/article/PPR/PPR357531; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR357531&type=FILE&fileName=EMS127953-pdf.pdf&mimeType=application/pdf
 PPR425049,https://doi.org/10.1101/2021.11.22.21266512,Association of COVID-19 with arterial and venous vascular diseases: a population-wide cohort study of 48 million adults in England and Wales,"Knight R, Walker V, Ip S, Cooper JA, Bolton T, Keene S, Denholm R, Akbari A, Abbasizanjani H, Torabi F, Omigie E, Hollings S, North T, Toms R, Di Angelantonio E, Denaxas S, Thygesen JH, Tomlinson C, Bray B, Smith CJ, Barber M, Smith GD, Chaturvedi N, Sudlow C, Whiteley WN, Wood A, Sterne JAC, for the CVD-COVID-UK/COVID-IMPACT consortium and the Longitudinal Health and Wellbeing COVID-19 National Core Study.",,No Journal Info,2021,2021-11-24,Y,,,,"<h4>Importance</h4> The long-term effects of COVID-19 on the incidence of vascular diseases are unclear. <h4>Objective</h4> To quantify the association between time since diagnosis of COVID-19 and vascular disease, overall and by age, sex, ethnicity, and pre-existing disease. <h4>Design</h4> Cohort study based on population-wide linked electronic health records, with follow up from January 1 st to December 7 th 2020. <h4>Setting and participants</h4> Adults registered with an NHS general practice in England or Wales and alive on January 1 st 2020. <h4>Exposures</h4> Time since diagnosis of COVID-19 (categorised as 0-6 days, 1-2 weeks, 3-4, 5-8, 9-12, 13-26 and 27-49 weeks since diagnosis), with and without hospitalisation within 28 days of diagnosis. <h4>Main outcomes and measures</h4> Primary outcomes were arterial thromboses (mainly acute myocardial infarction and ischaemic stroke) and venous thromboembolic events (VTE, mainly pulmonary embolism and lower limb deep vein thrombosis). We also studied other vascular events (transient ischaemic attack, haemorrhagic stroke, heart failure and angina). Hazard ratios were adjusted for demographic characteristics, previous disease diagnoses, comorbidities and medications. <h4>Results</h4> Among 48 million adults, 130,930 were and 1,315,471 were not hospitalised within 28 days of COVID-19. In England, there were 259,742 first arterial thromboses and 60,066 first VTE during 41.6 million person-years follow-up. Adjusted hazard ratios (aHRs) for first arterial thrombosis compared with no COVID-19 declined rapidly from 21.7 (95% CI 21.0-22.4) to 3.87 (3.58-4.19) in weeks 1 and 2 after COVID-19, 2.80 (2.61-3.01) during weeks 3-4 then to 1.34 (1.21-1.48) during weeks 27-49. aHRs for first VTE declined from 33.2 (31.3-35.2) and 8.52 (7.59-9.58) in weeks 1 and 2 to 7.95 (7.28-8.68) and 4.26 (3.86-4.69) during weeks 3-4 and 5-8, then 2.20 (1.99-2.44) and 1.80 (1.50-2.17) during weeks 13-26 and 27-49 respectively. aHRs were higher, for longer after diagnosis, after hospitalised than non-hospitalised COVID-19. aHRs were also higher among people of Black and Asian than White ethnicity and among people without than with a previous event. Across the whole population estimated increases in risk of arterial thromboses and VTEs were 2.5% and 0.6% respectively 49 weeks after COVID-19, corresponding to 7,197 and 3,517 additional events respectively after 1.4 million COVID-19 diagnoses. <h4>Conclusions and Relevance</h4> High rates of vascular disease early after COVID-19 diagnosis decline more rapidly for arterial thromboses than VTEs but rates remain elevated up to 49 weeks after COVID_19. These results support continued policies to avoid COVID-19 infection with effective COVID-19 vaccines and use of secondary preventive agents in high-risk patients. <h4>Key points</h4> <h4>Question</h4> Is COVID-19 associated with higher long-term incidence of vascular diseases? <h4>Findings</h4> In this cohort study of 48 million adults in England and Wales, COVID-19 was associated with higher incidence, that declined with time since diagnosis, of both arterial thromboses [week 1: adjusted HR [aHR] 21.7 (95% CI 21.0-22.4) weeks 27-49: aHR 1.34 (1.21-1.48)] and venous thromboembolism [week 1: aHR 33.2 (31.3-35.2), weeks 27–49 1.80 (1.50-2.17)]. aHRs were higher, for longer, after hospitalised than non-hospitalised COVID-19. The estimated excess number of arterial thromboses and venous thromboembolisms was 10,500. <h4>Meaning</h4> Avoidance of COVID-19 infection through vaccination, and use of secondary preventive agents after infection in high-risk patients, may reduce post-COVID-19 acute vascular diseases.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/11/24/2021.11.22.21266512.full.pdf; doi:https://doi.org/10.1101/2021.11.22.21266512; html:https://europepmc.org/article/PPR/PPR425049; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR425049&type=FILE&fileName=EMS140221-pdf.pdf&mimeType=application/pdf
@@ -159,8 +159,8 @@ PPR230575,https://doi.org/10.1101/2020.10.26.20219725,"Declining prevalence of a
 PPR265251,https://doi.org/10.1101/2021.01.15.21249724,Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments,"Cake C, Ogburn E, Pinches H, Coleman G, Seymour D, Woodard F, Manohar S, Monsur M, Landray M, Dalton G, Morris AD, Chinnery PF, Hobbs FR, Butler C, UK COVID-19 National Core Studies Consortium.",,No Journal Info,2021,2021-01-15,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> The COVID-19 pandemic has presented unique challenges for rapidly designing, initiating, and delivering therapeutic clinical trials. PRINCIPLE is the UK national platform investigating repurposed therapies for COVID-19 treatment of older people in the community at high risk of complications. Standard methods of patient recruitment were failing to meet the required pace and scale of enrolment. This paper describes the development and appraisal of a near real-time, data-driven, ethical approach for enhancing recruitment in community care by contacting people with a recent COVID-19 positive test result from the central NHS Test and Trace service within 24-48 hours of their test result. <h4>Methods</h4> A multi-disciplinary team was formed to solve the technical, ethical, public perception, logistical and information governance issues required to provide a near-real time (within 24-48 hours of receiving a positive test) feed of potential trial participants from test result data to the research team. PRINCIPLE was also given unique access to the Summary Care Record (SCR) to ensure safe prescribing, and to enable the trial team to quickly and safely bring consented patients into the trial. A survey of the public was used to understand public perceptions of the use of test data for this proposed methodology. <h4>Results</h4> Prior to establishing the data service, PRINCIPLE registered on average 87 participants per week. This increased by up to 87 additional people registered per week from the test data, contributing to an increase from 1,013 recruits to PRINCIPLE at the start of October 2020 to 2,802 recruits by 20 th December 2020. While procedural caveats were identified by the public consultation, out of 2,639 people contacted by PRINCIPLE following a positive test result, no one raised a concern about being approached. <h4>Conclusions</h4> This paper describes a novel approach to using near-real time NHS operational data to recruit community-based patients within a few days of presentation with acute illness. This approach increased recruitment, and reduced time between positive test and randomisation, allowing more rapid evaluation of treatments and increased safety for participants. End-to-end public and patient involvement in the design of the approach provided evidence to inform information governance decisions. <h4>Trial registration</h4> PRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research. EudraCT number: 2020-001209-22 ISRCTN registry: ISRCTN86534580 REC number: 20/SC/058 IRAS number: 281958",,pdf:https://ora.ox.ac.uk/objects/uuid:2e47c438-bed2-4d19-bf8f-3b0584f66a99/download_file?safe_filename=Cake_et_al_2022_Development_and_evaluation.pdf&file_format=pdf&type_of_work=Journal+article; doi:https://doi.org/10.1101/2021.01.15.21249724; html:https://europepmc.org/article/PPR/PPR265251; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR265251&type=FILE&fileName=EMS110588-pdf.pdf&mimeType=application/pdf
 PPR241057,https://doi.org/10.1101/2020.11.18.20233932,REACT-1 round 6 updated report: high prevalence of SARS-CoV-2 swab positivity with reduced rate of growth in England at the start of November 2020,"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.",,No Journal Info,2020,2020-11-20,Y,,,,"<h4>Background</h4> England is now in the midst of its second wave of the COVID-19 pandemic. Multiple regions of the country are at high infection prevalence and all areas experienced rapid recent growth of the epidemic during October 2020. <h4>Methods</h4> REACT-1 is a series of community surveys of SARS-CoV-2 RT-PCR swab-positivity in England designed to monitor the spread of the epidemic and thus increase situational awareness. Round 6 of REACT-1 commenced swab-collection on 16th October. A prior interim report included data from 16th to 25th October for 85,971 participants. Here, we report data for the entire round on 160,175 participants with swab results obtained up to 2nd November 2020. <h4>Results</h4> Overall weighted prevalence of infection in the community in England was 1.3% or 130 people per 10,000 infected, up from 60 people per 10,000 in the round 5 report (18th September to 5th October 2020), doubling every 24 days on average since the prior round. The corresponding R number was estimated to be 1.2. Prevalence of infection was highest in North West (2.4%, up from 1.2%), followed by Yorkshire and The Humber (2.3% up from 0.84%), West Midlands (1.6% up from 0.60%), North East (1.5% up from 1.1%), East Midlands (1.3% up from 0.56%), London (0.97%, up from 0.54%), South West (0.80% up from 0.33%), South East (0.69% up from 0.29%), and East of England (0.69% up from 0.30%). Rapid growth in the South observed in the first half of round 6 was no longer apparent in the second half of round 6. We also observed a decline in prevalence in Yorkshire and The Humber during this period. Comparing the first and second halves of round 6, there was a suggestion of decline in weighted prevalence in participants aged 5 to 12 years and in those aged 25 to 44 years. While prevalence remained high, in the second half of round 6 there was suggestion of a slight fall then rise that was seen nationally and also separately in both the North and the South. <h4>Conclusion</h4> The impact of the second national lockdown in England is not yet known. We provide here a detailed description of swab-positivity patterns at national, regional and local scales for the period immediately preceding lockdown, against which future trends in prevalence can be evaluated.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/11/20/2020.11.18.20233932.full.pdf; doi:https://doi.org/10.1101/2020.11.18.20233932; html:https://europepmc.org/article/PPR/PPR241057; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR241057&type=FILE&fileName=EMS104966-pdf.pdf&mimeType=application/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,,,,"<h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Discussion</h4> 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.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/06/21/2021.06.17.21259103.full.pdf; 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
-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,,,,"<h4>Background</h4> Vaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics. <h4>Objectives</h4> 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). <h4>Design</h4> 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. <h4>Setting and participants</h4> <h4>Objective: </h4> 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. <h4>Outcomes</h4> 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. <h4>Results</h4> <h4>Population-level data linkage (objective 1)</h4> 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. <h4>Survey responses (objective 2)</h4> 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. <h4>Conclusion</h4> 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.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/05/11/2022.05.09.22274769.full.pdf; 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
 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,,,,"<h4>Background</h4> 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). <h4>Methods</h4> 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. <h4>Results</h4> 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). <h4>Conclusions</h4> 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. <h4>Trial Registration Number</h4> ISRCTN 14447421",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/01/27/2022.01.21.22269605.full.pdf; 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
+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,,,,"<h4>Background</h4> Vaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics. <h4>Objectives</h4> 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). <h4>Design</h4> 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. <h4>Setting and participants</h4> <h4>Objective: </h4> 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. <h4>Outcomes</h4> 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. <h4>Results</h4> <h4>Population-level data linkage (objective 1)</h4> 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. <h4>Survey responses (objective 2)</h4> 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. <h4>Conclusion</h4> 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.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/05/11/2022.05.09.22274769.full.pdf; 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
 PPR233362,https://doi.org/10.1101/2020.10.30.20223123,High prevalence of SARS-CoV-2 swab positivity and increasing R number in England during October 2020: REACT-1 round 6 interim report,"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.",,No Journal Info,2020,2020-11-03,Y,,,,"<h4>Background</h4> REACT-1 measures prevalence of SARS-CoV-2 infection in representative samples of the population in England using PCR testing from self-administered nose and throat swabs. Here we report interim results for round 6 of observations for swabs collected from the 16th to 25th October 2020 inclusive. <h4>Methods</h4> REACT-1 round 6 aims to collect data and swab results from 160,000 people aged 5 and above. Here we report results from the first 86,000 individuals. We estimate prevalence of PCR-confirmed SARS-CoV-2 infection, reproduction numbers (R) and temporal trends using exponential growth or decay models. Prevalence estimates are presented both unweighted and weighted to be representative of the population of England, accounting for response rate, region, deprivation and ethnicity. We compare these interim results with data from round 5, based on swabs collected from 18th September to 5th October 2020 inclusive. <h4>Results</h4> Overall prevalence of infection in the community in England was 1.28% or 128 people per 10,000, up from 60 per 10,000 in the previous round. Infections were doubling every 9.0 (6.1, 18) days with a national reproduction number (R) estimated at 1.56 (1.27, 1.88) compared to 1.16 (1.05, 1.27) in the previous round. Prevalence of infection was highest in Yorkshire and The Humber at 2.72% (2.12%, 3.50%), up from 0.84% (0.60%, 1.17%), and the North West at 2.27% (1.90%, 2.72%), up from 1.21% (1.01%, 1.46%), and lowest in South East at 0.55% (0.45%, 0.68%), up from 0.29% (0.23%, 0.37%). Clustering of cases was more prevalent in Lancashire, Manchester, Liverpool and West Yorkshire, West Midlands and East Midlands. Interim estimates of R were above 2 in the South East, East of England, London and South West, but with wide confidence intervals. Nationally, prevalence increased across all age groups with the greatest increase in those aged 55-64 at 1.20% (0.99%, 1.46%), up 3-fold from 0.37% (0.30%, 0.46%). In those aged over 65, prevalence was 0.81% (0.58%, 0.96%) up 2-fold from 0.35% (0.28%, 0.43%). Prevalence remained highest in 18 to 24-year olds at 2.25% (1.47%, 3.42%). <h4>Conclusion</h4> The co-occurrence of high prevalence and rapid growth means that the second wave of the epidemic in England has now reached a critical stage. Whether via regional or national measures, it is now time-critical to control the virus and turn R below one if further hospital admissions and deaths from COVID-19 are to be avoided.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/11/03/2020.10.30.20223123.full.pdf; doi:https://doi.org/10.1101/2020.10.30.20223123; html:https://europepmc.org/article/PPR/PPR233362; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR233362&type=FILE&fileName=EMS103475-pdf.pdf&mimeType=application/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,,,,"<h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Findings</h4> 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. <h4>Interpretation</h4> 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. <h4>Research in Context</h4> <h4>Evidence before the study</h4> 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. <h4>Added value of this study</h4> 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. <h4>Implications of all the available evidence</h4> 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.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/11/09/2021.11.08.21265312.full.pdf; 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
 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.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/10/01/2021.10.01.21264408.full.pdf; 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
@@ -179,15 +179,15 @@ PPR258079,https://doi.org/10.1101/2020.12.24.20248822,Estimated transmissibility
 PPR247290,https://doi.org/10.1101/2020.11.30.20239806,REACT-1 round 7 interim report: fall in prevalence of swab-positivity in England during national lockdown,"Riley S, Eales O, Walters CE, Wang H, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,No Journal Info,2020,2020-12-02,Y,,,,"<h4>Background</h4> The second wave of the 2020 COVID-19 pandemic in England has been characterized by high growth and prevalence in the North with lower prevalence in the South. High prevalence was first observed at younger adult ages before spreading out to school-aged children and older adults. Local tiered interventions were in place up to 5th November 2020 at which time a second national lockdown was implemented. <h4>Methods</h4> REACT-1 is a repeated cross-sectional survey of SARS-CoV-2 swab-positivity in random samples of the population of England. The current period of data collection (round 7) commenced on 13th November 2020 and we report interim results here for swabs collected up to and including 24th November 2020. Because there were two distinct periods of growth during the previous round 6, here we compare results from round 7 (mainly) with the second half of round 6, which obtained swabs between 26th October and 2nd November 2020. We report prevalence both unweighted and reweighted to be representative of the population of England. We describe trends in unweighted prevalence with daily growth rates, doubling times, reproduction numbers (R) and splines. We estimated odds ratios for swab-positivity using mutually-adjusted multivariable logistic regression models. <h4>Results</h4> We found 821 positives from 105,123 swabs giving an unweighted prevalence of 0.78% (95% CI, 0.73%, 0.84%) and a weighted prevalence of 0.96% (0.87%, 1.05%). The weighted prevalence estimate was ∼30% lower than that of 1.32% (1.20%, 1.45%) obtained in the second half of round 6. This decrease corresponds to a halving time of 37 (30, 47) days and an R number of 0.88 (0.86, 0.91). Using only data from the most recent period, we estimate an R number of 0.71 (0.54, 0.90). A spline fit to prevalence showed a rise shortly after the previous period of data collection followed by a fall coinciding with the start of lockdown. The national trends were driven mainly by reductions in higher-prevalence northern regions, with prevalence approximately unchanged in the Midlands and London, and smaller reductions in southern lower-prevalence regions. Sub-regional analyses showed variable changes in prevalence at the local level including marked declines in the North, but also local areas of growth in East and West Midlands. Mutually adjusted models in the most recent period indicated: people of Asian ethnicity, those living in the most deprived neighbourhoods, and those living in the largest households, had higher odds of swab-positivity. <h4>Conclusion</h4> Three weeks into the second national lockdown in England there has been a ∼30% proportionate reduction in prevalence overall, with greater reductions in the North. As a result, inter-regional heterogeneity has reduced, although average absolute prevalence remains high at ∼1%. Continued monitoring of the epidemic in the community remains essential until prevalence is reliably suppressed to much lower levels, for example, through widespread vaccination.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/12/02/2020.11.30.20239806.full.pdf; doi:https://doi.org/10.1101/2020.11.30.20239806; html:https://europepmc.org/article/PPR/PPR247290; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR247290&type=FILE&fileName=EMS107598-pdf.pdf&mimeType=application/pdf
 PPR167068,https://doi.org/10.1101/2020.05.19.20106278,Benefit-risk analysis of health benefits of routine childhood immunisation against the excess risk of SARS-CoV-2 infections during the COVID-19 pandemic in Africa,"Abbas K, Procter SR, van Zandvoort K, Clark A, Funk S, Mengistu T, Hogan D, Dansereau E, Jit M, Flasche S, LSHTM CMMID CMMID COVID-19 Working Group.",,No Journal Info,2020,2020-05-26,Y,,,,"<h4>Summary</h4> <h4>Background</h4> National immunisation programmes globally are at risk of suspension due to the severe health system constraints and physical distancing measures in place to mitigate the ongoing COVID-19 pandemic. Our aim is to compare the health benefits of sustaining routine childhood immunisation in Africa against the risk of acquiring SARS-CoV-2 infections through visiting routine vaccination service delivery points. <h4>Methods</h4> We used two scenarios to approximate the child deaths that may be caused by immunisation coverage reductions during COVID-19 outbreaks. First, we used previously reported country-specific child mortality impact estimates of childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, pneumococcal, rotavirus, measles, meningitis A, rubella, and yellow fever (DTP3, HepB3, Hib3, PCV3, RotaC, MCV1, MCV2, MenA, RCV, YFV) to approximate the future deaths averted before completing five years of age by routine childhood vaccination during a 6-month COVID-19 risk period without catch-up campaigns. Second, we analysed an alternative scenario that approximates the health benefits of sustaining routine childhood immunisation to only the child deaths averted from measles outbreaks during the COVID-19 risk period. The excess number of infections due to additional SARS-CoV-2 exposure during immunisation visits assumes that contact reducing interventions flatten the outbreak curve during the COVID-19 risk period, that 60% of the population will have been infected by the end of that period, that children can be infected by either vaccinators or during transport and that upon child infection the whole household would be infected. Country specific household age structure estimates and age dependent infection fatality rates are then applied to calculate the number of deaths attributable to the vaccination clinic visits. We present benefit-risk ratios for routine childhood immunisation alongside 95% uncertainty range estimates from probabilistic sensitivity analysis. <h4>Findings</h4> For every one excess COVID-19 death attributable to SARS-CoV-2 infections acquired during routine vaccination clinic visits, there could be 84 (14-267) deaths in children prevented by sustaining routine childhood immunisation in Africa. The benefit-risk ratio for the vaccinated children, siblings, parents or adult care-givers, and older adults in the households of vaccinated children are 85,000 (4,900 - 546,000), 75,000 (4,400 - 483,000), 769 (148 - 2,700), and 96 (14 - 307) respectively. In the alternative scenario that approximates the health benefits to only the child deaths averted from measles outbreaks, the benefit-risk ratio to the households of vaccinated children is 3 (0 - 10) under these highly conservative assumptions and if the risk to only the vaccinated children is considered, the benefit-risk ratio is 3,000 (182 - 21,000). <h4>Interpretation</h4> Our analysis suggests that the health benefits of deaths prevented by sustaining routine childhood immunisation in Africa far outweighs the excess risk of COVID-19 deaths associated with vaccination clinic visits, especially for the vaccinated children. However, there are other factors that must be considered for strategic decision making to sustain routine childhood immunisation in African countries during the COVID-19 pandemic. These include logistical constraints of vaccine supply chain problems caused by the COVID-19 pandemic, reallocation of immunisation providers to other prioritised health services, healthcare staff shortages caused by SARS-CoV-2 infections among the staff, decreased demand for vaccination arising from community reluctance to visit vaccination clinics for fear of contracting SARS-CoV-2 infections, and infection risk to healthcare staff providing immunisation services as well as to their households and onward SARS-CoV-2 transmission into the wider community. <h4>Funding</h4> Gavi, the Vaccine Alliance and Bill & Melinda Gates Foundation (OPP1157270) <h4>Research in context</h4> <h4>Evidence before the study</h4> National immunisation programmes globally are at risk of disruption due to the severe health system constraints caused by the ongoing COVID-19 pandemic and the physical distancing measures to mitigate the outbreak. The decrease in vaccination coverage increases the proportion of susceptible children at risk of increased morbidity and mortality from vaccine-preventable disease outbreaks. Outbreaks of vaccine preventable disease have been observed during previous interruptions to routine immunisation services during an ongoing infectious disease epidemic, such as during the 2013-2016 Ebola outbreak in West Africa, when most health resources were shifted towards the Ebola response which led to decreasing vaccination coverage and consequently outbreaks of measles and other vaccine-preventable diseases. <h4>Added value of this study</h4> We estimated the benefit-risk ratio by comparing the deaths prevented by sustaining routine childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, pneumococcal, rotavirus, measles, meningitis A, rubella, and yellow fever vaccines with the excess COVID-19 deaths associated with vaccination clinic visits. The benefit of routine childhood immunization programmes in all the 54 countries of Africa is higher than the COVID-19 risk associated with these vaccination clinic visits. <h4>Implications of all the available evidence</h4> Routine childhood immunisation programmes should be safeguarded for continued service delivery and prioritised for the prevention of infectious diseases, as logistically possible, as part of delivering essential health services during the COVID-19 pandemic in Africa. The current immunisation service models will require adaptation, including physical distancing measures, personal protective equipment, and good hygiene practices for infection control at the vaccination clinics, and have to be complemented by new immunisation service models for sustaining routine childhood immunisation in the African countries during the COVID-19 risk period.",,doi:https://doi.org/10.1016/s2214-109x(20)30308-9; doi:https://doi.org/10.1101/2020.05.19.20106278; html:https://europepmc.org/article/PPR/PPR167068; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR167068&type=FILE&fileName=EMS90726-pdf.pdf&mimeType=application/pdf
 PPR340395,https://doi.org/10.1101/2021.05.13.21257144,REACT-1 round 11 report: low prevalence of SARS-CoV-2 infection in the community prior to the third step of the English roadmap out of lockdown,"Riley S, Haw D, Walters CE, Wang H, Eales O, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, Trotter AJ, Le Viet T, Alikhan N, O’Grady J, 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,2021,2021-05-17,Y,,,,"<h4>Background</h4> National epidemic dynamics of SARS-CoV-2 infections are being driven by: the degree of recent indoor mixing (both social and workplace), vaccine coverage, intrinsic properties of the circulating lineages, and prior history of infection (via natural immunity). In England, infections, hospitalisations and deaths fell during the first two steps of the “roadmap” for exiting the third national lockdown. The third step of the roadmap in England takes place on 17 May 2021. <h4>Methods</h4> We report the most recent findings on community infections from the REal-time Assessment of Community Transmission-1 (REACT-1) study in which a swab is obtained from a representative cross-sectional sample of the population in England and tested using PCR. Round 11 of REACT-1 commenced self-administered swab-collection on 15 April 2021 and completed collections on 3 May 2021. We compare the results of REACT-1 round 11 to round 10, in which swabs were collected from 11 to 30 March 2021. <h4>Results</h4> Between rounds 10 and 11, prevalence of swab-positivity dropped by 50% in England from 0.20% (0.17%, 0.23%) to 0.10% (0.08%, 0.13%), with a corresponding R estimate of 0.90 (0.87, 0.94). Rates of swab-positivity fell in the 55 to 64 year old group from 0.17% (0.12%, 0.25%) in round 10 to 0.06% (0.04%, 0.11%) in round 11. Prevalence in round 11 was higher in the 25 to 34 year old group at 0.21% (0.12%, 0.38%) than in the 55 to 64 year olds and also higher in participants of Asian ethnicity at 0.31% (0.16%, 0.60%) compared with white participants at 0.09% (0.07%, 0.11%). Based on sequence data for positive samples for which a lineage could be identified, we estimate that 92.3% (75.9%, 97.9%, n=24) of infections were from the B.1.1.7 lineage compared to 7.7% (2.1%, 24.1%, n=2) from the B.1.617.2 lineage. Both samples from the B.1.617.2 lineage were detected in London from participants not reporting travel in the previous two weeks. Also, allowing for suitable lag periods, the prior close alignment between prevalence of infections and hospitalisations and deaths nationally has diverged. <h4>Discussion</h4> We observed marked reductions in prevalence from March to April and early May 2021 in England reflecting the success of the vaccination programme and despite easing of restrictions during lockdown. However, there is potential upwards pressure on prevalence from the further easing of lockdown regulations and presence of the B.1.617.2 lineage. If prevalence rises in the coming weeks, policy-makers will need to assess the possible impact on hospitalisations and deaths. In addition, consideration should be given to other health and economic impacts if increased levels of community transmission occur.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/05/17/2021.05.13.21257144.full.pdf; doi:https://doi.org/10.1101/2021.05.13.21257144; html:https://europepmc.org/article/PPR/PPR340395; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR340395&type=FILE&fileName=EMS124703-pdf.pdf&mimeType=application/pdf
-PPR626309,https://doi.org/10.21203/rs.3.rs-2573712/v1,How much did the Covid-19 shielding policy cost in Wales? A Retrospective Cost analysis within the EVITE Immunity study,"Sewell B, Farr A, Akbari A, Carson-Stevens A, Edwards A, Evans BA, John A, Torabi F, Dale J, Jolles S, Kingston MR, Lyons J, Lyons RA, Porter A, Watkins A, Williams V, Snooks H.",,No Journal Info,2023,2023-03-06,Y,,,,"<h4>Background: </h4> The EVITE Immunity study investigates the effects of shielding Clinically Extremely Vulnerable (CEV) people during the COVID-19 pandemic on health outcomes and healthcare costs in Wales, UK, to help prepare for future pandemics. Shielding was intended to protect those at highest risk of serious harm from COVID-19. We report the cost of implementing shielding in Wales. <h4>Methods:</h4> The number of people shielding was extracted from the Secure Anonymised Information Linkage Databank. Resources supporting shielding between March and June 2020 were mapped using published reports, web pages, freedom of information requests to Welsh Government and personal communications (e.g. the office of the Chief Medical Officer for Wales). <h4>Results:</h4> At the beginning of shielding, 117,415 people were on the shielding list. The total additional cost to support those advised to stay home during the initial 14 weeks of the pandemic was £13,307,654 (£113 per person shielded). This included the new resources required to compile the shielding list, inform CEV people of the shielding intervention and provide medicine and food deliveries. The list was adjusted weekly over the 3-month period (130,000 people identified by June 2020) therefore the cost per person shielded lies between £102 and £113. <h4>Conclusion:</h4> This is the first evaluation of the cost of the measures put in place to support those identified to shield in Wales. However, no data on opportunity cost was available. The true cost of shielding including its budget impact and opportunity costs need to be investigated to decide whether shielding is a worthwhile policy for future health emergencies.",,pdf:https://www.researchsquare.com/article/rs-2573712/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-2573712/v1; html:https://europepmc.org/article/PPR/PPR626309; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR626309&type=FILE&fileName=EMS171864-pdf.pdf&mimeType=application/pdf
 PPR287082,https://doi.org/10.1101/2021.02.18.21251973,REACT-1 round 9 interim report: downward trend of SARS-CoV-2 in England in February 2021 but still at high prevalence,"Riley S, Walters CE, Wang H, Eales O, Haw D, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,No Journal Info,2021,2021-02-23,Y,,,,"<h4>Background and Methods</h4> England entered its third national lockdown of the COVID-19 pandemic on 6th January 2021 with the aim of reducing the daily number of deaths and pressure on healthcare services. The real-time assessment of community transmission study (REACT-1) obtains throat and nose swabs from randomly selected people in England in order to describe patterns of SARS-CoV-2 prevalence. Here, we report data from round 9a of REACT-1 for swabs collected between 4th and 13th February 2021. <h4>Results</h4> Out of 85,473 tested-swabs, 378 were positive. Overall weighted prevalence of infection in the community in England was 0.51%, a fall of more than two thirds since our last report (round 8) in January 2021 when 1.57% of people tested positive. We estimate a halving time of 14.6 days and a reproduction number R of 0.72, based on the difference in prevalence between the end of round 8 and the beginning of round 9. Although prevalence fell in all nine regions of England over the same period, there was greater uncertainty in the trend for North West, North East, and Yorkshire and The Humber. Prevalence fell substantially across all age groups with highest prevalence among 18- to 24-year olds at 0.89% (0.47%, 1.67%) and those aged 5 to12 years at 0.86% (0.60%, 1.24%). Large household size, living in a deprived neighbourhood, and Asian ethnicity were all associated with increased prevalence. Healthcare and care home workers were more likely to test positive compared to other workers. <h4>Conclusions</h4> There is a strong decline in prevalence of SARS-CoV-2 in England among the general population five to six weeks into lockdown, but prevalence remains high: at levels similar to those observed in late September 2020. Also, the number of COVID-19 cases in hospitals is higher than at the peak of the first wave in April 2020. The effects of easing of social distancing when we transition out of lockdown need to be closely monitored to avoid a resurgence in infections and renewed pressure on health services.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/02/23/2021.02.18.21251973.full.pdf; doi:https://doi.org/10.1101/2021.02.18.21251973; html:https://europepmc.org/article/PPR/PPR287082; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR287082&type=FILE&fileName=EMS117383-pdf.pdf&mimeType=application/pdf
+PPR626309,https://doi.org/10.21203/rs.3.rs-2573712/v1,How much did the Covid-19 shielding policy cost in Wales? A Retrospective Cost analysis within the EVITE Immunity study,"Sewell B, Farr A, Akbari A, Carson-Stevens A, Edwards A, Evans BA, John A, Torabi F, Dale J, Jolles S, Kingston MR, Lyons J, Lyons RA, Porter A, Watkins A, Williams V, Snooks H.",,No Journal Info,2023,2023-03-06,Y,,,,"<h4>Background: </h4> The EVITE Immunity study investigates the effects of shielding Clinically Extremely Vulnerable (CEV) people during the COVID-19 pandemic on health outcomes and healthcare costs in Wales, UK, to help prepare for future pandemics. Shielding was intended to protect those at highest risk of serious harm from COVID-19. We report the cost of implementing shielding in Wales. <h4>Methods:</h4> The number of people shielding was extracted from the Secure Anonymised Information Linkage Databank. Resources supporting shielding between March and June 2020 were mapped using published reports, web pages, freedom of information requests to Welsh Government and personal communications (e.g. the office of the Chief Medical Officer for Wales). <h4>Results:</h4> At the beginning of shielding, 117,415 people were on the shielding list. The total additional cost to support those advised to stay home during the initial 14 weeks of the pandemic was £13,307,654 (£113 per person shielded). This included the new resources required to compile the shielding list, inform CEV people of the shielding intervention and provide medicine and food deliveries. The list was adjusted weekly over the 3-month period (130,000 people identified by June 2020) therefore the cost per person shielded lies between £102 and £113. <h4>Conclusion:</h4> This is the first evaluation of the cost of the measures put in place to support those identified to shield in Wales. However, no data on opportunity cost was available. The true cost of shielding including its budget impact and opportunity costs need to be investigated to decide whether shielding is a worthwhile policy for future health emergencies.",,pdf:https://www.researchsquare.com/article/rs-2573712/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-2573712/v1; html:https://europepmc.org/article/PPR/PPR626309; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR626309&type=FILE&fileName=EMS171864-pdf.pdf&mimeType=application/pdf
 PPR166764,https://doi.org/10.1101/2020.05.20.20107904,Coronavirus (COVID-19) infection in children at a specialist centre: outcome and implications of underlying ‘high-risk’ comorbidities in a paediatric population,"Issitt R, Booth J, Bryant W, Spiridou A, Taylor A, du Pré P, Ramnarayan P, Hartley J, Cortina-Borja M, Moshal K, Dunn H, Hemingway H, Sebire N.",,No Journal Info,2020,2020-05-25,Y,,,,"<h4>Background</h4> There is evolving evidence of significant differences in severity and outcomes of coronavirus disease 2019 (COVID-19) in children compared to adults. Underlying medical conditions associated with increased risk of severe disease are based on adult data, but have been applied across all ages resulting in large numbers of families undertaking social ‘shielding’ (vulnerable group). We conducted a retrospective analysis of children with suspected COVID-19 at a Specialist Children’s Hospital to determine outcomes based on COVID-19 testing status and underlying health vulnerabilities. <h4>Methods</h4> Routine clinical data were extracted retrospectively from the Institution’s Electronic Health Record system and Digital Research Environment for patients with suspected and confirmed COVID-19 diagnoses. Data were compared between Sars-CoV-2 positive and negative patients (CoVPos / CoVNeg respectively), and in relation to presence of underlying health vulnerabilities based on Public Health England guidance. <h4>Findings</h4> Between 1 st March and 15 th May 2020, 166 children (<18 years of age) presented to a specialist children’s hospital with clinical features of possible COVID-19 infection. 65 patients (39.2%) tested positive for SARS-CoV-2 virus. CoVPos patients were older (median 9 [0.9 - 14] years vs median 1 [0.1 - 5.7.5] years respectively, p <0.001). There was a significantly reduced proportion of vulnerable cases (47.7% vs 72.3%, p =0.002), but no difference in proportion of vulnerable patients requiring ventilation (61% vs 64.3%, p = 0.84) between CoVPos and CoVNeg groups. However, a significantly lower proportion of CoVPos patients required mechanical ventilation support compared to CoVNeg patients (27.7 vs 57.4%, p <0.001). Mortality was not significantly different between CoVPos and CoVNeg groups (1.5 vs 4% respectively, p =0.67) although there were no direct COVID-19 related deaths in this highly preselected paediatric population. <h4>Interpretation</h4> COVID-19 infection may be associated with severe disease in childhood presenting to a specialist hospital, but does not appear significantly different in severity to other causes of similar clinical presentations. In children presenting with pre-existing ‘COVID-19 vulnerable’ medical conditions at a specialist centre, there does not appear to be significantly increased risk of either contracting COVID-19 or severe complications, apart from those undergoing chemotherapy, who are over-represented.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/05/25/2020.05.20.20107904.full.pdf; doi:https://doi.org/10.1101/2020.05.20.20107904; html:https://europepmc.org/article/PPR/PPR166764; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR166764&type=FILE&fileName=EMS91012-pdf.pdf&mimeType=application/pdf
 PPR487927,https://doi.org/10.1101/2022.05.03.22274602,Accident and emergency (AE) attendance in England following infection with SARS-CoV-2 Omicron or Delta,"Grint DJ, Wing K, Gibbs HP, Evans SJ, Williamson E, Bhaskaran K, McDonald HI, Walker AJ, Evans D, Hickman G, Mathur R, Schultze A, Rentsch CT, Tazare J, Douglas IJ, Curtis HJ, Morton CE, Bacon S, Davy S, MacKenna B, Inglesby P, Croker R, Parry J, Hester F, Harper S, DeVito NJ, Hulme W, Bates C, Cockburn J, Mehrkar A, Goldacre B, Eggo RM, Tomlinson L.",,No Journal Info,2022,2022-05-03,Y,,,,"The SARS-CoV-2 Omicron variant is increasing in prevalence around the world. Accurate estimation of disease severity associated with Omicron is critical for pandemic planning. We found lower risk of accident and emergency (AE) attendance following SARS-CoV-2 infection with Omicron compared to Delta (HR: 0.39 (95% CI: 0.30 – 0.51; P<.0001). For AE attendances that lead to hospital admission, Omicron was associated with an 85% lower hazard compared with Delta (HR: 0.14 (95% CI: 0.09 – 0.24; P<.0001)). <h4>Conflicts of Interests</h4> Nothing to declare. <h4>Funding statement</h4> This work was supported by the Medical Research Council MR/V015737/1. TPP provided technical expertise and infrastructure within their data centre pro bono in the context of a national emergency. Rosalind Eggo is funded by HDR UK (grant: MR/S003975/1), MRC (grant: MC_PC 19065), NIHR (grant: NIHR200908).",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/05/03/2022.05.03.22274602.full.pdf; doi:https://doi.org/10.1101/2022.05.03.22274602; html:https://europepmc.org/article/PPR/PPR487927; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR487927&type=FILE&fileName=EMS144768-pdf.pdf&mimeType=application/pdf
 PPR496331,https://doi.org/10.1101/2022.05.09.22274846,"Assessing the impacts of timing on the health benefits, cost-effectiveness and relative affordability of COVID-19 vaccination programmes in 27 African Countries","Liu Y, Pearson CA, Madriz Montero A, Torres-Rueda S, Asfaw E, Uzochukwu B, Drake T, Bergren E, Eggo RM, Ruiz F, Ndembi N, Nonvignon J, Jit M, Vassall A.",,No Journal Info,2022,2022-05-10,Y,,,,"<h4>Background</h4> The COVID-19 vaccine supply shortage in 2021 constrained rollout efforts in Africa while populations experienced waves of epidemics. As supply picks up, a key question becomes if vaccination remains an impactful and cost-effective strategy given changes in the timing of implementation. <h4>Methods</h4> We assessed the impact of timing using an epidemiological and economic model. We fitted our mathematical epidemiological model to reported COVID-19 deaths in 27 African countries to estimate the existing immunity (resulting from infection) before substantial vaccine rollout. We then projected health outcomes for different programme start dates (2021-01-01 to 2021-12-01, n = 12) and roll-out rates (slow, medium, fast; 275, 826, and 2066 doses/ million population-day, respectively) for viral vector and mRNA vaccines. Rollout rates used were derived from observed uptake trajectories. We collected data on vaccine delivery costs by country income group. Lastly, we calculated incremental cost-effectiveness ratios and relative affordability. <h4>Findings</h4> Vaccination programmes with early start dates incur the most health benefits and are most cost-effective. While incurring the most health benefits, fast vaccine roll-outs are not always the most cost-effective. At a willingness-to-pay threshold of 0.5xGDP per capita, vaccine programmes starting in August 2021 using mRNA and viral vector vaccines were cost-effective in 6-10 and 17-18 of 27 countries, respectively. <h4>Interpretation</h4> African countries with large proportions of their populations unvaccinated by late 2021 may find vaccination programmes less cost-effective than they could have been earlier in 2021. Lower vaccine purchasing costs and/or the emergence of new variants may improve cost-effectiveness. <h4>Funding</h4> Bill and Melinda Gates Foundation, World Health Organization, National Institute of Health Research (UK), Health Data Research (UK)",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/05/10/2022.05.09.22274846.full.pdf; doi:https://doi.org/10.1101/2022.05.09.22274846; html:https://europepmc.org/article/PPR/PPR496331; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR496331&type=FILE&fileName=EMS149567-pdf.pdf&mimeType=application/pdf
 PPR301060,https://doi.org/10.1101/2021.03.20.21254010,Older biological age 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.",,No Journal Info,2021,2021-03-22,Y,,,,"<h4>Background</h4> Older chronological age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain, however, whether older biological age, as assessed by leucocyte telomere length (LTL), is also associated with COVID-19 outcomes. <h4>Methods</h4> 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 131 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. <h4>Findings</h4> Of 6,775 participants in UKB who had 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 1·05-1·31; P=0·004) per 1-SD shorter usual LTL, after adjustment for chronological 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. <h4>Interpretation</h4> Shorter LTL, indicative of older biological age, is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including chronological age. Further data are needed to determine whether this association reflects causality. <h4>Funding</h4> UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/03/22/2021.03.20.21254010.full.pdf; doi:https://doi.org/10.1101/2021.03.20.21254010; html:https://europepmc.org/article/PPR/PPR301060; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR301060&type=FILE&fileName=EMS120573-pdf.pdf&mimeType=application/pdf
 PPR293368,https://doi.org/10.1101/2021.03.03.21252856,REACT-1 round 9 final report: Continued but slowing decline of prevalence of SARS-CoV-2 during national lockdown in England in February 2021,"Riley S, Wang H, Eales O, Haw D, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,No Journal Info,2021,2021-03-06,Y,,,,"<h4>Background</h4> England will start to exit its third national lockdown in response to the COVID-19 pandemic on 8th March 2021, with safe effective vaccines being rolled out rapidly against a background of emerging transmissible and immunologically novel variants of SARS-CoV-2. A subsequent increase in community prevalence of infection could delay further relaxation of lockdown if vaccine uptake and efficacy are not sufficiently high to prevent increased pressure on healthcare services. <h4>Methods</h4> The PCR self-swab arm of the REal-time Assessment of Community Transmission Study (REACT-1) estimates community prevalence of SARS-CoV-2 infection in England based on random cross-sections of the population ages five and over. Here, we present results from the complete round 9 of REACT-1 comprising round 9a in which swabs were collected from 4th to 12th February 2021 and round 9b from 13th to 23rd February 2021. We also compare the results of REACT-1 round 9 to round 8, in which swabs were collected mainly from 6th January to 22nd January 2021. <h4>Results</h4> Out of 165,456 results for round 9 overall, 689 were positive. Overall weighted prevalence of infection in the community in England was 0.49% (0.44%, 0.55%), representing a fall of over two thirds from round 8. However the rate of decline of the epidemic has slowed from 15 (13, 17) days, estimated for the period from the end of round 8 to the start of round 9, to 31 days estimated using data from round 9 alone (lower confidence limit 17 days). When comparing round 9a to 9b there were apparent falls in four regions, no apparent change in one region and apparent rises in four regions, including London where there was a suggestion of sub-regional heterogeneity in growth and decline. Smoothed prevalence maps suggest large contiguous areas of growth and decline that do not align with administrative regions. Prevalence fell by 50% or more across all age groups in round 9 compared to round 8, with prevalence (round 9) ranging from 0.21% in those aged 65 and over to 0.71% in those aged 13 to 17 years. Round 9 prevalence was highest among Pakistani participants at 2.1% compared to white participants at 0.45% and Black participants at 0.83%. There were higher adjusted odds of infection for healthcare and care home workers, for those working in public transport and those working in education, school, nursery or childcare and lower adjusted odds for those not required to work outside the home. <h4>Conclusions</h4> Community prevalence of swab-positivity has declined markedly between January and February 2021 during lockdown in England, but remains high; the rate of decline has slowed in the most recent period, with a suggestion of pockets of growth. Continued adherence to social distancing and public health measures is required so that infection rates fall to much lower levels. This will help to ensure that the benefits of the vaccination roll-out programme in England are fully realised.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/03/06/2021.03.03.21252856.full.pdf; doi:https://doi.org/10.1101/2021.03.03.21252856; html:https://europepmc.org/article/PPR/PPR293368; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR293368&type=FILE&fileName=EMS118777-pdf.pdf&mimeType=application/pdf
-PPR683852,https://doi.org/10.21203/rs.3.rs-3054644/v1,Implementing Germ Defence digital behaviour change intervention via all primary care practices in England to reduce respiratory infections during the COVID-19 pandemic: an efficient cluster randomised controlled trial using the OpenSAFELY platform.,"Ainsworth B, Horwood J, Walter SR, Miller S, Chalder M, De Vocht F, Denison-Day J, Elwenspoek M, Curtis H, Bates C, Mehrkar A, Bacon S, Goldacre B, Collaborative TO, Craggs P, Amlot R, Francis N, Little P, MacLeod J, Moore M, Morton K, Rice C, Sterne J, Stuart B, Towler L, Willcox M, Yardley L.",,No Journal Info,2023,2023-06-29,Y,,,,"<h4>Background: </h4> Germ Defence (www.germdefence.org) is an evidence-based interactive website that promotes behaviour change for infection control within households. To maximise the potential of Germ Defence to effectively reduce the spread of COVID-19 the intervention needed to be implemented at scale rapidly.  <h4>Methods: </h4>: With the approval of NHS England, we implemented an efficient two-arm (1:1 ratio) cluster randomised controlled trial (RCT) to examine the effectiveness of randomising implementation of Germ Defence via GP practices across England, UK, compared with usual care. GP practices randomised to the intervention arm (n=3292) were emailed and asked to disseminate the Germ Defence intervention to all adult patients via mobile phone text, email or social media. GP practices randomised to the usual care arm (n=3287) maintained standard management for the 4-month trial period after and then asked to share Germ Defence with their adult patients. The primary outcome was the rate of GP presentations for respiratory tract infections (RTI) per patient. Secondary outcomes comprised rates of acute RTIs, confirmed COVID-19 diagnoses, suspected COVID-19 diagnoses, COVID-19 symptoms, gastrointestinal infection diagnoses, antibiotic usage, hospital admissions. The impact of the intervention on outcome rates was assessed using negative binomial regression modelling within the OpenSAFELY platform. The uptake of intervention by GP practice, and by patients were measured via website analytics.  <h4>Results: </h4>: Germ Defence was used 310,731 times. The average satisfaction score after using the website was 7.52 (0-10 not at all to very satisfied, N = 9933). There was no evidence of a difference in the rate of RTIs between intervention and control practices (rate ratio (RR) 1.01, 95%CI 0.96, 1.06, p=0.70). This was similar to all other eight health outcomes. Patient engagement within intervention arm practices ranged from 0- 48% of a practice list. Practices with high levels of intervention uptake (>11%) had a lower proportion of minority ethnic groups.  <h4>Conclusions: </h4>: We demonstrated that rapid large-scale implementation of a digital behavioural intervention can be evaluated with a novel efficient prospective RCT methodology analysing routinely collected patient data entirely within a trusted research environment.  Trial registration: This trial was registered in the ISRCTN registry (14602359) on 12 August 2020.",,pdf:https://www.researchsquare.com/article/rs-3054644/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-3054644/v1; html:https://europepmc.org/article/PPR/PPR683852; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR683852&type=FILE&fileName=EMS178343-pdf.pdf&mimeType=application/pdf
 PPR277515,https://doi.org/10.1101/2021.02.01.21250839,Extremely high SARS-CoV-2 seroprevalence in a strictly-Orthodox Jewish community in the UK,"Gaskell KM, Johnson M, Gould V, Hunt A, Stone NR, Waites W, Kasstan B, Chantler T, Lal S, Roberts Ch, Goldblatt D, Eggo RM, Marks M.",,No Journal Info,2021,2021-02-03,Y,,,,"<h4>Background</h4> Ethnic and religious minorities have been disproportionately affected by SARS-CoV-2 worldwide. The UK strictly-Orthodox Jewish community has been severely affected by the pandemic. This group shares characteristics with other ethnic minorities including larger family sizes, higher rates of household crowding and relative socioeconomic deprivation. We studied a UK strictly-Orthodox Jewish population to understand how COVID-19 had spread within this community. <h4>Methods</h4> We performed a household-focused cross-sectional SARS-CoV-2 serosurvey specific to three antigen targets. Randomly-selected households completed a standardised questionnaire and underwent serological testing with a multiplex assay for SARS-CoV-2 IgG antibodies. We report clinical illness and testing before the serosurvey, seroprevalence stratified by age and gender. We used random-effects models to identify factors associated with infection and antibody titres. <h4>Findings</h4> A total of 343 households, consisting of 1,759 individuals, were recruited. Serum was available for 1,242 participants. The overall seroprevalence for SARS-CoV-2 was 64.3% (95% CI 61.6-67.0%). The lowest seroprevalence was 27.6% in children under 5 years and rose to 73.8% in secondary school children and 74% in adults. Antibody titres were higher in symptomatic individuals and declined over time since reported COVID-19 symptoms, with the decline more marked for nucleocapsid titres. <h4>Interpretation</h4> In this tight-knit religious minority population in the UK, we report one of the highest SARS-CoV-2 seroprevalence levels in the world to date. In the context of this high force of infection, all age groups experienced a high burden of infection. Actions to reduce the burden of disease in this and other minority populations are urgently required. <h4>Funding</h4> This work was jointly funded by UKRI and NIHR [COV0335; MR/V027956/1], a donation from the LSHTM Alumni COVID-19 response fund, HDR UK, the MRC and the Wellcome Trust. The funders had no role in the design, conduct or analysis of the study or the decision to publish. The authors have no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. <h4>Research In Context</h4> <h4>Evidence before the study</h4> In January 2020, we searched PubMed for articles on rates of SARS-CoV-2 infection amongst ethnic minority groups and amongst the Jewish population. Search teams included “COVID-19”, “SARS-CoV-2”, seroprevalence, “ethnic minority”, and “Jewish” with no language restrictions. We also searched UK government documents on SARS-CoV-2 infection amongst minority groups. By January 2020, a large number of authors had reported that ethnic minority groups experienced higher numbers of cases and increased hospitalisations due to COVID-19. A small number of articles provided evidence that strictly-Orthodox Jewish populations had experienced a high rate of SARS-CoV-2 infection but extremely limited data was available on overall population level rates of infection amongst specific ethnic minority population groups. There was also extremely limited data on rates of infection amongst young children from ethnic minority groups. <h4>Added value of the study</h4> We report findings from a population representative, household survey of SARS-CoV-2 infection amongst a UK strictly Orthodox Jewish population. We demonstrate an extremely high seroprevalence rate of SARS-CoV-2 in this population which is more than five times the estimated seroprevalence nationally and five times the estimated seroprevalence in London. In addition the large number of children in our survey, reflective of the underlying population structure, allows us to demonstrate that in this setting there is a significant burden of disease in all age groups with secondary school aged children having an equivalent seroprevalence to adults. <h4>Implications of the available evidence</h4> Our data provide clear evidence of the markedly disproportionate impact of SARS-CoV-2 in minority populations. In this setting infection occurs at high rates across all age groups including pre-school, primary school and secondary school-age children. Contextually appropriate measures to specifically reduce the impact of SARS-CoV-2 amongst minority populations are urgently required.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/02/03/2021.02.01.21250839.full.pdf; doi:https://doi.org/10.1101/2021.02.01.21250839; html:https://europepmc.org/article/PPR/PPR277515; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR277515&type=FILE&fileName=EMS115861-pdf.pdf&mimeType=application/pdf
+PPR683852,https://doi.org/10.21203/rs.3.rs-3054644/v1,Implementing Germ Defence digital behaviour change intervention via all primary care practices in England to reduce respiratory infections during the COVID-19 pandemic: an efficient cluster randomised controlled trial using the OpenSAFELY platform.,"Ainsworth B, Horwood J, Walter SR, Miller S, Chalder M, De Vocht F, Denison-Day J, Elwenspoek M, Curtis H, Bates C, Mehrkar A, Bacon S, Goldacre B, Collaborative TO, Craggs P, Amlot R, Francis N, Little P, MacLeod J, Moore M, Morton K, Rice C, Sterne J, Stuart B, Towler L, Willcox M, Yardley L.",,No Journal Info,2023,2023-06-29,Y,,,,"<h4>Background: </h4> Germ Defence (www.germdefence.org) is an evidence-based interactive website that promotes behaviour change for infection control within households. To maximise the potential of Germ Defence to effectively reduce the spread of COVID-19 the intervention needed to be implemented at scale rapidly.  <h4>Methods: </h4>: With the approval of NHS England, we implemented an efficient two-arm (1:1 ratio) cluster randomised controlled trial (RCT) to examine the effectiveness of randomising implementation of Germ Defence via GP practices across England, UK, compared with usual care. GP practices randomised to the intervention arm (n=3292) were emailed and asked to disseminate the Germ Defence intervention to all adult patients via mobile phone text, email or social media. GP practices randomised to the usual care arm (n=3287) maintained standard management for the 4-month trial period after and then asked to share Germ Defence with their adult patients. The primary outcome was the rate of GP presentations for respiratory tract infections (RTI) per patient. Secondary outcomes comprised rates of acute RTIs, confirmed COVID-19 diagnoses, suspected COVID-19 diagnoses, COVID-19 symptoms, gastrointestinal infection diagnoses, antibiotic usage, hospital admissions. The impact of the intervention on outcome rates was assessed using negative binomial regression modelling within the OpenSAFELY platform. The uptake of intervention by GP practice, and by patients were measured via website analytics.  <h4>Results: </h4>: Germ Defence was used 310,731 times. The average satisfaction score after using the website was 7.52 (0-10 not at all to very satisfied, N = 9933). There was no evidence of a difference in the rate of RTIs between intervention and control practices (rate ratio (RR) 1.01, 95%CI 0.96, 1.06, p=0.70). This was similar to all other eight health outcomes. Patient engagement within intervention arm practices ranged from 0- 48% of a practice list. Practices with high levels of intervention uptake (>11%) had a lower proportion of minority ethnic groups.  <h4>Conclusions: </h4>: We demonstrated that rapid large-scale implementation of a digital behavioural intervention can be evaluated with a novel efficient prospective RCT methodology analysing routinely collected patient data entirely within a trusted research environment.  Trial registration: This trial was registered in the ISRCTN registry (14602359) on 12 August 2020.",,pdf:https://www.researchsquare.com/article/rs-3054644/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-3054644/v1; html:https://europepmc.org/article/PPR/PPR683852; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR683852&type=FILE&fileName=EMS178343-pdf.pdf&mimeType=application/pdf
 PPR435279,https://doi.org/10.1101/2021.12.20.21268098,"Therapies for Long COVID in non-hospitalised individuals - from symptoms, patient-reported outcomes, and immunology to targeted therapies (The TLC Study): Study protocol","Haroon S, Nirantharakumar K, Hughes SE, Subramanian A, Aiyegbusi OL, Davies EH, Myles P, Williams T, Turner GM, Chandan JS, McMullan C, Lord J, Wraith D, McGee K, Denniston A, Taverner T, Jackson L, Sapey E, Gkoutos G, Gokhale K, Leggett E, Iles C, Frost C, McNamara G, Bamford A, Marshall T, Zemedikun D, 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.",,No Journal Info,2021,2021-12-21,Y,,,,"<h4>Introduction</h4> 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. <h4>Methods and analysis</h4> 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 (CPRD) 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 one year. Statistical clustering methods will be used to identify distinct Long COVID symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear sub-study which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy. We will review existing evidence on interventions for post-viral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulated 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. <h4>Ethics and dissemination</h4> Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). The study is registered on the ISRCTN Registry (1567490). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers. <h4>Article Summary</h4> <h4>Strengths and limitations of the study</h4> The study will generate a nationally representative cohort of individuals with Long COVID recruited from primary care. We will recruit controls matched on a wide range of demographic and clinical factors to assess differences in symptoms between people with Long COVID and similar individuals without a history of COVID-19. We will use a newly developed electronic patient reported outcome measure (Symptom Burden Questionnaire™) for Long COVID to comprehensively assess a wide range of symptoms highlighted by existing literature, patients, and clinicians. Immunological, proteomic, genetic, and wearable data captured in the study will allow deep phenotyping of Long COVID syndromes to help better target therapies. A limitation is that a significant proportion of non-hospitalised individuals affected by COVID-19 in the first wave of the pandemic will lack confirmatory testing and will be excluded from recruitment to the study.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/12/21/2021.12.20.21268098.full.pdf; doi:https://doi.org/10.1101/2021.12.20.21268098; html:https://europepmc.org/article/PPR/PPR435279; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR435279&type=FILE&fileName=EMS141852-pdf.pdf&mimeType=application/pdf
 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
 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,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Conclusions</h4> 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. <h4>Funding</h4> Medical Research Council and NIHR (Grant ref: MC_PC_19056). <h4>Trial registrations</h4> The trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ).",,pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022926?articleTools=true; 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
@@ -220,12 +220,12 @@ PPR450835,https://doi.org/10.1101/2022.02.04.22270426,Appropriately smoothing pr
 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,,,,"<h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Findings</h4> 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. <h4>Interpretation</h4> 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. <h4>Funding</h4> None. <h4>Research in context</h4> <h4>Evidence before this study</h4> 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. <h4>Added value of this study</h4> 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. <h4>Implications of all the available evidence</h4> 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.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/06/07/2023.06.06.23290826.full.pdf; 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
 PPR211110,https://doi.org/10.1101/2020.09.05.20188821,Ethnicity and clinical outcomes in COVID-19: A Systematic Review and Meta-analysis,"Sze S, Pan D, Gray LJ, Nevill CR, Martin CA, Nazareth J, Minhas JS, Divall P, Khunti K, Abrams KR, Nellums LB, Pareek M.",,No Journal Info,2020,2020-09-08,N,,,,"<h4>ABSTRACT</h4> <h4>Importance</h4> The association of ethnicity with outcomes in patients with COVID-19 is unclear. <h4>Objective</h4> To determine whether the risk of SARS-CoV-2 infection, COVID-19 intensive care unit (ICU) admission and mortality are associated with ethnicity. <h4>Data Sources</h4> We searched all English language articles published 1 st December 2019 - 30 th June 2020 within MEDLINE, EMBASE, PROSPERO and the Cochrane library using indexing terms for COVID-19 and ethnicity, as well as manuscripts awaiting peer review on MedRxiv during the same period. <h4>Study Selection</h4> Included studies reported original clinical data, disaggregated by ethnicity, on patients with confirmed or suspected COVID-19. We excluded correspondence, area level, modelling and basic science articles. Two independent reviewers screened articles for inclusion. Of 926 identified articles, 35 were included in the meta-analyses. <h4>Data Extraction and Synthesis</h4> The review was conducted according to PRISMA guidelines. Reviewers independently extracted data using a piloted form on: (1) rates of infection, ICU admission and mortality by ethnicity; and (2) unadjusted and adjusted data comparing ethnic minority and White groups. Data were pooled using random effects models. <h4>Main Outcomes and Measures</h4> Outcomes were: (1) infection with SARS-CoV-2 confirmed on molecular testing; (2) ICU admission; and (3) mortality in COVID-19 confirmed and suspected cases. <h4>Results</h4> 13,535,562 patients from 35 studies were included in the meta-analyses. Black, Asian and Hispanic individuals had a greater risk of infection compared to White individuals (Black: pooled adjusted RR: 2.06, 95% CI: 1.59-2.67; Asian: 1.35, 95%CI: 1.15-1.59; Hispanic: 1.77, 95% CI: 1.39-2.25). Black individuals were significantly more likely to be admitted to ICU than White individuals (pooled adjusted RR: 1.61, 95% CI: 1.02-2.55). Risk of mortality was similar across ethnicities among hospitalised patients, but increased among Asian and Mixed ethnic groups in the general population. <h4>Conclusions</h4> Black, Asian and Hispanic ethnic groups are at increased risk of SARS-CoV-2 infection. Black individuals may be more likely to require ICU admission for COVID-19. There may also be disparities in risk of death from COVID-19 at a population level. Our findings are of critical public health importance and should inform policy on minimising SARS-CoV-2 exposure in ethnic minority groups. <h4>KEY POINTS</h4> <h4>Question</h4> Is ethnicity associated with vulnerability to, and outcomes from, coronavirus disease 2019 (COVID-19)? <h4>Findings</h4> In this systematic review and meta-analysis, rates of infection and outcomes from COVID-19 were compared between ethnic groups. Individuals from Black, Asian and Hispanic ethnicity were significantly more vulnerable to SARS-CoV-2 infection than those of White ethnicity. Black individuals were more likely to need intensive care unit (ICU) admission for COVID-19 than White individuals. Risk of mortality was similar across ethnicities among hospitalised patients, but increased among Asian and Mixed ethnic groups in the general population. <h4>Meaning</h4> There is strong evidence for an increased risk of SARS-CoV-2 infection amongst ethnic minorities, and targeted public health policies are required to reduce this risk.",,doi:https://doi.org/10.1016/j.eclinm.2020.100630; doi:https://doi.org/10.1101/2020.09.05.20188821; html:https://europepmc.org/article/PPR/PPR211110; doi:https://doi.org/10.1101/2020.09.05.20188821
 PPR318575,https://doi.org/10.21203/rs.3.rs-322366/v1,Within and between classroom transmission patterns of seasonal influenza and implications for pandemic management strategies at schools,"Endo A, Uchida M, Liu Y, Atkins K, Kucharski A, Funk S, CMMID COVID-19 Working Group.",,No Journal Info,2021,2021-03-23,Y,,,,"Schools can play a central role in driving infectious disease transmission. Strategies for safe operation of schools during pandemics therefore need to carefully consider both the efficiency of measures for infection control and the impact on children through lost face-to face schooling time. Heterogeneous social contact patterns associated with the social structures of schools (i.e. classes/grades) are likely to influence the within-school transmission dynamics; however, empirical evidence on the fine-scale transmission patterns between students has been limited. Using a mathematical model, we analysed a large-scale dataset of seasonal influenza outbreaks in Matsumoto city, Japan to infer social interactions within and between classes/grades from observed transmission patterns. The overall within-school reproduction number, which determines the initial growth of cases and the risk of sustained transmission, was only minimally associated with class sizes and the number of classes per grade. We then used these patterns in a model parameterised separately to COVID-19 and pandemic influenza, and simulated school outbreaks under multiple strategies for minimising the risk of within-school transmission. Simulations suggested that with such transmission patterns, interventions changing class structures (e.g. reduced class sizes) may not be effective in reducing the risk of major school outbreaks upon introduction of a case and that other precautionary measures (e.g. screening and isolation) need to be employed. Class-level closures in response to detection of a case were suggested to be effective in reducing the size of an outbreak when regular screening tests for students are not available.",,pdf:https://www.researchsquare.com/article/rs-322366/v1.pdf?c=1631894367000; doi:https://doi.org/10.21203/rs.3.rs-322366/v1; html:https://europepmc.org/article/PPR/PPR318575; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR318575&type=FILE&fileName=EMS123500-pdf.pdf&mimeType=application/pdf
-PPR703602,https://doi.org/10.1101/2023.08.02.23293505,COVID pandemic impact on hypertension management in North-East London: an observational cohort study using electronic health records,"Rison SC, Redfern O, Mathur R, Dostal I, Carvalho C, Raisi-Estabragh Z, Robson JP.",,No Journal Info,2023,2023-08-06,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> The COVID19 pandemic had a major impact on primary care management of long-term conditions such as hypertension. This observational cohort study of adults with hypertension registered in 193 primary care practices in North-East London between January 2019 and October 2022 investigated the impact of the COVID19 pandemic on the treatment and control of blood pressure including demographic and social inequities. <h4>Method and findings</h4> In 224,329 adults with hypertension, the proportion with a blood pressure (BP) recorded within the preceding 1 year fell from a 91% pre-pandemic peak to 62% at the end of the pandemic lock-down phase and improved to 77% by the end of the study. The proportion with controlled hypertension (<80 years old, BP ≤140/90mmHg; 80 or more years old: ≤150/90mmHg) for the same time points was 81%, 50% and 60% respectively. Using ‘blood pressure control’ (which considered only patients with a valid blood pressure recording) as the indicator attenuated the reduction to 83%, 80% and 78% respectively. The study used multivariable logistic analysis at four representative time points (Pre-pandemic: April 2019; Pre lockdown: April 2020; Lockdown: April 2021; Post-lockdown: April 2022) to identify temporal, clinical and demographic influences on blood pressure monitoring and control. Pre-pandemic inequities in the management of hypertension were not significantly altered by the pandemic. Throughout the pandemic phases, in comparison to the White ethnic group, the Black ethnic group was less likely to achieve blood pressure control (ORs 0.81 [95% CI = 0.78 to 0.85, p-value<0.001] to 0.87 [95% CI = 0.84 to 0.91, p-value<0.001]). Conversely, the Asian ethnic group was more likely to have controlled blood pressure (ORs 1.09 [95% CI = 1.05 to 1.14, p-value<0.001] to 1.28 [95% CI = 1.23 to 1.32, p-value<0.001]). Younger, male, more affluent individuals, individuals with unknown or unrecorded ethnicity or those untreated were less likely to have blood pressure controlled to target throughout the study. <h4>Conclusion</h4> The COVID pandemic had a greater impact on blood pressure recording than on blood pressure control. Although recording and control have improved, these had not returned to pre-pandemic levels by the end of the study period. Ethnic inequalities in blood pressure control persisted during the pandemic and remain outstanding.",,doi:https://doi.org/10.1101/2023.08.02.23293505; html:https://europepmc.org/article/PPR/PPR703602; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR703602&type=FILE&fileName=EMS184893-pdf.pdf&mimeType=application/pdf
 PPR393066,https://doi.org/10.1101/2021.09.02.21262480,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, Read JM, Cooper BS, Robotham JV, ISARIC4C Investigators, CMMID COVID-19 working group.",,No Journal Info,2021,2021-09-10,Y,,,,"<h4>Background</h4> SARS-CoV-2 spreads in hospitals, but the contribution of these settings to the overall COVID-19 burden at a national level is unknown. <h4>Methods</h4> We used comprehensive national English datasets and simulation modelling to determine the total burden (identified and unidentified) of symptomatic hospital-acquired infections. Those unidentified would either be 1) discharged before symptom onset (“missed”), or 2) have symptom onset 7 days or fewer from admission (“misclassified”). We estimated the contribution of “misclassified” cases and transmission from “missed” symptomatic infections to the English epidemic before 31st July 2020. <h4>Findings</h4> In our dataset of hospitalised COVID-19 patients in acute English Trusts with a recorded symptom onset date (n = 65,028), 7% were classified as hospital-acquired (with symptom onset 8 or more days after admission and before discharge). We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified. Misclassified cases and onward transmission from missed infections could account for 15% (mean, 95% range over 200 simulations: 14·1%-15·8%) of cases currently classified as community-acquired COVID-19. From this, 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. <h4>Conclusions</h4> Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the “first wave”, but fewer than 1% of all SARS-CoV-2 infections in England. Using symptom onset as a detection method for hospital-acquired SARS-CoV-2 likely misses a substantial proportion (>60%) of hospital-acquired infections. <h4>Funding</h4> National Institute for Health Research, UK Medical Research Council, Society for Laboratory Automation and Screening, UKRI, Wellcome Trust, Singapore National Medical Research Council. <h4>Research in context</h4> <h4>Evidence before this study</h4> We searched PubMed with the terms “((national OR country) AND (contribution OR burden OR estimates) AND (“hospital-acquired” OR “hospital-associated” OR “nosocomial”)) AND Covid-19” for articles published in English up to July 1st 2021. This identified 42 studies, with no studies that had aimed to produce comprehensive national estimates of the contribution of hospital settings to the COVID-19 pandemic. Most studies focused on estimating seroprevalence or levels of infection in healthcare workers only, which were not our focus. Removing the initial national/country terms identified 120 studies, with no country level estimates. Several single hospital setting estimates exist for England and other countries, but the percentage of hospital-associated infections reported relies on identified cases in the absence of universal testing. <h4>Added value of this study</h4> This study provides the first national-level estimates of all symptomatic hospital-acquired infections with SARS-CoV-2 in England up to the 31st July 2020. Using comprehensive data, we calculate how many infections would be unidentified and hence can generate a total burden, impossible from just notification data. Moreover, our burden estimates for onward transmission suggest the contribution of hospitals to the overall infection burden. <h4>Implications of all the available evidence</h4> Large numbers of patients may become infected with SARS-CoV-2 in hospitals though only a small proportion of such infections are identified. Further work is needed to better understand how interventions can reduce such transmission and to better understand the contributions of hospital transmission to mortality.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4666152/7/Knight_etal_2022_The-contribution-of-hospital-acquired.pdf; doi:https://doi.org/10.1101/2021.09.02.21262480; html:https://europepmc.org/article/PPR/PPR393066; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR393066&type=FILE&fileName=EMS134823-pdf.pdf&mimeType=application/pdf
+PPR703602,https://doi.org/10.1101/2023.08.02.23293505,COVID pandemic impact on hypertension management in North-East London: an observational cohort study using electronic health records,"Rison SC, Redfern O, Mathur R, Dostal I, Carvalho C, Raisi-Estabragh Z, Robson JP.",,No Journal Info,2023,2023-08-06,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> The COVID19 pandemic had a major impact on primary care management of long-term conditions such as hypertension. This observational cohort study of adults with hypertension registered in 193 primary care practices in North-East London between January 2019 and October 2022 investigated the impact of the COVID19 pandemic on the treatment and control of blood pressure including demographic and social inequities. <h4>Method and findings</h4> In 224,329 adults with hypertension, the proportion with a blood pressure (BP) recorded within the preceding 1 year fell from a 91% pre-pandemic peak to 62% at the end of the pandemic lock-down phase and improved to 77% by the end of the study. The proportion with controlled hypertension (<80 years old, BP ≤140/90mmHg; 80 or more years old: ≤150/90mmHg) for the same time points was 81%, 50% and 60% respectively. Using ‘blood pressure control’ (which considered only patients with a valid blood pressure recording) as the indicator attenuated the reduction to 83%, 80% and 78% respectively. The study used multivariable logistic analysis at four representative time points (Pre-pandemic: April 2019; Pre lockdown: April 2020; Lockdown: April 2021; Post-lockdown: April 2022) to identify temporal, clinical and demographic influences on blood pressure monitoring and control. Pre-pandemic inequities in the management of hypertension were not significantly altered by the pandemic. Throughout the pandemic phases, in comparison to the White ethnic group, the Black ethnic group was less likely to achieve blood pressure control (ORs 0.81 [95% CI = 0.78 to 0.85, p-value<0.001] to 0.87 [95% CI = 0.84 to 0.91, p-value<0.001]). Conversely, the Asian ethnic group was more likely to have controlled blood pressure (ORs 1.09 [95% CI = 1.05 to 1.14, p-value<0.001] to 1.28 [95% CI = 1.23 to 1.32, p-value<0.001]). Younger, male, more affluent individuals, individuals with unknown or unrecorded ethnicity or those untreated were less likely to have blood pressure controlled to target throughout the study. <h4>Conclusion</h4> The COVID pandemic had a greater impact on blood pressure recording than on blood pressure control. Although recording and control have improved, these had not returned to pre-pandemic levels by the end of the study period. Ethnic inequalities in blood pressure control persisted during the pandemic and remain outstanding.",,doi:https://doi.org/10.1101/2023.08.02.23293505; html:https://europepmc.org/article/PPR/PPR703602; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR703602&type=FILE&fileName=EMS184893-pdf.pdf&mimeType=application/pdf
 PPR466607,https://doi.org/10.1101/2022.03.07.22272026,"Trends, variation and clinical characteristics of recipients of antivirals and neutralising monoclonal antibodies for non-hospitalised COVID-19: a descriptive cohort study of 23.4 million people in OpenSAFELY","The OpenSAFELY Collaborative, Green A, Curtis HJ, Higgins R, Smith R, Mehrkar A, Inglesby P, Mahalingasivam V, Drysdale H, DeVito NJ, Croker R, Rentsch CT, Bhaskaran K, Andrews C, Bacon S, Davy S, Dillingham I, Evans D, Fisher L, Hickman G, Hopcroft L, Hulme WJ, Nab L, Massey J, McDonald O, Morley J, Morton CE, Park R, Walker AJ, Ward T, Wiedemann M, Bates C, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Evans SJ, Tomlinson L, MacKenna B, Goldacre B.",,No Journal Info,2022,2022-03-10,Y,,,,"<h4>ABSTRACT</h4> <h4>Objectives</h4> Ascertain patient eligibility status and describe coverage of antivirals and neutralising monoclonal antibodies (nMAB) as treatment for COVID-19 in community settings in England. <h4>Design</h4> Cohort study, approved by NHS England. <h4>Setting</h4> Routine clinical data from 23.4m people linked to data on COVID-19 infection and treatment, within the OpenSAFELY-TPP database. <h4>Participants</h4> Non-hospitalised COVID-19 patients at high-risk of severe outcomes. <h4>Interventions</h4> Nirmatrelvir/ritonavir (Paxlovid), sotrovimab, molnupiravir, casirivimab or remdesivir, administered in the community by COVID-19 Medicine Delivery Units. <h4>Results</h4> We identified 102,170 non-hospitalised patients with COVID-19 between 11 th December 2021 and 28 th April 2022 at high-risk of severe outcomes and therefore potentially eligible for antiviral and/or nMAB treatment. Of these patients, 18,210 (18%) received treatment; sotrovimab, 9,340 (51%); molnupiravir, 4,500 (25%); Paxlovid, 4,290 (24%); casirivimab, 50 (<1%); and remdesivir, 20 (<1%). The proportion of patients treated increased from 8% (180/2,380) in the first week of treatment availability to 22% (420/1870) in the latest week. The proportion treated varied by high risk group, lowest in those with Liver disease (12%; 95% CI 11 to 13); by treatment type, with sotrovimab favoured over molnupiravir/Paxlovid in all but three high risk groups: Down syndrome (36%; 95% CI 31 to 40), Rare neurological conditions (46%; 95% CI 44 to 48), and Primary immune deficiencies (49%; 95% CI 48 to 51); by ethnicity, from Black (10%; 95% CI 9 to 11) to White (18%; 95% CI 18 to 19); by NHS Region, from 11% (95% CI 10 to 12) in Yorkshire and the Humber to 23% (95% CI 22 to 24) in the East of England); and by deprivation level, from 12% (95% CI 12 to 13) in the most deprived areas to 21% (95% CI 21 to 22) in the least deprived areas. There was also lower coverage among unvaccinated patients (5%; 95% CI 4 to 7), those with dementia (5%; 95% CI 4 to 6) and care home residents (6%; 95% CI 5 to 6). <h4>Conclusions</h4> Using the OpenSAFELY platform we were able to identify patients who were potentially eligible to receive treatment and assess the coverage of these new treatments amongst these patients. Targeted activity may be needed to address apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, socioeconomically deprived areas, and care homes. <h4>What is already known about this topic</h4> Since the emergence of COVID-19, a number of approaches to treatment have been tried and evaluated. These have mainly consisted of treatments such as dexamethasone, which were used in UK hospitals,from early on in the pandemic to prevent progression to severe disease. Until recently (December 2021), no treatments have been widely used in community settings across England. <h4>What this study adds</h4> Following the rollout of antiviral medicines and neutralising monoclonal antibodies (nMABs) as treatment for patients with COVID-19, we were able to identify patients who were potentially eligible to receive antivirals or nMABs and assess the coverage of these new treatments amongst these patients, in as close to real-time as the available data flows would support. While the proportion of the potentially eligible patients receiving treatment increased over time, rising from 8% (180/2,380) in the first week of the roll out to 22% (420/1870) in the last week of April 2022, there were variations in coverage between key clinical, geographic, and demographic subgroup. <h4>How this study might affect research, practice, or policy</h4> Targeted activity may therefore be needed to address lower treatment rates observed among certain geographic areas and key groups including ethnic minorities, people living in areas of higher deprivation, and in care homes.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/06/01/2022.03.07.22272026.full.pdf; doi:https://doi.org/10.1101/2022.03.07.22272026; html:https://europepmc.org/article/PPR/PPR466607; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR466607&type=FILE&fileName=EMS145672-pdf.pdf&mimeType=application/pdf
 PPR341361,https://doi.org/10.1101/2021.05.13.21257146,Sociodemographic inequality in COVID-19 vaccination coverage amongst elderly adults in England: a national linked data study,"Nafilyan V, Dolby T, Razieh C, Gaughan C, Morgan J, Ayoubkhani D, Walker AS, Khunti K, Glickman M, Yates T.",,No Journal Info,2021,2021-05-17,Y,,,,"<h4>Objective</h4> To examine inequalities in COVID-19 vaccination rates amongst elderly adults in England <h4>Design</h4> Cohort study <h4>Setting</h4> People living in private households and communal establishments in England <h4>Participants</h4> 6,829,643 adults aged ≥ 70 years (mean 78.7 years, 55.2% female) who were alive on 15 March 2021. <h4>Main outcome measures</h4> Having received the first dose of a vaccine against COVID-19 by 15 March 2021. We calculated vaccination rates and estimated unadjusted and adjusted odds ratios using logistic regression models. <h4>Results</h4> By 15 March 2021, 93.2% of people living in England aged 70 years and over had received at least one dose of a COVID-19 vaccine. While vaccination rates differed across all factors considered apart from sex, the greatest disparities were seen between ethnic and religious groups. The lowest rates were in people of Black African and Black Caribbean ethnic backgrounds, where only 67.2% and 73.9% had received a vaccine, with adjusted odds of not being vaccinated at 5.01 (95% CI 4.86 - 5.16) and 4.85 (4.75 - 4.96) times greater than the White British group. The proportion of individuals self-identifying as Muslim and Buddhist who had received a vaccine was 79.1% and 84.1%, respectively. Older age, greater area deprivation, less advantaged socio-economic position (proxied by living in a rented home), being disabled and living either alone or in a multi-generational household were also associated with higher odds of not having received the vaccine. <h4>Conclusion</h4> People disproportionately affected seem most hesitant to COVID-19 vaccinations. Policy Interventions to improve these disparities are urgently needed. <h4>Summary Box</h4> <h4>What is already known on this subject?</h4> The UK began an ambitious vaccination programme to combat the COVID-19 pandemic on 8th December 2020. Existing evidence suggests that COVID-19 vaccination rates differ by level of area deprivation, ethnicity and certain underlying health conditions, such as learning disability and mental health problems. <h4>What does this study add?</h4> Our study shows that first dose vaccination rates in adults aged 70 or over differed markedly by ethnic group and self-reported religious affiliation, even after adjusting for geography, socio-demographic factors and underlying health conditions. Our study also highlights differences in vaccination rates by deprivation, household composition, and disability status, factors disproportionately associated with SARS-CoV-2 infection. Public health policy and community engagement aimed at promoting vaccination uptake is these groups are urgently needed. <h4>Strengths and limitations of this study</h4> Using nationwide linked population-level data from clinical records and the 2011 Census, we examined a wide range of socio-demographic characteristics not available n electronic health records Most demographic and socio-economic characteristics are derived from the 2011 Census and therefore are 10 years old. However, we focus primarily on characteristics that are unlikely to change over time, such as ethnicity or religion, or likely to be stable for our population Because the data are based on the 2011 Census, it excluded people living in England in 2011 but not taking part in the 2011 Census; respondents who could not be linked to the 2011-2013 NHS patients register; recent migrants. Consequently, we excluded 5.4% of vaccinated people who could not be linked",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e053402.full.pdf; doi:https://doi.org/10.1101/2021.05.13.21257146; html:https://europepmc.org/article/PPR/PPR341361; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR341361&type=FILE&fileName=EMS124797-pdf.pdf&mimeType=application/pdf
-PPR316137,https://doi.org/10.1101/2021.04.26.21255788,Ethnic differences in SARS-CoV-2 vaccine hesitancy in United Kingdom healthcare workers: Results from the UK-REACH prospective nationwide cohort study,"Woolf K, McManus IC, Martin CA, Nellums LB, Guyatt AL, Melbourne C, Bryant L, Gogoi M, Wobi F, Al-Oraibi A, Hassan O, 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,2021,2021-04-28,Y,,,,"<h4>Background</h4> In most countries, healthcare workers (HCWs) represent a priority group for vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) due to their elevated risk of COVID-19 and potential contribution to nosocomial SARS-CoV-2 transmission. Concerns have been raised that HCWs from ethnic minority groups are more likely to be vaccine hesitant (defined by the World Health Organisation as refusing or delaying a vaccination) than those of White ethnicity, but there are limited data on SARS-CoV-2 vaccine hesitancy and its predictors in UK HCWs. <h4>Methods</h4> Nationwide prospective cohort study and qualitative study in a multi-ethnic cohort of clinical and non-clinical UK HCWs. We analysed ethnic differences in SARS-CoV-2 vaccine hesitancy adjusting for demographics, vaccine trust, and perceived risk of COVID-19. We explored reasons for hesitancy in qualitative data using a framework analysis. <h4>Findings</h4> 11,584 HCWs were included in the cohort analysis. 23% (2704) reported vaccine hesitancy. Compared to White British HCWs (21.3% hesitant), HCWs from Black Caribbean (54.2%), Mixed White and Black Caribbean (38.1%), Black African (34.4%), Chinese (33.1%), Pakistani (30.4%), and White Other (28.7%) ethnic groups were significantly more likely to be hesitant. In adjusted analysis, Black Caribbean (aOR 3.37, 95% CI 2.11 - 5.37), Black African (aOR 2.05, 95% CI 1.49 - 2.82), White Other ethnic groups (aOR 1.48, 95% CI 1.19 - 1.84) were significantly more likely to be hesitant. Other independent predictors of hesitancy were younger age, female sex, higher score on a COVID-19 conspiracy beliefs scale, lower trust in employer, lack of influenza vaccine uptake in the previous season, previous COVID-19, and pregnancy. Qualitative data from 99 participants identified the following contributors to hesitancy: lack of trust in government and employers, safety concerns due to the speed of vaccine development, lack of ethnic diversity in vaccine studies, and confusing and conflicting information. Participants felt uptake in ethnic minority communities might be improved through inclusive communication, involving HCWs in the vaccine rollout, and promoting vaccination through trusted networks. <h4>Interpretation</h4> Despite increased risk of COVID-19, HCWs from some ethnic minority groups are more likely to be vaccine hesitant than their White British colleagues. Strategies to build trust and dispel myths surrounding the COVID-19 vaccine in these communities are urgently required. Public health communications should be inclusive, non-stigmatising and utilise trusted networks. <h4>Funding</h4> MRC-UK Research and Innovation (MR/V027549/1), the Department of Health and Social Care through the National Institute for Health Research (NIHR), and NIHR Biomedical Research Centres and NIHR Applied Research Collaboration East Midlands. <h4>Research in context</h4> <h4>Evidence before this study</h4> We searched Pubmed using the following search terms ((COVID-19).ti,ab OR (SARS-CoV-2).ti,ab) AND ((vaccine).ti,ab OR (vaccination).ti,ab OR (immunisation).ti,ab)) AND ((healthcare worker).ti,ab OR (health worker).ti,ab OR (doctor).ti,ab OR (nurse).ti,ab OR (healthcare professional).ti,ab)) AND ((hesitancy).ti,ab OR (refusal).ti,ab OR (uptake).ti,ab)). The search returned 60 results, of which 38 were excluded after title and abstract screening, 11 studies were not conducted in a population of healthcare workers, 20 did not present data on vaccine intention or uptake, 5 were related to vaccines other than the SARS-CoV-2 vaccine, 1 was unrelated to vaccination and 1 had been withdrawn. The 22 remaining articles were survey studies focussed on SARS-CoV-2 vaccine intention in healthcare workers. Estimates of SARS-CoV-2 vaccine acceptance varied widely from 27·7% - 94·5% depending on the country in which the study was performed, and the occupational group studied. Only 2 studies (both conducted in the USA) had a sample size greater than 10,000. Most studies found females, non-medical healthcare staff and those refusing influenza vaccine to be more likely to be hesitant. There was conflicting evidence about the effects of age and previous COVID-19 on hesitancy. Only 3 studies (all from the USA), presented data disaggregated by ethnicity, all finding Black ethnic HCWs were most likely to be hesitant. Common themes amongst studies that investigated reasons for vaccine hesitancy were concerns about safety of vaccines, fear of side effects and short development timeframes. We did not find any studies on SARS-CoV-2 vaccine hesitancy in UK healthcare workers in the published literature. <h4>Added value of this study</h4> This study is amongst the largest SARS-CoV-2 vaccine hesitancy studies in the literature. It is the largest study outside the USA and is the only study in UK HCWs. Our work focusses on the association of ethnicity with vaccine hesitancy, and we are the first study outside the USA to present results by ethnic group. The large number of ethnic minority HCWs in our study allows for examination of the outcome by more granular ethnicity categories than have previously been studied, allowing us to detect important differences in vaccine hesitancy levels within the broad White and Asian ethnic groupings. Our large sample size and the richness of our cohort study dataset allows us to control for many potential confounders in our multivariable analysis, and provide novel data on important potential drivers of hesitancy including discrimination, COVID-19 conspiracy beliefs, religion/religiosity and personality traits. Additionally, we combine quantitative with qualitative data providing a deeper understanding of the drivers of hesitancy and potential strategies to improve vaccine uptake in HCWs from ethnic minority communities. <h4>Implications of all the available evidence</h4> Around a quarter of UK healthcare workers reported SARS-CoV-2 vaccine hesitancy. In accordance with previous studies in other countries, we determined that female sex and lack of influenza vaccine in the previous season were important predictors of SARS-CoV-2 vaccine hesitancy in UK HCWs, although in contrast to most studies in the published literature, after adjustment we do not demonstrate differences in hesitancy levels by occupational role. Importantly, previous literature provides conflicting evidence of the effects of age and previous SARS-CoV-2 infection on vaccine hesitancy. In our study, younger HCWs and those with evidence of previous COVID-19 were more likely to be hesitant. This study provides novel data on increased hesitancy levels within Black Caribbean, Mixed White and Black Caribbean, Black African, Chinese, Pakistani and White Other ethnic groups. Mistrust (of vaccines in general, in SARS-CoV-2 vaccines specifically, in healthcare systems and research) and misinformation appear to be important drivers of hesitancy within HCWS in the UK. Our data indicate that despite facing an increased risk of COVID-19 compared to their White colleagues, UK HCWs from some ethnic minority groups continue to exhibit greater levels of SARS-CoV-2 vaccine hesitancy. This study provides policy makers with evidence to inform strategies to improve uptake.",,doi:https://doi.org/10.1016/j.lanepe.2021.100180; doi:https://doi.org/10.1101/2021.04.26.21255788; html:https://europepmc.org/article/PPR/PPR316137; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR316137&type=FILE&fileName=EMS123592-pdf.pdf&mimeType=application/pdf
 PPR230634,https://doi.org/10.1101/2020.10.25.20218875,"Baseline phenotype and 30-day outcomes of people tested for COVID-19: an international network cohort including >3.32 million people tested with real-time PCR and >219,000 tested positive for SARS-CoV-2 in South Korea, Spain and the United States","Golozar A, Lai LY, Sena AG, Vizcaya D, Schilling LM, Huser V, Nyberg F, Duvall SL, Morales DR, Alshammari TM, Abedtash H, Ahmed W, Alser O, Alghoul H, Zhang Y, Gong M, Guan Y, Areia C, Jonnagaddala J, Shah K, Lane JC, Prats-Uribe A, Posada JD, Shah NH, Subbian V, Zhang L, Fernandes Abrahão MT, Rijnbeek PR, You SC, Casajust P, Roel E, Recalde M, Fernández-Bertolín S, Andryc A, Thomas JA, Wilcox AB, Fortin S, Blacketer C, DeFalco F, Natarajan K, Falconer T, Spotnitz M, Ostropolets A, Hripcsak G, Suchard M, Lynch KE, Matheny ME, Williams A, Reich C, Duarte-Salles T, Kostka K, Ryan PB, Prieto-Alhambra D.",,No Journal Info,2020,2020-10-27,Y,,,,"<h4>ABSTRACT</h4> Early identification of symptoms and comorbidities most predictive of COVID-19 is critical to identify infection, guide policies to effectively contain the pandemic, and improve health systems’ response. Here, we characterised socio-demographics and comorbidity in 3,316,107persons tested and 219,072 persons tested positive for SARS-CoV-2 since January 2020, and their key health outcomes in the month following the first positive test. Routine care data from primary care electronic health records (EHR) from Spain, hospital EHR from the United States (US), and claims data from South Korea and the US were used. The majority of study participants were women aged 18-65 years old. Positive/tested ratio varied greatly geographically (2.2:100 to 31.2:100) and over time (from 50:100 in February-April to 6.8:100 in May-June). Fever, cough and dyspnoea were the most common symptoms at presentation. Between 4%-38% required admission and 1-10.5% died within a month from their first positive test. Observed disparity in testing practices led to variable baseline characteristics and outcomes, both nationally (US) and internationally. Our findings highlight the importance of large scale characterization of COVID-19 international cohorts to inform planning and resource allocation including testing as countries face a second wave.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605581; doi:https://doi.org/10.1101/2020.10.25.20218875; html:https://europepmc.org/article/PPR/PPR230634; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR230634&type=FILE&fileName=EMS101593-pdf.pdf&mimeType=application/pdf
+PPR316137,https://doi.org/10.1101/2021.04.26.21255788,Ethnic differences in SARS-CoV-2 vaccine hesitancy in United Kingdom healthcare workers: Results from the UK-REACH prospective nationwide cohort study,"Woolf K, McManus IC, Martin CA, Nellums LB, Guyatt AL, Melbourne C, Bryant L, Gogoi M, Wobi F, Al-Oraibi A, Hassan O, 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,2021,2021-04-28,Y,,,,"<h4>Background</h4> In most countries, healthcare workers (HCWs) represent a priority group for vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) due to their elevated risk of COVID-19 and potential contribution to nosocomial SARS-CoV-2 transmission. Concerns have been raised that HCWs from ethnic minority groups are more likely to be vaccine hesitant (defined by the World Health Organisation as refusing or delaying a vaccination) than those of White ethnicity, but there are limited data on SARS-CoV-2 vaccine hesitancy and its predictors in UK HCWs. <h4>Methods</h4> Nationwide prospective cohort study and qualitative study in a multi-ethnic cohort of clinical and non-clinical UK HCWs. We analysed ethnic differences in SARS-CoV-2 vaccine hesitancy adjusting for demographics, vaccine trust, and perceived risk of COVID-19. We explored reasons for hesitancy in qualitative data using a framework analysis. <h4>Findings</h4> 11,584 HCWs were included in the cohort analysis. 23% (2704) reported vaccine hesitancy. Compared to White British HCWs (21.3% hesitant), HCWs from Black Caribbean (54.2%), Mixed White and Black Caribbean (38.1%), Black African (34.4%), Chinese (33.1%), Pakistani (30.4%), and White Other (28.7%) ethnic groups were significantly more likely to be hesitant. In adjusted analysis, Black Caribbean (aOR 3.37, 95% CI 2.11 - 5.37), Black African (aOR 2.05, 95% CI 1.49 - 2.82), White Other ethnic groups (aOR 1.48, 95% CI 1.19 - 1.84) were significantly more likely to be hesitant. Other independent predictors of hesitancy were younger age, female sex, higher score on a COVID-19 conspiracy beliefs scale, lower trust in employer, lack of influenza vaccine uptake in the previous season, previous COVID-19, and pregnancy. Qualitative data from 99 participants identified the following contributors to hesitancy: lack of trust in government and employers, safety concerns due to the speed of vaccine development, lack of ethnic diversity in vaccine studies, and confusing and conflicting information. Participants felt uptake in ethnic minority communities might be improved through inclusive communication, involving HCWs in the vaccine rollout, and promoting vaccination through trusted networks. <h4>Interpretation</h4> Despite increased risk of COVID-19, HCWs from some ethnic minority groups are more likely to be vaccine hesitant than their White British colleagues. Strategies to build trust and dispel myths surrounding the COVID-19 vaccine in these communities are urgently required. Public health communications should be inclusive, non-stigmatising and utilise trusted networks. <h4>Funding</h4> MRC-UK Research and Innovation (MR/V027549/1), the Department of Health and Social Care through the National Institute for Health Research (NIHR), and NIHR Biomedical Research Centres and NIHR Applied Research Collaboration East Midlands. <h4>Research in context</h4> <h4>Evidence before this study</h4> We searched Pubmed using the following search terms ((COVID-19).ti,ab OR (SARS-CoV-2).ti,ab) AND ((vaccine).ti,ab OR (vaccination).ti,ab OR (immunisation).ti,ab)) AND ((healthcare worker).ti,ab OR (health worker).ti,ab OR (doctor).ti,ab OR (nurse).ti,ab OR (healthcare professional).ti,ab)) AND ((hesitancy).ti,ab OR (refusal).ti,ab OR (uptake).ti,ab)). The search returned 60 results, of which 38 were excluded after title and abstract screening, 11 studies were not conducted in a population of healthcare workers, 20 did not present data on vaccine intention or uptake, 5 were related to vaccines other than the SARS-CoV-2 vaccine, 1 was unrelated to vaccination and 1 had been withdrawn. The 22 remaining articles were survey studies focussed on SARS-CoV-2 vaccine intention in healthcare workers. Estimates of SARS-CoV-2 vaccine acceptance varied widely from 27·7% - 94·5% depending on the country in which the study was performed, and the occupational group studied. Only 2 studies (both conducted in the USA) had a sample size greater than 10,000. Most studies found females, non-medical healthcare staff and those refusing influenza vaccine to be more likely to be hesitant. There was conflicting evidence about the effects of age and previous COVID-19 on hesitancy. Only 3 studies (all from the USA), presented data disaggregated by ethnicity, all finding Black ethnic HCWs were most likely to be hesitant. Common themes amongst studies that investigated reasons for vaccine hesitancy were concerns about safety of vaccines, fear of side effects and short development timeframes. We did not find any studies on SARS-CoV-2 vaccine hesitancy in UK healthcare workers in the published literature. <h4>Added value of this study</h4> This study is amongst the largest SARS-CoV-2 vaccine hesitancy studies in the literature. It is the largest study outside the USA and is the only study in UK HCWs. Our work focusses on the association of ethnicity with vaccine hesitancy, and we are the first study outside the USA to present results by ethnic group. The large number of ethnic minority HCWs in our study allows for examination of the outcome by more granular ethnicity categories than have previously been studied, allowing us to detect important differences in vaccine hesitancy levels within the broad White and Asian ethnic groupings. Our large sample size and the richness of our cohort study dataset allows us to control for many potential confounders in our multivariable analysis, and provide novel data on important potential drivers of hesitancy including discrimination, COVID-19 conspiracy beliefs, religion/religiosity and personality traits. Additionally, we combine quantitative with qualitative data providing a deeper understanding of the drivers of hesitancy and potential strategies to improve vaccine uptake in HCWs from ethnic minority communities. <h4>Implications of all the available evidence</h4> Around a quarter of UK healthcare workers reported SARS-CoV-2 vaccine hesitancy. In accordance with previous studies in other countries, we determined that female sex and lack of influenza vaccine in the previous season were important predictors of SARS-CoV-2 vaccine hesitancy in UK HCWs, although in contrast to most studies in the published literature, after adjustment we do not demonstrate differences in hesitancy levels by occupational role. Importantly, previous literature provides conflicting evidence of the effects of age and previous SARS-CoV-2 infection on vaccine hesitancy. In our study, younger HCWs and those with evidence of previous COVID-19 were more likely to be hesitant. This study provides novel data on increased hesitancy levels within Black Caribbean, Mixed White and Black Caribbean, Black African, Chinese, Pakistani and White Other ethnic groups. Mistrust (of vaccines in general, in SARS-CoV-2 vaccines specifically, in healthcare systems and research) and misinformation appear to be important drivers of hesitancy within HCWS in the UK. Our data indicate that despite facing an increased risk of COVID-19 compared to their White colleagues, UK HCWs from some ethnic minority groups continue to exhibit greater levels of SARS-CoV-2 vaccine hesitancy. This study provides policy makers with evidence to inform strategies to improve uptake.",,doi:https://doi.org/10.1016/j.lanepe.2021.100180; doi:https://doi.org/10.1101/2021.04.26.21255788; html:https://europepmc.org/article/PPR/PPR316137; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR316137&type=FILE&fileName=EMS123592-pdf.pdf&mimeType=application/pdf
 PPR416505,https://doi.org/10.1101/2021.11.08.21265380,Describing the population experiencing COVID-19 vaccine breakthrough following second vaccination in England: A cohort study from OpenSAFELY,"The OpenSAFELY Collaborative:, Green A, Curtis H, Hulme W, Williamson E, McDonald H, Bhaskaran K, Rentsch C, Schultze A, MacKenna B, Mahalingasivam V, Tomlinson L, Walker A, Fisher L, Massey J, Andrews C, Hopcroft L, Morton C, Croker R, Morley J, Mehrkar A, Bacon S, Evans D, Inglesby P, Hickman G, Ward T, Davy S, Mathur R, Tazare J, Eggo RM, Wing K, Wong A, Forbes H, Bates C, Cockburn J, Parry J, Hester F, Harper S, Douglas I, Evans S, Smeeth L, Goldacre B.",,No Journal Info,2021,2021-11-08,Y,,,,"<h4>Background</h4> While the vaccines against COVID-19 are considered to be highly effective, COVID-19 vaccine breakthrough is likely and a small number of people will still fall ill, be hospitalised, or die from COVID-19, despite being fully vaccinated. With the continued increase in numbers of positive SARS-CoV-2 tests, describing the characters of individuals who have experienced a COVID-19 vaccine breakthrough could be hugely important in helping to determine who may be at greatest risk. <h4>Method</h4> With the approval of NHS England we conducted a retrospective cohort study using routine clinical data from the OpenSAFELY TPP database of fully vaccinated individuals, linked to secondary care and death registry data, and described the characteristics of those experiencing a COVID-19 vaccine breakthrough. <h4>Results</h4> As of 01 st November 2021, a total of 15,436,455 individuals were identified as being fully vaccinated against COVID-19, with a median follow-up time of 149 days (IQR: 107-179). From within this population, a total of 577245 (<4%) individuals reported a positive SARS-CoV-2 test. For every 1000 years of patient follow-up time, the corresponding incidence rate was 98.02 (95% CI 97.9-98.15). There were 16,120 COVID-19-related hospital admissions, 1,100 COVID-19 critical care admission patients and 3,925 COVID-19-related deaths; corresponding incidence rates of 2.72 (95% C 2.7-2.74), 0.19 (95% C 0.18-0.19) and 0.66 (95% C 0.65-0.67), respectively. When broken down by the initial priority group, higher rates of hospitalisation and death were seen in those in care homes and those over 80 years of age. Comorbidities with the highest rates of breakthrough COVID-19 included chronic kidney disease, dialysis, transplant, haematological malignancy, and immunocompromised. <h4>Conclusion</h4> The majority of COVID-19 vaccine breakthrough cases in England were mild with relatively few fully vaccinated individuals being hospitalised or dying as a result. However, some concerning differences in rates of breakthrough cases were identified in several clinical and demographic groups. While it is important to note that these findings are simply descriptive and cannot be used to answer why certain groups have higher rates of COVID-19 breakthrough than others, the emergence of the Omicron variant of COVID-19 coupled with the continued increase in numbers of positive SARS-CoV-2 tests are concerning. As numbers of fully vaccinated individuals increases and follow-up time lengthens, so too will the number of COVID-19 breakthrough cases. Additional analyses, aimed at identifying individuals at higher risk, are therefore required.",,pdf:https://qmro.qmul.ac.uk/xmlui/bitstream/123456789/83135/2/Mathur%20Describing%20the%20population%20experiencing%20COVID-19%20vaccine%20breakthrough%20following%20second%20vaccination%20in%20England%3a%20a%20cohort%20study%20from%20OpenSAFELY%202022%20Published.pdf; doi:https://doi.org/10.1101/2021.11.08.21265380; html:https://europepmc.org/article/PPR/PPR416505; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR416505&type=FILE&fileName=EMS138253-pdf.pdf&mimeType=application/pdf
 PPR371439,https://doi.org/10.1101/2021.07.16.21260628,"Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: cohort study in OpenSAFELY using linked primary care, secondary care and death registration data","Bhaskaran K, Rentsch CT, Hickman G, Hulme WJ, Schultze A, Curtis HJ, Wing K, Warren-Gash C, Tomlinson L, Bates CJ, Mathur R, MacKenna B, Mahalingasivam V, Wong A, Walker AJ, Morton CE, Grint D, Mehrkar A, Eggo RM, Inglesby P, Douglas IJ, McDonald HI, Cockburn J, Williamson EJ, Evans D, Parry J, Hester F, Harper S, Evans SJ, Bacon S, Smeeth L, Goldacre B.",,No Journal Info,2021,2021-07-19,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> There is concern about medium to long-term adverse outcomes following acute COVID-19, but little relevant evidence exists. We aimed to investigate whether risks of hospital admission and death, overall and by specific cause, are raised following discharge from a COVID-19 hospitalisation. <h4>Methods and Findings</h4> Working on behalf of NHS-England, we used linked primary care and hospital data in OpenSAFELY to compare risks of hospital admission and death, overall and by specific cause, between people discharged from COVID-19 hospitalisation (February-December 2020), and (i) demographically-matched controls from the 2019 general population; (ii) people discharged from influenza hospitalisation in 2017-19. We used Cox regression adjusted for personal and clinical characteristics. 24,673 post-discharge COVID-19 patients, 123,362 general population controls, and 16,058 influenza controls were followed for ≤315 days. Overall risk of hospitalisation or death (30968 events) was higher in the COVID-19 group than general population controls (adjusted-HR 2.23, 2.14-2.31) but similar to the influenza group (adjusted-HR 0.94, 0.91-0.98). All-cause mortality (7439 events) was highest in the COVID-19 group (adjusted-HR 4.97, 4.58-5.40 vs general population controls and 1.73, 1.60-1.87 vs influenza controls). Risks for cause-specific outcomes were higher in COVID-19 survivors than general population controls, and largely comparable between COVID-19 and influenza patients. However, COVID-19 patients were more likely than influenza patients to be readmitted/die due to their initial infection/other lower respiratory tract infection (adjusted-HR 1.37, 1.22-1.54), and to experience mental health or cognitive-related admission/death (adjusted-HR 1.36, 1.01-2.83); in particular, COVID-19 survivors with pre-existing dementia had higher risk of dementia death. One limitation of our study is that reasons for hospitalisation/death may have been misclassified in some cases due to inconsistent use of codes. <h4>Conclusions</h4> People discharged from a COVID-19 hospital admission had markedly higher risks for rehospitalisation and death than the general population, suggesting a substantial extra burden on healthcare. Most risks were similar to those observed after influenza hospitalisations; but COVID-19 patients had higher risks of all-cause mortality, readmissions/death due to the initial infection, and dementia death, highlighting the importance of post-discharge monitoring.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/19/2021.07.16.21260628.full.pdf; doi:https://doi.org/10.1101/2021.07.16.21260628; html:https://europepmc.org/article/PPR/PPR371439; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR371439&type=FILE&fileName=EMS130897-pdf.pdf&mimeType=application/pdf
 PPR361566,https://doi.org/10.1101/2021.06.21.21259254,"Acceptability, usability and performance of lateral flow immunoassay tests for SARS-CoV-2 antibodies: REACT-2 study of self-testing in non-healthcare key workers","Davies B, Araghi M, Moshe M, Gao H, Bennet K, Jenkins J, Atchison C, Darzi A, Ashby D, Riley S, Barclay W, Elliott P, Ward H, Cooke G.",,No Journal Info,2021,2021-06-25,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> Seroprevalence studies in key worker populations are essential to understand the epidemiology of SARS-CoV-2. Various technologies, including laboratory assays and point-of-care self-tests, are available for antibody testing. The interpretation of seroprevalence studies requires comparative data on the performance of antibody tests. <h4>Methods</h4> In June 2020, current and former members of the UK Police forces and Fire service performed a self-test lateral flow immunoassay (LFIA) and provided a saliva sample, nasopharyngeal swab, venous blood samples for Abbott ELISA and had a nurse performed LFIA. We present the prevalence of PCR positivity and antibodies to SARS-CoV-2 in this cohort following the first wave of infection in England; the acceptability and usability of self-test LFIAs (defined as use of the LFIA kit and provision of a valid result, respectively); and determine the sensitivity and specificity of LFIAs compared to laboratory ELISAs. <h4>Results</h4> In this cohort of non-healthcare key workers, 7.4% (396/5,348; 95% CI, 6.7-8.1) were antibody positive. Seroprevalence was 8.9% (6.9-11.4) in those under 40 years, 11.5% (8.8-15.0) in those of non-white British ethnicity and 7.8% (7.1-8.7) in those currently working. The self-test LFIA had an acceptability of 97.7% and a usability of 90.0%. There was substantial agreement between within-participant LFIA results (kappa 0.80; 0.77-0.83). The LFIAs (self-test and nurse-performed) had a similar performance: compared to ELISA, sensitivity was 82.1% (77.7-86.0) self-test and 76.4% (71.9-80.5) nurse-performed with specificity of 97.8% (97.3-98.2) and 98.5% (98.1-98.8) respectively. <h4>Conclusion</h4> A greater proportion of the non-healthcare key worker cohort showed evidence of previous infection with SARS-CoV-2 than the general population at 6.0% (5.8-6.1) following the first wave in England. The high acceptability and usability reported by participants and the similar performance of self-test and nurse-performed LFIAs indicate that the self-test LFIA is fit for purpose for home-testing in occupational and community prevalence studies.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/91887/11/ofab496.pdf; doi:https://doi.org/10.1101/2021.06.21.21259254; html:https://europepmc.org/article/PPR/PPR361566; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR361566&type=FILE&fileName=EMS128927-pdf.pdf&mimeType=application/pdf
@@ -240,8 +240,8 @@ PPR270071,https://doi.org/,Key Questions for Modelling COVID-19 Exit Strategies,
 PPR186981,https://doi.org/10.1101/2020.07.12.20152298,The effect of international travel restrictions on internal spread of COVID-19,"Russell TW, Wu JT, Clifford S, Edmunds WJ, Kucharski AJ, Jit M, CMMID COVID-19 working group.",,No Journal Info,2020,2020-07-14,Y,,,,"<h4>Background</h4> Countries have restricted international arrivals to delay the spread of COVID-19. These measures carry a high economic and social cost. They may have little impact on COVID-19 epidemics if there are many more cases resulting from local transmission compared to imported cases. <h4>Methods</h4> To inform decisions about international travel restrictions, we compared the ratio of expected COVID-19 cases from international travel (assuming no travel restrictions) to the expected COVID-19 cases arising from internal spread on an average day in May 2020 in each country. COVID-19 prevalence and incidence were estimated using a modelling framework that adjusts reported cases for under-ascertainment and asymptomatic infections. <h4>Findings</h4> With May 2019 travel volumes, imported cases account for <10% of total incidence in 103 (95% credible interval: 76 − 130) out of 142 countries, and <1% in 48 (95% CrI: 9 − 95). If we assume that travel would decrease compared to May 2019 even in the absence of formal restrictions, then imported cases account for <10% of total incidence in 109-123 countries and <1% in 61-88 countries (depending on the assumptions about travel reductions). <h4>Interpretation</h4> While countries can expect infected travellers to arrive in the absence of travel restrictions, in most countries these imported cases likely contribute little to local COVID-19 epidemics. Stringent travel restrictions may have limited impact on epidemic dynamics except in countries with low COVID-19 incidence and large numbers of arrivals from other countries. <h4>Funding</h4> Wellcome Trust, UK Department for International Development, European Commission, National Institute for Health Research, Medical Research Council, Bill & Melinda Gates Foundation <h4>Research in context</h4> <h4>Evidence before this study</h4> Countries are at different stages of COVID-19 epidemics, so many have implemented policies to minimise the risk of importing cases via international travel. Such policies include border closures, flight suspensions, quarantine and self-isolation on international arrivals. Searching PubMed and MedRxiv using the search: (“covid” OR “coronavirus” OR “SARS-CoV-2”) AND (“travel” OR “restrictions” OR “flight” OR “flights” OR “border”) from 1 January – 10 July 2020 returned 118 and 84 studies respectively, of which 39 were relevant to our study. These studies either concentrated in detail on the risk of importation to specific countries or used a single epidemiological or travel dataset to estimate risk. Most of them focused on the risk of COVID-19 introduction from China or other countries with cases earlier in 2020. No study combined country-specific travel data, prevalence estimates and incidence estimates to assess the global risk of importation relative to current local transmission within countries. <h4>Added value of this study</h4> We combined data on airline passengers and flight frequencies with estimates of COVID-19 prevalence and incidence (adjusted for underreporting and asymptomatic cases), to estimate the risk of imported cases, relative to the level of local transmission in each country. This allows decision makers to determine where travel restriction policies make large contributions to slowing local transmission, and where they have very little overall effect. <h4>Implications of all the available evidence</h4> In most countries, imported cases would make a relatively small contribution to local transmission, so travel restrictions would have very little effect on epidemics. Countries where travel restrictions would have a large effect on local transmission are those with strong travel links to countries with high COVID-19 prevalence and/or countries which have successfully managed to control their local outbreaks.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/07/14/2020.07.12.20152298.full.pdf; doi:https://doi.org/10.1101/2020.07.12.20152298; html:https://europepmc.org/article/PPR/PPR186981; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR186981&type=FILE&fileName=EMS87133-pdf.pdf&mimeType=application/pdf
 PPR373497,https://doi.org/10.1101/2021.07.22.21260416,"Obesity, Ethnicity, and Covid-19 Mortality: A population-based cohort study of 12.6 Million Adults in England","Yates T, Summerfield A, Razieh C, Banerjee A, Chudasama Y, Davies MJ, Gillies C, Islam N, Lawson C, Mirkes E, Zaccardi F, Khunti K, Nafilyan V.",,No Journal Info,2021,2021-07-23,Y,,,,"<h4>Importance</h4> Obesity and ethnicity are well characterised risk factors for severe COVID-19 outcomes, but the differential effects of obesity on COVID-19 outcomes by race/ethnicity has not been examined robustly in the general population. <h4>Objective</h4> To investigate the association between body mass index (BMI) and COVID-19 mortality across different ethnic groups. <h4>Design, Setting, and Participants</h4> This is a retrospective cohort study using linked national Census, electronic health records and mortality data for English adults aged 40 years or older who were alive at the start of pandemic (24 th January 2020). <h4>Exposures</h4> BMI obtained from electronic health records. Self-reported ethnicity (white, black, South Asian, other) was the effect-modifying variable. <h4>Main Outcomes and Measures</h4> COVID-19 related death identified by ICD-10 codes U07.1 or U07.2 mentioned on the death certificate from 24 th January 2020 until December 28 th 2020. <h4>Results</h4> The analysis included white (n = 11,074,708; mean age 61.9 [±13.4] years; 54% women), black (n = 416,542; 56.4 [±11.7] years; 57% women), South Asian (621,691; 55.7 [±12.4] years; 51% women) and other (n = 478,196; 55.3 [±11.6] years; 55% women) ethnicities with linked BMI data. The association between BMI and COVID-19 mortality was stronger in ethnic minority groups. Compared to a BMI of 22.5 kg/m 2 in white ethnicities, the adjusted HR for COVID-19 mortality at a BMI of 30 kg/m 2 in white, black, South Asian and other ethnicities was 0.95 (95% CI: 0.87-1.03), 1.72 (1.52-1.94), 2.00 (1.78-2.25) and 1.39 (1.21-1.61), respectively. The estimated risk of COVID-19 mortality at a BMI of 40 kg/m 2 in white ethnicities (HR = 1.73) was equivalent to the risk observed at a BMI of 30.1 kg/m 2 , 27.0 kg/m 2 , and 32.2 kg/m 2 in black, South Asian and other ethnic groups, respectively. <h4>Conclusions</h4> This population-based study using linked Census and electronic health care records demonstrates that the risk of COVID-19 mortality associated with obesity is greater in ethnic minority groups compared to white populations. <h4>Question</h4> Does the association between BMI and COVID-19 mortality vary by ethnicity? <h4>Findings</h4> In this study of 12.6 million adults, BMI was associated with COVID-19 in all ethnicities, but with stronger associations in ethnic minority populations such that the risk of COVID-19 mortality for a BMI of 40 kg/m 2 in white ethnicities was observed at a BMI of 30.1 kg/m 2 , 27.0 kg/m 2 , and 32.2 kg/m 2 in black, South Asian and other ethnicities, respectively. <h4>Meaning</h4> BMI is a stronger risk factor for COVID-19 mortality in ethnic minorities. Obesity management is therefore a priority in these populations.",,pdf:https://www.nature.com/articles/s41467-022-28248-1.pdf; doi:https://doi.org/10.1101/2021.07.22.21260416; html:https://europepmc.org/article/PPR/PPR373497; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR373497&type=FILE&fileName=EMS132179-pdf.pdf&mimeType=application/pdf
 PPR463503,https://doi.org/10.1101/2022.03.02.22271623,"Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis","RECOVERY Collaborative Group, Horby PW, Emberson JR, Mafham M, Campbell M, Peto L, Pessoa-Amorim G, Spata E, Staplin N, Lowe C, Chadwick DR, Brightling C, Stewart R, Collini P, Ashish A, Green CA, Prudon B, Felton T, Kerry A, 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 MJ.",,No Journal Info,2022,2022-03-03,Y,,,,"<h4>SUMMARY</h4> <h4>Background</h4> We evaluated the use of baricitinib, a Janus kinase (JAK) 1/2 inhibitor, for the treatment of patients admitted to hospital because of COVID-19. <h4>Methods</h4> 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 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 conducted that 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 ). <h4>Findings</h4> Between 2 February 2021 and 29 December 2021, 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% receiving tocilizumab (with planned use within the next 24 hours recorded for a further 9%). Overall, 513 (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 0·77-0·98; p=0·026). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of 8 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 into an updated meta-analysis of all 9 completed trials (involving 11,888 randomised patients and 1484 deaths) allocation to baricitinib or other JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0.80; 95% CI 0.71-0.89; p<0.001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no excess of thrombosis, or other safety outcomes. <h4>Interpretation</h4> In patients hospitalised for 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. <h4>Funding</h4> UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).",,pdf:https://nottingham-repository.worktribe.com/preview/9409854/PIIS0140673622011096.pdf; doi:https://doi.org/10.1101/2022.03.02.22271623; html:https://europepmc.org/article/PPR/PPR463503; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR463503&type=FILE&fileName=EMS148878-pdf.pdf&mimeType=application/pdf
-PPR630589,https://doi.org/10.1101/2023.03.15.23287292,Living alone and mental health: parallel analyses in longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic,"McElroy E, Herrett E, Patel K, Piehlmaier DM, Di Gessa G, Huggins C, Green MJ, Kwong A, Thompson EJ, Zhu J, Mansfield KE, Silverwood RJ, Mansfield R, Maddock J, Mathur R, Costello RE, Matthews A, Tazare J, Henderson A, Wing K, Bridges L, Bacon S, Mehrkar A, Shaw RJ, Wels J, Katikireddi SV, Chaturvedi N, Tomlinson L, Patalay P, OpenSafely Collaborative.",,No Journal Info,2023,2023-03-15,Y,,,,"<h4>ABSTRACT</h4> <h4>Objectives</h4> To describe the mental health gap between those who live alone and those who live with others, and to examine whether the COVID-19 pandemic had an impact on this gap. <h4>Design</h4> Ten population based prospective cohort studies, and a retrospective descriptive cohort study based on electronic health records (EHRs). <h4>Setting</h4> UK Longitudinal population-based surveys (LPS), and primary and secondary care records within the OpenSAFELY-TPP database. <h4>Participants</h4> Participants from the LPS were included if they had information on living status in early 2020, valid data on mental ill-health at the closest pre-pandemic assessment and at least once during the pandemic, and valid data on a key minimum set of covariates. The EHR dataset included 16 million adults registered with primary care practices in England using TPP SystmOne software on 1st February 2020, with at least three months of registration, valid address data, and living in households of <16 people. <h4>Main outcome measures</h4> In the LPS, self-reported survey measures of psychological distress and life satisfaction were assessed in the nearest pre-pandemic sweep and three periods during the pandemic: April-June 2020, July-October 2020, and November 2020-March 2021. In the EHR analyses, outcomes were morbidity codes recorded in primary or secondary care between March 2018 and January 2022 reflecting the diagnoses of depression, self-harm, anxiety, obsessive compulsive disorder, eating disorders, and severe mental illnesses. <h4>Results</h4> The LPS consisted of 37,544 participants (15.2% living alone) and we found greater psychological distress (SMD: 0.09 (95% CI: 0.04, 0.14) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30, -0.15) in those living alone pre-pandemic, and the gap between the two groups stayed similar after the onset of the pandemic. In the EHR analysis of almost 16 million records (21.4% living alone), codes indicating mental health conditions were more common in those who lived alone compared to those who lived with others (e.g., depression 26 and severe mental illness 58 cases more per 100,000). Recording of mental health conditions fell during the pandemic for common mental health disorders and the gap between the two groups narrowed. <h4>Conclusions</h4> Multiple sources of data indicate that those who live alone experience greater levels of common and severe mental illnesses, and lower life satisfaction. During the pandemic this gap in need remained, however, there was a narrowing of the gap in service use, suggesting greater barriers to healthcare access for those who live alone. <h4>Summary Box</h4> <h4>What is already known on the topic?</h4> Households with one individual are an increasing demographic, comprising over a quarter of all households in the UK in 2021. However, the mental health gap between those who live alone compared to those who live with others is not well described and even less is known about the relative gaps in need and healthcare-seeking and access. The pandemic and associated restrictive measures further increased the likelihood of isolation for this group, which may have impacted mental health. <h4>What this study adds?</h4> We present comprehensive evidence from both population-based surveys and electronic health records regarding the greater levels of mental health symptoms and in recorded diagnoses for common (anxiety, depression) and less common (OCD, eating disorders, SMIs) mental health conditions for people living alone compared to those living with others. Our analyses indicate that mental health conditions are more common among those who live alone compared to those who live with others. Although levels of reported distress increased for both groups during the pandemic, healthcare-seeking dropped in both groups, and the rates of healthcare-seeking among those who live alone converged with those who live with others for common mental health conditions. This suggests greater barriers for treatment access among those that live alone. The findings have implications for mental health service planning and efforts to reduce barriers to treatment access, especially for individuals who live on their own.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/03/15/2023.03.15.23287292.full.pdf; doi:https://doi.org/10.1101/2023.03.15.23287292; html:https://europepmc.org/article/PPR/PPR630589; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR630589&type=FILE&fileName=EMS172468-pdf.pdf&mimeType=application/pdf
 PPR601851,https://doi.org/10.2139/ssrn.3970709,Impact of First UK COVID-19 Lockdown on Hospital Admissions: Interrupted Time Series Study of 32 Million People,"Shah SA, Brophy S, Kennedy J, Fisher L, Walker A, Mackenna B, Curtis H, Inglesby P, Davy S, Bacon S, Goldacre B, Group OC, Agrawal U, Moore E, Simpson C, Macleod J, Cooksey R, Sheikh A, Katikireddi SV.",,No Journal Info,2021,2021-11-24,N,,,,"Background: Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such disruption was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for exemplar non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups. <br><br>Methods: We used OpenSAFELY (for England), EAVEII (Scotland), and SAIL Databank (Wales) to extract weekly hospital admission rates for cancer, cardiovascular and respiratory conditions (excluding COVID-19) from the pre-pandemic period until 25/10/2020 and conducted a controlled interrupted time series analysis. We undertook stratified analyses and assessed admission rates over seven months during which lockdown restrictions were gradually lifted.<br><br>Findings: Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% in England, 20.9% in Scotland, and 24.7% in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5%, 21.9%, and 19.0% in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% for Whites, but 44.3%, 34.6%, and 25.6% for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0% respectively when compared to the same period (August-September) during the pre-pandemic years.<br><br>Interpretation: Hospital care for non-COVID diseases fell substantially across England, Scotland, and Wales during the first lockdown, with disruptions persisting for at least six months. The most deprived and minority ethnic groups were impacted more severely. <br><br>Funding Information: Medical Research Council; Health Data Research UK; Industrial Strategy Challenge Fund; Scottish Government; National Institute for Health Research; Asthma UK-BLF; Wellcome Trust<br><br>Declaration of Interests: SVK is co-chair of the Scottish Government’s Expert Reference Group on ethnicity and COVID-19 and is a member of the Scientific Advisory Group on Emergencies subgroup on ethnicity. AS is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and its Standing Committee on Pandemics, and NERVTAG’s Risk Stratification Subgroup. All other authors declare no conflict of interest related to this work.<br><br>Ethics Approval Statement: There were database-specific ethics approvals that allowed the use of the anonymised datasets for the current research study. These approvals were by the Health Research Authority (20/LO/0651) and LSHTM Ethics Board (21863) for OpenSAFELY, South East Scotland Research Ethics Committee 02 (12/SS/0201) and Public Benefit and Privacy Panel Committee of Public Health Scotland (1920-0279) for EAVE-II, and SAIL’s independent Information Governance Review Panel (IGRP) for the SAIL Databank.",,pdf:http://www.thelancet.com/article/S2589537022001924/pdf; doi:https://doi.org/10.2139/ssrn.3970709; html:https://europepmc.org/article/PPR/PPR601851; doi:https://doi.org/10.2139/ssrn.3970709
+PPR630589,https://doi.org/10.1101/2023.03.15.23287292,Living alone and mental health: parallel analyses in longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic,"McElroy E, Herrett E, Patel K, Piehlmaier DM, Di Gessa G, Huggins C, Green MJ, Kwong A, Thompson EJ, Zhu J, Mansfield KE, Silverwood RJ, Mansfield R, Maddock J, Mathur R, Costello RE, Matthews A, Tazare J, Henderson A, Wing K, Bridges L, Bacon S, Mehrkar A, Shaw RJ, Wels J, Katikireddi SV, Chaturvedi N, Tomlinson L, Patalay P, OpenSafely Collaborative.",,No Journal Info,2023,2023-03-15,Y,,,,"<h4>ABSTRACT</h4> <h4>Objectives</h4> To describe the mental health gap between those who live alone and those who live with others, and to examine whether the COVID-19 pandemic had an impact on this gap. <h4>Design</h4> Ten population based prospective cohort studies, and a retrospective descriptive cohort study based on electronic health records (EHRs). <h4>Setting</h4> UK Longitudinal population-based surveys (LPS), and primary and secondary care records within the OpenSAFELY-TPP database. <h4>Participants</h4> Participants from the LPS were included if they had information on living status in early 2020, valid data on mental ill-health at the closest pre-pandemic assessment and at least once during the pandemic, and valid data on a key minimum set of covariates. The EHR dataset included 16 million adults registered with primary care practices in England using TPP SystmOne software on 1st February 2020, with at least three months of registration, valid address data, and living in households of <16 people. <h4>Main outcome measures</h4> In the LPS, self-reported survey measures of psychological distress and life satisfaction were assessed in the nearest pre-pandemic sweep and three periods during the pandemic: April-June 2020, July-October 2020, and November 2020-March 2021. In the EHR analyses, outcomes were morbidity codes recorded in primary or secondary care between March 2018 and January 2022 reflecting the diagnoses of depression, self-harm, anxiety, obsessive compulsive disorder, eating disorders, and severe mental illnesses. <h4>Results</h4> The LPS consisted of 37,544 participants (15.2% living alone) and we found greater psychological distress (SMD: 0.09 (95% CI: 0.04, 0.14) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30, -0.15) in those living alone pre-pandemic, and the gap between the two groups stayed similar after the onset of the pandemic. In the EHR analysis of almost 16 million records (21.4% living alone), codes indicating mental health conditions were more common in those who lived alone compared to those who lived with others (e.g., depression 26 and severe mental illness 58 cases more per 100,000). Recording of mental health conditions fell during the pandemic for common mental health disorders and the gap between the two groups narrowed. <h4>Conclusions</h4> Multiple sources of data indicate that those who live alone experience greater levels of common and severe mental illnesses, and lower life satisfaction. During the pandemic this gap in need remained, however, there was a narrowing of the gap in service use, suggesting greater barriers to healthcare access for those who live alone. <h4>Summary Box</h4> <h4>What is already known on the topic?</h4> Households with one individual are an increasing demographic, comprising over a quarter of all households in the UK in 2021. However, the mental health gap between those who live alone compared to those who live with others is not well described and even less is known about the relative gaps in need and healthcare-seeking and access. The pandemic and associated restrictive measures further increased the likelihood of isolation for this group, which may have impacted mental health. <h4>What this study adds?</h4> We present comprehensive evidence from both population-based surveys and electronic health records regarding the greater levels of mental health symptoms and in recorded diagnoses for common (anxiety, depression) and less common (OCD, eating disorders, SMIs) mental health conditions for people living alone compared to those living with others. Our analyses indicate that mental health conditions are more common among those who live alone compared to those who live with others. Although levels of reported distress increased for both groups during the pandemic, healthcare-seeking dropped in both groups, and the rates of healthcare-seeking among those who live alone converged with those who live with others for common mental health conditions. This suggests greater barriers for treatment access among those that live alone. The findings have implications for mental health service planning and efforts to reduce barriers to treatment access, especially for individuals who live on their own.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/03/15/2023.03.15.23287292.full.pdf; doi:https://doi.org/10.1101/2023.03.15.23287292; html:https://europepmc.org/article/PPR/PPR630589; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR630589&type=FILE&fileName=EMS172468-pdf.pdf&mimeType=application/pdf
 PPR289244,https://doi.org/10.2139/ssrn.3789264,Effectiveness of First Dose of COVID-19 Vaccines Against Hospital Admissions in Scotland: National Prospective Cohort Study of 5.4 Million People,"Vasileiou E, Simpson CR, Robertson C, Shi T, Kerr S, Agrawal U, Akbari A, Bedston S, Beggs J, Bradley D, Chuter A, Lusignan Sd, Docherty A, Ford D, Hobbs R, Joy M, Katikireddi SV, Marple J, McCowan C, McGagh D, McMenamin J, Moore E, Murray J, Pan J, Ritchie LD, Shah SA, Stock S, Torabi F, Tsang RSM, Wood R, Woolhouse M, Sheikh A.",,No Journal Info,2021,2021-02-19,N,,,,"Background: The BNT162b2 mRNA (Pfizer-BioNTech) and ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines have demonstrated high efficacy against infection in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. There is an urgent need to study the ‘real-world’ effects of these vaccines. The aim of our study was to estimate the effectiveness of the first dose of these COVID-19 vaccines in preventing hospital admissions.<br><br>Methods: We conducted a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) database comprising of linked vaccination, primary care, Real-Time Polymerase Chain Reaction (RT-PCR) testing, hospitalisation and mortality records for 5.4 million people in Scotland (covering ~99% of population). A time-dependent Cox model and Poisson regression models were fitted to estimate effectiveness against COVID-19 related hospitalisation (defined as 1- Adjusted Hazard Ratio) following the first dose of vaccine.<br><br>Findings: The first dose of the BNT162b2 vaccine was associated with a vaccine effect of 85% (95% confidence interval [CI] 76 to 91) for COVID-19 related hospitalisation at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 94% (95% CI 73 to 99). Results of combined vaccine effect for prevention of COVID-19 related hospitalisation were comparable when restricting the analysis to those aged ≥80 years (81%; 95% CI 65 to 90 at 28-34 days post-vaccination).<br><br>Interpretation: A single dose of the BNT162b2 mRNA and ChAdOx1 vaccines resulted in substantial reductions in the risk of COVID-19 related hospitalisation in Scotland.<br><br>Funding: UK Research and Innovation (Medical Research Council); Research and Innovation Industrial Strategy Challenge Fund; Health Data Research UK.<br><br>Conflict of Interest: AS is a member of the Scottish Government Chief Medical Officer’s COVID-19Advisory Group and the New and Emerging Respiratory Virus Threats (NERVTAG) Risk Stratification Subgroup. CRS declares funding from the MRC, NIHR, CSO and New Zealand Ministry for Business, Innovation and Employment and Health Research Council during the conduct of this study. SVK is co-chair of the Scottish Government’s Expert Reference Group on COVID-19 and ethnicity, is a member of the Scientific Advisory Group on Emergencies (SAGE) subgroup on ethnicity and acknowledges funding from a NRS Senior Clinical Fellowship, MRC and CSO. All other authors report no conflicts of interest.<br><br>Ethical Approval: Approvals were obtained from the National Research Ethics Service Committee, Southeast Scotland 02 (reference number: 12/SS/0201) and Public Benefit and Privacy Panel for Health and Social Care (reference number: 1920-0279).",,pdf:https://www.pure.ed.ac.uk/ws/files/197030199/SSRN_id3789264.pdf; doi:https://doi.org/10.2139/ssrn.3789264; html:https://europepmc.org/article/PPR/PPR289244; doi:https://doi.org/10.2139/ssrn.3789264
 PPR371921,https://doi.org/,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.",,No Journal Info,2021,2021-07-16,Y,,,,"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 correlation among medical codes which can potentially be exploited to improve the performance. 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 COVID-19 shielding codes. Experiments were conducted to compare HLAN and LE initialisation to the state-of-the-art neural network based methods. HLAN achieved the best Micro-level AUC and $F_1$ on the top-50 code prediction and comparable results on the NHS COVID-19 shielding code prediction to other models. By highlighting the most salient words and sentences for each label, HLAN showed more meaningful and comprehensive model interpretation compared to its downgraded baselines and the CNN-based models. LE initialisation consistently boosted most deep learning models for automated medical coding.",,arxiv:https://arxiv.org/abs/2010.15728v4; html:https://europepmc.org/article/PPR/PPR371921; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR371921&type=FILE&fileName=EMS130963-pdf.pdf&mimeType=application/pdf
 PPR605310,https://doi.org/10.2139/ssrn.4237731,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 EH, Wong JY, Xiao J, Ho F, Gao H, Wang L, Xu X, Du Z, Wu P, Leung G, Cowling BJ.",,No Journal Info,2022,2022-10-04,N,,,,"Background: The serial interval distribution is used to approximate the generation time distribution, an essential parameter to infer the transmissibility (<i>R<sub>t</sub></i>) of an epidemic. However, serial interval distributions may change as an epidemic progresses rather than remaining constant.<br><br>Method: We examined detailed contact tracing data on laboratory-confirmed cases of COVID-19 in Hong Kong during the five waves from January 2020 to July 2022. We reconstructed the transmission pairs and estimated time-varying effective serial interval distributions using Bayesian inferential framework with a sliding window of 7-14 days. We used regression models to identify the factors of temporal changes in serial intervals and quantify their respective impacts. Finally, we assessed the biases in estimating transmissibility using constant over time-varying serial interval distributions.<br><br>Findings: 2497 transmission pairs were identified for the ancestral strain of SARS-CoV-2 during the first two years of the COVID-19 pandemic in Hong Kong. We found clear temporal changes in mean serial interval estimates within each epidemic wave studied and across waves, with mean serial intervals ranged from 5.5 days (95% CrI: 4.4, 6.6) to 2.7 (95% CrI: 2.2, 3.2) days. The mean serial intervals shortened or lengthened over time, which were found to be closely associated with the temporal variation in COVID-19 case profiles and public health and social measures and could lead to the biases in predicting <i>R<sub>t</sub></i>.<br><br>Interpretation: Accounting for the impact of these factors, the time-varying quantification of serial interval distributions could lead to improved estimation of <i>R<sub>t</sub></i>, and provide additional insights into the impact of public health measures on transmission.<br><br>Funding Information: This study was supported by the Health and Medical Research Fund (project no. 20190712); the Collaborative Research Fund of the Research Grants Council of the Hong Kong Special Administrative Region, China (project No. C7123-20G); AIR@InnoHK administered by Innovation and Technology Commission, European Research Council (grant no. 804744); the Grand Challenges ICODA pilot initiative, delivered by Health Data Research UK and funded by the Bill & Melinda Gates Foundation and the Minderoo Foundation. <br><br>Declaration of Interests: BJC received honoraria from AstraZeneca, Fosun Pharma, GSK, Moderna, Pfizer, Roche, and Sanofi. The authors report no other potential conflicts of interest.",,doi:https://doi.org/10.1101/2022.08.29.22279351; doi:https://doi.org/10.2139/ssrn.4237731; html:https://europepmc.org/article/PPR/PPR605310; doi:https://doi.org/10.2139/ssrn.4237731
@@ -285,8 +285,8 @@ PPR404742,https://doi.org/10.1101/2021.10.07.21264681,Monitoring sociodemographi
 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,,,,"<h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Conclusions</h4> 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.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/12/11/2020.12.08.20246231.full.pdf; 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
 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,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Conclusions</h4> 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.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa57688/Download/57688__23941__69a222d696ec4cd991ed01d7cb47ee8e.pdf; 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
 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,,,,"<h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Findings</h4> 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. <h4>Interpretation</h4> 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. <h4>Funding</h4> 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. <h4>Research in context</h4> <h4>Evidence before this study</h4> 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. <h4>Added value of this study</h4> 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. <h4>Implications of all the available evidence</h4> 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
-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,,,,"<h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Conclusions</h4> 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.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/10/10/2022.10.07.22280819.full.pdf; 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
 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,,,,"<h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Conclusion</h4> 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. <h4>Funding</h4> This research was funded by the Office for National Statistics.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/0141076821999973; 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
+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,,,,"<h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Conclusions</h4> 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.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/10/10/2022.10.07.22280819.full.pdf; 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
 PPR249199,https://doi.org/10.1101/2020.12.02.20242933,Pre-existing cardiovascular disease rather than cardiovascular risk factors drives mortality in COVID-19,"O’Gallagher K, Shek A, Bean DM, Bendayan R, Teo JTH, Dobson RJB, Shah AM, Zakeri R.",,No Journal Info,2020,2020-12-04,Y,,,,"<h4>Background</h4> The association between cardiovascular (CV) risk factors, such as hypertension and diabetes, established CV disease (CVD), and susceptibility to CV complications or mortality in COVID-19 remains unclear. <h4>Methods</h4> We conducted a cohort study of consecutive adults hospitalised for severe COVID-19 between 1 st March and 30 th June 2020. Pre-existing CVD, CV risk factors and associations with mortality and CV complications were ascertained. <h4>Findings</h4> Among 1,721 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 (<70y aHR 1.21 [95%CI 0.72-2.01], ≥70y 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. <h4>Interpretation</h4> 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.",,pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-021-02137-9; doi:https://doi.org/10.1101/2020.12.02.20242933; html:https://europepmc.org/article/PPR/PPR249199; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR249199&type=FILE&fileName=EMS107885-pdf.pdf&mimeType=application/pdf
 PPR704199,https://doi.org/10.2139/ssrn.4547861,Hospital Admission Related to Common Infections in Primary Care in England: Risk Prediction and Evaluation of the Impact of COVID-19 Pandemic Using OpenSAFELY,"Fahmi A, Palin V, Zhong X, Yang Y, Watts S, Ashcroft D, Goldacre B, Mackenna B, Fisher L, Massey J, Mehrkar A, Bacon S, Group OC, Hand K, Staa TPV.",,No Journal Info,2023,2023-08-28,N,,,,"Background: Antimicrobial resistance (AMR) is a multifaceted global challenge, partly driven by inappropriate antibiotic prescribing. The COVID-19 pandemic impacted antibiotic prescribing for common bacterial infections. This highlights the need to examine risk of hospital admissions related to common infections, excluding COVID-19 infections during the pandemic<br><br>Methods: With the approval of NHS England, we accessed electronic health records from The Phoenix Partnership (TPP) through OpenSAFELY platform. We included patients with primary care diagnosis of common infections, including lower respiratory tract infection (LRTI), upper respiratory tract infections (URTI), and lower urinary tract infection (UTI), from January 2019 to August 2022. We excluded patients with a COVID-19 record 90 days before to 30 days after the infection diagnosis. Using Cox proportional-hazard regression models, we predicted risk of infection-related hospital admission in 30 days follow-up period after the diagnosis.<br><br>Findings: We found 12,745,165 infection diagnoses from January 2019 to August 2022. Of them, 80,395 (2·05%) cases were admitted to hospital in the follow-up period. Counts of hospital admission for infections dropped during COVID-19, e.g., LRTI from 3,950 in December 2019 to 520 in April 2020. Comparing those prescribed an antibiotic to those without, reduction in risk of hospital admission were largest with LRTI (adjusted odds ratio (OR) of 0·35; 95% confidence interval (CI), 0·35-0·36) and UTI (adjusted OR 0·45; 95% CI, 0·44-0·46), compared to URTI (adjusted OR 1·04; 95% CI, 1·03-1·06).<br><br>Interpretation: Large effectiveness of antibiotics in preventing complications related to LRTI and UTI can support better targeting of antibiotics to patients with higher complication risks.<br><br>Funding: Health Data Research UK and National Institute for Health Research.<br><br>Declaration of Interest: All authors declare the following: BG and OpenSAFELY 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, NHS England, 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, the Health Foundation, the World Health Organisation, UKRI MRC, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme; he is a Non-Executive Director at NHS Digital; he also receives personal income from speaking and writing for lay audiences on the misuse of science. AM has received consultancy fees (from https://inductionhealthcare.com) and is member of RCGP health informatics group and the NHS Digital GP data Professional Advisory Group that advises on access to GP Data for Pandemic Planning and Research (GDPPR). For the latter, he received payment for the GDPPR role.<br><br>Ethical Approval: This study was approved by the Health Research Authority and NHS Research Ethics Committee [REC reference 21/SC/0287].",,doi:https://doi.org/10.2139/ssrn.4547861; html:https://europepmc.org/article/PPR/PPR704199; doi:https://doi.org/10.2139/ssrn.4547861
 PPR191969,https://doi.org/10.1101/2020.07.22.20159772,Projecting contact matrices in 177 geographical regions: an update and comparison with empirical data for the COVID-19 era,"Prem K, van Zandvoort K, Klepac P, Eggo RM, Davies NG, Cook AR, Jit M, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group.",,No Journal Info,2020,2020-07-25,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 reproduce the main traits of 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. <h4>Author summary</h4> The risk of contracting a directly transmitted infectious disease such as the Coronavirus Disease 2019 (COVID-19) depends on who interacts with whom. Such person-to-person interactions vary by age and locations—e.g., at home, at work, at school, or in the community—due to the different social structures. These social structures, and thus contact patterns, vary across and within countries. Although social contact patterns can be measured using contact surveys, the majority of countries around the world, particularly low- and middle-income countries, lack nationally representative contact surveys. A simple way to present contact data is to use matrices where the elements represent the rate of contact between subgroups such as age groups represented by the columns and rows. In 2017, we generated age- and location-specific synthetic contact matrices for 152 geographical regions by adapting contact pattern data from eight European countries using country-specific data on household size, school and workplace composition. We have now updated these matrices with the most recent data (Demographic Household Surveys, World Bank, UN Population Division) extending the coverage to 177 geographical locations, covering 97.2% of the world’s population. We also quantified contact patterns in rural and urban settings. When compared to out-of-sample empirically-measured contact patterns, we found that the synthetic matrices reproduce the main features of these contact patterns.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/07/28/2020.07.22.20159772.full.pdf; doi:https://doi.org/10.1101/2020.07.22.20159772; html:https://europepmc.org/article/PPR/PPR191969; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR191969&type=FILE&fileName=EMS87995-pdf.pdf&mimeType=application/pdf
@@ -311,9 +311,9 @@ PPR223257,https://doi.org/10.1101/2020.10.06.328328,MAJORA: Continuous integrati
 PPR305511,https://doi.org/10.2139/ssrn.3805856,An External Validation of the QCovid Risk Prediction Algorithm for Risk of Mortality from COVID-19 in Adults: National Validation Cohort Study in Scotland,"Simpson C, Robertson C, Kerr S, Shi T, Vasileiou E, Moore E, McCowan C, Agrawal U, Stagg H, Docherty A, Mulholland R, Murray J, Ritchie LD, McMenamin J, Hippisley-Cox J, Sheikh A.",,No Journal Info,2021,2021-03-16,N,,,,"Background:  The QCovid algorithm is a risk prediction tool for COVID-19 hospitalisation and mortality that can be used to stratify patients by risk into vulnerability groups . We carried out an external validation of the QCovid algorithm in Scotland.<br><br>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 polymerase chain reaction (RT-PCR) virology testing, hospitalisation and mortality data. We assessed the performance of the QCovid algorithm in predicting COVID-19 hospitalisation and deaths in our dataset for two time periods: 1 March, 2020 to 30 April, 2020, and 1 May, 2020 to 30 June, 2020.<br><br>Findings: Our dataset comprised 5,384,819 individuals, representing 99% of the estimated population (5,463,300) resident in Scotland in 2020. The algorithm showed excellent calibration in both time periods with close correspondence between observed and predicted risks. Harrell ’s C for deaths in males and females in the first period was 0.946 (95% CI: 0.941 - 0.951) and 0.925 (95% CI: 0.919 - 0.931) respectively. Harrell’s C for hospitalisations in males and females in the first period was 0.809 (95% CI: 0.801 - 0.817) and 0.816 (95% CI: 0.808 - 0.823) respectively.<br><br>Interpretation: The QCovid algorithm shows high levels of external validity in predicting the risk of COVID- 19 hospitalisation and death in the population of Scotland.<br><br>Funding:  Medical Research Council, National Institute for Health Research Health Technology Assessment Programme, funded through the UK Research and Innovation Industrial Strategy Challenge Fund Health Data Research UK.<br><br>Declaration of Interests: Dr. Hippisley-Cox reports grants from MRC, grants from Wellcome Trrust, grants from NIHR, during the conduct of the study; other from ClinRisk Ltd, outside the submitted work. Dr. Sheikh reports grants from NIHR, grants from MRC, grants from HRR UK, during the conduct of the study. All other authors report no conflict of interest.<br><br>Ethics Approval Statement: Ethical permission for this study was granted from South East Scotland Research Ethics Committee 02 [12/SS/0201]. The Public Benefit and Privacy Panel Committee of Public Health Scotland, approved the linkage and analysis of the de-identified datasets for this project [1920-0279].",,doi:https://doi.org/10.2139/ssrn.3805856; html:https://europepmc.org/article/PPR/PPR305511; doi:https://doi.org/10.2139/ssrn.3805856
 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,,,,"<h4>Background</h4> 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. <h4>Methods</h4> 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). <h4>Findings</h4> 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. <h4>Interpretation</h4> 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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0237298&type=printable; 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
 PPR272966,https://doi.org/10.1101/2021.01.22.21250304,Rates of serious clinical outcomes in survivors of hospitalisation with COVID-19: a descriptive cohort study within the OpenSAFELY platform,"The OpenSAFELY Collaborative, Tazare J, Tazare J, Walker AJ, Tomlinson L, Hickman G, Rentsch CT, Williamson EJ, Bhaskaran K, Evans D, Wing K, Mathur R, Wong AY, Schultze A, Bacon S, Bates C, Morton CE, Curtis HJ, Nightingale E, McDonald HI, Mehrkar A, Inglesby P, Davy S, MacKenna B, Cockburn J, Hulme WJ, Hulme WJ, Warren-Gash C, Bhate K, Nitsch D, Powell E, Mulick A, Forbes H, Minassian C, Croker R, Parry J, Hester F, Harper S, Eggo RM, Evans SJ, Smeeth L, Douglas IJ, Goldacre B.",,No Journal Info,2021,2021-01-25,Y,,,,"<h4>Background</h4> Patients with COVID-19 are thought to be at higher risk of cardiometabolic and pulmonary complications, but quantification of that risk is limited. We aimed to describe the overall burden of these complications in survivors of severe COVID-19. <h4>Methods</h4> Working on behalf of NHS England, we used linked primary care records, death certificate and hospital data from the OpenSAFELY platform. We constructed three cohorts: patients discharged following hospitalisation with COVID-19, patients discharged following hospitalisation with pneumonia in 2019, and a frequency-matched cohort from the general population in 2019. We studied eight cardiometabolic and pulmonary outcomes. Absolute rates were measured in each cohort and Cox regression models were fitted to estimate age/sex adjusted hazard ratios comparing outcome rates between discharged COVID-19 patients and the two comparator cohorts. <h4>Results</h4> Amongst the population of 31,716 patients discharged following hospitalisation with COVID-19, rates for majority of outcomes peaked in the first month post-discharge, then declined over the following four months. Patients in the COVID-19 population had markedly increased risk of all outcomes compared to matched controls from the 2019 general population, especially for pulmonary embolism (HR 12.86; 95% CI: 11.23 - 14.74). Outcome rates were more similar when comparing patients discharged with COVID-19 to those discharged with pneumonia in 2019, although COVID-19 patients had increased risk of type 2 diabetes (HR 1.23; 95% CI: 1.05 - 1.44). <h4>Interpretation</h4> Cardiometabolic and pulmonary adverse outcomes are markedly raised following hospitalisation for COVID-19 compared to the general population. However, the excess risks were more comparable to those seen following hospitalisation with pneumonia. Identifying patients at particularly high risk of outcomes would inform targeted preventive measures. <h4>Funding</h4> Wellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, UK Research and Innovation, Health and Safety Executive.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/04/13/2021.01.22.21250304.full.pdf; doi:https://doi.org/10.1101/2021.01.22.21250304; html:https://europepmc.org/article/PPR/PPR272966; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR272966&type=FILE&fileName=EMS114490-pdf.pdf&mimeType=application/pdf
-PPR639769,https://doi.org/10.1101/2023.04.01.23287538,Trends in weight gain recorded in English primary care before and during the Coronavirus-19 pandemic: an observational cohort study using the OpenSAFELY platform,"Samuel M, Park RY, Eastwood SV, Eto F, Morton CE, Stow D, Bacon S, Mehrkar A, Morley J, Dillingham I, Inglesby P, Hulme WJ, Khunti K, Mathur R, Valabhji J, MacKenna B, Finer S, The OpenSAFELY Collaborative.",,No Journal Info,2023,2023-04-03,Y,,,,"<h4>Background</h4> We investigated which clinical and sociodemographic characteristics were associated with unhealthy patterns of weight gain amongst adults living in England during the pandemic. <h4>Methods</h4> With the approval of NHS England we conducted an observational cohort study of Body Mass Index (BMI) changes between March 2015 and March 2022 using the OpenSAFELY-TPP platform. We estimated individual rates of weight gain before and during the pandemic, and identified individuals with rapid weight gain (>0·5kg/m 2 /year) in each period. We also estimated the change in rate of weight gain between the prepandemic and pandemic period and defined extreme-accelerators as the ten percent of individuals with the greatest increase (>1·84kg/m 2 /year). We estimated associations with these outcomes using multivariate logistic regression. <h4>Findings</h4> We extracted data on 17,742,365 adults (50·1% female, 76·1% White British). Median BMI increased from 27·8kg/m 2 [IQR:24·3-32·1] in 2019 (March 2019 to February 2020) to 28·0kg/m 2 [24·4-32·6] in 2021. Rapid pandemic weight gain (n=3,214,155) was associated with female sex (male vs female: aOR 0·76 [95%CI:0·76-0·76]); younger age (50-59-years vs 18–29-years: aOR 0·60 [0·60-0·61]); White British ethnicity (Black Caribbean vs White British: aOR 0·91 [0·89-0·94]); deprivation (least-deprived-IMD-quintile vs most-deprived: aOR 0·77 [0·77-0·78]); and long-term conditions, of which mental health conditions had the greatest effect (e.g. depression (aOR 1·18[1·17-1·18])). Similar characteristics increased risk of extreme acceleration (n=2,768,695). <h4>Interpretation</h4> We found female sex, younger age, deprivation and mental health conditions increased risk of unhealthy patterns of pandemic weight gain. This highlights the need to incorporate sociodemographic, physical, and mental health characteristics when formulating post-pandemic research, policies, and interventions targeting BMI. <h4>Funding</h4> NIHR",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/04/03/2023.04.01.23287538.full.pdf; doi:https://doi.org/10.1101/2023.04.01.23287538; html:https://europepmc.org/article/PPR/PPR639769; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR639769&type=FILE&fileName=EMS173550-pdf.pdf&mimeType=application/pdf
 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,,,,"<h4>Purpose</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Conclusion</h4> 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.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/01/15/2021.01.12.21249672.full.pdf; 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
 PPR184933,https://doi.org/10.1101/2020.07.07.20148460,Reconstructing the early global dynamics of under-ascertained COVID-19 cases and infections,"Russell TW, Russell TW, Golding N, Hellewell J, Abbott S, Wright L, Pearson CAB, Pearson CAB, Zandvoort Kv, Jarvis CI, Gibbs H, Liu Y, Eggo RM, Edmunds WJ, Kucharski AJ.",,No Journal Info,2020,2020-07-08,Y,,,,"<h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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 6th 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 the 7th June, our seroprevalence estimates range from 0% (many countries) to 13% (95% CrI: 5.6% – 24%) (Belgium). <h4>Conclusions</h4> 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. <h4>Funding</h4> Wellcome Trust, Bill & Melinda Gates Foundation, DFID, NIHR, GCRF, ARC.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01790-9; doi:https://doi.org/10.1101/2020.07.07.20148460; html:https://europepmc.org/article/PPR/PPR184933; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR184933&type=FILE&fileName=EMS87337-pdf.pdf&mimeType=application/pdf
+PPR639769,https://doi.org/10.1101/2023.04.01.23287538,Trends in weight gain recorded in English primary care before and during the Coronavirus-19 pandemic: an observational cohort study using the OpenSAFELY platform,"Samuel M, Park RY, Eastwood SV, Eto F, Morton CE, Stow D, Bacon S, Mehrkar A, Morley J, Dillingham I, Inglesby P, Hulme WJ, Khunti K, Mathur R, Valabhji J, MacKenna B, Finer S, The OpenSAFELY Collaborative.",,No Journal Info,2023,2023-04-03,Y,,,,"<h4>Background</h4> We investigated which clinical and sociodemographic characteristics were associated with unhealthy patterns of weight gain amongst adults living in England during the pandemic. <h4>Methods</h4> With the approval of NHS England we conducted an observational cohort study of Body Mass Index (BMI) changes between March 2015 and March 2022 using the OpenSAFELY-TPP platform. We estimated individual rates of weight gain before and during the pandemic, and identified individuals with rapid weight gain (>0·5kg/m 2 /year) in each period. We also estimated the change in rate of weight gain between the prepandemic and pandemic period and defined extreme-accelerators as the ten percent of individuals with the greatest increase (>1·84kg/m 2 /year). We estimated associations with these outcomes using multivariate logistic regression. <h4>Findings</h4> We extracted data on 17,742,365 adults (50·1% female, 76·1% White British). Median BMI increased from 27·8kg/m 2 [IQR:24·3-32·1] in 2019 (March 2019 to February 2020) to 28·0kg/m 2 [24·4-32·6] in 2021. Rapid pandemic weight gain (n=3,214,155) was associated with female sex (male vs female: aOR 0·76 [95%CI:0·76-0·76]); younger age (50-59-years vs 18–29-years: aOR 0·60 [0·60-0·61]); White British ethnicity (Black Caribbean vs White British: aOR 0·91 [0·89-0·94]); deprivation (least-deprived-IMD-quintile vs most-deprived: aOR 0·77 [0·77-0·78]); and long-term conditions, of which mental health conditions had the greatest effect (e.g. depression (aOR 1·18[1·17-1·18])). Similar characteristics increased risk of extreme acceleration (n=2,768,695). <h4>Interpretation</h4> We found female sex, younger age, deprivation and mental health conditions increased risk of unhealthy patterns of pandemic weight gain. This highlights the need to incorporate sociodemographic, physical, and mental health characteristics when formulating post-pandemic research, policies, and interventions targeting BMI. <h4>Funding</h4> NIHR",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/04/03/2023.04.01.23287538.full.pdf; doi:https://doi.org/10.1101/2023.04.01.23287538; html:https://europepmc.org/article/PPR/PPR639769; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR639769&type=FILE&fileName=EMS173550-pdf.pdf&mimeType=application/pdf
 PPR425646,https://doi.org/10.1101/2021.11.27.21266930,Dosing interval strategies for two-dose COVID-19 vaccination in 13 low- and middle-income countries of Europe: health impact modelling and benefit-risk analysis,"Liu Y, Pearson CA, Sandmann FG, Barnard RC, Kim J, Flasche S, Jit M, Abbas K, CMMID COVID-19 Working Group.",,No Journal Info,2021,2021-11-28,Y,,,,"<h4>Summary</h4> <h4>Background</h4> In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine could let 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 for low- and middle-income countries of Europe. <h4>Methods</h4> We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 low- and middle-income countries in the World Health Organization European Region (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 the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies related 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 into the model, and also conducted a benefit-risk assessment to quantify the trade-off between health benefits versus adverse events following immunisation. <h4>Findings</h4> In 12 of the 13 countries, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20-59 years). These strategies lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.2% [range: 4.0% - 22.5%; n = 13 (countries)] more deaths. There is generally a negative association between dosing interval and COVID-19 mortality within the range we investigated. Assuming a shorter first dose waning duration of 120 days, as opposed to 360 days in the base case, led to shorter optimal dosing intervals of 8-12 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks. <h4>Interpretation</h4> We infer that longer dosing intervals of over six months, which are substantially longer than the current label recommendation for most vaccine products, could reduce COVID-19 mortality in low- and middle-income countries of WHO/Europe. Certain vaccine features, such as fast waning of first doses, significantly shorten the optimal dosing intervals. <h4>Funding</h4> World Health Organization",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/11/28/2021.11.27.21266930.full.pdf; doi:https://doi.org/10.1101/2021.11.27.21266930; html:https://europepmc.org/article/PPR/PPR425646; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR425646&type=FILE&fileName=EMS140311-pdf.pdf&mimeType=application/pdf
 PPR387586,https://doi.org/10.1101/2021.08.23.21262209,Population birth outcomes in 2020 and experiences of expectant mothers during the COVID-19 pandemic: a ‘Born in Wales’ mixed methods study using routine data,"Jones H, Seaborne M, Cowley L, Odd D, Paranjothy S, Akbari A, Brophy S.",,No Journal Info,2021,2021-08-23,Y,,,,"<h4>Background</h4> Pregnancy can be a stressful time and the COVID-19 pandemic has affected all aspects of life. This study aims to investigate the impact of the pandemic on population birth outcomes in Wales, rates of primary immunisations and examine expectant mothers’ experiences of pregnancy including self-reported levels of stress and anxiety. <h4>Methods</h4> Population-level birth outcomes in Wales: Stillbirths, prematurity, birth weight and Caesarean section births before (2016–2019) and during (2020) the pandemic were compared using national-level routine anonymised data held in the Secure Anonymised Information Linkage (SAIL) Databank. The first three scheduled primary immunisations were compared between 2019 and 2020. Self-reported pregnancy experience: 215 expectant mothers (aged 16+) in Wales completed an online survey about their experiences of pregnancy during the pandemic. The qualitative survey data was analysed using codebook thematic analysis. <h4>Findings</h4> There was no significant difference between annual outcomes including gestation and birth weight, stillbirths, and Caesarean sections for infants born in 2020 compared to 2016-2019. There was an increase in late term births (≥42 weeks gestation) during the first lockdown (OR: 1.28, p=0.019) and a decrease in moderate to late preterm births (32-36 weeks gestation) during the second lockdown (OR: 0.74, p=0.001). Fewer babies were born in 2020 (N=29,031) compared to 2016-2019 (average N=32,582). All babies received their immunisations in 2020, but there were minor delays in the timings of vaccines. Those due at 8-weeks were 8% less likely to be on time (within 28-days) and at 16-weeks, they were 19% less likely to be on time. The pandemic had a negative impact on the mental health of 71% of survey respondents, who reported anxiety, stress and loneliness; this was associated with attending scans without their partner, giving birth alone, and minimal contact with midwives. <h4>Interpretation</h4> The pandemic had a negative impact on mothers’ experiences of pregnancy; however, population-level data suggests that this did not translate to adverse birth outcomes for babies born during the pandemic.",,pdf:https://aura.abdn.ac.uk/bitstream/2164/18632/1/Jones_etal_PO_Population_Birth_Outcomes_VoR.pdf; doi:https://doi.org/10.1101/2021.08.23.21262209; html:https://europepmc.org/article/PPR/PPR387586; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR387586&type=FILE&fileName=EMS134441-pdf.pdf&mimeType=application/pdf
 PPR645696,https://doi.org/10.1101/2023.04.14.23287661,"Determining prescriptions in electronic healthcare record (EHR) 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.",,No Journal Info,2023,2023-04-17,Y,,,,"<h4>ABSTRACT</h4> <h4>Objective</h4> Epidemiological research using electronic healthcare records(EHR) informing everyday patient care uses combinations of codes (“codelists”) to define diseases and prescriptions (or phenotypes). Yet methodology for codelist generation varies, manifesting in misclassification bias, while there are drug-specific codelist considerations. <h4>Materials and Methods</h4> We developed methods to generate drug codelists, testing this using the Clinical Practice Research Datalink (CPRD) Aurum database, accounting for missing data in “attribute” search variables. 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 on all search variables (A,”gold standard”) to B) chemical and C) ontological information only. <h4>Results</h4> In Search A we determined 165,150 patients prescribed cardiovascular drugs(49.2% of cohort), and 317,963 prescribed COPD inhalers (94.7% of cohort). Considering output per value set, Search C missed substantial prescriptions, including vasodilator anti-hypertensives (A and B:19,696 prescriptions; C:1,145) and SAMA inhalers (A and B:35,310; C:564). <h4>Discussion</h4> We recommend the full methods (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. <h4>Conclusions</h4> <h4>Methods: </h4> must have end-to-end clinical input, and be standardizable, reproducible, and understandable to all researchers across data contexts. <h4>LAY ABSTRACT</h4> Health research using patient records informs everyday medicine, using groups of codes (“codelists”) to define diseases and drugs. Yet methods to create drug codelists are inconsistent, may not include physician expertise, nor be reported. We developed a reproducible method to create drug codelists, testing it using de-identified healthcare records. We generated codelists for 1) heart conditions and 2) inhalers to identify prescriptions in a sample group of 335,931 patients with chronic lung disease. We compared our full methods (Search A) to two restricted searches to show prescriptions can be missed if necessary considerations are not made. In search A, we determined 165,150 people (49.2% of sample group) prescribed drugs from the heart codelist. For lung inhalers, we determined 317,963 prescriptions (94.7% of group). Search C missed substantial prescriptions, for drugs lowering blood pressure by opening vessels (A and B:19,696 prescriptions; C: 1,145), and short-term inhalers opening airways (A and B: 35,310; C:564). We recommend full methods(A) for completeness. Drug codelist methods must be consistent, duplicable, and include physician input at all research stages, and have special considerations including status (eg, new, taken off market), disease, and drug categorical system. Quality methods should be freely accessible and usable across study contexts.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/04/17/2023.04.14.23287661.full.pdf; doi:https://doi.org/10.1101/2023.04.14.23287661; html:https://europepmc.org/article/PPR/PPR645696; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR645696&type=FILE&fileName=EMS174337-pdf.pdf&mimeType=application/pdf
@@ -323,8 +323,8 @@ PPR197688,https://doi.org/10.1101/2020.08.07.20169490,HIV infection and COVID-19
 PPR693212,https://doi.org/10.1101/2023.07.16.23292723,Evaluation of the impact of COVID-19 pandemic on hospital admission related to common infections,"Fahmi A, Palin V, Zhong X, Yang Y, Watts S, Ashcroft DM, Goldacre B, Mackenna B, Fisher L, Massey J, Mehrkar A, Bacon S, Hand K, Staa TPv, OpenSAFELY collaborative.",,No Journal Info,2023,2023-07-18,Y,,,,"<h4>Background</h4> Antimicrobial resistance (AMR) is a multifaceted global challenge, partly driven by inappropriate antibiotic prescribing. The COVID-19 pandemic impacted antibiotic prescribing for common bacterial infections. This highlights the need to examine risk of hospital admissions related to common infections, excluding COVID-19 infections during the pandemic. <h4>Methods</h4> With the approval of NHS England, we accessed electronic health records from The Phoenix Partnership (TPP) through OpenSAFELY platform. We included patients with primary care diagnosis of common infections, including lower respiratory tract infection (LRTI), upper respiratory tract infections (URTI), and lower urinary tract infection (UTI), from January 2019 to August 2022. We excluded patients with a COVID-19 record 90 days before to 30 days after the infection diagnosis. Using Cox proportional-hazard regression models, we predicted risk of infection-related hospital admission in 30 days follow-up period after the diagnosis. <h4>Results</h4> We found 12,745,165 infection diagnoses from January 2019 to August 2022. Of them, 80,395 (2.05%) cases were admitted to hospital in the follow-up period. Counts of hospital admission for infections dropped during COVID-19, e.g., LRTI from 3,950 in December 2019 to 520 in April 2020. Comparing those prescribed an antibiotic to those without, reduction in risk of hospital admission were largest with LRTI (adjusted odds ratio (OR) of 0.35; 95% CI, 0.35-0.36) and UTI (adjusted OR 0.45; 95% CI, 0.44-0.46), compared to URTI (adjusted OR 1.04; 95% CI, 1.03-1.06). <h4>Conclusion</h4> Large effectiveness of antibiotics in preventing complications related to LRTI and UTI can support better targeting of antibiotics to patients with higher complication risks. <h4>Key messages</h4> - The main drivers of infection-related hospital admission are age, Charlson comorbidity index, and history of prior antibiotics. - Antibiotics are more effective in preventing hospital admission related to infections such as lower respiratory tract infection and urinary tract infection, rather than upper respiratory tract infection. - Common antibiotic types are associated with more reduction in the risk of infection-related hospital admission.",,doi:https://doi.org/10.1101/2023.07.16.23292723; html:https://europepmc.org/article/PPR/PPR693212; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR693212&type=FILE&fileName=EMS181508-pdf.pdf&mimeType=application/pdf
 PPR181164,https://doi.org/10.1101/2020.06.28.20141986,Protocol for the development and evaluation of a tool for predicting risk of short-term adverse outcomes due to COVID-19 in the general UK population,"Hippisley-Cox J, Clift AK, Coupland C, Keogh R, Diaz-Ordaz K, Williamson E, Harrison EM, Hayward A, Hemingway H, Horby P, Mehta N, Benger J, Khunti K, Speigelhalter D, Sheikh A, Valabhji J, Lyons RA, Robson J, Semple C, Kee F, Johnson P, Jebb S, Williams T, Coggon D.",,No Journal Info,2020,2020-06-29,Y,,,,"<h4>Introduction</h4> Novel coronavirus 2019 (COVID-19) has propagated a global pandemic with significant health, economic and social costs. Emerging emergence has suggested that several factors may be associated with increased risk from severe outcomes or death from COVID-19. Clinical risk prediction tools have significant potential to generate individualised assessment of risk and may be useful for population stratification and other use cases. <h4>Methods and analysis</h4> We will use a prospective open cohort study of routinely collected data from 1205 general practices in England in the QResearch database. The primary outcome is COVID-19 mortality (in or out-of-hospital) defined as confirmed or suspected COVID-19 mentioned on the death certificate, or death occurring in a person with SARS-CoV-2 infection between 24 th January and 30 th April 2020. Our primary outcome in adults is COVID-19 mortality (including out of hospital and in hospital deaths). We will also examine COVID-19 hospitalisation in children. Time-to-event models will be developed in the training data to derive separate risk equations in adults (19-100 years) for males and females for evaluation of risk of each outcome within the 3-month follow-up period (24 th January to 30 th April 2020), accounting for competing risks. Predictors considered will include age, sex, ethnicity, deprivation, smoking status, alcohol intake, body mass index, pre-existing medical co-morbidities, and concurrent medication. Measures of performance (prediction errors, calibration and discrimination) will be determined in the test data for men and women separately and by ten-year age group. For children, descriptive statistics will be undertaken if there are currently too few serious events to allow development of a risk model. The final model will be externally evaluated in (a) geographically separate practices and (b) other relevant datasets as they become available. <h4>Ethics and dissemination</h4> The project has ethical approval and the results will be submitted for publication in a peer-reviewed journal. <h4>Strengths and limitations of the study</h4> The individual-level linkage of general practice, Public Health England testing, Hospital Episode Statistics and Office of National Statistics death register datasets enable a robust and accurate ascertainment of outcomes The models will be trained and evaluated in population-representative datasets of millions of individuals Shielding for clinically extremely vulnerable was advised and in place during the study period, therefore risk predictions influenced by the presence of some ‘shielding’ conditions may require careful consideration",,pdf:https://cronfa.swan.ac.uk/Record/cronfa56443/Download/56443__19579__328488e6081241e6ac52f898b33353dc.pdf; doi:https://doi.org/10.1101/2020.06.28.20141986; html:https://europepmc.org/article/PPR/PPR181164; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR181164&type=FILE&fileName=EMS87472-pdf.pdf&mimeType=application/pdf
 PPR609122,https://doi.org/10.1101/2023.01.25.23285005,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.",,No Journal Info,2023,2023-01-28,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 transmissibility. 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. <h4>Author Summary</h4> Predicting the sub-national spread of infectious disease requires accurate measurements of inter-regional travel networks. Often, this information is derived from the patterns of mobile device connections to the cellular network. This travel data is then used as an input to epidemiological models of infection transmission, defining the likelihood that disease is “exported” between regions. In this paper, we use one mobile device dataset collected in Ghana in 2021, aggregated according to two different methodologies which represent different aspects of inter-regional travel. We show how the choice of aggregation methodology leads to different predicted epidemics, and highlight the conditions under which models of infection transmission may be influenced by methodological choices in the aggregation of travel data used to parameterize these models. For example, we show how aggregation methodology changes predicted epidemics for less-transmissible infections and under certain models of human movement. We also highlight areas of relative stability, where aggregation choices do not alter predicted epidemics, such as cases where an infection is highly transmissible or is introduced into a central location.",,doi:https://doi.org/10.1101/2023.01.25.23285005; html:https://europepmc.org/article/PPR/PPR609122; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR609122&type=FILE&fileName=EMS163650-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2023/01/28/2023.01.25.23285005.full.pdf
-PPR296515,https://doi.org/10.1101/2021.03.11.21253189,"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, Hertog HMd, Ribbers T, Nieuwkamp D, Houwelingen RCv, Dias A, Uden IWv, Kerklaan JP, Bienfait HP, Vermeer SE, de Jong SW, Ali M, Wermer MJ, de Graaf MT, Brouwers PJ, Asselbergs FW, Kappelle LJ, van der Worp HB, Algra AM.",,No Journal Info,2021,2021-03-12,N,,,,"<h4>Background and purpose</h4> The frequency of ischemic stroke in patients with 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. <h4>Methods</h4> We included patients with a laboratory confirmed SARS-CoV-2 infection admitted in 16 hospitals participating in the international CAPACITY-COVID registry between March 1 st and August 1 st , 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. <h4>Results</h4> We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit (ICU). 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 onset of COVID-19 symptoms and diagnosis of stroke was two weeks. The incidence of ischemic stroke was higher among patients who were treated at an ICU (16/586; 2.7% versus 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 RR: 2.08; 95%CI:1.52-2.84). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functional dependent at discharge and in-hospital mortality. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted RR 1.56; 95%CI:1.13-2.15) than patients without stroke. <h4>Conclusions</h4> In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was approximately 2%, with a higher risk in patients treated at an ICU. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.121.034787; doi:https://doi.org/10.1101/2021.03.11.21253189; html:https://europepmc.org/article/PPR/PPR296515; doi:https://doi.org/10.1101/2021.03.11.21253189
 PPR256751,https://doi.org/10.1101/2020.12.10.20245944,"Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial","Horby PW, Roddick A, Spata E, Staplin N, Emberson JR, Pessoa-Amorim G, Peto L, Campbell M, Brightling C, Prudon B, Chadwick D, Ustianowski A, Ashish A, Todd S, Yates B, Buttery R, Scott S, Maseda D, 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, Haynes R, Landray MJ, RECOVERY Collaborative Group.",,No Journal Info,2020,2020-12-14,Y,,,,"<h4>SUMMARY</h4> <h4>Background</h4> Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We evaluated the efficacy and safety of azithromycin in hospitalised patients with COVID-19. <h4>Methods</h4> In this randomised, controlled, open-label, adaptive platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once daily by mouth or intravenously for 10 days or until discharge (or one of the other treatment arms). Patients were twice as likely to be randomised to usual care as to any of the active treatment groups. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ). <h4>Findings</h4> Between 7 April and 27 November 2020, 2582 patients were randomly allocated to receive azithromycin and 5182 patients to receive usual care alone. Overall, 496 (19%) patients allocated to azithromycin and 997 (19%) patients allocated to usual care died within 28 days (rate ratio 1·00; 95% confidence interval [CI] 0·90-1·12; p=0·99). Consistent results were seen in all pre-specified subgroups of patients. There was no difference in duration of hospitalisation (median 12 days vs. 13 days) or the proportion of patients discharged from hospital alive within 28 days (60% vs. 59%; rate ratio 1·03; 95% CI 0·97-1·10; p=0·29). Among those not on invasive mechanical ventilation at baseline, there was no difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0·97; 95% CI 0·89-1·07; p=0·54). <h4>Interpretation</h4> In patients hospitalised with COVID-19, azithromycin did not provide any clinical benefit. Azithromycin use in patients hospitalised with COVID-19 should be restricted to patients where there is a clear antimicrobial indication. <h4>Funding</h4> UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/12/14/2020.12.10.20245944.full.pdf; doi:https://doi.org/10.1101/2020.12.10.20245944; html:https://europepmc.org/article/PPR/PPR256751; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR256751&type=FILE&fileName=EMS109114-pdf.pdf&mimeType=application/pdf
+PPR296515,https://doi.org/10.1101/2021.03.11.21253189,"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, Hertog HMd, Ribbers T, Nieuwkamp D, Houwelingen RCv, Dias A, Uden IWv, Kerklaan JP, Bienfait HP, Vermeer SE, de Jong SW, Ali M, Wermer MJ, de Graaf MT, Brouwers PJ, Asselbergs FW, Kappelle LJ, van der Worp HB, Algra AM.",,No Journal Info,2021,2021-03-12,N,,,,"<h4>Background and purpose</h4> The frequency of ischemic stroke in patients with 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. <h4>Methods</h4> We included patients with a laboratory confirmed SARS-CoV-2 infection admitted in 16 hospitals participating in the international CAPACITY-COVID registry between March 1 st and August 1 st , 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. <h4>Results</h4> We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit (ICU). 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 onset of COVID-19 symptoms and diagnosis of stroke was two weeks. The incidence of ischemic stroke was higher among patients who were treated at an ICU (16/586; 2.7% versus 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 RR: 2.08; 95%CI:1.52-2.84). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functional dependent at discharge and in-hospital mortality. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted RR 1.56; 95%CI:1.13-2.15) than patients without stroke. <h4>Conclusions</h4> In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was approximately 2%, with a higher risk in patients treated at an ICU. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.121.034787; doi:https://doi.org/10.1101/2021.03.11.21253189; html:https://europepmc.org/article/PPR/PPR296515; doi:https://doi.org/10.1101/2021.03.11.21253189
 PPR235017,https://doi.org/10.1101/2020.11.05.20223289,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 M, Dutton EE, Tapeng L, Richard AC, Kirk PDW, Behmoaras J, Sandhu E, McAdoo SP, Prendecki MF, Pickering MC, Botto M, Willicombe M, Thomas DC, Peters JE.",,No Journal Info,2020,2020-11-06,Y,,,,"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. 203 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.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/02/15/2020.11.05.20223289.full.pdf; doi:https://doi.org/10.1101/2020.11.05.20223289; html:https://europepmc.org/article/PPR/PPR235017; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR235017&type=FILE&fileName=EMS103818-pdf.pdf&mimeType=application/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,,,,"<h4>ABSTRACT</h4> <h4>Objective</h4> 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). <h4>Method and Findings</h4> 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. <h4>Conclusions</h4> 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.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/01/17/2022.01.16.22269146.full.pdf; 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
 PPR341842,https://doi.org/10.2139/ssrn.3817437,Risk Factors for Developing COVID-19: A Population-Based Longitudinal Study (COVIDENCE UK),"Holt H, Talaei M, Greenig M, Zenner D, Symons J, Relton C, Young KS, Davies MR, Thompson KN, Ashman J, Rajpoot SS, Kayyale AA, Rifai SE, Lloyd PJ, Jolliffe DA, Finer S, Ilidriomiti S, Miners A, Hopkinson NS, Alam B, Pfeffer PE, McCoy D, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Breen G, Shaheen SO, Martineau AR.",,No Journal Info,2021,2021-04-01,N,,,,"Background: Risk factors for severe COVID-19 include older age, male sex, obesity, Black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain.<br><br>Methods: We undertook a prospective, population-based cohort study   (COVIDENCE UK) from 1  st  May 2020 to 5  th  February 2021  . Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted odds ratios (aORs) for associations between potential risk factors and risk of COVID-19.<br><br>Findings: We recorded 446 incident cases of COVID-19 in 15,227 participants (2.9%). Increased risk of developing COVID-19 was independently associated with Asian/Asian British  vs  . White ethnicity (aOR 2.31, 95% CI 1.35-3.95), household overcrowding  (aOR per additional 0.5 people/bedroom 1.26, 1.11-1.43)  , any  vs  . no visits to/from other households in previous week (aOR 1.33, 1.07-1.64), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.01-1.09), frontline occupation excluding health/social care  vs.  no frontline occupation (aOR 1.49, 1.12-1.98), and raised body mass index (BMI) (aOR 1.51 [1.20-1.90] for BMI 25.0-30.0 kg/m  2  and 1.38 [1.05-1.82] for BMI >30.0 kg/m  2  vs.  BMI <25.0 kg/m  2  ). Atopic disease was independently associated with decreased risk (aOR 0.76, 0.59-0.98). No independent associations were seen for age, sex, other medical conditions, diet, or micronutrient supplement use.<br><br>Interpretation: After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased risk of developing COVID-19, while atopic disease was associated with decreased risk.<br><br>Trial Registration: It is registered with ClinicalTrials.gov (NCT04330599).<br><br>Funding: Barts Charity, Health Data Research UK<br><br>Declaration of Interest: None to declare. <br><br>Ethical Approval: The study was sponsored by Queen Mary University of London and approved by<br>Leicester South Research Ethics Committee (ref 20/EM/0117).",,pdf:http://pure-oai.bham.ac.uk/ws/files/148236929/holth2021risk.pdf; doi:https://doi.org/10.2139/ssrn.3817437; html:https://europepmc.org/article/PPR/PPR341842; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR341842&type=FILE&fileName=EMS124907-pdf.pdf&mimeType=application/pdf; doi:https://doi.org/10.2139/ssrn.3817437
diff --git a/data/covid/papers.csv b/data/covid/papers.csv
index 7d31b668..84f5dadc 100644
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@@ -140,8 +140,8 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 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; doi:https://doi.org/10.1016/j.lanepe.2023.100638; html:https://europepmc.org/articles/PMC10139952; pdf:https://europepmc.org/articles/PMC10139952?pdf=render
 34850818,https://doi.org/10.1093/ageing/afab223,"COVID-19 infection risk amongst 14,104 vaccinated care home residents: a national observational longitudinal cohort study in Wales, UK, December 2020-March 2021. ","Hollinghurst J, North L, Perry M, Akbari A, Gravenor MB, Lyons RA, Fry R.",,Age and ageing,2022,2022-01-01,Y,,,,"vaccinations for COVID-19 have been prioritised for older people living in care homes. However, vaccination trials included limited numbers of older people. we aimed to study infection rates of SARS-CoV-2 for older care home residents following vaccination and identify factors associated with increased risk of infection. we conducted an observational data-linkage study including 14,104 vaccinated older care home residents in Wales (UK) using anonymised electronic health records and administrative data. we used Cox proportional hazards models to estimate hazard ratios (HRs) for the risk of testing positive for SARS-CoV-2 infection following vaccination, after landmark times of either 7 or 21 days post-vaccination. We adjusted HRs for age, sex, frailty, prior SARS-CoV-2 infections and vaccination type. we observed a small proportion of care home residents with positive polymerase chain reaction (tests following vaccination 1.05% (N = 148), with 90% of infections occurring within 28 days. For the 7-day landmark analysis we found a reduced risk of SARS-CoV-2 infection for vaccinated individuals who had a previous infection; HR (95% confidence interval) 0.54 (0.30, 0.95). For the 21-day landmark analysis, we observed high HRs for individuals with low and intermediate frailty compared with those without; 4.59 (1.23, 17.12) and 4.85 (1.68, 14.04), respectively. increased risk of infection after 21 days was associated with frailty. We found most infections occurred within 28 days of vaccination, suggesting extra precautions to reduce transmission risk should be taken in this time frame.",,pdf:https://academic.oup.com/ageing/article-pdf/51/1/afab223/42083726/afab223.pdf; doi:https://doi.org/10.1093/ageing/afab223; html:https://europepmc.org/articles/PMC8690013; pdf:https://europepmc.org/articles/PMC8690013?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>UK Government Department of Health and Social Care.",,doi:https://doi.org/10.1016/s2666-7568(22)00147-7; 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
-37674175,https://doi.org/10.1186/s12884-023-05958-y,Using the COM-B framework to elucidate facilitators and barriers to COVID-19 vaccine uptake in pregnant women: a qualitative study.,"Patterson L, Berry E, Parsons C, Clarke B, Little A, Beggs J, Chuter A, Jackson T, Hsia Y, McGrath H, Millman C, Murphy S, Bradley DT, Milligan S.",,BMC pregnancy and childbirth,2023,2023-09-06,Y,Pregnancy; Qualitative; Barriers; Facilitators; Com-b; Covid-19 Vaccination,,,"Since April 2021, COVID-19 vaccines have been recommended for pregnant women. Despite this, COVID-19 vaccine uptake in this group is low compared to the non-pregnant population of childbearing age. Our aim was to understand barriers and facilitators to COVID-19 vaccine uptake among pregnant women in Northern Ireland using the COM-B framework, and so to make recommendations for public health interventions. The COM-B proposes that human behaviour is influenced by the extent to which a person has the capability, opportunity, and motivation to enact that behaviour. Understanding the factors underpinning behaviour through this lens helps discern what needs to change to change behaviour, therefore supporting the development of targeted interventions.This study consisted of eight semi-structured interviews with new/expectant mothers who did not receive a COVID-19 vaccine dose while pregnant since April 2021, and a focus group with five participants who received at least one COVID-19 vaccine dose while pregnant. Interview and focus group data were analysed using semi-deductive reflexive thematic analysis framed by a subtle realist approach. The COM-B was used to categorise codes and subthemes were developed within each COM-B construct.Within Psychological Capability, subthemes captured the need for consistent and reliable COVID-19 vaccine information and access to balanced and jargon-free, risk-benefit information that is tailored to the pregnant individual. The behaviour/opinions of family, friends, and local healthcare providers had a powerful influence on COVID-19 vaccine decisions (Social Opportunity). Integrating the COVID-19 vaccine as part of routine antenatal pathways was believed to support access and sense of familiarity (Physical Opportunity). Participants valued health autonomy, however experienced internal conflict driven by concerns about long-term side effects for their baby (Reflective Motivation). Feelings of fear, lack of empathy from healthcare providers, and anticipated guilt commonly underpinned indecision as to whether to get the vaccine (Automatic Motivation).Our study highlighted that the choice to accept a vaccine during pregnancy generates internal conflict and worry. Several participants cited their concern was primarily around the safety for their baby. Healthcare professionals (HCPs) play a significant part when it comes to decision making about COVID-19 vaccines among pregnant women. HCPs and pregnant women should be involved in the development of interventions to improve the delivery and communication of information.",,pdf:https://bmcpregnancychildbirth.biomedcentral.com/counter/pdf/10.1186/s12884-023-05958-y; doi:https://doi.org/10.1186/s12884-023-05958-y; html:https://europepmc.org/articles/PMC10481472; pdf:https://europepmc.org/articles/PMC10481472?pdf=render
 35501391,https://doi.org/10.1038/s41416-022-01830-6,"Impact of the SARS-CoV-2 pandemic on female breast, colorectal and non-small cell lung cancer incidence, stage and healthcare pathway to diagnosis during 2020 in Wales, UK, using a national cancer clinical record system.","Greene G, Griffiths R, Han J, Akbari A, Jones M, Lyons J, Lyons RA, Rolles M, Torabi F, Warlow J, Morris ERA, Lawler M, Huws DW.",,British journal of cancer,2022,2022-05-02,Y,,,,"<h4>Background</h4>COVID-19 pandemic responses impacted behaviour and health services. We estimated the impact on incidence, stage and healthcare pathway to diagnosis for female breast, colorectal and non-small cell lung cancers at population level in Wales.<h4>Methods</h4>Cancer e-record and hospital admission data linkage identified adult cases, stage and healthcare pathway to diagnosis (population ~2.5 million). Using multivariate Poisson regressions, we compared 2019 and 2020 counts and estimated incidence rate ratios (IRR).<h4>Results</h4>Cases decreased 15.2% (n = -1011) overall. Female breast annual IRR was 0.81 (95% CI: 0.76-0.86, p < 0.001), colorectal 0.80 (95% CI: 0.79-0.81, p < 0.001) and non-small cell lung 0.91 (95% CI: 0.90-0.92, p < 0.001). Decreases were largest in 50-69 year olds for female breast and 80+ year olds for all cancers. Stage I female breast cancer declined 41.6%, but unknown stage increased 55.8%. Colorectal stages I-IV declined (range 26.6-29.9%), while unknown stage increased 803.6%. Colorectal Q2-2020 GP-urgent suspected cancer diagnoses decreased 50.0%, and 53.9% for non-small cell lung cancer. Annual screen-detected female breast and colorectal cancers fell 47.8% and 13.3%, respectively. Non-smal -cell lung cancer emergency presentation diagnoses increased 9.5% (Q2-2020) and 16.3% (Q3-2020).<h4>Conclusion</h4>Significantly fewer cases of three common cancers were diagnosed in 2020. Detrimental impacts on outcomes varied between cancers. Ongoing surveillance with health service optimisation will be needed to mitigate impacts.",,pdf:https://www.nature.com/articles/s41416-022-01830-6.pdf; doi:https://doi.org/10.1038/s41416-022-01830-6; html:https://europepmc.org/articles/PMC9060409; pdf:https://europepmc.org/articles/PMC9060409?pdf=render
+37674175,https://doi.org/10.1186/s12884-023-05958-y,Using the COM-B framework to elucidate facilitators and barriers to COVID-19 vaccine uptake in pregnant women: a qualitative study.,"Patterson L, Berry E, Parsons C, Clarke B, Little A, Beggs J, Chuter A, Jackson T, Hsia Y, McGrath H, Millman C, Murphy S, Bradley DT, Milligan S.",,BMC pregnancy and childbirth,2023,2023-09-06,Y,Pregnancy; Qualitative; Barriers; Facilitators; Com-b; Covid-19 Vaccination,,,"Since April 2021, COVID-19 vaccines have been recommended for pregnant women. Despite this, COVID-19 vaccine uptake in this group is low compared to the non-pregnant population of childbearing age. Our aim was to understand barriers and facilitators to COVID-19 vaccine uptake among pregnant women in Northern Ireland using the COM-B framework, and so to make recommendations for public health interventions. The COM-B proposes that human behaviour is influenced by the extent to which a person has the capability, opportunity, and motivation to enact that behaviour. Understanding the factors underpinning behaviour through this lens helps discern what needs to change to change behaviour, therefore supporting the development of targeted interventions.This study consisted of eight semi-structured interviews with new/expectant mothers who did not receive a COVID-19 vaccine dose while pregnant since April 2021, and a focus group with five participants who received at least one COVID-19 vaccine dose while pregnant. Interview and focus group data were analysed using semi-deductive reflexive thematic analysis framed by a subtle realist approach. The COM-B was used to categorise codes and subthemes were developed within each COM-B construct.Within Psychological Capability, subthemes captured the need for consistent and reliable COVID-19 vaccine information and access to balanced and jargon-free, risk-benefit information that is tailored to the pregnant individual. The behaviour/opinions of family, friends, and local healthcare providers had a powerful influence on COVID-19 vaccine decisions (Social Opportunity). Integrating the COVID-19 vaccine as part of routine antenatal pathways was believed to support access and sense of familiarity (Physical Opportunity). Participants valued health autonomy, however experienced internal conflict driven by concerns about long-term side effects for their baby (Reflective Motivation). Feelings of fear, lack of empathy from healthcare providers, and anticipated guilt commonly underpinned indecision as to whether to get the vaccine (Automatic Motivation).Our study highlighted that the choice to accept a vaccine during pregnancy generates internal conflict and worry. Several participants cited their concern was primarily around the safety for their baby. Healthcare professionals (HCPs) play a significant part when it comes to decision making about COVID-19 vaccines among pregnant women. HCPs and pregnant women should be involved in the development of interventions to improve the delivery and communication of information.",,pdf:https://bmcpregnancychildbirth.biomedcentral.com/counter/pdf/10.1186/s12884-023-05958-y; doi:https://doi.org/10.1186/s12884-023-05958-y; html:https://europepmc.org/articles/PMC10481472; pdf:https://europepmc.org/articles/PMC10481472?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'.",,pdf:https://www.nature.com/articles/s41467-022-32096-4.pdf; doi:https://doi.org/10.1038/s41467-022-32096-4; html:https://europepmc.org/articles/PMC9330949; pdf:https://europepmc.org/articles/PMC9330949?pdf=render
 34301672,https://doi.org/10.1136/bmjopen-2021-053402,Sociodemographic inequality in COVID-19 vaccination coverage among elderly adults in England: a national linked data study.,"Nafilyan V, Dolby T, Razieh C, Gaughan CH, Morgan J, Ayoubkhani D, Walker S, Khunti K, Glickman M, Yates T.",,BMJ open,2021,2021-07-23,Y,Infection control; epidemiology; Covid-19,,,"<h4>Objective</h4>To examine inequalities in COVID-19 vaccination rates among elderly adults in England.<h4>Design</h4>Cohort study.<h4>Setting</h4>People living in private households and communal establishments in England.<h4>Participants</h4>6 655 672 adults aged ≥70 years (mean 78.8 years, 55.2% women) who were alive on 15 March 2021.<h4>Main outcome measures</h4>Having received the first dose of a vaccine against COVID-19 by 15 March 2021. We calculated vaccination rates and estimated unadjusted and adjusted ORs using logistic regression models.<h4>Results</h4>By 15 March 2021, 93.2% of people living in England aged 70 years and over had received at least one dose of a COVID-19 vaccine. While vaccination rates differed across all factors considered apart from sex, the greatest disparities were seen between ethnic and religious groups. The lowest rates were in people of black African and black Caribbean ethnic backgrounds, where only 67.2% and 73.8% had received a vaccine, with adjusted odds of not being vaccinated at 5.01 (95% CI 4.86 to 5.16) and 4.85 (4.75 to 4.96) times greater than the white British group. The proportion of individuals self-identifying as Muslim and Buddhist who had received a vaccine was 79.1% and 84.1%, respectively. Older age, greater area deprivation, less advantaged socioeconomic position (proxied by living in a rented home), being disabled and living either alone or in a multigenerational household were also associated with higher odds of not having received the vaccine.<h4>Conclusion</h4>Research is now urgently needed to understand why disparities exist in these groups and how they can best be addressed through public health policy and community engagement.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e053402.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053402; html:https://europepmc.org/articles/PMC8313303; pdf:https://europepmc.org/articles/PMC8313303?pdf=render
 34132940,https://doi.org/10.1007/s10654-021-00765-1,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.",,European journal of epidemiology,2021,2021-06-16,Y,Mortality; Ethnicity; Covid-19,,,"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. Using data from the Office for National Statistics Public Health Data Asset, a linked dataset combining the 2011 Census with primary care and hospital records and death registrations, 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 24th January 2020 until 31st August 2020) and the first part of the second wave (from 1st September to 28th 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. 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. 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.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-021-00765-1.pdf; doi:https://doi.org/10.1007/s10654-021-00765-1; html:https://europepmc.org/articles/PMC8206182; pdf:https://europepmc.org/articles/PMC8206182?pdf=render
@@ -164,13 +164,13 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 35131989,https://doi.org/10.1097/mcp.0000000000000863,A clinical review of long-COVID with a focus on the respiratory system.,"Daines L, Zheng B, Pfeffer P, Hurst JR, Sheikh A.",,Current opinion in pulmonary medicine,2022,2022-02-07,N,,,,"<h4>Purpose of review</h4>Persistence of symptoms after acute coronavirus disease 2019 (COVID-19), often described as long- COVID, is common and debilitating. In this article, we review the epidemiology, clinical features, and research priorities for long-COVID focusing on the respiratory system.<h4>Recent findings</h4>Breathlessness, cough and chest pain were the most commonly reported respiratory symptoms associated with long-COVID. In hospitalised patients, abnormalities on lung function testing or chest imaging were observed less commonly at 12 months compared to six months since discharge. Clinical assessment of patients with persisting symptoms after acute COVID-19 requires a comprehensive evaluation to exclude other possible causes for symptoms. With no robust current evidence for interventions to treat long-COVID respiratory symptoms, symptomatic treatment, supported self-management and pulmonary rehabilitation should be considered to help individuals with respiratory symptoms associated with long-COVID.<h4>Summary</h4>Long-COVID is a debilitating syndrome that often includes persisting respiratory symptoms and to a lesser degree, abnormalities in lung physiology or imaging. Respiratory features of long-COVID may reduce over time, yet resolution is not seen in all cases. Future research is needed to understand the natural history of long-COVID, identify factors associated with spontaneous improvement/persistence, investigate mechanisms for persisting symptoms, and test interventions to prevent and treat long-COVID.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612723; doi:https://doi.org/10.1097/MCP.0000000000000863; html:https://europepmc.org/articles/PMC7612723; pdf:https://europepmc.org/articles/PMC7612723?pdf=render; doi:https://doi.org/10.1097/mcp.0000000000000863
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>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
 35051442,https://doi.org/10.1016/j.jviromet.2022.114471,Reduced amplification efficiency of the RNA-dependent-RNA-polymerase 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 MA, Boulle A, Doolabh D, Laubscher M, Wojno J, Deetlefs JD, Maritz J, Scott L, Msomi N, Naicker C, Tegally H, de Oliveira T, Bhiman J, Williamson C, Preiser W, Hardie D, Hsiao NY.",,Journal of virological methods,2022,2022-01-18,Y,Surveillance; Diagnostic test; South Africa; Covid-19; Sars-cov-2; Delta Variant,,,"Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced RT-PCR amplification efficiency of the RdRp-gene target of the Seegene, Allplex 2019-nCoV diagnostic assay from June 2021 when detecting the Delta variant. We investigated whether the reduced amplification efficiency denoted by an increased RT-PCR cycle threshold value (RΔE) can be used as an indirect measure of SARS-CoV-2 Delta variant prevalence. We found a significant increase in the median RΔE for patient samples tested from June 2021, which coincided with the emergence of the SARS-CoV-2 Delta variant within our sample set. Whole genome sequencing on a subset of patient samples identified a highly conserved G15451A, non-synonymous mutation exclusively within the RdRp gene of Delta variants, which may cause reduced RT-PCR amplification efficiency. While whole genome sequencing plays an important in identifying novel SARS-CoV-2 variants, monitoring RΔE value can serve as a useful surrogate for rapid tracking of Delta variant prevalence.",,doi:https://doi.org/10.1016/j.jviromet.2022.114471; doi:https://doi.org/10.1016/j.jviromet.2022.114471; html:https://europepmc.org/articles/PMC8763409; pdf:https://europepmc.org/articles/PMC8763409?pdf=render
-37748493,https://doi.org/10.1016/s2213-2600(23)00262-x,"Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study.",C-MORE/PHOSP-COVID Collaborative Group.,,The Lancet. Respiratory medicine,2023,2023-09-22,Y,,,,"<h4>Introduction</h4>The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.<h4>Methods</h4>In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025.<h4>Findings</h4>Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2-6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5-5·8]; p<sub>adjusted</sub>=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4-10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32-4·82]; p<sub>adjusted</sub>=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23-11·88]; p<sub>adjusted</sub>=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.<h4>Interpretation</h4>After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification.<h4>Funding</h4>UK Research and Innovation and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S221326002300262X/pdf; doi:https://doi.org/10.1016/S2213-2600(23)00262-X; html:https://europepmc.org/articles/PMC7615263; pdf:https://europepmc.org/articles/PMC7615263?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://www.nature.com/articles/s43856-022-00146-z.pdf; doi:https://doi.org/10.1038/s43856-022-00146-z; html:https://europepmc.org/articles/PMC9259560; pdf:https://europepmc.org/articles/PMC9259560?pdf=render
+37748493,https://doi.org/10.1016/s2213-2600(23)00262-x,"Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study.",C-MORE/PHOSP-COVID Collaborative Group.,,The Lancet. Respiratory medicine,2023,2023-09-22,Y,,,,"<h4>Introduction</h4>The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.<h4>Methods</h4>In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025.<h4>Findings</h4>Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2-6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5-5·8]; p<sub>adjusted</sub>=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4-10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32-4·82]; p<sub>adjusted</sub>=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23-11·88]; p<sub>adjusted</sub>=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.<h4>Interpretation</h4>After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification.<h4>Funding</h4>UK Research and Innovation and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S221326002300262X/pdf; doi:https://doi.org/10.1016/S2213-2600(23)00262-X; html:https://europepmc.org/articles/PMC7615263; pdf:https://europepmc.org/articles/PMC7615263?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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/11/e042813.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042813; html:https://europepmc.org/articles/PMC7691999; pdf:https://europepmc.org/articles/PMC7691999?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.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-022-00962-6.pdf; doi:https://doi.org/10.1007/s10654-022-00962-6; html:https://europepmc.org/articles/PMC9860244; pdf:https://europepmc.org/articles/PMC9860244?pdf=render
 35192598,https://doi.org/10.1371/journal.pmed.1003927,"First dose ChAdOx1 and BNT162b2 COVID-19 vaccinations and cerebral venous sinus thrombosis: A pooled self-controlled case series study of 11.6 million individuals in England, Scotland, and Wales.","Kerr S, Joy M, Torabi F, Bedston S, Akbari A, Agrawal U, Beggs J, Bradley D, Chuter A, Docherty AB, Ford D, Hobbs R, Katikireddi SV, Lowthian E, de Lusignan S, Lyons R, Marple J, McCowan C, McGagh D, McMenamin J, Moore E, Murray JK, Owen RK, Pan J, Ritchie L, Shah SA, Shi T, Stock S, Tsang RSM, Vasileiou E, Woolhouse M, Simpson CR, Robertson C, Sheikh A.",,PLoS medicine,2022,2022-02-22,Y,,,,"<h4>Background</h4>Several countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales.<h4>Methods and findings</h4>We created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates.<h4>Conclusions</h4>In this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk-benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003927&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003927; html:https://europepmc.org/articles/PMC8863261; pdf:https://europepmc.org/articles/PMC8863261?pdf=render
-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.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/20/eurosurv-26-20-1.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.20.2100428&mimeType=pdf&containerItemId=content/eurosurveillance; 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
+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.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-022-00962-6.pdf; doi:https://doi.org/10.1007/s10654-022-00962-6; html:https://europepmc.org/articles/PMC9860244; pdf:https://europepmc.org/articles/PMC9860244?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>Those of South Asian ethnicity appear at risk of worse COVID-19 outcomes. Further studies need to establish the underlying mechanistic pathways.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/7/1/e000644.full.pdf; doi:https://doi.org/10.1136/bmjresp-2020-000644; html:https://europepmc.org/articles/PMC7467523; pdf:https://europepmc.org/articles/PMC7467523?pdf=render
+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.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/20/eurosurv-26-20-1.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.20.2100428&mimeType=pdf&containerItemId=content/eurosurveillance; 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
 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,,,,"<h4>Objective</h4>To assess the association between covid-19 vaccines and risk of thrombocytopenia and thromboembolic events in England among adults.<h4>Design</h4>Self-controlled case series study using national data on covid-19 vaccination and hospital admissions.<h4>Setting</h4>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).<h4>Participants</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://www.bmj.com/content/bmj/374/bmj.n1931.full.pdf; doi:https://doi.org/10.1136/bmj.n1931; html:https://europepmc.org/articles/PMC8388189; pdf:https://europepmc.org/articles/PMC8388189?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,,,,"<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>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.<h4>Translation</h4>For the Portuguese translation of the abstract see Supplementary Materials section.",,pdf:http://www.thelancet.com/article/S0140673621027549/pdf; doi:https://doi.org/10.1016/S0140-6736(21)02754-9; html:https://europepmc.org/articles/PMC8687670
 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.,pdf:https://www.nature.com/articles/s42254-020-0178-4.pdf; doi:https://doi.org/10.1038/s42254-020-0178-4; html:https://europepmc.org/articles/PMC7201389; pdf:https://europepmc.org/articles/PMC7201389?pdf=render
@@ -185,8 +185,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 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; doi:https://doi.org/10.7189/jogh.11.01011; html:https://europepmc.org/articles/PMC8763337; pdf:https://europepmc.org/articles/PMC8763337?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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] <i>vs</i> 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.<h4>Interpretation</h4>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.<h4>Funding</h4>UK Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S2666756822000939/pdf; 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
 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.",,pdf:https://www.nature.com/articles/s41591-022-01736-z.pdf; doi:https://doi.org/10.1038/s41591-022-01736-z; html:https://europepmc.org/articles/PMC9117137; pdf:https://europepmc.org/articles/PMC9117137?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; Covid-19; Nhs Digital Tre For England; Sail Databank; Trusted Research Environments; Data Harmonisation,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-02093-0; doi:https://doi.org/10.1186/s12911-022-02093-0; html:https://europepmc.org/articles/PMC9842203; pdf:https://europepmc.org/articles/PMC9842203?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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).<h4>Interpretation</h4>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.<h4>Funding</h4>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; doi:https://doi.org/10.1016/S2589-7500(21)00105-9; html:https://europepmc.org/articles/PMC8257056
+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; Covid-19; Nhs Digital Tre For England; Sail Databank; Trusted Research Environments; Data Harmonisation,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-02093-0; doi:https://doi.org/10.1186/s12911-022-02093-0; html:https://europepmc.org/articles/PMC9842203; pdf:https://europepmc.org/articles/PMC9842203?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.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/345820/2/pul2.12192.pdf; doi:https://doi.org/10.1002/pul2.12192; html:https://europepmc.org/articles/PMC9881210; pdf:https://europepmc.org/articles/PMC9881210?pdf=render
 36112916,https://doi.org/10.1177/09622802211055853,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, Sarah Walker A.",,Statistical methods in medical research,2022,2022-09-01,Y,Infection; Model; epidemic; risk factors; Covid-19,,,"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 COVID-19 Infection Survey 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 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 of 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.",,doi:https://doi.org/10.1177/09622802211055853; doi:https://doi.org/10.1177/09622802211055853; html:https://europepmc.org/articles/PMC9465559; pdf:https://europepmc.org/articles/PMC9465559?pdf=render
 36503414,https://doi.org/10.1186/s12879-022-07856-8,"COVID-19 vaccination in pregnancy: views and vaccination uptake rates in pregnancy, a mixed methods analysis from SAIL and the Born-In-Wales Birth Cohort.","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Beeson S, Akbari A, Zuccolo L, Davies A, Brophy S.",,BMC infectious diseases,2022,2022-12-12,Y,Pregnancy; Vaccine Uptake; Vaccine Hesitancy; Sail; Covid-19 Vaccination,,,"<h4>Background</h4>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 record (EHR) data 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).<h4>Methods</h4>This was a mixed-methods study utilising routinely collected linked data from the Secure Anonymised Information Linkage (SAIL) Databank (Objective 1) and the Born-In-Wales Birth Cohort participants (Objective 2). Pregnant women were identified from 13th April 2021 to 31st December 2021. Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy, and variation in uptake by; age, ethnic group, and deprivation area was examined using hazard ratios (HR) from Cox regression. Survey respondents were women who had a baby during the COVID-19 pandemic or were pregnant between 1st November 2021 and 24th March 2022 and participating in Born-In-Wales. Codebook thematic analysis was used to generate themes from an open-ended question on the survey.<h4>Results</h4>Population-level data linkage (objective 1): Within the population cohort, 8203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, 8572 (34.1%) remained unvaccinated throughout the follow-up period, and 8336 (33.2%) 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 with White women (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): 207 (69%) of participants stated that they would be happy to have the vaccine during pregnancy. The remaining 94 (31%) indicated they would not have the vaccine during pregnancy. 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.<h4>Conclusion</h4>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 decrease vaccine hesitancy. A targeted approach to vaccinations may be required for groups such as younger people and those living in higher deprivation areas.",,pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-022-07856-8; doi:https://doi.org/10.1186/s12879-022-07856-8; html:https://europepmc.org/articles/PMC9742024; pdf:https://europepmc.org/articles/PMC9742024?pdf=render
@@ -220,8 +220,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 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,,,"<h4>Objective</h4>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.<h4>Design</h4>Retrospective, descriptive cohort study, approved by NHS England.<h4>Setting</h4>Routine clinical data from 23.4 million people linked to data on covid-19 infection and treatment, within the OpenSAFELY-TPP database.<h4>Participants</h4>Outpatients with covid-19 at high risk of severe outcomes.<h4>Interventions</h4>Nirmatrelvir/ritonavir (paxlovid), sotrovimab, molnupiravir, casirivimab/imdevimab, or remdesivir, used in the community by covid-19 medicine delivery units.<h4>Results</h4>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%).<h4>Conclusions</h4>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.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000276.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000276; html:https://europepmc.org/articles/PMC9951378; pdf:https://europepmc.org/articles/PMC9951378?pdf=render
 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,,,"<h4>Introduction</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Discussion</h4>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.",,pdf:https://ijpds.org/article/download/1656/3219; doi:https://doi.org/10.23889/ijpds.v5i4.1656; html:https://europepmc.org/articles/PMC8280712; pdf:https://europepmc.org/articles/PMC8280712?pdf=render
 36168404,https://doi.org/10.1016/j.lanepe.2022.100501,Risk factors for SARS-CoV-2 infection after primary vaccination with ChAdOx1 nCoV-19 or BNT162b2 and after booster vaccination with BNT162b2 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.",,The Lancet regional health. Europe,2022,2022-09-23,Y,Vaccination; Breakthrough Infection; Chadox1; Sars-cov-2; Bnt162b2; Mrna-1273,,,"<h4>Background</h4>Little is known about how demographic, behavioural, and vaccine-related factors affect risk of post-vaccination SARS-CoV-2 infection. We aimed to identify risk factors for SARS-CoV-2 infection after primary and booster vaccinations.<h4>Methods</h4>This prospective, population-based, UK study in adults (≥16 years) vaccinated against SARS-CoV-2 assessed risk of breakthrough SARS-CoV-2 infection up to February, 2022, for participants who completed a primary vaccination course (ChAdOx1 nCoV-19 or BNT162b2) and those who received a booster dose (BNT162b2 or mRNA-1273). Cox regression models explored associations between sociodemographic, behavioural, clinical, pharmacological, and nutritional factors and test-positive breakthrough infection, adjusted for local weekly SARS-CoV-2 incidence.<h4>Findings</h4>1051 (7·1%) of 14 713 post-primary participants and 1009 (9·5%) of 10 665 post-booster participants reported breakthrough infection, over a median follow-up of 203 days (IQR 195-216) and 85 days (66-103), respectively. Primary vaccination with ChAdOx1 (<i>vs</i> BNT162b2) was associated with higher risk of infection in both post-primary analysis (adjusted hazard ratio 1·63, 95% CI 1·41-1·88) and after an mRNA-1273 booster (1·26 [1·00-1·57] <i>vs</i> BNT162b2 primary and booster). Lower risk of infection was associated with older age (post-primary: 0·97 [0·96-0·97] per year; post-booster: 0·97 [0·97-0·98]), whereas higher risk of infection was associated with lower educational attainment (post-primary: 1·78 [1·44-2·20] for primary/secondary <i>vs</i> postgraduate; post-booster: 1·46 [1·16-1·83]) and at least three weekly visits to indoor public places (post-primary: 1·36 [1·13-1·63] <i>vs</i> none; post-booster: 1·29 [1·07-1·56]).<h4>Interpretation</h4>Vaccine type, socioeconomic status, age, and behaviours affect risk of breakthrough infection after primary and booster vaccinations.<h4>Funding</h4>Barts Charity, UK Research and Innovation Industrial Strategy Challenge Fund.",,doi:https://doi.org/10.1016/j.lanepe.2022.100501; doi:https://doi.org/10.1016/j.lanepe.2022.100501; html:https://europepmc.org/articles/PMC9499825; pdf:https://europepmc.org/articles/PMC9499825?pdf=render
-36134546,https://doi.org/10.7189/jogh.12.05044,Risk of COVID-19 hospitalizations among school-aged children in Scotland: A national incident cohort study.,"Shi T, Pan J, Moore E, Katikireddi SV, Docherty AB, Fenton L, McCowan C, Agrawal U, Kerr S, Shah SA, Stock SJ, Simpson CR, Robertson C, Sheikh A, Public Health Scotland and the EAVE II Collaborators.",,Journal of global health,2022,2022-09-23,Y,,,,"<h4>Background</h4>There is considerable policy, clinical and public interest about whether children should be vaccinated against SARS-CoV-2 and, if so, which children should be prioritised (particularly if vaccine resources are limited). To inform such deliberations, we sought to identify children and young people at highest risk of hospitalization from COVID-19.<h4>Methods</h4>We used the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform to undertake a national incident cohort analysis to investigate the risk of hospitalization among 5-17 years old living in Scotland in risk groups defined by the living risk prediction algorithm (QCOVID). A Cox proportional hazard model was used to derive hazard ratios (HR) and 95% confidence intervals (CIs) for the association between risk groups and COVID-19 hospital admission. Adjustments were made for age, sex, socioeconomic status, co-morbidity, and prior hospitalization.<h4>Results</h4>Between March 1, 2020 and November 22, 2021, there were 146 183 (19.4% of all 752 867 children in Scotland) polymerase chain reaction (PCR) confirmed SARS-CoV-2 infections among 5-17 years old. Of those with confirmed infection, 973 (0.7%) were admitted to hospital with COVID-19. The rate of COVID-19 hospitalization was higher in those within each QCOVID risk group compared to those without the condition. Similar results were found in age stratified analyses (5-11 and 12-17 years old). Risk groups associated with an increased risk of COVID-19 hospital admission, included (adjusted HR, 95% CIs): sickle cell disease 14.35 (8.48-24.28), chronic kidney disease 11.34 (4.61-27.87), blood cancer 6.32 (3.24-12.35), rare pulmonary diseases 5.04 (2.58-9.86), type 2 diabetes 3.04 (1.34-6.92), epilepsy 2.54 (1.69-3.81), type 1 diabetes 2.48 (1.47-4.16), Down syndrome 2.45 (0.96-6.25), cerebral palsy 2.37 (1.26-4.47), severe mental illness 1.43 (0.63-3.24), fracture 1.41 (1.02-1.95), congenital heart disease 1.35 (0.82-2.23), asthma 1.28 (1.06-1.55), and learning disability (excluding Down syndrome) 1.08 (0.82-1.42), when compared to those without these conditions. Although our Cox models were adjusted for a number of potential confounders, residual confounding remains a possibility.<h4>Conclusions</h4>In this national study, we observed an increased risk of COVID-19 hospital admissions among school-aged children with specific underlying long-term health conditions compared with children without these conditions.",,pdf:https://jogh.org/wp-content/uploads/2022/10/jogh-12-05044.pdf; doi:https://doi.org/10.7189/jogh.12.05044; html:https://europepmc.org/articles/PMC9494196; pdf:https://europepmc.org/articles/PMC9494196?pdf=render
 34210356,https://doi.org/10.1186/s13059-021-02395-y,CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance.,"Nicholls SM, Poplawski R, Bull MJ, Underwood A, Chapman M, Abu-Dahab K, Taylor B, Colquhoun RM, Rowe WPM, Jackson B, Hill V, O'Toole Á, Rey S, Southgate J, Amato R, Livett R, Gonçalves S, Harrison EM, Peacock SJ, Aanensen DM, Rambaut A, Connor TR, Loman NJ, COVID-19 Genomics UK (COG-UK) Consortium.",,Genome biology,2021,2021-07-01,Y,,,,"In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network.",,pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-021-02395-y; doi:https://doi.org/10.1186/s13059-021-02395-y; html:https://europepmc.org/articles/PMC8247108; pdf:https://europepmc.org/articles/PMC8247108?pdf=render
+36134546,https://doi.org/10.7189/jogh.12.05044,Risk of COVID-19 hospitalizations among school-aged children in Scotland: A national incident cohort study.,"Shi T, Pan J, Moore E, Katikireddi SV, Docherty AB, Fenton L, McCowan C, Agrawal U, Kerr S, Shah SA, Stock SJ, Simpson CR, Robertson C, Sheikh A, Public Health Scotland and the EAVE II Collaborators.",,Journal of global health,2022,2022-09-23,Y,,,,"<h4>Background</h4>There is considerable policy, clinical and public interest about whether children should be vaccinated against SARS-CoV-2 and, if so, which children should be prioritised (particularly if vaccine resources are limited). To inform such deliberations, we sought to identify children and young people at highest risk of hospitalization from COVID-19.<h4>Methods</h4>We used the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform to undertake a national incident cohort analysis to investigate the risk of hospitalization among 5-17 years old living in Scotland in risk groups defined by the living risk prediction algorithm (QCOVID). A Cox proportional hazard model was used to derive hazard ratios (HR) and 95% confidence intervals (CIs) for the association between risk groups and COVID-19 hospital admission. Adjustments were made for age, sex, socioeconomic status, co-morbidity, and prior hospitalization.<h4>Results</h4>Between March 1, 2020 and November 22, 2021, there were 146 183 (19.4% of all 752 867 children in Scotland) polymerase chain reaction (PCR) confirmed SARS-CoV-2 infections among 5-17 years old. Of those with confirmed infection, 973 (0.7%) were admitted to hospital with COVID-19. The rate of COVID-19 hospitalization was higher in those within each QCOVID risk group compared to those without the condition. Similar results were found in age stratified analyses (5-11 and 12-17 years old). Risk groups associated with an increased risk of COVID-19 hospital admission, included (adjusted HR, 95% CIs): sickle cell disease 14.35 (8.48-24.28), chronic kidney disease 11.34 (4.61-27.87), blood cancer 6.32 (3.24-12.35), rare pulmonary diseases 5.04 (2.58-9.86), type 2 diabetes 3.04 (1.34-6.92), epilepsy 2.54 (1.69-3.81), type 1 diabetes 2.48 (1.47-4.16), Down syndrome 2.45 (0.96-6.25), cerebral palsy 2.37 (1.26-4.47), severe mental illness 1.43 (0.63-3.24), fracture 1.41 (1.02-1.95), congenital heart disease 1.35 (0.82-2.23), asthma 1.28 (1.06-1.55), and learning disability (excluding Down syndrome) 1.08 (0.82-1.42), when compared to those without these conditions. Although our Cox models were adjusted for a number of potential confounders, residual confounding remains a possibility.<h4>Conclusions</h4>In this national study, we observed an increased risk of COVID-19 hospital admissions among school-aged children with specific underlying long-term health conditions compared with children without these conditions.",,pdf:https://jogh.org/wp-content/uploads/2022/10/jogh-12-05044.pdf; doi:https://doi.org/10.7189/jogh.12.05044; html:https://europepmc.org/articles/PMC9494196; pdf:https://europepmc.org/articles/PMC9494196?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,,,"<b>Background:</b> 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. <b>Methods:</b> With the approval of NHS England, a cohort study was conducted of 3.21 million children and adolescents' records in general practice in England,  <i>in situ</i> 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. <b>Results:</b> 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. <b>Conclusion:</b> 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
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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).<h4>Interpretation</h4>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.<h4>Funding</h4>UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Scottish Government, and Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2213260021003805/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00380-5; html:https://europepmc.org/articles/PMC8480963
 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; doi:https://doi.org/10.1056/NEJMc2113864; html:https://europepmc.org/articles/PMC8552534; pdf:https://europepmc.org/articles/PMC8552534?pdf=render
@@ -231,8 +231,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 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.",,pdf:https://www.jmir.org/2020/8/e20169/PDF; doi:https://doi.org/10.2196/20169; html:https://europepmc.org/articles/PMC7450371
 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,,,"<h4>Objective</h4>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.<h4>Design/setting/participants</h4>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.<h4>Results</h4>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&lt;0.0001) and being of black ethnicity (6.21 (95% CI 2.69 to 14.3); p&lt;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&lt;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).<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e063159.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063159; html:https://europepmc.org/articles/PMC9644078; pdf:https://europepmc.org/articles/PMC9644078?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,,,,,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000151.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000151; html:https://europepmc.org/articles/PMC9951363; pdf:https://europepmc.org/articles/PMC9951363?pdf=render
-35915500,https://doi.org/10.1186/s12911-022-01947-x,The impact of changes in coding on mortality reports using the example of sepsis.,"Atkin C, Pankhurst T, McNulty D, Keogh A, Gallier S, Pagano D, Sapey E, Ball S.",,BMC medical informatics and decision making,2022,2022-08-01,Y,Mortality; Sepsis; Morbidity; epidemiology; Clinical Coding; Real World Data,,,"<h4>Objectives</h4>NHS Digital issued new guidance on sepsis coding in April 2017 which was further modified in April 2018. During these timeframes some centres reported increased sepsis associated mortality, whilst others reported reduced mortality, in some cases coincident with specific quality improvement programmes. We hypothesised that changes in reported mortality could not be separated from changes in coding practice.<h4>Methods</h4>Hospital Episode Statistics from the Admitted Patient Care dataset for NHS hospitals in England, from April 2016 to March 2020 were analysed. Admissions of adults with sepsis: an International Classification of Diseases 10 (ICD-10) code associated with the Agency for Healthcare Research and Quality Clinical Classifications Software class 'Septicaemia (except in labour)', were assessed. Patient comorbidities were defined by other ICD-10 codes recorded within the admission episode.<h4>Results</h4>1,081,565 hospital episodes with a coded diagnosis of sepsis were studied. After April 2017 there was a significant increase in admission episodes with sepsis coded as the primary reason for admission. There were significant changes in the case-mix of patients with a primary diagnosis of sepsis after April 2017. An analysis of case-mix, hospital and year treated as random effects, defined a small reduction in sepsis associated mortality across England following the first change in coding guidance. No centre specific improvement in outcome could be separated from these random-effects.<h4>Conclusion</h4>Changes in sepsis coding practice altered case-mix and case selection, in ways that varied between centres. This was associated with changes in centre-specific sepsis associated mortality, over time. According to the direction of change these may be interpreted either as requiring local investigation for cause or as supporting coincident changes in clinical practice. A whole system analysis showed that centre specific changes in mortality cannot be separated from system-wide changes. Caution is therefore required when interpreting sepsis outcomes in England, particularly when using single centre studies to inform or support guidance or policy.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-01947-x; doi:https://doi.org/10.1186/s12911-022-01947-x; html:https://europepmc.org/articles/PMC9341053; pdf:https://europepmc.org/articles/PMC9341053?pdf=render
 33560344,https://doi.org/10.1210/clinem/dgab067,Association of Metformin with Susceptibility to COVID-19 in People with Type 2 Diabetes.,"Wang J, Cooper JM, Gokhale K, Acosta-Mena D, Dhalla S, Byne N, Chandan JS, Anand A, Okoth K, Subramanian A, Bangash MN, Jackson T, Zemedikun D, Taverner T, Hanif W, Ghosh S, Narendran P, Toulis KA, Tahrani AA, Surenthirakumaran R, Adderley NJ, Haroon S, Khunti K, Sainsbury C, Thomas GN, Nirantharakumar K.",,The Journal of clinical endocrinology and metabolism,2021,2021-04-01,Y,Type 2 diabetes mellitus; Metformin; Covid-19; Sars-cov-2 Infection,,,"<h4>Objective</h4>Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes.<h4>Research design and methods</h4>We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed.<h4>Results</h4>There were 29 558 and 10 271 patients in the MF+ and MF- groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding.<h4>Conclusion</h4>Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.",,pdf:https://academic.oup.com/jcem/article-pdf/106/5/1255/41848481/dgab067.pdf; doi:https://doi.org/10.1210/clinem/dgab067; html:https://europepmc.org/articles/PMC7928949
+35915500,https://doi.org/10.1186/s12911-022-01947-x,The impact of changes in coding on mortality reports using the example of sepsis.,"Atkin C, Pankhurst T, McNulty D, Keogh A, Gallier S, Pagano D, Sapey E, Ball S.",,BMC medical informatics and decision making,2022,2022-08-01,Y,Mortality; Sepsis; Morbidity; epidemiology; Clinical Coding; Real World Data,,,"<h4>Objectives</h4>NHS Digital issued new guidance on sepsis coding in April 2017 which was further modified in April 2018. During these timeframes some centres reported increased sepsis associated mortality, whilst others reported reduced mortality, in some cases coincident with specific quality improvement programmes. We hypothesised that changes in reported mortality could not be separated from changes in coding practice.<h4>Methods</h4>Hospital Episode Statistics from the Admitted Patient Care dataset for NHS hospitals in England, from April 2016 to March 2020 were analysed. Admissions of adults with sepsis: an International Classification of Diseases 10 (ICD-10) code associated with the Agency for Healthcare Research and Quality Clinical Classifications Software class 'Septicaemia (except in labour)', were assessed. Patient comorbidities were defined by other ICD-10 codes recorded within the admission episode.<h4>Results</h4>1,081,565 hospital episodes with a coded diagnosis of sepsis were studied. After April 2017 there was a significant increase in admission episodes with sepsis coded as the primary reason for admission. There were significant changes in the case-mix of patients with a primary diagnosis of sepsis after April 2017. An analysis of case-mix, hospital and year treated as random effects, defined a small reduction in sepsis associated mortality across England following the first change in coding guidance. No centre specific improvement in outcome could be separated from these random-effects.<h4>Conclusion</h4>Changes in sepsis coding practice altered case-mix and case selection, in ways that varied between centres. This was associated with changes in centre-specific sepsis associated mortality, over time. According to the direction of change these may be interpreted either as requiring local investigation for cause or as supporting coincident changes in clinical practice. A whole system analysis showed that centre specific changes in mortality cannot be separated from system-wide changes. Caution is therefore required when interpreting sepsis outcomes in England, particularly when using single centre studies to inform or support guidance or policy.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-01947-x; doi:https://doi.org/10.1186/s12911-022-01947-x; html:https://europepmc.org/articles/PMC9341053; pdf:https://europepmc.org/articles/PMC9341053?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-19<sup>1-13</sup>. 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.",,pdf:https://www.nature.com/articles/s41586-022-04569-5.pdf; doi:https://doi.org/10.1038/s41586-022-04569-5; html:https://europepmc.org/articles/PMC9046077; pdf:https://europepmc.org/articles/PMC9046077?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,,,"<h4>Background</h4>Colchicine has been proposed as a COVID-19 treatment.<h4>Aim</h4>To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community.<h4>Design and setting</h4>Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE).<h4>Method</h4>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.<h4>Results</h4>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 (<i>n</i> = 156), usual care (<i>n</i> = 1145), and other treatments (<i>n</i> = 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).<h4>Conclusion</h4>Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.",,pdf:https://bjgp.org/content/bjgp/72/720/e446.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0083; html:https://europepmc.org/articles/PMC9037186; pdf:https://europepmc.org/articles/PMC9037186?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,,,"<h4>Background</h4>A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.<h4>Objective</h4>We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1017337/pdf; doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render
@@ -253,8 +253,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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).<h4>Conclusions</h4>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.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.1924; doi:https://doi.org/10.1002/ejhf.1924; html:https://europepmc.org/articles/PMC7301045; pdf:https://europepmc.org/articles/PMC7301045?pdf=render
 34796246,https://doi.org/10.1093/ofid/ofab496,"Acceptability, Usability, and Performance of Lateral Flow Immunoassay Tests for Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies: REACT-2 Study of Self-Testing in Nonhealthcare Key Workers.","Davies B, Araghi M, Moshe M, Gao H, Bennet K, Jenkins J, Atchison C, Darzi A, Ashby D, Riley S, Barclay W, Elliott P, Ward H, Cooke G.",,Open forum infectious diseases,2021,2021-10-04,Y,Sensitivity and specificity; Antibody testing; Sars-cov-2; Covid-19 Diagnostic Testing,,,"<h4>Background</h4>Seroprevalence studies are essential to understand the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Various technologies, including laboratory assays and point-of-care self-tests, are available for antibody testing. The interpretation of seroprevalence studies requires comparative data on the performance of antibody tests.<h4>Methods</h4>In June 2020, current and former members of the United Kingdom police forces and fire service performed a self-test lateral flow immunoassay (LFIA), had a nurse-performed LFIA, and provided a venous blood sample for enzyme-linked immunosorbent assay (ELISA). We present the prevalence of antibodies to SARS-CoV-2 and the acceptability and usability of self-test LFIAs, and we determine the sensitivity and specificity of LFIAs compared with laboratory ELISA.<h4>Results</h4>In this cohort of 5189 current and former members of the police service and 263 members of the fire service, 7.4% (396 of 5348; 95% confidence interval [CI], 6.7-8.1) were antibody positive. Seroprevalence was 8.9% (95% CI, 6.9-11.4) in those under 40 years, 11.5% (95% CI, 8.8-15.0) in those of nonwhite ethnicity, and 7.8% (95% CI, 7.1-8.7) in those currently working. Self-test LFIA had an acceptability of 97.7% and a usability of 90.0%. There was substantial agreement between within-participant LFIA results (kappa 0.80; 95% CI, 0.77-0.83). The LFIAs had a similar performance: compared with ELISA, sensitivity was 82.1% (95% CI, 77.7-86.0) self-test and 76.4% (95% CI, 71.9-80.5) nurse-performed with specificity of 97.8% (95% CI, 97.3-98.2) and 98.5% (95% CI, 98.1-98.8), respectively.<h4>Conclusions</h4>A greater proportion of this nonhealthcare key worker cohort showed evidence of previous infection with SARS-CoV-2 than the general population at 6.0% (95% CI, 5.8-6.1) after the first wave in England. The high acceptability and usability reported by participants and similar performance of self-test and nurse-performed LFIAs indicate that the self-test LFIA is fit for purpose for home testing in occupational and community prevalence studies.",,pdf:https://academic.oup.com/ofid/article-pdf/8/11/ofab496/41174715/ofab496.pdf; doi:https://doi.org/10.1093/ofid/ofab496; html:https://europepmc.org/articles/PMC8522420; pdf:https://europepmc.org/articles/PMC8522420?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.",,pdf:https://www.nature.com/articles/s41467-022-28517-z.pdf; doi:https://doi.org/10.1038/s41467-022-28517-z; html:https://europepmc.org/articles/PMC8927425; pdf:https://europepmc.org/articles/PMC8927425?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; Ba.5; Death, Severe Hospitalization",,,"<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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; 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
 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.",,pdf:https://www.nature.com/articles/s41591-020-0916-2.pdf; 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
+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; Ba.5; Death, Severe Hospitalization",,,"<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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; 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
 34870142,https://doi.org/10.1016/j.infpip.2021.100192,"Effectiveness of infection prevention and control interventions, excluding personal protective equipment, to prevent nosocomial transmission of SARS-CoV-2: a systematic review and call for action.","Jafari Y, Yin M, Lim C, Pople D, Evans S, Stimson J, Pham TM, LSHTM CMMID COVID-19 working group, Read JM, Robotham JV, Cooper BS, Knight GM.",,Infection prevention in practice,2022,2021-11-29,Y,,,,"Many infection prevention and control (IPC) interventions have been adopted by hospitals to limit nosocomial transmission of SARS-CoV-2. The aim of this systematic review is to identify evidence on the effectiveness of these interventions. We conducted a literature search of five databases (OVID MEDLINE, Embase, CENTRAL, COVID-19 Portfolio (pre-print), Web of Science). SWIFT ActiveScreener software was used to screen English titles and abstracts published between 1st January 2020 and 6th April 2021. Intervention studies, defined by Cochrane Effective Practice and Organisation of Care, that evaluated IPC interventions with an outcome of SARS-CoV-2 infection in either patients or healthcare workers were included. Personal protective equipment (PPE) was excluded as this intervention had been previously reviewed. Risks of bias were assessed using the Cochrane tool for randomised trials (RoB2) and non-randomized studies of interventions (ROBINS-I). From 23,156 screened articles, we identified seven articles that met the inclusion criteria, all of which evaluated interventions to prevent infections in healthcare workers and the majority of which were focused on effectiveness of prophylaxes. Due to heterogeneity in interventions, we did not conduct a meta-analysis. All agents used for prophylaxes have little to no evidence of effectiveness against SARS-CoV-2 infections. We did not find any studies evaluating the effectiveness of interventions including but not limited to screening, isolation and improved ventilation. There is limited evidence from interventional studies, excluding PPE, evaluating IPC measures for SARS-CoV-2. This review calls for urgent action to implement such studies to inform policies to protect our most vulnerable populations and healthcare workers.",,doi:https://doi.org/10.1016/j.infpip.2021.100192; doi:https://doi.org/10.1016/j.infpip.2021.100192; html:https://europepmc.org/articles/PMC8628369; pdf:https://europepmc.org/articles/PMC8628369?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,,,"<h4>Introduction</h4>We investigated the potential association of COVID-19 vaccination with three acute neurological events: Guillain-Barré syndrome (GBS), transverse myelitis and Bell's palsy.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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; 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
 36720568,https://doi.org/10.1136/bmjopen-2022-066164,Factors associated with COVID-19 vaccine uptake in people with kidney disease: an OpenSAFELY cohort study.,"OpenSAFELY Collaborative, Parker EP, Tazare J, Hulme WJ, Bates C, Carr EJ, Cockburn J, Curtis HJ, Fisher L, Green AC, Harper S, Hester F, Horne EM, Loud F, Lyon S, Mahalingasivam V, Mehrkar A, Nab L, Parry J, Santhakumaran S, Steenkamp R, Sterne JA, Walker AJ, Williamson EJ, Willicombe M, Zheng B, Goldacre B, Nitsch D, Tomlinson LA.",,BMJ open,2023,2023-01-31,Y,Public Health; Kidney & Urinary Tract Disorders; Covid-19,,,"<h4>Objective</h4>To characterise factors associated with COVID-19 vaccine uptake among people with kidney disease in England.<h4>Design</h4>Retrospective cohort study using the OpenSAFELY-TPP platform, performed with the approval of NHS England.<h4>Setting</h4>Individual-level routine clinical data from 24 million people across GPs in England using TPP software. Primary care data were linked directly with COVID-19 vaccine records up to 31 August 2022 and with renal replacement therapy (RRT) status via the UK Renal Registry (UKRR).<h4>Participants</h4>A cohort of adults with stage 3-5 chronic kidney disease (CKD) or receiving RRT at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate (eGFR) or inclusion in the UKRR.<h4>Main outcome measures</h4>Dose-specific vaccine coverage over time was determined from 1 December 2020 to 31 August 2022. Individual-level factors associated with receipt of a 3-dose or 4-dose vaccine series were explored via Cox proportional hazards models.<h4>Results</h4>992 205 people with stage 3-5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 31 August 2022 was 97.5%, 97.0% and 93.9% for doses 1, 2 and 3, respectively, and 81.9% for dose 4 among individuals with one or more indications for eligibility. Delayed 3-dose vaccine uptake was associated with younger age, minority ethnicity, social deprivation and severe mental illness-associations that were consistent across CKD severity subgroups, dialysis patients and kidney transplant recipients. Similar associations were observed for 4-dose uptake.<h4>Conclusion</h4>Although high primary vaccine and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across clinical and demographic groups and 4-dose coverage is suboptimal. Targeted interventions are needed to identify barriers to vaccine uptake among under-vaccinated subgroups identified in the present study.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/1/e066164.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066164; html:https://europepmc.org/articles/PMC9890277; pdf:https://europepmc.org/articles/PMC9890277?pdf=render
@@ -273,8 +273,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 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.",,pdf:https://academic.oup.com/jcem/article-pdf/105/12/e4230/41829325/dgaa627.pdf; doi:https://doi.org/10.1210/clinem/dgaa627; html:https://europepmc.org/articles/PMC7499588; pdf:https://europepmc.org/articles/PMC7499588?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.",,pdf:https://www.nature.com/articles/s41467-021-23935-x.pdf; doi:https://doi.org/10.1038/s41467-021-23935-x; html:https://europepmc.org/articles/PMC8213785; pdf:https://europepmc.org/articles/PMC8213785?pdf=render
 37570411,https://doi.org/10.3390/healthcare11152171,Patient Experiences of Communication with Healthcare Professionals on Their Healthcare Management around Chronic Respiratory Diseases.,"Zhang X, Buttery SC, Sterniczuk K, Brownrigg A, Kennington E, Quint JK.",,"Healthcare (Basel, Switzerland)",2023,2023-07-31,Y,Communication; experience; Healthcare Professionals; Chronic Respiratory Disease,,,"<h4>Background</h4>Communication is an important clinical tool for the prevention and control of diseases, to advise and inform patients and the public, providing them with essential knowledge regarding healthcare and disease management. This study explored the experience of communication between healthcare professionals (HCPs) and people with long-term lung conditions, from the patient perspective.<h4>Methods</h4>This qualitative study analyzed the experience of people with chronic lung disease, recruited via Asthma & Lung UK (A&LUK) and COPD research databases. A&LUK invited people who had expressed a desire to be involved in research associated with their condition via their Expert Patient Panel and associated patients' groups. Two focus group interviews (12 participants) and one individual interview (1 participant) were conducted. Thematic analysis was used for data analysis.<h4>Results</h4>Two main themes were identified and we named them 'involving communication' and 'communication needs to be improved. 'They included seven subthemes: community-led support increased the patients' social interaction with peers; allied-HCP-led support increased patients' satisfaction; disliking being repeatedly asked the same basic information; feeling communication was unengaging, lacking personal specifics and the use of medical terminology and jargon.<h4>Conclusions</h4>The study has identified what most matters in the process of communication with HCPs in people with long-term respiratory diseases of their healthcare management. The findings of the study can be used to improve the patient-healthcare professional relationship and facilitate a better communication flow in long-term healthcare management.",,doi:https://doi.org/10.3390/healthcare11152171; html:https://europepmc.org/articles/PMC10418967; pdf:https://europepmc.org/articles/PMC10418967?pdf=render
-37656609,https://doi.org/10.1093/aje/kwad179,Challenges in Estimating Effectiveness of 2 Doses of COVID-19 Vaccines Beyond 6 Months in England.,"Horne EMF, Hulme WJ, Keogh RH, Palmer TM, Williamson EJ, Parker EPK, Walker VM, Knight R, Wie Y, Taylor K, Fisher L, Morley J, Mehrkar A, Dillingham I, Bacon S, Goldacre B, Sterne JAC, Collaborative TO.",,American journal of epidemiology,2023,2023-09-01,N,severe acute respiratory syndrome; Covid-19; Covid-19 Vaccines,,,,,doi:https://doi.org/10.1093/aje/kwad179
 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; doi:https://doi.org/10.1016/j.socscimed.2022.115237; html:https://europepmc.org/articles/PMC9357441; pdf:https://europepmc.org/articles/PMC9357441?pdf=render
+37656609,https://doi.org/10.1093/aje/kwad179,Challenges in Estimating Effectiveness of 2 Doses of COVID-19 Vaccines Beyond 6 Months in England.,"Horne EMF, Hulme WJ, Keogh RH, Palmer TM, Williamson EJ, Parker EPK, Walker VM, Knight R, Wie Y, Taylor K, Fisher L, Morley J, Mehrkar A, Dillingham I, Bacon S, Goldacre B, Sterne JAC, Collaborative TO.",,American journal of epidemiology,2023,2023-09-01,N,severe acute respiratory syndrome; Covid-19; Covid-19 Vaccines,,,,,doi:https://doi.org/10.1093/aje/kwad179
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://thorax.bmj.com/content/thoraxjnl/77/5/497.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-217580; html:https://europepmc.org/articles/PMC8595052; pdf:https://europepmc.org/articles/PMC8595052?pdf=render
 35411997,https://doi.org/10.1111/tmi.13752,"Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa.","Davies MA, Kassanjee R, Rousseau P, Morden E, Johnson L, Solomon W, Hsiao NY, Hussey H, Meintjes G, Paleker M, Jacobs T, Raubenheimer P, Heekes A, Dane P, Bam JL, Smith M, Preiser W, Pienaar D, Mendelson M, Naude J, Schrueder N, Mnguni A, Le Roux S, Murie K, Prozesky H, Mahomed H, Rossouw L, Wasserman S, Maughan D, Boloko L, Smith B, Taljaard J, Symons G, Ntusi NAB, Parker A, Wolter N, Jassat W, Cohen C, Lessells R, Wilkinson RJ, Arendse J, Kariem S, Moodley M, Wolmarans M, Cloete K, Boulle A, Western Cape and South African National Departments of Health in collaboration with the National Institute for Communicable Diseases in South Africa Affiliations.",,Tropical medicine & international health : TM & IH,2022,2022-05-10,Y,Vaccination; Immunity; DELTA; Sub-Saharan Africa; Covid-19; Prior Infection; Omicron,,,"<h4>Objectives</h4>The objective was to compare COVID-19 outcomes in the Omicron-driven fourth wave with prior waves in the Western Cape, assess the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection and determine whether protection against severe disease conferred by prior infection and/or vaccination was maintained.<h4>Methods</h4>In this cohort study, we included public sector patients aged ≥20 years with a laboratory-confirmed COVID-19 diagnosis between 14 November and 11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalisation or death and any hospitalisation or death (all ≤14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection.<h4>Results</h4>We included 5144 patients from wave four and 11,609 from prior waves. The risk of all outcomes was lower in wave four compared to the Delta-driven wave three (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR: 0.41, 95% CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95% CI: 0.10; 0.58).<h4>Conclusions</h4>In the Omicron-driven wave, severe COVID-19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for a modest reduction in risk of severe hospitalisation or death compared to the Delta-driven wave.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/tmi.13752; doi:https://doi.org/10.1111/tmi.13752; html:https://europepmc.org/articles/PMC9115442; pdf:https://europepmc.org/articles/PMC9115442?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.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020355; doi:https://doi.org/10.1128/jcm.02408-21; html:https://europepmc.org/articles/PMC9020355; pdf:https://europepmc.org/articles/PMC9020355?pdf=render
@@ -283,8 +283,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 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; doi:https://doi.org/10.1016/j.vaccine.2022.02.056; html:https://europepmc.org/articles/PMC8849863
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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 1·73m<sup>2</sup>, 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.<h4>Findings</h4>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).<h4>Interpretation</h4>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.<h4>Funding</h4>UK Research and Innovation (Medical Research Council), National Institute of Health Research, and Wellcome Trust.",,pdf:http://www.thelancet.com/article/S2213260021004355/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00435-5; html:https://europepmc.org/articles/PMC8523117
 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,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081749; 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
-35611160,https://doi.org/10.1016/j.eclinm.2022.101462,Impact of first UK COVID-19 lockdown on hospital admissions: Interrupted time series study of 32 million people.,"Shah SA, Brophy S, Kennedy J, Fisher L, Walker A, Mackenna B, Curtis H, Inglesby P, Davy S, Bacon S, Goldacre B, Agrawal U, Moore E, Simpson CR, Macleod J, Cooksey R, Sheikh A, Katikireddi SV.",,EClinicalMedicine,2022,2022-05-20,Y,Pandemic; Healthcare Inequalities; Covid-19; Sars-cov-2; Interrupted Time Series Analysis; Healthcare Disruption,,,"<h4>Background</h4>Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such unprecedented impact was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for tracer non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups.<h4>Methods</h4>We used OpenSAFELY (for England), EAVEII (Scotland), and SAIL Databank (Wales) to extract weekly hospital admission rates for cancer, cardiovascular and respiratory conditions (excluding COVID-19) from the pre-pandemic period until 25/10/2020 and conducted a controlled interrupted time series analysis. We undertook stratified analyses and assessed admission rates over seven months during which lockdown restrictions were gradually lifted.<h4>Findings</h4>Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% (Confidence Interval (CI): -43.0, -25.3) in England, 20.9% (CI: -27.8, -14.1) in Scotland, and 24.7% (CI: -36.7, -12.7) in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5% (CI: -47.4, -33.6), 21.9% (CI: -35.4, -8.4), and 19.0% (CI: -30.6, -7.4) in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% (CI: -20.2, 1.2) for Whites, but 44.3% (CI: -71.0, -17.6), 34.6% (CI: -63.8, -5.3), and 25.6% (CI: -45.0, -6.3) for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0%, respectively when compared to the same period (August-September) during the pre-pandemic years. This corresponds to a reduction of 26.2, 23.8 and 30.2 admissions per 100,000 people in England, Scotland, and Wales respectively.<h4>Interpretation</h4>Hospital care for non-COVID diseases fell substantially across England, Scotland, and Wales during the first lockdown, with reductions persisting for at least six months. The most deprived and minority ethnic groups were impacted more severely.<h4>Funding</h4>This work was funded by the Medical Research Council as part of the Lifelong Health and Wellbeing study as part of National Core Studies (MC_PC_20030). SVK acknowledges funding from the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). EAVE II is funded by the Medical Research Council (MR/R008345/1) 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. BG has received research funding from the NHS National Institute for Health Research (NIHR), the Wellcome Trust, Health Data Research UK, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme.",,pdf:http://www.thelancet.com/article/S2589537022001924/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101462; html:https://europepmc.org/articles/PMC9121886; pdf:https://europepmc.org/articles/PMC9121886?pdf=render
 35365070,https://doi.org/10.1186/s12879-022-07268-8,Impact of non-pharmaceutical interventions on SARS-CoV-2 outbreaks in English care homes: a modelling study.,"Rosello A, Barnard RC, Smith DRM, Evans S, Grimm F, Davies NG, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Modelling Working Group, Deeny SR, Knight GM, Edmunds WJ.",,BMC infectious diseases,2022,2022-04-01,Y,PCR; Testing; mathematical model; Long-term Care Facility; Care Home; Non-pharmaceutical Interventions; Covid-19; Sars-cov-2,,,"<h4>Background</h4>COVID-19 outbreaks still occur in English care homes despite the interventions in place.<h4>Methods</h4>We developed a stochastic compartmental model to simulate the spread of SARS-CoV-2 within an English care home. We quantified the outbreak risk with baseline non-pharmaceutical interventions (NPIs) already in place, the role of community prevalence in driving outbreaks, and the relative contribution of all importation routes into a fully susceptible care home. We also considered the potential impact of additional control measures in care homes with and without immunity, namely: increasing staff and resident testing frequency, using lateral flow antigen testing (LFD) tests instead of polymerase chain reaction (PCR), enhancing infection prevention and control (IPC), increasing the proportion of residents isolated, shortening the delay to isolation, improving the effectiveness of isolation, restricting visitors and limiting staff to working in one care home. We additionally present a Shiny application for users to apply this model to their facility of interest, specifying care home, outbreak and intervention characteristics.<h4>Results</h4>The model suggests that importation of SARS-CoV-2 by staff, from the community, is the main driver of outbreaks, that importation by visitors or from hospitals is rare, and that the past testing strategy (monthly testing of residents and daily testing of staff by PCR) likely provides negligible benefit in preventing outbreaks. Daily staff testing by LFD was 39% (95% 18-55%) effective in preventing outbreaks at 30 days compared to no testing.<h4>Conclusions</h4>Increasing the frequency of testing in staff and enhancing IPC are important to preventing importations to the care home. Further work is needed to understand the impact of vaccination in this population, which is likely to be very effective in preventing outbreaks.",,pdf:https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/s12879-022-07268-8; doi:https://doi.org/10.1186/s12879-022-07268-8; html:https://europepmc.org/articles/PMC8972713; pdf:https://europepmc.org/articles/PMC8972713?pdf=render
+35611160,https://doi.org/10.1016/j.eclinm.2022.101462,Impact of first UK COVID-19 lockdown on hospital admissions: Interrupted time series study of 32 million people.,"Shah SA, Brophy S, Kennedy J, Fisher L, Walker A, Mackenna B, Curtis H, Inglesby P, Davy S, Bacon S, Goldacre B, Agrawal U, Moore E, Simpson CR, Macleod J, Cooksey R, Sheikh A, Katikireddi SV.",,EClinicalMedicine,2022,2022-05-20,Y,Pandemic; Healthcare Inequalities; Covid-19; Sars-cov-2; Interrupted Time Series Analysis; Healthcare Disruption,,,"<h4>Background</h4>Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such unprecedented impact was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for tracer non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups.<h4>Methods</h4>We used OpenSAFELY (for England), EAVEII (Scotland), and SAIL Databank (Wales) to extract weekly hospital admission rates for cancer, cardiovascular and respiratory conditions (excluding COVID-19) from the pre-pandemic period until 25/10/2020 and conducted a controlled interrupted time series analysis. We undertook stratified analyses and assessed admission rates over seven months during which lockdown restrictions were gradually lifted.<h4>Findings</h4>Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% (Confidence Interval (CI): -43.0, -25.3) in England, 20.9% (CI: -27.8, -14.1) in Scotland, and 24.7% (CI: -36.7, -12.7) in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5% (CI: -47.4, -33.6), 21.9% (CI: -35.4, -8.4), and 19.0% (CI: -30.6, -7.4) in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% (CI: -20.2, 1.2) for Whites, but 44.3% (CI: -71.0, -17.6), 34.6% (CI: -63.8, -5.3), and 25.6% (CI: -45.0, -6.3) for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0%, respectively when compared to the same period (August-September) during the pre-pandemic years. This corresponds to a reduction of 26.2, 23.8 and 30.2 admissions per 100,000 people in England, Scotland, and Wales respectively.<h4>Interpretation</h4>Hospital care for non-COVID diseases fell substantially across England, Scotland, and Wales during the first lockdown, with reductions persisting for at least six months. The most deprived and minority ethnic groups were impacted more severely.<h4>Funding</h4>This work was funded by the Medical Research Council as part of the Lifelong Health and Wellbeing study as part of National Core Studies (MC_PC_20030). SVK acknowledges funding from the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). EAVE II is funded by the Medical Research Council (MR/R008345/1) 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. BG has received research funding from the NHS National Institute for Health Research (NIHR), the Wellcome Trust, Health Data Research UK, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme.",,pdf:http://www.thelancet.com/article/S2589537022001924/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101462; html:https://europepmc.org/articles/PMC9121886; pdf:https://europepmc.org/articles/PMC9121886?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,,,"<h4>Objectives</h4>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.<h4>Design</h4>An EHR-based, retrospective cohort study.<h4>Setting</h4>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).<h4>Participants</h4>In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged ≥30 years, respectively.<h4>Main outcome measures</h4>One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221131897; 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
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13219-4; doi:https://doi.org/10.1186/s12889-022-13219-4; html:https://europepmc.org/articles/PMC9115545; pdf:https://europepmc.org/articles/PMC9115545?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,,,"<h4>Background and purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%; <i>P</i>=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.<h4>Conclusions</h4>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.",,pdf:https://europepmc.org/articles/pmc8607920?pdf=render; doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?pdf=render
@@ -293,8 +293,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>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.<h4>Interpretation</h4>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 R<sub>0</sub> and the duration of infectiousness.<h4>Funding</h4>Bill & Melinda Gates Foundation, National Institute for Health Research, Wellcome Trust, and Health Data Research UK.",,pdf:https://repository.publisso.de/resource/frl:6420088/data; doi:https://doi.org/10.1016/S2468-2667(20)30073-6; html:https://europepmc.org/articles/PMC7158905
 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,,,"<h4>Background</h4>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.<h4>Aim</h4>To examine the association between home death and socioeconomic position during the Covid-19 pandemic, and how this changed between 2019 and 2020.<h4>Design</h4>Retrospective cohort study using population-based individual-level mortality data.<h4>Setting/participants</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10125882; doi:https://doi.org/10.1177/02692163231167212; html:https://europepmc.org/articles/PMC10125882; pdf:https://europepmc.org/articles/PMC10125882?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,,,"<h4>Objective</h4>To explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato-pancreato-biliary (HPB) conditions.<h4>Design</h4>Cross-sectional study.<h4>Setting</h4>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.<h4>Participants</h4>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.<h4>Main outcome measure</h4>COVID-19 incidence and mortality.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/4/e045077.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-045077; html:https://europepmc.org/articles/PMC8057071; pdf:https://europepmc.org/articles/PMC8057071?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 <i>in situ</i> 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,,,"<h4>Background</h4>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.<h4>Aim</h4>To describe the use of long-COVID codes, and variation of use by general practice, demographic variables, and over time.<h4>Design and setting</h4>Population-based cohort study in English primary care.<h4>Method</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.",,pdf:https://bjgp.org/content/bjgp/71/712/e806.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0301; html:https://europepmc.org/articles/PMC8340730; pdf:https://europepmc.org/articles/PMC8340730?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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).<h4>Interpretation</h4>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.<h4>Funding</h4>Medical Research Council and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S0140673620320134/pdf; doi:https://doi.org/10.1016/S0140-6736(20)32013-4; html:https://europepmc.org/articles/PMC7535623
+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 <i>in situ</i> 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,,,"<h4>Background</h4>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.<h4>Aim</h4>To describe the use of long-COVID codes, and variation of use by general practice, demographic variables, and over time.<h4>Design and setting</h4>Population-based cohort study in English primary care.<h4>Method</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.",,pdf:https://bjgp.org/content/bjgp/71/712/e806.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0301; html:https://europepmc.org/articles/PMC8340730; pdf:https://europepmc.org/articles/PMC8340730?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",,,,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCOUTCOMES.120.007085; doi:https://doi.org/10.1161/CIRCOUTCOMES.120.007085; html:https://europepmc.org/articles/PMC7819531; pdf:https://europepmc.org/articles/PMC7819531?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.",,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>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.",,pdf:http://www.thelancet.com/article/S2589537022000475/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101317; html:https://europepmc.org/articles/PMC8898170; pdf:https://europepmc.org/articles/PMC8898170?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Medical Research Council.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4659476/13/PIIS0140673621006346.pdf; 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
@@ -302,10 +302,10 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>Databases (MEDLINE, EMBASE, PROSPERO, Cochrane library and <i>MedRxiv</i>) 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.<h4>Findings</h4>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]).<h4>Interpretation</h4>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.",,pdf:https://figshare.com/articles/journal_contribution/Ethnicity_and_clinical_outcomes_in_COVID-19_A_Systematic_Review_and_Meta-analysis/13147892/1/files/25502810.pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100630; html:https://europepmc.org/articles/PMC7658622; pdf:https://europepmc.org/articles/PMC7658622?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02000-w; doi:https://doi.org/10.1186/s12916-021-02000-w; html:https://europepmc.org/articles/PMC8126470; pdf:https://europepmc.org/articles/PMC8126470?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,,,"<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.mdpi.com/2077-0383/11/23/7163/pdf?version=1670311452; doi:https://doi.org/10.3390/jcm11237163; html:https://europepmc.org/articles/PMC9738639; pdf:https://europepmc.org/articles/PMC9738639?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,,,"<h4>Background</h4>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.<h4>Methods</h4>RdRp target delay (RTD) in the Seegene Allplex<sup>TM</sup> 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 Allplex<sup>TM</sup> 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.<h4>Results</h4>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).<h4>Conclusion</h4>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; 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
 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,,,,,,pdf:https://academic.oup.com/ije/article-pdf/50/4/1064/40146583/dyab028.pdf; doi:https://doi.org/10.1093/ije/dyab028; html:https://europepmc.org/articles/PMC8195245; pdf:https://europepmc.org/articles/PMC8195245?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>LSHTM COVID-19 Response Grant (DONAT15912).",,pdf:http://www.thelancet.com/article/S2589537023002547/pdf; doi:https://doi.org/10.1016/j.eclinm.2023.102077; html:https://europepmc.org/articles/PMC10331810; pdf:https://europepmc.org/articles/PMC10331810?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,,,"<h4>Background</h4>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.<h4>Methods</h4>RdRp target delay (RTD) in the Seegene Allplex<sup>TM</sup> 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 Allplex<sup>TM</sup> 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.<h4>Results</h4>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).<h4>Conclusion</h4>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; 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
 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,,,,"<h4>Objective</h4>To derive and validate a risk prediction algorithm to estimate hospital admission and mortality outcomes from coronavirus disease 2019 (covid-19) in adults.<h4>Design</h4>Population based cohort study.<h4>Setting and participants</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>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 (R<sup>2</sup>); 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.<h4>Conclusion</h4>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.",,pdf:https://www.bmj.com/content/bmj/371/bmj.m3731.full.pdf; doi:https://doi.org/10.1136/bmj.m3731; html:https://europepmc.org/articles/PMC7574532; pdf:https://europepmc.org/articles/PMC7574532?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>LSHTM COVID-19 Response Grant (DONAT15912).",,pdf:http://www.thelancet.com/article/S2589537023002547/pdf; doi:https://doi.org/10.1016/j.eclinm.2023.102077; html:https://europepmc.org/articles/PMC10331810; pdf:https://europepmc.org/articles/PMC10331810?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,,,,"<h4>Background</h4>This study assesses COVID-19 hospitalised patient demography and outcomes during wave 1 and wave 2, prior to new variants of the virus.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>Prior to new SARS-CoV-2 variants, outcomes for hospitalised patients with COVID-19 were improving but with similar intensive care needs.",,
 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,,,,,,pdf:https://europepmc.org/articles/pmc7592804?pdf=render; doi:https://doi.org/10.7326/M20-4986; html:https://europepmc.org/articles/PMC7592804; pdf:https://europepmc.org/articles/PMC7592804?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,,,"<h4>Objectives</h4>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.<h4>Design and setting</h4>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.<h4>Intervention</h4>A temporary cancellation of elective services for 2 months in winter 2017.<h4>Outcomes</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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; doi:https://doi.org/10.1136/bmjopen-2022-066398; html:https://europepmc.org/articles/PMC10193088; pdf:https://europepmc.org/articles/PMC10193088?pdf=render
@@ -333,8 +333,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 35567479,https://doi.org/10.1093/rheumatology/keac283,Shielding reduced incidence of COVID-19 in patients with inflammatory arthritis but vulnerability is associated with increased mortality.,"Cooksey R, Underwood J, Brophy S, Atkinson M, Kennedy J, Choy E.",,"Rheumatology (Oxford, England)",2022,2022-06-01,Y,RA; As; PSA; Electronic Health Records; Covid-19; Inflammatory Arthritis,,,"<h4>Objectives</h4>Investigate whether individuals with inflammatory arthritis (IA), their treatments and shielding status affect the risk of adverse outcomes from COVID-19 for the entire population of Wales, UK.<h4>Methods</h4>Retrospective, population-based cohort study using linked, anonymized electronic health data from SAIL Databank, including primary/secondary care, rheumatology, Office for National Statistics Mortality and COVID-19 laboratory data. Individuals aged 18 years and over testing positive for COVID-19 between March 2020 and May 2021 with READ Codes present for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis formed the study cases.<h4>Results</h4>A total of 1966 people with IA and 166 602 without tested positive for COVID-19. The incidence rate was 3.5% (1966/56 914) in IA, vs 6% in the general population (166 602/2 760 442), (difference: 2.5%, 95% CI: 2.4%, 2.7%, P ≤0.001). In an adjusted Cox proportional hazard model, IA was not associated with higher mortality (HR: 0.56, 95% CI: 0.18, 1.64, P=0.286). Significant risk factors included shielding (HR: 1.52, 95% CI: 1.40, 1.64, P ≤0.001), hospitalization for previous infections (HR: 1.20, 95% CI: 1.12, 1.28, P ≤0.001), hospitalizations one year pre-pandemic (HR: 1.34, 95% CI: 1.25, 1.44, P ≤0.001) and glucocorticoid use (HR: 1.17, 95% CI: 1.09, 1.25, P ≤0.001).<h4>Conclusions</h4>Individuals with IA had a lower incidence of COVID-19, probably due to shielding. IA was not associated with increased mortality following COVID-19 infection; being vulnerable (shielded), comorbidities and other factors were associated with increased risk. These key risk factors can identify individuals with IA at greater risk from COVID-19 and advised to shield during high community prevalence.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62372/Download/62372__26337__5539f4f995224d80a2156218d11a03cb.pdf; doi:https://doi.org/10.1093/rheumatology/keac283; html:https://europepmc.org/articles/PMC9248059; pdf:https://europepmc.org/articles/PMC9248059?pdf=render
 34308406,https://doi.org/10.1016/j.lanepe.2021.100180,Ethnic differences in SARS-CoV-2 vaccine hesitancy in United Kingdom healthcare workers: Results from the UK-REACH prospective nationwide cohort study.,"Woolf K, McManus IC, Martin CA, Nellums LB, Guyatt AL, Melbourne C, Bryant L, Gogoi M, Wobi F, Al-Oraibi A, Hassan O, Gupta A, John C, Tobin MD, Carr S, Simpson S, Gregary B, Aujayeb A, Zingwe S, Reza R, Gray LJ, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,The Lancet regional health. Europe,2021,2021-07-19,Y,,,,"<h4>Background</h4>In most countries, healthcare workers (HCWs) represent a priority group for vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) due to their elevated risk of COVID-19 and potential contribution to nosocomial SARS-CoV-2 transmission. Concerns have been raised that HCWs from ethnic minority groups are more likely to be vaccine hesitant (defined by the World Health Organisation as refusing or delaying a vaccination) than those of White ethnicity, but there are limited data on SARS-CoV-2 vaccine hesitancy and its predictors in UK HCWs.<h4>Methods</h4>Nationwide prospective cohort study and qualitative study in a multi-ethnic cohort of clinical and non-clinical UK HCWs. We analysed ethnic differences in SARS-CoV-2 vaccine hesitancy adjusting for demographics, vaccine trust, and perceived risk of COVID-19. We explored reasons for hesitancy in qualitative data using a framework analysis.<h4>Findings</h4>11,584 HCWs were included in the cohort analysis. 23% (2704) reported vaccine hesitancy. Compared to White British HCWs (21.3% hesitant), HCWs from Black Caribbean (54.2%), Mixed White and Black Caribbean (38.1%), Black African (34.4%), Chinese (33.1%), Pakistani (30.4%), and White Other (28.7%) ethnic groups were significantly more likely to be hesitant. In adjusted analysis, Black Caribbean (aOR 3.37, 95% CI 2.11 - 5.37), Black African (aOR 2.05, 95% CI 1.49 - 2.82), White Other ethnic groups (aOR 1.48, 95% CI 1.19 - 1.84) were significantly more likely to be hesitant. Other independent predictors of hesitancy were younger age, female sex, higher score on a COVID-19 conspiracy beliefs scale, lower trust in employer, lack of influenza vaccine uptake in the previous season, previous COVID-19, and pregnancy. Qualitative data from 99 participants identified the following contributors to hesitancy: lack of trust in government and employers, safety concerns due to the speed of vaccine development, lack of ethnic diversity in vaccine studies, and confusing and conflicting information. Participants felt uptake in ethnic minority communities might be improved through inclusive communication, involving HCWs in the vaccine rollout, and promoting vaccination through trusted networks.<h4>Interpretation</h4>Despite increased risk of COVID-19, HCWs from some ethnic minority groups are more likely to be vaccine hesitant than their White British colleagues. Strategies to build trust and dispel myths surrounding the COVID-19 vaccine in these communities are urgently required. Emphasis should be placed on the safety and benefit of SARS-CoV-2 vaccination in pregnancy and in those with previous COVID-19. Public health communications should be inclusive, non-stigmatising and utilise trusted networks.<h4>Funding</h4>UKRI-MRC and NIHR.",,doi:https://doi.org/10.1016/j.lanepe.2021.100180; doi:https://doi.org/10.1016/j.lanepe.2021.100180; html:https://europepmc.org/articles/PMC8287519; pdf:https://europepmc.org/articles/PMC8287519?pdf=render
 34972825,https://doi.org/10.1038/s41564-021-01029-0,Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework.,"Nicholson G, Lehmann B, Padellini T, Pouwels KB, Jersakova R, Lomax J, King RE, Mallon AM, Diggle PJ, Richardson S, Blangiardo M, Holmes C.",,Nature microbiology,2022,2021-12-31,Y,,,,"Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, R<sub>t</sub>, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and R<sub>t</sub>. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of R<sub>t</sub> are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and R<sub>t</sub> that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.",,pdf:https://www.nature.com/articles/s41564-021-01029-0.pdf; doi:https://doi.org/10.1038/s41564-021-01029-0; html:https://europepmc.org/articles/PMC8727294; pdf:https://europepmc.org/articles/PMC8727294?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",,,"<h4>Introduction</h4>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 (<i>Complexo da Maré</i>) in Rio de Janeiro, Brazil.<h4>Methods</h4>We performed a difference-in-differences (DID) analysis to estimate the impact of the multicomponent intervention in <i>Maré,</i> 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 <i>Maré</i>.<h4>Results</h4>Before the intervention, <i>Maré</i> 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, <i>Maré</i> 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 <i>Maré</i> 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 <i>Maré</i> after intervention onset.<h4>Conclusion</h4>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; doi:https://doi.org/10.1136/bmjgh-2022-009997; html:https://europepmc.org/articles/PMC10230340; pdf:https://europepmc.org/articles/PMC10230340?pdf=render
 33879890,https://doi.org/10.1038/s41591-021-01329-2,Single-cell multi-omics analysis of the immune response in COVID-19.,"Stephenson E, Reynolds G, Botting RA, Calero-Nieto FJ, Morgan MD, 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 LCS, Goh I, Horsfall D, McGrath J, Webb S, Mather MW, Lindeboom RGH, Dann E, Huang N, Polanski K, Prigmore E, Gothe F, Scott J, Payne RP, Baker KF, Hanrath AT, Schim van der Loeff ICD, 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, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID-19 BioResource Collaboration, Rostron AJ, Simpson AJ, Hambleton S, Laurenti E, Lyons PA, Meyer KB, Nikolić MZ, Duncan CJA, Smith KGC, Teichmann SA, Clatworthy MR, Marioni JC, Göttgens B, Haniffa M.",,Nature medicine,2021,2021-04-20,Y,,,,"Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16<sup>+</sup>C1QA/B/C<sup>+</sup>) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34<sup>+</sup> hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8<sup>+</sup> T cells and an increased ratio of CD8<sup>+</sup> effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.",,pdf:https://www.nature.com/articles/s41591-021-01329-2.pdf; doi:https://doi.org/10.1038/s41591-021-01329-2; html:https://europepmc.org/articles/PMC8121667; pdf:https://europepmc.org/articles/PMC8121667?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",,,"<h4>Introduction</h4>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 (<i>Complexo da Maré</i>) in Rio de Janeiro, Brazil.<h4>Methods</h4>We performed a difference-in-differences (DID) analysis to estimate the impact of the multicomponent intervention in <i>Maré,</i> 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 <i>Maré</i>.<h4>Results</h4>Before the intervention, <i>Maré</i> 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, <i>Maré</i> 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 <i>Maré</i> 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 <i>Maré</i> after intervention onset.<h4>Conclusion</h4>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; doi:https://doi.org/10.1136/bmjgh-2022-009997; html:https://europepmc.org/articles/PMC10230340; pdf:https://europepmc.org/articles/PMC10230340?pdf=render
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://openres.ersjournals.com/content/erjor/early/2023/01/26/23120541.00274-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00274-2022; html:https://europepmc.org/articles/PMC9790090; pdf:https://europepmc.org/articles/PMC9790090?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,,,,,,pdf:https://link.springer.com/content/pdf/10.1007/s00134-023-07039-2.pdf; doi:https://doi.org/10.1007/s00134-023-07039-2; html:https://europepmc.org/articles/PMC10108805; pdf:https://europepmc.org/articles/PMC10108805?pdf=render
 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,,,,,,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221095245; doi:https://doi.org/10.1177/01410768221095245; html:https://europepmc.org/articles/PMC9234890; pdf:https://europepmc.org/articles/PMC9234890?pdf=render
@@ -342,9 +342,9 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Department of Health and Social Care, England.",,pdf:http://www.thelancet.com/article/S2213260021005427/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00542-7; html:https://europepmc.org/articles/PMC8786320
 35151397,https://doi.org/10.1016/s0140-6736(22)00163-5,"Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2022,2022-02-01,Y,,,,"<h4>Background</h4>Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19.<h4>Methods</h4>RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).<h4>Findings</h4>Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69-0·91; p=0·0009). In an analysis of all randomly assigned patients (regardless of baseline antibody status), 943 (19%) of 4839 patients allocated to casirivimab and imdevimab versus 1029 (21%) of 4946 patients allocated to usual care died within 28 days (RR 0·94, 95% CI 0·86-1·02; p=0·14). The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity=0·002). There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions reported in seven (<1%) participants were believed by the local investigator to be related to treatment with casirivimab and imdevimab.<h4>Interpretation</h4>In patients admitted to hospital with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab reduced 28-day mortality in patients who were seronegative (and therefore had not mounted their own humoral immune response) at baseline but not in those who were seropositive at baseline.<h4>Funding</h4>UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/95149/5/1-s2.0-S0140673622001635-main.pdf; doi:https://doi.org/10.1016/S0140-6736(22)00163-5; html:https://europepmc.org/articles/PMC8830904
 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.",,pdf:https://academic.oup.com/ageing/article-pdf/50/1/25/42362959/afaa207.pdf; doi:https://doi.org/10.1093/ageing/afaa207; html:https://europepmc.org/articles/PMC7546151; pdf:https://europepmc.org/articles/PMC7546151?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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/10/e043010.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043010; html:https://europepmc.org/articles/PMC7580065; pdf:https://europepmc.org/articles/PMC7580065?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 (<i>Phase 0</i>, the date before February 26, 2020) and four pandemic phases (<i>Phases 1-4</i>) 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; doi:https://doi.org/10.1177/08862605231163885; html:https://europepmc.org/articles/PMC10064198; pdf:https://europepmc.org/articles/PMC10064198?pdf=render
 36276403,https://doi.org/10.3389/fpubh.2022.875198,The mental health experiences of ethnic minorities in the UK during the Coronavirus pandemic: A qualitative exploration.,"Van Bortel T, Lombardo C, Guo L, Solomon S, Martin S, Hughes K, Weeks L, Crepaz-Keay D, McDaid S, Chantler O, Thorpe L, Morton A, Davidson G, John A, Kousoulis AA.",,Frontiers in public health,2022,2022-10-06,Y,Mental health; United Kingdom; Inequalities; Ethnic Minorities; Covid-19; Coronavirus Pandemic; Bame Ethnicity,,,"<h4>Background</h4>Worldwide, the Coronavirus pandemic has had a major impact on people's health, lives, and livelihoods. However, this impact has not been felt equally across various population groups. People from ethnic minority backgrounds in the UK have been more adversely affected by the pandemic, especially in terms of their physical health. Their mental health, on the other hand, has received less attention. This study aimed to explore the mental health experiences of UK adults from ethnic minorities during the Coronavirus pandemic. This work forms part of our wider long-term UK population study ""Mental Health in the Pandemic.""<h4>Methods</h4>We conducted an exploratory qualitative study with people from ethnic minority communities across the UK. A series of in-depth interviews were conducted with 15 women, 14 men and 1 non-binary person from ethnic minority backgrounds, aged between 18 and 65 years old (mean age = 40). We utilized purposefully selected maximum variation sampling in order to capture as wide a variety of views, perceptions and experiences as possible. Inclusion criteria: adults (18+) from ethnic minorities across the UK; able to provide full consent to participate; able to participate in a video- or phone-call interview. All interviews took place <i>via</i> MS Teams or Zoom. The gathered data were transcribed verbatim and underwent thematic analysis following Braun and Clarke carried out using NVivo 12 software.<h4>Results</h4>The qualitative data analysis yielded seven overarching themes: (1) pandemic-specific mental health and wellbeing experiences; (2) issues relating to the media; (3) coping mechanisms; (4) worries around and attitudes toward vaccination; (5) suggestions for support in moving forward; (6) best and worst experiences during pandemic and lockdowns; (7) biggest areas of change in personal life. Generally, participants' mental health experiences varied with some not being affected by the pandemic in a way related to their ethnicity, some sharing positive experiences and coping strategies (exercising more, spending more time with family, community cohesion), and some expressing negative experiences (eating or drinking more, feeling more isolated, or even racism and abuse, especially toward Asian communities). Concerns were raised around trust issues in relation to the media, the inadequate representation of ethnic minorities, and the spread of fake news especially on social media. Attitudes toward vaccinations varied too, with some people more willing to have the vaccine than others.<h4>Conclusion</h4>This study's findings highlight the diversity in the pandemic mental health experiences of ethnic minorities in the UK and has implications for policy, practice and further research. To enable moving forward beyond the pandemic, our study surfaced the need for culturally appropriate mental health support, financial support (as a key mental health determinant), accurate media representation, and clear communication messaging from the Governments of the UK.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.875198/pdf; doi:https://doi.org/10.3389/fpubh.2022.875198; html:https://europepmc.org/articles/PMC9582845; pdf:https://europepmc.org/articles/PMC9582845?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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/10/e043010.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043010; html:https://europepmc.org/articles/PMC7580065; pdf:https://europepmc.org/articles/PMC7580065?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/ ).",,pdf:https://www.nature.com/articles/s41467-020-19996-z.pdf; doi:https://doi.org/10.1038/s41467-020-19996-z; html:https://europepmc.org/articles/PMC7744536; pdf:https://europepmc.org/articles/PMC7744536?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",,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>World Health Organization.",,doi:https://doi.org/10.1016/j.lanepe.2022.100381; doi:https://doi.org/10.1016/j.lanepe.2022.100381; html:https://europepmc.org/articles/PMC8996067; pdf:https://europepmc.org/articles/PMC8996067?pdf=render
 36476601,https://doi.org/10.1186/s12911-022-02055-6,Neural-signature methods for structured EHR prediction.,"Vauvelle A, Creed P, Denaxas S.",,BMC medical informatics and decision making,2022,2022-12-07,Y,Machine Learning; Electronic Healthcare Records; Signature Methods,,,"Models that can effectively represent structured Electronic Healthcare Records (EHR) are central to an increasing range of applications in healthcare. Due to the sequential nature of health data, Recurrent Neural Networks have emerged as the dominant component within state-of-the-art architectures. The signature transform represents an alternative modelling paradigm for sequential data. This transform provides a non-learnt approach to creating a fixed vector representation of temporal features and has shown strong performances across an increasing number of domains, including medical data. However, the signature method has not yet been applied to structured EHR data. To this end, we follow recent work that enables the signature to be used as a differentiable layer within a neural architecture enabling application in high dimensional domains where calculation would have previously been intractable. Using a heart failure prediction task as an exemplar, we provide an empirical evaluation of different variations of the signature method and compare against state-of-the-art baselines. This first application of neural-signature methods in real-world healthcare data shows a competitive performance when compared to strong baselines and thus warrants further investigation within the health domain.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-02055-6; doi:https://doi.org/10.1186/s12911-022-02055-6; html:https://europepmc.org/articles/PMC9730578; pdf:https://europepmc.org/articles/PMC9730578?pdf=render
@@ -372,8 +372,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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)].<h4>Conclusion</h4>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.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02096-0; doi:https://doi.org/10.1186/s12916-021-02096-0; html:https://europepmc.org/articles/PMC8404408; pdf:https://europepmc.org/articles/PMC8404408?pdf=render
 34458849,https://doi.org/10.1093/oxfimm/iqab014,Protease inhibitor plasma concentrations associate with COVID-19 infection.,"Medjeral-Thomas NR, Troldborg A, Hansen AG, Pihl R, Clarke CL, Peters JE, Thomas DC, Willicombe M, Palarasah Y, Botto M, Pickering MC, Thiel S.",,Oxford open immunology,2021,2021-07-07,Y,Coronavirus; Protease inhibitors; innate immunity; Covid-19,,,"Protease inhibitors influence a range of innate immunity and inflammatory pathways. We quantified plasma concentrations of key anti-inflammatory protease inhibitors in chronic haemodialysis patients with coronavirus disease 2019 (COVID-19). The samples were collected early in the disease course to determine whether plasma protease inhibitor levels associated with the presence and severity of COVID-19. We used antibody-based immunoassays to measure plasma concentrations of C1 esterase inhibitor, alpha2-macroglobulin, antithrombin and inter-alpha-inhibitor heavy chain 4 (ITIH4) in 100 serial samples from 27 haemodialysis patients with COVID-19. ITIH4 was tested in two assays, one measuring intact ITIH4 and another also detecting any fragmented ITIH4 (total ITIH4). Control cohorts were 32 haemodialysis patients without COVID-19 and 32 healthy controls. We compared protease inhibitor concentration based on current and future COVID-19 severity and with C-reactive protein. Results were adjusted for repeated measures and multiple comparisons. Analysis of all available samples demonstrated lower plasma C1 esterase inhibitor and α2M and higher total ITIH4 in COVID-19 compared with dialysis controls. These differences were also seen in the first sample collected after COVID-19 diagnosis, a median of 4 days from diagnostic swab. Plasma ITIH4 levels were higher in severe than the non-severe COVID-19. Serum C-reactive protein correlated positively with plasma levels of antithrombin, intact ITIH4 and total ITIH4. In conclusion, plasma protease inhibitor concentrations are altered in COVID-19.",,pdf:https://academic.oup.com/ooim/article-pdf/2/1/iqab014/48744499/iqab014.pdf; doi:https://doi.org/10.1093/oxfimm/iqab014; html:https://europepmc.org/articles/PMC8371939; pdf:https://europepmc.org/articles/PMC8371939?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Interpretation</h4>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.<h4>Funding</h4>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.",,pdf:http://www.thelancet.com/article/S2352301820303052/pdf; 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
-37468148,https://doi.org/10.1136/bmj-2023-075133,Associations between self-reported healthcare disruption due to covid-19 and avoidable hospital admission: evidence from seven linked longitudinal studies for England.,"Green MA, McKee M, Hamilton OK, Shaw RJ, Macleod J, Boyd A, Katikireddi SV, LH&W NCS Collaborative.",,BMJ (Clinical research ed.),2023,2023-07-19,Y,,,,"<h4>Objectives</h4>To examine whether there is an association between people who experienced disrupted access to healthcare during the covid-19 pandemic and risk of an avoidable hospital admission.<h4>Design</h4>Observational analysis using evidence from seven linked longitudinal cohort studies for England.<h4>Setting</h4>Studies linked to electronic health records from NHS Digital from 1 March 2020 to 25 August 2022. Data were accessed using the UK Longitudinal Linkage Collaboration trusted research environment.<h4>Participants</h4>Individual level records for 29 276 people.<h4>Main outcome measures</h4>Avoidable hospital admissions defined as emergency hospital admissions for ambulatory care sensitive and emergency urgent care sensitive conditions.<h4>Results</h4>9742 participants (weighted percentage 35%, adjusted for sample structure of longitudinal cohorts) self-reported some form of disrupted access to healthcare during the covid-19 pandemic. People with disrupted access were at increased risk of any (odds ratio 1.80, 95% confidence interval 1.39 to 2.34), acute (2.01, 1.39 to 2.92), and chronic (1.80, 1.31 to 2.48) ambulatory care sensitive hospital admissions. For people who experienced disrupted access to appointments (eg, visiting their doctor or an outpatient department) and procedures (eg, surgery, cancer treatment), positive associations were found with measures of avoidable hospital admissions.<h4>Conclusions</h4>Evidence from linked individual level data shows that people whose access to healthcare was disrupted were more likely to have a potentially preventable hospital admission. The findings highlight the need to increase healthcare investment to tackle the short and long term implications of the pandemic, and to protect treatments and procedures during future pandemics.",,doi:https://doi.org/10.1136/bmj-2023-075133; html:https://europepmc.org/articles/PMC10354595; pdf:https://europepmc.org/articles/PMC10354595?pdf=render
 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.",,pdf:https://www.science.org/cms/asset/e974db95-138d-4a9f-aa91-2f8f6c705f36/pap.pdf; doi:https://doi.org/10.1126/science.abf9648; html:https://europepmc.org/articles/PMC8139426; pdf:https://europepmc.org/articles/PMC8139426?pdf=render
+37468148,https://doi.org/10.1136/bmj-2023-075133,Associations between self-reported healthcare disruption due to covid-19 and avoidable hospital admission: evidence from seven linked longitudinal studies for England.,"Green MA, McKee M, Hamilton OK, Shaw RJ, Macleod J, Boyd A, Katikireddi SV, LH&W NCS Collaborative.",,BMJ (Clinical research ed.),2023,2023-07-19,Y,,,,"<h4>Objectives</h4>To examine whether there is an association between people who experienced disrupted access to healthcare during the covid-19 pandemic and risk of an avoidable hospital admission.<h4>Design</h4>Observational analysis using evidence from seven linked longitudinal cohort studies for England.<h4>Setting</h4>Studies linked to electronic health records from NHS Digital from 1 March 2020 to 25 August 2022. Data were accessed using the UK Longitudinal Linkage Collaboration trusted research environment.<h4>Participants</h4>Individual level records for 29 276 people.<h4>Main outcome measures</h4>Avoidable hospital admissions defined as emergency hospital admissions for ambulatory care sensitive and emergency urgent care sensitive conditions.<h4>Results</h4>9742 participants (weighted percentage 35%, adjusted for sample structure of longitudinal cohorts) self-reported some form of disrupted access to healthcare during the covid-19 pandemic. People with disrupted access were at increased risk of any (odds ratio 1.80, 95% confidence interval 1.39 to 2.34), acute (2.01, 1.39 to 2.92), and chronic (1.80, 1.31 to 2.48) ambulatory care sensitive hospital admissions. For people who experienced disrupted access to appointments (eg, visiting their doctor or an outpatient department) and procedures (eg, surgery, cancer treatment), positive associations were found with measures of avoidable hospital admissions.<h4>Conclusions</h4>Evidence from linked individual level data shows that people whose access to healthcare was disrupted were more likely to have a potentially preventable hospital admission. The findings highlight the need to increase healthcare investment to tackle the short and long term implications of the pandemic, and to protect treatments and procedures during future pandemics.",,doi:https://doi.org/10.1136/bmj-2023-075133; html:https://europepmc.org/articles/PMC10354595; pdf:https://europepmc.org/articles/PMC10354595?pdf=render
 37751444,https://doi.org/10.1371/journal.pone.0290583,Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.,"Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.",,PloS one,2023,2023-09-26,Y,,,,"<h4>Background</h4>Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.<h4>Aims</h4>To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.<h4>Methods</h4>We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.<h4>Results</h4>We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.<h4>Conclusions</h4>Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0290583&type=printable; doi:https://doi.org/10.1371/journal.pone.0290583; html:https://europepmc.org/articles/PMC10521988; pdf:https://europepmc.org/articles/PMC10521988?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; doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; html:https://europepmc.org/articles/PMC7843148
 35476839,https://doi.org/10.1371/journal.pone.0266967,"Healthcare contacts with self-harm during COVID-19: An e-cohort whole-population-based study using individual-level linked routine electronic health records in Wales, UK, 2016-March 2021.","DelPozo-Banos M, Lee SC, Friedmann Y, Akbari A, Torabi F, Lloyd K, Lyons RA, John A.",,PloS one,2022,2022-04-27,Y,,,,"<h4>Introduction</h4>Reduced rates of help seeking by those who self-harmed during the COVID-19 pandemic have been reported.<h4>Objectives</h4>To understand changes in healthcare service contacts for self-harm during the COVID-19 pandemic across primary, emergency and secondary care.<h4>Methods</h4>This retrospective cohort study used routine electronic healthcare data for Wales, United Kingdom, from 2016 to March 14, 2021. Population-based data from primary care, emergency departments and hospital admissions were linked at individual-level. All Welsh residents aged ≥10 years over the study period were included in the study. Primary, emergency and secondary care contacts with self-harm at any time between 2016 and March 14, 2021 were identified. Outcomes were counts, incidence, prevalence and proportion of self-harm contacts relative to all contacts in each and all settings, as well as the proportion of people contacting one or more settings with self-harm. Weekly trends were modelled using generalised estimated equations, with differences between 2020 (to March 2021) and comparison years 2016-2018 (to March 2017-2019) quantified using difference in differences, from which mean rate of odds ratios (μROR) across years was reported.<h4>Results</h4>The study included 3,552,210 individuals over the study period. Self-harm contacts reduced across services in March and December 2020 compared to previous years. Primary care contacts with self-harm reduced disproportionately compared to non-self-harm contacts (μROR = 0.7, p<0.05), while their proportion increased in emergency departments during April 2020 (μROR = 1.3, p<0.05 in 2/3 comparison years) and hospital admissions during April-May 2020 (μROR = 1.2, p<0.05 in 2/3 comparison years). Despite this, those who self-harmed in April 2020 were more likely to be seen in primary care than other settings compared to previous years (μROR = 1.2, p<0.05). A lower proportion of those with self-harm contacts in emergency departments were subsequently admitted to hospital in December 2020 compared to previous years (μROR = 0.5, p<0.05).<h4>Conclusions</h4>These findings suggest that those who self-harmed during the COVID-19 pandemic may have been less likely to seek help, and those who did so faced more stringent criteria for admission. Communications encouraging those who self-harm to seek help during pandemics may be beneficial. However, this needs to be supported by maintained provision of mental health services.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0266967&type=printable; doi:https://doi.org/10.1371/journal.pone.0266967; html:https://europepmc.org/articles/PMC9045644; pdf:https://europepmc.org/articles/PMC9045644?pdf=render
@@ -387,8 +387,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 32616598,https://doi.org/10.1183/13993003.01809-2020,Using imaging to combat a pandemic: rationale for developing the UK National COVID-19 Chest Imaging Database. ,"Jacob J, Alexander D, Baillie JK, Berka R, Bertolli O, Blackwood J, Buchan I, Bloomfield C, Cushnan D, Docherty A, Edey A, Favaro A, Gleeson F, Halling-Brown M, Hare S, Jefferson E, Johnstone A, Kirby M, McStay R, Nair A, Openshaw PJM, Parker G, Reilly G, Robinson G, Roditi G, Rodrigues JCL, Sebire N, Semple MG, Sudlow C, Woznitza N, Joshi I.",,The European respiratory journal,2020,2020-08-13,Y,,,,"The National COVID-19 Chest Imaging Database (NCCID) is a repository of chest radiographs, CT and MRI images and clinical data from COVID-19 patients across the UK, to support research and development of AI technology and give insight into COVID-19 disease https://bit.ly/3eQeuha",,pdf:https://erj.ersjournals.com/content/erj/56/2/2001809.full.pdf; doi:https://doi.org/10.1183/13993003.01809-2020; html:https://europepmc.org/articles/PMC7331656; pdf:https://europepmc.org/articles/PMC7331656?pdf=render
 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.",,pdf:https://www.nature.com/articles/s41467-022-28157-3.pdf; doi:https://doi.org/10.1038/s41467-022-28157-3; html:https://europepmc.org/articles/PMC8789777; pdf:https://europepmc.org/articles/PMC8789777?pdf=render
 35820692,https://doi.org/10.1136/bmj-2021-069881,Clinical prediction models for mortality in patients with covid-19: external validation and individual participant data meta-analysis.,"de Jong VMT, Rousset RZ, Antonio-Villa NE, Buenen AG, Van Calster B, Bello-Chavolla OY, Brunskill NJ, Curcin V, Damen JAA, Fermín-Martínez CA, Fernández-Chirino L, Ferrari D, Free RC, Gupta RK, Haldar P, Hedberg P, Korang SK, Kurstjens S, Kusters R, Major RW, Maxwell L, Nair R, Naucler P, Nguyen TL, Noursadeghi M, Rosa R, Soares F, Takada T, van Royen FS, van Smeden M, Wynants L, Modrák M, CovidRetro collaboration, Asselbergs FW, Linschoten M, CAPACITY-COVID consortium, Moons KGM, Debray TPA.",,BMJ (Clinical research ed.),2022,2022-07-12,Y,,,,"<h4>Objective</h4>To externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19.<h4>Design</h4>Two stage individual participant data meta-analysis.<h4>Setting</h4>Secondary and tertiary care.<h4>Participants</h4>46 914 patients across 18 countries, admitted to a hospital with polymerase chain reaction confirmed covid-19 from November 2019 to April 2021.<h4>Data sources</h4>Multiple (clustered) cohorts in Brazil, Belgium, China, Czech Republic, Egypt, France, Iran, Israel, Italy, Mexico, Netherlands, Portugal, Russia, Saudi Arabia, Spain, Sweden, United Kingdom, and United States previously identified by a living systematic review of covid-19 prediction models published in <i>The BMJ</i>, and through PROSPERO, reference checking, and expert knowledge.<h4>Model selection and eligibility criteria</h4>Prognostic models identified by the living systematic review and through contacting experts. A priori models were excluded that had a high risk of bias in the participant domain of PROBAST (prediction model study risk of bias assessment tool) or for which the applicability was deemed poor.<h4>Methods</h4>Eight prognostic models with diverse predictors were identified and validated. A two stage individual participant data meta-analysis was performed of the estimated model concordance (C) statistic, calibration slope, calibration-in-the-large, and observed to expected ratio (O:E) across the included clusters.<h4>Main outcome measures</h4>30 day mortality or in-hospital mortality.<h4>Results</h4>Datasets included 27 clusters from 18 different countries and contained data on 46 914patients. The pooled estimates ranged from 0.67 to 0.80 (C statistic), 0.22 to 1.22 (calibration slope), and 0.18 to 2.59 (O:E ratio) and were prone to substantial between study heterogeneity. The 4C Mortality Score by Knight et al (pooled C statistic 0.80, 95% confidence interval 0.75 to 0.84, 95% prediction interval 0.72 to 0.86) and clinical model by Wang et al (0.77, 0.73 to 0.80, 0.63 to 0.87) had the highest discriminative ability. On average, 29% fewer deaths were observed than predicted by the 4C Mortality Score (pooled O:E 0.71, 95% confidence interval 0.45 to 1.11, 95% prediction interval 0.21 to 2.39), 35% fewer than predicted by the Wang clinical model (0.65, 0.52 to 0.82, 0.23 to 1.89), and 4% fewer than predicted by Xie et al's model (0.96, 0.59 to 1.55, 0.21 to 4.28).<h4>Conclusion</h4>The prognostic value of the included models varied greatly between the data sources. Although the Knight 4C Mortality Score and Wang clinical model appeared most promising, recalibration (intercept and slope updates) is needed before implementation in routine care.",,pdf:https://www.bmj.com/content/bmj/378/bmj-2021-069881.full.pdf; doi:https://doi.org/10.1136/bmj-2021-069881; html:https://europepmc.org/articles/PMC9273913; pdf:https://europepmc.org/articles/PMC9273913?pdf=render
-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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/ije/article-pdf/51/6/1745/47882630/dyac158.pdf; doi:https://doi.org/10.1093/ije/dyac158; html:https://europepmc.org/articles/PMC9384728; pdf:https://europepmc.org/articles/PMC9384728?pdf=render
 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,,,"<h4>Background</h4>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 (R<sub>0</sub>).<h4>Methods</h4>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 R<sub>0</sub>.<h4>Results</h4>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.<h4>Conclusion</h4>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 R<sub>0</sub> 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.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01779-4; doi:https://doi.org/10.1186/s12916-020-01779-4; html:https://europepmc.org/articles/PMC7533154; pdf:https://europepmc.org/articles/PMC7533154?pdf=render
+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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/ije/article-pdf/51/6/1745/47882630/dyac158.pdf; doi:https://doi.org/10.1093/ije/dyac158; html:https://europepmc.org/articles/PMC9384728; pdf:https://europepmc.org/articles/PMC9384728?pdf=render
 35879886,https://doi.org/10.1017/s0033291722002501,"Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.","Young KS, Purves KL, Hübel C, Davies MR, Thompson KN, Bristow S, Krebs G, Danese A, Hirsch C, Parsons CE, Vassos E, Adey BN, Bright S, Hegemann L, Lee YT, Kalsi G, Monssen D, Mundy J, Peel AJ, Rayner C, Rogers HC, Ter Kuile A, Ward C, York K, Lin Y, Palmos AB, Schmidt U, Veale D, Nicholson TR, Pollak TA, Stevelink SAM, Moukhtarian T, Martineau AR, Holt H, Maughan B, Al-Chalabi A, Chaudhuri KR, Richardson MP, Bradley JR, Chinnery PF, Kingston N, Papadia S, Stirrups KE, Linger R, Hotopf M, Eley TC, Breen G.",,Psychological medicine,2023,2022-07-26,Y,Depression; Anxiety; Ptsd; Covid-19,,,"<h4>Background</h4>The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.<h4>Method</h4>Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (<i>n</i> = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.<h4>Results</h4>Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.<h4>Conclusions</h4>We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/8C3760ED596F1ED8B80F729AC5E47B9B/S0033291722002501a.pdf/div-class-title-depression-anxiety-and-ptsd-symptoms-before-and-during-the-covid-19-pandemic-in-the-uk-div.pdf; doi:https://doi.org/10.1017/S0033291722002501; html:https://europepmc.org/articles/PMC10482709; pdf:https://europepmc.org/articles/PMC10482709?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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]).<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/ageing/article-pdf/50/4/1019/40971734/afab060.pdf; doi:https://doi.org/10.1093/ageing/afab060; html:https://europepmc.org/articles/PMC7989651; pdf:https://europepmc.org/articles/PMC7989651?pdf=render
 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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>NCT05240742.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e065142.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-065142; html:https://europepmc.org/articles/PMC9709810; pdf:https://europepmc.org/articles/PMC9709810?pdf=render
@@ -413,9 +413,9 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 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,,,"<h4>Introduction</h4>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).<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>ISRCTN11811602; Pre-results.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/9/e050647.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-050647; html:https://europepmc.org/articles/PMC8450967; pdf:https://europepmc.org/articles/PMC8450967?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.",pdf:https://www.science.org/cms/asset/fb31d61b-4be3-483a-b040-2ee970dfb432/pap.pdf; doi:https://doi.org/10.1126/science.abc0473; html:https://europepmc.org/articles/PMC7200009; pdf:https://europepmc.org/articles/PMC7200009?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,,,"<h4>Objective</h4>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.<h4>Method</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.<h4>Public significance</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/eat.23834; doi:https://doi.org/10.1002/eat.23834; html:https://europepmc.org/articles/PMC9874817; pdf:https://europepmc.org/articles/PMC9874817?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>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; doi:https://doi.org/10.1016/j.lanepe.2021.100267; html:https://europepmc.org/articles/PMC8629724; pdf:https://europepmc.org/articles/PMC8629724?pdf=render
 33203640,https://doi.org/10.1136/bmjopen-2020-043828,"Estimated impact of the COVID-19 pandemic on cancer services and excess 1-year mortality in people with cancer and multimorbidity: near real-time data on cancer care, cancer deaths and a population-based cohort study.","Lai AG, Pasea L, Banerjee A, Hall G, Denaxas S, Chang WH, Katsoulis M, Williams B, Pillay D, Noursadeghi M, Linch D, Hughes D, Forster MD, Turnbull C, Fitzpatrick NK, Boyd K, Foster GR, Enver T, Nafilyan V, Humberstone B, Neal RD, Cooper M, Jones M, Pritchard-Jones K, Sullivan R, Davie C, Lawler M, Hemingway H.",,BMJ open,2020,2020-11-17,Y,Oncology; Health Informatics; Covid-19,,,"<h4>Objectives</h4>To estimate the impact of the COVID-19 pandemic on cancer care services and overall (direct and indirect) excess deaths in people with cancer.<h4>Methods</h4>We employed near real-time weekly data on cancer care to determine the adverse effect of the pandemic on cancer services. We also used these data, together with national death registrations until June 2020 to model deaths, in excess of background (pre-COVID-19) mortality, in people with cancer. Background mortality risks for 24 cancers with and without COVID-19-relevant comorbidities were obtained from population-based primary care cohort (Clinical Practice Research Datalink) on 3 862 012 adults in England.<h4>Results</h4>Declines in urgent referrals (median=-70.4%) and chemotherapy attendances (median=-41.5%) to a nadir (lowest point) in the pandemic were observed. By 31 May, these declines have only partially recovered; urgent referrals (median=-44.5%) and chemotherapy attendances (median=-31.2%). There were short-term excess death registrations for cancer (without COVID-19), with peak relative risk (RR) of 1.17 at week ending on 3 April. The peak RR for all-cause deaths was 2.1 from week ending on 17 April. Based on these findings and recent literature, we modelled 40% and 80% of cancer patients being affected by the pandemic in the long-term. At 40% affected, we estimated 1-year total (direct and indirect) excess deaths in people with cancer as between 7165 and 17 910, using RRs of 1.2 and 1.5, respectively, where 78% of excess deaths occured in patients with ≥1 comorbidity.<h4>Conclusions</h4>Dramatic reductions were detected in the demand for, and supply of, cancer services which have not fully recovered with lockdown easing. These may contribute, over a 1-year time horizon, to substantial excess mortality among people with cancer and multimorbidity. It is urgent to understand how the recovery of general practitioner, oncology and other hospital services might best mitigate these long-term excess mortality risks.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/11/e043828.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043828; html:https://europepmc.org/articles/PMC7674020; pdf:https://europepmc.org/articles/PMC7674020?pdf=render
 32502389,https://doi.org/10.1016/s2468-2667(20)30133-x,"Effects of non-pharmaceutical interventions on COVID-19 cases, deaths, and demand for hospital services in the UK: a modelling study.","Davies NG, Kucharski AJ, Eggo RM, Gimma A, Edmunds WJ, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 working group.",,The Lancet. Public health,2020,2020-06-02,Y,,,,"<h4>Background</h4>Non-pharmaceutical interventions have been implemented to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the UK. Projecting the size of an unmitigated epidemic and the potential effect of different control measures has been crucial to support evidence-based policy making during the early stages of the epidemic. This study assesses the potential impact of different control measures for mitigating the burden of COVID-19 in the UK.<h4>Methods</h4>We used a stochastic age-structured transmission model to explore a range of intervention scenarios, tracking 66·4 million people aggregated to 186 county-level administrative units in England, Wales, Scotland, and Northern Ireland. The four base interventions modelled were school closures, physical distancing, shielding of people aged 70 years or older, and self-isolation of symptomatic cases. We also modelled the combination of these interventions, as well as a programme of intensive interventions with phased lockdown-type restrictions that substantially limited contacts outside of the home for repeated periods. We simulated different triggers for the introduction of interventions, and estimated the impact of varying adherence to interventions across counties. For each scenario, we projected estimated new cases over time, patients requiring inpatient and critical care (ie, admission to the intensive care units [ICU]) treatment, and deaths, and compared the effect of each intervention on the basic reproduction number, R<sub>0</sub>.<h4>Findings</h4>We projected a median unmitigated burden of 23 million (95% prediction interval 13-30) clinical cases and 350 000 deaths (170 000-480 000) due to COVID-19 in the UK by December, 2021. We found that the four base interventions were each likely to decrease R<sub>0</sub>, but not sufficiently to prevent ICU demand from exceeding health service capacity. The combined intervention was more effective at reducing R<sub>0</sub>, but only lockdown periods were sufficient to bring R<sub>0</sub> near or below 1; the most stringent lockdown scenario resulted in a projected 120 000 cases (46 000-700 000) and 50 000 deaths (9300-160 000). Intensive interventions with lockdown periods would need to be in place for a large proportion of the coming year to prevent health-care demand exceeding availability.<h4>Interpretation</h4>The characteristics of SARS-CoV-2 mean that extreme measures are probably required to bring the epidemic under control and to prevent very large numbers of deaths and an excess of demand on hospital beds, especially those in ICUs.<h4>Funding</h4>Medical Research Council.","The paper identifies the following; This paper identifies the influence of different interventions on COVID on cases, deaths, and demands for hospital services in the UK. This was achieved utilising modelling techniques. The paper concludes that the characteristics of SARS-CoV-2 mean that extreme measures are probably required to bring the epidemic under control and to prevent very large numbers of deaths and an excess of demand on hospital beds, especially those in ICUs. However, Biobank is not very representative of age, ethniticity and deprivation.",doi:https://doi.org/10.1016/s2468-2667(20)30133-x; doi:https://doi.org/10.1016/S2468-2667(20)30133-X; html:https://europepmc.org/articles/PMC7266572; pdf:https://europepmc.org/articles/PMC7266572?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>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; doi:https://doi.org/10.1016/j.lanepe.2021.100267; html:https://europepmc.org/articles/PMC8629724; pdf:https://europepmc.org/articles/PMC8629724?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,,,"<h4>Purpose</h4>To prospectively validate two risk scores to predict mortality (4C Mortality) and in-hospital deterioration (4C Deterioration) among adults hospitalised with COVID-19.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.<h4>Trial registration number</h4>ISRCTN66726260.",,pdf:https://thorax.bmj.com/content/thoraxjnl/77/6/606.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-217629; html:https://europepmc.org/articles/PMC8610617; pdf:https://europepmc.org/articles/PMC8610617?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,,,"<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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). <b>Conclusion:</b> 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.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364733; doi:https://doi.org/10.1080/20008066.2022.2105577; html:https://europepmc.org/articles/PMC9364733; pdf:https://europepmc.org/articles/PMC9364733?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.",,pdf:https://www.mdpi.com/1660-4601/19/23/15544/pdf?version=1669349785; doi:https://doi.org/10.3390/ijerph192315544; html:https://europepmc.org/articles/PMC9738189; pdf:https://europepmc.org/articles/PMC9738189?pdf=render
@@ -425,8 +425,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 37193316,https://doi.org/10.1016/j.xops.2023.100293,"A Datasheet for the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Screening Dataset.","Kale AU, Mills A, Guggenheim E, Gee D, Bodza S, Anumakonda A, Doal R, Williams R, Gallier S, Lee WH, Galsworthy P, Benning M, Fanning H, Keane PA, Denniston AK, Mollan SP.",,Ophthalmology science,2023,2023-02-26,Y,Diabetes mellitus; Diabetic retinopathy; Imaging; Dataset; Biomedical Data,,,"<h4>Purpose</h4>Diabetic retinopathy (DR) is the most common microvascular complication associated with diabetes mellitus (DM), affecting approximately 40% of this patient population. Early detection of DR is vital to ensure monitoring of disease progression and prompt sight saving treatments as required. This article describes the data contained within the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Dataset.<h4>Design</h4>Dataset descriptor for routinely collected eye screening data.<h4>Participants</h4>All diabetic patients aged 12 years and older, attending annual digital retinal photography-based screening within the Birmingham, Solihull, and Black Country Eye Screening Programme.<h4>Methods</h4>The INSIGHT Health Data Research Hub for Eye Health is a National Health Service (NHS)-led ophthalmic bioresource that provides researchers with safe access to anonymized, routinely collected data from contributing NHS hospitals to advance research for patient benefit. This report describes the INSIGHT Birmingham, Solihull, and Black Country DR Screening Dataset, a dataset of anonymized images and linked screening data derived from the United Kingdom's largest regional DR screening program.<h4>Main outcome measures</h4>This dataset consists of routinely collected data from the eye screening program. The data primarily include retinal photographs with the associated DR grading data. Additional data such as corresponding demographic details, information regarding patients' diabetic status, and visual acuity data are also available. Further details regarding available data points are available in the supplementary information, in addition to the INSIGHT webpage included below.<h4>Results</h4>At the time point of this analysis (December 31, 2019), the dataset comprised 6 202 161 images from 246 180 patients, with a dataset inception date of January 1, 2007. The dataset includes 1 360 547 grading episodes between R0M0 and R3M1.<h4>Conclusions</h4>This dataset descriptor article summarizes the content of the dataset, how it has been curated, and what its potential uses are. Data are available through a structured application process for research studies that support discovery, clinical evidence analyses, and innovation in artificial intelligence technologies for patient benefit. Further information regarding the data repository and contact details can be found at https://www.insight.hdrhub.org/.<h4>Financial disclosures</h4>Proprietary or commercial disclosure may be found after the references.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182318; doi:https://doi.org/10.1016/j.xops.2023.100293; html:https://europepmc.org/articles/PMC10182318; pdf:https://europepmc.org/articles/PMC10182318?pdf=render
 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,,,,"<h4>Objective</h4>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).<h4>Design</h4>Multiphase, prospective mixed methods study.<h4>Setting</h4>Remote data collection and social media channels in the United Kingdom, 14 April to 1 August 2021.<h4>Participants</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.bmj.com/content/bmj/377/bmj-2022-070230.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070230; html:https://europepmc.org/articles/PMC9043395; pdf:https://europepmc.org/articles/PMC9043395?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,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755653; 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
-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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/03/29/thoraxjnl-2021-218629.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-218629; html:https://europepmc.org/articles/PMC8983409; pdf:https://europepmc.org/articles/PMC8983409?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; doi:https://doi.org/10.7189/jogh.10.010348; html:https://europepmc.org/articles/PMC7211415; pdf:https://europepmc.org/articles/PMC7211415?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/03/29/thoraxjnl-2021-218629.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-218629; html:https://europepmc.org/articles/PMC8983409; pdf:https://europepmc.org/articles/PMC8983409?pdf=render
 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,,,,"<h4>Objective</h4>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.<h4>Design</h4>Test accuracy study.<h4>Setting</h4>Laboratory based evaluation.<h4>Participants</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>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%).<h4>Conclusions</h4>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.<h4>Study registration</h4>ISRCTN 56609224.",,pdf:https://www.bmj.com/content/bmj/371/bmj.m4262.full.pdf; doi:https://doi.org/10.1136/bmj.m4262; html:https://europepmc.org/articles/PMC7656121; pdf:https://europepmc.org/articles/PMC7656121?pdf=render
 36769519,https://doi.org/10.3390/jcm12030872,Patterns of Healthcare Resource Utilisation of Critical Care Survivors between 2006 and 2017 in Wales: A Population-Based Study.,"Alsallakh M, Tan L, Pugh R, Akbari A, Bailey R, Griffiths R, Lyons RA, Szakmany T.",,Journal of clinical medicine,2023,2023-01-21,Y,Wales; Healthcare Resource Utilisation; Critical Care Survivorship,,,"In this retrospective cohort study, we used the Secure Anonymised Information Linkage (SAIL) Databank to characterise and identify predictors of the one-year post-discharge healthcare resource utilisation (HRU) of adults who were admitted to critical care units in Wales between 1 April 2006 and 31 December 2017. We modelled one-year post-critical-care HRU using negative binomial models and used linear models for the difference from one-year pre-critical-care HRU. We estimated the association between critical illness and post-hospitalisation HRU using multilevel negative binomial models among people hospitalised in 2015. We studied 55,151 patients. Post-critical-care HRU was 11-87% greater than pre-critical-care levels, whereas emergency department (ED) attendances decreased by 30%. Age ≥50 years was generally associated with greater post-critical-care HRU; those over 80 had three times longer hospital readmissions than those younger than 50 (incidence rate ratio (IRR): 2.96, 95% CI: 2.84, 3.09). However, ED attendances were higher in those younger than 50. High comorbidity was associated with 22-62% greater post-critical-care HRU than no or low comorbidity. The most socioeconomically deprived quintile was associated with 24% more ED attendances (IRR: 1.24 [1.16, 1.32]) and 13% longer hospital stays (IRR: 1.13 [1.09, 1.17]) than the least deprived quintile. Critical care survivors had greater 1-year post-discharge HRU than non-critical inpatients, including 68% longer hospital stays (IRR: 1.68 [1.63, 1.74]). Critical care survivors, particularly those with older ages, high comorbidity, and socioeconomic deprivation, used significantly more primary and secondary care resources after discharge compared with their baseline and non-critical inpatients. Interventions are needed to ensure that key subgroups are identified and adequately supported.",,pdf:https://www.mdpi.com/2077-0383/12/3/872/pdf?version=1674984751; doi:https://doi.org/10.3390/jcm12030872; html:https://europepmc.org/articles/PMC9917699; pdf:https://europepmc.org/articles/PMC9917699?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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 (<i>p</i> < 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, <i>p</i> < 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, <i>p</i> = 0.012).<h4>Interpretation</h4>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.<h4>Funding</h4>PIONEER, the Health Data Research UK (HDR-UK) Health Data Research Hub in acute care.",,pdf:http://www.thelancet.com/article/S2589537022001584/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101428; html:https://europepmc.org/articles/PMC9096912; pdf:https://europepmc.org/articles/PMC9096912?pdf=render
@@ -455,8 +455,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 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.",,pdf:https://www.nature.com/articles/s41591-022-02158-7.pdf; doi:https://doi.org/10.1038/s41591-022-02158-7
 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,,,"<h4>Background</h4>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.<h4>Findings</h4>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.<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/gigascience/article-pdf/10/11/giab076/41395024/giab076.pdf; doi:https://doi.org/10.1093/gigascience/giab076; html:https://europepmc.org/articles/PMC8633457; pdf:https://europepmc.org/articles/PMC8633457?pdf=render
 33493433,https://doi.org/10.1016/s1470-2045(20)30743-9,"The impact of the COVID-19 pandemic on radiotherapy services in England, UK: a population-based study.","Spencer K, Jones CM, Girdler R, Roe C, Sharpe M, Lawton S, Miller L, Lewis P, Evans M, Sebag-Montefiore D, Roques T, Smittenaar R, Morris E.",,The Lancet. Oncology,2021,2021-01-22,Y,,,,"<h4>Background</h4>The indirect impact of the COVID-19 pandemic on cancer outcomes is of increasing concern. However, the extent to which key treatment modalities have been affected is unclear. We aimed to assess the impact of the pandemic on radiotherapy activity in England.<h4>Methods</h4>In this population-based study, data relating to all radiotherapy delivered for cancer in the English NHS, between Feb 4, 2019, and June 28, 2020, were extracted from the National Radiotherapy Dataset. Changes in mean weekly radiotherapy courses, attendances (reflecting fractions), and fractionation patterns following the start of the UK lockdown were compared with corresponding months in 2019 overall, for specific diagnoses, and across age groups. The significance of changes in radiotherapy activity during lockdown was examined using interrupted time-series (ITS) analysis.<h4>Findings</h4>In 2020, mean weekly radiotherapy courses fell by 19·9% in April, 6·2% in May, and 11·6% in June compared with corresponding months in 2019. A relatively greater fall was observed for attendances (29·1% in April, 31·4% in May, and 31·5% in June). These changes were significant on ITS analysis (p<0·0001). A greater reduction in treatment courses between 2019 and 2020 was seen for patients aged 70 years or older compared with those aged younger than 70 years (34·4% vs 7·3% in April). By diagnosis, the largest reduction from 2019 to 2020 in treatment courses was for prostate cancer (77·0% in April) and non-melanoma skin cancer (72·4% in April). Conversely, radiotherapy courses in April, 2020, compared with April, 2019, increased by 41·2% in oesophageal cancer, 64·2% in bladder cancer, and 36·3% in rectal cancer. Increased use of ultra-hypofractionated (26 Gy in five fractions) breast radiotherapy as a percentage of all courses (0·2% in April, 2019, to 60·6% in April, 2020; ITS p<0·0001) contributed to the substantial reduction in attendances.<h4>Interpretation</h4>Radiotherapy activity fell significantly, but use of hypofractionated regimens rapidly increased in the English NHS during the first peak of the COVID-19 pandemic. An increase in treatments for some cancers suggests that radiotherapy compensated for reduced surgical activity. These data will assist health-care providers in understanding the indirect consequences of the pandemic and the role of radiotherapy services in minimising these consequences.<h4>Funding</h4>None.",,pdf:http://www.thelancet.com/article/S1470204520307439/pdf; doi:https://doi.org/10.1016/S1470-2045(20)30743-9; html:https://europepmc.org/articles/PMC7825861; pdf:https://europepmc.org/articles/PMC7825861?pdf=render
-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,Y,Causal Inference; Observational Data; Target Trial; Trial Emulation,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%).<h4>Conclusion</h4>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; html:https://europepmc.org/articles/PMC10428565; pdf:https://europepmc.org/articles/PMC10428565?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Design</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/0272989X21994035; doi:https://doi.org/10.1177/0272989X21994035
+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,Y,Causal Inference; Observational Data; Target Trial; Trial Emulation,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%).<h4>Conclusion</h4>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; html:https://europepmc.org/articles/PMC10428565; pdf:https://europepmc.org/articles/PMC10428565?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Funding</h4>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
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.<h4>Trial registration</h4>Clinicaltrials.gov : NCT03071107 registered 06/03/2017.",,pdf:https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-023-03126-0; doi:https://doi.org/10.1186/s12882-023-03126-0; html:https://europepmc.org/articles/PMC10062243; pdf:https://europepmc.org/articles/PMC10062243?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
@@ -484,9 +484,9 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 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.",,pdf:https://bmcmedethics.biomedcentral.com/counter/pdf/10.1186/s12910-022-00875-9; doi:https://doi.org/10.1186/s12910-022-00875-9; html:https://europepmc.org/articles/PMC9756740; pdf:https://europepmc.org/articles/PMC9756740?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
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>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.",pdf:https://discovery.ucl.ac.uk/10097486/1/Lancet%20final%201%20year%20mortality.pdf; doi:https://doi.org/10.1016/S0140-6736(20)30854-0; html:https://europepmc.org/articles/PMC7217641
-37650027,https://doi.org/10.23889/ijpds.v7i1.1724,"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 RA.",,International journal of population data science,2022,2022-07-18,Y,Intensive Care; Critical Care; Electronic Health Records; Icnarc; Linkable Research Data,,,"<h4>Introduction</h4>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.<h4>Objective</h4>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.<h4>Method</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,doi:https://doi.org/10.23889/ijpds.v7i1.1724; html:https://europepmc.org/articles/PMC10464871; pdf:https://europepmc.org/articles/PMC10464871?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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://medinform.jmir.org/2021/4/e21547/PDF; doi:https://doi.org/10.2196/21547; html:https://europepmc.org/articles/PMC8023380
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-020-01336-2; doi:https://doi.org/10.1186/s12911-020-01336-2; html:https://europepmc.org/articles/PMC7736131; pdf:https://europepmc.org/articles/PMC7736131?pdf=render
+37650027,https://doi.org/10.23889/ijpds.v7i1.1724,"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 RA.",,International journal of population data science,2022,2022-07-18,Y,Intensive Care; Critical Care; Electronic Health Records; Icnarc; Linkable Research Data,,,"<h4>Introduction</h4>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.<h4>Objective</h4>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.<h4>Method</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,doi:https://doi.org/10.23889/ijpds.v7i1.1724; html:https://europepmc.org/articles/PMC10464871; pdf:https://europepmc.org/articles/PMC10464871?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,,,"<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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
 34320164,https://doi.org/10.1093/cvr/cvab239,"The RECOVERY trial: cardiovascular implications of a large, simple randomized trial in COVID-19.","Pessoa-Amorim G, Mafham MM.",,Cardiovascular research,2021,2021-07-01,Y,Immunomodulation; Antiviral; Randomized Trial; Antithrombotic; Covid-19,,,,,pdf:https://academic.oup.com/cardiovascres/article-pdf/117/9/e110/39354428/cvab239.pdf; doi:https://doi.org/10.1093/cvr/cvab239; html:https://europepmc.org/articles/PMC8318096; pdf:https://europepmc.org/articles/PMC8318096?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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 <i>vs</i> 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.<h4>Interpretation</h4>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.<h4>Funding</h4>None.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4669009/1/Russell_etal_2022_Incidence-and-management-of-inflammatory.pdf; 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
@@ -502,8 +502,8 @@ PMC9644982,https://doi.org/,Assessing the impacts of COVID-19 on Care Homes in W
 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.",,pdf:https://www.rcpjournals.org/content/futurehosp/8/2/e243.full.pdf; 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
 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
 37284234,https://doi.org/10.1140/epjds/s13688-023-00391-9,"The shock, the coping, the resilience: smartphone application use reveals Covid-19 lockdown effects on human behaviors.","Liu XF, Wang ZZ, Xu XK, Wu Y, Zhao Z, Deng H, Wang P, Chao N, Huang YC.",,EPJ data science,2023,2023-06-05,Y,Human behaviors; Natural Experiment; Lockdown; Smartphone Apps; Covid-19,,,"Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming ""digital residents."" This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9.",,doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?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,,,"<h4>Objectives</h4>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.<h4>Design</h4>Retrospective assessment of routinely collected data from electronic healthcare records.<h4>Setting</h4>Single large urban tertiary care centre.<h4>Participants</h4>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.<h4>Main outcome measures</h4>Sensitivity, specificity, positive and negative predictive value of the Amb score and GAPS in identifying patients discharged within 12 hours of arrival.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e064910.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064910; html:https://europepmc.org/articles/PMC9764605; pdf:https://europepmc.org/articles/PMC9764605?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,,,"<h4>Objectives</h4>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.<h4>Design</h4>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.<h4>Setting</h4>SW at a time considered early in the pandemic, where National Health Service authorities required evidence to guide localised planning and support decision-making.<h4>Participants</h4>Publicly available data on patients with COVID-19.<h4>Primary and secondary outcome measures</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e041536.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-041536; html:https://europepmc.org/articles/PMC7797241; pdf:https://europepmc.org/articles/PMC7797241?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,,,"<h4>Objectives</h4>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.<h4>Design</h4>Retrospective assessment of routinely collected data from electronic healthcare records.<h4>Setting</h4>Single large urban tertiary care centre.<h4>Participants</h4>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.<h4>Main outcome measures</h4>Sensitivity, specificity, positive and negative predictive value of the Amb score and GAPS in identifying patients discharged within 12 hours of arrival.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e064910.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064910; html:https://europepmc.org/articles/PMC9764605; pdf:https://europepmc.org/articles/PMC9764605?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://www.dovepress.com/getfile.php?fileID=78337; doi:https://doi.org/10.2147/POR.S353400; html:https://europepmc.org/articles/PMC8859726; pdf:https://europepmc.org/articles/PMC8859726?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; doi:https://doi.org/10.7554/eLife.58699; html:https://europepmc.org/articles/PMC7527238; pdf:https://europepmc.org/articles/PMC7527238?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,,,,"<h4>Importance</h4>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.<h4>Objective</h4>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.<h4>Design, setting, and participants</h4>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.<h4>Exposures</h4>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.<h4>Main outcomes and measures</h4>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.<h4>Results</h4>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.<h4>Conclusions and relevance</h4>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; pdf:https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2785080/izadi_2021_oi_210864_1633624160.94853.pdf
@@ -521,9 +521,9 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420473; doi:https://doi.org/10.1111/tri.14010; html:https://europepmc.org/articles/PMC8420473; pdf:https://europepmc.org/articles/PMC8420473?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
 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; doi:https://doi.org/10.12688/wellcomeopenres.15786.1; html:https://europepmc.org/articles/PMC7255910; pdf:https://europepmc.org/articles/PMC7255910?pdf=render
-37751239,https://doi.org/10.2196/49438,Design and Evaluation of an Intensive Care Unit Dashboard Built in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Wac M, Craddock I, Chantziara S, Campbell T, Santos-Rodriguez R, Davidson B, McWilliams C.",,JMIR human factors,2023,2023-09-26,Y,Design; Health; ICU; EPR; intensive care unit; Interview; Intensive Care; Critical Care; Electronic Patient Record; Participatory Design; Ehr; Electronic Health Record; Software Engineering; Clinical Information System; Cis; Thematic Analysis; Dashboard; Human-centered Design; Covid-19; Interactive Display,,,"<h4>Background</h4>Dashboards and interactive displays are becoming increasingly prevalent in most health care settings and have the potential to streamline access to information, consolidate disparate data sources and deliver new insights. Our research focuses on intensive care units (ICUs) which are heavily instrumented, critical care environments that generate vast amounts of data and frequently require individualized support for each patient. Consequently, clinicians experience a high cognitive load, which can translate to suboptimal performance. The global COVID-19 pandemic exacerbated this problem by generating a large number of additional hospitalizations, which necessitated a new tool that would help manage ICUs' census. In a previous study, we interviewed clinicians at the University Hospitals Bristol and Weston National Health Service Foundation Trust to capture the requirements for bespoke dashboards that would alleviate this problem.<h4>Objective</h4>This study aims to design, implement, and evaluate an ICU dashboard to allow for monitoring of the high volume of patients in need of critical care, particularly tailored to high-demand situations, such as those seen during the COVID-19 pandemic.<h4>Methods</h4>Building upon the previously gathered requirements, we developed a dashboard, integrated it within the ICU of a National Health Service trust, and allowed all staff to access our tool. For evaluation purposes, participants were recruited and interviewed following a 25-day period during which they were able to use the dashboard clinically. The semistructured interviews followed a topic guide aimed at capturing the usability of the dashboard, supplemented with additional questions asked post hoc to probe themes established during the interview. Interview transcripts were analyzed using a thematic analysis framework that combined inductive and deductive approaches and integrated the Technology Acceptance Model.<h4>Results</h4>A total of 10 participants with 4 different roles in the ICU (6 consultants, 2 junior doctors, 1 nurse, and 1 advanced clinical practitioner) participated in the interviews. Our analysis generated 4 key topics that prevailed across the data: our dashboard met the usability requirements of the participants and was found useful and intuitive; participants perceived that it impacted their delivery of patient care by improving the access to the information and better equipping them to do their job; the tool was used in a variety of ways and for different reasons and tasks; and there were barriers to integration of our dashboard into practice, including familiarity with existing systems, which stifled the adoption of our tool.<h4>Conclusions</h4>Our findings show that the perceived utility of the dashboard had a positive impact on the clinicians' workflows in the ICU. Improving access to information translated into more efficient patient care and transformed some of the existing processes. The introduction of our tool was met with positive reception, but its integration during the COVID-19 pandemic limited its adoption into practice.",,doi:https://doi.org/10.2196/49438; html:https://europepmc.org/articles/PMC10565627
 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,,,"<h4>Background</h4>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.<h4>Objective</h4>To evaluate the impact of COVID-19 on dispensing patterns of medications.<h4>Methods</h4>Retrospective observational study using population-scale, individual-level dispensing records in Wales, UK. Total dispensed drug items for the population between 1 <sup><i>st</i></sup> January 2016 and 31 <sup><i>st</i></sup> December 2019 (3-years, pre-COVID-19) were compared to 2020 with follow up until 27 <sup><i>th</i></sup> 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.<h4>Result</h4>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).<h4>Conclusions</h4>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.",,pdf:https://ijpds.org/article/download/1715/3382; doi:https://doi.org/10.23889/ijpds.v5i4.1715; html:https://europepmc.org/articles/PMC9135049; pdf:https://europepmc.org/articles/PMC9135049?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions and relevance</h4>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; doi:https://doi.org/10.1016/j.retram.2021.103276; html:https://europepmc.org/articles/PMC7857048; pdf:https://europepmc.org/articles/PMC7857048?pdf=render
+37751239,https://doi.org/10.2196/49438,Design and Evaluation of an Intensive Care Unit Dashboard Built in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Wac M, Craddock I, Chantziara S, Campbell T, Santos-Rodriguez R, Davidson B, McWilliams C.",,JMIR human factors,2023,2023-09-26,Y,Design; Health; ICU; EPR; intensive care unit; Interview; Intensive Care; Critical Care; Electronic Patient Record; Participatory Design; Ehr; Electronic Health Record; Software Engineering; Clinical Information System; Cis; Thematic Analysis; Dashboard; Human-centered Design; Covid-19; Interactive Display,,,"<h4>Background</h4>Dashboards and interactive displays are becoming increasingly prevalent in most health care settings and have the potential to streamline access to information, consolidate disparate data sources and deliver new insights. Our research focuses on intensive care units (ICUs) which are heavily instrumented, critical care environments that generate vast amounts of data and frequently require individualized support for each patient. Consequently, clinicians experience a high cognitive load, which can translate to suboptimal performance. The global COVID-19 pandemic exacerbated this problem by generating a large number of additional hospitalizations, which necessitated a new tool that would help manage ICUs' census. In a previous study, we interviewed clinicians at the University Hospitals Bristol and Weston National Health Service Foundation Trust to capture the requirements for bespoke dashboards that would alleviate this problem.<h4>Objective</h4>This study aims to design, implement, and evaluate an ICU dashboard to allow for monitoring of the high volume of patients in need of critical care, particularly tailored to high-demand situations, such as those seen during the COVID-19 pandemic.<h4>Methods</h4>Building upon the previously gathered requirements, we developed a dashboard, integrated it within the ICU of a National Health Service trust, and allowed all staff to access our tool. For evaluation purposes, participants were recruited and interviewed following a 25-day period during which they were able to use the dashboard clinically. The semistructured interviews followed a topic guide aimed at capturing the usability of the dashboard, supplemented with additional questions asked post hoc to probe themes established during the interview. Interview transcripts were analyzed using a thematic analysis framework that combined inductive and deductive approaches and integrated the Technology Acceptance Model.<h4>Results</h4>A total of 10 participants with 4 different roles in the ICU (6 consultants, 2 junior doctors, 1 nurse, and 1 advanced clinical practitioner) participated in the interviews. Our analysis generated 4 key topics that prevailed across the data: our dashboard met the usability requirements of the participants and was found useful and intuitive; participants perceived that it impacted their delivery of patient care by improving the access to the information and better equipping them to do their job; the tool was used in a variety of ways and for different reasons and tasks; and there were barriers to integration of our dashboard into practice, including familiarity with existing systems, which stifled the adoption of our tool.<h4>Conclusions</h4>Our findings show that the perceived utility of the dashboard had a positive impact on the clinicians' workflows in the ICU. Improving access to information translated into more efficient patient care and transformed some of the existing processes. The introduction of our tool was met with positive reception, but its integration during the COVID-19 pandemic limited its adoption into practice.",,doi:https://doi.org/10.2196/49438; html:https://europepmc.org/articles/PMC10565627
 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; doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?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,,,"<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%.<h4>Conclusions</h4>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.",,pdf:http://www.journalofinfection.com/article/S0163445321001158/pdf; 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
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 R<sub>0</sub>. 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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01789-2; doi:https://doi.org/10.1186/s12916-020-01789-2; html:https://europepmc.org/articles/PMC7553800; pdf:https://europepmc.org/articles/PMC7553800?pdf=render
@@ -557,8 +557,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 33838587,https://doi.org/10.1016/j.epidem.2021.100460,Competition between RSV and influenza: Limits of modelling inference from surveillance data.,"Waterlow NR, Flasche S, Minter A, Eggo RM.",,Epidemics,2021,2021-03-26,Y,Interaction; Competition; Influenza; Respiratory syncytial virus; Inference,,,"Respiratory Syncytial Virus (RSV) and Influenza cause a large burden of disease. Evidence of their interaction via temporary cross-protection implies that prevention of one could inadvertently lead to an increase in the burden of the other. However, evidence for the public health impact of such interaction is sparse and largely derives from ecological analyses of peak shifts in surveillance data. To test the robustness of estimates of interaction parameters between RSV and Influenza from surveillance data we conducted a simulation and back-inference study. We developed a two-pathogen interaction model, parameterised to simulate RSV and Influenza epidemiology in the UK. Using the infection model in combination with a surveillance-like stochastic observation process we generated a range of possible RSV and Influenza trajectories and then used Markov Chain Monte Carlo (MCMC) methods to back-infer parameters including those describing competition. We find that in most scenarios both the strength and duration of RSV and Influenza interaction could be estimated from the simulated surveillance data reasonably well. However, the robustness of inference declined towards the extremes of the plausible parameter ranges, with misleading results. It was for instance not possible to tell the difference between low/moderate interaction and no interaction. In conclusion, our results illustrate that in a plausible parameter range, the strength of RSV and Influenza interaction can be estimated from a single season of high-quality surveillance data but also highlights the importance to test parameter identifiability a priori in such situations.",,doi:https://doi.org/10.1016/j.epidem.2021.100460; doi:https://doi.org/10.1016/j.epidem.2021.100460; html:https://europepmc.org/articles/PMC8193815
 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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://formative.jmir.org/2023/1/e45849/PDF; doi:https://doi.org/10.2196/45849; html:https://europepmc.org/articles/PMC10337440; pdf:https://europepmc.org/articles/PMC10337440?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.",,pdf:https://www.nature.com/articles/s41746-022-00730-6.pdf; doi:https://doi.org/10.1038/s41746-022-00730-6; html:https://europepmc.org/articles/PMC9770568; pdf:https://europepmc.org/articles/PMC9770568?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>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]).<h4>Interpretation</h4>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.<h4>Funding</h4>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; 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
 33545096,https://doi.org/10.1016/s0140-6736(21)00149-5,"Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2021,2021-02-02,Y,,,,"<h4>Background</h4>Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.<h4>Methods</h4>In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. 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 azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.<h4>Findings</h4>Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87-1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98-1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87-1·03; p=0·24).<h4>Interpretation</h4>In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication.<h4>Funding</h4>UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://www.thelancet.com/article/S0140673621001495/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00149-5; html:https://europepmc.org/articles/PMC7884931; pdf:https://europepmc.org/articles/PMC7884931?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>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]).<h4>Interpretation</h4>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.<h4>Funding</h4>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; 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
 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; Covid-19; Covid-19 Vaccines; Health Database; Vaccine Effect; Clinical Coding System,,,"<h4>Background</h4>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.<h4>Objective</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://formative.jmir.org/2022/8/e37821/PDF; doi:https://doi.org/10.2196/37821; html:https://europepmc.org/articles/PMC9400842; pdf:https://europepmc.org/articles/PMC9400842?pdf=render
 35642867,https://doi.org/10.1111/bjhp.12606,"Perceived threat of COVID-19, attitudes towards vaccination, and vaccine hesitancy: A prospective longitudinal study in the UK.","Phillips R, Gillespie D, Hallingberg B, Evans J, Taiyari K, Torrens-Burton A, Cannings-John R, Williams D, Sheils E, Ashfield-Watt P, Akbari A, Hughes K, Thomas-Jones E, James D, Wood F.",,British journal of health psychology,2022,2022-06-01,Y,Risk Perception; Behaviour Change; Vaccine Hesitancy; Covid-19; Sars Cov2,,,"<h4>Objectives</h4>Using the Health Belief Model as a conceptual framework, we investigated the association between attitudes towards COVID-19, COVID-19 vaccinations, and vaccine hesitancy and change in these variables over a 9-month period in a UK cohort.<h4>Methods</h4>The COPE study cohort (n = 11,113) was recruited via an online survey at enrolment in March/April 2020. The study was advertised via the HealthWise Wales research registry and social media. Follow-up data were available for 6942 people at 3 months (June/July 2020) and 5037 at 12 months (March/April 2021) post-enrolment. Measures included demographics, perceived threat of COVID-19, perceived control, intention to accept or decline a COVID-19 vaccination, and attitudes towards vaccination. Logistic regression models were fitted cross-sectionally at 3 and 12 months to assess the association between motivational factors and vaccine hesitancy. Longitudinal changes in motivational variables for vaccine-hesitant and non-hesitant groups were examined using mixed-effect analysis of variance models.<h4>Results</h4>Fear of COVID-19, perceived susceptibility to COVID-19, and perceived personal control over COVID-19 infection transmission decreased between the 3- and 12-month surveys. Vaccine hesitancy at 12 months was independently associated with low fear of the disease and more negative attitudes towards COVID-19 vaccination. Specific barriers to COVID-19 vaccine uptake included concerns about safety and efficacy in light of its rapid development, mistrust of government and pharmaceutical companies, dislike of coercive policies, and perceived lack of relaxation in COVID-19-related restrictions as the vaccination programme progressed.<h4>Conclusions</h4>Decreasing fear of COVID-19, perceived susceptibility to the disease, and perceptions of personal control over reducing infection-transmission may impact future COVID-19 vaccination uptake.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa60128/Download/60128__24479__4d74009536e649b0b17180e2bfd80435.pdf; doi:https://doi.org/10.1111/bjhp.12606; html:https://europepmc.org/articles/PMC9347957; pdf:https://europepmc.org/articles/PMC9347957?pdf=render
 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,,,"<h4>Introduction</h4>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).<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>NCT03463694.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/5/e049964.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049964; html:https://europepmc.org/articles/PMC8103393; pdf:https://europepmc.org/articles/PMC8103393?pdf=render
@@ -645,8 +645,8 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI
 34227657,https://doi.org/10.1093/bjs/znab183,Machine learning risk prediction of mortality for patients undergoing surgery with perioperative SARS-CoV-2: the COVIDSurg mortality score.,"COVIDSurg Collaborative
 .",,The British journal of surgery,2021,2021-11-01,Y,,,,,,pdf:https://academic.oup.com/bjs/article-pdf/108/11/1274/47371055/znab183.pdf; doi:https://doi.org/10.1093/bjs/znab183; html:https://europepmc.org/articles/PMC8344569; pdf:https://europepmc.org/articles/PMC8344569?pdf=render
 37650026,https://doi.org/10.23889/ijpds.v7i1.1727,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,2022,2022-05-23,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.",,doi:https://doi.org/10.23889/ijpds.v7i1.1727; html:https://europepmc.org/articles/PMC10464868; pdf:https://europepmc.org/articles/PMC10464868?pdf=render
-37798805,https://doi.org/10.1186/s13063-023-07576-7,"Medicines and Healthcare products Regulatory Agency's ""Consultation on proposals for legislative changes for clinical trials"": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.","Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.",,Trials,2023,2023-10-05,Y,Legislation; data sharing; Consultation,,,"In the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals ""to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines"". The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research. Two topics arose frequently in the discussion: the emphasis on legislation, and the absence of questions on data sharing. It is our opinion that the proposals rely heavily on legislation to change practice. However, clinical trials are heterogeneous, and as a result some trials will struggle to comply with all of the proposed legislation. Furthermore, adaptive design clinical trials are even more heterogeneous than their non-adaptive counterparts, and face more challenges. Consequently, it is possible that increased legislation could have a greater negative impact on adaptive designs than non-adaptive designs. Overall, we are sceptical that the introduction of legislation will achieve the desired outcomes, with some exceptions. Meanwhile the topic of data sharing - making anonymised individual-level clinical trial data available to other investigators for further use - is entirely absent from the proposals and the consultation in general. However, as an aspect of the wider concept of open science and reproducible research, data sharing is an increasingly important aspect of clinical trials. The benefits of data sharing include faster innovation, improved surveillance of drug safety and effectiveness and decreasing participant exposure to unnecessary risk. There are already a number of UK-focused documents that discuss and encourage data sharing, for example, the Concordat on Open Research Data and the Medical Research Council's Data Sharing Policy. We strongly suggest that data sharing should be the norm rather than the exception, and hope that the forthcoming proposals on clinical trials invite discussion on this important topic.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07576-7; doi:https://doi.org/10.1186/s13063-023-07576-7; html:https://europepmc.org/articles/PMC10552399; pdf:https://europepmc.org/articles/PMC10552399?pdf=render
 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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/1/e064364.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064364; html:https://europepmc.org/articles/PMC9872487; pdf:https://europepmc.org/articles/PMC9872487?pdf=render
+37798805,https://doi.org/10.1186/s13063-023-07576-7,"Medicines and Healthcare products Regulatory Agency's ""Consultation on proposals for legislative changes for clinical trials"": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.","Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.",,Trials,2023,2023-10-05,Y,Legislation; data sharing; Consultation,,,"In the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals ""to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines"". The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research. Two topics arose frequently in the discussion: the emphasis on legislation, and the absence of questions on data sharing. It is our opinion that the proposals rely heavily on legislation to change practice. However, clinical trials are heterogeneous, and as a result some trials will struggle to comply with all of the proposed legislation. Furthermore, adaptive design clinical trials are even more heterogeneous than their non-adaptive counterparts, and face more challenges. Consequently, it is possible that increased legislation could have a greater negative impact on adaptive designs than non-adaptive designs. Overall, we are sceptical that the introduction of legislation will achieve the desired outcomes, with some exceptions. Meanwhile the topic of data sharing - making anonymised individual-level clinical trial data available to other investigators for further use - is entirely absent from the proposals and the consultation in general. However, as an aspect of the wider concept of open science and reproducible research, data sharing is an increasingly important aspect of clinical trials. The benefits of data sharing include faster innovation, improved surveillance of drug safety and effectiveness and decreasing participant exposure to unnecessary risk. There are already a number of UK-focused documents that discuss and encourage data sharing, for example, the Concordat on Open Research Data and the Medical Research Council's Data Sharing Policy. We strongly suggest that data sharing should be the norm rather than the exception, and hope that the forthcoming proposals on clinical trials invite discussion on this important topic.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07576-7; doi:https://doi.org/10.1186/s13063-023-07576-7; html:https://europepmc.org/articles/PMC10552399; pdf:https://europepmc.org/articles/PMC10552399?pdf=render
 35304633,https://doi.org/10.1007/s00520-022-06976-w,An exploration of wellbeing in men diagnosed with prostate cancer undergoing active surveillance: a qualitative study.,"Eymech O, Brunckhorst O, Fox L, Jawaid A, Van Hemelrijck M, Stewart R, Dasgupta P, Ahmed K.",,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,2022,2022-03-19,Y,Quality of life; Mental health; prostate cancer; Active Surveillance; Mental Wellbeing; Psa Anxiety,,,"<h4>Purpose</h4>There is a growing emphasis on improving quality of life of people with prostate cancer. However, those undergoing active surveillance remain underrepresented in the literature with less known about their unique challenges. Therefore, we aimed to explore their lived experiences post diagnosis and its effect on their mental, social, and physical wellbeing.<h4>Methods</h4>Qualitative semi-structured interviews were conducted with 13 men undergoing active surveillance for low-risk disease. Thematic analysis was used to inductively co-construct themes through the lens of the biopsychosocial model.<h4>Results</h4>Mental wellbeing was strongly affected in our participants due to the overwhelming emotional impact of their diagnosis resulting in an 'Emotional Diagnostic Disequilibrium'. Informational awareness and education about prostate cancer helped patients with 'Recognition of the Impact'. Patients experienced an 'Unsettling Monitoring Cycle' due to the increased fear and anxiety around PSA monitoring appointments, with some men ignoring their mental wellbeing needs as their disease is 'A Future Problem'. 'Concealment of Diagnosis' left many feeling isolated and highlighted an important coping mechanisms in the 'Importance of a Social Support Network' theme. Finally, physical health mostly changed through alterations in health behaviour, leading to 'A Healthier Lifestyle' with increasing attribution of physical symptoms to age through 'Symptomatic Overshadowing'.<h4>Conclusion</h4>The greatest disease impact on men's wellbeing was at the time of diagnosis, with a subsequent cyclical anxiety and fear of disease progression prominent around monitoring appointments. Future research should explore ways to better support patients with these issues and at these times, improving their quality of life.",,pdf:https://link.springer.com/content/pdf/10.1007/s00520-022-06976-w.pdf; doi:https://doi.org/10.1007/s00520-022-06976-w; html:https://europepmc.org/articles/PMC8933126; pdf:https://europepmc.org/articles/PMC8933126?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,,,,,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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>With respect to hip-replacement surgery in England and Wales, policy ambitions to reduce healthcare inequities have not been realised.<h4>Funding</h4>This work was supported by Health Data Research UK.",,doi:https://doi.org/10.1016/j.lanepe.2022.100475; doi:https://doi.org/10.1016/j.lanepe.2022.100475; html:https://europepmc.org/articles/PMC9340533; pdf:https://europepmc.org/articles/PMC9340533?pdf=render
@@ -672,8 +672,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-01924-7; doi:https://doi.org/10.1186/s12916-021-01924-7; html:https://europepmc.org/articles/PMC7892289; pdf:https://europepmc.org/articles/PMC7892289?pdf=render
 34562388,https://doi.org/10.1016/s0140-6736(21)01258-7,"Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050.",Global Burden of Disease 2020 Health Financing Collaborator Network.,,"Lancet (London, England)",2021,2021-09-22,Y,,,,"<h4>Background</h4>The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020.<h4>Methods</h4>We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050.<h4>Findings</h4>In 2019, health spending globally reached $8·8 trillion (95% uncertainty interval [UI] 8·7-8·8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40·4 billion (0·5%, 95% UI 0·5-0·5) was development assistance for health provided to low-income and middle-income countries, which made up 24·6% (UI 24·0-25·1) of total spending in low-income countries. We estimate that $54·8 billion in development assistance for health was disbursed in 2020. Of this, $13·7 billion was targeted toward the COVID-19 health response. $12·3 billion was newly committed and $1·4 billion was repurposed from existing health projects. $3·1 billion (22·4%) of the funds focused on country-level coordination and $2·4 billion (17·9%) was for supply chain and logistics. Only $714·4 million (7·7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34·3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied.<h4>Interpretation</h4>Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all.<h4>Funding</h4>Bill & Melinda Gates Foundation.",,pdf:https://europepmc.org/articles/pmc8457757?pdf=render; doi:https://doi.org/10.1016/S0140-6736(21)01258-7; html:https://europepmc.org/articles/PMC8457757; pdf:https://europepmc.org/articles/PMC8457757?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,,,"<h4>Objectives</h4>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.<h4>Materials and methods</h4>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.<h4>Results</h4>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.<h4>Discussion and conclusion</h4>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.",,pdf:https://academic.oup.com/jamiaopen/article-pdf/3/4/545/36625793/ooaa047.pdf; doi:https://doi.org/10.1093/jamiaopen/ooaa047; html:https://europepmc.org/articles/PMC7717266; pdf:https://europepmc.org/articles/PMC7717266?pdf=render
-37185641,https://doi.org/10.1136/bmjopen-2022-070022,EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.,"Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, Müllerová H.",,BMJ open,2023,2023-04-26,Y,epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease,,,"<h4>Introduction</h4>In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.<h4>Methods and analysis</h4>Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.<h4>Ethics and dissemination</h4>Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>ClinicalTrials.gov NCT04435041; https://clinicaltrials.gov/ct2/show/NCT04435041.<h4>International registered report identifier (irrid)</h4>DERR1-10.2196/30083.",,pdf:https://www.researchprotocols.org/2021/10/e30083/PDF; doi:https://doi.org/10.2196/30083; html:https://europepmc.org/articles/PMC8494068
+37185641,https://doi.org/10.1136/bmjopen-2022-070022,EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.,"Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, Müllerová H.",,BMJ open,2023,2023-04-26,Y,epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease,,,"<h4>Introduction</h4>In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.<h4>Methods and analysis</h4>Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.<h4>Ethics and dissemination</h4>Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?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,Y,epidemiology; Electronic Medical Records; Misclassification Bias; Value Sets; Health Data Science; Code Sets,,,"<h4>Objective</h4>To develop a standardizable, reproducible method for creating drug codelists that incorporates clinical expertise and is adaptable to other studies and databases.<h4>Materials and methods</h4>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.<h4>Results</h4>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).<h4>Discussion</h4>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.<h4>Conclusions</h4>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; html:https://europepmc.org/articles/PMC10463548; pdf:https://europepmc.org/articles/PMC10463548?pdf=render
 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,2023,2022-04-29,Y,Mortality; Schizophrenia; Psychosis; Physical Health; Multimorbidity,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,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; doi:https://doi.org/10.1017/S003329172200109X; html:https://europepmc.org/articles/PMC10388332; pdf:https://europepmc.org/articles/PMC10388332?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'.",,pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rstb.2018.0276; doi:https://doi.org/10.1098/rstb.2018.0276; html:https://europepmc.org/articles/PMC6558557; pdf:https://europepmc.org/articles/PMC6558557?pdf=render
@@ -727,8 +727,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 37679419,https://doi.org/10.1038/s41588-023-01462-3,"GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.","Lagou V, Jiang L, Ulrich A, Zudina L, González KSG, Balkhiyarova Z, Faggian A, Maina JG, Chen S, Todorov PV, Sharapov S, David A, Marullo L, Mägi R, Rujan RM, Ahlqvist E, Thorleifsson G, Gao Η, Εvangelou Ε, Benyamin B, Scott RA, Isaacs A, Zhao JH, Willems SM, Johnson T, Gieger C, Grallert H, Meisinger C, Müller-Nurasyid M, Strawbridge RJ, Goel A, Rybin D, Albrecht E, Jackson AU, Stringham HM, Corrêa IR, Farber-Eger E, Steinthorsdottir V, Uitterlinden AG, Munroe PB, Brown MJ, Schmidberger J, Holmen O, Thorand B, Hveem K, Wilsgaard T, Mohlke KL, Wang Z, GWA-PA Consortium, Shmeliov A, den Hoed M, Loos RJF, Kratzer W, Haenle M, Koenig W, Boehm BO, Tan TM, Tomas A, Salem V, Barroso I, Tuomilehto J, Boehnke M, Florez JC, Hamsten A, Watkins H, Njølstad I, Wichmann HE, Caulfield MJ, Khaw KT, van Duijn CM, Hofman A, Wareham NJ, Langenberg C, Whitfield JB, Martin NG, Montgomery G, Scapoli C, Tzoulaki I, Elliott P, Thorsteinsdottir U, Stefansson K, Brittain EL, McCarthy MI, Froguel P, Sexton PM, Wootten D, Groop L, Dupuis J, Meigs JB, Deganutti G, Demirkan A, Pers TH, Reynolds CA, Aulchenko YS, Kaakinen MA, Jones B, Prokopenko I, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC).",,Nature genetics,2023,2023-09-07,Y,,,,"Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.",,doi:https://doi.org/10.1038/s41588-023-01462-3; html:https://europepmc.org/articles/PMC10484788; pdf:https://europepmc.org/articles/PMC10484788?pdf=render
 34225492,https://doi.org/10.1128/mbio.02531-20,Structural Basis for a Neutralizing Antibody Response Elicited by a Recombinant Hantaan Virus Gn Immunogen.,"Rissanen I, Krumm SA, Stass R, Whitaker A, Voss JE, Bruce EA, Rothenberger S, Kunz S, Burton DR, Huiskonen JT, Botten JW, Bowden TA, Doores KJ.",,mBio,2021,2021-07-06,Y,Structure; Glycoprotein; Hantavirus; Neutralizing antibody; Zoonosis,,,"Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two glycoproteins, Gn and Gc, which are responsible for negotiating host cell entry and constitute key therapeutic targets. Here, we demonstrate that recombinantly derived Gn from Hantaan virus (HTNV) elicits a neutralizing antibody response (serum dilution that inhibits 50% infection [ID<sub>50</sub>], 1:200 to 1:850) in an animal model. Using antigen-specific B cell sorting, we isolated monoclonal antibodies (mAbs) exhibiting neutralizing and non-neutralizing activity, termed mAb HTN-Gn1 and mAb nnHTN-Gn2, respectively. Crystallographic analysis reveals that these mAbs target spatially distinct epitopes at disparate sites of the N-terminal region of the HTNV Gn ectodomain. Epitope mapping onto a model of the higher order (Gn-Gc)<sub>4</sub> spike supports the immune accessibility of the mAb HTN-Gn1 epitope, a hypothesis confirmed by electron cryo-tomography of the antibody with virus-like particles. These data define natively exposed regions of the hantaviral Gn that can be targeted in immunogen design. <b>IMPORTANCE</b> The spillover of pathogenic hantaviruses from rodent reservoirs into the human population poses a continued threat to human health. Here, we show that a recombinant form of the Hantaan virus (HTNV) surface-displayed glycoprotein, Gn, elicits a neutralizing antibody response in rabbits. We isolated a neutralizing (HTN-Gn1) and a non-neutralizing (nnHTN-Gn2) monoclonal antibody and provide the first molecular-level insights into how the Gn glycoprotein may be targeted by the antibody-mediated immune response. These findings may guide rational vaccine design approaches focused on targeting the hantavirus glycoprotein envelope.",,pdf:https://helda.helsinki.fi/bitstream/10138/341549/1/mBio.02531_20.pdf; doi:https://doi.org/10.1128/mBio.02531-20; html:https://europepmc.org/articles/PMC8406324; pdf:https://europepmc.org/articles/PMC8406324?pdf=render
 33017023,https://doi.org/10.1001/jamaneurol.2020.3502,Trends in Optic Neuritis Incidence and Prevalence in the UK and Association With Systemic and Neurologic Disease.,"Braithwaite T, Subramanian A, Petzold A, Galloway J, Adderley NJ, Mollan SP, Plant GT, Nirantharakumar K, Denniston AK.",,JAMA neurology,2020,2020-12-01,N,,,,"<h4>Importance</h4>Epidemiologic data on optic neuritis (ON) incidence and associations with immune-mediated inflammatory diseases (IMIDs) are sparse.<h4>Objective</h4>To estimate 22-year trends in ON prevalence and incidence and association with IMIDs in the United Kingdom.<h4>Design, setting, and participants</h4>This cohort study analyzed data from The Health Improvement Network from January 1, 1995, to September 1, 2019. The study included 10 937 511 patients 1 year or older with 75.2 million person-years' follow-up. Annual ON incidence rates were estimated yearly (January 1, 1997, to December 31, 2018), and annual ON prevalence was estimated by performing sequential cross-sectional studies on data collected on January 1 each year for the same period. Data for 1995, 1996, and 2019 were excluded as incomplete. Risk factors for ON were explored in a cohort analysis from January 1, 1997, to December 31, 2018. Matched case-control and retrospective cohort studies were performed using data from January 1, 1995, to September 1, 2019, to explore the odds of antecedent diagnosis and hazard of incident diagnosis of 66 IMIDs in patients compared with controls.<h4>Exposures</h4>Optic neuritis.<h4>Main outcomes and measures</h4>Annual point prevalence and incidence rates of ON, adjusted incident rate ratios (IRRs) for risk factors, and adjusted odds ratios (ORs) and adjusted hazard ratios (HRs) for 66 IMIDs.<h4>Results</h4>A total of 10 937 511 patients (median [IQR] age at cohort entry, 32.6 [18.0-50.4] years; 5 571 282 [50.9%] female) were studied. A total of 1962 of 2826 patients (69.4%) with incident ON were female and 1192 of 1290 92.4%) were White, with a mean (SD) age of 35.6 (15.6) years. Overall incidence across 22 years was stable at 3.7 (95% CI, 3.6-3.9) per 100 000 person-years. Annual point prevalence (per 100 000 population) increased with database maturity, from 69.3 (95% CI, 57.2-81.3) in 1997 to 114.8 (95% CI, 111.0-118.6) in 2018. The highest risk of incident ON was associated with female sex, obesity, reproductive age, smoking, and residence at higher latitude, with significantly lower risk in South Asian or mixed race/ethnicity compared with White people. Patients with ON had significantly higher odds of prior multiple sclerosis (MS) (OR, 98.22; 95% CI, 65.40-147.52), syphilis (OR, 5.76; 95% CI, 1.39-23.96), Mycoplasma (OR, 3.90; 95% CI, 1.09-13.93), vasculitis (OR, 3.70; 95% CI, 1.68-8.15), sarcoidosis (OR, 2.50; 95% CI, 1.21-5.18), Epstein-Barr virus (OR, 2.29; 95% CI, 1.80-2.92), Crohn disease (OR, 1.97; 95% CI, 1.13-3.43), and psoriasis (OR, 1.28; 95% CI, 1.03-1.58). Patients with ON had a significantly higher hazard of incident MS (HR, 284.97; 95% CI, 167.85-483.81), Behçet disease (HR, 17.39; 95% CI, 1.55-195.53), sarcoidosis (HR, 14.80; 95% CI, 4.86-45.08), vasculitis (HR, 4.89; 95% CI, 1.82-13.10), Sjögren syndrome (HR, 3.48; 95% CI, 1.38-8.76), and herpetic infection (HR, 1.68; 95% CI, 1.24-2.28).<h4>Conclusions and relevance</h4>The UK incidence of ON is stable. Even though predominantly associated with MS, ON has numerous other associations with IMIDs. Although individually rare, together these associations outnumber MS-associated ON and typically require urgent management to preserve sight.",,pdf:http://pure-oai.bham.ac.uk/ws/files/100688542/NEU20_1602R_Merged_PDF.pdf; doi:https://doi.org/10.1001/jamaneurol.2020.3502; html:https://europepmc.org/articles/PMC7536630; doi:https://doi.org/10.1001/jamaneurol.2020.3502
-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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Discussion</h4>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.<h4>Trial registration</h4>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
 33644414,https://doi.org/10.23889/ijpds.v5i3.1371,Public involvement & engagement in the work of a data safe haven: a case study of the SAIL Databank.,"Jones KH, Heys S, Thompson R, Cross L, Ford D.",,International journal of population data science,2020,2020-08-24,Y,Public Engagement; Data Safe Haven,,,"<h4>Background</h4>The SAIL Databank is a data safe haven established in 2007 at Swansea University (Wales). It was set up to create new opportunities for research using routinely-collected health and other public service datasets in linkable anonymised form. SAIL forms the bedrock of other Population Data Science initiatives made possible by the data and safe haven environment.<h4>Aim</h4>The aim of this paper is to provide an overview of public involvement & engagement in connection with the SAIL Databank and related Population Data Science initiatives.<h4>Approach</h4>We have a public involvement & engagement policy for SAIL in the context of Population Data Science. We established a Consumer Panel to provide advice on the work of SAIL and associated initiatives, including on proposed uses of SAIL data. We reviewed the topics discussed and provide examples of advice to researchers. We carried out a survey with members on their experiences of being on the Panel and their perceptions of the work of SAIL. We have a programme of wider public engagement and provide illustrations of this work.<h4>Discussion</h4>We summarise what this paper adds and some lessons learned. In the rapidly developing area of Population Data Science it is important that people feel welcome, that they are encouraged to ask questions and are provided with digestible information and adequate consideration time. Citizens have provided us with valuable anticipated and unanticipated opinions and novel viewpoints. We seek to take a pragmatic approach, prioritising the communication modes that allow maximum public input commensurate with the purpose of the activity.<h4>Conclusion</h4>This paper has set out our policy, rationale, scope and practical approaches to public involvement & engagement for SAIL and our related Population Data Science initiatives. Although there will be jurisdictional, cultural and organizational differences, we believe that the material covered in this paper will be of interest to other data focused enterprises across the world.",,pdf:https://ijpds.org/article/download/1371/2815; doi:https://doi.org/10.23889/ijpds.v5i3.1371; html:https://europepmc.org/articles/PMC7893854; pdf:https://europepmc.org/articles/PMC7893854?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Discussion</h4>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.<h4>Trial registration</h4>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
 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.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.1016032/pdf; doi:https://doi.org/10.3389/fcvm.2022.1016032; html:https://europepmc.org/articles/PMC9681217; pdf:https://europepmc.org/articles/PMC9681217?pdf=render
 34641870,https://doi.org/10.1186/s12911-021-01638-z,An informatics consult approach for generating clinical evidence for treatment decisions.,"Lai AG, Chang WH, Parisinos CA, Katsoulis M, Blackburn RM, Shah AD, Nguyen V, Denaxas S, Davey Smith G, Gaunt TR, Nirantharakumar K, Cox MP, Forde D, Asselbergs FW, Harris S, Richardson S, Sofat R, Dobson RJB, Hingorani A, Patel R, Sterne J, Banerjee A, Denniston AK, Ball S, Sebire NJ, Shah NH, Foster GR, Williams B, Hemingway H.",,BMC medical informatics and decision making,2021,2021-10-12,Y,,,,"<h4>Background</h4>An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis.<h4>Methods</h4>We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems.<h4>Results</h4>We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39-1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49-0.76) and ischaemic stroke (HR = 0.27, CI 0.08-0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results.<h4>Conclusion</h4>We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on 'patients like me'. We identify the key challenges in offering such an Informatics Consult as a service.",,doi:https://doi.org/10.1186/s12911-021-01638-z; doi:https://doi.org/10.1186/s12911-021-01638-z; html:https://europepmc.org/articles/PMC8506488; pdf:https://europepmc.org/articles/PMC8506488?pdf=render
 37645022,https://doi.org/10.1183/20734735.0058-2023,The impact of poor housing and indoor air quality on respiratory health in children.,"Holden KA, Lee AR, Hawcutt DB, Sinha IP.",,"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.<h4>Educational aims</h4>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.",,doi:https://doi.org/10.1183/20734735.0058-2023; html:https://europepmc.org/articles/PMC10461733; pdf:https://europepmc.org/articles/PMC10461733?pdf=render
@@ -755,8 +755,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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,,,"<h4>Background</h4>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.<h4>Objective</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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 (R<sup>2</sup>=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 (R<sup>2</sup>=0.338, RMSE=4.547).<h4>Conclusions</h4>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.",,pdf:https://mhealth.jmir.org/2021/7/e29840/PDF; doi:https://doi.org/10.2196/29840; html:https://europepmc.org/articles/PMC8367113
 36692937,https://doi.org/10.2196/42866,The Feasibility of Implementing Remote Measurement Technologies in Psychological Treatment for Depression: Mixed Methods Study on Engagement.,"de Angel V, Adeleye F, Zhang Y, Cummins N, Munir S, Lewis S, Laporta Puyal E, Matcham F, Sun S, Folarin AA, Ranjan Y, Conde P, Rashid Z, Dobson R, Hotopf M.",,JMIR mental health,2023,2023-01-24,Y,Depression; Mobile phone; Anxiety; Smartphone; Mhealth; Mobile Health; Wearable Devices; Digital Health; Digital Phenotyping; Passive Sensing,,,"<h4>Background</h4>Remote measurement technologies (RMTs) such as smartphones and wearables can help improve treatment for depression by providing objective, continuous, and ecologically valid insights into mood and behavior. Engagement with RMTs is varied and highly context dependent; however, few studies have investigated their feasibility in the context of treatment.<h4>Objective</h4>A mixed methods design was used to evaluate engagement with active and passive data collection via RMT in people with depression undergoing psychotherapy. We evaluated the effects of treatment on 2 different types of engagement: study attrition (engagement with study protocol) and patterns of missing data (engagement with digital devices), which we termed data availability. Qualitative interviews were conducted to help interpret the differences in engagement.<h4>Methods</h4>A total of 66 people undergoing psychological therapy for depression were followed up for 7 months. Active data were gathered from weekly questionnaires and speech and cognitive tasks, and passive data were gathered from smartphone sensors and a Fitbit (Fitbit Inc) wearable device.<h4>Results</h4>The overall retention rate was 60%. Higher-intensity treatment (χ<sup>2</sup><sub>1</sub>=4.6; P=.03) and higher baseline anxiety (t<sub>56.28</sub>=-2.80, 2-tailed; P=.007) were associated with attrition, but depression severity was not (t<sub>50.4</sub>=-0.18; P=.86). A trend toward significance was found for the association between longer treatments and increased attrition (U=339.5; P=.05). Data availability was higher for active data than for passive data initially but declined at a sharper rate (90%-30% drop in 7 months). As for passive data, wearable data availability fell from a maximum of 80% to 45% at 7 months but showed higher overall data availability than smartphone-based data, which remained stable at the range of 20%-40% throughout. Missing data were more prevalent among GPS location data, followed by among Bluetooth data, then among accelerometry data. As for active data, speech and cognitive tasks had lower completion rates than clinical questionnaires. The participants in treatment provided less Fitbit data but more active data than those on the waiting list.<h4>Conclusions</h4>Different data streams showed varied patterns of missing data, despite being gathered from the same device. Longer and more complex treatments and clinical characteristics such as higher baseline anxiety may reduce long-term engagement with RMTs, and different devices may show opposite patterns of missingness during treatment. This has implications for the scalability and uptake of RMTs in health care settings, the generalizability and accuracy of the data collected by these methods, feature construction, and the appropriateness of RMT use in the long term.",,pdf:https://mental.jmir.org/2023/1/e42866/PDF; doi:https://doi.org/10.2196/42866; html:https://europepmc.org/articles/PMC9906314
 37477803,https://doi.org/10.1007/s11897-023-00615-z,Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review.,"Meijs C, Handoko ML, Savarese G, Vernooij RWM, Vaartjes I, Banerjee A, Koudstaal S, Brugts JJ, Asselbergs FW, Uijl A.",,Current heart failure reports,2023,2023-07-21,Y,Clustering; Phenotyping; Heart Failure; Machine Learning; Precision Medicine,,,"<h4>Review purpose</h4>This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice.<h4>Findings</h4>34 studies were identified (n = 19 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. HF = heart failure, EF = ejection fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, CKD = chronic kidney disease, AF = atrial fibrillation, IHD = ischaemic heart disease, CAD = coronary artery disease, ICD = implantable cardioverter-defibrillator, CRT = cardiac resynchronization therapy, NT-proBNP = N-terminal pro b-type natriuretic peptide, BMI = Body Mass Index, COPD = Chronic obstructive pulmonary disease.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00615-z.pdf; doi:https://doi.org/10.1007/s11897-023-00615-z; html:https://europepmc.org/articles/PMC10589200; pdf:https://europepmc.org/articles/PMC10589200?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; doi:https://doi.org/10.1016/j.xgen.2021.100004; html:https://europepmc.org/articles/PMC9451133; pdf:https://europepmc.org/articles/PMC9451133?pdf=render
 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),,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Prospero registration number</h4>CRD42019140361 and CRD42019161764.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e048008.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-048008; html:https://europepmc.org/articles/PMC8273461; pdf:https://europepmc.org/articles/PMC8273461?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; doi:https://doi.org/10.1016/j.xgen.2021.100004; html:https://europepmc.org/articles/PMC9451133; pdf:https://europepmc.org/articles/PMC9451133?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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://medinform.jmir.org/2022/11/e38168/PDF; doi:https://doi.org/10.2196/38168; html:https://europepmc.org/articles/PMC9682451
 37649471,https://doi.org/10.23889/ijpds.v6i3.1705,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 AB, Laing H.",,International journal of population data science,2021,2021-01-01,Y,"Colitis, ulcerative; Health Policy; Patient Reported Outcome Measure; Routinely Collected Health Data; Data Science; Value-based Health Care",,,"<h4>Introduction</h4>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.<h4>Objectives</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,doi:https://doi.org/10.23889/ijpds.v6i3.1705; html:https://europepmc.org/articles/PMC10464864; pdf:https://europepmc.org/articles/PMC10464864?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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 <i>cis</i>-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.<h4>Results</h4>Forty-four of ninety proteins were positively associated with risk of incident HF (<i>P</i><6.0×10<sup>-4</sup>). 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.<h4>Conclusions</h4>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.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.056663; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.056663; html:https://europepmc.org/articles/PMC9010023; pdf:https://europepmc.org/articles/PMC9010023?pdf=render
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@@ -3,8 +3,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 34994801,https://doi.org/10.1093/pubmed/fdab400,COVID-19 vaccination uptake amongst ethnic minority communities in England: a linked study exploring the drivers of differential vaccination rates.,"Gaughan CH, Razieh C, Khunti K, Banerjee A, Chudasama YV, Davies MJ, Dolby T, Gillies CL, Lawson C, Mirkes EM, Morgan J, Tingay K, Zaccardi F, Yates T, Nafilyan V.",,"Journal of public health (Oxford, England)",2023,2023-03-01,Y,Vaccination; Cultural; Ethnicity; Social; Sociodemographic Factors; Demographic; Covid-19,,,"<h4>Background</h4>Despite generally high coronavirus disease 2019 (COVID-19) vaccination rates in the UK, vaccination hesitancy and lower take-up rates have been reported in certain ethnic minority communities.<h4>Methods</h4>We used vaccination data from the National Immunisation Management System (NIMS) linked to the 2011 Census and individual health records for subjects aged ≥40 years (n = 24 094 186). We estimated age-standardized vaccination rates, stratified by ethnic group and key sociodemographic characteristics, such as religious affiliation, deprivation, educational attainment, geography, living conditions, country of birth, language skills and health status. To understand the association of ethnicity with lower vaccination rates, we conducted a logistic regression model adjusting for differences in geographic, sociodemographic and health characteristics. ResultsAll ethnic groups had lower age-standardized rates of vaccination compared with the white British population, whose vaccination rate of at least one dose was 94% (95% CI: 94%-94%). Black communities had the lowest rates, with 75% (74-75%) of black African and 66% (66-67%) of black Caribbean individuals having received at least one dose. The drivers of these lower rates were partly explained by accounting for sociodemographic differences. However, modelled estimates showed significant differences remained for all minority ethnic groups, compared with white British individuals.<h4>Conclusions</h4>Lower COVID-19 vaccination rates are consistently observed amongst all ethnic minorities.",,pdf:https://academic.oup.com/jpubhealth/article-pdf/45/1/e65/49527132/fdab400.pdf; doi:https://doi.org/10.1093/pubmed/fdab400; html:https://europepmc.org/articles/PMC8755382; pdf:https://europepmc.org/articles/PMC8755382?pdf=render
 35057841,https://doi.org/10.1186/s13063-021-05965-4,Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments.,"Cake C, Ogburn E, Pinches H, Coleman G, Seymour D, Woodard F, Manohar S, Monsur M, Landray M, Dalton G, Morris AD, Chinnery PF, UK COVID-19 National Core Studies Consortium, Hobbs FDR, Butler C.",,Trials,2022,2022-01-20,Y,Recruitment; Data; Clinical Trials; Primary Care; Healthcare; Covid-19; Public And Patient Involvement And Engagement,,,"<h4>Background</h4>The COVID-19 pandemic has presented unique challenges for rapidly designing, initiating, and delivering therapeutic clinical trials. PRINCIPLE (Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses) is the UK national platform investigating repurposed therapies for COVID-19 treatment of older people in the community at high risk of complications. Standard methods of patient recruitment were failing to meet the required pace and scale of enrolment. This paper describes the development and appraisal of a near real-time, data-driven, ethical approach for enhancing recruitment in community care by contacting people with a recent COVID-19 positive test result from the central NHS Test and Trace service within approximately 24-48 h of their test result.<h4>Methods</h4>A multi-disciplinary team was formed to solve the technical, ethical, public perception, logistical and information governance issues required to provide a near-real time (approximately within 24-48 h of receiving a positive test) feed of potential trial participants from test result data to the research team. PRINCIPLE was also given unique access to the Summary Care Record (SCR) to ensure safe prescribing, and to enable the trial team to quickly and safely bring consented patients into the trial. A survey of the public was used to understand public perceptions of the use of test data for this proposed methodology.<h4>Results</h4>Prior to establishing the data service, PRINCIPLE registered on average 87 participants per week. This increased by up to 87 additional people registered per week from the test data, contributing to an increase from 1013 recruits to PRINCIPLE at the start of October 2020 to 2802 recruits by 20 December 2020. Whilst procedural caveats were identified by the public consultation, out of 2639 people contacted by PRINCIPLE following a positive test result, no one raised a concern about being approached.<h4>Conclusions</h4>This paper describes a novel approach to using near-real time NHS operational data to recruit community-based patients within a few days of presentation with acute illness. This approach increased recruitment and reduced time between positive test and randomisation, allowing more rapid evaluation of treatments and increased safety for participants. End-to-end public and patient involvement in the design of the approach provided evidence to inform information governance decisions.<h4>Trial registration</h4>PRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research. EudraCT number: 2020-001209-22 . 26/03/2020 ISRCTN registry: ISRCTN86534580 . 20/03/2020 REC number: 20/SC/058 IRAS number: 281958.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-021-05965-4; doi:https://doi.org/10.1186/s13063-021-05965-4; html:https://europepmc.org/articles/PMC8771189; pdf:https://europepmc.org/articles/PMC8771189?pdf=render
 36576189,https://doi.org/10.1136/bmjopen-2022-064320,Assessing medication use patterns in patients hospitalised with COVID-19: a retrospective study.,"Mueller T, Kurdi A, Hall E, Bullard I, Wapshott J, Goodfellow A, Platt N, Proud E, McTaggart S, Bennie M, Sheikh A, EAVE II Collaboration.",,BMJ open,2022,2022-12-05,Y,Therapeutics; clinical pharmacology; Health Informatics; Covid-19,,,"<h4>Objective</h4>To describe patterns of medication use-that is, dexamethasone; remdesivir; and tocilizumab-in the management of patients hospitalised with COVID-19.<h4>Design and setting</h4>Retrospective observational study, using routinely collected, linked electronic data from clinical practice in Scotland. Data on drug exposure in secondary care has been obtained from the Hospital Electronic Prescribing and Medicines Administration System.<h4>Participants</h4>Patients being treated with the drugs of interest and hospitalised for COVID-19 between 1 March 2020 and 10 November 2021.<h4>Outcomes</h4>Identification of patients subject to the treatments of interest; summary of patients' baseline characteristics; description of medication use patterns and treatment episodes. Analyses were descriptive in nature.<h4>Results</h4>Overall, 4063 patients matching the inclusion criteria were identified in Scotland, with a median (IQR) age of 64 years (52-76). Among all patients, 81.4% (n=3307) and 17.8% (n=725) were treated with one or two medicines, respectively; dexamethasone monotherapy accounted for the majority (n=3094, 76.2%) followed by dexamethasone in combination with tocilizumab (n=530, 13.0%). Treatment patterns were variable over time but roughly followed the waves of COVID-19 infections; however, the different drugs were used to varying degrees during the study period.The median (IQR) treatment duration differed by medicine: dexamethasone 5 days (2-9); remdesivir 5 days (2-5); and tocilizumab 1 day (1-1). The overall median (IQR) length of hospital stay among all patients included in the study cohort was 9 days (5-17); 24.7% of patients died in hospital.<h4>Conclusion</h4>The use of adjuvant medicines in patients hospitalised with COVID-19 appears in line with evolving evidence and changing treatment guidelines. In-hospital electronic prescribing systems are a valuable source of information, providing detailed patient-level data on in-hospital drug use.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e064320.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064320; html:https://europepmc.org/articles/PMC9723413; pdf:https://europepmc.org/articles/PMC9723413?pdf=render
-37875536,https://doi.org/10.1038/s41467-023-41879-2,"Long-term health impacts of COVID-19 among 242,712 adults in England.","Atchison CJ, Davies B, Cooper E, Lound A, Whitaker M, Hampshire A, Azor A, Donnelly CA, Chadeau-Hyam M, Cooke GS, Ward H, Elliott P.",,Nature communications,2023,2023-10-24,Y,,,,"The COVID-19 pandemic is having a lasting impact on health and well-being. We compare current self-reported health, quality of life and symptom profiles for people with ongoing symptoms following COVID-19 to those who have never tested positive for SARS-CoV-2 infection and those who have recovered from COVID-19. Overall, 276,840/800,000 (34·6%) of invited participants took part. Mental health and health-related quality of life were worse among participants with ongoing persistent symptoms post-COVID compared with those who had never had COVID-19 or had recovered. In this study, median duration of COVID-related symptoms (N = 130,251) was 1·3 weeks (inter-quartile range 6 days to 2 weeks), with 7·5% and 5·2% reporting ongoing symptoms ≥12 weeks and ≥52 weeks respectively. Female sex, ≥1 comorbidity and being infected when Wild-type variant was dominant were associated with higher probability of symptoms lasting ≥12 weeks and longer recovery time in those with persistent symptoms. Although COVID-19 is usually of short duration, some adults experience persistent and burdensome illness.",,pdf:https://www.nature.com/articles/s41467-023-41879-2.pdf; doi:https://doi.org/10.1038/s41467-023-41879-2; html:https://europepmc.org/articles/PMC10598213; pdf:https://europepmc.org/articles/PMC10598213?pdf=render
 36350644,https://doi.org/10.1093/nar/gkac1017,GWAS Central: an expanding resource for finding and visualising genotype and phenotype data from genome-wide association studies.,"Beck T, Rowlands T, Shorter T, Brookes AJ.",,Nucleic acids research,2023,2023-01-01,Y,,,,"The GWAS Central resource gathers and curates extensive summary-level genome-wide association study (GWAS) data and puts a range of user-friendly but powerful website tools for the comparison and visualisation of GWAS data at the fingertips of researchers. Through our continued efforts to harmonise and import data received from GWAS authors and consortia, and data sets actively collected from public sources, the database now contains over 72.5 million P-values for over 5000 studies testing over 7.4 million unique genetic markers investigating over 1700 unique phenotypes. Here, we describe an update to integrate this extensive data collection with mouse disease model data to support insights into the functional impact of human genetic variation. GWAS Central has expanded to include mouse gene-phenotype associations observed during mouse gene knockout screens. To allow similar cross-species phenotypes to be compared, terms from mammalian and human phenotype ontologies have been mapped. New interactive interfaces to find, correlate and view human and mouse genotype-phenotype associations are included in the website toolkit. Additionally, the integrated browser for interrogating multiple association data sets has been updated and a GA4GH Beacon API endpoint has been added for discovering variants tested in GWAS. The GWAS Central resource is accessible at https://www.gwascentral.org/.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825503; doi:https://doi.org/10.1093/nar/gkac1017; html:https://europepmc.org/articles/PMC9825503; pdf:https://europepmc.org/articles/PMC9825503?pdf=render
+37875536,https://doi.org/10.1038/s41467-023-41879-2,"Long-term health impacts of COVID-19 among 242,712 adults in England.","Atchison CJ, Davies B, Cooper E, Lound A, Whitaker M, Hampshire A, Azor A, Donnelly CA, Chadeau-Hyam M, Cooke GS, Ward H, Elliott P.",,Nature communications,2023,2023-10-24,Y,,,,"The COVID-19 pandemic is having a lasting impact on health and well-being. We compare current self-reported health, quality of life and symptom profiles for people with ongoing symptoms following COVID-19 to those who have never tested positive for SARS-CoV-2 infection and those who have recovered from COVID-19. Overall, 276,840/800,000 (34·6%) of invited participants took part. Mental health and health-related quality of life were worse among participants with ongoing persistent symptoms post-COVID compared with those who had never had COVID-19 or had recovered. In this study, median duration of COVID-related symptoms (N = 130,251) was 1·3 weeks (inter-quartile range 6 days to 2 weeks), with 7·5% and 5·2% reporting ongoing symptoms ≥12 weeks and ≥52 weeks respectively. Female sex, ≥1 comorbidity and being infected when Wild-type variant was dominant were associated with higher probability of symptoms lasting ≥12 weeks and longer recovery time in those with persistent symptoms. Although COVID-19 is usually of short duration, some adults experience persistent and burdensome illness.",,pdf:https://www.nature.com/articles/s41467-023-41879-2.pdf; doi:https://doi.org/10.1038/s41467-023-41879-2; html:https://europepmc.org/articles/PMC10598213; pdf:https://europepmc.org/articles/PMC10598213?pdf=render
 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,,,"<h4>Objectives</h4>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.<h4>Design</h4>Retrospective observational cohort study using routinely collected health data.<h4>Setting</h4>122 NHS Trusts in England for national reporting and an acute hospital in England for local reporting.<h4>Participants</h4>6 602 706 patient-days were analysed using 3-month national data and 1 039 592 patient-days, using 3-year single centre data.<h4>Main outcome measures</h4>Variability in R2R-related metrics reported to NHSE. Performance of eR2R in predicting discharge within 24 hours.<h4>Results</h4>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%).<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e065862.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-065862; html:https://europepmc.org/articles/PMC9805825; pdf:https://europepmc.org/articles/PMC9805825?pdf=render
 37308303,https://doi.org/10.3399/bjgp.2023.0044,Diagnostic windows in non-neoplastic diseases: a systematic review.,"Whitfield E, White B, Denaxas S, Lyratzopoulos G.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-08-31,Y,Diagnosis; Primary Health Care; Electronic Health Records,,,"<h4>Background</h4>Investigating changes in prediagnostic healthcare utilisation can help identify how much earlier conditions could be diagnosed. Such 'diagnostic windows' are established for cancer but remain relatively unexplored for non-neoplastic conditions.<h4>Aim</h4>To extract evidence on the presence and length of diagnostic windows for non-neoplastic conditions.<h4>Design and setting</h4>A systematic review of studies of prediagnostic healthcare utilisation was carried out.<h4>Method</h4>A search strategy was developed to identify relevant studies from PubMed and Connected Papers. Data were extracted on prediagnostic healthcare use, and evidence of diagnostic window presence and length was assessed.<h4>Results</h4>Of 4340 studies screened, 27 were included, covering 17 non-neoplastic conditions, including both chronic (for example, Parkinson's disease) and acute conditions (for example, stroke). Prediagnostic healthcare events included primary care encounters and presentations with relevant symptoms. For 10 conditions, sufficient evidence to determine diagnostic window presence and length was available, ranging from 28 days (herpes simplex encephalitis) to 9 years (ulcerative colitis). For the remaining conditions, diagnostic windows were likely to be present, but insufficient study duration was often a barrier to robustly determining their length, meaning that diagnostic window length may exceed 10 years for coeliac disease, for example.<h4>Conclusion</h4>Evidence of changing healthcare use before diagnosis exists for many non-neoplastic conditions, establishing that early diagnosis is possible, in principle. In particular, some conditions may be detectable many years earlier than they are currently diagnosed. Further research is required to accurately estimate diagnostic windows and to determine how much earlier diagnosis may be possible, and how this might be achieved.",,pdf:https://bjgp.org/content/bjgp/early/2023/04/04/BJGP.2023.0044.full.pdf; doi:https://doi.org/10.3399/BJGP.2023.0044; html:https://europepmc.org/articles/PMC10285689; pdf:https://europepmc.org/articles/PMC10285689?pdf=render
 37720555,https://doi.org/10.1016/j.xops.2023.100388,A Datasheet for the INSIGHT University Hospitals Birmingham Retinal Vein Occlusion Data Set.,"Bilton EJ, Guggenheim EJ, Baranyi B, Radovanovic C, Williams RL, Bradlow W, Denniston AK, Mollan SP.",,Ophthalmology science,2023,2023-08-22,Y,Myocardial infarction; Retinal Vein Occlusion; Major Cardiovascular Events; Data Set; Biomedical Data,,,"<h4>Purpose</h4>Retinal vein occlusion (RVO) is the second leading cause of visual loss due to retinal disease. Retinal vein occlusion increases the risk of cardiovascular mortality and the risk of stroke. This article describes the data contained within the INSIGHT eye health data set for RVO and cardiovascular disease.<h4>Design</h4>Data set descriptor for routinely collected eye and systemic disease data.<h4>Participants</h4>All people who had suffered an RVO aged ≥ 18 years old, attending the Ophthalmology Clinic at Queen Elizabeth Hospital, University Hospitals Birmingham (UHB) National Health Service (NHS) Trust were included.<h4>Methods</h4>The INSIGHT Health Data Research Hub for Eye Health is an NHS-led ophthalmic bioresource. It provides researchers with safe access to anonymized routinely collected data from contributing NHS hospitals to advance research for patient benefit. This report describes the INSIGHT UHB RVO and major adverse cardiovascular events data set, a data set of ophthalmology and systemic data derived from the United Kingdom's largest acute care trust.<h4>Main outcome measures</h4>This data set consists of routinely collected data from the hospital's electronic patient records. The data set primarily includes structured data (relating to their hospital eye care and any cardiovascular data held for the individual) and OCT ocular images. Further details regarding the available data points are available in the supplementary information.<h4>Results</h4>At the time point of this analysis (September 30, 2022) the data set was composed of clinical data from 1521 patients, from Medisoft records inception. The data set includes 2196 occurrences of RVO affecting 2026 eyes, longitudinal eye follow-up clinical parameters, over 6217 eye-related procedures, and 982 encountered complications. The data set contains information on 2534 major adverse cardiovascular event occurrences, their subtype, number experienced per patient, and chronological relation to RVO event. Longitudinal follow-up data including laboratory results, regular medications, and all-cause mortality are also available within the data set.<h4>Conclusions</h4>This data set descriptor article summarizes the data set contents, the process of its curation, and potential uses. The data set is available through the structured application process that ensures research studies are for patient benefit. Further information regarding the data repository and contact details can be found at https://www.insight.hdrhub.org/.<h4>Financial disclosures</h4>Proprietary or commercial disclosure may be found after the references.",,doi:https://doi.org/10.1016/j.xops.2023.100388; html:https://europepmc.org/articles/PMC10500462; pdf:https://europepmc.org/articles/PMC10500462?pdf=render
@@ -94,8 +94,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 35909577,https://doi.org/10.23889/ijpds.v7i1.1725,Educational achievements of children aged 10-11 years with cystic fibrosis. A data linkage study in Wales.,"Schlüter DK, Griffiths R, Akbari A, Taylor-Robinson D.",,International journal of population data science,2022,2022-06-27,Y,Education; Cystic Fibrosis; Data Linkage; Sail Databank,,,"<h4>Introduction</h4>As people with cystic fibrosis (CF) lead longer, healthier lives, educational qualifications and employment prospects are increasingly important. However, little is known about the social consequences of CF, in particular, any impact on educational achievements and the support children with CF receive in schools.<h4>Objectives</h4>To assess the educational achievements of children with CF in Wales compared to the general Welsh population, and the additional learning support children with CF receive in schools.<h4>Methods</h4>We conducted a population-scale data linkage study of all children born in Wales using the Secure Anonymised Information Linkage (SAIL) Databank. We used anonymised individual-level population-scale health and administrative data sources to identify children with CF born between 2000 - 2015, linked to educational attainment records. We calculated the percentage of children that reached expected levels in statutory assessment at age 10-11, Key Stage 2 (KS2), and compared this to educational outcomes in the general population. We also assessed the percentage of children with CF that received extra learning support.<h4>Results</h4>Out of 150 eligible children, 119 had KS2 results. 77% (95% CI: 69%-84%) of children achieved expected levels in English, 81% (95% CI: 73% -87%) in Mathematics and 82% (95% CI: 75% - 88%) in Science. In the comparable general Welsh population, 83.4% to 91.1% achieved the expected level in English, 84.9% to 91.6% in Maths, and 87.1% to 92.2% in Science across the years of the study. 70% of children with CF received extra learning support.<h4>Conclusions</h4>Children with CF in Wales may have worse educational achievements than the general population. More research is needed to inform policies and interventions to better support children with CF to reach their full educational potential and employment opportunities.",,pdf:https://ijpds.org/article/download/1725/3455; doi:https://doi.org/10.23889/ijpds.v7i1.1725; html:https://europepmc.org/articles/PMC9284509; pdf:https://europepmc.org/articles/PMC9284509?pdf=render
 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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5446; doi:https://doi.org/10.1002/gps.5446; html:https://europepmc.org/articles/PMC7984448; pdf:https://europepmc.org/articles/PMC7984448?pdf=render
 36647011,https://doi.org/10.1186/s12882-022-03031-y,Does acute kidney injury alerting improve patient outcomes?,"Atia J, Evison F, Gallier S, Hewins P, Ball S, Gavin J, Coleman J, Garrick M, Pankhurst T.",,BMC nephrology,2023,2023-01-17,Y,Acute Kidney Injury; Referral; Electronic Patient Records; Electronic Health Records; Patient Outcomes,,,"<h4>Background</h4>Electronic alerts (e-alerts) for Acute Kidney Injury (AKI) have been implemented into a variety of different Electronic Health Records (EHR) systems worldwide in order to improve recognition and encourage early appropriate management of AKI. We were interested in the impact on patient safety, specialist referral and clinical management.<h4>Methods</h4>All patients admitted to our institution with AKI were included in the study. We studied AKI progression, dialysis dependency, length of hospital stay, emergency readmission, ICU readmission, and death, before and after the introduction of electronic alerts. The impact on prescription of high risk drugs, fluid administration, and referral to renal services was also analysed.<h4>Results</h4>After the introduction of the e-alert, progression to higher AKI stage, emergency readmission to hospital and death during admission were significantly reduced. More prescriptions were stopped for drugs that adversely affect renal function in AKI and there was a significant increase in the ICU admissions and in the number of patients having dialysis, especially in earlier stages. Longer term mortality, renal referrals, and fluid alteration did not change significantly after the AKI e-alert introduction.<h4>Conclusions</h4>AKI e-alerts can improve clinical outcomes in hospitalised patients.",,pdf:https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-022-03031-y; doi:https://doi.org/10.1186/s12882-022-03031-y; html:https://europepmc.org/articles/PMC9843843; pdf:https://europepmc.org/articles/PMC9843843?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 <i>via</i> 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.",,pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1146702/pdf; doi:https://doi.org/10.3389/fimmu.2023.1146702; html:https://europepmc.org/articles/PMC10087108; pdf:https://europepmc.org/articles/PMC10087108?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.",,pdf:https://academic.oup.com/ageing/article-pdf/50/4/1208/38839537/afaa252.pdf; 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
+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 <i>via</i> 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.",,pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1146702/pdf; 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,,,"<h4>Objectives</h4>To identify risk factors associated with prolonged length of hospital stay and staying in hospital longer than medically necessary following primary knee replacement surgery.<h4>Design</h4>Retrospective, longitudinal observational study.<h4>Setting</h4>Elective knee replacement surgeries between 2016 and 2019 were identified using routinely collected data from an NHS Trust in England.<h4>Participants</h4>There were 2295 knee replacement patients with complete data included in analysis. The mean age was 68 (SD 11) and 60% were female.<h4>Outcome measures</h4>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.<h4>Results</h4>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 (<i>b=</i>0.08, 95% CI 0.07 to 0.09), female sex (<i>b</i>=0.36, 95% CI 0.06 to 0.67), high deprivation (<i>b</i>=0.98, 95% CI 0.47 to 1.48) and more comorbidities (<i>b</i>=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).<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e068252.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-068252; html:https://europepmc.org/articles/PMC9764602; pdf:https://europepmc.org/articles/PMC9764602?pdf=render
 35780805,https://doi.org/10.1016/s2213-8587(22)00158-9,"Associations of BMI with COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination in England: a population-based cohort study.","Piernas C, Patone M, Astbury NM, Gao M, Sheikh A, Khunti K, Shankar-Hari M, Dixon S, Coupland C, Aveyard P, Hippisley-Cox J, Jebb SA.",,The lancet. Diabetes & endocrinology,2022,2022-07-01,Y,,,,"<h4>Background</h4>A high BMI has been associated with a reduced immune response to vaccination against influenza. We aimed to investigate the association between BMI and COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination by using a large, representative population-based cohort from England.<h4>Methods</h4>In this population-based cohort study, we used the QResearch database of general practice records and included patients aged 18 years or older who were registered at a practice that was part of the database in England between Dec 8, 2020 (date of the first vaccination in the UK), to Nov 17, 2021, with available data on BMI. Uptake was calculated as the proportion of people with zero, one, two, or three doses of the vaccine across BMI categories. Effectiveness was assessed through a nested matched case-control design to estimate odds ratios (OR) for severe COVID-19 outcomes (ie, admission to hospital or death) in people who had been vaccinated versus those who had not, considering vaccine dose and time periods since vaccination. Vaccine effectiveness against infection with SARS-CoV-2 was also investigated. Multivariable Cox proportional hazard models estimated the risk of severe COVID-19 outcomes associated with BMI (reference BMI 23 kg/m<sup>2</sup>) after vaccination.<h4>Findings</h4>Among 9 171 524 participants (mean age 52 [SD 19] years; BMI 26·7 [5·6] kg/m<sup>2</sup>), 566 461 tested positive for SARS-CoV-2 during follow-up, of whom 32 808 were admitted to hospital and 14 389 died. Of the total study sample, 19·2% (1 758 689) were unvaccinated, 3·1% (287 246) had one vaccine dose, 52·6% (4 828 327) had two doses, and 25·0% (2 297 262) had three doses. In people aged 40 years and older, uptake of two or three vaccine doses was more than 80% among people with overweight or obesity, which was slightly lower in people with underweight (70-83%). Although significant heterogeneity was found across BMI groups, protection against severe COVID-19 disease (comparing people who were vaccinated vs those who were not) was high after 14 days or more from the second dose for hospital admission (underweight: OR 0·51 [95% CI 0·41-0·63]; healthy weight: 0·34 [0·32-0·36]; overweight: 0·32 [0·30-0·34]; and obesity: 0·32 [0·30-0·34]) and death (underweight: 0·60 [0·36-0·98]; healthy weight: 0·39 [0·33-0·47]; overweight: 0·30 [0·25-0·35]; and obesity: 0·26 [0·22-0·30]). In the vaccinated cohort, there were significant linear associations between BMI and COVID-19 hospitalisation and death after the first dose, and J-shaped associations after the second dose.<h4>Interpretation</h4>Using BMI categories, there is evidence of protection against severe COVID-19 in people with overweight or obesity who have been vaccinated, which was of a similar magnitude to that of people of healthy weight. Vaccine effectiveness was slightly lower in people with underweight, in whom vaccine uptake was also the lowest for all ages. In the vaccinated cohort, there were increased risks of severe COVID-19 outcomes for people with underweight or obesity compared with the vaccinated population with a healthy weight. These results suggest the need for targeted efforts to increase uptake in people with low BMI (<18·5 kg/m<sup>2</sup>), in whom uptake is lower and vaccine effectiveness seems to be reduced. Strategies to achieve and maintain a healthy weight should be prioritised at the population level, which could help reduce the burden of COVID-19 disease.<h4>Funding</h4>UK Research and Innovation and National Institute for Health Research Oxford Biomedical Research Centre.",,pdf:http://www.thelancet.com/article/S2213858722001589/pdf; doi:https://doi.org/10.1016/S2213-8587(22)00158-9; html:https://europepmc.org/articles/PMC9246477; pdf:https://europepmc.org/articles/PMC9246477?pdf=render
 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 (<i>n</i> = 317,601), we conducted a prospective study linking residential air pollution exposure (PM<sub>2.5</sub>, PM<sub>10</sub>, NO<sub>2</sub>, NO<sub>x</sub>) 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
@@ -112,9 +112,9 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-020-01336-2; doi:https://doi.org/10.1186/s12911-020-01336-2; html:https://europepmc.org/articles/PMC7736131; pdf:https://europepmc.org/articles/PMC7736131?pdf=render
 36253471,https://doi.org/10.1038/s41467-022-33937-y,A population-based matched cohort study of early pregnancy outcomes following COVID-19 vaccination and SARS-CoV-2 infection.,"Calvert C, Carruthers J, Denny C, Donaghy J, Hillman S, Hopcroft LEM, Hopkins L, Goulding A, Lindsay L, McLaughlin T, Moore E, Pan J, Taylor B, Almaghrabi F, Auyeung B, Bhaskaran K, Gibbons CL, Katikireddi SV, McCowan C, Murray J, O'Leary M, Ritchie LD, Shah SA, Simpson CR, Robertson C, Sheikh A, Stock SJ, Wood R.",,Nature communications,2022,2022-10-17,Y,,,,"Data on the safety of COVID-19 vaccines in early pregnancy are limited. We conducted a national, population-based, matched cohort study assessing associations between COVID-19 vaccination and miscarriage prior to 20 weeks gestation and, separately, ectopic pregnancy. We identified women in Scotland 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). Matched, unvaccinated women from the pre-pandemic and, separately, pandemic periods were used as controls. Here we show no association between vaccination and miscarriage (adjusted Odds Ratio [aOR], pre-pandemic controls = 1.02, 95% Confidence Interval [CI] = 0.96-1.09) or ectopic pregnancy (aOR = 1.13, 95% CI = 0.92-1.38). We undertook additional analyses examining confirmed SARS-CoV-2 infection as the exposure and similarly found no association with miscarriage or ectopic pregnancy. 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/10.1038/s41467-022-33937-y; html:https://europepmc.org/articles/PMC9574832; pdf:https://europepmc.org/articles/PMC9574832?pdf=render; pdf:https://www.nature.com/articles/s41467-022-33937-y.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,,,"<h4>Background</h4>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.<h4>Aim</h4>To examine the association between home death and socioeconomic position during the Covid-19 pandemic, and how this changed between 2019 and 2020.<h4>Design</h4>Retrospective cohort study using population-based individual-level mortality data.<h4>Setting/participants</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10125882; doi:https://doi.org/10.1177/02692163231167212; html:https://europepmc.org/articles/PMC10125882; pdf:https://europepmc.org/articles/PMC10125882?pdf=render
-36600681,https://doi.org/10.1177/17562848221145612,Artificial intelligence-based personalized nutrition and prediction of irritable bowel syndrome patients.,"Acharjee A, Choudhury SP.",,Therapeutic advances in gastroenterology,2022,2022-12-26,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806427; doi:https://doi.org/10.1177/17562848221145612; html:https://europepmc.org/articles/PMC9806427; pdf:https://europepmc.org/articles/PMC9806427?pdf=render
-35501368,https://doi.org/10.1038/s41431-022-01107-9,"Genetic analysis of the PCSK9 locus in psychological, psychiatric, metabolic and cardiovascular traits in UK Biobank.","Hay R, Cullen B, Graham N, Lyall DM, Aman A, Pell JP, Ward J, Smith DJ, Strawbridge RJ.",,European journal of human genetics : EJHG,2022,2022-05-02,Y,,,,"The association between severe mental illness (SMI) and cardiovascular and metabolic disease (CMD) is poorly understood. PCSK9 is expressed in systems critical to both SMI and CMD and influences lipid homeostasis and brain function. We systematically investigated relationships between genetic variation within the PCSK9 locus and risk for both CMD and SMI. UK Biobank recruited ~500,000 volunteers and assessed a wide range of SMI and CMD phenotypes. We used genetic data from white British ancestry individuals of UK Biobank. Genetic association analyses were conducted in PLINK, with statistical significance defined by the number of independent SNPs. Conditional analyses and linkage disequilibrium assessed the independence of SNPs and the presence of multiple signals. Two genetic risk scores of lipid-lowering alleles were calculated and used as proxies for putative lipid-lowering effects of PCSK9. PCSK9 variants were associated with central adiposity, venous thrombosis embolism, systolic blood pressure, mood instability, and neuroticism (all p < 1.16 × 10<sup>-4</sup>). No secondary signals were identified. Conditional analyses and high linkage disequilibrium (r<sup>2</sup> = 0.98) indicated that mood instability and central obesity may share a genetic signal. Genetic risk scores suggested that the lipid-lowering effects of PCSK9 may be causal for greater mood instability and higher neuroticism. This is the first study to implicate the PCSK9 locus in mood-disorder symptoms and related traits, as well as the shared pathology of SMI and CMD. PCSK9 effects on mood may occur via lipid-lowering mechanisms. Further work is needed to understand whether repurposing PCSK9-targeting therapies might improve SMI symptoms and prevent CMD.",,pdf:https://www.nature.com/articles/s41431-022-01107-9.pdf; doi:https://doi.org/10.1038/s41431-022-01107-9; html:https://europepmc.org/articles/PMC9712543; pdf:https://europepmc.org/articles/PMC9712543?pdf=render
 34216888,https://doi.org/10.1016/j.compbiomed.2021.104556,NFnetFu: A novel workflow for microbiome data fusion.,"Bisht V, Acharjee A, Gkoutos GV.",,Computers in biology and medicine,2021,2021-06-08,Y,Clustering; Microbiome; Fuzzy Inference; Network Fusion,,,"Microbiome data analysis and its interpretation into meaningful biological insights remain very challenging for numerous reasons, perhaps most prominently, due to the need to account for multiple factors, including collinearity, sparsity (excessive zeros) and effect size, that the complex experimental workflow and subsequent downstream data analysis require. Moreover, a meaningful microbiome data analysis necessitates the development of interpretable models that incorporate inferences across available data as well as background biomedical knowledge. We developed a multimodal framework that considers sparsity (excessive zeros), lower effect size, intrinsically microbial correlations, i.e., collinearity, as well as background biomedical knowledge in the form of a cluster-infused enriched network architecture. Finally, our framework also provides a candidate taxa/Operational Taxonomic Unit (OTU) that can be targeted for future validation experiments. We have developed a tool, the term NFnetFU (Neuro Fuzzy network Fusion), that encompasses our framework and have made it freely available at https://github.com/VartikaBisht6197/NFnetFu.",,doi:https://doi.org/10.1016/j.compbiomed.2021.104556; doi:https://doi.org/10.1016/j.compbiomed.2021.104556; html:https://europepmc.org/articles/PMC8404037
+35501368,https://doi.org/10.1038/s41431-022-01107-9,"Genetic analysis of the PCSK9 locus in psychological, psychiatric, metabolic and cardiovascular traits in UK Biobank.","Hay R, Cullen B, Graham N, Lyall DM, Aman A, Pell JP, Ward J, Smith DJ, Strawbridge RJ.",,European journal of human genetics : EJHG,2022,2022-05-02,Y,,,,"The association between severe mental illness (SMI) and cardiovascular and metabolic disease (CMD) is poorly understood. PCSK9 is expressed in systems critical to both SMI and CMD and influences lipid homeostasis and brain function. We systematically investigated relationships between genetic variation within the PCSK9 locus and risk for both CMD and SMI. UK Biobank recruited ~500,000 volunteers and assessed a wide range of SMI and CMD phenotypes. We used genetic data from white British ancestry individuals of UK Biobank. Genetic association analyses were conducted in PLINK, with statistical significance defined by the number of independent SNPs. Conditional analyses and linkage disequilibrium assessed the independence of SNPs and the presence of multiple signals. Two genetic risk scores of lipid-lowering alleles were calculated and used as proxies for putative lipid-lowering effects of PCSK9. PCSK9 variants were associated with central adiposity, venous thrombosis embolism, systolic blood pressure, mood instability, and neuroticism (all p < 1.16 × 10<sup>-4</sup>). No secondary signals were identified. Conditional analyses and high linkage disequilibrium (r<sup>2</sup> = 0.98) indicated that mood instability and central obesity may share a genetic signal. Genetic risk scores suggested that the lipid-lowering effects of PCSK9 may be causal for greater mood instability and higher neuroticism. This is the first study to implicate the PCSK9 locus in mood-disorder symptoms and related traits, as well as the shared pathology of SMI and CMD. PCSK9 effects on mood may occur via lipid-lowering mechanisms. Further work is needed to understand whether repurposing PCSK9-targeting therapies might improve SMI symptoms and prevent CMD.",,pdf:https://www.nature.com/articles/s41431-022-01107-9.pdf; doi:https://doi.org/10.1038/s41431-022-01107-9; html:https://europepmc.org/articles/PMC9712543; pdf:https://europepmc.org/articles/PMC9712543?pdf=render
+36600681,https://doi.org/10.1177/17562848221145612,Artificial intelligence-based personalized nutrition and prediction of irritable bowel syndrome patients.,"Acharjee A, Choudhury SP.",,Therapeutic advances in gastroenterology,2022,2022-12-26,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806427; doi:https://doi.org/10.1177/17562848221145612; html:https://europepmc.org/articles/PMC9806427; pdf:https://europepmc.org/articles/PMC9806427?pdf=render
 34850818,https://doi.org/10.1093/ageing/afab223,"COVID-19 infection risk amongst 14,104 vaccinated care home residents: a national observational longitudinal cohort study in Wales, UK, December 2020-March 2021. ","Hollinghurst J, North L, Perry M, Akbari A, Gravenor MB, Lyons RA, Fry R.",,Age and ageing,2022,2022-01-01,Y,,,,"vaccinations for COVID-19 have been prioritised for older people living in care homes. However, vaccination trials included limited numbers of older people. we aimed to study infection rates of SARS-CoV-2 for older care home residents following vaccination and identify factors associated with increased risk of infection. we conducted an observational data-linkage study including 14,104 vaccinated older care home residents in Wales (UK) using anonymised electronic health records and administrative data. we used Cox proportional hazards models to estimate hazard ratios (HRs) for the risk of testing positive for SARS-CoV-2 infection following vaccination, after landmark times of either 7 or 21 days post-vaccination. We adjusted HRs for age, sex, frailty, prior SARS-CoV-2 infections and vaccination type. we observed a small proportion of care home residents with positive polymerase chain reaction (tests following vaccination 1.05% (N = 148), with 90% of infections occurring within 28 days. For the 7-day landmark analysis we found a reduced risk of SARS-CoV-2 infection for vaccinated individuals who had a previous infection; HR (95% confidence interval) 0.54 (0.30, 0.95). For the 21-day landmark analysis, we observed high HRs for individuals with low and intermediate frailty compared with those without; 4.59 (1.23, 17.12) and 4.85 (1.68, 14.04), respectively. increased risk of infection after 21 days was associated with frailty. We found most infections occurred within 28 days of vaccination, suggesting extra precautions to reduce transmission risk should be taken in this time frame.",,pdf:https://academic.oup.com/ageing/article-pdf/51/1/afab223/42083726/afab223.pdf; doi:https://doi.org/10.1093/ageing/afab223; html:https://europepmc.org/articles/PMC8690013; pdf:https://europepmc.org/articles/PMC8690013?pdf=render
 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,,,"<h4>Introduction</h4>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.<h4>Background</h4>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.<h4>Risks</h4>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.<h4>Discussion</h4>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.",,pdf:http://www.cell.com/article/S2405844023023502/pdf; doi:https://doi.org/10.1016/j.heliyon.2023.e15143; html:https://europepmc.org/articles/PMC10130764; pdf:https://europepmc.org/articles/PMC10130764?pdf=render
 34864250,https://doi.org/10.1016/j.seizure.2021.11.017,Epilepsy mortality in Wales during COVID-19.,"Daniels H, Lacey AS, Mikadze D, Akbari A, Fonferko-Shadrach B, Hollinghurst J, Lyons RA, Rees MI, Sawhney IM, Powell RH, Kerr MP, Pickrell WO.",,Seizure,2022,2021-11-27,Y,Pandemic; Data Linkage; Electronic Health Records; Covid-19,,,"<h4>Purpose</h4>The COVID-19 pandemic has increased mortality worldwide and those with chronic conditions may have been disproportionally affected. However, it is unknown whether the pandemic has changed mortality rates for people with epilepsy. We aimed to compare mortality rates in people with epilepsy in Wales during the pandemic with pre-pandemic rates.<h4>Methods</h4>We performed a retrospective study using individual-level linked population-scale anonymised electronic health records. We identified deaths in people with epilepsy (DPWE), i.e. those with a diagnosis of epilepsy, and deaths associated with epilepsy (DAE), where epilepsy was recorded as a cause of death on death certificates. We compared death rates in 2020 with average rates in 2015-2019 using Poisson models to calculate death rate ratios.<h4>Results</h4>There were 188 DAE and 628 DPWE in Wales in 2020 (death rates: 7.7/100,000/year and 25.7/100,000/year). The average rates for DAE and DPWE from 2015 to 2019 were 5.8/100,000/year and 23.8/100,000/year, respectively. Death rate ratios (2020 compared to 2015-2019) for DAE were 1.34 (95%CI 1.14-1.57, p<0.001) and for DPWE were 1.08 (0.99-1.17, p = 0.09). The death rate ratios for non-COVID deaths (deaths without COVID mentioned on death certificates) for DAE were 1.17 (0.99-1.39, p = 0.06) and for DPWE were 0.96 (0.87-1.05, p = 0.37).<h4>Conclusions</h4>The significant increase in DAE in Wales during 2020 could be explained by the direct effect of COVID-19 infection. Non-COVID-19 deaths have not increased significantly but further work is needed to assess the longer-term impact.",,doi:https://doi.org/10.1016/j.seizure.2021.11.017; doi:https://doi.org/10.1016/j.seizure.2021.11.017; html:https://europepmc.org/articles/PMC8626872
@@ -139,16 +139,16 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 36035235,https://doi.org/10.1212/nxg.0000000000200015,"Frequency and Phenotype Associations of Rare Variants in 5 Monogenic Cerebral Small Vessel Disease Genes in 200,000 UK Biobank Participants.","Ferguson AC, Thrippleton S, Henshall D, Whittaker E, Conway B, MacLeod M, Malik R, Rawlik K, Tenesa A, Sudlow C, Rannikmae K.",,Neurology. Genetics,2022,2022-08-24,Y,,,,"<h4>Background and objectives</h4>Based on previous case reports and disease-based cohorts, a minority of patients with cerebral small vessel disease (cSVD) have a monogenic cause, with many also manifesting extracerebral phenotypes. We investigated the frequency, penetrance, and phenotype associations of putative pathogenic variants in cSVD genes in the UK Biobank (UKB), a large population-based study.<h4>Methods</h4>We used a systematic review of previous literature and ClinVar to identify putative pathogenic rare variants in <i>CTSA</i>, <i>TREX1</i>, <i>HTRA1</i>, and <i>COL4A1/2</i>. We mapped phenotypes previously attributed to these variants (phenotypes-of-interest) to disease coding systems used in the UKB's linked health data from UK hospital admissions, death records, and primary care. Among 199,313 exome-sequenced UKB participants, we assessed the following: the proportion of participants carrying ≥1 variant(s); phenotype-of-interest penetrance; and the association between variant carrier status and phenotypes-of-interest using a binary (any phenotype present/absent) and phenotype burden (linear score of the number of phenotypes a participant possessed) approach.<h4>Results</h4>Among UKB participants, 0.5% had ≥1 variant(s) in studied genes. Using hospital admission and death records, 4%-20% of variant carriers per gene had an associated phenotype. This increased to 7%-55% when including primary care records. Only <i>COL4A1</i> variant carrier status was significantly associated with having ≥1 phenotype-of-interest and a higher phenotype score (OR = 1.29, <i>p</i> = 0.006).<h4>Discussion</h4>While putative pathogenic rare variants in monogenic cSVD genes occur in 1:200 people in the UKB population, only approximately half of variant carriers have a relevant disease phenotype recorded in their linked health data. We could not replicate most previously reported gene-phenotype associations, suggesting lower penetrance rates, overestimated pathogenicity, and/or limited statistical power.",,pdf:https://ng.neurology.org/content/nng/8/5/e200015.full.pdf; doi:https://doi.org/10.1212/NXG.0000000000200015; html:https://europepmc.org/articles/PMC9403885; pdf:https://europepmc.org/articles/PMC9403885?pdf=render
 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,,,"<h4>Objectives</h4>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.<h4>Design</h4>We developed a Bayesian model to infer incident cases and reproduction number (<i>R</i>) in England, from incident death data. We then used this to forecast excess cases and deaths in multiple plausible scenarios in which <i>R</i> increases at one or more time points.<h4>Setting</h4>England.<h4>Participants</h4>Publicly available national incident death data for COVID-19 were examined.<h4>Primary outcome</h4>Excess cumulative cases and deaths forecast at 90 days, in simulated scenarios of plausible increases in <i>R</i> after successive easing of lockdown in England, compared with a baseline scenario where <i>R</i> remained constant.<h4>Results</h4>Our model inferred an <i>R</i> of 0.75 on 13 May when England first started easing lockdown. In the most conservative scenario modelled where <i>R</i> 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 <i>R</i> (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 <i>R</i> increased to 0.85 on 1 June, and 0.9 on 4 July.<h4>Conclusions</h4>When levels of transmission are high, even small changes in <i>R</i> with easing of lockdown can have significant impacts on expected cases and deaths, even if <i>R</i> 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 <i>R</i> ≤1 would substantially mitigate the impact of the COVID-19 epidemic within England.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/9/e042483.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042483; html:https://europepmc.org/articles/PMC8438582; pdf:https://europepmc.org/articles/PMC8438582?pdf=render
 34799365,https://doi.org/10.1136/bmjopen-2021-054861,Retrospective cohort study to evaluate medication use in patients hospitalised with COVID-19 in Scotland: protocol for a national observational study.,"Mueller T, Kerr S, McTaggart S, Kurdi A, Vasileiou E, Docherty A, Fraser K, Shi T, Simpson CR, Bennie M, Sheikh A.",,BMJ open,2021,2021-11-19,Y,Therapeutics; clinical pharmacology; Covid-19,,,"<h4>Introduction</h4>COVID-19 has caused millions of hospitalisations and deaths globally. A range of vaccines have been developed and are being deployed at scale in the UK to prevent SARS-CoV-2 infection, which have reduced risk of infection and severe COVID-19 outcomes. Those with COVID-19 are now being treated with several repurposed drugs based on evidence emerging from recent clinical trials. However, there is currently limited real-world data available related to the use of these drugs in routine clinical practice. The purpose of this study is to address the prevailing knowledge gaps regarding the use of dexamethasone, remdesivir and tocilizumab by conducting an exploratory drug utilisation study, aimed at providing in-depth descriptions of patients receiving these drugs as well as the treatment patterns observed in Scotland.<h4>Methods and analysis</h4>Retrospective cohort study, comprising adult patients admitted to hospital with confirmed or suspected COVID-19 across five Scottish Health Boards using data from in-hospital ePrescribing linked to the Early Estimation of Vaccine and Anti-Viral Effectiveness (EAVE II) COVID-19 surveillance platform. The primary outcome will be exposure to the medicines of interest (dexamethasone, remdesivir, tocilizumab), either alone or in combination; exposure will be described in terms of drug(s) of choice; prescribed and administered dose; treatment duration; and any changes in treatment, for example, dose escalation and/or switching to an alternative drug. Analyses will primarily be descriptive in nature.<h4>Ethics and dissemination</h4>Ethical and information governance approvals have been obtained by the National Research Ethics Service Committee, South East Scotland 02 and the Public Benefit and Privacy Panel for Health and Social Care, respectively. Findings from this study will be presented at academic and clinical conferences, and to the funders and other interested parties as appropriate; study findings will also be published in peer-reviewed journals. Publications will be available on the EAVE II website (https://www.ed.ac.uk/usher/eave-ii/key-outputs/our-publications), alongside lay summaries and infographics aimed at the general public. Press releases will also be considered, if appropriate.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/11/e054861.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054861; html:https://europepmc.org/articles/PMC8609490; pdf:https://europepmc.org/articles/PMC8609490?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.",,pdf:https://www.degruyter.com/document/doi/10.1515/dx-2022-0052/pdf; doi:https://doi.org/10.1515/dx-2022-0052
 32741245,https://doi.org/10.1177/0954411920946526,Artificial intelligence approaches to predict coronary stenosis severity using non-invasive fractional flow reserve.,"Carson JM, Chakshu NK, Sazonov I, Nithiarasu P.",,"Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine",2020,2020-08-03,Y,Artificial intelligence; Biomedical engineering; Coronary Heart Disease; Fractional Flow Reserve; Computational Mechanics; Haemodynamic Modelling,,,"Fractional flow reserve is the current reference standard in the assessment of the functional impact of a stenosis in coronary heart disease. In this study, three models of artificial intelligence of varying degrees of complexity were compared to fractional flow reserve measurements. The three models are the multivariate polynomial regression, which is a statistical method used primarily for correlation; the feed-forward neural network; and the long short-term memory, which is a type of recurrent neural network that is suited to modelling sequences. The models were initially trained using a virtual patient database that was generated from a validated one-dimensional physics-based model. The feed-forward neural network performed the best for all test cases considered, which were a single vessel case from a virtual patient database, a multi-vessel network from a virtual patient database, and 25 clinically invasive fractional flow reserve measurements from real patients. The feed-forward neural network model achieved around 99% diagnostic accuracy in both tests involving virtual patients, and a respectable 72% diagnostic accuracy when compared to the invasive fractional flow reserve measurements. The multivariate polynomial regression model performed well in the single vessel case, but struggled on network cases as the variation of input features was much larger. The long short-term memory performed well for the single vessel cases, but tended to have a bias towards a positive fractional flow reserve prediction for the virtual multi-vessel case, and for the patient cases. Overall, the feed-forward neural network shows promise in successfully predicting fractional flow reserve in real patients, and could be a viable option if trained using a large enough data set of real patients.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/0954411920946526; doi:https://doi.org/10.1177/0954411920946526; html:https://europepmc.org/articles/PMC7675765; pdf:https://europepmc.org/articles/PMC7675765?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.",,pdf:https://www.degruyter.com/document/doi/10.1515/dx-2022-0052/pdf; doi:https://doi.org/10.1515/dx-2022-0052
 34911741,https://doi.org/10.1136/heartjnl-2021-320047,Impact of cardiometabolic multimorbidity and ethnicity on cardiovascular/renal complications in patients with COVID-19.,"Norris T, Razieh C, Zaccardi F, Yates T, Islam N, Gillies CL, Chudasama YV, Rowlands AV, Davies MJ, McCann GP, Banerjee A, Lam CSP, Docherty AB, Openshaw PJ, Baillie JK, Semple MG, Lawson CA, Khunti K, ISARIC4C investigators.",,Heart (British Cardiac Society),2022,2022-07-13,Y,epidemiology; risk factors; Covid-19,,,"<h4>Objective</h4>Using a large national database of people hospitalised with COVID-19, we investigated the contribution of cardio-metabolic conditions, multi-morbidity and ethnicity on the risk of in-hospital cardiovascular complications and death.<h4>Methods</h4>A multicentre, prospective cohort study in 302 UK healthcare facilities of adults hospitalised with COVID-19 between 6 February 2020 and 16 March 2021. Logistic models were used to explore associations between baseline patient ethnicity, cardiometabolic conditions and multimorbidity (0, 1, 2, >2 conditions), and in-hospital cardiovascular complications (heart failure, arrhythmia, cardiac ischaemia, cardiac arrest, coagulation complications, stroke), renal injury and death.<h4>Results</h4>Of 65 624 patients hospitalised with COVID-19, 44 598 (68.0%) reported at least one cardiometabolic condition on admission. Cardiovascular/renal complications or death occurred in 24 609 (38.0%) patients. Baseline cardiometabolic conditions were independently associated with increased odds of in-hospital complications and this risk increased in the presence of cardiometabolic multimorbidity. For example, compared with having no cardiometabolic conditions, 1, 2 or ≥3 conditions was associated with 1.46 (95% CI 1.39 to 1.54), 2.04 (95% CI 1.93 to 2.15) and 3.10 (95% CI 2.92 to 3.29) times higher odds of any cardiovascular/renal complication, respectively. A similar pattern was observed for all-cause death. Compared with the white group, the South Asian (OR 1.19, 95% CI 1.10 to 1.29) and black (OR 1.53 to 95% CI 1.37 to 1.72) ethnic groups had higher risk of any cardiovascular/renal complication.<h4>Conclusions</h4>In hospitalised patients with COVID-19, cardiovascular complications or death impacts just under half of all patients, with the highest risk in those of South Asian or Black ethnicity and in patients with cardiometabolic multimorbidity.",,pdf:https://heart.bmj.com/content/heartjnl/108/15/1200.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-320047; html:https://europepmc.org/articles/PMC8678560; pdf:https://europepmc.org/articles/PMC8678560?pdf=render
 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.",,pdf:https://www.nature.com/articles/s41591-022-01701-w.pdf; doi:https://doi.org/10.1038/s41591-022-01701-w; html:https://europepmc.org/articles/PMC9018414; pdf:https://europepmc.org/articles/PMC9018414?pdf=render
 36581868,https://doi.org/10.1186/s12911-022-02045-8,"Effectiveness of clinical decision support in controlling inappropriate red blood cell and platelet transfusions, speciality specific responses and behavioural change.","Atia J, Evison F, Gallier S, Pettler S, Garrick M, Ball S, Lester W, Morton S, Coleman J, Pankhurst T.",,BMC medical informatics and decision making,2022,2022-12-29,Y,Red blood cells; Platelets; CdS; Transfusion; Clinical Decision Support; Haemoglobin; Electronic Health Records; Ehr; E-alerts; Segmented Linear Regression Of Interrupted Time Series,,,"<h4>Background</h4>Electronic clinical decision support (CDS) within Electronic Health Records has been used to improve patient safety, including reducing unnecessary blood product transfusions. We assessed the effectiveness of CDS in controlling inappropriate red blood cell (RBC) and platelet transfusion in a large acute hospital and how speciality specific behaviours changed in response.<h4>Methods</h4>We used segmented linear regression of interrupted time series models to analyse the instantaneous and long term effect of introducing blood product electronic warnings to prescribers. We studied the impact on transfusions for patients in critical care (CC), haematology/oncology (HO) and elsewhere.<h4>Results</h4>In non-CC or HO, there was significant and sustained decrease in the numbers of RBC transfusions after introduction of alerts. In CC the alerts reduced transfusions but this was not sustained, and in HO there was no impact on RBC transfusion. For platelet transfusions outside of CC and HO, the introduction of alerts stopped a rising trend of administration of platelets above recommended targets. In CC, alerts reduced platelet transfusions, but in HO alerts had little impact on clinician prescribing.<h4>Conclusion</h4>The findings suggest that CDS can result in immediate change in user behaviour which is more obvious outside specialist settings of CC and HO. It is important that this is then sustained. In CC and HO, blood transfusion practices differ. CDS thus needs to take specific circumstances into account. In this case there are acceptable reasons to transfuse outside of these crude targets and CDS should take these into account.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-02045-8; doi:https://doi.org/10.1186/s12911-022-02045-8; html:https://europepmc.org/articles/PMC9798655; pdf:https://europepmc.org/articles/PMC9798655?pdf=render
 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,,,,"<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004156&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004156; html:https://europepmc.org/articles/PMC9879484; pdf:https://europepmc.org/articles/PMC9879484?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,,,,"<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>The reviewers showed good agreement. Machine learning classifiers trained on signal-time course measures and QR can assess quality. Combining multiple measures reduces misclassification.<h4>Advances in knowledge</h4>A new automated quality control method was developed, which trained machine learning classifiers using QR results.",,doi:https://doi.org/10.1259/bjr.20201465; doi:https://doi.org/10.1259/bjr.20201465; html:https://europepmc.org/articles/PMC10161906; pdf:https://europepmc.org/articles/PMC10161906?pdf=render
 37751994,https://doi.org/10.1136/emermed-2022-212440,Triage in major incidents: development and external validation of novel machine learning-derived primary and secondary triage tools.,"Xu Y, Malik N, Chernbumroong S, Vassallo J, Keene D, Foster M, Lord J, Belli A, Hodgetts T, Bowley D, Gkoutos G.",,Emergency medicine journal : EMJ,2023,2023-09-26,N,Major Incident; Disaster Planning; Triage; Pre-hospital Care; Major Trauma Management,,,"<h4>Background</h4>Major incidents (MIs) are an important cause of death and disability. Triage tools are crucial to identifying priority 1 (P1) patients-those needing time-critical, life-saving interventions. Existing expert opinion-derived tools have limited evidence supporting their use. This study employs machine learning (ML) to develop and validate models for novel primary and secondary triage tools.<h4>Methods</h4>Adults (16+ years) from the UK Trauma Audit and Research Network (TARN) registry (January 2008-December 2017) served as surrogates for MI victims, with P1 patients identified using predefined criteria. The TARN database was split chronologically into model training and testing (70:30) datasets. Input variables included physiological parameters, age, mechanism and anatomical location of injury. Random forest, extreme gradient boosted tree, logistic regression and decision tree models were trained to predict P1 status, and compared with existing tools (Battlefield Casualty Drills (BCD) Triage Sieve, CareFlight, Modified Physiological Triage Tool, MPTT-24, MSTART, National Ambulance Resilience Unit Triage Sieve and RAMP). Primary and secondary candidate models were selected; the latter was externally validated on patients from the UK military's Joint Theatre Trauma Registry (JTTR).<h4>Results</h4>Models were internally tested in 57 979 TARN patients. The best existing tool was the BCD Triage Sieve (sensitivity 68.2%, area under the receiver operating curve (AUC) 0.688). Inability to breathe spontaneously, presence of chest injury and mental status were most predictive of P1 status. A decision tree model including these three variables exhibited the best test characteristics (sensitivity 73.0%, AUC 0.782), forming the candidate primary tool. The proposed secondary tool (sensitivity 77.9%, AUC 0.817), applicable via a portable device, includes a fourth variable (injury mechanism). This performed favourably on external validation (sensitivity of 97.6%, AUC 0.778) in 5956 JTTR patients.<h4>Conclusion</h4>Novel triage tools developed using ML outperform existing tools in a nationally representative trauma population. The proposed primary tool requires external validation prior to consideration for practical use. The secondary tool demonstrates good external validity and may be used to support decision-making by healthcare workers responding to MIs.",,pdf:https://emj.bmj.com/content/emermed/early/2023/09/25/emermed-2022-212440.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212440
-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; doi:https://doi.org/10.1016/j.lanepe.2023.100638; html:https://europepmc.org/articles/PMC10139952; pdf:https://europepmc.org/articles/PMC10139952?pdf=render
 34376975,https://doi.org/10.1177/11779322211035921,Cloud Computing Enabled Big Multi-Omics Data Analytics.,"Koppad S, B A, Gkoutos GV, Acharjee A.",,Bioinformatics and biology insights,2021,2021-07-28,Y,Data integration; Cloud Computing; Big Data; Multi-omics Data; Data Analytics,,,"High-throughput experiments enable researchers to explore complex multifactorial diseases through large-scale analysis of omics data. Challenges for such high-dimensional data sets include storage, analyses, and sharing. Recent innovations in computational technologies and approaches, especially in cloud computing, offer a promising, low-cost, and highly flexible solution in the bioinformatics domain. Cloud computing is rapidly proving increasingly useful in molecular modeling, omics data analytics (eg, RNA sequencing, metabolomics, or proteomics data sets), and for the integration, analysis, and interpretation of phenotypic data. We review the adoption of advanced cloud-based and big data technologies for processing and analyzing omics data and provide insights into state-of-the-art cloud bioinformatics applications.",,doi:https://doi.org/10.1177/11779322211035921; doi:https://doi.org/10.1177/11779322211035921; html:https://europepmc.org/articles/PMC8323418; pdf:https://europepmc.org/articles/PMC8323418?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; doi:https://doi.org/10.1016/j.lanepe.2023.100638; html:https://europepmc.org/articles/PMC10139952; pdf:https://europepmc.org/articles/PMC10139952?pdf=render
 37765085,https://doi.org/10.3390/ph16091277,The Effects of CYP2C19 Genotype on Proxies of SSRI Antidepressant Response in the UK Biobank.,"Wong WLE, Fabbri C, Laplace B, Li D, van Westrhenen R, Lewis CM, Dawe GS, Young AH.",,"Pharmaceuticals (Basel, Switzerland)",2023,2023-09-11,Y,Cytochrome p450; Antidepressants; Pharmacogenetics; Treatment Response,,,"Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used psychopharmaceutical treatment for major depressive disorder (MDD), but individual responses to SSRIs vary greatly. CYP2C19 is a key enzyme involved in the metabolism of several drugs, including SSRIs. Variations in the CYP2C19 gene are associated with differential metabolic activity, and thus differential SSRI exposure; accordingly, the CYP2C19 genotype may affect the therapeutic response and clinical outcomes, though existing evidence of this link is not entirely consistent. Therefore, we analysed data from the UK Biobank, a large, deeply phenotyped prospective study, to investigate the effects of CYP2C19 metaboliser phenotypes on several clinical outcomes derived from primary care records, including multiple measures of antidepressant switching, discontinuation, duration, and side effects. In this dataset, 24,729 individuals were prescribed citalopram, 3012 individuals were prescribed escitalopram, and 12,544 individuals were prescribed sertraline. Consistent with pharmacological expectations, CYP2C19 poor metabolisers on escitalopram were more likely to switch antidepressants, have side effects following first prescription, and be on escitalopram for a shorter duration compared to normal metabolisers. CYP2C19 poor and intermediate metabolisers on citalopram also exhibited increased odds of discontinuation and shorter durations relative to normal metabolisers. Generally, no associations were found between metabolic phenotypes and proxies of response to sertraline. Sensitivity analyses in a depression subgroup and metabolic activity scores corroborated results from the primary analysis. In summary, our findings suggest that CYP2C19 genotypes, and thus metabolic phenotypes, may have utility in determining clinical responses to SSRIs, particularly escitalopram and citalopram, though further investigation of such a relationship is warranted.",,doi:https://doi.org/10.3390/ph16091277; html:https://europepmc.org/articles/PMC10535191; pdf:https://europepmc.org/articles/PMC10535191?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.",,pdf:https://www.nature.com/articles/s41562-023-01522-y.pdf; doi:https://doi.org/10.1038/s41562-023-01522-y; html:https://europepmc.org/articles/PMC10129868; pdf:https://europepmc.org/articles/PMC10129868?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.",,pdf:https://www.mdpi.com/1660-4601/19/23/15544/pdf?version=1669349785; doi:https://doi.org/10.3390/ijerph192315544; html:https://europepmc.org/articles/PMC9738189; pdf:https://europepmc.org/articles/PMC9738189?pdf=render
@@ -170,14 +170,14 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 34430954,https://doi.org/10.1016/s2666-7568(21)00168-9,Profile of humoral and cellular immune responses to single doses of BNT162b2 or ChAdOx1 nCoV-19 vaccines in residents and staff within residential care homes (VIVALDI): an observational study.,"Tut G, Lancaster T, Krutikov M, Sylla P, Bone D, Kaur N, Spalkova E, Bentley C, Amin U, Jadir AT, Hulme S, Butler MS, Ayodele M, Bruton R, Shrotri M, Azmi B, Fuller C, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,The lancet. Healthy longevity,2021,2021-08-19,Y,,,,"<h4>Background</h4>Residents of long-term care facilities (LTCFs) have been prioritised for COVID-19 vaccination because of the high COVID-19 mortality in this population. Several countries have implemented an extended interval of up to 12 weeks between the first and second vaccine doses to increase population coverage of single-dose vaccination. We aimed to assess the magnitude and quality of adaptive immune responses following a single dose of COVID-19 vaccine in LTCF residents and staff.<h4>Methods</h4>From the LTCFs participating in the ongoing VIVALDI study (ISRCTN14447421), staff and residents who had received a first dose of COVID-19 vaccine (BNT162b2 [tozinameran] or ChAdOx1 nCoV-19), had pre-vaccination and post-vaccination blood samples (collected between Dec 11, 2020, and Feb 16, 2021), and could be linked to a pseudoidentifier in the COVID-19 Data Store were included in our cohort. Past infection with SARS-CoV-2 was defined on the basis of nucleocapsid-specific IgG antibodies being detected through a semiquantitative immunoassay, and participants who tested positive on this assay after but not before vaccination were excluded from the study. Processed blood samples were assessed for spike-specific immune responses, including spike-specific IgG antibody titres, T-cell responses to spike protein peptide mixes, and inhibition of ACE2 binding by spike protein from four variants of SARS-CoV-2 (the original strain as well as the B.1.1.7, B.1.351, and P.1 variants). Responses before and after vaccination were compared on the basis of age, previous infection status, role (staff or resident), and time since vaccination.<h4>Findings</h4>Our cohort comprised 124 participants from 14 LTCFs: 89 (72%) staff (median age 48 years [IQR 35·5-56]) and 35 (28%) residents (87 years [77-90]). Blood samples were collected a median 40 days (IQR 25-47; range 6-52) after vaccination. 30 (24%) participants (18 [20%] staff and 12 [34%] residents) had serological evidence of previous SARS-CoV-2 infection. All participants with previous infection had high antibody titres following vaccination that were independent of age (<i>r</i> <sub>s</sub>=0·076, p=0·70). In participants without evidence of previous infection, titres were negatively correlated with age (<i>r</i> <sub>s</sub>=-0·434, p<0·0001) and were 8·2-times lower in residents than in staff. This effect appeared to result from a kinetic delay antibody generation in older infection-naive participants, with the negative age correlation disappearing only in samples taken more than 42 days post-vaccination (<i>r</i> <sub>s</sub>=-0·207, p=0·20; n=40), in contrast to samples taken after 0-21 days (<i>r</i> <sub>s</sub>=-0·774, p=0·0043; n=12) or 22-42 days (<i>r</i> <sub>s</sub>=-0·437, p=0·0034; n=43). Spike-specific cellular responses were similar between older and younger participants. In infection-naive participants, antibody inhibition of ACE2 binding by spike protein from the original SARS-CoV-2 strain was negatively correlated with age (<i>r</i> <sub>s</sub>=-0·439, p<0·0001), and was significantly lower against spike protein from the B.1.351 variant (median inhibition 31% [14-100], p=0·010) and the P.1 variant (23% [14-97], p<0·0001) than against the original strain (58% [27-100]). By contrast, a single dose of vaccine resulted in around 100% inhibition of the spike-ACE2 interaction against all variants in people with a history of infection.<h4>Interpretation</h4>History of SARS-CoV-2 infection impacts the magnitude and quality of antibody response after a single dose of COVID-19 vaccine in LTCF residents. Residents who are infection-naive have delayed antibody responses to the first dose of vaccine and should be considered for an early second dose where possible.<h4>Funding</h4>UK Government Department of Health and Social Care.",,pdf:https://discovery.ucl.ac.uk/10133388/1/1-s2.0-S2666756821001689-main.pdf; doi:https://doi.org/10.1016/S2666-7568(21)00168-9; html:https://europepmc.org/articles/PMC8376213
 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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279381&type=printable; doi:https://doi.org/10.1371/journal.pone.0279381; html:https://europepmc.org/articles/PMC9799310; pdf:https://europepmc.org/articles/PMC9799310?pdf=render
 36215226,https://doi.org/10.1136/bmj-2022-071230,Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT).,"Jolliffe DA, Holt H, Greenig M, Talaei M, Perdek N, Pfeffer P, Vivaldi G, Maltby S, Symons J, Barlow NL, Normandale A, Garcha R, Richter AG, Faustini SE, Orton C, Ford D, Lyons RA, Davies GA, Kee F, Griffiths CJ, Norrie J, Sheikh A, Shaheen SO, Relton C, Martineau AR.",,BMJ (Clinical research ed.),2022,2022-09-07,Y,,,,"<h4>Objective</h4>To determine the effect of population level implementation of a test-and-treat approach to correction of suboptimal vitamin D status (25-hydroxyvitamin D (25(OH)D) <75 nmol/L) on risk of all cause acute respiratory tract infection and covid 19.<h4>Design</h4>Phase 3 open label randomised controlled trial.<h4>Setting</h4>United Kingdom.<h4>Participants</h4>6200 people aged ≥16 years who were not taking vitamin D supplements at baseline.<h4>Interventions</h4>Offer of a postal finger prick test of blood 25(OH)D concentration with provision of a six month supply of lower dose vitamin D (800 IU/day, n=1550) or higher dose vitamin D (3200 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, compared with no offer of testing or supplementation (n=3100). Follow-up was for six months.<h4>Main outcome measures</h4>The primary outcome was the proportion of participants with at least one swab test or doctor confirmed acute respiratory tract infection of any cause. A secondary outcome was the proportion of participants with swab test confirmed covid-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals. The primary analysis was conducted by intention to treat.<h4>Results</h4>Of 3100 participants offered a vitamin D test, 2958 (95.4%) accepted and 2674 (86.3%) had 25(OH)D concentrations <75 nmol/L and received vitamin D supplements (n=1328 lower dose, n=1346 higher dose). Compared with 136/2949 (4.6%) participants in the no offer group, at least one acute respiratory tract infection of any cause occurred in 87/1515 (5.7%) in the lower dose group (odds ratio 1.26, 95% confidence interval 0.96 to 1.66) and 76/1515 (5.0%) in the higher dose group (1.09, 0.82 to 1.46). Compared with 78/2949 (2.6%) participants in the no offer group, 55/1515 (3.6%) developed covid-19 in the lower dose group (1.39, 0.98 to 1.97) and 45/1515 (3.0%) in the higher dose group (1.13, 0.78 to 1.63).<h4>Conclusions</h4>Among people aged 16 years and older with a high baseline prevalence of suboptimal vitamin D status, implementation of a population level test-and-treat approach to vitamin D supplementation was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19.<h4>Trial registration</h4>ClinicalTrials.gov NCT04579640.",,pdf:https://www.bmj.com/content/bmj/378/bmj-2022-071230.full.pdf; doi:https://doi.org/10.1136/bmj-2022-071230; html:https://europepmc.org/articles/PMC9449358; pdf:https://europepmc.org/articles/PMC9449358?pdf=render
-36810667,https://doi.org/10.1210/clinem/dgad103,Morbidity Associated With Primary Hyperparathyroidism-A Population-based Study With a Subanalysis on Vitamin D.,"Soto-Pedre E, Lin YY, Soto-Hernaez J, Newey PJ, Leese GP.",,The Journal of clinical endocrinology and metabolism,2023,2023-08-01,Y,Calcium; Vitamin D; Mortality; Primary Hyperparathyroidism,,,"<h4>Context</h4>Primary hyperparathyroidism (PHPT) is associated with increased risk of morbidity and death, and vitamin D levels are a potentially confounding variable.<h4>Objective</h4>The aim of this study was to assess morbidity and mortality associated with primary hyperparathyroidism (PHPT).<h4>Methods</h4>In this population-based retrospective matched cohort study, data linkage of biochemistry, hospital admissions, prescribing, imaging, pathology, and deaths was used to identify patients across the region of Tayside, Scotland, who had PHPT from 1997 to 2019. Cox proportional hazards models and hazards ratios (HR) were used to explore the relationship between exposure to PHPT and several clinical outcomes. Comparisons were made with an age- and gender-matched cohort.<h4>Results</h4>In 11 616 people with PHPT (66.8% female), with a mean follow-up period of 8.8 years, there was an adjusted HR of death of 2.05 (95% CI, 1.97-2.13) for those exposed to PHPT. There was also an increased risk of cardiovascular disease (HR = 1.34; 95% CI, 1.24-1.45), cerebrovascular disease (HR = 1.29; 95% CI, 1.15-1.45), diabetes (HR = 1.39; 95% CI, 1.26-1.54), renal stones (HR = 3.02; 95% CI, 2.19-4.17) and osteoporosis (HR = 1.31; 95% CI, 1.16-1.49). Following adjustment for serum vitamin D concentrations (n = 2748), increased risks for death, diabetes, renal stones, and osteoporosis persisted, but not for cardiovascular or cerebrovascular disease.<h4>Conclusion</h4>In a large population-based study, PHPT was associated with death, diabetes, renal stones, and osteoporosis, independent of serum vitamin D concentration.",,pdf:https://academic.oup.com/jcem/advance-article-pdf/doi/10.1210/clinem/dgad103/49516503/dgad103.pdf; doi:https://doi.org/10.1210/clinem/dgad103; html:https://europepmc.org/articles/PMC10438903
 33969335,https://doi.org/10.1016/j.lanepe.2021.100098,"Prevalence of antibody positivity to SARS-CoV-2 following the first peak of infection in England: Serial cross-sectional studies of 365,000 adults.","Ward H, Cooke GS, Atchison C, Whitaker M, Elliott J, Moshe M, Brown JC, Flower B, Daunt A, Ainslie K, Ashby D, Donnelly CA, Riley S, Darzi A, Barclay W, Elliott P.",,The Lancet regional health. Europe,2021,2021-05-02,Y,,,,"<h4>Background</h4>The time-concentrated nature of the first wave of the COVID-19 epidemic in England in March and April 2020 provides a natural experiment to measure changes in antibody positivity at the population level before onset of the second wave and initiation of the vaccination programme.<h4>Methods</h4>Three cross-sectional national surveys with non-overlapping random samples of the population in England undertaken between late June and September 2020 (REACT-2 study). 365,104 adults completed questionnaires and self-administered lateral flow immunoassay (LFIA) tests for IgG against SARS-CoV-2.<h4>Findings</h4>Overall, 17,576 people had detectable antibodies, a prevalence of 4.9% (95% confidence intervals 4.9, 5.0) when adjusted for test characteristics and weighted to the adult population of England. The prevalence declined from 6.0% (5.8, 6.1), to 4.8% (4.7, 5.0) and 4.4% (4.3, 4.5), over the three rounds of the study a difference of -26.5% (-29.0, -23.8). The highest prevalence and smallest overall decline in positivity was in the youngest age group (18-24 years) at -14.9% (-21.6, -8.1), and lowest prevalence and largest decline in the oldest group (>74 years) at -39.0% (-50.8, -27.2). The decline from June to September 2020 was largest in those who did not report a history of COVID-19 at -64.0% (-75.6, -52.3), compared to -22.3% (-27.0, -17.7) in those with SARS-CoV-2 infection confirmed on PCR.<h4>Interpretation</h4>A large proportion of the population remained susceptible to SARS-CoV-2 infection in England based on naturally acquired immunity from the first wave. Widespread vaccination is needed to confer immunity and control the epidemic at population level.<h4>Funding</h4>This work was funded by the Department of Health and Social Care in England.",,doi:https://doi.org/10.1016/j.lanepe.2021.100098; doi:https://doi.org/10.1016/j.lanepe.2021.100098; html:https://europepmc.org/articles/PMC8088780; pdf:https://europepmc.org/articles/PMC8088780?pdf=render
+36810667,https://doi.org/10.1210/clinem/dgad103,Morbidity Associated With Primary Hyperparathyroidism-A Population-based Study With a Subanalysis on Vitamin D.,"Soto-Pedre E, Lin YY, Soto-Hernaez J, Newey PJ, Leese GP.",,The Journal of clinical endocrinology and metabolism,2023,2023-08-01,Y,Calcium; Vitamin D; Mortality; Primary Hyperparathyroidism,,,"<h4>Context</h4>Primary hyperparathyroidism (PHPT) is associated with increased risk of morbidity and death, and vitamin D levels are a potentially confounding variable.<h4>Objective</h4>The aim of this study was to assess morbidity and mortality associated with primary hyperparathyroidism (PHPT).<h4>Methods</h4>In this population-based retrospective matched cohort study, data linkage of biochemistry, hospital admissions, prescribing, imaging, pathology, and deaths was used to identify patients across the region of Tayside, Scotland, who had PHPT from 1997 to 2019. Cox proportional hazards models and hazards ratios (HR) were used to explore the relationship between exposure to PHPT and several clinical outcomes. Comparisons were made with an age- and gender-matched cohort.<h4>Results</h4>In 11 616 people with PHPT (66.8% female), with a mean follow-up period of 8.8 years, there was an adjusted HR of death of 2.05 (95% CI, 1.97-2.13) for those exposed to PHPT. There was also an increased risk of cardiovascular disease (HR = 1.34; 95% CI, 1.24-1.45), cerebrovascular disease (HR = 1.29; 95% CI, 1.15-1.45), diabetes (HR = 1.39; 95% CI, 1.26-1.54), renal stones (HR = 3.02; 95% CI, 2.19-4.17) and osteoporosis (HR = 1.31; 95% CI, 1.16-1.49). Following adjustment for serum vitamin D concentrations (n = 2748), increased risks for death, diabetes, renal stones, and osteoporosis persisted, but not for cardiovascular or cerebrovascular disease.<h4>Conclusion</h4>In a large population-based study, PHPT was associated with death, diabetes, renal stones, and osteoporosis, independent of serum vitamin D concentration.",,pdf:https://academic.oup.com/jcem/advance-article-pdf/doi/10.1210/clinem/dgad103/49516503/dgad103.pdf; doi:https://doi.org/10.1210/clinem/dgad103; html:https://europepmc.org/articles/PMC10438903
 34183745,https://doi.org/10.1038/s41598-021-92874-w,Frailty assessed by administrative tools and mortality in patients with pneumonia admitted to the hospital and ICU in Wales.,"Szakmany T, Hollinghurst J, Pugh R, Akbari A, Griffiths R, Bailey R, Lyons RA.",,Scientific reports,2021,2021-06-28,Y,,,,"The ideal method of identifying frailty is uncertain, and data on long-term outcomes is relatively limited. We examined frailty indices derived from population-scale linked data on Intensive Care Unit (ICU) and hospitalised non-ICU patients with pneumonia to elucidate the influence of frailty on mortality. Longitudinal cohort study between 2010-2018 using population-scale anonymised data linkage of healthcare records for adults admitted to hospital with pneumonia in Wales. Primary outcome was in-patient mortality. Odds Ratios (ORs [95% confidence interval]) for age, hospital frailty risk score (HFRS), electronic frailty index (eFI), Charlson comorbidity index (CCI), and social deprivation index were estimated using multivariate logistic regression models. The area under the receiver operating characteristic curve (AUC) was estimated to determine the best fitting models. Of the 107,188 patients, mean (SD) age was 72.6 (16.6) years, 50% were men. The models adjusted for the two frailty indices and the comorbidity index had an increased odds of in-patient mortality for individuals with an ICU admission (ORs for ICU admission in the eFI model 2.67 [2.55, 2.79], HFRS model 2.30 [2.20, 2.41], CCI model 2.62 [2.51, 2.75]). Models indicated advancing age, increased frailty and comorbidity were also associated with an increased odds of in-patient mortality (eFI, baseline fit, ORs: mild 1.09 [1.04, 1.13], moderate 1.13 [1.08, 1.18], severe 1.17 [1.10, 1.23]. HFRS, baseline low, ORs: intermediate 2.65 [2.55, 2.75], high 3.31 [3.17, 3.45]). CCI, baseline < 1, ORs: '1-10' 1.15 [1.11, 1.20], > 10 2.50 [2.41, 2.60]). For predicting inpatient deaths, the CCI and HFRS based models were similar, however for longer term outcomes the CCI based model was superior. Frailty and comorbidity are significant risk factors for patients admitted to hospital with pneumonia. Frailty and comorbidity scores based on administrative data have only moderate ability to predict outcome.",,pdf:https://www.nature.com/articles/s41598-021-92874-w.pdf; doi:https://doi.org/10.1038/s41598-021-92874-w; html:https://europepmc.org/articles/PMC8239046; pdf:https://europepmc.org/articles/PMC8239046?pdf=render
 37247403,https://doi.org/10.1093/ageing/afad077,Attainment of NICE blood pressure targets among older people with newly diagnosed hypertension: nationwide linked electronic health records cohort study.,"Todd O, Johnson O, Wilkinson C, Hollinghurst J, Dondo TB, Yadegarfar ME, Sheppard JP, McManus RJ, Gale CP, Clegg A.",,Age and ageing,2023,2023-05-01,Y,Hypertension; Blood pressure; Frailty; Older People; Treatment Target,,,"<h4>Background</h4>it is not known if clinical practice reflects guideline recommendations for the management of hypertension in older people and whether guideline adherence varies according to overall health status.<h4>Aims</h4>to describe the proportion of older people attaining National Institute for Health and Care Excellence (NICE) guideline blood pressure targets within 1 year of hypertension diagnosis and determine predictors of target attainment.<h4>Methods</h4>a nationwide cohort study of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged ≥65 years newly diagnosed with hypertension between 1st June 2011 and 1st June 2016. The primary outcome was attainment of NICE guideline blood pressure targets as measured by the latest blood pressure recording up to 1 year after diagnosis. Predictors of target attainment were investigated using logistic regression.<h4>Results</h4>there were 26,392 patients (55% women, median age 71 [IQR 68-77] years) included, of which 13,939 (52.8%) attained a target blood pressure within a median follow-up of 9 months. Success in attaining target blood pressure was associated with a history of atrial fibrillation (OR 1.26, 95% CI 1.11, 1.43), heart failure (OR 1.25, 95% CI 1.06, 1.49) and myocardial infarction (OR 1.20, 95% CI 1.10, 1.32), all compared to no history of each, respectively. Care home residence, the severity of frailty, and increasing co-morbidity were not associated with target attainment following adjustment for confounder variables.<h4>Conclusions</h4>blood pressure remains insufficiently controlled 1 year after diagnosis in nearly half of older people with newly diagnosed hypertension, but target attainment appears unrelated to baseline frailty, multi-morbidity or care home residence.",,doi:https://doi.org/10.1093/ageing/afad077; doi:https://doi.org/10.1093/ageing/afad077; html:https://europepmc.org/articles/PMC10226747; pdf:https://europepmc.org/articles/PMC10226747?pdf=render
 35092316,https://doi.org/10.1002/pds.5412,Transparency of high-dimensional propensity score analyses: Guidance for diagnostics and reporting.,"Tazare J, Wyss R, Franklin JM, Smeeth L, Evans SJW, Wang SV, Schneeweiss S, Douglas IJ, Gagne JJ, Williamson EJ.",,Pharmacoepidemiology and drug safety,2022,2022-02-12,Y,Diagnostics; Reporting; Database Research; Confounder Adjustment; High Dimensional Propensity Score,,,"<h4>Purpose</h4>The high-dimensional propensity score (HDPS) is a semi-automated procedure for confounder identification, prioritisation and adjustment in large healthcare databases that requires investigators to specify data dimensions, prioritisation strategy and tuning parameters. In practice, reporting of these decisions is inconsistent and this can undermine the transparency, and reproducibility of results obtained. We illustrate reporting tools, graphical displays and sensitivity analyses to increase transparency and facilitate evaluation of the robustness of analyses involving HDPS.<h4>Methods</h4>Using a study from the UK Clinical Practice Research Datalink that implemented HDPS we demonstrate the application of the proposed recommendations.<h4>Results</h4>We identify seven considerations surrounding the implementation of HDPS, such as the identification of data dimensions, method for code prioritisation and number of variables selected. Graphical diagnostic tools include assessing the balance of key confounders before and after adjusting for empirically selected HDPS covariates and the identification of potentially influential covariates. Sensitivity analyses include varying the number of covariates selected and assessing the impact of covariates behaving empirically as instrumental variables. In our example, results were robust to both the number of covariates selected and the inclusion of potentially influential covariates. Furthermore, our HDPS models achieved good balance in key confounders.<h4>Conclusions</h4>The data-adaptive approach of HDPS and the resulting benefits have led to its popularity as a method for confounder adjustment in pharmacoepidemiological studies. Reporting of HDPS analyses in practice may be improved by the considerations and tools proposed here to increase the transparency and reproducibility of study results.",,doi:https://doi.org/10.1002/pds.5412; doi:https://doi.org/10.1002/pds.5412; html:https://europepmc.org/articles/PMC9305520; pdf:https://europepmc.org/articles/PMC9305520?pdf=render
+32276644,https://doi.org/10.1186/s12942-020-00208-2,GIS-modelled built-environment exposures reflecting daily mobility for applications in child health research.,"Mizen A, Fry R, Rodgers S.",,International journal of health geographics,2020,2020-04-10,Y,Environmental exposure; Child Health; Walking; Weighted Network; Daily Mobility; School Commute,,,"<h4>Background</h4>Inaccurately modelled environmental exposures may have important implications for evidence-based policy targeting health promoting or hazardous facilities. Travel routes modelled using GIS generally use shortest network distances or Euclidean buffers to represent journeys with corresponding built-environment exposures calculated along these routes. These methods, however, are an unreliable proxy for calculating child built-environment exposures as child route choice is more complex than shortest network routes.<h4>Methods</h4>We hypothesised that a GIS model informed by characteristics of the built-environment known to influence child route choice could be developed to more accurately model exposures. Using GPS-derived walking commutes to and from school we used logistic regression models to highlight built-environment features important in child route choice (e.g. road type, traffic light count). We then recalculated walking commute routes using a weighted network to incorporate built-environment features. Multilevel regression analyses were used to validate exposure predictions to the retail food environment along the different routing methods.<h4>Results</h4>Children chose routes with more traffic lights and residential roads compared to the modelled shortest network routes. Compared to standard shortest network routes, the GPS-informed weighted network enabled GIS-based walking commutes to be derived with more than three times greater accuracy (38%) for the route to school and more than 12 times greater accuracy (92%) for the route home.<h4>Conclusions</h4>This research advocates using weighted GIS networks to accurately reflect child walking journeys to school. The improved accuracy in route modelling has in turn improved estimates of children's exposures to potentially hazardous features in the environment. Further research is needed to explore if the built-environment features are important internationally. Route and corresponding exposure estimates can be scaled to the population level which will contribute to a better understanding of built-environment exposures on child health and contribute to mobility-based child health policy.",,pdf:https://ij-healthgeographics.biomedcentral.com/track/pdf/10.1186/s12942-020-00208-2; doi:https://doi.org/10.1186/s12942-020-00208-2; html:https://europepmc.org/articles/PMC7147039; pdf:https://europepmc.org/articles/PMC7147039?pdf=render
 36350946,https://doi.org/10.1093/bjsopen/zrac130,Major adverse cardiovascular events and all-cause mortality after emergency general surgery among kidney failure patients.,"Anderson B, Zou X, Evison F, Gallier S, Inston N, Sharif A.",,BJS open,2022,2022-11-01,Y,,,,"<h4>Background</h4>Emergency general surgery (EGS) is associated with increased mortality, with kidney failure a contributing risk, but comparative outcomes between patients with kidney failure and the general population are lacking.<h4>Methods</h4>In this retrospective population-cohort study, data were analysed for all EGS procedures performed in England between 1 April 2004 and 31 March 2019. EGS was defined as partial colectomy, small bowel resection, cholecystectomy, appendicectomy, lysis of peritoneal adhesions, surgery for peptic ulcer, or laparotomy. The main outcome measure was major adverse cardiovascular events (MACEs) and all-cause mortality after surgery.<h4>Results</h4>From 691 064 procedures, 0.16 per cent (n = 1097) and 0.23 per cent (n = 1567) were performed on kidney transplant and dialysis recipients respectively. Laparotomy was the most frequent EGS procedure for kidney transplant (46 per cent of procedures, n = 507) and dialysis (45 per cent of procedures, n = 704) recipients, with the highest 30-day and 1-year mortality. In logistic regression analysis, both kidney failure cohorts had higher risk for experiencing MACEs in the postoperative interval after emergency laparotomy; within 3 months (dialysis; OR 2.44 (95 per cent c.i. 2.08 to 2.87), P &lt; 0.001 and transplant; OR 2.05 (95 per cent c.i. 1.57 to 2.68), P &lt; 0.001) and within 1 year (dialysis; OR 2.39 (95 per cent c.i. 2.06 to 2.77), P &lt; 0.001 and transplant; OR 2.21 (95 per cent c.i. 1.76 to 2.77), P &lt; 0.001); however, in a propensity-score-matched cohort, increased risk for MACEs was observed among dialysis patients after emergency laparotomy (HR 2.10 (95 per cent c.i. 1.82 to 2.43), P &lt; 0.001) but not kidney transplant recipients (HR 1.17 (95 per cent c.i. 0.97 to 1.41), P = 0.096).<h4>Conclusion</h4>Mortality after emergency surgery is higher for patients with kidney failure and dialysis is worse than kidney transplantation, with cardiovascular deaths more common than the general population.",,pdf:https://academic.oup.com/bjsopen/article-pdf/6/6/zrac130/46906578/zrac130.pdf; doi:https://doi.org/10.1093/bjsopen/zrac130; html:https://europepmc.org/articles/PMC9645564; pdf:https://europepmc.org/articles/PMC9645564?pdf=render
 36322788,https://doi.org/10.2196/40035,A Hybrid Architecture (CO-CONNECT) to Facilitate Rapid Discovery and Access to Data Across the United Kingdom in Response to the COVID-19 Pandemic: Development Study.,"Jefferson E, Cole C, Mumtaz S, Cox S, Giles TC, Adejumo S, Urwin E, Lea D, Macdonald C, Best J, Masood E, Milligan G, Johnston J, Horban S, Birced I, Hall C, Jackson AS, Collins C, Rising S, Dodsley C, Hampton J, Hadfield A, Santos R, Tarr S, Panagi V, Lavagna J, Jackson T, Chuter A, Beggs J, Martinez-Queipo M, Ward H, von Ziegenweidt J, Burns F, Martin J, Sebire N, Morris C, Bradley D, Baxter R, Ahonen-Bishopp A, Smith P, Shoemark A, Valdes AM, Ollivere B, Manisty C, Eyre D, Gallant S, Joy G, McAuley A, Connell D, Northstone K, Jeffery K, Di Angelantonio E, McMahon A, Walker M, Semple MG, Sims JM, Lawrence E, Davies B, Baillie JK, Tang M, Leeming G, Power L, Breeze T, Murray D, Orton C, Pierce I, Hall I, Ladhani S, Gillson N, Whitaker M, Shallcross L, Seymour D, Varma S, Reilly G, Morris A, Hopkins S, Sheikh A, Quinlan P.",,Journal of medical Internet research,2022,2022-12-27,Y,Meta-analysis; Health care; Public Health; Clinical Care; Data Extraction; Data Privacy; Health Data; Federated Network; Data Governance; Infrastructure Model; Covid-19; Health Care Record,,,"<h4>Background</h4>COVID-19 data have been generated across the United Kingdom as a by-product of clinical care and public health provision, as well as numerous bespoke and repurposed research endeavors. Analysis of these data has underpinned the United Kingdom's response to the pandemic, and informed public health policies and clinical guidelines. However, these data are held by different organizations, and this fragmented landscape has presented challenges for public health agencies and researchers as they struggle to find relevant data to access and interrogate the data they need to inform the pandemic response at pace.<h4>Objective</h4>We aimed to transform UK COVID-19 diagnostic data sets to be findable, accessible, interoperable, and reusable (FAIR).<h4>Methods</h4>A federated infrastructure model (COVID - Curated and Open Analysis and Research Platform [CO-CONNECT]) was rapidly built to enable the automated and reproducible mapping of health data partners' pseudonymized data to the Observational Medical Outcomes Partnership Common Data Model without the need for any data to leave the data controllers' secure environments, and to support federated cohort discovery queries and meta-analysis.<h4>Results</h4>A total of 56 data sets from 19 organizations are being connected to the federated network. The data include research cohorts and COVID-19 data collected through routine health care provision linked to longitudinal health care records and demographics. The infrastructure is live, supporting aggregate-level querying of data across the United Kingdom.<h4>Conclusions</h4>CO-CONNECT was developed by a multidisciplinary team. It enables rapid COVID-19 data discovery and instantaneous meta-analysis across data sources, and it is researching streamlined data extraction for use in a Trusted Research Environment for research and public health analysis. CO-CONNECT has the potential to make UK health data more interconnected and better able to answer national-level research questions while maintaining patient confidentiality and local governance procedures.",,pdf:https://www.jmir.org/2022/12/e40035/PDF; doi:https://doi.org/10.2196/40035; html:https://europepmc.org/articles/PMC9822177
-32276644,https://doi.org/10.1186/s12942-020-00208-2,GIS-modelled built-environment exposures reflecting daily mobility for applications in child health research.,"Mizen A, Fry R, Rodgers S.",,International journal of health geographics,2020,2020-04-10,Y,Environmental exposure; Child Health; Walking; Weighted Network; Daily Mobility; School Commute,,,"<h4>Background</h4>Inaccurately modelled environmental exposures may have important implications for evidence-based policy targeting health promoting or hazardous facilities. Travel routes modelled using GIS generally use shortest network distances or Euclidean buffers to represent journeys with corresponding built-environment exposures calculated along these routes. These methods, however, are an unreliable proxy for calculating child built-environment exposures as child route choice is more complex than shortest network routes.<h4>Methods</h4>We hypothesised that a GIS model informed by characteristics of the built-environment known to influence child route choice could be developed to more accurately model exposures. Using GPS-derived walking commutes to and from school we used logistic regression models to highlight built-environment features important in child route choice (e.g. road type, traffic light count). We then recalculated walking commute routes using a weighted network to incorporate built-environment features. Multilevel regression analyses were used to validate exposure predictions to the retail food environment along the different routing methods.<h4>Results</h4>Children chose routes with more traffic lights and residential roads compared to the modelled shortest network routes. Compared to standard shortest network routes, the GPS-informed weighted network enabled GIS-based walking commutes to be derived with more than three times greater accuracy (38%) for the route to school and more than 12 times greater accuracy (92%) for the route home.<h4>Conclusions</h4>This research advocates using weighted GIS networks to accurately reflect child walking journeys to school. The improved accuracy in route modelling has in turn improved estimates of children's exposures to potentially hazardous features in the environment. Further research is needed to explore if the built-environment features are important internationally. Route and corresponding exposure estimates can be scaled to the population level which will contribute to a better understanding of built-environment exposures on child health and contribute to mobility-based child health policy.",,pdf:https://ij-healthgeographics.biomedcentral.com/track/pdf/10.1186/s12942-020-00208-2; doi:https://doi.org/10.1186/s12942-020-00208-2; html:https://europepmc.org/articles/PMC7147039; pdf:https://europepmc.org/articles/PMC7147039?pdf=render
 37429634,https://doi.org/10.3399/bjgpo.2023.0057,UK research data resources based on primary care electronic health records: review and summary for potential users.,"Edwards L, Pickett J, Ashcroft DM, Dambha-Miller H, Majeed A, Mallen C, Petersen I, Qureshi N, van Staa T, Abel G, Carvalho C, Denholm R, Kontopantelis E, Macaulay A, Macleod J.",,BJGP open,2023,2023-09-19,N,Population; Primary Health Care; Electronic Health Records; Primary Care Databases; Population Level Linked Data,,,"<h4>Background</h4>The range and scope of electronic health record (EHR) data assets in the UK has recently increased, which has been mainly in response to the COVID-19 pandemic. Summarising and comparing the large primary care resources will help researchers to choose the data resources most suited to their needs.<h4>Aim</h4>To describe the current landscape of UK EHR databases and considerations of access and use of these resources relevant to researchers.<h4>Design & setting</h4>Narrative review of EHR databases in the UK.<h4>Method</h4>Information was collected from the Health Data Research Innovation Gateway, publicly available websites and other published data, and from key informants. The eligibility criteria were population-based open-access databases sampling EHRs across the whole population of one or more countries in the UK. Published database characteristics were extracted and summarised, and these were corroborated with resource providers. Results were synthesised narratively.<h4>Results</h4>Nine large national primary care EHR data resources were identified and summarised. These resources are enhanced by linkage to other administrative data to a varying extent. Resources are mainly intended to support observational research, although some can support experimental studies. There is considerable overlap of populations covered. While all resources are accessible to bona fide researchers, access mechanisms, costs, timescales, and other considerations vary across databases.<h4>Conclusion</h4>Researchers are currently able to access primary care EHR data from several sources. Choice of data resource is likely to be driven by project needs and access considerations. The landscape of data resources based on primary care EHRs in the UK continues to evolve.",,doi:https://doi.org/10.3399/bjgpo.2023.0057; doi:https://doi.org/10.3399/BJGPO.2023.0057
 37363696,https://doi.org/10.1155/2023/5885059,Gender Disparity in Expression of Sarcopenia in Haemodialysis Recipients: Analysis from the FITNESS Cohort.,"Anderson BM, Wilson DV, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,International journal of nephrology,2023,2023-06-17,Y,,,,"<h4>Background</h4>There has been little exploration of the interplay between sarcopenia and frailty in haemodialysis, particularly regarding gender difference. We aimed to (1) assess whether ultrasound-derived low muscle mass (LMM) and sarcopenia are more common in male or female haemodialysis recipients; (2) assess whether age influences any observed gender difference, and (3) explore the interplay between sarcopenia, frailty, and gender in haemodialysis recipients.<h4>Methods</h4>This was an exploratory analysis of a subgroup of adult prevalent (≥3 months) haemodialysis with frailty phenotype (FP) scores. Bilateral anterior thigh thickness (BATT) was obtained according to an established ultrasound protocol. Associations with frailty were explored via both linear and logistic regressions for BATT, LMM, and sarcopenia with a priori covariables, stratified by gender.<h4>Results</h4>In total of 223 studies, participants had ultrasound measurements. Males showed greater prevalence of LMM. On adjusted analyses, LMM was associated with lower hand grip strength in males (<i>β</i> = -4.17; 95% C.I. -7.57 to -0.77; <i>P</i>=0.02), but not females (<i>β</i> = -1.88; 95% C.I. -5.41 to 1.64; <i>P</i>=0.29). LMM was also associated with slower walking speed in both males (<i>β</i> = -0.115; 95% C.I. -0.258 to -0.013; <i>P</i>=0.03) and females (<i>β</i> = -0.152; 95% C.I. -0.300 to -0.005; <i>P</i>=0.04). Sarcopenia was associated with greater odds of frailty on adjusted models in males (OR = 9.86; 95% C.I. 1.8 to 54.0; <i>P</i>=0.01), but not females (OR = 5.16; 95% C.I. 0.22 to 124; <i>P</i>=0.31).<h4>Conclusions</h4>The clinical expression and significance of sarcopenia differ substantially between males and females on haemodialysis. Further work is required to elucidate underlying mechanisms and guide tailored treatment.",,doi:https://doi.org/10.1155/2023/5885059; html:https://europepmc.org/articles/PMC10290558; pdf:https://europepmc.org/articles/PMC10290558?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,,,"<h4>Objectives</h4>Two interlinked surveys were organised by the British Heart Foundation Data Science Centre, which aimed to establish national priorities for cardiovascular imaging research.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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
@@ -189,8 +189,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 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.",,pdf:https://www.nature.com/articles/s41591-021-01666-2.pdf; doi:https://doi.org/10.1038/s41591-021-01666-2; html:https://europepmc.org/articles/PMC8938271; pdf:https://europepmc.org/articles/PMC8938271?pdf=render
 36798088,https://doi.org/10.1177/26335565221148616,Classification of long-term condition patterns in rheumatoid arthritis and associations with adverse health events: a UK Biobank cohort study.,"McLoone P, Jani BD, Siebert S, Morton FR, Canning J, Macdonald S, Mair FS, Nicholl BI.",,Journal of multimorbidity and comorbidity,2023,2023-01-01,Y,Rheumatoid arthritis; Mortality; Comorbidity; Latent Class Analysis; Multimorbidity,,,"<h4>Purpose</h4>We aimed to classify individuals with RA and ≥2 additional long-term conditions (LTCs) and describe the association between different LTC classes, number of LTCs and adverse health outcomes.<h4>Methods</h4>We used UK Biobank participants who reported RA (n=5,625) and employed latent class analysis (LCA) to create classes of LTC combinations for those with ≥2 additional LTCs. Cox-proportional hazard and negative binomial regression were used to compare the risk of all-cause mortality, major adverse cardiac events (MACE), and number of emergency hospitalisations over an 11-year follow-up across the different LTC classes and in those with RA plus one additional LTC. Persons with RA without LTCs were the reference group. Analyses were adjusted for demographic characteristics, smoking, BMI, alcohol consumption and physical activity.<h4>Results</h4>A total of 2,566 (46%) participants reported ≥2 LTCs in addition to RA. This involved 1,138 distinct LTC combinations of which 86% were reported by ≤2 individuals. LCA identified 5 morbidity-classes. The distinctive condition in the class with the highest mortality was cancer (class 5; HR 2.66 95%CI (1.91-3.70)). The highest MACE (HR 2.95 95%CI (2.11-4.14)) and emergency hospitalisations (rate ratio 3.01 (2.56-3.54)) were observed in class 3 which comprised asthma, COPD & CHD. There was an increase in mortality, MACE and emergency hospital admissions within each class as the number of LTCs increased.<h4>Conclusions</h4>The risk of adverse health outcomes in RA varied with different patterns of multimorbidity. The pattern of multimorbidity should be considered in risk assessment and formulating management plans in patients with RA.",,doi:https://doi.org/10.1177/26335565221148616; doi:https://doi.org/10.1177/26335565221148616; html:https://europepmc.org/articles/PMC9926377; pdf:https://europepmc.org/articles/PMC9926377?pdf=render
 35756853,https://doi.org/10.1016/j.lanepe.2022.100428,"Impact of COVID-19 pandemic on asthma exacerbations: Retrospective cohort study of over 500,000 patients in a national English primary care database.","Shah SA, Quint JK, Sheikh A.",,The Lancet regional health. Europe,2022,2022-06-15,Y,Asthma; Pandemic; Asthma Exacerbations; Covid-19,,,"<h4>Background</h4>Several countries reported a substantial reduction in asthma exacerbations associated with COVID-19 pandemic-related restrictions. However, it is not known if these early reported declines were short-term and if these have rebounded to pre-pandemic levels following easing of lockdown restrictions.<h4>Methods</h4>We undertook a retrospective, cohort study of all asthma patients in a national primary care database of almost 10 million patients, Optimum Patient Care Database (OPCRD), identified from January 1, 2010, to December 31, 2015, using a previously validated algorithm. We subsequently followed the identified cohort of asthma patients from January 1, 2016, to October 3, 2021, and identified every asthma exacerbation episode with a validated algorithm. To quantify any pandemic-related change in exacerbations, we created a control time-series (mean of 2016-2019) and then compared the change in exacerbation rate in 2020-2021 over quarterly periods when compared with the control period (the pre-pandemic period). We undertook overall and stratified analyses by age group, sex, and English region.<h4>Findings</h4>We identified 100,362 asthma patients (502,669 patient-years) from across England who experienced at least one exacerbation episode (298,390 exacerbation episodes during the entire follow-up). Except for the first quarter of 2020, the exacerbation rates were substantially lower (>25%) during all quarters in 2020-2021 when compared with the rates during 2016-2019 (39.7% (95% Confidence Interval (CI): 34.6, 44.9) in quarter-2, 2020; 46.5% (95%CI: 36.7, 56.4) in quarter-3, 2020; 56.3% (95%CI: 48.7, 63.9) in quarter-4, 2020; 63.2% (95%CI: 53.9, 72.5) in quarter-1, 2021; 57.7% (95%CI: 52.9, 62.4) in quarter-2, 2021; 53.3% (95%CI: 43.8, 62.8) in quarter-3, 2021).<h4>Interpretation</h4>There was a substantial and persistent reduction in asthma exacerbations across England over the first 18 months after the first lockdown. This is unlikely to be adequately explained by changes in health-seeking behaviour, pandemic-related healthcare service disruption, or any air-quality improvements.<h4>Funding</h4>Asthma UK, Health Data Research UK (HDR UK), Medical Research Council (MRC), National Institute for Health Research (NIHR).",,doi:https://doi.org/10.1016/j.lanepe.2022.100428; doi:https://doi.org/10.1016/j.lanepe.2022.100428; html:https://europepmc.org/articles/PMC9213032; pdf:https://europepmc.org/articles/PMC9213032?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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e059813.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059813; html:https://europepmc.org/articles/PMC9461087; pdf:https://europepmc.org/articles/PMC9461087?pdf=render
 32300742,https://doi.org/10.1016/j.eclinm.2020.100296,Violence-related knife injuries in a UK city; epidemiology and impact on secondary care resources.,"Malik NS, Munoz B, de Courcey C, Imran R, Lee KC, Chernbumroong S, Bishop J, Lord JM, Gkoutos G, Bowley DM, Foster MA.",,EClinicalMedicine,2020,2020-03-03,Y,,,,"<h4>Background</h4>The incidence of knife-related injuries is rising across the UK. This study aimed to determine the spectrum of knife-related injuries in a major UK city, with regards to patient and injury characteristics. A secondary aim was to quantify their impact on secondary care resources.<h4>Methods</h4>Observational study of patients aged 16+ years admitted to a major trauma centre following knife-related injuries resulting from interpersonal violence (May 2015 to April 2018). Patients were identified using Emergency Department and discharge coding, blood bank and UK national Trauma Audit and Research prospective registries. Patient and injury characteristics, outcome and resource utilisation were collected from ambulance and hospital records.<h4>Findings</h4>532 patients were identified; 93% male, median age 26 years (IQR 20-35). Median injury severity score was 9 (IQR 3-13). 346 (65%) underwent surgery; 133 (25%) required intensive care; 95 (17·9%) received blood transfusion. Median length of stay was 3·3 days (IQR 1·7-6·0). In-hospital mortality was 10/532 (1·9%). 98 patients (18·5%) had previous attendance with violence-related injuries. 24/37 females (64·9%) were injured in a domestic setting. Intoxication with alcohol (19·2%) and illicit drugs (17·6%) was common. Causative weapon was household knife in 9%, knife (other/unspecified) in 38·0%, machete in 13·9%, small folding blade (2·8%) and, unrecorded in 36·3%.<h4>Interpretation</h4>Knife injuries constitute 12·9% of trauma team workload. Violence recidivism and intoxication are common, and females are predominantly injured in a domestic setting, presenting opportunities for targeted violence reduction interventions. 13·9% of injuries involved machetes, with implications for law enforcement strategies.",,pdf:http://www.thelancet.com/article/S2589537020300407/pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100296; html:https://europepmc.org/articles/PMC7152819; pdf:https://europepmc.org/articles/PMC7152819?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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e059813.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059813; html:https://europepmc.org/articles/PMC9461087; pdf:https://europepmc.org/articles/PMC9461087?pdf=render
 36629285,https://doi.org/10.1093/eurheartj/ehac758,Artificial intelligence to enhance clinical value across the spectrum of cardiovascular healthcare.,"Gill SK, Karwath A, Uh HW, Cardoso VR, Gu Z, Barsky A, Slater L, Acharjee A, Duan J, Dall'Olio L, El Bouhaddani S, Chernbumroong S, Stanbury M, Haynes S, Asselbergs FW, Grobbee DE, Eijkemans MJC, Gkoutos GV, Kotecha D, BigData@Heart Consortium and the cardAIc group.",,European heart journal,2023,2023-03-01,Y,Artificial intelligence; Management; Treatment; Healthcare,,,"Artificial intelligence (AI) is increasingly being utilized in healthcare. This article provides clinicians and researchers with a step-wise foundation for high-value AI that can be applied to a variety of different data modalities. The aim is to improve the transparency and application of AI methods, with the potential to benefit patients in routine cardiovascular care. Following a clear research hypothesis, an AI-based workflow begins with data selection and pre-processing prior to analysis, with the type of data (structured, semi-structured, or unstructured) determining what type of pre-processing steps and machine-learning algorithms are required. Algorithmic and data validation should be performed to ensure the robustness of the chosen methodology, followed by an objective evaluation of performance. Seven case studies are provided to highlight the wide variety of data modalities and clinical questions that can benefit from modern AI techniques, with a focus on applying them to cardiovascular disease management. Despite the growing use of AI, further education for healthcare workers, researchers, and the public are needed to aid understanding of how AI works and to close the existing gap in knowledge. In addition, issues regarding data access, sharing, and security must be addressed to ensure full engagement by patients and the public. The application of AI within healthcare provides an opportunity for clinicians to deliver a more personalized approach to medical care by accounting for confounders, interactions, and the rising prevalence of multi-morbidity.",,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehac758/48602276/ehac758.pdf; doi:https://doi.org/10.1093/eurheartj/ehac758; html:https://europepmc.org/articles/PMC9976986; pdf:https://europepmc.org/articles/PMC9976986?pdf=render
 36750952,https://doi.org/10.1186/s12911-023-02109-3,A multi-granular stacked regression for forecasting long-term demand in Emergency Departments.,"James C, Wood R, Denholm R.",,BMC medical informatics and decision making,2023,2023-02-07,Y,Forecasting; Emergency Department; Machine Learning; Population Health; Service Demand,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Measures of service capacity explain 41 ± 4% of the variance in monthly ED attendances and measures of population health explain 62 ± 22%. The MGSR leads to an overall improvement in performance, with an R-squared of 0.79 ± 0.02 and MAPE of 3% 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 1000 per month after 2 years.<h4>Conclusion</h4>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.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-023-02109-3; doi:https://doi.org/10.1186/s12911-023-02109-3; html:https://europepmc.org/articles/PMC9903450; pdf:https://europepmc.org/articles/PMC9903450?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,,,"<h4>Introduction</h4>We investigated the potential association of COVID-19 vaccination with three acute neurological events: Guillain-Barré syndrome (GBS), transverse myelitis and Bell's palsy.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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; 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
@@ -234,14 +234,14 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/ecco-jcc/article-pdf/14/7/935/33550802/jjaa021.pdf; doi:https://doi.org/10.1093/ecco-jcc/jjaa021; html:https://europepmc.org/articles/PMC7392170; pdf:https://europepmc.org/articles/PMC7392170?pdf=render
 37180154,https://doi.org/10.3389/fimmu.2023.1083072,Real-time assessment of neutrophil metabolism and oxidative burst using extracellular flux analysis.,"Grudzinska FS, Jasper A, Sapey E, Thickett DR, Mauro C, Scott A, Barlow J.",,Frontiers in immunology,2023,2023-04-25,Y,Neutrophils; Oxidative burst; glycolysis; Immunometabolism; Extracellular Flux Analysis,,,"Neutrophil responses are critical during inflammatory and infective events, and neutrophil dysregulation has been associated with poor patient outcomes. Immunometabolism is a rapidly growing field that has provided insights into cellular functions in health and disease. Neutrophils are highly glycolytic when activated, with inhibition of glycolysis associated with functional deficits. There is currently very limited data available assessing metabolism in neutrophils. Extracellular flux (XF) analysis assesses real time oxygen consumption and the rate of proton efflux in cells. This technology allows for the automated addition of inhibitors and stimulants to visualise the effect on metabolism. We describe optimised protocols for an XFe96 XF Analyser to (i) probe glycolysis in neutrophils under basal and stimulated conditions, (ii) probe phorbol 12-myristate 13-acetate induced oxidative burst, and (iii) highlight challenges of using XF technology to examine mitochondrial function in neutrophils. We provide an overview of how to analyze XF data and identify pitfalls of probing neutrophil metabolism with XF analysis. In summary we describe robust methods for assessing glycolysis and oxidative burst in human neutrophils and discuss the challenges around using this technique to assess mitochondrial respiration. XF technology is a powerful platform with a user-friendly interface and data analysis templates, however we suggest caution when assessing neutrophil mitochondrial respiration.",,pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1083072/pdf; doi:https://doi.org/10.3389/fimmu.2023.1083072; html:https://europepmc.org/articles/PMC10166867; pdf:https://europepmc.org/articles/PMC10166867?pdf=render
 37595069,https://doi.org/10.1093/ageing/afad141,Effectiveness of successive booster vaccine doses against SARS-CoV-2 related mortality in residents of long-term care facilities in the VIVALDI study.,"Stirrup O, Shrotri M, Adams NL, Krutikov M, Azmi B, Monakhov I, Tut G, Moss P, Hayward A, Copas A, Shallcross L.",,Age and ageing,2023,2023-08-01,Y,Older People; Vaccine Effectiveness; Long-term Care Facilities; Covid-19; Sars-cov-2; Omicron,,,"<h4>Background</h4>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused severe disease in unvaccinated long-term care facility (LTCF) residents. Initial booster vaccination following primary vaccination is known to provide strong short-term protection, but data are limited on duration of protection and the protective effect of further booster vaccinations.<h4>Objective</h4>To evaluate the effectiveness of third, fourth and fifth dose booster vaccination against SARS-CoV-2 related mortality amongst older residents of LTCFs.<h4>Design</h4>Prospective cohort study.<h4>Setting</h4>LTCFs for older people in England participating in the VIVALDI study.<h4>Methods</h4>Residents aged >65 years at participating LTCFs were eligible for inclusion if they had at least one polymerase chain reaction or lateral flow device result within the analysis period 1 January 2022 to 31 December 2022. We excluded individuals who had not received at least two vaccine doses before the analysis period. Cox regression was used to estimate relative hazards of SARS-CoV-2 related mortality following 1-3 booster vaccinations compared with primary vaccination, stratified by previous SARS-CoV-2 infection and adjusting for age, sex and LTCF size (total beds).<h4>Results</h4>A total of 13,407 residents were included. Our results indicate that third, fourth and fifth dose booster vaccination provide additional short-term protection against SARS-CoV-2 related mortality relative to primary vaccination, with consistent stabilisation beyond 112 days to 45-75% reduction in risk relative to primary vaccination.<h4>Conclusions</h4>Successive booster vaccination doses provide additional short-term protection against SARS-CoV-2 related mortality amongst older LTCF residents. However, we did not find evidence of a longer-term reduction in risk beyond that provided by initial booster vaccination.",,pdf:https://academic.oup.com/ageing/article-pdf/52/8/afad141/51124726/afad141.pdf; doi:https://doi.org/10.1093/ageing/afad141; html:https://europepmc.org/articles/PMC10438206; pdf:https://europepmc.org/articles/PMC10438206?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,,,"<h4>Introduction</h4>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?<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>ISRCTN16230629.",,doi:https://doi.org/10.1136/bmjopen-2023-076296; doi:https://doi.org/10.1136/bmjopen-2023-076296; html:https://europepmc.org/articles/PMC10445367; pdf:https://europepmc.org/articles/PMC10445367?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).",pdf:https://academic.oup.com/ageing/article-pdf/49/5/716/33676968/afaa018.pdf; doi:https://doi.org/10.1093/ageing/afaa018; html:https://europepmc.org/articles/PMC7444666; pdf:https://europepmc.org/articles/PMC7444666?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,,,"<h4>Introduction</h4>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?<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>ISRCTN16230629.",,doi:https://doi.org/10.1136/bmjopen-2023-076296; doi:https://doi.org/10.1136/bmjopen-2023-076296; html:https://europepmc.org/articles/PMC10445367; pdf:https://europepmc.org/articles/PMC10445367?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,,,"<h4>Objectives</h4>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.<h4>Design</h4>Retrospective assessment of routinely collected data from electronic healthcare records.<h4>Setting</h4>Single large urban tertiary care centre.<h4>Participants</h4>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.<h4>Main outcome measures</h4>Sensitivity, specificity, positive and negative predictive value of the Amb score and GAPS in identifying patients discharged within 12 hours of arrival.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e064910.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064910; html:https://europepmc.org/articles/PMC9764605; pdf:https://europepmc.org/articles/PMC9764605?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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>1567490.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e060413.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060413; html:https://europepmc.org/articles/PMC9044550; pdf:https://europepmc.org/articles/PMC9044550?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,,,,,,pdf:https://academic.oup.com/ije/article-pdf/51/5/e245/46495259/dyab243.pdf; doi:https://doi.org/10.1093/ije/dyab243; html:https://europepmc.org/articles/PMC9557859; pdf:https://europepmc.org/articles/PMC9557859?pdf=render
 37678881,https://doi.org/10.1093/ageing/afad157,Survival and critical care use among people with dementia in a large English cohort.,"Yorganci E, Sleeman KE, Sampson EL, Stewart R, EMBED-Care Programme.",,Age and ageing,2023,2023-09-01,Y,Survival; Dementia; Intensive Care; Older People; Critical Care; Routine Data,,,"<h4>Background</h4>Admitting people with dementia to critical care units may not always lead to a clear survival benefit. Critical care admissions of people with dementia vary across countries. Little is known about the use and trends of critical care admissions of people with dementia in England.<h4>Objective</h4>To investigate critical care use and survival among people with dementia in a large London catchment area.<h4>Methods</h4>A retrospective cohort study using data from dementia assessment services in south London, UK (2007-20) linked with national hospitalisation data to ascertain critical care admissions. Outcomes included age-sex-standardised critical care use and 1-year post-critical care admission survival by dementia severity (binary: mild versus moderate/severe). We used logistic regression and Kaplan-Meier survival plots for investigating 1-year survival following a critical care admission and linear regressions for time trends.<h4>Results</h4>Of 19,787 people diagnosed with dementia, 726 (3.7%) had ≥1 critical care admission at any time after receiving their dementia diagnosis. The overall 1-year survival of people with dementia, who had a CCA, was 47.5% (n = 345). Dementia severity was not associated with 1-year survival following a critical care admission (mild dementia versus moderate-severe dementia odds of 1-year mortality OR: 0.90, 95% CI [0.66-1.22]). Over the 12-year period from 2008 to 2019, overall critical care use decreased (β = -0.05; 95% CI = -0.01, -0.0003; P = 0.03), while critical care admissions occurring during the last year of life increased (β = 0.11, 95% CI = 0.01, 0.20, P = 0.03).<h4>Conclusions</h4>In this cohort, while critical care use among people with dementia declined overall, its use increased among those in their last year of life. Survival remains comparable to that observed in general older populations.",,doi:https://doi.org/10.1093/ageing/afad157; html:https://europepmc.org/articles/PMC10484725; pdf:https://europepmc.org/articles/PMC10484725?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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>1567490.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e060413.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060413; html:https://europepmc.org/articles/PMC9044550; pdf:https://europepmc.org/articles/PMC9044550?pdf=render
-37480048,https://doi.org/10.1186/s12872-023-03394-6,"Associations of circulating fatty acids with incident coronary heart disease: a prospective study of 89,242 individuals in UK Biobank.","Jin D, Trichia E, Islam N, Lewington S, Lacey B.",,BMC cardiovascular disorders,2023,2023-07-21,Y,Fatty acids; Lipids; Nuclear magnetic resonance; Coronary Heart Disease; Uk Biobank,,,"<h4>Background</h4>The role of fatty acids in coronary heart disease (CHD) remains uncertain. There is little evidence from large-scale epidemiological studies on the relevance of circulating fatty acids levels to CHD risk. This study aims to examine the independent associations of the major circulating types of fatty acids with CHD risk.<h4>Methods</h4>UK Biobank is a prospective study of adults aged 40-69 in 2006-2010; in 2012-2013, a subset of the participants were resurveyed. Analyses were restricted to 89,242 participants with baseline plasma fatty acids (measured using nuclear magnetic resonance spectroscopy) and without prior CHD. Cox proportional hazards models were used to estimate hazard ratios (HRs) for the associations with incidence CHD, defined as the first-ever myocardial infarction, unstable angina pectoris, coronary-related death, or relevant procedure. And the major types of fatty acids were mutually adjusted to examine the independent associations. Hazard ratios were corrected for regression dilution using the correlation of baseline and resurvey fatty acids measures.<h4>Results</h4>During a median follow-up of 11.8 years, 3,815 incident cases of CHD occurred. Independently of other fatty acids, CHD risk was positively associated with saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA), inversely associated with omega-3 polyunsaturated fatty acids (PUFA), but there was no strong evidence of an association with omega-6 PUFA: HR per standard deviation higher were 1.14 (95% CI, 1.09-1.20), 1.15 (1.10-1.21), 0.91 (0.87-0.94), and 1.04 (0.99-1.09) respectively. Independently of triglycerides and cholesterol, the inverse association with omega-3 PUFA was not materially changed, but the positive associations with SFA and MUFA attenuated to null after adjusting for triglycerides levels.<h4>Conclusions</h4>This large-scale study has quantitated the independent associations of circulating fatty acids with CHD risk. Omega-3 PUFA was inversely related to CHD risk, independently of other fatty acids and major lipid fractions. By contrast, independently of other fatty acids, the positive associations of circulating SFA and MUFA with CHD risk were mostly attributed to their relationship with triglycerides.",,pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-023-03394-6; doi:https://doi.org/10.1186/s12872-023-03394-6; html:https://europepmc.org/articles/PMC10362581; pdf:https://europepmc.org/articles/PMC10362581?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedgenomics.biomedcentral.com/track/pdf/10.1186/s12920-020-00826-6; doi:https://doi.org/10.1186/s12920-020-00826-6; html:https://europepmc.org/articles/PMC7685541; pdf:https://europepmc.org/articles/PMC7685541?pdf=render
+37480048,https://doi.org/10.1186/s12872-023-03394-6,"Associations of circulating fatty acids with incident coronary heart disease: a prospective study of 89,242 individuals in UK Biobank.","Jin D, Trichia E, Islam N, Lewington S, Lacey B.",,BMC cardiovascular disorders,2023,2023-07-21,Y,Fatty acids; Lipids; Nuclear magnetic resonance; Coronary Heart Disease; Uk Biobank,,,"<h4>Background</h4>The role of fatty acids in coronary heart disease (CHD) remains uncertain. There is little evidence from large-scale epidemiological studies on the relevance of circulating fatty acids levels to CHD risk. This study aims to examine the independent associations of the major circulating types of fatty acids with CHD risk.<h4>Methods</h4>UK Biobank is a prospective study of adults aged 40-69 in 2006-2010; in 2012-2013, a subset of the participants were resurveyed. Analyses were restricted to 89,242 participants with baseline plasma fatty acids (measured using nuclear magnetic resonance spectroscopy) and without prior CHD. Cox proportional hazards models were used to estimate hazard ratios (HRs) for the associations with incidence CHD, defined as the first-ever myocardial infarction, unstable angina pectoris, coronary-related death, or relevant procedure. And the major types of fatty acids were mutually adjusted to examine the independent associations. Hazard ratios were corrected for regression dilution using the correlation of baseline and resurvey fatty acids measures.<h4>Results</h4>During a median follow-up of 11.8 years, 3,815 incident cases of CHD occurred. Independently of other fatty acids, CHD risk was positively associated with saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA), inversely associated with omega-3 polyunsaturated fatty acids (PUFA), but there was no strong evidence of an association with omega-6 PUFA: HR per standard deviation higher were 1.14 (95% CI, 1.09-1.20), 1.15 (1.10-1.21), 0.91 (0.87-0.94), and 1.04 (0.99-1.09) respectively. Independently of triglycerides and cholesterol, the inverse association with omega-3 PUFA was not materially changed, but the positive associations with SFA and MUFA attenuated to null after adjusting for triglycerides levels.<h4>Conclusions</h4>This large-scale study has quantitated the independent associations of circulating fatty acids with CHD risk. Omega-3 PUFA was inversely related to CHD risk, independently of other fatty acids and major lipid fractions. By contrast, independently of other fatty acids, the positive associations of circulating SFA and MUFA with CHD risk were mostly attributed to their relationship with triglycerides.",,pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-023-03394-6; doi:https://doi.org/10.1186/s12872-023-03394-6; html:https://europepmc.org/articles/PMC10362581; pdf:https://europepmc.org/articles/PMC10362581?pdf=render
 37674175,https://doi.org/10.1186/s12884-023-05958-y,Using the COM-B framework to elucidate facilitators and barriers to COVID-19 vaccine uptake in pregnant women: a qualitative study.,"Patterson L, Berry E, Parsons C, Clarke B, Little A, Beggs J, Chuter A, Jackson T, Hsia Y, McGrath H, Millman C, Murphy S, Bradley DT, Milligan S.",,BMC pregnancy and childbirth,2023,2023-09-06,Y,Pregnancy; Qualitative; Barriers; Facilitators; Com-b; Covid-19 Vaccination,,,"Since April 2021, COVID-19 vaccines have been recommended for pregnant women. Despite this, COVID-19 vaccine uptake in this group is low compared to the non-pregnant population of childbearing age. Our aim was to understand barriers and facilitators to COVID-19 vaccine uptake among pregnant women in Northern Ireland using the COM-B framework, and so to make recommendations for public health interventions. The COM-B proposes that human behaviour is influenced by the extent to which a person has the capability, opportunity, and motivation to enact that behaviour. Understanding the factors underpinning behaviour through this lens helps discern what needs to change to change behaviour, therefore supporting the development of targeted interventions.This study consisted of eight semi-structured interviews with new/expectant mothers who did not receive a COVID-19 vaccine dose while pregnant since April 2021, and a focus group with five participants who received at least one COVID-19 vaccine dose while pregnant. Interview and focus group data were analysed using semi-deductive reflexive thematic analysis framed by a subtle realist approach. The COM-B was used to categorise codes and subthemes were developed within each COM-B construct.Within Psychological Capability, subthemes captured the need for consistent and reliable COVID-19 vaccine information and access to balanced and jargon-free, risk-benefit information that is tailored to the pregnant individual. The behaviour/opinions of family, friends, and local healthcare providers had a powerful influence on COVID-19 vaccine decisions (Social Opportunity). Integrating the COVID-19 vaccine as part of routine antenatal pathways was believed to support access and sense of familiarity (Physical Opportunity). Participants valued health autonomy, however experienced internal conflict driven by concerns about long-term side effects for their baby (Reflective Motivation). Feelings of fear, lack of empathy from healthcare providers, and anticipated guilt commonly underpinned indecision as to whether to get the vaccine (Automatic Motivation).Our study highlighted that the choice to accept a vaccine during pregnancy generates internal conflict and worry. Several participants cited their concern was primarily around the safety for their baby. Healthcare professionals (HCPs) play a significant part when it comes to decision making about COVID-19 vaccines among pregnant women. HCPs and pregnant women should be involved in the development of interventions to improve the delivery and communication of information.",,pdf:https://bmcpregnancychildbirth.biomedcentral.com/counter/pdf/10.1186/s12884-023-05958-y; doi:https://doi.org/10.1186/s12884-023-05958-y; html:https://europepmc.org/articles/PMC10481472; pdf:https://europepmc.org/articles/PMC10481472?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; 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
 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,Frailty; Older People; Geriatric Medicine; Health Informatics; Electronic Health Record; Home Interventions,Improving Public Health,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/8/10/e026290.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-026290; html:https://europepmc.org/articles/PMC6224723; pdf:https://europepmc.org/articles/PMC6224723?pdf=render
@@ -264,8 +264,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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, <i>N</i> = 98,233), round 14 (9 to 27 September 2021, <i>N</i> = 100,527) and round 15 (19 October to 5 November 2021, <i>N</i> = 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.<h4>Findings</h4>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).<h4>Interpretation</h4>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.<h4>Funding</h4>Department of Health and Social Care, England.",,pdf:http://www.thelancet.com/article/S2589537022001493/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101419; html:https://europepmc.org/articles/PMC9076030; pdf:https://europepmc.org/articles/PMC9076030?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,,,"<h4>Background</h4>This study aimed to predict risks of potentially inappropriate antibiotic type and repeat prescribing and assess changes during COVID-19.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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; 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
 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,,,"<h4>Background</h4>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.<h4>Findings</h4>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.<h4>Conclusions</h4>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).",,pdf:https://academic.oup.com/gigascience/article-pdf/doi/10.1093/gigascience/giad030/50383140/giad030.pdf; doi:https://doi.org/10.1093/gigascience/giad030; html:https://europepmc.org/articles/PMC10176503; pdf:https://europepmc.org/articles/PMC10176503?pdf=render
-37400731,https://doi.org/10.1007/s10802-023-01086-5,Maternal Mental Health and Children's Problem Behaviours: A Bi-directional Relationship?,"Lowthian E, Bedston S, Kristensen SM, Akbari A, Fry R, Huxley K, Johnson R, Kim HS, Owen RK, Taylor C, Griffiths L.",,Research on child and adolescent psychopathology,2023,2023-07-04,Y,Child Development; Bayesian analysis; Structural Equation Modelling; Maternal Mental Health; Millennium Cohort Study,,,"Transactional theory and the coercive family process model have illustrated how the parent-child relationship is reciprocal. Emerging research using advanced statistical methods has examined these theories, but further investigations are necessary. In this study, we utilised linked health data on maternal mental health disorders and explored their relationship with child problem behaviours via the Strengths and Difficulties Questionnaire for over 13 years. We accessed data from the Millennium Cohort Study, linked to anonymised individual-level population-scale health and administrative data within the Secure Anonymised Information Linkage (SAIL) Databank. We used Bayesian Structural Equation Modelling, specifically Random-Intercept Cross-Lagged Panel Models, to analyse the relationships between mothers and their children. We then explored these models with the addition of time-invariant covariates. We found that a mother's mental health was strongly associated over time, as were children's problem behaviours. We found mixed evidence for bi-directional relationships, with only emotional problems showing bi-directional associations in mid to late childhood. Only child-to-mother pathways were identified for the overall problem behaviour score and peer problems; no associations were found for conduct problems or hyperactivity. All models had strong between-effects and clear socioeconomic and sex differences. We encourage the use of whole family-based support for mental health and problem behaviours, and recommend that socioeconomic, sex and wider differences should be considered as factors in tailoring family-based interventions and support.",,pdf:https://link.springer.com/content/pdf/10.1007/s10802-023-01086-5.pdf; doi:https://doi.org/10.1007/s10802-023-01086-5; html:https://europepmc.org/articles/PMC10628040; pdf:https://europepmc.org/articles/PMC10628040?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,,,"<h4>Background</h4>The link between cardiometabolic and psychiatric illness has long been attributed to human behaviour, however recent research highlights shared biological mechanisms. The <i>ASTN2</i> locus has been previously implicated in psychiatric and cardiometabolic traits, therefore this study aimed to systematically investigate the genetic architecture of <i>ASTN2</i> in relation to a wide range of relevant traits.<h4>Methods</h4>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.<h4>Results</h4>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 <i>ASTN2</i>, however most of the other signals are likely acting through other genes in the locus.<h4>Conclusions</h4>Our systematic analysis demonstrates that <i>ASTN2</i> has pleiotropic effects on cardiometabolic and psychiatric traits, rather than contributing to shared pathology.",,pdf:https://www.mdpi.com/2073-4425/12/8/1194/pdf?version=1627984735; doi:https://doi.org/10.3390/genes12081194; html:https://europepmc.org/articles/PMC8391428; pdf:https://europepmc.org/articles/PMC8391428?pdf=render
+37400731,https://doi.org/10.1007/s10802-023-01086-5,Maternal Mental Health and Children's Problem Behaviours: A Bi-directional Relationship?,"Lowthian E, Bedston S, Kristensen SM, Akbari A, Fry R, Huxley K, Johnson R, Kim HS, Owen RK, Taylor C, Griffiths L.",,Research on child and adolescent psychopathology,2023,2023-07-04,Y,Child Development; Bayesian analysis; Structural Equation Modelling; Maternal Mental Health; Millennium Cohort Study,,,"Transactional theory and the coercive family process model have illustrated how the parent-child relationship is reciprocal. Emerging research using advanced statistical methods has examined these theories, but further investigations are necessary. In this study, we utilised linked health data on maternal mental health disorders and explored their relationship with child problem behaviours via the Strengths and Difficulties Questionnaire for over 13 years. We accessed data from the Millennium Cohort Study, linked to anonymised individual-level population-scale health and administrative data within the Secure Anonymised Information Linkage (SAIL) Databank. We used Bayesian Structural Equation Modelling, specifically Random-Intercept Cross-Lagged Panel Models, to analyse the relationships between mothers and their children. We then explored these models with the addition of time-invariant covariates. We found that a mother's mental health was strongly associated over time, as were children's problem behaviours. We found mixed evidence for bi-directional relationships, with only emotional problems showing bi-directional associations in mid to late childhood. Only child-to-mother pathways were identified for the overall problem behaviour score and peer problems; no associations were found for conduct problems or hyperactivity. All models had strong between-effects and clear socioeconomic and sex differences. We encourage the use of whole family-based support for mental health and problem behaviours, and recommend that socioeconomic, sex and wider differences should be considered as factors in tailoring family-based interventions and support.",,pdf:https://link.springer.com/content/pdf/10.1007/s10802-023-01086-5.pdf; doi:https://doi.org/10.1007/s10802-023-01086-5; html:https://europepmc.org/articles/PMC10628040; pdf:https://europepmc.org/articles/PMC10628040?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,,,"<h4>Background</h4>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.<h4>Aim</h4>To describe cancer incidence for four common cancers (breast, lung, colorectal and prostate).<h4>Methods</h4>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).<h4>Results</h4>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), <i>p</i> = 0.0005, and MSWM compared with MSEW, 1.43 (1.03-1.99), <i>p</i> = 0.031; after adjustment for smoking, this difference was no longer significant.<h4>Conclusions</h4>Sexual minority groups have a higher risk for lung cancer, due to greater exposure to smoking.",,pdf:https://www.mdpi.com/2072-6694/15/7/2031/pdf?version=1680080044; doi:https://doi.org/10.3390/cancers15072031; html:https://europepmc.org/articles/PMC10093616; pdf:https://europepmc.org/articles/PMC10093616?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,,,,"<h4>Objective</h4>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.<h4>Design and outcome measures</h4>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.<h4>Setting</h4>Four UK centres in London, North England, Scotland and Wales (23 university partners), 2013-2018.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://ijpds.org/article/download/1128/2865; doi:https://doi.org/10.23889/ijpds.v5i1.1128; html:https://europepmc.org/articles/PMC7480324; pdf:https://europepmc.org/articles/PMC7480324?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.",,pdf:https://www.mdpi.com/2218-1989/12/4/276/pdf?version=1647939572; doi:https://doi.org/10.3390/metabo12040276; html:https://europepmc.org/articles/PMC9031427; pdf:https://europepmc.org/articles/PMC9031427?pdf=render
@@ -275,13 +275,13 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 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,,,,"<h4>Objective</h4>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.<h4>Research design and methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://diabetesjournals.org/care/article-pdf/46/5/967/702262/dc221238.pdf; doi:https://doi.org/10.2337/dc22-1238; html:https://europepmc.org/articles/PMC10154665; pdf:https://europepmc.org/articles/PMC10154665?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,,,"<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://link.springer.com/content/pdf/10.1007/s00394-020-02372-4.pdf; doi:https://doi.org/10.1007/s00394-020-02372-4; html:https://europepmc.org/articles/PMC7449523; pdf:https://europepmc.org/articles/PMC7449523?pdf=render
 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
-37795045,https://doi.org/10.1177/26320843221147855,Monitoring metrics over time: Why clinical trialists need to systematically collect site performance metrics.,"Yorke-Edwards V, Diaz-Montana C, Murray ML, Sydes MR, Love SB.",,Research methods in medicine & health sciences,2023,2022-12-21,N,Clinical Trials; Risk-based Monitoring; Central Monitoring; Centralised Monitoring; Study-Within-A-Trial (Swat),,,"<h4>Background</h4>Over the last decade, there has been an increasing interest in risk-based monitoring (RBM) in clinical trials, resulting in a number of guidelines from regulators and its inclusion in ICH GCP. However, there is a lack of detail on how to approach RBM from a practical perspective, and insufficient understanding of best practice.<h4>Purpose</h4>We present a method for clinical trials units to track their metrics within clinical trials using descriptive statistics and visualisations.<h4>Research design</h4>We suggest descriptive statistics and visualisations within a SWAT methodology.<h4>Study sample</h4>We illustrate this method using the metrics from TEMPER, a monitoring study carried out in three trials at the MRC Clinical Trials Unit at UCL.<h4>Data collection</h4>The data collection for TEMPER is described in <i>DOI: 10.1177/1740774518793379</i>.<h4>Results</h4>We show the results and discuss a protocol for a Study-Within-A-Trial (SWAT 167) for those wishing to use the method.<h4>Conclusions</h4>The potential benefits metric tracking brings to clinical trials include enhanced assessment of sites for potential corrective action, improved evaluation and contextualisation of the influence of metrics and their thresholds, and the establishment of best practice in RBM. The standardisation of the collection of such monitoring data would benefit both individual trials and the clinical trials community.",,doi:https://doi.org/10.1177/26320843221147855; html:https://europepmc.org/articles/PMC7615148; pdf:https://europepmc.org/articles/PMC7615148?pdf=render; doi:https://doi.org/10.1177/26320843221147855
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity ± T2D (<i>n</i> = 80, T2D = 42) with participants who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (pre and 3-months post-surgery; <i>n</i> = 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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://www.nature.com/articles/s43856-022-00185-6.pdf; doi:https://doi.org/10.1038/s43856-022-00185-6; html:https://europepmc.org/articles/PMC9546886; pdf:https://europepmc.org/articles/PMC9546886?pdf=render
+37795045,https://doi.org/10.1177/26320843221147855,Monitoring metrics over time: Why clinical trialists need to systematically collect site performance metrics.,"Yorke-Edwards V, Diaz-Montana C, Murray ML, Sydes MR, Love SB.",,Research methods in medicine & health sciences,2023,2022-12-21,N,Clinical Trials; Risk-based Monitoring; Central Monitoring; Centralised Monitoring; Study-Within-A-Trial (Swat),,,"<h4>Background</h4>Over the last decade, there has been an increasing interest in risk-based monitoring (RBM) in clinical trials, resulting in a number of guidelines from regulators and its inclusion in ICH GCP. However, there is a lack of detail on how to approach RBM from a practical perspective, and insufficient understanding of best practice.<h4>Purpose</h4>We present a method for clinical trials units to track their metrics within clinical trials using descriptive statistics and visualisations.<h4>Research design</h4>We suggest descriptive statistics and visualisations within a SWAT methodology.<h4>Study sample</h4>We illustrate this method using the metrics from TEMPER, a monitoring study carried out in three trials at the MRC Clinical Trials Unit at UCL.<h4>Data collection</h4>The data collection for TEMPER is described in <i>DOI: 10.1177/1740774518793379</i>.<h4>Results</h4>We show the results and discuss a protocol for a Study-Within-A-Trial (SWAT 167) for those wishing to use the method.<h4>Conclusions</h4>The potential benefits metric tracking brings to clinical trials include enhanced assessment of sites for potential corrective action, improved evaluation and contextualisation of the influence of metrics and their thresholds, and the establishment of best practice in RBM. The standardisation of the collection of such monitoring data would benefit both individual trials and the clinical trials community.",,doi:https://doi.org/10.1177/26320843221147855; html:https://europepmc.org/articles/PMC7615148; pdf:https://europepmc.org/articles/PMC7615148?pdf=render; doi:https://doi.org/10.1177/26320843221147855
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0280943&type=printable; doi:https://doi.org/10.1371/journal.pone.0280943; html:https://europepmc.org/articles/PMC9879384; pdf:https://europepmc.org/articles/PMC9879384?pdf=render
-37798357,https://doi.org/10.1038/s41598-023-42331-7,"An angiopoietin 2, FGF23, and BMP10 biomarker signature differentiates atrial fibrillation from other concomitant cardiovascular conditions.","Chua W, Cardoso VR, Guasch E, Sinner MF, Al-Taie C, Brady P, Casadei B, Crijns HJGM, Dudink EAMP, Hatem SN, Kääb S, Kastner P, Mont L, Nehaj F, Purmah Y, Reyat JS, Schotten U, Sommerfeld LC, Zeemering S, Ziegler A, Gkoutos GV, Kirchhof P, Fabritz L.",,Scientific reports,2023,2023-10-05,Y,,,,"Early detection of atrial fibrillation (AF) enables initiation of anticoagulation and early rhythm control therapy to reduce stroke, cardiovascular death, and heart failure. In a cross-sectional, observational study, we aimed to identify a combination of circulating biomolecules reflecting different biological processes to detect prevalent AF in patients with cardiovascular conditions presenting to hospital. Twelve biomarkers identified by reviewing literature and patents were quantified on a high-precision, high-throughput platform in 1485 consecutive patients with cardiovascular conditions (median age 69 years [Q1, Q3 60, 78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. Logistic regression with backward elimination and a neural network approach considering 7 key clinical characteristics and 12 biomarker concentrations were applied to a randomly sampled discovery cohort (n = 933) and validated in the remaining patients (n = 552). In addition to age, sex, and body mass index (BMI), BMP10, ANGPT2, and FGF23 identified patients with prevalent AF (AUC 0.743 [95% CI 0.712, 0.775]). These circulating biomolecules represent distinct pathways associated with atrial cardiomyopathy and AF. Neural networks identified the same variables as the regression-based approach. The validation using regression yielded an AUC of 0.719 (95% CI 0.677, 0.762), corroborated using deep neural networks (AUC 0.784 [95% CI 0.745, 0.822]). Age, sex, BMI and three circulating biomolecules (BMP10, ANGPT2, FGF23) are associated with prevalent AF in unselected patients presenting to hospital. Findings should be externally validated. Results suggest that age and different disease processes approximated by these three biomolecules contribute to AF in patients. Our findings have the potential to improve screening programs for AF after external validation.",,pdf:https://www.nature.com/articles/s41598-023-42331-7.pdf; doi:https://doi.org/10.1038/s41598-023-42331-7; html:https://europepmc.org/articles/PMC10556075; pdf:https://europepmc.org/articles/PMC10556075?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,Experimental design; Gene Regulatory Network; Causal Modelling; Omics Integration,,,"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 <i>UGT1A</i> family genes were identified as key regulators while upon analysing the PDAC dataset, the <i>SULF1</i> and <i>THBS2</i> 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.",,pdf:https://www.mdpi.com/1422-0067/21/21/7886/pdf?version=1604329387; doi:https://doi.org/10.3390/ijms21217886; html:https://europepmc.org/articles/PMC7660606; pdf:https://europepmc.org/articles/PMC7660606?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,,,"<h4>Introduction</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>There was agreement between admission and discharge codes. When more than ten coding fields were used the misclassification rate was less than 1%.<h4>Conclusion</h4>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.",,pdf:https://ijpds.org/article/download/1373/3264; doi:https://doi.org/10.23889/ijpds.v6i1.1373; html:https://europepmc.org/articles/PMC8103565; pdf:https://europepmc.org/articles/PMC8103565?pdf=render
+37798357,https://doi.org/10.1038/s41598-023-42331-7,"An angiopoietin 2, FGF23, and BMP10 biomarker signature differentiates atrial fibrillation from other concomitant cardiovascular conditions.","Chua W, Cardoso VR, Guasch E, Sinner MF, Al-Taie C, Brady P, Casadei B, Crijns HJGM, Dudink EAMP, Hatem SN, Kääb S, Kastner P, Mont L, Nehaj F, Purmah Y, Reyat JS, Schotten U, Sommerfeld LC, Zeemering S, Ziegler A, Gkoutos GV, Kirchhof P, Fabritz L.",,Scientific reports,2023,2023-10-05,Y,,,,"Early detection of atrial fibrillation (AF) enables initiation of anticoagulation and early rhythm control therapy to reduce stroke, cardiovascular death, and heart failure. In a cross-sectional, observational study, we aimed to identify a combination of circulating biomolecules reflecting different biological processes to detect prevalent AF in patients with cardiovascular conditions presenting to hospital. Twelve biomarkers identified by reviewing literature and patents were quantified on a high-precision, high-throughput platform in 1485 consecutive patients with cardiovascular conditions (median age 69 years [Q1, Q3 60, 78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. Logistic regression with backward elimination and a neural network approach considering 7 key clinical characteristics and 12 biomarker concentrations were applied to a randomly sampled discovery cohort (n = 933) and validated in the remaining patients (n = 552). In addition to age, sex, and body mass index (BMI), BMP10, ANGPT2, and FGF23 identified patients with prevalent AF (AUC 0.743 [95% CI 0.712, 0.775]). These circulating biomolecules represent distinct pathways associated with atrial cardiomyopathy and AF. Neural networks identified the same variables as the regression-based approach. The validation using regression yielded an AUC of 0.719 (95% CI 0.677, 0.762), corroborated using deep neural networks (AUC 0.784 [95% CI 0.745, 0.822]). Age, sex, BMI and three circulating biomolecules (BMP10, ANGPT2, FGF23) are associated with prevalent AF in unselected patients presenting to hospital. Findings should be externally validated. Results suggest that age and different disease processes approximated by these three biomolecules contribute to AF in patients. Our findings have the potential to improve screening programs for AF after external validation.",,pdf:https://www.nature.com/articles/s41598-023-42331-7.pdf; doi:https://doi.org/10.1038/s41598-023-42331-7; html:https://europepmc.org/articles/PMC10556075; pdf:https://europepmc.org/articles/PMC10556075?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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3267; doi:https://doi.org/10.1002/cnm.3267; html:https://europepmc.org/articles/PMC9286682; pdf:https://europepmc.org/articles/PMC9286682?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,,,"<h4>Introduction</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>There was agreement between admission and discharge codes. When more than ten coding fields were used the misclassification rate was less than 1%.<h4>Conclusion</h4>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.",,pdf:https://ijpds.org/article/download/1373/3264; doi:https://doi.org/10.23889/ijpds.v6i1.1373; html:https://europepmc.org/articles/PMC8103565; pdf:https://europepmc.org/articles/PMC8103565?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,,,,"<h4>Background</h4>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 [SpO<sub>2</sub>]) and RECAP-oxygen saturation score (RECAP-O2; with SpO<sub>2</sub>).<h4>Methods</h4>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.<h4>Findings</h4>Data were available from 8311 individuals. Observations, such as SpO<sub>2</sub>, were mostly missing in the northwest London, RCGP-RSC, and CCAS data; however, SpO<sub>2</sub> 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 SpO<sub>2</sub> 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).<h4>Interpretation</h4>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 SpO<sub>2</sub> is available, RECAP-O2 is useful to assess the need for treatment escalation.<h4>Funding</h4>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; 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
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-16202-9; doi:https://doi.org/10.1186/s12889-023-16202-9; html:https://europepmc.org/articles/PMC10326925; pdf:https://europepmc.org/articles/PMC10326925?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",,,"<h4>Background</h4>Cancer survivors have a higher risk for developing cardiovascular diseases than the general population.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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; 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
@@ -301,8 +301,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform,"Zheng B, Tazare J, Nab L, Green A, Curtis H, Mahalingasivam V, Herrett E, Costello R, Eggo R, Speed V, Bacon S, Bates C, Parry J, Cockburn J, Hester F, Harper S, Schaffer A, Hulme W, Mehrkar A, Evans S, MacKenna B, Goldacre B, Douglas I, Tomlinson L.",,The Lancet regional health. Europe,2023,2023-10-08,Y,Comparative Effectiveness; Real-world Data; Covid-19; Sotrovimab; Paxlovid,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624988/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624988/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC10624988; pdf:https://europepmc.org/articles/PMC10624988?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.",,pdf:https://www.mdpi.com/2076-393X/11/3/604/pdf?version=1678670919; doi:https://doi.org/10.3390/vaccines11030604; html:https://europepmc.org/articles/PMC10055803; pdf:https://europepmc.org/articles/PMC10055803?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02877-9; doi:https://doi.org/10.1186/s12916-023-02877-9; html:https://europepmc.org/articles/PMC10283271; pdf:https://europepmc.org/articles/PMC10283271?pdf=render
-35567479,https://doi.org/10.1093/rheumatology/keac283,Shielding reduced incidence of COVID-19 in patients with inflammatory arthritis but vulnerability is associated with increased mortality.,"Cooksey R, Underwood J, Brophy S, Atkinson M, Kennedy J, Choy E.",,"Rheumatology (Oxford, England)",2022,2022-06-01,Y,RA; As; PSA; Electronic Health Records; Covid-19; Inflammatory Arthritis,,,"<h4>Objectives</h4>Investigate whether individuals with inflammatory arthritis (IA), their treatments and shielding status affect the risk of adverse outcomes from COVID-19 for the entire population of Wales, UK.<h4>Methods</h4>Retrospective, population-based cohort study using linked, anonymized electronic health data from SAIL Databank, including primary/secondary care, rheumatology, Office for National Statistics Mortality and COVID-19 laboratory data. Individuals aged 18 years and over testing positive for COVID-19 between March 2020 and May 2021 with READ Codes present for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis formed the study cases.<h4>Results</h4>A total of 1966 people with IA and 166 602 without tested positive for COVID-19. The incidence rate was 3.5% (1966/56 914) in IA, vs 6% in the general population (166 602/2 760 442), (difference: 2.5%, 95% CI: 2.4%, 2.7%, P ≤0.001). In an adjusted Cox proportional hazard model, IA was not associated with higher mortality (HR: 0.56, 95% CI: 0.18, 1.64, P=0.286). Significant risk factors included shielding (HR: 1.52, 95% CI: 1.40, 1.64, P ≤0.001), hospitalization for previous infections (HR: 1.20, 95% CI: 1.12, 1.28, P ≤0.001), hospitalizations one year pre-pandemic (HR: 1.34, 95% CI: 1.25, 1.44, P ≤0.001) and glucocorticoid use (HR: 1.17, 95% CI: 1.09, 1.25, P ≤0.001).<h4>Conclusions</h4>Individuals with IA had a lower incidence of COVID-19, probably due to shielding. IA was not associated with increased mortality following COVID-19 infection; being vulnerable (shielded), comorbidities and other factors were associated with increased risk. These key risk factors can identify individuals with IA at greater risk from COVID-19 and advised to shield during high community prevalence.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62372/Download/62372__26337__5539f4f995224d80a2156218d11a03cb.pdf; doi:https://doi.org/10.1093/rheumatology/keac283; html:https://europepmc.org/articles/PMC9248059; pdf:https://europepmc.org/articles/PMC9248059?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),,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/6/e039097.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-039097; html:https://europepmc.org/articles/PMC7311023; pdf:https://europepmc.org/articles/PMC7311023?pdf=render
+35567479,https://doi.org/10.1093/rheumatology/keac283,Shielding reduced incidence of COVID-19 in patients with inflammatory arthritis but vulnerability is associated with increased mortality.,"Cooksey R, Underwood J, Brophy S, Atkinson M, Kennedy J, Choy E.",,"Rheumatology (Oxford, England)",2022,2022-06-01,Y,RA; As; PSA; Electronic Health Records; Covid-19; Inflammatory Arthritis,,,"<h4>Objectives</h4>Investigate whether individuals with inflammatory arthritis (IA), their treatments and shielding status affect the risk of adverse outcomes from COVID-19 for the entire population of Wales, UK.<h4>Methods</h4>Retrospective, population-based cohort study using linked, anonymized electronic health data from SAIL Databank, including primary/secondary care, rheumatology, Office for National Statistics Mortality and COVID-19 laboratory data. Individuals aged 18 years and over testing positive for COVID-19 between March 2020 and May 2021 with READ Codes present for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis formed the study cases.<h4>Results</h4>A total of 1966 people with IA and 166 602 without tested positive for COVID-19. The incidence rate was 3.5% (1966/56 914) in IA, vs 6% in the general population (166 602/2 760 442), (difference: 2.5%, 95% CI: 2.4%, 2.7%, P ≤0.001). In an adjusted Cox proportional hazard model, IA was not associated with higher mortality (HR: 0.56, 95% CI: 0.18, 1.64, P=0.286). Significant risk factors included shielding (HR: 1.52, 95% CI: 1.40, 1.64, P ≤0.001), hospitalization for previous infections (HR: 1.20, 95% CI: 1.12, 1.28, P ≤0.001), hospitalizations one year pre-pandemic (HR: 1.34, 95% CI: 1.25, 1.44, P ≤0.001) and glucocorticoid use (HR: 1.17, 95% CI: 1.09, 1.25, P ≤0.001).<h4>Conclusions</h4>Individuals with IA had a lower incidence of COVID-19, probably due to shielding. IA was not associated with increased mortality following COVID-19 infection; being vulnerable (shielded), comorbidities and other factors were associated with increased risk. These key risk factors can identify individuals with IA at greater risk from COVID-19 and advised to shield during high community prevalence.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62372/Download/62372__26337__5539f4f995224d80a2156218d11a03cb.pdf; doi:https://doi.org/10.1093/rheumatology/keac283; html:https://europepmc.org/articles/PMC9248059; pdf:https://europepmc.org/articles/PMC9248059?pdf=render
 36529825,https://doi.org/10.1007/s40258-022-00777-2,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,2023,2022-12-18,Y,,,,"<h4>Background</h4>It is a stated ambition of many healthcare systems to eliminate delayed transfers of care (DTOCs) between acute and step-down community services.<h4>Objective</h4>This study aims to demonstrate how, counter to intuition, pursual of such a policy is likely to be uneconomical, as it would require large amounts of community capacity to accommodate even the rarest of demand peaks, leaving much capacity unused for much of the time.<h4>Methods</h4>Some standard results from queueing theory-a mathematical discipline for considering the dynamics of queues and queueing systems-are used to provide a model of patient flow from the acute to community setting. While queueing models have a track record of application in healthcare, they have not before been used to address this question.<h4>Results</h4>Results show that 'eliminating' DTOCs is a false economy: the additional community costs required are greater than the possible acute cost saving. While a substantial proportion of DTOCs can be attributed to inefficient use of resources, the remainder can be considered economically essential to ensuring cost-efficient service operation. For England's National Health Service (NHS), our modelling estimates annual cost savings of £117m if DTOCs are reduced to the 12% of current levels that can be regarded as economically essential.<h4>Conclusion</h4>This study discourages the use of 'zero DTOC' targets and instead supports an assessment based on the specific characteristics of the healthcare system considered.",,doi:https://doi.org/10.1007/s40258-022-00777-2; html:https://europepmc.org/articles/PMC9760184; pdf:https://europepmc.org/articles/PMC9760184?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s40258-022-00777-2.pdf
 36857859,https://doi.org/10.1016/j.ebiom.2023.104489,"Identifying subtypes of chronic kidney disease with machine learning: development, internal validation and prognostic validation using linked electronic health records in 350,067 individuals.","Dashtban A, Mizani MA, Pasea L, Denaxas S, Corbett R, Mamza JB, Gao H, Morris T, Hemingway H, Banerjee A.",,EBioMedicine,2023,2023-02-27,Y,Cluster analysis; Survival analysis; Machine Learning; Unsupervised Clustering; Ckd Subtype,,,"<h4>Background</h4>Although chronic kidney disease (CKD) is associated with high multimorbidity, polypharmacy, morbidity and mortality, existing classification systems (mild to severe, usually based on estimated glomerular filtration rate, proteinuria or urine albumin-creatinine ratio) and risk prediction models largely ignore the complexity of CKD, its risk factors and its outcomes. Improved subtype definition could improve prediction of outcomes and inform effective interventions.<h4>Methods</h4>We analysed individuals ≥18 years with incident and prevalent CKD (n = 350,067 and 195,422 respectively) from a population-based electronic health record resource (2006-2020; Clinical Practice Research Datalink, CPRD). We included factors (n = 264 with 2670 derived variables), e.g. demography, history, examination, blood laboratory values and medications. Using a published framework, we identified subtypes through seven unsupervised machine learning (ML) methods (K-means, Diana, HC, Fanny, PAM, Clara, Model-based) with 66 (of 2670) variables in each dataset. We evaluated subtypes for: (i) internal validity (within dataset, across methods); (ii) prognostic validity (predictive accuracy for 5-year all-cause mortality and admissions); and (iii) medications (new and existing by British National Formulary chapter).<h4>Findings</h4>After identifying five clusters across seven approaches, we labelled CKD subtypes: 1. Early-onset, 2. Late-onset, 3. Cancer, 4. Metabolic, and 5. Cardiometabolic. Internal validity: We trained a high performing model (using XGBoost) that could predict disease subtypes with 95% accuracy for incident and prevalent CKD (Sensitivity: 0.81-0.98, F1 score:0.84-0.97). Prognostic validity: 5-year all-cause mortality, hospital admissions, and incidence of new chronic diseases differed across CKD subtypes. The 5-year risk of mortality and admissions in the overall incident CKD population were highest in cardiometabolic subtype: 43.3% (42.3-42.8%) and 29.5% (29.1-30.0%), respectively, and lowest in the early-onset subtype: 5.7% (5.5-5.9%) and 18.7% (18.4-19.1%).<h4>Medications</h4>Across CKD subtypes, the distribution of prescription medication classes at baseline varied, with highest medication burden in cardiometabolic and metabolic subtypes, and higher burden in prevalent than incident CKD.<h4>Interpretation</h4>In the largest CKD study using ML, to-date, we identified five distinct subtypes in individuals with incident and prevalent CKD. These subtypes have relevance to study of aetiology, therapeutics and risk prediction.<h4>Funding</h4>AstraZeneca UK Ltd, Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2352396423000543/pdf; doi:https://doi.org/10.1016/j.ebiom.2023.104489; html:https://europepmc.org/articles/PMC9989643; pdf:https://europepmc.org/articles/PMC9989643?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.",,pdf:https://www.nature.com/articles/s41467-022-29521-z.pdf; doi:https://doi.org/10.1038/s41467-022-29521-z; html:https://europepmc.org/articles/PMC9005552; pdf:https://europepmc.org/articles/PMC9005552?pdf=render
@@ -325,23 +325,23 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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).<h4>Interpretation</h4>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.<h4>Funding</h4>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; doi:https://doi.org/10.1016/S2589-7500(21)00105-9; html:https://europepmc.org/articles/PMC8257056
 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.",,pdf:https://www.rcpjournals.org/content/clinmedicine/21/6/e620.full.pdf; 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
 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.",,pdf:http://www.cell.com/article/S2666389922000514/pdf; doi:https://doi.org/10.1016/j.patter.2022.100471; html:https://europepmc.org/articles/PMC9122960; pdf:https://europepmc.org/articles/PMC9122960?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 (P<sub>interaction</sub> < 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).<h4>Conclusions</h4>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.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02921-8; doi:https://doi.org/10.1186/s12916-023-02921-8; html:https://europepmc.org/articles/PMC10280894; pdf:https://europepmc.org/articles/PMC10280894?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,,,"<h4>Aims/objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/20552076211007661; doi:https://doi.org/10.1177/20552076211007661; html:https://europepmc.org/articles/PMC8054217; pdf:https://europepmc.org/articles/PMC8054217?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 (P<sub>interaction</sub> < 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).<h4>Conclusions</h4>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.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02921-8; doi:https://doi.org/10.1186/s12916-023-02921-8; html:https://europepmc.org/articles/PMC10280894; pdf:https://europepmc.org/articles/PMC10280894?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%.<h4>Conclusions</h4>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.",,pdf:https://openheart.bmj.com/content/openhrt/9/2/e002142.full.pdf; doi:https://doi.org/10.1136/openhrt-2022-002142; html:https://europepmc.org/articles/PMC9639145; pdf:https://europepmc.org/articles/PMC9639145?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>LSHTM COVID-19 Response Grant (DONAT15912).",,pdf:http://www.thelancet.com/article/S2589537023002547/pdf; doi:https://doi.org/10.1016/j.eclinm.2023.102077; html:https://europepmc.org/articles/PMC10331810; pdf:https://europepmc.org/articles/PMC10331810?pdf=render
 32989456,https://doi.org/10.1093/ije/dyaa144,Emulating a target trial in case-control designs: an application to statins and colorectal cancer.,"Dickerman BA, García-Albéniz X, Logan RW, Denaxas S, Hernán MA.",,International journal of epidemiology,2020,2020-10-01,N,Causal Inference; Electronic Health Records; Case-control; Comparative Effectiveness; Target Trial,,,"<h4>Background</h4>Previous case-control studies have reported a strong association between statin use and lower cancer risk. It is unclear whether this association reflects a benefit of statins or is the result of design decisions that cannot be mapped to a (hypothetical) target trial (that would answer the question of interest).<h4>Methods</h4>We outlined the protocol of a target trial to estimate the effect of statins on colorectal cancer incidence among adults with low-density lipoprotein (LDL) cholesterol below 5 mmol/L. We then emulated the target trial using linked electronic health records of 752 469 eligible UK adults (CALIBER 1999-2016) under both a cohort design and a case-control sampling of the cohort. We used pooled logistic regression to estimate intention-to-treat and per-protocol effects of statins on colorectal cancer, with adjustment for baseline and time-varying risk factors via inverse-probability weighting. Finally, we compared our case-control effect estimates with those obtained using previous case-control procedures.<h4>Results</h4>Over the 6-year follow-up, 3596 individuals developed colorectal cancer. Estimated intention-to-treat and per-protocol hazard ratios were 1.00 (95% confidence interval [CI]: 0.87, 1.16) and 0.90 (95% CI: 0.71, 1.12), respectively. As expected, adequate case-control sampling yielded the same estimates. By contrast, previous case-control analytical approaches yielded estimates that appeared strongly protective (odds ratio 0.57, 95% CI: 0.36, 0.91, for ≥5 vs. <5 years of statin use).<h4>Conclusions</h4>Our study demonstrates how to explicitly emulate a target trial using case-control data to reduce discrepancies between observational and randomized trial evidence. This approach may inform future case-control analyses for comparative effectiveness research.",,pdf:https://academic.oup.com/ije/article-pdf/49/5/1637/34947124/dyaa144.pdf; doi:https://doi.org/10.1093/ije/dyaa144; html:https://europepmc.org/articles/PMC7746409; pdf:https://europepmc.org/articles/PMC7746409?pdf=render; doi:https://doi.org/10.1093/ije/dyaa144
 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
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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; <i>P</i> = .006], hospitalization [incidence rate ratio (IRR) 1.13; 95% CI 1.03, 1.25; <i>P</i> = .010] and lower quality of life (Coef. -0.401; 95% CI -0.511, -0.292; <i>P</i> < .001). PHQ-9 score was independently associated with lower quality of life (Coef. -0.042; 95% CI -0.063, -0.021; <i>P</i> < .001), but not mortality (HR 1.00; 95% CI 0.96, 1.04; <i>P</i> = .901) or hospitalization (IRR 0.99; 95% CI 0.97, 1.01; <i>P</i> = .351). In an adjusted model including CFS, moderate depression was associated with reduced hospitalization (IRR 0.72; 95% CI 0.56, 0.93; <i>P</i> = .013).<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/ckj/article-pdf/16/2/342/49100412/sfac241.pdf; doi:https://doi.org/10.1093/ckj/sfac241; html:https://europepmc.org/articles/PMC9900564; pdf:https://europepmc.org/articles/PMC9900564?pdf=render
-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,,,,"<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003777&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003777; html:https://europepmc.org/articles/PMC8478234; pdf:https://europepmc.org/articles/PMC8478234?pdf=render
 32341912,https://doi.org/10.1177/2235042x19893470,Urban-rural and socioeconomic status: Impact on multimorbidity prevalence in hospitalized patients.,"Robertson L, Ayansina D, Johnston M, Marks A, Black C.",,Journal of comorbidity,2020,2020-01-01,Y,Prevalence; Socioeconomic status; Hospitalization; Electronic Health Records; Multimorbidity; Urban–rural,,,"<h4>Objective</h4>The aim of this study was to describe multimorbidity prevalence in hospitalized adults, by urban-rural area of residence and socioeconomic status (SES).<h4>Methods</h4>Linked hospital episode data were used. Adults (≥18 years) admitted to hospital as an inpatient during 2014 in Grampian, Scotland, were included. Conditions were identified from admissions during the 5 years prior to the first admission in 2014. Multimorbidity was defined as ≥2 conditions and measured using Tonelli et al. based on International Classification of Diseases-10 coding (preselected list of 30 conditions). We used proportions and 95% confidence intervals (CIs) to summarize the prevalence of multimorbidity by age group, sex, urban-rural category and deprivation. The association between multimorbidity and patient characteristics was assessed using the <i>χ</i> <sup>2</sup> test.<h4>Results</h4>Forty one thousand five hundred and forty-five patients were included (median age 62, 52.6% female). Overall, 27.4% (95% CI 27.0, 27.8) of patients were multimorbid. Multimorbidity prevalence was 28.8% (95% CI 28.1, 29.5) in large urban versus 22.0% (95% CI 20.9, 23.3) in remote rural areas and 28.7% (95% CI 27.2, 30.3) in the most deprived versus 26.0% (95% CI 25.2, 26.9) in the least deprived areas. This effect was consistent in all age groups, but not statistically significant in the age group 18-29 years. Multimorbidity increased with age but was similar for males and females.<h4>Conclusion</h4>Given the scarcity of research into the effect of urban-rural area and SES on multimorbidity prevalence among hospitalized patients, these findings should inform future research into new models of care, including the consideration of urban-rural area and SES.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/2235042X19893470; doi:https://doi.org/10.1177/2235042X19893470; html:https://europepmc.org/articles/PMC7171988; pdf:https://europepmc.org/articles/PMC7171988?pdf=render
+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,,,,"<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003777&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003777; html:https://europepmc.org/articles/PMC8478234; pdf:https://europepmc.org/articles/PMC8478234?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/63FA124CF816896E02CAEE14215D590E/S0924933822023240a.pdf/div-class-title-cardiac-surgery-receipt-and-outcomes-for-people-using-secondary-mental-health-care-services-retrospective-cohort-study-using-a-large-mental-healthcare-database-in-south-london-div.pdf; doi:https://doi.org/10.1192/j.eurpsy.2022.2324; html:https://europepmc.org/articles/PMC9677442; pdf:https://europepmc.org/articles/PMC9677442?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,,,"<h4>Background</h4>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.<h4>Aim</h4>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.<h4>Design and setting</h4>With the approval of NHS England, a cohort study was conducted of 23.8 million patient records in general practice, in situ using OpenSAFELY.<h4>Method</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.",,pdf:https://bjgp.org/content/bjgp/early/2023/01/31/BJGP.2022.0301.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0301; html:https://europepmc.org/articles/PMC10131234; pdf:https://europepmc.org/articles/PMC10131234?pdf=render
 35079067,https://doi.org/10.1038/s41598-022-05414-5,Asthma in paediatric intensive care in England residents: observational study.,"Mukherjee M, Cunningham S, Bhuia MR, Lo TM, Been JV, Sheikh A.",,Scientific reports,2022,2022-01-25,Y,,,,"Despite high prevalence of asthma in children in the UK, there were no prior report on asthma admissions in paediatric intensive care units (PICU). We investigated the epidemiology and healthcare resource utilisation in children with asthma presenting to PICUs in England. PICANet, a UK national PICU database, was queried for asthma as the primary reason for admission, of children resident in England from April 2006 until March 2013. There were 2195 admissions to PICU for a median stay of 1.4 days. 59% were males and 51% aged 0-4 years. The fourth and fifth most deprived quintiles represented 61% (1329) admissions and 73% (11) of the 15 deaths. Deaths were most frequent in 10-14 years age (n = 11, 73%), with no deaths in less than 5 years age. 38% of admissions (828/2193) received invasive ventilation, which was more frequent with increasing deprivation (13% (108/828) in least deprived to 31% (260/828) in most deprived) and with decreasing age (0-4-year-olds: 49%, 409/828). This first multi-centre PICU study in England found that children from more deprived neighbourhoods represented the majority of asthma admissions, invasive ventilation and deaths in PICU. Children experiencing socioeconomic deprivation could benefit from enhanced asthma support in the community.",,pdf:https://www.nature.com/articles/s41598-022-05414-5.pdf; doi:https://doi.org/10.1038/s41598-022-05414-5; html:https://europepmc.org/articles/PMC8789863; pdf:https://europepmc.org/articles/PMC8789863?pdf=render
 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,,,"<h4>Aims and objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.",,pdf:https://bmjopenquality.bmj.com/content/bmjqir/12/1/e001704.full.pdf; doi:https://doi.org/10.1136/bmjoq-2021-001704; html:https://europepmc.org/articles/PMC9853220; pdf:https://europepmc.org/articles/PMC9853220?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Medical Research Council, UK, and EU/EFPIA Innovative Medicines Initiative BigData@Heart.",,doi:https://doi.org/10.1016/s0140-6736(21)01638-x; doi:https://doi.org/10.1016/S0140-6736(21)01638-X; html:https://europepmc.org/articles/PMC8542730
 34746717,https://doi.org/10.1016/j.eclinm.2021.101100,Paediatric major incident triage: UK military tool offers best performance in predicting the need for time-critical major surgical and resuscitative intervention.,"Malik NS, Chernbumroong S, Xu Y, Vassallo J, Lee J, Moran CG, Newton T, Arul GS, Lord JM, Belli A, Keene D, Foster M, Hodgetts T, Bowley DM, Gkoutos GV.",,EClinicalMedicine,2021,2021-08-23,Y,,,,"<h4>Background</h4>Children are frequently injured during major incidents (MI), including terrorist attacks, conflict and natural disasters. Triage facilitates healthcare resource allocation in order to maximise overall survival. A critical function of MI triage tools is to identify patients needing time-critical major resuscitative and surgical intervention (Priority 1 (P1) status). This study compares the performance of 11 MI triage tools in predicting P1 status in children from the UK Trauma Audit and Research Network (TARN) registry.<h4>Methods</h4>Patients aged <16 years within TARN (January 2008-December 2017) were included. 11 triage tools were applied to patients' first recorded pre-hospital physiology. Patients were retrospectively assigned triage categories (P1, P2, P3, Expectant or Dead) using predefined intervention-based criteria. Tools' performance in <16s were evaluated within four-yearly age subgroups, comparing tool-predicted and intervention-based priority status.<h4>Findings</h4>Amongst 4962 patients, mortality was 1.1% (<i>n</i> = 53); median Injury Severity Score (ISS) was 9 (IQR 9-16). Blunt injuries predominated (94.4%). 1343 (27.1%) met intervention-based criteria for P1, exhibiting greater intensive care requirement (60.2% vs. 8.5%, <i>p</i> < 0.01) and ISS (median 17 vs 9, <i>p</i> < 0.01) compared with P2 patients. The Battlefield Casualty Drills (BCD) Triage Sieve had greatest sensitivity (75.7%) in predicting P1 status in children <16 years, demonstrating a 38.4-49.8% improvement across all subgroups of children <12 years compared with the UK's current Paediatric Triage Tape (PTT). JumpSTART demonstrated low sensitivity in predicting P1 status in 4 to 8 year olds (35.5%) and 0 to 4 year olds (28.5%), and was outperformed by its adult counterpart START (60.6% and 59.6%).<h4>Interpretation</h4>The BCD Triage Sieve had greatest sensitivity in predicting P1 status in this paediatric trauma registry population: we recommend it replaces the PTT in UK practice. Users of JumpSTART may consider alternative tools. We recommend Lerner's triage category definitions when conducting MI evaluations.",,pdf:http://www.thelancet.com/article/S2589537021003801/pdf; doi:https://doi.org/10.1016/j.eclinm.2021.101100; html:https://europepmc.org/articles/PMC8548919; pdf:https://europepmc.org/articles/PMC8548919?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.",,pdf:https://www.nature.com/articles/s41467-023-39193-y.pdf; doi:https://doi.org/10.1038/s41467-023-39193-y; html:https://europepmc.org/articles/PMC10263377; pdf:https://europepmc.org/articles/PMC10263377?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,,,,,,pdf:https://academic.oup.com/ije/article-pdf/50/4/1064/40146583/dyab028.pdf; doi:https://doi.org/10.1093/ije/dyab028; html:https://europepmc.org/articles/PMC8195245; pdf:https://europepmc.org/articles/PMC8195245?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.",,pdf:https://www.nature.com/articles/s41467-023-39193-y.pdf; doi:https://doi.org/10.1038/s41467-023-39193-y; html:https://europepmc.org/articles/PMC10263377; pdf:https://europepmc.org/articles/PMC10263377?pdf=render
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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).<h4>Interpretation</h4>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.<h4>Funding</h4>UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Scottish Government, and Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2213260021003805/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00380-5; html:https://europepmc.org/articles/PMC8480963
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Discussion</h4>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.",,pdf:https://diagnprognres.biomedcentral.com/counter/pdf/10.1186/s41512-022-00137-7; doi:https://doi.org/10.1186/s41512-022-00137-7; html:https://europepmc.org/articles/PMC9761974; pdf:https://europepmc.org/articles/PMC9761974?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; Chadox1 Ncov-19 Oxford–astrazeneca; Bnt162b2 Pfizer,,,"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.",,pdf:https://www.mdpi.com/2072-6643/14/18/3821/pdf?version=1663570353; doi:https://doi.org/10.3390/nu14183821; html:https://europepmc.org/articles/PMC9506404; pdf:https://europepmc.org/articles/PMC9506404?pdf=render
@@ -353,8 +353,8 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 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,,,"<h4>Objectives</h4>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.<h4>Design</h4>Retrospective cohort study using an online cohort survey (January 2018 to February 2020) linked with routine PCR SARS-CoV-2 test results.<h4>Setting</h4>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.<h4>Participants</h4>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).<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e061344.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061344; html:https://europepmc.org/articles/PMC9453425; pdf:https://europepmc.org/articles/PMC9453425?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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)].<h4>Conclusion</h4>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.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02096-0; doi:https://doi.org/10.1186/s12916-021-02096-0; html:https://europepmc.org/articles/PMC8404408; pdf:https://europepmc.org/articles/PMC8404408?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:http://www.bjanaesthesia.org/article/S0007091221003123/pdf; 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
-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,,,"<h4>Objective</h4>To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England.<h4>Design</h4>Serial cross-sectional study.<h4>Setting</h4>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).<h4>Study population</h4>Children aged 5-17 years in the community.<h4>Predictors</h4>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.<h4>Main outcome measures</h4>Prevalence of persistent symptoms, reported as those lasting ≥3 months post-COVID-19.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://adc.bmj.com/content/archdischild/early/2023/03/01/archdischild-2022-325152.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-325152; html:https://europepmc.org/articles/PMC10313975; pdf:https://europepmc.org/articles/PMC10313975?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),,,"<h4>Introduction</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://ijpds.org/article/download/1717/3510; doi:https://doi.org/10.23889/ijpds.v7i1.1717; html:https://europepmc.org/articles/PMC9284510; pdf:https://europepmc.org/articles/PMC9284510?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,,,"<h4>Objective</h4>To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England.<h4>Design</h4>Serial cross-sectional study.<h4>Setting</h4>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).<h4>Study population</h4>Children aged 5-17 years in the community.<h4>Predictors</h4>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.<h4>Main outcome measures</h4>Prevalence of persistent symptoms, reported as those lasting ≥3 months post-COVID-19.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://adc.bmj.com/content/archdischild/early/2023/03/01/archdischild-2022-325152.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-325152; html:https://europepmc.org/articles/PMC10313975; pdf:https://europepmc.org/articles/PMC10313975?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,,,"<h4>Background</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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 .",,pdf:https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/s12859-022-04641-x; doi:https://doi.org/10.1186/s12859-022-04641-x; html:https://europepmc.org/articles/PMC8974006; pdf:https://europepmc.org/articles/PMC8974006?pdf=render
 34210356,https://doi.org/10.1186/s13059-021-02395-y,CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance.,"Nicholls SM, Poplawski R, Bull MJ, Underwood A, Chapman M, Abu-Dahab K, Taylor B, Colquhoun RM, Rowe WPM, Jackson B, Hill V, O'Toole Á, Rey S, Southgate J, Amato R, Livett R, Gonçalves S, Harrison EM, Peacock SJ, Aanensen DM, Rambaut A, Connor TR, Loman NJ, COVID-19 Genomics UK (COG-UK) Consortium.",,Genome biology,2021,2021-07-01,Y,,,,"In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network.",,pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-021-02395-y; doi:https://doi.org/10.1186/s13059-021-02395-y; html:https://europepmc.org/articles/PMC8247108; pdf:https://europepmc.org/articles/PMC8247108?pdf=render
 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,,,,"<h4>Objectives</h4>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.<h4>Methods and findings</h4>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).<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0237676&type=printable; doi:https://doi.org/10.1371/journal.pone.0237676; html:https://europepmc.org/articles/PMC7500586; pdf:https://europepmc.org/articles/PMC7500586?pdf=render
@@ -372,10 +372,10 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 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,,,"<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/2055207620965046; doi:https://doi.org/10.1177/2055207620965046; html:https://europepmc.org/articles/PMC7675911; pdf:https://europepmc.org/articles/PMC7675911?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-IMT<sub>mean</sub>, C-IMT<sub>max</sub>), 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-IMT<sub>mean</sub> (OR:1.27;1.06-1.47), CC-IMT<sub>mean</sub> (OR:1.22;1.04-1.44) and ICA-IMT<sub>mean</sub> (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.",,pdf:https://www.nature.com/articles/s41598-021-86324-w.pdf; doi:https://doi.org/10.1038/s41598-021-86324-w; html:https://europepmc.org/articles/PMC8042105; pdf:https://europepmc.org/articles/PMC8042105?pdf=render
 37634386,https://doi.org/10.1016/j.schres.2023.08.014,Trends in socioeconomic inequalities in incidence of severe mental illness - A population-based linkage study using primary and secondary care routinely collected data between 2000 and 2017.,"Lee SC, DelPozo-Banos M, Lloyd K, Jones I, Walters JTR, John A.",,Schizophrenia research,2023,2023-08-25,N,Deprivation; Severe Mental Illness; Inequality; Recession; Urbanicity; Austerity,,,"<h4>Objective</h4>In 2008, the UK entered a period of economic recession followed by sustained austerity measures. We investigate changes in inequalities by area deprivation and urbanicity in incidence of severe mental illness (SMI, including schizophrenia-related disorders and bipolar disorder) between 2000 and 2017.<h4>Methods</h4>We analysed 4.4 million individuals from primary and secondary care routinely collected datasets (2000-2017) in Wales and estimated the incidence of SMI by deprivation and urbanicity measured by the Welsh Index of Multiple Deprivation (WIMD) and urban/rural indicator respectively. Using linear modelling and joinpoint regression approaches, we examined time trends of the incidence and incidence rate ratios (IRR) of SMI by the WIMD and urban/rural indicator adjusted for available confounders.<h4>Results</h4>We observed a turning point of time trends of incidence of SMI at 2008/2009 where slope changes of time trends were significantly increasing. IRRs by deprivation/urbanicity remained stable or significantly decreased over the study period except for those with bipolar disorder sourced from secondary care settings, with increasing trend of IRRs (increase in IRR by deprivation after 2010: 1.6 % per year, 95 % CI: 1.0 %-2.2 %; increase in IRR by urbanicity 1.0 % per year, 95 % CI: 0.6 %-1.3 %).<h4>Conclusions</h4>There was an association between recession/austerity and an increase in the incidence of SMI over time. There were variations in the effects of deprivation/urbanicity on incidence of SMI associated with short- and long-term socioeconomic change. These findings may support targeted interventions and social protection systems to reduce incidence of SMI.",,doi:https://doi.org/10.1016/j.schres.2023.08.014
-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; doi:https://doi.org/10.1371/journal.pdig.0000218; html:https://europepmc.org/articles/PMC10168555; pdf:https://europepmc.org/articles/PMC10168555?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,pdf:https://www.nature.com/articles/s41598-019-53454-1.pdf; doi:https://doi.org/10.1038/s41598-019-53454-1; html:https://europepmc.org/articles/PMC6874647; pdf:https://europepmc.org/articles/PMC6874647?pdf=render
-37185201,https://doi.org/10.1136/bmjopen-2022-067337,Prevalence of HIV in mental health service users: a retrospective cohort study.,"Heslin M, Jewell A, Croxford S, Chau C, Smith S, Pittrof R, Covshoff E, Sullivan A, Delpech V, Brown A, King HP, Kakaiya M, Campbell L, Hughes E, Stewart R.",,BMJ open,2023,2023-04-25,Y,Mental health; Hiv & Aids; Sexual Medicine,,,"<h4>Objective</h4>To examine the prevalence of HIV in a cohort of people who have used secondary mental health services in the UK.<h4>Design</h4>Retrospective cohort study.<h4>Setting</h4>Routinely collected clinical data from secondary mental health services in South London, UK available for research through the Clinical Record Interactive Search tool at the National Institute for Health and Care Research Maudsley Biomedical Research Centre were matched with pseudonymised national HIV surveillance data held by the UK Health Security Agency using a deterministic matching algorithm.<h4>Participants</h4>All adults aged 16+ who presented for the first time to mental health services in the South London and Maudsley (SLaM) National Health Service Trust between 1 January 2007 and 31 December 2018 were included.<h4>Primary outcome</h4>Point prevalence of HIV.<h4>Results</h4>There were 181 177 people who had contact with mental health services for the first time between 2007 and 2018 in SLaM. Overall, 2.47% (n=4481) of those had a recorded HIV diagnosis in national HIV surveillance data at any time (before, during or after contact with mental health services), 24.73 people per 1000. HIV point prevalence was highest in people with a diagnosed substance use disorder at 3.77% (n=784). A substantial percentage of the sample did not have a formal mental health diagnosis (27%), but even with those excluded, the point prevalence remained high at 2.31%. Around two-thirds of people had their diagnosis of HIV before contact with mental health services (67%; n=1495).<h4>Conclusions</h4>The prevalence of HIV in people who have had contact with mental health services was approximately 2.5 times higher than the general population in the same geographical area. Future work should investigate risk factors and disparities in HIV outcomes between those with and without mental health service contact.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e067337.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-067337; html:https://europepmc.org/articles/PMC10186409; pdf:https://europepmc.org/articles/PMC10186409?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; doi:https://doi.org/10.1371/journal.pdig.0000218; html:https://europepmc.org/articles/PMC10168555; pdf:https://europepmc.org/articles/PMC10168555?pdf=render
 32723851,https://doi.org/10.1136/bmjhci-2019-100122,HDR UK supporting mobilising computable biomedical knowledge in the UK. ,"Sebire NJ, Cake C, Morris AD.",,BMJ health & care informatics,2020,2020-07-01,Y,,,,"Computable biomedical knowledge (CBK) represents an evolving area of health informatics, with potential for rapid translational patient benefit. Health Data Research UK (HDR UK) is the national Institute for Health Data Science, whose aim is to unite the UK's health data to enable discoveries that improve people's lives. The three main components include the UK HDR Alliance of data custodians, committed to making health data available for research and innovation purposes for public benefit while ensuring safe use of data and building public trust, the HDR Hubs, as centres of expertise for curating data and providing expert domain-specific services, and the HDR Innovation Gateway ('Gateway'), providing discovery, accessibility, security and interoperability services. To support CBK developments, HDR UK is encouraging use of open data standards for research purposes, with guidance around areas in which standards are emerging, aims to work closely with the international CBK community to support initiatives and aid with evaluation and collaboration, and has established a phenomics workstream to create a national platform for dissemination of machine readable and computable phenotypical algorithms to reduce duplication of effort and improve reproducibility in clinical studies.",,pdf:https://informatics.bmj.com/content/bmjhci/27/2/e100122.full.pdf; doi:https://doi.org/10.1136/bmjhci-2019-100122; html:https://europepmc.org/articles/PMC7388881; pdf:https://europepmc.org/articles/PMC7388881?pdf=render
+37185201,https://doi.org/10.1136/bmjopen-2022-067337,Prevalence of HIV in mental health service users: a retrospective cohort study.,"Heslin M, Jewell A, Croxford S, Chau C, Smith S, Pittrof R, Covshoff E, Sullivan A, Delpech V, Brown A, King HP, Kakaiya M, Campbell L, Hughes E, Stewart R.",,BMJ open,2023,2023-04-25,Y,Mental health; Hiv & Aids; Sexual Medicine,,,"<h4>Objective</h4>To examine the prevalence of HIV in a cohort of people who have used secondary mental health services in the UK.<h4>Design</h4>Retrospective cohort study.<h4>Setting</h4>Routinely collected clinical data from secondary mental health services in South London, UK available for research through the Clinical Record Interactive Search tool at the National Institute for Health and Care Research Maudsley Biomedical Research Centre were matched with pseudonymised national HIV surveillance data held by the UK Health Security Agency using a deterministic matching algorithm.<h4>Participants</h4>All adults aged 16+ who presented for the first time to mental health services in the South London and Maudsley (SLaM) National Health Service Trust between 1 January 2007 and 31 December 2018 were included.<h4>Primary outcome</h4>Point prevalence of HIV.<h4>Results</h4>There were 181 177 people who had contact with mental health services for the first time between 2007 and 2018 in SLaM. Overall, 2.47% (n=4481) of those had a recorded HIV diagnosis in national HIV surveillance data at any time (before, during or after contact with mental health services), 24.73 people per 1000. HIV point prevalence was highest in people with a diagnosed substance use disorder at 3.77% (n=784). A substantial percentage of the sample did not have a formal mental health diagnosis (27%), but even with those excluded, the point prevalence remained high at 2.31%. Around two-thirds of people had their diagnosis of HIV before contact with mental health services (67%; n=1495).<h4>Conclusions</h4>The prevalence of HIV in people who have had contact with mental health services was approximately 2.5 times higher than the general population in the same geographical area. Future work should investigate risk factors and disparities in HIV outcomes between those with and without mental health service contact.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e067337.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-067337; html:https://europepmc.org/articles/PMC10186409; pdf:https://europepmc.org/articles/PMC10186409?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'.",,pdf:https://www.nature.com/articles/s41467-022-32096-4.pdf; doi:https://doi.org/10.1038/s41467-022-32096-4; html:https://europepmc.org/articles/PMC9330949; pdf:https://europepmc.org/articles/PMC9330949?pdf=render
 37068951,https://doi.org/10.1136/thorax-2022-219901,Asthma hospitalisations and heat exposure in England: a case-crossover study during 2002-2019.,"Konstantinoudis G, Minelli C, Lam HCY, Fuertes E, Ballester J, Davies B, Vicedo-Cabrera AM, Gasparrini A, Blangiardo M.",,Thorax,2023,2023-04-17,Y,Asthma Epidemiology,,,"<h4>Background</h4>Previous studies have reported an association between warm temperature and asthma hospitalisation. They have reported different sex-related and age-related vulnerabilities; nevertheless, little is known about how this effect has changed over time and how it varies in space. This study aims to evaluate the association between asthma hospitalisation and warm temperature and investigate vulnerabilities by age, sex, time and space.<h4>Methods</h4>We retrieved individual-level data on summer asthma hospitalisation at high temporal (daily) and spatial (postcodes) resolutions during 2002-2019 in England from the NHS Digital. Daily mean temperature at 1 km×1 km resolution was retrieved from the UK Met Office. We focused on lag 0-3 days. We employed a case-crossover study design and fitted Bayesian hierarchical Poisson models accounting for possible confounders (rainfall, relative humidity, wind speed and national holidays).<h4>Results</h4>After accounting for confounding, we found an increase of 1.11% (95% credible interval: 0.88% to 1.34%) in the asthma hospitalisation risk for every 1°C increase in the ambient summer temperature. The effect was highest for males aged 16-64 (2.10%, 1.59% to 2.61%) and during the early years of our analysis. We also found evidence of a decreasing linear trend of the effect over time. Populations in Yorkshire and the Humber and East and West Midlands were the most vulnerable.<h4>Conclusion</h4>This study provides evidence of an association between warm temperature and hospital admission for asthma. The effect has decreased over time with potential explanations including temporal differences in patterns of heat exposure, adaptive mechanisms, asthma management, lifestyle, comorbidities and occupation.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2023/04/17/thorax-2022-219901.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219901; html:https://europepmc.org/articles/PMC10447396; pdf:https://europepmc.org/articles/PMC10447396?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,,,"<h4>Summary</h4>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).",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/4FEB5E5A08973A5347ABA87F440CF09B/S2056472422000242a.pdf/div-class-title-birth-without-intervention-in-women-with-severe-mental-illness-cohort-study-div.pdf; doi:https://doi.org/10.1192/bjo.2022.24; html:https://europepmc.org/articles/PMC8935938; pdf:https://europepmc.org/articles/PMC8935938?pdf=render
@@ -420,12 +420,12 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 35608440,https://doi.org/10.1126/science.abq4411,Twin peaks: The Omicron SARS-CoV-2 BA.1 and BA.2 epidemics in England.,"Elliott P, Eales O, Steyn N, Tang D, Bodinier B, Wang H, Elliott J, Whitaker M, Atchison C, Diggle PJ, Page AJ, Trotter AJ, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke GS, Donnelly CA, Chadeau-Hyam M.",,"Science (New York, N.Y.)",2022,2022-06-24,Y,,,,"Rapid transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has led to record-breaking incidence rates around the world. The Real-time Assessment of Community Transmission-1 (REACT-1) study has tracked SARS-CoV-2 infection in England using reverse transcription polymerase chain reaction (RT-PCR) results from self-administered throat and nose swabs from randomly selected participants aged 5 years and older approximately monthly from May 2020 to March 2022. Weighted prevalence in March 2022 was the highest recorded in REACT-1 at 6.37% (<i>N</i> = 109,181), with the Omicron BA.2 variant largely replacing the BA.1 variant. Prevalence was increasing overall, with the greatest increase in those aged 65 to 74 years and 75 years and older. This was associated with increased hospitalizations and deaths, but at much lower levels than in previous waves against a backdrop of high levels of vaccination.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161371; doi:https://doi.org/10.1126/science.abq4411; html:https://europepmc.org/articles/PMC9161371; pdf:https://europepmc.org/articles/PMC9161371?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://thorax.bmj.com/content/thoraxjnl/77/5/497.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-217580; html:https://europepmc.org/articles/PMC8595052; pdf:https://europepmc.org/articles/PMC8595052?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,,,,"<h4>Aims</h4>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.<h4>Methods & findings</h4>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.<h4>Conclusion</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264529&type=printable; doi:https://doi.org/10.1371/journal.pone.0264529; html:https://europepmc.org/articles/PMC8880762; pdf:https://europepmc.org/articles/PMC8880762?pdf=render
-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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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/).<h4>Trial registration number</h4>ISRCTN11811602.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e046392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046392; html:https://europepmc.org/articles/PMC8245289; pdf:https://europepmc.org/articles/PMC8245289?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 (FEV<sub>1</sub>) 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.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/14799731211053332; doi:https://doi.org/10.1177/14799731211053332; html:https://europepmc.org/articles/PMC8543738; pdf:https://europepmc.org/articles/PMC8543738?pdf=render
+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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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/).<h4>Trial registration number</h4>ISRCTN11811602.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e046392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046392; html:https://europepmc.org/articles/PMC8245289; pdf:https://europepmc.org/articles/PMC8245289?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,,,"<b>Objectives:</b> 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. <b>Method:</b> 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. <b>Results:</b> 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; <i>P</i> = 0.001) and Moment (1) (HR, 1.212, 95%CI: 1.032-1.423; <i>P</i> = 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 (<i>P</i> < 0.05). <b>Conclusion:</b> 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.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.766287/pdf; doi:https://doi.org/10.3389/fcvm.2021.766287; html:https://europepmc.org/articles/PMC8702805; pdf:https://europepmc.org/articles/PMC8702805?pdf=render
 33838587,https://doi.org/10.1016/j.epidem.2021.100460,Competition between RSV and influenza: Limits of modelling inference from surveillance data.,"Waterlow NR, Flasche S, Minter A, Eggo RM.",,Epidemics,2021,2021-03-26,Y,Interaction; Competition; Influenza; Respiratory syncytial virus; Inference,,,"Respiratory Syncytial Virus (RSV) and Influenza cause a large burden of disease. Evidence of their interaction via temporary cross-protection implies that prevention of one could inadvertently lead to an increase in the burden of the other. However, evidence for the public health impact of such interaction is sparse and largely derives from ecological analyses of peak shifts in surveillance data. To test the robustness of estimates of interaction parameters between RSV and Influenza from surveillance data we conducted a simulation and back-inference study. We developed a two-pathogen interaction model, parameterised to simulate RSV and Influenza epidemiology in the UK. Using the infection model in combination with a surveillance-like stochastic observation process we generated a range of possible RSV and Influenza trajectories and then used Markov Chain Monte Carlo (MCMC) methods to back-infer parameters including those describing competition. We find that in most scenarios both the strength and duration of RSV and Influenza interaction could be estimated from the simulated surveillance data reasonably well. However, the robustness of inference declined towards the extremes of the plausible parameter ranges, with misleading results. It was for instance not possible to tell the difference between low/moderate interaction and no interaction. In conclusion, our results illustrate that in a plausible parameter range, the strength of RSV and Influenza interaction can be estimated from a single season of high-quality surveillance data but also highlights the importance to test parameter identifiability a priori in such situations.",,doi:https://doi.org/10.1016/j.epidem.2021.100460; doi:https://doi.org/10.1016/j.epidem.2021.100460; html:https://europepmc.org/articles/PMC8193815
-37203546,https://doi.org/10.3233/shti230319,On the Difficulty of Predicting Engagement with Digital Health for Substance Use.,"Günther F, Yau C, Elison-Davies S, Wong D.",,Studies in health technology and informatics,2023,2023-05-01,N,Prediction; Engagement; Substance Use; Digital Health,,,"Digital interventions can be an important instrument in treating substance use disorder. However, most digital mental health interventions suffer from early, frequent user dropout. Early prediction of engagement would allow identification of individuals whose engagement with digital interventions may be too limited to support behaviour change, and subsequently offering them support. To investigate this, we used machine learning models to predict different metrics of real-world engagement with a digital cognitive behavioural therapy intervention widely available in UK addiction services. Our predictor set consisted of baseline data from routinely-collected standardised psychometric measures. Areas under the ROC curve, and correlations between predicted and observed values indicated that baseline data do not contain sufficient information about individual patterns of engagement.",,pdf:https://ebooks.iospress.nl/pdf/doi/10.3233/SHTI230319; doi:https://doi.org/10.3233/SHTI230319
 35310465,https://doi.org/10.23889/ijpds.v5i4.1697,"Validating the QCOVID risk prediction algorithm for risk of mortality from COVID-19 in the adult population in Wales, UK.","Lyons J, Nafilyan V, Akbari A, Davies G, Griffiths R, Harrison EM, Hippisley-Cox J, Hollinghurst J, Khunti K, North L, Sheikh A, Torabi F, Lyons RA.",,International journal of population data science,2020,2020-01-01,Y,Risk Prediction Models; Sail Databank; Covid-19 Outcomes; Population Data-Linkage; Qcovid Algorithm,,,"<h4>Introduction</h4>COVID-19 risk prediction algorithms can be used to identify at-risk individuals from short-term serious adverse COVID-19 outcomes such as hospitalisation and death. It is important to validate these algorithms in different and diverse populations to help guide risk management decisions and target vaccination and treatment programs to the most vulnerable individuals in society.<h4>Objectives</h4>To validate externally the QCOVID risk prediction algorithm that predicts mortality outcomes from COVID-19 in the adult population of Wales, UK.<h4>Methods</h4>We conducted a retrospective cohort study using routinely collected individual-level data held in the Secure Anonymised Information Linkage (SAIL) Databank. The cohort included individuals aged between 19 and 100 years, living in Wales on 24<sup>th</sup> January 2020, registered with a SAIL-providing general practice, and followed-up to death or study end (28<sup>th</sup> July 2020). Demographic, primary and secondary healthcare, and dispensing data were used to derive all the predictor variables used to develop the published QCOVID algorithm. Mortality data were used to define time to confirmed or suspected COVID-19 death. Performance metrics, including R<sup>2</sup> values (explained variation), Brier scores, and measures of discrimination and calibration were calculated for two periods (24<sup>th</sup> January-30<sup>th</sup> April 2020 and 1<sup>st</sup> May-28<sup>th</sup> July 2020) to assess algorithm performance.<h4>Results</h4>1,956,760 individuals were included. 1,192 (0.06%) and 610 (0.03%) COVID-19 deaths occurred in the first and second time periods, respectively. The algorithms fitted the Welsh data and population well, explaining 68.8% (95% CI: 66.9-70.4) of the variation in time to death, Harrell's C statistic: 0.929 (95% CI: 0.921-0.937) and D statistic: 3.036 (95% CI: 2.913-3.159) for males in the first period. Similar results were found for females and in the second time period for both sexes.<h4>Conclusions</h4>The QCOVID algorithm developed in England can be used for public health risk management for the adult Welsh population.",,pdf:https://ijpds.org/article/download/1697/3337; doi:https://doi.org/10.23889/ijpds.v5i4.1697; html:https://europepmc.org/articles/PMC8900650; pdf:https://europepmc.org/articles/PMC8900650?pdf=render
+37203546,https://doi.org/10.3233/shti230319,On the Difficulty of Predicting Engagement with Digital Health for Substance Use.,"Günther F, Yau C, Elison-Davies S, Wong D.",,Studies in health technology and informatics,2023,2023-05-01,N,Prediction; Engagement; Substance Use; Digital Health,,,"Digital interventions can be an important instrument in treating substance use disorder. However, most digital mental health interventions suffer from early, frequent user dropout. Early prediction of engagement would allow identification of individuals whose engagement with digital interventions may be too limited to support behaviour change, and subsequently offering them support. To investigate this, we used machine learning models to predict different metrics of real-world engagement with a digital cognitive behavioural therapy intervention widely available in UK addiction services. Our predictor set consisted of baseline data from routinely-collected standardised psychometric measures. Areas under the ROC curve, and correlations between predicted and observed values indicated that baseline data do not contain sufficient information about individual patterns of engagement.",,pdf:https://ebooks.iospress.nl/pdf/doi/10.3233/SHTI230319; doi:https://doi.org/10.3233/SHTI230319
 33879450,https://doi.org/10.1136/heartjnl-2021-319118,Sex differences in investigations and outcomes among patients with type 2 myocardial infarction.,"Kimenai DM, Lindahl B, Chapman AR, Baron T, Gard A, Wereski R, Meex SJR, Jernberg T, Mills NL, Eggers KM.",,Heart (British Cardiac Society),2021,2021-04-20,Y,Myocardial infarction; acute coronary syndrome; risk factors,,,"<h4>Objectives</h4>Type 2 myocardial infarction (MI) is a heterogenous condition and whether there are differences between women and men is unknown. We evaluated sex differences in clinical characteristics, investigations and outcomes in patients with type 2 MI.<h4>Methods</h4>In the Swedish Web based system for Enhancement and Development of Evidence based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, we compared patients admitted to coronary care units with a diagnosis of type 1 or type 2 MI. Sex-stratified Cox regression models evaluated the association with all-cause death in men and women separately.<h4>Results</h4>We included 57 264 (median age 73 years, 65% men) and 6485 (median age 78 years, 50% men) patients with type 1 and type 2 MI, respectively. No differences were observed in the proportion of men and women with type 2 MI who underwent echocardiography and coronary angiography, but women were less likely than men to have left ventricular (LV) impairment and obstructive coronary artery disease (CAD). Compared with type 1 MI, patients with type 2 MI had higher risk of death regardless of sex (men: adjusted HR 1.55 (95% CI 1.44 to 1.67); women: adjusted HR 1.34 (95% CI 1.24 to 1.45)). In those with type 2 MI, the risk of death was lower for women than men (adjusted HR 0.85 (95% CI 0.76 to 0.92) (men, reference)).<h4>Conclusions</h4>Type 2 MI occurred in men and women equally and we found no evidence of sex bias in the selection of patients for cardiac investigations. Patients with type 2 MI had worse outcomes, but women were less likely to have obstructive CAD or severe LV impairment and were more likely to survive than men.",,pdf:https://heart.bmj.com/content/heartjnl/107/18/1480.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-319118; html:https://europepmc.org/articles/PMC8408584; pdf:https://europepmc.org/articles/PMC8408584?pdf=render
 31658860,https://doi.org/10.1161/jaha.119.012812,Early Discontinuation of P2Y<sub>12</sub> 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 P2Y<sub>12</sub> 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 P2Y<sub>12</sub> 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.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.119.012812; doi:https://doi.org/10.1161/JAHA.119.012812; html:https://europepmc.org/articles/PMC6898825; pdf:https://europepmc.org/articles/PMC6898825?pdf=render
 35291009,https://doi.org/10.1093/ageing/afac072,Intensity of COVID-19 in care homes following hospital discharge in the early stages of the UK epidemic.,"Hollinghurst J, North L, Emmerson C, Akbari A, Torabi F, Williams C, Lyons RA, Hawkes AG, Bennett E, Gravenor MB, Fry R.",,Age and ageing,2022,2022-05-01,Y,Older People; Care Homes; Hospital Discharge; Linked Data; Hawkes Process; Multi-level Model; Covid-19,,,"<h4>Background</h4>defining features of the COVID-19 pandemic in many countries were the tragic extent to which care home residents were affected and the difficulty in preventing the introduction and subsequent spread of infection. Management of risk in care homes requires good evidence on the most important transmission pathways. One hypothesised route at the start of the pandemic, prior to widespread testing, was the transfer of patients from hospitals that were experiencing high levels of nosocomial events.<h4>Methods</h4>we tested the hypothesis that hospital discharge events increased the intensity of care home cases using a national individually linked health record cohort in Wales, UK. We monitored 186,772 hospital discharge events over the period from March to July 2020, tracking individuals to 923 care homes and recording the daily case rate in the homes populated by 15,772 residents. We estimated the risk of an increase in case rates following exposure to a hospital discharge using multi-level hierarchical logistic regression and a novel stochastic Hawkes process outbreak model.<h4>Findings</h4>in regression analysis, after adjusting for care home size, we found no significant association between hospital discharge and subsequent increases in care home case numbers (odds ratio: 0.99, 95% CI: 0.82, 1.90). Risk factors for increased cases included care home size, care home resident density and provision of nursing care. Using our outbreak model, we found a significant effect of hospital discharge on the subsequent intensity of cases. However, the effect was small and considerably less than the effect of care home size, suggesting the highest risk of introduction came from interaction with the community. We estimated that approximately 1.8% of hospital discharged patients may have been infected.<h4>Interpretation</h4>there is growing evidence in the UK that the risk of transfer of COVID-19 from the high-risk hospital setting to the high-risk care home setting during the early stages of the pandemic was relatively small. Although access to testing was limited to initial symptomatic cases in each care home at this time, our results suggest that reduced numbers of discharges, selection of patients and action taken within care homes following transfer all may have contributed to the mitigation. The precise key transmission routes from the community remain to be quantified.",,pdf:https://academic.oup.com/ageing/article-pdf/51/5/afac072/43616755/afac072.pdf; doi:https://doi.org/10.1093/ageing/afac072; html:https://europepmc.org/articles/PMC8992303; pdf:https://europepmc.org/articles/PMC8992303?pdf=render
@@ -445,8 +445,8 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 37185641,https://doi.org/10.1136/bmjopen-2022-070022,EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.,"Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, Müllerová H.",,BMJ open,2023,2023-04-26,Y,epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease,,,"<h4>Introduction</h4>In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.<h4>Methods and analysis</h4>Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.<h4>Ethics and dissemination</h4>Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?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,,,"<h4>Background and purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 &lt; 0.001; 45% vs. 37.9%, p &lt; 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).<h4>Conclusions</h4>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.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62203/Download/62203__26254__0c88bfc9ff7e4fe2acaea5e2a2d74058.pdf; 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>UK Government Department of Health and Social Care.",,doi:https://doi.org/10.1016/s2666-7568(22)00147-7; 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
-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
 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.",,pdf:https://www.nature.com/articles/s41467-021-23935-x.pdf; doi:https://doi.org/10.1038/s41467-021-23935-x; html:https://europepmc.org/articles/PMC8213785; pdf:https://europepmc.org/articles/PMC8213785?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
 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.",,pdf:https://www.mdpi.com/2076-393X/11/3/680/pdf?version=1679031223; doi:https://doi.org/10.3390/vaccines11030680; html:https://europepmc.org/articles/PMC10057771; pdf:https://europepmc.org/articles/PMC10057771?pdf=render
 37663407,https://doi.org/10.1093/jamiaopen/ooad072,Identifying factors associated with user retention and outcomes of a digital intervention for substance use disorder: a retrospective analysis of real-world data.,"Günther F, Wong D, Elison-Davies S, Yau C.",,JAMIA open,2023,2023-09-02,Y,Substance Use Disorder; Secondary Use; Digital Health Intervention; Real-World Data Exploration; Real-World Uptake,,,"<h4>Objectives</h4>Successful delivery of digital health interventions is affected by multiple real-world factors. These factors may be identified in routinely collected, ecologically valid data from these interventions. We propose ideas for exploring these data, focusing on interventions targeting complex, comorbid conditions.<h4>Materials and methods</h4>This study retrospectively explores pre-post data collected between 2016 and 2019 from users of digital cognitive behavioral therapy (CBT)-containing psychoeducation and practical exercises-for substance use disorder (SUD) at UK addiction services. To identify factors associated with heterogenous user responses to the technology, we employed multivariable and multivariate regressions and random forest models of user-reported questionnaire data.<h4>Results</h4>The dataset contained information from 14 078 individuals of which 12 529 reported complete data at baseline and 2925 did so again after engagement with the CBT. Ninety-three percent screened positive for dependence on 1 of 43 substances at baseline, and 73% screened positive for anxiety or depression. Despite pre-post improvements independent of user sociodemographics, women reported more frequent and persistent symptoms of SUD, anxiety, and depression. Retention-minimum 2 use events recorded-was associated more with deployment environment than user characteristics. Prediction accuracy of post-engagement outcomes was acceptable (Area Under Curve [AUC]: 0.74-0.79), depending non-trivially on user characteristics.<h4>Discussion</h4>Traditionally, performance of digital health interventions is determined in controlled trials. Our analysis showcases multivariate models with which real-world data from these interventions can be explored and sources of user heterogeneity in retention and symptom reduction uncovered.<h4>Conclusion</h4>Real-world data from digital health interventions contain information on natural user-technology interactions which could enrich results from controlled trials.",,doi:https://doi.org/10.1093/jamiaopen/ooad072; html:https://europepmc.org/articles/PMC10474970; pdf:https://europepmc.org/articles/PMC10474970?pdf=render
 32180562,https://doi.org/10.1016/j.molmet.2020.01.009,Genome-wide association study of adipocyte lipolysis in the GENetics of adipocyte lipolysis (GENiAL) cohort.,"Kulyté A, Lundbäck V, Lindgren CM, Luan J, Lotta LA, Langenberg C, Arner P, Strawbridge RJ, Dahlman I.",,Molecular metabolism,2020,2020-01-25,Y,Adipocytes; Gene Expression; Subcutaneous; Genetic Variants; Lipolysis,The Human Phenome,,"<h4>Objectives</h4>Lipolysis, hydrolysis of triglycerides to fatty acids in adipocytes, is tightly regulated, poorly understood, and, if perturbed, can lead to metabolic diseases including obesity and type 2 diabetes. The goal of this study was to identify the genetic regulators of lipolysis and elucidate their molecular mechanisms.<h4>Methods</h4>Adipocytes from abdominal subcutaneous adipose tissue biopsies were isolated and were incubated without (spontaneous lipolysis) or with a catecholamine (stimulated lipolysis) to analyze lipolysis. DNA was extracted and genome-wide genotyping and imputation conducted. After quality control, 939 samples with genetic and lipolysis data were available. Genome-wide association studies of spontaneous and stimulated lipolysis were conducted. Subsequent in vitro gene expression analyses were used to identify candidate genes and explore their regulation of adipose tissue biology.<h4>Results</h4>One locus on chromosome 19 demonstrated genome-wide significance with spontaneous lipolysis. 60 loci showed suggestive associations with spontaneous or stimulated lipolysis, of which many influenced both traits. In the chromosome 19 locus, only HIF3A was expressed in the adipocytes and displayed genotype-dependent gene expression. HIF3A knockdown in vitro increased lipolysis and the expression of key lipolysis-regulating genes.<h4>Conclusions</h4>In conclusion, we identified a genetic regulator of spontaneous lipolysis and provided evidence of HIF3A as a novel key regulator of lipolysis in subcutaneous adipocytes as the mechanism through which the locus influences adipose tissue biology.","How the body breaks down fat is poorly understood, and, if this mechanism does not happen effiently in the body it can lead to metabolic diseases including obesity and type 2 diabetes. The goal of this study was to identify the genetic regulators of how the body break down fat and explain their molecular mechanisms.",doi:https://doi.org/10.1016/j.molmet.2020.01.009; doi:https://doi.org/10.1016/j.molmet.2020.01.009; html:https://europepmc.org/articles/PMC7021539; pdf:https://europepmc.org/articles/PMC7021539?pdf=render
@@ -461,8 +461,8 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development:
 36936262,https://doi.org/10.1136/bmjmed-2022-000371,Association between coeliac disease and cardiovascular disease: prospective analysis of UK Biobank data.,"Conroy M, Allen N, Lacey B, Soilleux E, Littlejohns T.",,BMJ medicine,2023,2023-01-04,Y,epidemiology; Cardiology; Celiac Disease,,,"<h4>Objectives</h4>To investigate whether people with coeliac disease are at increased risk of cardiovascular disease, including ischaemic heart disease, myocardial infarction, and stroke.<h4>Design</h4>Prospective analysis of a large cohort study.<h4>Setting</h4>UK Biobank database.<h4>Participants</h4>469 095 adults, of which 2083 had coeliac disease, aged 40-69 years from England, Scotland, and Wales between 2006 and 2010 without cardiovascular disease at baseline.<h4>Main outcome measure</h4>A composite primary outcome was relative risk of cardiovascular disease, ischaemic heart disease, myocardial infarction, and stroke in people with coeliac disease compared with people who do not have coeliac disease, assessed using Cox proportional hazard models.<h4>Results</h4>40 687 incident cardiovascular disease events occurred over a median follow-up of 12.4 years (interquartile range 11.5-13.1), with 218 events among people with coeliac disease. Participants with coeliac disease were more likely to have a lower body mass index and systolic blood pressure, less likely to smoke, and more likely to have an ideal cardiovascular risk score than people who do not have coeliac disease. Despite this, participants with coeliac disease had an incidence rate of 9.0 cardiovascular disease cases per 1000 person years (95% confidence interval 7.9 to 10.3) compared with 7.4 per 1000 person years (7.3 to 7.4) in people with no coeliac disease. Coeliac disease was associated with an increased risk of cardiovascular disease (hazard ratio 1.27 (95% confidence interval 1.11 to 1.45)), which was not influenced by adjusting for lifestyle factors (1.27 (1.11 to 1.45)), but was strengthened by further adjusting for other cardiovascular risk factors (1.44 (1.26 to 1.65)). Similar associations were identified for ischaemic heart disease and myocardial infarction but fewer stroke events were reported and no evidence of an association between coeliac disease and risk of stroke.<h4>Conclusions</h4>Individuals with coeliac disease had a lower prevalence of traditional cardiovascular risk factors but had a higher risk of developing cardiovascular disease than did people with no coeliac disease. Cardiovascular risk scores used in clinical practice might therefore not adequately capture the excess risk of cardiovascular disease in people with coeliac disease, and clinicians should be aware of the need to optimise cardiovascular health in this population.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000371.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000371; html:https://europepmc.org/articles/PMC9951384; pdf:https://europepmc.org/articles/PMC9951384?pdf=render
 36921681,https://doi.org/10.1016/j.cca.2023.117271,"Letter to the editor regarding: ""A haemochromatosis-causing HFE mutation is associated with SARS-CoV-2 susceptibility in the Czech population"" clinica chimica acta 538 (2023) 211-215.","Atkins JL, Lucas MR, Pilling LC, Melzer D.",,Clinica chimica acta; international journal of clinical chemistry,2023,2023-03-13,Y,Iron; Haemochromatosis; Hfe; Covd-19,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009995; doi:https://doi.org/10.1016/j.cca.2023.117271; html:https://europepmc.org/articles/PMC10009995; pdf:https://europepmc.org/articles/PMC10009995?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,,,"<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://bjsm.bmj.com/content/bjsports/early/2022/02/15/bjsports-2021-104050.full.pdf; doi:https://doi.org/10.1136/bjsports-2021-104050; html:https://europepmc.org/articles/PMC9484395; pdf:https://europepmc.org/articles/PMC9484395?pdf=render
-37934728,https://doi.org/10.1093/jamia/ocad212,Multi-faceted analysis and prediction for the outbreak of pediatric respiratory syncytial virus.,"Yang C, Gao J, Glass L, Cross A, Sun J.",,Journal of the American Medical Informatics Association : JAMIA,2023,2023-11-02,N,Respiratory syncytial virus (RSV); Pediatric Diseases; Deep Learning; Tensor Factorization,,,"<h4>Objectives</h4>Respiratory syncytial virus (RSV) is a significant cause of pediatric hospitalizations. This article aims to utilize multisource data and leverage the tensor methods to uncover distinct RSV geographic clusters and develop an accurate RSV prediction model for future seasons.<h4>Materials and methods</h4>This study utilizes 5-year RSV data from sources, including medical claims, CDC surveillance data, and Google search trends. We conduct spatiotemporal tensor analysis and prediction for pediatric RSV in the United States by designing (i) a nonnegative tensor factorization model for pediatric RSV diseases and location clustering; (ii) and a recurrent neural network tensor regression model for county-level trend prediction using the disease and location features.<h4>Results</h4>We identify a clustering hierarchy of pediatric diseases: Three common geographic clusters of RSV outbreaks were identified from independent sources, showing an annual RSV trend shifting across different US regions, from the South and Southeast regions to the Central and Northeast regions and then to the West and Northwest regions, while precipitation and temperature were found as correlative factors with the coefficient of determination R2≈0.5, respectively. Our regression model accurately predicted the 2022-2023 RSV season at the county level, achieving R2≈0.3 mean absolute error MAE < 0.4 and a Pearson correlation greater than 0.75, which significantly outperforms the baselines with P-values <.05.<h4>Conclusion</h4>Our proposed framework provides a thorough analysis of RSV disease in the United States, which enables healthcare providers to better prepare for potential outbreaks, anticipate increased demand for services and supplies, and save more lives with timely interventions.",,doi:https://doi.org/10.1093/jamia/ocad212
 32613083,https://doi.org/10.12688/wellcomeopenres.15922.2,"Black, Asian and Minority Ethnic groups in England are at increased risk of death from COVID-19: indirect standardisation of NHS mortality data.","Aldridge RW, Lewer D, Katikireddi SV, Mathur R, Pathak N, Burns R, Fragaszy EB, Johnson AM, Devakumar D, Abubakar I, Hayward A.",,Wellcome open research,2020,2020-06-24,Y,Mortality; Minority Ethnic Groups; Covid-19; Sars-cov-2,,,"<b>Background</b>: International and UK data suggest that Black, Asian and Minority Ethnic (BAME) groups are at increased risk of infection and death from COVID-19. We aimed to explore the risk of death in minority ethnic groups in England using data reported by NHS England. <b>Methods</b>: We used NHS data on patients with a positive COVID-19 test who died in hospitals in England published on 28th April, with deaths by ethnicity available from 1st March 2020 up to 5pm on 21 April 2020. We undertook indirect standardisation of these data (using the whole population of England as the reference) to produce ethnic specific standardised mortality ratios (SMRs) adjusted for age and geographical region. <b>Results</b>: The largest total number of deaths in minority ethnic groups were Indian (492 deaths) and Black Caribbean (460 deaths) groups. Adjusting for region we found a lower risk of death for White Irish (SMR 0.52; 95%CIs 0.45-0.60) and White British ethnic groups (0.88; 95%CIs 0.86-0.0.89), but increased risk of death for Black African (3.24; 95%CIs 2.90-3.62), Black Caribbean (2.21; 95%CIs 2.02-2.41), Pakistani (3.29; 95%CIs 2.96-3.64), Bangladeshi (2.41; 95%CIs 1.98-2.91) and Indian (1.70; 95%CIs 1.56-1.85) minority ethnic groups. <b>Conclusion:</b> Our analysis adds to the evidence that BAME people are at increased risk of death from COVID-19 even after adjusting for geographical region, but was limited by the lack of data on deaths outside of NHS settings and ethnicity denominator data being based on the 2011 census. Despite these limitations, we believe there is an urgent need to take action to reduce the risk of death for BAME groups and better understand why some ethnic groups experience greater risk. Actions that are likely to reduce these inequities include ensuring adequate income protection, reducing occupational risks, reducing barriers in accessing healthcare and providing culturally and linguistically appropriate public health communications.",,doi:https://doi.org/10.12688/wellcomeopenres.15922.2; html:https://europepmc.org/articles/PMC7317462; pdf:https://europepmc.org/articles/PMC7317462?pdf=render
+37934728,https://doi.org/10.1093/jamia/ocad212,Multi-faceted analysis and prediction for the outbreak of pediatric respiratory syncytial virus.,"Yang C, Gao J, Glass L, Cross A, Sun J.",,Journal of the American Medical Informatics Association : JAMIA,2023,2023-11-02,N,Respiratory syncytial virus (RSV); Pediatric Diseases; Deep Learning; Tensor Factorization,,,"<h4>Objectives</h4>Respiratory syncytial virus (RSV) is a significant cause of pediatric hospitalizations. This article aims to utilize multisource data and leverage the tensor methods to uncover distinct RSV geographic clusters and develop an accurate RSV prediction model for future seasons.<h4>Materials and methods</h4>This study utilizes 5-year RSV data from sources, including medical claims, CDC surveillance data, and Google search trends. We conduct spatiotemporal tensor analysis and prediction for pediatric RSV in the United States by designing (i) a nonnegative tensor factorization model for pediatric RSV diseases and location clustering; (ii) and a recurrent neural network tensor regression model for county-level trend prediction using the disease and location features.<h4>Results</h4>We identify a clustering hierarchy of pediatric diseases: Three common geographic clusters of RSV outbreaks were identified from independent sources, showing an annual RSV trend shifting across different US regions, from the South and Southeast regions to the Central and Northeast regions and then to the West and Northwest regions, while precipitation and temperature were found as correlative factors with the coefficient of determination R2≈0.5, respectively. Our regression model accurately predicted the 2022-2023 RSV season at the county level, achieving R2≈0.3 mean absolute error MAE < 0.4 and a Pearson correlation greater than 0.75, which significantly outperforms the baselines with P-values <.05.<h4>Conclusion</h4>Our proposed framework provides a thorough analysis of RSV disease in the United States, which enables healthcare providers to better prepare for potential outbreaks, anticipate increased demand for services and supplies, and save more lives with timely interventions.",,doi:https://doi.org/10.1093/jamia/ocad212
 37868035,https://doi.org/10.1016/j.xgen.2023.100385,Gene expression and RNA splicing explain large proportions of the heritability for complex traits in cattle.,"Xiang R, Fang L, Liu S, Macleod IM, Liu Z, Breen EJ, Gao Y, Liu GE, Tenesa A, CattleGTEx Consortium, Mason BA, Chamberlain AJ, Wray NR, Goddard ME.",,Cell genomics,2023,2023-08-23,Y,RNA splicing; Heritability; Gene Expression; Complex Traits; Eqtl; Sqtl; Bayesr; Bayesrc,,,"Many quantitative trait loci (QTLs) are in non-coding regions. Therefore, QTLs are assumed to affect gene regulation. Gene expression and RNA splicing are primary steps of transcription, so DNA variants changing gene expression (eVariants) or RNA splicing (sVariants) are expected to significantly affect phenotypes. We quantify the contribution of eVariants and sVariants detected from 16 tissues (n = 4,725) to 37 traits of ∼120,000 cattle (average magnitude of genetic correlation between traits = 0.13). Analyzed in Bayesian mixture models, averaged across 37 traits, <i>cis</i> and <i>trans</i> eVariants and sVariants detected from 16 tissues jointly explain 69.2% (SE = 0.5%) of heritability, 44% more than expected from the same number of random variants. This 69.2% includes an average of 24% from <i>trans</i> e-/sVariants (14% more than expected). Averaged across 56 lipidomic traits, multi-tissue <i>cis</i> and <i>trans</i> e-/sVariants also explain 71.5% (SE = 0.3%) of heritability, demonstrating the essential role of proximal and distal regulatory variants in shaping mammalian phenotypes.",,doi:https://doi.org/10.1016/j.xgen.2023.100385; html:https://europepmc.org/articles/PMC10589627; pdf:https://europepmc.org/articles/PMC10589627?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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://medinform.jmir.org/2020/5/e16452/PDF; doi:https://doi.org/10.2196/16452; html:https://europepmc.org/articles/PMC7290450
 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.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010234&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010234; html:https://europepmc.org/articles/PMC9262224; pdf:https://europepmc.org/articles/PMC9262224?pdf=render
@@ -486,8 +486,8 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development:
 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,,,"<h4>Objective</h4>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.<h4>Methods and analysis</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration number</h4>NCT00056836.",,pdf:https://discovery.ucl.ac.uk/10164981/1/267.full.pdf; doi:https://doi.org/10.1136/bjophthalmol-2021-319383; html:https://europepmc.org/articles/PMC9887382; pdf:https://europepmc.org/articles/PMC9887382?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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/eurheartj/article-pdf/43/2/127/42182731/ehab581.pdf; doi:https://doi.org/10.1093/eurheartj/ehab581; html:https://europepmc.org/articles/PMC8757580; pdf:https://europepmc.org/articles/PMC8757580?pdf=render
 37550086,https://doi.org/10.1136/bmjment-2023-300762,Associations between air pollution and mental health service use in dementia: a retrospective cohort study.,"Ronaldson A, Stewart R, Mueller C, Das-Munshi J, Newbury JB, Mudway IS, Broadbent M, Fisher HL, Beevers S, Dajnak D, Hotopf M, Hatch SL, Bakolis I.",,BMJ mental health,2023,2023-07-01,Y,Psychiatry; Adult Psychiatry; Delirium & Cognitive Disorders,,,"<h4>Background</h4>Little is known about the role of air pollution in how people with dementia use mental health services.<h4>Objective</h4>We examined longitudinal associations between air pollution exposure and mental health service use in people with dementia.<h4>Methods</h4>In 5024 people aged 65 years or older with dementia in South London, high resolution estimates of nitrogen dioxide (NO<sub>2</sub>) and particulate matter (PM<sub>2.5</sub> and PM<sub>10</sub>) levels in ambient air were linked to residential addresses. Associations between air pollution and Community Mental Health Team (CMHT) events (recorded over 9 years) were examined using negative binomial regression models. Cognitive function was measured using the Mini Mental State Examination (MMSE) and health and social functioning was measured using the Health of the Nation Outcomes Scale (HoNOS65+). Associations between air pollution and both MMSE and HoNOS65+ scores were assessed using linear regression models.<h4>Findings</h4>In the first year of follow-up, increased exposure to all air pollutants was associated with an increase in the use of CMHTs in a dose-response manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) (eg, NO<sub>2</sub>: adjusted incidence rate ratio (aIRR) 1.27, 95% CI 1.11 to 1.45, p<0.001). Dose-response patterns between PM<sub>2.5</sub> and CMHT events remained at 5 and 9 years. Associations were strongest for patients with vascular dementia. NO<sub>2</sub> levels were linked with poor functional status, but not cognitive function.<h4>Conclusions</h4>Residential air pollution exposure is associated with increased CMHT usage among people with dementia.<h4>Clinical implications</h4>Efforts to reduce pollutant exposures in urban settings might reduce the use of mental health services in people with dementia, freeing up resources in already considerably stretched psychiatric services.",,doi:https://doi.org/10.1136/bmjment-2023-300762; html:https://europepmc.org/articles/PMC10577765; pdf:https://europepmc.org/articles/PMC10577765?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-15345-z; doi:https://doi.org/10.1186/s12889-023-15345-z; html:https://europepmc.org/articles/PMC10031708; pdf:https://europepmc.org/articles/PMC10031708?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,,,,"<h4>Introduction</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://link.springer.com/content/pdf/10.1007/s40801-021-00256-5.pdf; doi:https://doi.org/10.1007/s40801-021-00256-5; html:https://europepmc.org/articles/PMC8605959; pdf:https://europepmc.org/articles/PMC8605959?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-15345-z; doi:https://doi.org/10.1186/s12889-023-15345-z; html:https://europepmc.org/articles/PMC10031708; pdf:https://europepmc.org/articles/PMC10031708?pdf=render
 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.",,pdf:https://link.springer.com/content/pdf/10.1007/s40653-021-00433-2.pdf; doi:https://doi.org/10.1007/s40653-021-00433-2; html:https://europepmc.org/articles/PMC9360289; pdf:https://europepmc.org/articles/PMC9360289?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,,,,"<h4>Background</h4>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.<h4>Aim</h4>A Delphi study was performed to reach consensus on which diseases may be described as fibrotic.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/qjmed/advance-article-pdf/doi/10.1093/qjmed/hcad050/50051055/hcad050.pdf; doi:https://doi.org/10.1093/qjmed/hcad050; html:https://europepmc.org/articles/PMC10250078; pdf:https://europepmc.org/articles/PMC10250078?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.",,pdf:https://www.pure.ed.ac.uk/ws/files/285303439/59583_4_merged_1655920711.pdf; doi:https://doi.org/10.1038/s41588-022-01153-5; html:https://europepmc.org/articles/PMC7613894; pdf:https://europepmc.org/articles/PMC7613894?pdf=render
@@ -511,8 +511,8 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development:
 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 <i>CYP2D6</i> and <i>CYP2C19</i> 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; <i>p</i> < 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; <i>p</i> < 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; <i>p</i> = 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.",,pdf:https://www.mdpi.com/2073-4425/12/11/1758/pdf?version=1637118460; doi:https://doi.org/10.3390/genes12111758; html:https://europepmc.org/articles/PMC8620997; pdf:https://europepmc.org/articles/PMC8620997?pdf=render
 35131989,https://doi.org/10.1097/mcp.0000000000000863,A clinical review of long-COVID with a focus on the respiratory system.,"Daines L, Zheng B, Pfeffer P, Hurst JR, Sheikh A.",,Current opinion in pulmonary medicine,2022,2022-02-07,N,,,,"<h4>Purpose of review</h4>Persistence of symptoms after acute coronavirus disease 2019 (COVID-19), often described as long- COVID, is common and debilitating. In this article, we review the epidemiology, clinical features, and research priorities for long-COVID focusing on the respiratory system.<h4>Recent findings</h4>Breathlessness, cough and chest pain were the most commonly reported respiratory symptoms associated with long-COVID. In hospitalised patients, abnormalities on lung function testing or chest imaging were observed less commonly at 12 months compared to six months since discharge. Clinical assessment of patients with persisting symptoms after acute COVID-19 requires a comprehensive evaluation to exclude other possible causes for symptoms. With no robust current evidence for interventions to treat long-COVID respiratory symptoms, symptomatic treatment, supported self-management and pulmonary rehabilitation should be considered to help individuals with respiratory symptoms associated with long-COVID.<h4>Summary</h4>Long-COVID is a debilitating syndrome that often includes persisting respiratory symptoms and to a lesser degree, abnormalities in lung physiology or imaging. Respiratory features of long-COVID may reduce over time, yet resolution is not seen in all cases. Future research is needed to understand the natural history of long-COVID, identify factors associated with spontaneous improvement/persistence, investigate mechanisms for persisting symptoms, and test interventions to prevent and treat long-COVID.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612723; doi:https://doi.org/10.1097/MCP.0000000000000863; html:https://europepmc.org/articles/PMC7612723; pdf:https://europepmc.org/articles/PMC7612723?pdf=render; doi:https://doi.org/10.1097/mcp.0000000000000863
 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.",,pdf:https://n.neurology.org/content/neurology/96/8/e1251.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000011463; html:https://europepmc.org/articles/PMC8055349; pdf:https://europepmc.org/articles/PMC8055349?pdf=render
-36997954,https://doi.org/10.1186/s13063-023-07251-x,A DELPHI study priority setting the remaining challenges for the use of routinely collected data in trials: COMORANT-UK.,"Williams ADN, Davies G, Farrin AJ, Mafham M, Robling M, Sydes MR, Lugg-Widger FV.",,Trials,2023,2023-03-30,Y,Priority Setting; Consensus; Routinely Collected Data; Trials Methodology,,,"<h4>Background</h4>Researchers are increasingly seeking to use routinely collected data to support clinical trials. This approach has the potential to transform the way clinical trials are conducted in the future. The availability of routinely collected data for research, whether healthcare or administrative, has increased, and infrastructure funding has enabled much of this. However, challenges remain at all stages of a trial life cycle. This study, COMORANT-UK, aimed to systematically identify, with key stakeholders across the UK, the ongoing challenges related to trials that seek to use routinely collected data.<h4>Methods</h4>This three-step Delphi method consisted of two rounds of anonymous web-based surveys and a virtual consensus meeting. Stakeholders included trialists, data infrastructures, funders of trials, regulators, data providers and the public. Stakeholders identified research questions or challenges that they considered were of particular importance and then selected their top 10 in the second survey. The ranked questions were taken forward to the consensus meeting for discussion with representatives invited from the stakeholder groups.<h4>Results</h4>In the first survey, 66 respondents yielded over 260 questions or challenges. These were thematically grouped and merged into a list of 40 unique questions. Eighty-eight stakeholders then ranked their top ten from the 40 questions in the second survey. The most common 14 questions were brought to the virtual consensus meeting in which stakeholders agreed a top list of seven questions. We report these seven questions which are within the following domains: trial design, Patient and Public Involvement, trial set-up, trial open and trial data. These questions address both evidence gaps (requiring further methodological research) and implementation gaps (requiring training and/or service re-organisation).<h4>Conclusion</h4>This prioritised list of seven questions should inform the direction of future research in this area and should direct efforts to ensure that the benefits in major infrastructure for routinely collected data are achieved and translated. Without this and future work to address these questions, the potential societal benefits of using routinely collected data to help answer important clinical questions will not be realised.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07251-x; doi:https://doi.org/10.1186/s13063-023-07251-x; html:https://europepmc.org/articles/PMC10064573; pdf:https://europepmc.org/articles/PMC10064573?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.<h4>Methods</h4>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.<h4>Results</h4>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; <i>P</i> = 0.017) and DQ4 (HR, 1.78; 95% CI, 1.07-2.96; <i>P</i> = 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; <i>P</i> < 0.001).<h4>Conclusion</h4>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; doi:https://doi.org/10.1097/TXD.0000000000001188; html:https://europepmc.org/articles/PMC9276282; pdf:https://europepmc.org/articles/PMC9276282?pdf=render
+36997954,https://doi.org/10.1186/s13063-023-07251-x,A DELPHI study priority setting the remaining challenges for the use of routinely collected data in trials: COMORANT-UK.,"Williams ADN, Davies G, Farrin AJ, Mafham M, Robling M, Sydes MR, Lugg-Widger FV.",,Trials,2023,2023-03-30,Y,Priority Setting; Consensus; Routinely Collected Data; Trials Methodology,,,"<h4>Background</h4>Researchers are increasingly seeking to use routinely collected data to support clinical trials. This approach has the potential to transform the way clinical trials are conducted in the future. The availability of routinely collected data for research, whether healthcare or administrative, has increased, and infrastructure funding has enabled much of this. However, challenges remain at all stages of a trial life cycle. This study, COMORANT-UK, aimed to systematically identify, with key stakeholders across the UK, the ongoing challenges related to trials that seek to use routinely collected data.<h4>Methods</h4>This three-step Delphi method consisted of two rounds of anonymous web-based surveys and a virtual consensus meeting. Stakeholders included trialists, data infrastructures, funders of trials, regulators, data providers and the public. Stakeholders identified research questions or challenges that they considered were of particular importance and then selected their top 10 in the second survey. The ranked questions were taken forward to the consensus meeting for discussion with representatives invited from the stakeholder groups.<h4>Results</h4>In the first survey, 66 respondents yielded over 260 questions or challenges. These were thematically grouped and merged into a list of 40 unique questions. Eighty-eight stakeholders then ranked their top ten from the 40 questions in the second survey. The most common 14 questions were brought to the virtual consensus meeting in which stakeholders agreed a top list of seven questions. We report these seven questions which are within the following domains: trial design, Patient and Public Involvement, trial set-up, trial open and trial data. These questions address both evidence gaps (requiring further methodological research) and implementation gaps (requiring training and/or service re-organisation).<h4>Conclusion</h4>This prioritised list of seven questions should inform the direction of future research in this area and should direct efforts to ensure that the benefits in major infrastructure for routinely collected data are achieved and translated. Without this and future work to address these questions, the potential societal benefits of using routinely collected data to help answer important clinical questions will not be realised.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07251-x; doi:https://doi.org/10.1186/s13063-023-07251-x; html:https://europepmc.org/articles/PMC10064573; pdf:https://europepmc.org/articles/PMC10064573?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,Y,epidemiology; Electronic Medical Records; Misclassification Bias; Value Sets; Health Data Science; Code Sets,,,"<h4>Objective</h4>To develop a standardizable, reproducible method for creating drug codelists that incorporates clinical expertise and is adaptable to other studies and databases.<h4>Materials and methods</h4>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.<h4>Results</h4>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).<h4>Discussion</h4>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.<h4>Conclusions</h4>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; html:https://europepmc.org/articles/PMC10463548; pdf:https://europepmc.org/articles/PMC10463548?pdf=render
 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.",,pdf:https://discovery.ucl.ac.uk/10145154/1/Bean_An%20open%20source%2C%20expert%20designed%20decision%20tree%20application%20to%20support%20accurate%20diagnosis%20of%20myeloid%20malignancies_VoR.pdf; doi:https://doi.org/10.1002/jha2.182; html:https://europepmc.org/articles/PMC9175663; pdf:https://europepmc.org/articles/PMC9175663?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.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-022-00962-6.pdf; doi:https://doi.org/10.1007/s10654-022-00962-6; html:https://europepmc.org/articles/PMC9860244; pdf:https://europepmc.org/articles/PMC9860244?pdf=render
@@ -521,8 +521,8 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development:
 31818272,https://doi.org/10.1186/s12889-019-8015-3,"Drinking beer, wine or spirits - does it matter for inequalities in alcohol-related hospital admission? A record-linked longitudinal study in Wales.","Gartner A, Trefan L, Moore S, Akbari A, Paranjothy S, Farewell D.",,BMC public health,2019,2019-12-09,Y,Alcohol; Inequalities; Deprivation; Hospital Admission; Beverage Type; Record Linked,Improving Public Health,,"<h4>Background</h4>Alcohol-related harm has been found to be higher in disadvantaged groups, despite similar alcohol consumption to advantaged groups. This is known as the alcohol harm paradox. Beverage type is reportedly socioeconomically patterned but has not been included in longitudinal studies investigating record-linked alcohol consumption and harm. We aimed to investigate whether and to what extent consumption by beverage type, BMI, smoking and other factors explain inequalities in alcohol-related harm.<h4>Methods</h4>11,038 respondents to the Welsh Health Survey answered questions on their health and lifestyle. Responses were record-linked to wholly attributable alcohol-related hospital admissions (ARHA) eight years before the survey month and until the end of 2016 within the Secure Anonymised Information Linkage (SAIL) Databank. We used survival analysis, specifically multi-level and multi-failure Cox mixed effects models, to calculate the hazard ratios of ARHA. In adjusted models we included the number of units consumed by beverage type and other factors, censoring for death or moving out of Wales.<h4>Results</h4>People living in more deprived areas had a higher risk of admission (HR 1.75; 95% CI 1.23-2.48) compared to less deprived. Adjustment for the number of units by type of alcohol consumed only reduced the risk of ARHA for more deprived areas by 4% (HR 1.72; 95% CI 1.21-2.44), whilst adding smoking and BMI reduced these inequalities by 35.7% (HR 1.48; 95% CI 1.01-2.17). These social patterns were similar for individual-level social class, employment, housing tenure and highest qualification. Inequalities were further reduced by including either health status (16.6%) or mental health condition (5%). Unit increases of spirits drunk were positively associated with increasing risk of ARHA (HR 1.06; 95% CI 1.01-1.12), higher than for other drink types.<h4>Conclusions</h4>Although consumption by beverage type was socioeconomically patterned, it did not help explain inequalities in alcohol-related harm. Smoking and BMI explained around a third of inequalities, but lower socioeconomic groups had a persistently higher risk of (multiple) ARHA. Comorbidities also explained a further proportion of inequalities and need further investigation, including the contribution of specific conditions. The increased harms from consumption of stronger alcoholic beverages may inform public health policy.","This longitudinal study investigated whether and to what extent consumption by beverage type, BMI, smoking and other factors explained inequalities in alcohol-related hospital admission (ARHA). Using statistical analysis methods, it was found that people living in more deprived areas had a higher risk of ARHA compared to less deprived. Smokers and people currently being treated for mental illness had higher risk of ARHA, while BMI appeared to be slightly protective. ",pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-019-8015-3; doi:https://doi.org/10.1186/s12889-019-8015-3; html:https://europepmc.org/articles/PMC6902530; pdf:https://europepmc.org/articles/PMC6902530?pdf=render
 37650026,https://doi.org/10.23889/ijpds.v7i1.1727,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,2022,2022-05-23,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.",,doi:https://doi.org/10.23889/ijpds.v7i1.1727; html:https://europepmc.org/articles/PMC10464868; pdf:https://europepmc.org/articles/PMC10464868?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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] <i>vs</i> 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.<h4>Interpretation</h4>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.<h4>Funding</h4>UK Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S2666756822000939/pdf; 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
-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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://bmcpulmmed.biomedcentral.com/counter/pdf/10.1186/s12890-022-02189-3; doi:https://doi.org/10.1186/s12890-022-02189-3; html:https://europepmc.org/articles/PMC9635147; pdf:https://europepmc.org/articles/PMC9635147?pdf=render
 31612961,https://doi.org/10.1093/nar/gkz895,GWAS Central: a comprehensive resource for the discovery and comparison of genotype and phenotype data from genome-wide association studies.,"Beck T, Shorter T, Brookes AJ.",,Nucleic acids research,2020,2020-01-01,Y,,,,"The GWAS Central resource provides a toolkit for integrative access and visualization of a uniquely extensive collection of genome-wide association study data, while ensuring safe open access to prevent research participant identification. GWAS Central is the world's most comprehensive openly accessible repository of summary-level GWAS association information, providing over 70 million P-values for over 3800 studies investigating over 1400 unique phenotypes. The database content comprises direct submissions received from GWAS authors and consortia, in addition to actively gathered data sets from various public sources. GWAS data are discoverable from the perspective of genetic markers, genes, genome regions or phenotypes, via graphical visualizations and detailed downloadable data reports. Tested genetic markers and relevant genomic features can be visually interrogated across up to sixteen multiple association data sets in a single view using the integrated genome browser. The semantic standardization of phenotype descriptions with Medical Subject Headings and the Human Phenotype Ontology allows the precise identification of genetic variants associated with diseases, phenotypes and traits of interest. Harmonization of the phenotype descriptions used across several GWAS-related resources has extended the phenotype search capabilities to enable cross-database study discovery using a range of ontologies. GWAS Central is updated regularly and available at https://www.gwascentral.org.",,pdf:https://academic.oup.com/nar/article-pdf/48/D1/D933/31697824/gkz895.pdf; doi:https://doi.org/10.1093/nar/gkz895; html:https://europepmc.org/articles/PMC7145571; pdf:https://europepmc.org/articles/PMC7145571?pdf=render
+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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://bmcpulmmed.biomedcentral.com/counter/pdf/10.1186/s12890-022-02189-3; 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.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.122.026432; doi:https://doi.org/10.1161/JAHA.122.026432; html:https://europepmc.org/articles/PMC9673731; pdf:https://europepmc.org/articles/PMC9673731?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.",,pdf:https://erj.ersjournals.com/content/erj/early/2023/03/15/13993003.01720-2022.full.pdf; doi:https://doi.org/10.1183/13993003.01720-2022; html:https://europepmc.org/articles/PMC10196345; pdf:https://europepmc.org/articles/PMC10196345?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>Databases (MEDLINE, EMBASE, PROSPERO, Cochrane library and <i>MedRxiv</i>) 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.<h4>Findings</h4>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]).<h4>Interpretation</h4>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.",,pdf:https://figshare.com/articles/journal_contribution/Ethnicity_and_clinical_outcomes_in_COVID-19_A_Systematic_Review_and_Meta-analysis/13147892/1/files/25502810.pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100630; html:https://europepmc.org/articles/PMC7658622; pdf:https://europepmc.org/articles/PMC7658622?pdf=render
@@ -541,8 +541,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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,,,"<h4>Objectives</h4>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.<h4>Design</h4>Population-based cohort study.<h4>Setting and population</h4>All live births in Scotland, 1 March 2020-31 January 2022.<h4>Results</h4>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.<h4>Implications and relevance</h4>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.",,pdf:https://fn.bmj.com/content/fetalneonatal/early/2023/01/05/archdischild-2022-324713.full.pdf; 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,,,"<h4>Objective</h4>To examine associations of birth weight with clinical and imaging indicators of cardiovascular health and evaluate mechanistic pathways in the UK Biobank.<h4>Methods</h4>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.<h4>Results</h4>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<sup>-5</sup>) 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).<h4>Conclusions</h4>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.",,pdf:https://heart.bmj.com/content/heartjnl/early/2022/11/15/heartjnl-2022-321733.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321733; html:https://europepmc.org/articles/PMC10086465; pdf:https://europepmc.org/articles/PMC10086465?pdf=render
 37781298,https://doi.org/10.3389/fcvm.2023.1141026,Radiomics analysis enhances the diagnostic performance of CMR stress perfusion: a proof-of-concept study using the Dan-NICAD dataset.,"Raisi-Estabragh Z, Martin-Isla C, Nissen L, Szabo L, Campello VM, Escalera S, Winther S, Bøttcher M, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2023,2023-09-15,Y,Machine Learning (Ml); Radiomics; Cmr (Cardiovascular Magnetic Resonance); Stress Perfusion Cardiac Mri; Dan-nicad,,,"<h4>Objectives</h4>To assess the feasibility of extracting radiomics signal intensity based features from the myocardium using cardiovascular magnetic resonance (CMR) imaging stress perfusion sequences. Furthermore, to compare the diagnostic performance of radiomics models against standard-of-care qualitative visual assessment of stress perfusion images, with the ground truth stenosis label being defined by invasive Fractional Flow Reserve (FFR) and quantitative coronary angiography.<h4>Methods</h4>We used the Dan-NICAD 1 dataset, a multi-centre study with coronary computed tomography angiography, 1,5 T CMR stress perfusion, and invasive FFR available for a subset of 148 patients with suspected coronary artery disease. Image segmentation was performed by two independent readers. We used the Pyradiomics platform to extract radiomics first-order (<i>n</i> = 14) and texture (<i>n</i> = 75) features from the LV myocardium (basal, mid, apical) in rest and stress perfusion images.<h4>Results</h4>Overall, 92 patients (mean age 62 years, 56 men) were included in the study, 39 with positive FFR. We double-cross validated the model and, in each inner fold, we trained and validated a per territory model. The conventional analysis results reported sensitivity of 41% and specificity of 84%. Our final radiomics model demonstrated an improvement on these results with an average sensitivity of 53% and specificity of 86%.<h4>Conclusion</h4>In this proof-of-concept study from the Dan-NICAD dataset, we demonstrate the feasibility of radiomics analysis applied to CMR perfusion images with a suggestion of superior diagnostic performance of radiomics models over conventional visual analysis of perfusion images in picking up perfusion defects defined by invasive coronary angiography.",,doi:https://doi.org/10.3389/fcvm.2023.1141026; html:https://europepmc.org/articles/PMC10541220; pdf:https://europepmc.org/articles/PMC10541220?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,,,"<h4>Objectives</h4>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.<h4>Setting</h4>A secondary care hospital in an NHS Trust in South West England.<h4>Participants</h4>Hospital admissions between September 2016 and March 2020, comprising 1291 days.<h4>Primary and secondary outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056523.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056523; html:https://europepmc.org/articles/PMC9021768; pdf:https://europepmc.org/articles/PMC9021768?pdf=render
 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; Lung Physiology,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%.<h4>Conclusion</h4>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.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/7/1/e000770.full.pdf; doi:https://doi.org/10.1136/bmjresp-2020-000770; html:https://europepmc.org/articles/PMC7754643; pdf:https://europepmc.org/articles/PMC7754643?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,,,"<h4>Objectives</h4>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.<h4>Setting</h4>A secondary care hospital in an NHS Trust in South West England.<h4>Participants</h4>Hospital admissions between September 2016 and March 2020, comprising 1291 days.<h4>Primary and secondary outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056523.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056523; html:https://europepmc.org/articles/PMC9021768; pdf:https://europepmc.org/articles/PMC9021768?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.",,pdf:https://thorax.bmj.com/content/thoraxjnl/76/8/835.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-215986; html:https://europepmc.org/articles/PMC8311087; pdf:https://europepmc.org/articles/PMC8311087?pdf=render
 31249320,https://doi.org/10.1038/s41598-019-45562-9,"Antenatal exposure to solar radiation and learning disabilities: Population cohort study of 422,512 children.","Hastie CE, Mackay DF, Clemens TL, Cherrie MPC, King A, Dibben C, Pell JP.",,Scientific reports,2019,2019-06-27,Y,,Improving Public Health,,"Learning disability varies by month of conception. The underlying mechanism is unknown but vitamin D, necessary for normal brain development, is commonly deficient over winter in high latitude countries due to insufficient ultraviolet radiation. We linked the 2007-2016 Scottish School Pupil Censuses to Scottish maternity records and to sunshine hours and antenatal ultraviolet A/B radiation exposure derived from weather stations and satellites respectively. Logistic regression analyses were used to explore the associations between solar radiation, then ultraviolet B, and learning disabilities, adjusting for the potential confounding effects of month of conception and sex. Of the 422,512 eligible, singleton schoolchildren born at term in Scotland, 79,616 (18.8%) had a learning disability. Total antenatal sunshine hours (highest quintile; adjusted OR 0.89; 95% CI: 0.86, 0.93; p < 0.001) and ultraviolet B exposure (highest quintile; adjusted OR 0.55; 95% CI: 0.51, 0.60; p < 0.001) were inversely associated with learning disabilities with evidence of a dose-relationship. The latter association was independent of ultraviolet A exposure. Significant associations were demonstrated for exposure in all three trimesters. Low maternal exposure to ultraviolet B radiation may play a role in the seasonal patterning of learning disabilities. Further studies are required to corroborate findings and determine the effectiveness of supplements.",,pdf:https://www.nature.com/articles/s41598-019-45562-9.pdf; doi:https://doi.org/10.1038/s41598-019-45562-9; html:https://europepmc.org/articles/PMC6597711; pdf:https://europepmc.org/articles/PMC6597711?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,,,,"<h4>Objectives</h4>To report on the long-term outcomes of the management of translated proximal humerus fractures.<h4>Design</h4>A prospective cohort study was conducted from January 2010 to December 2018.<h4>Setting</h4>Academic Level 1 trauma center.<h4>Participants/patients</h4>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.<h4>Intervention</h4>Patients were managed nonoperatively with sling immobilization or with operative management as determined by the treating surgeon.<h4>Main outcome measures</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>Translated proximal humerus fractures with ≥100% displacement demonstrate improved health status and radiological outcomes after surgical fixation.<h4>Level of evidence</h4>Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.",,doi:https://doi.org/10.1097/BOT.0000000000002612
@@ -551,8 +551,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 37272361,https://doi.org/10.2340/actadv.v103.5268,Relationship between Eczema and Self-reported Difficulties Keeping up with School Education: A Cross-sectional Study.,"Beckman L, Hagquist C, Svensson Å, Langan SM, Von Kobyletzki L.",,Acta dermato-venereologica,2023,2023-06-05,Y,,,,"Eczema is a common chronic disease that affects both children and adults, and may have an adverse impact on school performance, as it is characteristically pruritic, and hence may lead to poor concentration and inadequate sleep. The aim of this study was to elucidate the relationship between eczema and self-reported difficulties keeping up with school education. The study was based on cross-sectional questionnaire data collected in schools among all 9th graders (15-16 years old) within a Swedish county. Logistic regression analyses were used to assess the association between having eczema and self-reported difficulties keeping up with school education. A total of 2,620 pupils participated (50.1% female). An increased odds ratio (OR) of self-reported difficulties keeping up with school education was found in adolescents with eczema compared with those without eczema after adjustment for sex and  family residence (OR 2.13, 95% confidence interval (95% CI) 1.32-3.44), and with additional adjustment for sleeping problems, attention-deficit hyperactivity disorder, allergy, rhinitis, asthma, and alcohol consumption (adjusted OR 1.78, CI 1.05-3.00). Eczema may be a relevant risk factor for difficulty keeping up with school education in adolescents. However, studies that can assess temporality, based in different settings with objective reports of both eczema and self-reported difficulties at school, are needed to confirm these findings.",,doi:https://doi.org/10.2340/actadv.v103.5268; html:https://europepmc.org/articles/PMC10259463; pdf:https://europepmc.org/articles/PMC10259463?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.",,pdf:https://www.nature.com/articles/s41467-022-35017-7.pdf; doi:https://doi.org/10.1038/s41467-022-35017-7; html:https://europepmc.org/articles/PMC9708841; pdf:https://europepmc.org/articles/PMC9708841?pdf=render
 33545096,https://doi.org/10.1016/s0140-6736(21)00149-5,"Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2021,2021-02-02,Y,,,,"<h4>Background</h4>Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.<h4>Methods</h4>In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. 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 azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.<h4>Findings</h4>Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87-1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98-1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87-1·03; p=0·24).<h4>Interpretation</h4>In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication.<h4>Funding</h4>UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://www.thelancet.com/article/S0140673621001495/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00149-5; html:https://europepmc.org/articles/PMC7884931; pdf:https://europepmc.org/articles/PMC7884931?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,,,"<h4>Objectives</h4>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.<h4>Design</h4>An EHR-based, retrospective cohort study.<h4>Setting</h4>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).<h4>Participants</h4>In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged ≥30 years, respectively.<h4>Main outcome measures</h4>One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221131897; 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
 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,,"<h4>Aims</h4>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.<h4>Method and results</h4>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.<h4>Conclusion</h4>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.",pdf:https://academic.oup.com/ehjcvp/advance-article-pdf/doi/10.1093/ehjcvp/pvz071/31700014/pvz071.pdf; doi:https://doi.org/10.1093/ehjcvp/pvz071; html:https://europepmc.org/articles/PMC7811400; pdf:https://europepmc.org/articles/PMC7811400?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,,,"<h4>Objectives</h4>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.<h4>Design</h4>An EHR-based, retrospective cohort study.<h4>Setting</h4>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).<h4>Participants</h4>In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged ≥30 years, respectively.<h4>Main outcome measures</h4>One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221131897; 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
 37745706,https://doi.org/10.3389/fendo.2023.1266557,"Editorial: Integrative multi-modal, multi-omics analytics for the better understanding of metabolic diseases.","Acharjee A, Agarwal P, Gkoutos GV.",,Frontiers in endocrinology,2023,2023-09-08,Y,Biomarker; Therapeutic; Diagnostic; Metabolic Disease; Omics,,,,,doi:https://doi.org/10.3389/fendo.2023.1266557; html:https://europepmc.org/articles/PMC10516571; pdf:https://europepmc.org/articles/PMC10516571?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,,,,"<h4>Objective</h4>To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England.<h4>Design</h4>Matched cohort study, emulating a comparative effectiveness trial.<h4>Setting</h4>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.<h4>Participants</h4>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.<h4>Intervention</h4>Vaccination with either BNT162b2 or mRNA-1273 as a booster vaccine dose.<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.bmj.com/content/bmj/380/bmj-2022-072808.full.pdf; doi:https://doi.org/10.1136/bmj-2022-072808; html:https://europepmc.org/articles/PMC10014664; pdf:https://europepmc.org/articles/PMC10014664?pdf=render
 35497059,https://doi.org/10.1016/j.eclinm.2022.101392,Health conditions in adults with HIV compared with the general population: A population-based cross-sectional analysis.,"Morales DR, Moreno-Martos D, Matin N, McGettigan P.",,EClinicalMedicine,2022,2022-04-21,Y,HIV; Comorbidity; Multimorbidity,,,"<h4>Background</h4>Life expectancy in adults with human immunodeficiency virus (HIV) has increased and managing other health conditions is increasingly important for patients and healthcare planning. The aim of this study was to examine the prevalence and association between different health conditions and HIV status.<h4>Methods</h4>We performed a cross-sectional analysis of adult UK Clinical Practice Research Datalink primary care electronic medical records linked to hospital admissions as of Nov 30, 2015. We examined 47 health condition groups and 304 physical and mental health conditions by HIV status, after adjustment for age, sex, social deprivation status using logistic regression.<h4>Findings</h4>There were 964 patients with HIV (61.7% male; 92.8% aged <65 years) and 941,113 non-HIV patients (49.4% male; 75.2% aged <65 years). Condition groups with the greatest prevalence in HIV that were also highly prevalent in adults without HIV included: lipid disorder (41.4% vs 40.2%), and hypertension (19.1% vs 24.6%). Following adjustment, 18 (37.5%) condition groups were more likely in adults with HIV and ten (20.8%) were less likely. Individual conditions that were less likely in adults with HIV included: atrial fibrillation (odds ratio [OR] 0.37 [95% CI 0.20-0.64]) and hypertension (OR_0.78 [0.65-0.94]); rheumatoid arthritis (OR 0.27 [0.05-0.84]); asthma (OR_0.65 (0.53-0.80]); and certain eye diseases such as macular degeneration (OR_0.30 [0.09-0.70]). Meanwhile individual conditions that were more likely included: liver fibrosis, sclerosis, and cirrhosis (OR_3.23 [1.85-5.20]); pulmonary embolism (OR_2.06 [1.15-3.36]); male infertility (OR_2.23 [1.50-3.16]) and female infertility (OR_2.01 [1.34-2.88]); bipolar disorder (OR_2.93 [1.52-5.05]) and depression (OR_1.49 [1.28-1.71]); cervical malignancy (OR_4.64 [1.15-12.15]); and infections.<h4>Interpretation</h4>Comorbidity is common in adults with HIV, with physical and mental health conditions spanning a wide spectrum. HIV management should consider multidisciplinary care models to provide optimal patient care.<h4>Funding</h4>The project was funded by the Bart's Charity; DRM was funded by a Wellcome Trust Clinical Research Career Development Fellowship; DRM and DMM received funding from the HDR-UK Precision therapeutics programme.",,pdf:http://www.thelancet.com/article/S2589537022001225/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101392; html:https://europepmc.org/articles/PMC9046106; pdf:https://europepmc.org/articles/PMC9046106?pdf=render
@@ -578,11 +578,11 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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,,,"<h4>Introduction</h4>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).<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>NCT03463694.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/5/e049964.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049964; html:https://europepmc.org/articles/PMC8103393; pdf:https://europepmc.org/articles/PMC8103393?pdf=render
 34141852,https://doi.org/10.1016/j.ssmph.2021.100828,Media representations of opposition to the 'junk food advertising ban' on the Transport for London (TfL) network: A thematic content analysis of UK news and trade press.,"Thompson C, Clary C, Er V, Adams J, Boyland E, Burgoine T, Cornelsen L, de Vocht F, Egan M, Lake AA, Lock K, Mytton O, Petticrew M, White M, Yau A, Cummins S.",,SSM - population health,2021,2021-05-27,Y,Regulation; Media; Advertising; Childhood Obesity,,,"<h4>Background</h4>Advertising of less healthy foods and drinks is hypothesised to be associated with obesity in adults and children. In February 2019, Transport for London implemented restrictions on advertisements for foods and beverages high in fat, salt or sugar across its network as part of a city-wide strategy to tackle childhood obesity. The policy was extensively debated in the press. This paper identifies arguments for and against the restrictions. Focusing on arguments against the restrictions, it then goes on to deconstruct the discursive strategies underpinning them.<h4>Methods</h4>A qualitative thematic content analysis of media coverage of the restrictions (the 'ban') in UK newspapers and trade press was followed by a document analysis of arguments against the ban. A search period of March 1, 2018 to May 31, 2019 covered: (i) the launch of the public consultation on the ban in May 2018; (ii) the announcement of the ban in November 2018; and (iii) its implementation in February 2019. A systematic search of printed and online publications in English distributed in the UK or published on UK-specific websites identified 152 articles.<h4>Results</h4>Arguments in favour of the ban focused on inequalities and childhood obesity. Arguments against the ban centred on two claims: that childhood obesity was not the 'right' priority; and that an advertising ban was not an effective way to address childhood obesity. These claims were justified via three discursive approaches: (i) claiming more 'important' priorities for action; (ii) disputing the science behind the ban; (iii) emphasising potential financial costs of the ban.<h4>Conclusion</h4>The discursive tactics used in media sources to argue against the ban draw on frames widely used by unhealthy commodities industries in response to structural public health interventions. Our analyses highlight the need for interventions to be framed in ways that can pre-emptively counter common criticisms.",,doi:https://doi.org/10.1016/j.ssmph.2021.100828; doi:https://doi.org/10.1016/j.ssmph.2021.100828; html:https://europepmc.org/articles/PMC8184652; pdf:https://europepmc.org/articles/PMC8184652?pdf=render
 33199838,https://doi.org/10.1038/s41598-020-76860-2,Path-based extensions of local link prediction methods for complex networks.,"Aziz F, Gul H, Uddin I, Gkoutos GV.",,Scientific reports,2020,2020-11-16,Y,,,,"Link prediction in a complex network is a problem of fundamental interest in network science and has attracted increasing attention in recent years. It aims to predict missing (or future) links between two entities in a complex system that are not already connected. Among existing methods, local similarity indices are most popular that take into account the information of common neighbours to estimate the likelihood of existence of a connection between two nodes. In this paper, we propose global and quasi-local extensions of some commonly used local similarity indices. We have performed extensive numerical simulations on publicly available datasets from diverse domains demonstrating that the proposed extensions not only give superior performance, when compared to their respective local indices, but also outperform some of the current, state-of-the-art, local and global link-prediction methods.",,pdf:https://www.nature.com/articles/s41598-020-76860-2.pdf; doi:https://doi.org/10.1038/s41598-020-76860-2; html:https://europepmc.org/articles/PMC7670409; pdf:https://europepmc.org/articles/PMC7670409?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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; doi:https://doi.org/10.1016/j.cct.2023.107162
 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,,,"<b>Background</b>: ""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.  <b>Methods</b>: 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. <b>Results</b>: 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. <b>Conclusions:</b> 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
+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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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; doi:https://doi.org/10.1016/j.cct.2023.107162
 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,,,,"<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003497&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003497; html:https://europepmc.org/articles/PMC7880491; pdf:https://europepmc.org/articles/PMC7880491?pdf=render
-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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad055/49604587/zwad055.pdf; doi:https://doi.org/10.1093/eurjpc/zwad055; html:https://europepmc.org/articles/PMC10442054; pdf:https://europepmc.org/articles/PMC10442054?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-021-05295-5; doi:https://doi.org/10.1186/s13063-021-05295-5; html:https://europepmc.org/articles/PMC8108438; pdf:https://europepmc.org/articles/PMC8108438?pdf=render
+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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad055/49604587/zwad055.pdf; doi:https://doi.org/10.1093/eurjpc/zwad055; html:https://europepmc.org/articles/PMC10442054; pdf:https://europepmc.org/articles/PMC10442054?pdf=render
 34527726,https://doi.org/10.1183/23120541.00167-2021,Identifying COPD in routinely collected electronic health records: a systematic scoping review. ,"Sivakumaran S, Alsallakh MA, Lyons RA, Quint JK, Davies GA.",,ERJ open research,2021,2021-07-01,Y,,,,"Although routinely collected electronic health records (EHRs) are widely used to examine outcomes related to COPD, consensus regarding the identification of cases from electronic healthcare databases is lacking. We systematically examine and summarise approaches from the recent literature. MEDLINE via EBSCOhost was searched for COPD-related studies using EHRs published from January 1, 2018 to November 30, 2019. Data were extracted relating to the case definition of COPD and determination of COPD severity and phenotypes. From 185 eligible studies, we found widespread variation in the definitions used to identify people with COPD in terms of code sets used (with 20 different code sets in use based on the ICD-10 classification alone) and requirement of additional criteria (relating to age (n=139), medication (n=31), multiplicity of events (n=21), spirometry (n=19) and smoking status (n=9)). Only seven studies used a case definition which had been validated against a reference standard in the same dataset. Various proxies of disease severity were used since spirometry results and patient-reported outcomes were not often available. To enable the research community to draw reliable insights from EHRs and aid comparability between studies, clear reporting and greater consistency of the definitions used to identify COPD and related outcome measures is key.",,pdf:https://openres.ersjournals.com/content/erjor/7/3/00167-2021.full.pdf; doi:https://doi.org/10.1183/23120541.00167-2021; html:https://europepmc.org/articles/PMC8435805; pdf:https://europepmc.org/articles/PMC8435805?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 (R<sub>t</sub>) 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 R<sub>t</sub> from case data. However, these are not easily adapted to point prevalence data nor can they infer R<sub>t</sub> 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 R<sub>t</sub> 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 R<sub>t</sub> over shorter periods tracking a temporary increase above one during late-May 2020, a gradual increase in R<sub>t</sub> over the summer of 2020 as restrictions were eased, and a reduction in R<sub>t</sub> 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.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/99415/2/Appropriately%20smoothing%20prevalence%20data%20to%20inform%20estimates%20of%20growth%20rate%20and%20reproduction%20number.pdf; doi:https://doi.org/10.1016/j.epidem.2022.100604; html:https://europepmc.org/articles/PMC9220254; pdf:https://europepmc.org/articles/PMC9220254?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,,,"<h4>Background</h4>Colchicine has been proposed as a COVID-19 treatment.<h4>Aim</h4>To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community.<h4>Design and setting</h4>Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE).<h4>Method</h4>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.<h4>Results</h4>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 (<i>n</i> = 156), usual care (<i>n</i> = 1145), and other treatments (<i>n</i> = 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).<h4>Conclusion</h4>Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.",,pdf:https://bjgp.org/content/bjgp/72/720/e446.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0083; html:https://europepmc.org/articles/PMC9037186; pdf:https://europepmc.org/articles/PMC9037186?pdf=render
@@ -592,8 +592,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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,,,"<h4>Aims</h4>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.<h4>Materials and methods</h4>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.<h4>Results</h4>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]).<h4>Conclusions</h4>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
 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.",,pdf:https://www.nature.com/articles/s41591-022-02158-7.pdf; doi:https://doi.org/10.1038/s41591-022-02158-7
 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,,,"<h4>Introduction</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://ijpds.org/article/download/1387/3155; doi:https://doi.org/10.23889/ijpds.v6i1.1387; html:https://europepmc.org/articles/PMC8103995; pdf:https://europepmc.org/articles/PMC8103995?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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279076&type=printable; doi:https://doi.org/10.1371/journal.pone.0279076; html:https://europepmc.org/articles/PMC10065228; pdf:https://europepmc.org/articles/PMC10065228?pdf=render
 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,2023,2022-04-29,Y,Mortality; Schizophrenia; Psychosis; Physical Health; Multimorbidity,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,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; doi:https://doi.org/10.1017/S003329172200109X; html:https://europepmc.org/articles/PMC10388332; pdf:https://europepmc.org/articles/PMC10388332?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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279076&type=printable; doi:https://doi.org/10.1371/journal.pone.0279076; html:https://europepmc.org/articles/PMC10065228; pdf:https://europepmc.org/articles/PMC10065228?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
 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,,,"<h4>Objective</h4>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.<h4>Design</h4>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.<h4>Setting</h4>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.<h4>Participants</h4>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.<h4>Outcome measures</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>State of the art NLP models can extract and classify clinical text on violence from EHRs at acceptable levels of scale, efficiency and accuracy.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e052911.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052911; html:https://europepmc.org/articles/PMC8852656; pdf:https://europepmc.org/articles/PMC8852656?pdf=render
 31594227,https://doi.org/10.3233/jad-190571,Partner Bereavement and Detection of Dementia: A UK-Based Cohort Study Using Routine Health Data.,"Forbes HJ, Wong AYS, Morton C, Bhaskaran K, Smeeth L, Richards M, Schmidt SAJ, Langan SM, Warren-Gash C.",,Journal of Alzheimer's disease : JAD,2019,2019-01-01,Y,Diagnosis; Dementia; epidemiology; Bereavement; Clinical Practice Research Datalink,"Improving Public Health, Understanding the Causes of Disease",,"<h4>Background</h4>In the UK, an estimated one third of people with dementia have not received a diagnosis. Good evidence suggests that dementia risk is increased among widowed individuals; however, it is not clear if they are being diagnosed in routine primary care.<h4>Objective</h4>This study aimed to investigate if bereavement influenced the probability of having received a dementia diagnosis.<h4>Methods</h4>A population-based cohort study using UK electronic health records, between 1997 and 2017, among 247,586 opposite-sex partners. Those experiencing partner bereavement were matched (age, sex, and date of bereavement) to a non-bereaved person living in a partnership. Multivariate cox regression was performed.<h4>Results</h4>Partner bereavement was associated with an increased risk of receiving a diagnosis of dementia in the first three months (hazard ratio (HR) 1.43, 95% CI 1.20-1.71) and first six months (HR 1.24, 95% CI 1.09-1.41), while there was a small reduced risk of getting a dementia diagnosis over all follow-up (HR 0.94, 95% CI 0.89-0.98).<h4>Conclusions</h4>Partner bereavement appears to lead to a short-term increased risk of the surviving partner receiving a diagnosis of dementia, suggesting that bereavement unmasks existing undiagnosed dementia. Over the longer term, however, bereaved individuals are less likely to have a diagnosis of dementia in their health records than non-bereaved individuals.",,pdf:https://europepmc.org/articles/pmc6918907?pdf=render; doi:https://doi.org/10.3233/JAD-190571; html:https://europepmc.org/articles/PMC6918907; pdf:https://europepmc.org/articles/PMC6918907?pdf=render
@@ -604,13 +604,13 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:http://www.bjanaesthesia.org/article/S0007091221002737/pdf; 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
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05025.pdf; doi:https://doi.org/10.7189/jogh.12.05025; html:https://europepmc.org/articles/PMC9269984; pdf:https://europepmc.org/articles/PMC9269984?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,,,"<h4>Background</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-022-02745-4; doi:https://doi.org/10.1186/s13059-022-02745-4; html:https://europepmc.org/articles/PMC9394047; pdf:https://europepmc.org/articles/PMC9394047?pdf=render
-37699069,https://doi.org/10.1093/ehjci/jead218,Phenotyping left ventricular systolic dysfunction in asymptomatic individuals for improved risk stratification.,"Rauseo E, Abdulkareem M, Khan A, Cooper J, Lee AM, Aung N, Slabaugh GG, Petersen SE.",,European heart journal. Cardiovascular Imaging,2023,2023-09-01,Y,Prognosis; Cardiovascular events; Risk stratification; Heart Failure; Cardiovascular Magnetic Resonance; Left Ventricular Systolic Dysfunction,,,"<h4>Aims</h4>Left ventricular systolic dysfunction (LSVD) is a heterogeneous condition with several factors influencing prognosis. Better phenotyping of asymptomatic individuals can inform preventative strategies. This study aims to explore the clinical phenotypes of LVSD in initially asymptomatic subjects and their association with clinical outcomes and cardiovascular abnormalities through multi-dimensional data clustering.<h4>Methods and results</h4>Clustering analysis was performed on 60 clinically available variables from 1563 UK Biobank participants without pre-existing heart failure (HF) and with left ventricular ejection fraction (LVEF) < 50% on cardiovascular magnetic resonance (CMR) assessment. Risks of developing HF, other cardiovascular events, death, and a composite of major adverse cardiovascular events (MACE) associated with clusters were investigated. Cardiovascular imaging characteristics, not included in the clustering analysis, were also evaluated. Three distinct clusters were identified, differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles. A stepwise increase in risk profile was observed from Cluster 1 to Cluster 3, independent of traditional risk factors and LVEF. Compared with Cluster 1, the lowest risk subset, the risk of MACE ranged from 1.42 [95% confidence interval (CI): 1.03-1.96; P < 0.05] for Cluster 2 to 1.72 (95% CI: 1.36-2.35; P < 0.001) for Cluster 3. Cluster 3, the highest risk profile, had features of adverse cardiovascular imaging with the greatest LV re-modelling, myocardial dysfunction, and decrease in arterial compliance.<h4>Conclusions</h4>Clustering of clinical variables identified three distinct risk profiles and clinical trajectories of LVSD amongst initially asymptomatic subjects. Improved characterization may facilitate tailored interventions based on the LVSD sub-type and improve clinical outcomes.",,doi:https://doi.org/10.1093/ehjci/jead218; html:https://europepmc.org/articles/PMC10531121; pdf:https://europepmc.org/articles/PMC10531121?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,,,"<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%.<h4>Conclusions</h4>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.",,pdf:http://www.journalofinfection.com/article/S0163445321001158/pdf; 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
+37699069,https://doi.org/10.1093/ehjci/jead218,Phenotyping left ventricular systolic dysfunction in asymptomatic individuals for improved risk stratification.,"Rauseo E, Abdulkareem M, Khan A, Cooper J, Lee AM, Aung N, Slabaugh GG, Petersen SE.",,European heart journal. Cardiovascular Imaging,2023,2023-09-01,Y,Prognosis; Cardiovascular events; Risk stratification; Heart Failure; Cardiovascular Magnetic Resonance; Left Ventricular Systolic Dysfunction,,,"<h4>Aims</h4>Left ventricular systolic dysfunction (LSVD) is a heterogeneous condition with several factors influencing prognosis. Better phenotyping of asymptomatic individuals can inform preventative strategies. This study aims to explore the clinical phenotypes of LVSD in initially asymptomatic subjects and their association with clinical outcomes and cardiovascular abnormalities through multi-dimensional data clustering.<h4>Methods and results</h4>Clustering analysis was performed on 60 clinically available variables from 1563 UK Biobank participants without pre-existing heart failure (HF) and with left ventricular ejection fraction (LVEF) < 50% on cardiovascular magnetic resonance (CMR) assessment. Risks of developing HF, other cardiovascular events, death, and a composite of major adverse cardiovascular events (MACE) associated with clusters were investigated. Cardiovascular imaging characteristics, not included in the clustering analysis, were also evaluated. Three distinct clusters were identified, differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles. A stepwise increase in risk profile was observed from Cluster 1 to Cluster 3, independent of traditional risk factors and LVEF. Compared with Cluster 1, the lowest risk subset, the risk of MACE ranged from 1.42 [95% confidence interval (CI): 1.03-1.96; P < 0.05] for Cluster 2 to 1.72 (95% CI: 1.36-2.35; P < 0.001) for Cluster 3. Cluster 3, the highest risk profile, had features of adverse cardiovascular imaging with the greatest LV re-modelling, myocardial dysfunction, and decrease in arterial compliance.<h4>Conclusions</h4>Clustering of clinical variables identified three distinct risk profiles and clinical trajectories of LVSD amongst initially asymptomatic subjects. Improved characterization may facilitate tailored interventions based on the LVSD sub-type and improve clinical outcomes.",,doi:https://doi.org/10.1093/ehjci/jead218; html:https://europepmc.org/articles/PMC10531121; pdf:https://europepmc.org/articles/PMC10531121?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,,,"<h4>Background</h4>The percentage of total body surface area (%TBSA) burned and burn depth provide valuable information on burn injury severity.<h4>Objective</h4>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.<h4>Method</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.<h4>Implications</h4>Greater consistency in the classification of burns is needed.",,doi:https://doi.org/10.1177/18333583221135710
 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,,,"<h4>Background</h4>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.<h4>Study design and methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>Personalized inter-donation intervals using post-donation testing combined with modeling of hemoglobin trajectories can help reduce deferrals, inappropriate bleeds, and costs.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/trf.17277; doi:https://doi.org/10.1111/trf.17277
-37468148,https://doi.org/10.1136/bmj-2023-075133,Associations between self-reported healthcare disruption due to covid-19 and avoidable hospital admission: evidence from seven linked longitudinal studies for England.,"Green MA, McKee M, Hamilton OK, Shaw RJ, Macleod J, Boyd A, Katikireddi SV, LH&W NCS Collaborative.",,BMJ (Clinical research ed.),2023,2023-07-19,Y,,,,"<h4>Objectives</h4>To examine whether there is an association between people who experienced disrupted access to healthcare during the covid-19 pandemic and risk of an avoidable hospital admission.<h4>Design</h4>Observational analysis using evidence from seven linked longitudinal cohort studies for England.<h4>Setting</h4>Studies linked to electronic health records from NHS Digital from 1 March 2020 to 25 August 2022. Data were accessed using the UK Longitudinal Linkage Collaboration trusted research environment.<h4>Participants</h4>Individual level records for 29 276 people.<h4>Main outcome measures</h4>Avoidable hospital admissions defined as emergency hospital admissions for ambulatory care sensitive and emergency urgent care sensitive conditions.<h4>Results</h4>9742 participants (weighted percentage 35%, adjusted for sample structure of longitudinal cohorts) self-reported some form of disrupted access to healthcare during the covid-19 pandemic. People with disrupted access were at increased risk of any (odds ratio 1.80, 95% confidence interval 1.39 to 2.34), acute (2.01, 1.39 to 2.92), and chronic (1.80, 1.31 to 2.48) ambulatory care sensitive hospital admissions. For people who experienced disrupted access to appointments (eg, visiting their doctor or an outpatient department) and procedures (eg, surgery, cancer treatment), positive associations were found with measures of avoidable hospital admissions.<h4>Conclusions</h4>Evidence from linked individual level data shows that people whose access to healthcare was disrupted were more likely to have a potentially preventable hospital admission. The findings highlight the need to increase healthcare investment to tackle the short and long term implications of the pandemic, and to protect treatments and procedures during future pandemics.",,doi:https://doi.org/10.1136/bmj-2023-075133; html:https://europepmc.org/articles/PMC10354595; pdf:https://europepmc.org/articles/PMC10354595?pdf=render
-33212507,https://doi.org/10.1093/molbev/msaa279,Genomic Analysis Revealed a Convergent Evolution of LINE-1 in Coat Color: A Case Study in Water Buffaloes (Bubalus bubalis).,"Liang D, Zhao P, Si J, Fang L, Pairo-Castineira E, Hu X, Xu Q, Hou Y, Gong Y, Liang Z, Tian B, Mao H, Yindee M, Faruque MO, Kongvongxay S, Khamphoumee S, Liu GE, Wu DD, Barker JSF, Han J, Zhang Y.",,Molecular biology and evolution,2021,2021-03-01,Y,Transposon; Water buffalo; Convergent Evolution; Line-1; Asip Gene; White Coat Color,,,"Visible pigmentation phenotypes can be used to explore the regulation of gene expression and the evolution of coat color patterns in animals. Here, we performed whole-genome and RNA sequencing and applied genome-wide association study, comparative population genomics and biological experiments to show that the 2,809-bp-long LINE-1 insertion in the ASIP (agouti signaling protein) gene is the causative mutation for the white coat phenotype in swamp buffalo (Bubalus bubalis). This LINE-1 insertion (3' truncated and containing only 5' UTR) functions as a strong proximal promoter that leads to a 10-fold increase in the transcription of ASIP in white buffalo skin. The 165 bp of 5' UTR transcribed from the LINE-1 is spliced into the first coding exon of ASIP, resulting in a chimeric transcript. The increased expression of ASIP prevents melanocyte maturation, leading to the absence of pigment in white buffalo skin and hairs. Phylogenetic analyses indicate that the white buffalo-specific ASIP allele originated from a recent genetic transposition event in swamp buffalo. Interestingly, as a similar LINE-1 insertion has been identified in the cattle ASIP gene, we discuss the convergent mechanism of coat color evolution in the Bovini tribe.",,pdf:https://academic.oup.com/mbe/article-pdf/38/3/1122/36533820/msaa279.pdf; doi:https://doi.org/10.1093/molbev/msaa279; html:https://europepmc.org/articles/PMC7947781; pdf:https://europepmc.org/articles/PMC7947781?pdf=render
 32424068,https://doi.org/10.1101/gr.250704.119,Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle.,"Fang L, Cai W, Liu S, Canela-Xandri O, Gao Y, Jiang J, Rawlik K, Li B, Schroeder SG, Rosen BD, Li CJ, Sonstegard TS, Alexander LJ, Van Tassell CP, VanRaden PM, Cole JB, Yu Y, Zhang S, Tenesa A, Ma L, Liu GE.",,Genome research,2020,2020-05-18,Y,,,,"By uniformly analyzing 723 RNA-seq data from 91 tissues and cell types, we built a comprehensive gene atlas and studied tissue specificity of genes in cattle. We demonstrated that tissue-specific genes significantly reflected the tissue-relevant biology, showing distinct promoter methylation and evolution patterns (e.g., brain-specific genes evolve slowest, whereas testis-specific genes evolve fastest). Through integrative analyses of those tissue-specific genes with large-scale genome-wide association studies, we detected relevant tissues/cell types and candidate genes for 45 economically important traits in cattle, including blood/immune system (e.g., <i>CCDC88C</i>) for male fertility, brain (e.g., <i>TRIM46</i> and <i>RAB6A</i>) for milk production, and multiple growth-related tissues (e.g., <i>FGF6</i> and <i>CCND2</i>) for body conformation. We validated these findings by using epigenomic data across major somatic tissues and sperm. Collectively, our findings provided novel insights into the genetic and biological mechanisms underlying complex traits in cattle, and our transcriptome atlas can serve as a primary source for biological interpretation, functional validation, studies of adaptive evolution, and genomic improvement in livestock.",,pdf:https://genome.cshlp.org/content/30/5/790.full.pdf; doi:https://doi.org/10.1101/gr.250704.119; html:https://europepmc.org/articles/PMC7263193; pdf:https://europepmc.org/articles/PMC7263193?pdf=render
+33212507,https://doi.org/10.1093/molbev/msaa279,Genomic Analysis Revealed a Convergent Evolution of LINE-1 in Coat Color: A Case Study in Water Buffaloes (Bubalus bubalis).,"Liang D, Zhao P, Si J, Fang L, Pairo-Castineira E, Hu X, Xu Q, Hou Y, Gong Y, Liang Z, Tian B, Mao H, Yindee M, Faruque MO, Kongvongxay S, Khamphoumee S, Liu GE, Wu DD, Barker JSF, Han J, Zhang Y.",,Molecular biology and evolution,2021,2021-03-01,Y,Transposon; Water buffalo; Convergent Evolution; Line-1; Asip Gene; White Coat Color,,,"Visible pigmentation phenotypes can be used to explore the regulation of gene expression and the evolution of coat color patterns in animals. Here, we performed whole-genome and RNA sequencing and applied genome-wide association study, comparative population genomics and biological experiments to show that the 2,809-bp-long LINE-1 insertion in the ASIP (agouti signaling protein) gene is the causative mutation for the white coat phenotype in swamp buffalo (Bubalus bubalis). This LINE-1 insertion (3' truncated and containing only 5' UTR) functions as a strong proximal promoter that leads to a 10-fold increase in the transcription of ASIP in white buffalo skin. The 165 bp of 5' UTR transcribed from the LINE-1 is spliced into the first coding exon of ASIP, resulting in a chimeric transcript. The increased expression of ASIP prevents melanocyte maturation, leading to the absence of pigment in white buffalo skin and hairs. Phylogenetic analyses indicate that the white buffalo-specific ASIP allele originated from a recent genetic transposition event in swamp buffalo. Interestingly, as a similar LINE-1 insertion has been identified in the cattle ASIP gene, we discuss the convergent mechanism of coat color evolution in the Bovini tribe.",,pdf:https://academic.oup.com/mbe/article-pdf/38/3/1122/36533820/msaa279.pdf; doi:https://doi.org/10.1093/molbev/msaa279; html:https://europepmc.org/articles/PMC7947781; pdf:https://europepmc.org/articles/PMC7947781?pdf=render
+37468148,https://doi.org/10.1136/bmj-2023-075133,Associations between self-reported healthcare disruption due to covid-19 and avoidable hospital admission: evidence from seven linked longitudinal studies for England.,"Green MA, McKee M, Hamilton OK, Shaw RJ, Macleod J, Boyd A, Katikireddi SV, LH&W NCS Collaborative.",,BMJ (Clinical research ed.),2023,2023-07-19,Y,,,,"<h4>Objectives</h4>To examine whether there is an association between people who experienced disrupted access to healthcare during the covid-19 pandemic and risk of an avoidable hospital admission.<h4>Design</h4>Observational analysis using evidence from seven linked longitudinal cohort studies for England.<h4>Setting</h4>Studies linked to electronic health records from NHS Digital from 1 March 2020 to 25 August 2022. Data were accessed using the UK Longitudinal Linkage Collaboration trusted research environment.<h4>Participants</h4>Individual level records for 29 276 people.<h4>Main outcome measures</h4>Avoidable hospital admissions defined as emergency hospital admissions for ambulatory care sensitive and emergency urgent care sensitive conditions.<h4>Results</h4>9742 participants (weighted percentage 35%, adjusted for sample structure of longitudinal cohorts) self-reported some form of disrupted access to healthcare during the covid-19 pandemic. People with disrupted access were at increased risk of any (odds ratio 1.80, 95% confidence interval 1.39 to 2.34), acute (2.01, 1.39 to 2.92), and chronic (1.80, 1.31 to 2.48) ambulatory care sensitive hospital admissions. For people who experienced disrupted access to appointments (eg, visiting their doctor or an outpatient department) and procedures (eg, surgery, cancer treatment), positive associations were found with measures of avoidable hospital admissions.<h4>Conclusions</h4>Evidence from linked individual level data shows that people whose access to healthcare was disrupted were more likely to have a potentially preventable hospital admission. The findings highlight the need to increase healthcare investment to tackle the short and long term implications of the pandemic, and to protect treatments and procedures during future pandemics.",,doi:https://doi.org/10.1136/bmj-2023-075133; html:https://europepmc.org/articles/PMC10354595; pdf:https://europepmc.org/articles/PMC10354595?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.",,pdf:https://pn.bmj.com/content/practneurol/early/2023/02/19/pn-2021-003286.full.pdf; doi:https://doi.org/10.1136/pn-2021-003286; html:https://europepmc.org/articles/PMC10423506; pdf:https://europepmc.org/articles/PMC10423506?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,,,,"<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Findings</h4>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 <i>vs</i> 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.<h4>Interpretation</h4>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.<h4>Funding</h4>UK Government Department of Health and Social Care.",,pdf:http://pure-oai.bham.ac.uk/ws/files/173553190/1_s2.0_S2666756822001180_main.pdf; 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
 33634312,https://doi.org/10.1093/bib/bbab006,Benchmarking network-based gene prioritization methods for cerebral small vessel disease.,"Zhang H, Ferguson A, Robertson G, Jiang M, Zhang T, Sudlow C, Smith K, Rannikmae K, Wu H.",,Briefings in bioinformatics,2021,2021-09-01,Y,Cerebral Small Vessel Disease; Protein–protein Interaction; Benchmarking; Disease Gene Association; Network-based Gene Prioritization,,,"Network-based gene prioritization algorithms are designed to prioritize disease-associated genes based on known ones using biological networks of protein interactions, gene-disease associations (GDAs) and other relationships between biological entities. Various algorithms have been developed based on different mechanisms, but it is not obvious which algorithm is optimal for a specific disease. To address this issue, we benchmarked multiple algorithms for their application in cerebral small vessel disease (cSVD). We curated protein-gene interactions (PGIs) and GDAs from databases and assembled PGI networks and disease-gene heterogeneous networks. A screening of algorithms resulted in seven representative algorithms to be benchmarked. Performance of algorithms was assessed using both leave-one-out cross-validation (LOOCV) and external validation with MEGASTROKE genome-wide association study (GWAS). We found that random walk with restart on the heterogeneous network (RWRH) showed best LOOCV performance, with median LOOCV rediscovery rank of 185.5 (out of 19 463 genes). The GenePanda algorithm had most GWAS-confirmable genes in top 200 predictions, while RWRH had best ranks for small vessel stroke-associated genes confirmed in GWAS. In conclusion, RWRH has overall better performance for application in cSVD despite its susceptibility to bias caused by degree centrality. Choice of algorithms should be determined before applying to specific disease. Current pure network-based gene prioritization algorithms are unlikely to find novel disease-associated genes that are not associated with known ones. The tools for implementing and benchmarking algorithms have been made available and can be generalized for other diseases.",,pdf:https://www.pure.ed.ac.uk/ws/files/198917679/bbab006.pdf; doi:https://doi.org/10.1093/bib/bbab006; html:https://europepmc.org/articles/PMC8425308; pdf:https://europepmc.org/articles/PMC8425308?pdf=render
@@ -623,16 +623,16 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 37907891,https://doi.org/10.1186/s12888-023-05217-6,"Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.","Bala JJ, Bala JD, Pell JP, Fleming M.",,BMC psychiatry,2023,2023-10-31,Y,attention deficit disorder with hyperactivity; Cohort studies; Education; Medical Record Linkage; Apgar Score,,,"<h4>Background</h4>Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings.<h4>Methods</h4>Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders.<h4>Results</h4>Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range.<h4>Conclusions</h4>In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.",,doi:https://doi.org/10.1186/s12888-023-05217-6; html:https://europepmc.org/articles/PMC10619264; pdf:https://europepmc.org/articles/PMC10619264?pdf=render
 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,,,,"<h4>Objective</h4>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.<h4>Design</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.<h4>Significance statement</h4>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.",,pdf:https://academic.oup.com/ejendo/article-pdf/184/5/637/45221794/eje-20-1163.pdf; doi:https://doi.org/10.1530/EJE-20-1163; html:https://europepmc.org/articles/PMC8052516; pdf:https://europepmc.org/articles/PMC8052516?pdf=render
 35105585,https://doi.org/10.1136/bmjopen-2021-054376,Development of an algorithm to classify primary care electronic health records of alcohol consumption: experience using data linkage from UK Biobank and primary care electronic health data sources.,"Fraile-Navarro D, Azcoaga-Lorenzo A, Agrawal U, Jani B, Fagbamigbe A, Currie D, Baldacchino A, Sullivan F.",,BMJ open,2022,2022-02-01,Y,Public Health; Primary Care; Health Informatics,,,"<h4>Objectives</h4>Develop a novel algorithm to categorise alcohol consumption using primary care electronic health records (EHRs) and asses its reliability by comparing this classification with self-reported alcohol consumption data obtained from the UK Biobank (UKB) cohort.<h4>Design</h4>Cross-sectional study.<h4>Setting</h4>The UKB, a population-based cohort with participants aged between 40 and 69 years recruited across the UK between 2006 and 2010.<h4>Participants</h4>UKB participants from Scotland with linked primary care data.<h4>Primary and secondary outcome measures</h4>Create a rule-based multiclass algorithm to classify alcohol consumption reported by Scottish UKB participants and compare it with their classification using data present in primary care EHRs based on Read Codes. We evaluated agreement metrics (simple agreement and kappa statistic).<h4>Results</h4>Among the Scottish UKB participants, 18 838 (69%) had at least one Read Code related to alcohol consumption and were used in the classification. The agreement of alcohol consumption categories between UKB and primary care data, including assessments within 5 years was 59.6%, and kappa was 0.23 (95% CI 0.21 to 0.24). Differences in classification between the two sources were statistically significant (p<0.001); More individuals were classified as 'sensible drinkers' and in lower alcohol consumption levels in primary care records compared with the UKB. Agreement improved slightly when using only numerical values (k=0.29; 95% CI 0.27 to 0.31) and decreased when using qualitative descriptors only (k=0.18;95% CI 0.16 to 0.20).<h4>Conclusion</h4>Our algorithm classifies alcohol consumption recorded in Primary Care EHRs into discrete meaningful categories. These results suggest that alcohol consumption may be underestimated in primary care EHRs. Using numerical values (alcohol units) may improve classification when compared with qualitative descriptors.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e054376.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054376; html:https://europepmc.org/articles/PMC8808438; pdf:https://europepmc.org/articles/PMC8808438?pdf=render
-36805366,https://doi.org/10.2196/43419,Prediction of Suicidal Behaviors in the Middle-aged Population: Machine Learning Analyses of UK Biobank.,"Wang J, Qiu J, Zhu T, Zeng Y, Yang H, Shang Y, Yin J, Sun Y, Qu Y, Valdimarsdóttir UA, Song H.",,JMIR public health and surveillance,2023,2023-02-20,Y,Sex; Model; Behavior; Genetic susceptibility; Data; Suicide; risk; Machine Learning; Risk Prediction; Cost-effective; Machine Learning Approach; Suicidal Behaviors,,,"<h4>Background</h4>Suicidal behaviors, including suicide deaths and attempts, are major public health concerns. However, previous suicide models required a huge amount of input features, resulting in limited applicability in clinical practice.<h4>Objective</h4>We aimed to construct applicable models (ie, with limited features) for short- and long-term suicidal behavior prediction. We further validated these models among individuals with different genetic risks of suicide.<h4>Methods</h4>Based on the prospective cohort of UK Biobank, we included 223 (0.06%) eligible cases of suicide attempts or deaths, according to hospital inpatient or death register data within 1 year from baseline and randomly selected 4460 (1.18%) controls (1:20) without such records. We similarly identified 833 (0.22%) cases of suicidal behaviors 1 to 6 years from baseline and 16,660 (4.42%) corresponding controls. Based on 143 input features, mainly including sociodemographic, environmental, and psychosocial factors; medical history; and polygenic risk scores (PRS) for suicidality, we applied a bagged balanced light gradient-boosting machine (LightGBM) with stratified 10-fold cross-validation and grid-search to construct the full prediction models for suicide attempts or deaths within 1 year or between 1 and 6 years. The Shapley Additive Explanations (SHAP) approach was used to quantify the importance of input features, and the top 20 features with the highest SHAP values were selected to train the applicable models. The external validity of the established models was assessed among 50,310 individuals who participated in UK Biobank repeated assessments both overall and by the level of PRS for suicidality.<h4>Results</h4>Individuals with suicidal behaviors were on average 56 years old, with equal sex distribution. The application of these full models in the external validation data set demonstrated good model performance, with the area under the receiver operating characteristic (AUROC) curves of 0.919 and 0.892 within 1 year and between 1 and 6 years, respectively. Importantly, the applicable models with the top 20 most important features showed comparable external-validated performance (AUROC curves of 0.901 and 0.885) as the full models, based on which we found that individuals in the top quintile of predicted risk accounted for 91.7% (n=11) and 80.7% (n=25) of all suicidality cases within 1 year and during 1 to 6 years, respectively. We further obtained comparable prediction accuracy when applying these models to subpopulations with different genetic susceptibilities to suicidality. For example, for the 1-year risk prediction, the AUROC curves were 0.907 and 0.885 for the high (>2nd tertile of PRS) and low (<1st) genetic susceptibilities groups, respectively.<h4>Conclusions</h4>We established applicable machine learning-based models for predicting both the short- and long-term risk of suicidality with high accuracy across populations of varying genetic risk for suicide, highlighting a cost-effective method of identifying individuals with a high risk of suicidality.",,pdf:https://publichealth.jmir.org/2023/1/e43419/PDF; doi:https://doi.org/10.2196/43419; html:https://europepmc.org/articles/PMC9989910
 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.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3235; doi:https://doi.org/10.1002/cnm.3235; html:https://europepmc.org/articles/PMC6851543; pdf:https://europepmc.org/articles/PMC6851543?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,,,"<h4>Background</h4>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).<h4>Objective</h4>We describe the deployment of the EHR interfacing information extraction and retrieval platform CogStack at University College London Hospitals (UCLH).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://medinform.jmir.org/2022/8/e38122/PDF; doi:https://doi.org/10.2196/38122; html:https://europepmc.org/articles/PMC9453582
+36805366,https://doi.org/10.2196/43419,Prediction of Suicidal Behaviors in the Middle-aged Population: Machine Learning Analyses of UK Biobank.,"Wang J, Qiu J, Zhu T, Zeng Y, Yang H, Shang Y, Yin J, Sun Y, Qu Y, Valdimarsdóttir UA, Song H.",,JMIR public health and surveillance,2023,2023-02-20,Y,Sex; Model; Behavior; Genetic susceptibility; Data; Suicide; risk; Machine Learning; Risk Prediction; Cost-effective; Machine Learning Approach; Suicidal Behaviors,,,"<h4>Background</h4>Suicidal behaviors, including suicide deaths and attempts, are major public health concerns. However, previous suicide models required a huge amount of input features, resulting in limited applicability in clinical practice.<h4>Objective</h4>We aimed to construct applicable models (ie, with limited features) for short- and long-term suicidal behavior prediction. We further validated these models among individuals with different genetic risks of suicide.<h4>Methods</h4>Based on the prospective cohort of UK Biobank, we included 223 (0.06%) eligible cases of suicide attempts or deaths, according to hospital inpatient or death register data within 1 year from baseline and randomly selected 4460 (1.18%) controls (1:20) without such records. We similarly identified 833 (0.22%) cases of suicidal behaviors 1 to 6 years from baseline and 16,660 (4.42%) corresponding controls. Based on 143 input features, mainly including sociodemographic, environmental, and psychosocial factors; medical history; and polygenic risk scores (PRS) for suicidality, we applied a bagged balanced light gradient-boosting machine (LightGBM) with stratified 10-fold cross-validation and grid-search to construct the full prediction models for suicide attempts or deaths within 1 year or between 1 and 6 years. The Shapley Additive Explanations (SHAP) approach was used to quantify the importance of input features, and the top 20 features with the highest SHAP values were selected to train the applicable models. The external validity of the established models was assessed among 50,310 individuals who participated in UK Biobank repeated assessments both overall and by the level of PRS for suicidality.<h4>Results</h4>Individuals with suicidal behaviors were on average 56 years old, with equal sex distribution. The application of these full models in the external validation data set demonstrated good model performance, with the area under the receiver operating characteristic (AUROC) curves of 0.919 and 0.892 within 1 year and between 1 and 6 years, respectively. Importantly, the applicable models with the top 20 most important features showed comparable external-validated performance (AUROC curves of 0.901 and 0.885) as the full models, based on which we found that individuals in the top quintile of predicted risk accounted for 91.7% (n=11) and 80.7% (n=25) of all suicidality cases within 1 year and during 1 to 6 years, respectively. We further obtained comparable prediction accuracy when applying these models to subpopulations with different genetic susceptibilities to suicidality. For example, for the 1-year risk prediction, the AUROC curves were 0.907 and 0.885 for the high (>2nd tertile of PRS) and low (<1st) genetic susceptibilities groups, respectively.<h4>Conclusions</h4>We established applicable machine learning-based models for predicting both the short- and long-term risk of suicidality with high accuracy across populations of varying genetic risk for suicide, highlighting a cost-effective method of identifying individuals with a high risk of suicidality.",,pdf:https://publichealth.jmir.org/2023/1/e43419/PDF; doi:https://doi.org/10.2196/43419; html:https://europepmc.org/articles/PMC9989910
 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,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.jmir.org/2019/4/e12286/PDF; doi:https://doi.org/10.2196/12286; html:https://europepmc.org/articles/PMC6473205
+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,,,"<h4>Background</h4>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).<h4>Objective</h4>We describe the deployment of the EHR interfacing information extraction and retrieval platform CogStack at University College London Hospitals (UCLH).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://medinform.jmir.org/2022/8/e38122/PDF; doi:https://doi.org/10.2196/38122; html:https://europepmc.org/articles/PMC9453582
 34249083,https://doi.org/10.3389/fgene.2021.652878,Polymorphism in <i>INSR</i> 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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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-<i>INSR</i> 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, <i>P</i> = 1.6e-02). The adjusted increased risk was highest within the first 3 years of exposure (RHR = 9.10, <i>P</i> = 8.5e-04). Sensitivity analysis yielded similar results. Effects were replicated in GoSHARE (<i>n</i> = 3,190).<h4>Conclusion</h4>Homozygous G/G genotype at the <i>INSR</i> 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.",,pdf:https://www.frontiersin.org/articles/10.3389/fgene.2021.652878/pdf; doi:https://doi.org/10.3389/fgene.2021.652878; html:https://europepmc.org/articles/PMC8260687; pdf:https://europepmc.org/articles/PMC8260687?pdf=render
 37859783,https://doi.org/10.1136/bmjmed-2023-000554,"Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog.","Hingorani AD, Gratton J, Finan C, Schmidt AF, Patel R, Sofat R, Kuan V, Langenberg C, Hemingway H, Morris JK, Wald NJ.",,BMJ medicine,2023,2023-10-17,Y,Public Health; Preventive Medicine,,,"<h4>Objective</h4>To clarify the performance of polygenic risk scores in population screening, individual risk prediction, and population risk stratification.<h4>Design</h4>Secondary analysis of data in the Polygenic Score Catalog.<h4>Setting</h4>Polygenic Score Catalog, April 2022. Secondary analysis of 3915 performance metric estimates for 926 polygenic risk scores for 310 diseases to generate estimates of performance in population screening, individual risk, and population risk stratification.<h4>Participants</h4>Individuals contributing to the published studies in the Polygenic Score Catalog.<h4>Main outcome measures</h4>Detection rate for a 5% false positive rate (DR<sub>5</sub>) and the population odds of becoming affected given a positive result; individual odds of becoming affected for a person with a particular polygenic score; and odds of becoming affected for groups of individuals in different portions of a polygenic risk score distribution. Coronary artery disease and breast cancer were used as illustrative examples.<h4>Results</h4>For performance in population screening, median DR<sub>5</sub> for all polygenic risk scores and all diseases studied was 11% (interquartile range 8-18%). Median DR<sub>5</sub> was 12% (9-19%) for polygenic risk scores for coronary artery disease and 10% (9-12%) for breast cancer. The population odds of becoming affected given a positive results were 1:8 for coronary artery disease and 1:21 for breast cancer, with background 10 year odds of 1:19 and 1:41, respectively, which are typical for these diseases at age 50. For individual risk prediction, the corresponding 10 year odds of becoming affected for individuals aged 50 with a polygenic risk score at the 2.5th, 25th, 75th, and 97.5th centiles were 1:54, 1:29, 1:15, and 1:8 for coronary artery disease and 1:91, 1:56, 1:34, and 1:21 for breast cancer. In terms of population risk stratification, at age 50, the risk of coronary artery disease was divided into five groups, with 10 year odds of 1:41 and 1:11 for the lowest and highest quintile groups, respectively. The 10 year odds was 1:7 for the upper 2.5% of the polygenic risk score distribution for coronary artery disease, a group that contributed 7% of cases. The corresponding estimates for breast cancer were 1:72 and 1:26 for the lowest and highest quintile groups, and 1:19 for the upper 2.5% of the distribution, which contributed 6% of cases.<h4>Conclusion</h4>Polygenic risk scores performed poorly in population screening, individual risk prediction, and population risk stratification. Strong claims about the effect of polygenic risk scores on healthcare seem to be disproportionate to their performance.",,doi:https://doi.org/10.1136/bmjmed-2023-000554; html:https://europepmc.org/articles/PMC10582890; pdf:https://europepmc.org/articles/PMC10582890?pdf=render
 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,,,,"<h4>Objective</h4>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.<h4>Design</h4>Observational controlled interrupted time series study.<h4>Setting</h4>UK primary and secondary care.<h4>Participants</h4>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.<h4>Intervention</h4>Fetal exposure to antibiotics shortly before birth (using pre-incision antibiotic policy as proxy) compared with no exposure.<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.bmj.com/content/bmj/377/bmj-2021-069704.full.pdf; doi:https://doi.org/10.1136/bmj-2021-069704; html:https://europepmc.org/articles/PMC9112858
 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; doi:https://doi.org/10.1016/j.vaccine.2022.02.056; html:https://europepmc.org/articles/PMC8849863
-37717234,https://doi.org/10.1111/1742-6723.14312,Prevalence of alcohol and other drug detections in non-transport injury events.,"Lau G, Mitra B, Gabbe BJ, Dietze PM, Reeder S, Cameron PA, Smit V, Schneider HG, Symons E, Koolstra C, Stewart C, Beck B.",,Emergency medicine Australasia : EMA,2023,2023-09-17,N,Alcoholic Intoxication; Illicit Drug; Blood Alcohol Content; Wounds And Injury; Substance-related Disorder; Substance Use Detection,,,"<h4>Objective</h4>To measure the prevalence of alcohol and/or other drug (AOD) detections in suspected major trauma patients with non-transport injuries who presented to an adult major trauma centre.<h4>Methods</h4>This registry-based cohort study examined the prevalence of AOD detections in patients aged ≥18 years who: (i) sustained non-transport injuries; and (ii) met predefined trauma call-out criteria and were therefore managed by an interdisciplinary trauma team between 1 July 2021 and 31 December 2022. Prevalence was measured using routine in-hospital blood alcohol and urine drug screens.<h4>Results</h4>A total of 1469 cases met the inclusion criteria. Of cases with a valid blood test (n = 1248, 85.0%), alcohol was detected in 313 (25.1%) patients. Of the 733 (49.9%) cases with urine drug screen results, cannabinoids were most commonly detected (n = 103, 14.1%), followed by benzodiazepines (n = 98, 13.4%), amphetamine-type substances (n = 80, 10.9%), opioids (n = 28, 3.8%) and cocaine (n = 17, 2.3%). Alcohol and/or at least one other drug was detected in 37.4% (n = 472) of cases with either a blood alcohol or urine drug test completed (n = 1263, 86.0%). Multiple substances were detected in 16.6% (n = 119) of cases with both blood alcohol and urine drug screens (n = 718, 48.9%). Detections were prevalent in cases of interpersonal violence (n = 123/179, 68.7%) and intentional self-harm (n = 50/106, 47.2%), and in those occurring on Friday and Saturday nights (n = 118/191, 61.8%).<h4>Conclusion</h4>AOD detections were common in trauma patients with non-transport injury causes. Population-level surveillance is needed to inform prevention strategies that address AOD use as a significant risk factor for serious injury.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.14312; doi:https://doi.org/10.1111/1742-6723.14312
 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.",,pdf:https://www.nature.com/articles/s41467-022-28157-3.pdf; doi:https://doi.org/10.1038/s41467-022-28157-3; html:https://europepmc.org/articles/PMC8789777; pdf:https://europepmc.org/articles/PMC8789777?pdf=render
+37717234,https://doi.org/10.1111/1742-6723.14312,Prevalence of alcohol and other drug detections in non-transport injury events.,"Lau G, Mitra B, Gabbe BJ, Dietze PM, Reeder S, Cameron PA, Smit V, Schneider HG, Symons E, Koolstra C, Stewart C, Beck B.",,Emergency medicine Australasia : EMA,2023,2023-09-17,N,Alcoholic Intoxication; Illicit Drug; Blood Alcohol Content; Wounds And Injury; Substance-related Disorder; Substance Use Detection,,,"<h4>Objective</h4>To measure the prevalence of alcohol and/or other drug (AOD) detections in suspected major trauma patients with non-transport injuries who presented to an adult major trauma centre.<h4>Methods</h4>This registry-based cohort study examined the prevalence of AOD detections in patients aged ≥18 years who: (i) sustained non-transport injuries; and (ii) met predefined trauma call-out criteria and were therefore managed by an interdisciplinary trauma team between 1 July 2021 and 31 December 2022. Prevalence was measured using routine in-hospital blood alcohol and urine drug screens.<h4>Results</h4>A total of 1469 cases met the inclusion criteria. Of cases with a valid blood test (n = 1248, 85.0%), alcohol was detected in 313 (25.1%) patients. Of the 733 (49.9%) cases with urine drug screen results, cannabinoids were most commonly detected (n = 103, 14.1%), followed by benzodiazepines (n = 98, 13.4%), amphetamine-type substances (n = 80, 10.9%), opioids (n = 28, 3.8%) and cocaine (n = 17, 2.3%). Alcohol and/or at least one other drug was detected in 37.4% (n = 472) of cases with either a blood alcohol or urine drug test completed (n = 1263, 86.0%). Multiple substances were detected in 16.6% (n = 119) of cases with both blood alcohol and urine drug screens (n = 718, 48.9%). Detections were prevalent in cases of interpersonal violence (n = 123/179, 68.7%) and intentional self-harm (n = 50/106, 47.2%), and in those occurring on Friday and Saturday nights (n = 118/191, 61.8%).<h4>Conclusion</h4>AOD detections were common in trauma patients with non-transport injury causes. Population-level surveillance is needed to inform prevention strategies that address AOD use as a significant risk factor for serious injury.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.14312; doi:https://doi.org/10.1111/1742-6723.14312
 37657941,https://doi.org/10.1212/wnl.0000000000207777,Exploring the Role of Plasma Lipids and Statin Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study.,"Almramhi MM, Finan C, Storm CS, Schmidt AF, Kia DA, Coneys R, Chopade S, Hingorani AD, Wood NW.",,Neurology,2023,2023-09-01,Y,,,,"<h4>Background and objectives</h4>There has been considerable interest in statins because of 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.<h4>Method</h4>We used two-sample Mendelian randomization (MR) to investigate (1) the causal role of genetically mimic both cholesterol-dependent (through low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (through 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).<h4>Results</h4>The results of MR using the inverse-variance weighted method show that genetically predicted <i>RAC2</i>, a member of cholesterol-independent pathway (OR 0.86 [95% CI 0.78-0.95], <i>p</i>-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. The MR results also show that lifelong higher HDL-C (OR 1.14 [95% CI 1.04-1.26], <i>p</i>-value 7.94E-03) increases 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.<h4>Discussion</h4>Evidence from this study suggests that <i>RAC2</i> is a genetic modifier of MS risk. Because <i>RAC2</i> has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins may reduce MS risk through a cholesterol-independent pathway (that is, RAC2-related mechanism(s)). MR analyses also support a causal effect of HDL-C on MS risk.",,pdf:https://n.neurology.org/content/neurology/early/2023/09/01/WNL.0000000000207777.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000207777; html:https://europepmc.org/articles/PMC10624499; pdf:https://europepmc.org/articles/PMC10624499?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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<sup>-4</sup>) 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.<h4>Interpretation</h4>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.<h4>Funding</h4>UK Medical Research Council, UK Biotechnology and Biological Sciences Research Council, and British Heart Foundation.",,pdf:http://www.thelancet.com/article/S2666756822000721/pdf; doi:https://doi.org/10.1016/S2666-7568(22)00072-1; html:https://europepmc.org/articles/PMC9068584
 36879385,https://doi.org/10.1097/ta.0000000000003950,Cost-effectiveness of a purpose-built ward environment and new allied health model of care for major trauma.,"Gabbe BJ, Reeder S, Ekegren CL, Mather A, Kimmel L, Cameron PA, Higgins AM.",,The journal of trauma and acute care surgery,2023,2023-03-07,N,,,,"<h4>Background</h4>Targeted rehabilitation within the acute inpatient setting could have a substantial impact on improving outcomes for major trauma patients. The aim of this study was to investigate the cost-effectiveness of the introduction of a purpose-built ward environment, and a new allied health model of care (AHMOC) delivered in the acute inpatient setting, in a major trauma population.<h4>Methods</h4>The statewide trauma registry, the trauma center's data warehouse, and electronic medical record data were used for this observational study. There were three phases: baseline, new ward, and new AHMOC. Cost-effectiveness was measured as cost per quality-adjusted life year using preinjury, hospital discharge, 1-month and 6-month 5-level, EQ-5D utility scores. Total costs included initial acute and inpatient rehabilitation care, as well as outpatient, readmission and ED presentations to 6-months.<h4>Results</h4>Four hundred eleven patients were included. Case-mix was stable between phases. The median (IQR) number of allied health services received by patients was 8 (5-17) at baseline, 10 (5-19) in the new ward phase, and 17 (9-23) in the AHMOC phase. The proportion discharged to rehabilitation was 37% at baseline, 45% with the new ward and 28% with the new AHMOC. Mean (SD) total Australian dollar costs were $69,335 ($141,175) at baseline, $55,943 ($82,706) with the new ward and $37,833 ($49,004) with the AHMOC. The probability of the AHMOC being cost-effective at a willingness-to-pay threshold of $50,000 per quality-adjusted life year was 99.4% compared with baseline and 98% compared with the new ward.<h4>Conclusion</h4>The new allied health model of care was found to be a cost-effective intervention. Uptake of this model of allied health care at other trauma centers has the potential to reduce the cost and burden of major trauma.<h4>Level of evidence</h4>Economic and Value-based Evaluations; Level III.",,doi:https://doi.org/10.1097/TA.0000000000003950
@@ -649,19 +649,19 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 35301875,https://doi.org/10.1161/jaha.121.023146,Long-Term Cardiovascular Risk and Management of Patients Recorded in Primary Care With Unattributed Chest Pain: An Electronic Health Record Study.,"Jordan KP, Rathod-Mistry T, Bailey J, Chen Y, Clarson L, Denaxas S, Hayward RA, Hemingway H, van der Windt DA, Mamas MA.",,Journal of the American Heart Association,2022,2022-03-18,Y,Cardiovascular disease; Chest pain; Primary Care; Electronic Health Records,,,"Background Most adults presenting with chest pain will not receive a diagnosis and be recorded with unattributed chest pain. The objective was to assess if they have increased risk of cardiovascular disease compared with those with noncoronary chest pain and determine whether investigations and interventions are targeted at those at highest risk. Methods and Results We used records from general practices in England linked to hospitalization and mortality information. The study population included patients aged 18 years or over with a new record of chest pain with a noncoronary cause or unattributed between 2002 and 2018, and no cardiovascular disease recorded up to 6 months (diagnostic window) afterward. We compared risk of a future cardiovascular event by type of chest pain, adjusting for cardiovascular risk factors and alternative explanations for chest pain. We determined prevalence of cardiac diagnostic investigations and preventative medication during the diagnostic window in patients with estimated cardiovascular risk ≥10%. There were 375 240 patients with unattributed chest pain (245 329 noncoronary chest pain). There was an increased risk of cardiovascular events for patients with unattributed chest pain, highest in the first year (hazard ratio, 1.25 [95% CI, 1.21-1.29]), persistent up to 10 years. Patients with unattributed chest pain had consistently increased risk of myocardial infarction over time but no increased risk of stroke. Thirty percent of patients at higher risk were prescribed lipid-lowering medication. Conclusions Patients presenting to primary care with unattributed chest pain are at increased risk of cardiovascular events. Primary prevention to reduce cardiovascular events appears suboptimal in those at higher risk.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.023146; doi:https://doi.org/10.1161/JAHA.121.023146; html:https://europepmc.org/articles/PMC9075433; pdf:https://europepmc.org/articles/PMC9075433?pdf=render
 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.",,pdf:https://www.nature.com/articles/s41597-019-0337-6.pdf; doi:https://doi.org/10.1038/s41597-019-0337-6; html:https://europepmc.org/articles/PMC6923383; pdf:https://europepmc.org/articles/PMC6923383?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.",,pdf:https://www.nature.com/articles/s41746-023-00749-3.pdf; doi:https://doi.org/10.1038/s41746-023-00749-3; html:https://europepmc.org/articles/PMC9938183; pdf:https://europepmc.org/articles/PMC9938183?pdf=render
-37777816,https://doi.org/10.1186/s13643-023-02337-8,Patient-reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.,"Taylor S, Law K, Coomber-Moore J, Davies M, Thistlewaite F, Calvert M, Aiyegbusi O, Yorke J.",,Systematic reviews,2023,2023-09-30,Y,Cancer; Systematic; Review; Quality of life; Patient-reported Outcomes (Pros); Adoptive Cell Therapy (Act),,,"<h4>Introduction</h4>Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life during and after treatment. The systematic review aims to characterise the breadth of PROs utilised in ACT cancer care and provide guidance for the use of PROs in this patient population in the future.<h4>Methods</h4>A systematic search was conducted (MEDLINE, PsycINFO, Embase and CINAHL) in August 2021 by two reviewers. Search terms covered the following: ""adoptive cell therapy"", ""patient-reported outcomes"" and ""cancer"". Studies were included if they used a PRO measure to report the impact of ACT. The methodological quality of PROs was assessed. Forward and backward reference searching was conducted of any relevant papers. A quality grading scale was applied based on Cochrane and Revenson criteria for classification of high-quality studies. Key data from the studies and the included PROs was extracted by two researchers and tabulated.<h4>Results</h4>One-hundred nine papers were identified; 11 papers were included. The majority of studies were single-arm trials or observational studies. Twenty-two different PROs were identified; none was ACT specific. The PROMIS-29 and EQ-5D were most commonly used. Few studies collected PRO data in the first 1-2 weeks. Four studies followed patients up for over a year, and a further four studies followed patients for approximately 3 months.<h4>Discussion</h4>None of the PROs identified have been designed specifically for ACT. Appropriateness of existing instruments should be considered. It should be considered whether it is appropriate to collect data more frequently in the acute stage and then less frequently during follow-up. It should be considered if one tool is suitable at all time points or if the tool should be adapted depending on time since treatment. More research is needed to identify the exact timings of PRO assessments, and qualitative work with patients is needed to determine the most important issues for them throughout the treatment and follow-up.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02337-8; doi:https://doi.org/10.1186/s13643-023-02337-8; html:https://europepmc.org/articles/PMC10541698; pdf:https://europepmc.org/articles/PMC10541698?pdf=render
 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,,,"<h4>Background/aim</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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-IMT<sub>max</sub>[- 0.17(95%CI - 0.32; - 0.02)], and Bif-IMT<sub>mean</sub>[- 0.07(95%CI - 0.13; - 0.01)] at baseline and decreasing C-IMT<sub>mean</sub>[- 0.006 (95%CI - 0.011; - 0.000)], Bif-IMT<sub>mean</sub>[- 0.016(95%CI - 0.027; - 0.005)], ICA-IMT<sub>mean</sub>[- 0.009(95% - 0.016; - 0.002)] and ICA-IMT<sub>max</sub>[- 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.<h4>Conclusion</h4>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.",,pdf:https://link.springer.com/content/pdf/10.1007/s00394-020-02220-5.pdf; doi:https://doi.org/10.1007/s00394-020-02220-5; html:https://europepmc.org/articles/PMC7867553; pdf:https://europepmc.org/articles/PMC7867553?pdf=render
+37777816,https://doi.org/10.1186/s13643-023-02337-8,Patient-reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.,"Taylor S, Law K, Coomber-Moore J, Davies M, Thistlewaite F, Calvert M, Aiyegbusi O, Yorke J.",,Systematic reviews,2023,2023-09-30,Y,Cancer; Systematic; Review; Quality of life; Patient-reported Outcomes (Pros); Adoptive Cell Therapy (Act),,,"<h4>Introduction</h4>Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life during and after treatment. The systematic review aims to characterise the breadth of PROs utilised in ACT cancer care and provide guidance for the use of PROs in this patient population in the future.<h4>Methods</h4>A systematic search was conducted (MEDLINE, PsycINFO, Embase and CINAHL) in August 2021 by two reviewers. Search terms covered the following: ""adoptive cell therapy"", ""patient-reported outcomes"" and ""cancer"". Studies were included if they used a PRO measure to report the impact of ACT. The methodological quality of PROs was assessed. Forward and backward reference searching was conducted of any relevant papers. A quality grading scale was applied based on Cochrane and Revenson criteria for classification of high-quality studies. Key data from the studies and the included PROs was extracted by two researchers and tabulated.<h4>Results</h4>One-hundred nine papers were identified; 11 papers were included. The majority of studies were single-arm trials or observational studies. Twenty-two different PROs were identified; none was ACT specific. The PROMIS-29 and EQ-5D were most commonly used. Few studies collected PRO data in the first 1-2 weeks. Four studies followed patients up for over a year, and a further four studies followed patients for approximately 3 months.<h4>Discussion</h4>None of the PROs identified have been designed specifically for ACT. Appropriateness of existing instruments should be considered. It should be considered whether it is appropriate to collect data more frequently in the acute stage and then less frequently during follow-up. It should be considered if one tool is suitable at all time points or if the tool should be adapted depending on time since treatment. More research is needed to identify the exact timings of PRO assessments, and qualitative work with patients is needed to determine the most important issues for them throughout the treatment and follow-up.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02337-8; doi:https://doi.org/10.1186/s13643-023-02337-8; html:https://europepmc.org/articles/PMC10541698; pdf:https://europepmc.org/articles/PMC10541698?pdf=render
 37840686,https://doi.org/10.3389/fdgth.2023.1184919,Understanding the performance and reliability of NLP tools: a comparison of four NLP tools predicting stroke phenotypes in radiology reports.,"Casey A, Davidson E, Grover C, Tobin R, Grivas A, Zhang H, Schrempf P, O'Neil AQ, Lee L, Walsh M, Pellie F, Ferguson K, Cvoro V, Wu H, Whalley H, Mair G, Whiteley W, Alex B.",,Frontiers in digital health,2023,2023-09-28,Y,Electronic Health Records; Natural Language Processing; Stroke Phenotype; Brain Radiology,,,"<h4>Background</h4>Natural language processing (NLP) has the potential to automate the reading of radiology reports, but there is a need to demonstrate that NLP methods are adaptable and reliable for use in real-world clinical applications.<h4>Methods</h4>We tested the F1 score, precision, and recall to compare NLP tools on a cohort from a study on delirium using images and radiology reports from NHS Fife and a population-based cohort (Generation Scotland) that spans multiple National Health Service health boards. We compared four off-the-shelf rule-based and neural NLP tools (namely, EdIE-R, ALARM+, ESPRESSO, and Sem-EHR) and reported on their performance for three cerebrovascular phenotypes, namely, ischaemic stroke, small vessel disease (SVD), and atrophy. Clinical experts from the EdIE-R team defined phenotypes using labelling techniques developed in the development of EdIE-R, in conjunction with an expert researcher who read underlying images.<h4>Results</h4>EdIE-R obtained the highest F1 score in both cohorts for ischaemic stroke, ≥93%, followed by ALARM+, ≥87%. The F1 score of ESPRESSO was ≥74%, whilst that of Sem-EHR is ≥66%, although ESPRESSO had the highest precision in both cohorts, 90% and 98%. For F1 scores for SVD, EdIE-R scored ≥98% and ALARM+ ≥90%. ESPRESSO scored lowest with ≥77% and Sem-EHR ≥81%. In NHS Fife, F1 scores for atrophy by EdIE-R and ALARM+ were 99%, dropping in Generation Scotland to 96% for EdIE-R and 91% for ALARM+. Sem-EHR performed lowest for atrophy at 89% in NHS Fife and 73% in Generation Scotland. When comparing NLP tool output with brain image reads using F1 scores, ALARM+ scored 80%, outperforming EdIE-R at 66% in ischaemic stroke. For SVD, EdIE-R performed best, scoring 84%, with Sem-EHR 82%. For atrophy, EdIE-R and both ALARM+ versions were comparable at 80%.<h4>Conclusions</h4>The four NLP tools show varying F1 (and precision/recall) scores across all three phenotypes, although more apparent for ischaemic stroke. If NLP tools are to be used in clinical settings, this cannot be performed ""out of the box."" It is essential to understand the context of their development to assess whether they are suitable for the task at hand or whether further training, re-training, or modification is required to adapt tools to the target task.",,doi:https://doi.org/10.3389/fdgth.2023.1184919; html:https://europepmc.org/articles/PMC10569314; pdf:https://europepmc.org/articles/PMC10569314?pdf=render
 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,,,"<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aor.14628; doi:https://doi.org/10.1111/aor.14628
-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,,,"<h4>Background</h4>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.<h4>Aim</h4>To explore the effects of COVID-19 on the recorded incidence of 17 long-term conditions.<h4>Design and setting</h4>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.<h4>Method</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://bjgp.org/content/bjgp/early/2023/03/06/BJGP.2022.0353.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0353; html:https://europepmc.org/articles/PMC9997656; pdf:https://europepmc.org/articles/PMC9997656?pdf=render
 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.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/1460458220977579; doi:https://doi.org/10.1177/1460458220977579
 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.",,pdf:https://www.nature.com/articles/s42003-020-01613-w.pdf; doi:https://doi.org/10.1038/s42003-020-01613-w; html:https://europepmc.org/articles/PMC7815736; pdf:https://europepmc.org/articles/PMC7815736?pdf=render
+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,,,"<h4>Background</h4>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.<h4>Aim</h4>To explore the effects of COVID-19 on the recorded incidence of 17 long-term conditions.<h4>Design and setting</h4>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.<h4>Method</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://bjgp.org/content/bjgp/early/2023/03/06/BJGP.2022.0353.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0353; html:https://europepmc.org/articles/PMC9997656; pdf:https://europepmc.org/articles/PMC9997656?pdf=render
 35365351,https://doi.org/10.1016/j.injury.2022.03.039,Injury severity and increased socioeconomic differences: A population-based cohort study.,"Madsen C, Gabbe BJ, Holvik K, Alver K, Grøholt EK, Lund J, Lyons J, Lyons RA, Ohm E.",,Injury,2022,2022-03-24,N,Injury; Socioeconomic status; Hospitalization; Iciss; Injury-vibes; Risk-adjusted Severity,,,"<h4>Background</h4>Several studies have documented an inverse gradient between socioeconomic status (SES) and injury mortality, but the evidence is less consistent for injury morbidity. The aim of this study was to investigate the association between SES and injury severity for acute hospitalizations in a nationwide population-based cohort.<h4>Methods</h4>We conducted a registry-based cohort study of all individuals aged 25-64 years residing in Norway by 1st of January 2008. This cohort was followed from 2008 through 2014 using inpatient registrations for acute hospitalizations due to all-cause injuries. We derived two measures of severity: threat-to-life using the International Classification of Disease-based Injury Severity Score (ICISS), and threat of disability using long-term disability weights from the Injury-VIBES project. Robust Poisson regression models, with adjustment for age, sex, marital status, immigrant status, municipality population size and healthcare region of residence, were used to calculate incidence rate ratios (IRRs) by SES measured as an index of education, income, and occupation.<h4>Results</h4>We identified 177,663 individuals (7% of the population) hospitalized with at least one acute injury in the observation period. Two percent (n = 4,186) had injuries categorized with high threat-to-life, while one quarter (n = 43,530) had injuries with high threat of disability. The overall adjusted IRR of hospitalization among people with low compared to high SES was 1.57 (95% CI 1.55, 1.60). Comparing low to high SES, injuries with low threat-to-life were associated with an IRR of 1.56 (95% CI 1.54, 1.59), while injuries with high threat-to-life had an IRR of 2.25 (95% CI 2.03, 2.51). Comparing low to high SES, injuries with low, medium, and high threat of disability were associated with IRRs of respectively, 1.15 (95% CI 1.11, 1.19), 1.70 (95% CI 1.66, 1.73) and 1.99 (95% CI 1.92, 2.07).<h4>Discussion</h4>We observed an inverse gradient between SES and injury morbidity, with the steepest gradient for the most severe injuries. This suggests a need for targeted preventive measures to reduce the magnitude and burden of severe injuries for patients with low socioeconomic status.",,pdf:http://www.injuryjournal.com/article/S0020138322002327/pdf; doi:https://doi.org/10.1016/j.injury.2022.03.039
 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,,,,,,pdf:https://academic.oup.com/bjs/advance-article-pdf/doi/10.1093/bjs/znad055/49561408/znad055.pdf; doi:https://doi.org/10.1093/bjs/znad055; html:https://europepmc.org/articles/PMC10416688; pdf:https://europepmc.org/articles/PMC10416688?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.",,pdf:https://www.nature.com/articles/s41467-023-36997-w.pdf; doi:https://doi.org/10.1038/s41467-023-36997-w; html:https://europepmc.org/articles/PMC10015012; pdf:https://europepmc.org/articles/PMC10015012?pdf=render
 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,,,"<h4>Objective</h4>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.<h4>Design</h4>A longitudinal cohort study based on anonymously linked, routinely collected multiple administrative data sets.<h4>Participants</h4>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.<h4>Outcome measures</h4>The risk factors associated with a binary LBW (outcome) variable were investigated with multivariable logistic regression (MLR) and decision tree (DT) models.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e063836.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063836; html:https://europepmc.org/articles/PMC9923297; pdf:https://europepmc.org/articles/PMC9923297?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
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>HLAN achieved the best Micro-level AUC and F<sub>1</sub> 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 F<sub>1</sub>. 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.<h4>Conclusion</h4>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; doi:https://doi.org/10.1016/j.jbi.2021.103728
+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
 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,,,"<h4>Objective</h4>To evaluate mental health burden in women with idiopathic intracranial hypertension (IIH) compared to matched women with migraine and population controls.<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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).<h4>Conclusion</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/head.14465; doi:https://doi.org/10.1111/head.14465
 36112916,https://doi.org/10.1177/09622802211055853,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, Sarah Walker A.",,Statistical methods in medical research,2022,2022-09-01,Y,Infection; Model; epidemic; risk factors; Covid-19,,,"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 COVID-19 Infection Survey 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 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 of 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.",,doi:https://doi.org/10.1177/09622802211055853; doi:https://doi.org/10.1177/09622802211055853; html:https://europepmc.org/articles/PMC9465559; pdf:https://europepmc.org/articles/PMC9465559?pdf=render
 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,,,"<h4>Introduction</h4>We report dementia incidence, comorbidities, reasons for health-care visits, mortality, causes of death, and examined dementia patterns by relative deprivation in the UK.<h4>Method</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>There is a considerable disparity of dementia that informs priorities of prevention and provision of patient care.",,pdf:https://discovery.ucl.ac.uk/10145566/1/ChungIncidence%2C%20morbidity%2C%20mortality%20and%20disparities%20in%20dementia_AOP.pdf; doi:https://doi.org/10.1002/alz.12635; html:https://europepmc.org/articles/PMC10078672; pdf:https://europepmc.org/articles/PMC10078672?pdf=render
@@ -683,8 +683,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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,,,"<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.",,pdf:https://openheart.bmj.com/content/openhrt/8/2/e001769.full.pdf; doi:https://doi.org/10.1136/openhrt-2021-001769; html:https://europepmc.org/articles/PMC8627412; pdf:https://europepmc.org/articles/PMC8627412?pdf=render
 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; Equivalent Dipole Layer; Ecgsim,,,"<b>Introduction:</b> 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. <b>Methods:</b> 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. <b>Results:</b> Hundred-fifty-three abnormal activation sequences were simulated. Median QRS-CC of delayed versus dyssynchronous were significantly different (1.00 vs. 0.97, <i>p</i> < 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. <b>Discussion:</b> 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.",,pdf:https://www.frontiersin.org/articles/10.3389/fphys.2022.1089343/pdf; doi:https://doi.org/10.3389/fphys.2022.1089343; html:https://europepmc.org/articles/PMC9814485; pdf:https://europepmc.org/articles/PMC9814485?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,,,"<h4>Aims</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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: <i>Bone Jt Open</i> 2022;3(12):941-952.",,pdf:https://boneandjoint.org.uk/article/10.1302/2633-1462.312.BJO-2022-0130.R1/pdf; 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
-37679419,https://doi.org/10.1038/s41588-023-01462-3,"GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.","Lagou V, Jiang L, Ulrich A, Zudina L, González KSG, Balkhiyarova Z, Faggian A, Maina JG, Chen S, Todorov PV, Sharapov S, David A, Marullo L, Mägi R, Rujan RM, Ahlqvist E, Thorleifsson G, Gao Η, Εvangelou Ε, Benyamin B, Scott RA, Isaacs A, Zhao JH, Willems SM, Johnson T, Gieger C, Grallert H, Meisinger C, Müller-Nurasyid M, Strawbridge RJ, Goel A, Rybin D, Albrecht E, Jackson AU, Stringham HM, Corrêa IR, Farber-Eger E, Steinthorsdottir V, Uitterlinden AG, Munroe PB, Brown MJ, Schmidberger J, Holmen O, Thorand B, Hveem K, Wilsgaard T, Mohlke KL, Wang Z, GWA-PA Consortium, Shmeliov A, den Hoed M, Loos RJF, Kratzer W, Haenle M, Koenig W, Boehm BO, Tan TM, Tomas A, Salem V, Barroso I, Tuomilehto J, Boehnke M, Florez JC, Hamsten A, Watkins H, Njølstad I, Wichmann HE, Caulfield MJ, Khaw KT, van Duijn CM, Hofman A, Wareham NJ, Langenberg C, Whitfield JB, Martin NG, Montgomery G, Scapoli C, Tzoulaki I, Elliott P, Thorsteinsdottir U, Stefansson K, Brittain EL, McCarthy MI, Froguel P, Sexton PM, Wootten D, Groop L, Dupuis J, Meigs JB, Deganutti G, Demirkan A, Pers TH, Reynolds CA, Aulchenko YS, Kaakinen MA, Jones B, Prokopenko I, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC).",,Nature genetics,2023,2023-09-07,Y,,,,"Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.",,doi:https://doi.org/10.1038/s41588-023-01462-3; html:https://europepmc.org/articles/PMC10484788; pdf:https://europepmc.org/articles/PMC10484788?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>As of June 2021, there are over 17,000 participants-largely from the United Kingdom-and enrollment is ongoing.<h4>Conclusions</h4>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.<h4>International registered report identifier (irrid)</h4>DERR1-10.2196/32587.",,pdf:https://www.researchprotocols.org/2021/12/e32587/PDF; doi:https://doi.org/10.2196/32587; html:https://europepmc.org/articles/PMC8658240
+37679419,https://doi.org/10.1038/s41588-023-01462-3,"GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.","Lagou V, Jiang L, Ulrich A, Zudina L, González KSG, Balkhiyarova Z, Faggian A, Maina JG, Chen S, Todorov PV, Sharapov S, David A, Marullo L, Mägi R, Rujan RM, Ahlqvist E, Thorleifsson G, Gao Η, Εvangelou Ε, Benyamin B, Scott RA, Isaacs A, Zhao JH, Willems SM, Johnson T, Gieger C, Grallert H, Meisinger C, Müller-Nurasyid M, Strawbridge RJ, Goel A, Rybin D, Albrecht E, Jackson AU, Stringham HM, Corrêa IR, Farber-Eger E, Steinthorsdottir V, Uitterlinden AG, Munroe PB, Brown MJ, Schmidberger J, Holmen O, Thorand B, Hveem K, Wilsgaard T, Mohlke KL, Wang Z, GWA-PA Consortium, Shmeliov A, den Hoed M, Loos RJF, Kratzer W, Haenle M, Koenig W, Boehm BO, Tan TM, Tomas A, Salem V, Barroso I, Tuomilehto J, Boehnke M, Florez JC, Hamsten A, Watkins H, Njølstad I, Wichmann HE, Caulfield MJ, Khaw KT, van Duijn CM, Hofman A, Wareham NJ, Langenberg C, Whitfield JB, Martin NG, Montgomery G, Scapoli C, Tzoulaki I, Elliott P, Thorsteinsdottir U, Stefansson K, Brittain EL, McCarthy MI, Froguel P, Sexton PM, Wootten D, Groop L, Dupuis J, Meigs JB, Deganutti G, Demirkan A, Pers TH, Reynolds CA, Aulchenko YS, Kaakinen MA, Jones B, Prokopenko I, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC).",,Nature genetics,2023,2023-09-07,Y,,,,"Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.",,doi:https://doi.org/10.1038/s41588-023-01462-3; html:https://europepmc.org/articles/PMC10484788; pdf:https://europepmc.org/articles/PMC10484788?pdf=render
 30727941,https://doi.org/10.1186/s12859-019-2633-8,DeepPVP: phenotype-based prioritization of causative variants using deep learning.,"Boudellioua I, Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.",,BMC bioinformatics,2019,2019-02-06,Y,Phenotype; Ontology; Machine Learning; Variant Prioritization,Applied Analytics,,"<h4>Background</h4>Prioritization of variants in personal genomic data is a major challenge. Recently, computational methods that rely on comparing phenotype similarity have shown to be useful to identify causative variants. In these methods, pathogenicity prediction is combined with a semantic similarity measure to prioritize not only variants that are likely to be dysfunctional but those that are likely involved in the pathogenesis of a patient's phenotype.<h4>Results</h4>We have developed DeepPVP, a variant prioritization method that combined automated inference with deep neural networks to identify the likely causative variants in whole exome or whole genome sequence data. We demonstrate that DeepPVP performs significantly better than existing methods, including phenotype-based methods that use similar features. DeepPVP is freely available at https://github.com/bio-ontology-research-group/phenomenet-vp .<h4>Conclusions</h4>DeepPVP further improves on existing variant prioritization methods both in terms of speed as well as accuracy.",,pdf:https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/s12859-019-2633-8; doi:https://doi.org/10.1186/s12859-019-2633-8; html:https://europepmc.org/articles/PMC6364462; pdf:https://europepmc.org/articles/PMC6364462?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,Y,,,,"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.",,pdf:https://link.springer.com/content/pdf/10.1007/s12687-023-00635-1.pdf; doi:https://doi.org/10.1007/s12687-023-00635-1; html:https://europepmc.org/articles/PMC10576689; pdf:https://europepmc.org/articles/PMC10576689?pdf=render
 34785588,https://doi.org/10.1136/openhrt-2021-001784,OpenSAFELY: impact of national guidance on switching anticoagulant therapy during COVID-19 pandemic.,"OpenSAFELY Collaborative, Curtis HJ, MacKenna B, Walker AJ, Croker R, Mehrkar A, Morton C, Bacon S, Hickman G, Inglesby P, Bates C, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Rentsch CT, Williamson E, Hulme W, Tomlinson L, Mathur R, Drysdale H, Eggo RM, Wong AY, Forbes H, Parry J, Hester F, Harper S, Douglas I, Smeeth L, Goldacre B.",,Open heart,2021,2021-11-01,Y,Stroke; Medication Adherence; Healthcare Economics And Organisations; Covid-19,,,"<h4>Background</h4>Early in the COVID-19 pandemic, the National Health Service (NHS) recommended that appropriate patients anticoagulated with warfarin should be switched to direct-acting oral anticoagulants (DOACs), requiring less frequent blood testing. Subsequently, a national safety alert was issued regarding patients being inappropriately coprescribed two anticoagulants following a medication change and associated monitoring.<h4>Objective</h4>To describe which people were switched from warfarin to DOACs; identify potentially unsafe coprescribing of anticoagulants; and assess whether abnormal clotting results have become more frequent during the pandemic.<h4>Methods</h4>With the approval of NHS England, we conducted a cohort study using routine clinical data from 24 million NHS patients in England.<h4>Results</h4>20 000 of 164 000 warfarin patients (12.2%) switched to DOACs between March and May 2020, most commonly to edoxaban and apixaban. Factors associated with switching included: older age, recent renal function test, higher number of recent INR tests recorded, atrial fibrillation diagnosis and care home residency. There was a sharp rise in coprescribing of warfarin and DOACs from typically 50-100 per month to 246 in April 2020, 0.06% of all people receiving a DOAC or warfarin. International normalised ratio (INR) testing fell by 14% to 506.8 patients tested per 1000 warfarin patients each month. We observed a very small increase in elevated INRs (n=470) during April compared with January (n=420).<h4>Conclusions</h4>Increased switching of anticoagulants from warfarin to DOACs was observed at the outset of the COVID-19 pandemic in England following national guidance. There was a small but substantial number of people coprescribed warfarin and DOACs during this period. Despite a national safety alert on the issue, a widespread rise in elevated INR test results was not found. Primary care has responded rapidly to changes in patient care during the COVID-19 pandemic.",,pdf:https://openheart.bmj.com/content/openhrt/8/2/e001784.full.pdf; doi:https://doi.org/10.1136/openhrt-2021-001784; html:https://europepmc.org/articles/PMC8595296; pdf:https://europepmc.org/articles/PMC8595296?pdf=render
@@ -712,8 +712,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 33856367,https://doi.org/10.1097/sla.0000000000004904,Optimizing Trauma Systems: A Geospatial Analysis of the Victorian State Trauma System.,"Beck B, Tack G, Cameron P, Smith K, Gabbe B.",,Annals of surgery,2023,2023-01-10,N,,,,"<h4>Objective</h4>The aim of this study was to develop a data-driven approach to assessing the influence of trauma system parameters and optimizing the configuration of the Victorian State Trauma System (VSTS).<h4>Summary background data</h4>Regionalized trauma systems have been shown to reduce the risk of mortality and improve patient function and health-related quality of life. However, major trauma case numbers are rapidly increasing and there is a need to evolve the configuration of trauma systems.<h4>Methods</h4>A retrospective review of major trauma patients from 2016 to 2018 in Victoria, Australia. Drive times and flight times were calculated for transport to each of 138 trauma receiving hospitals. Changes to the configuration of the VSTS were modeled using a Mixed Integer Linear Programming algorithm across 156 simulations.<h4>Results</h4>There were 8327 patients included in the study, of which 58% were transported directly to a major trauma service (MTS). For adult patients, the proportion of patients transported directly to an MTS increased with higher transport time limit, greater probability of helicopter emergency medical service utilization, and lower hospital patient threshold numbers. The proportion of adult patients transported directly to an MTS varied from 66% to 90% across simulations. Across all simulations for pediatric patients, only 1 pediatric MTS was assigned.<h4>Conclusions</h4>We have developed a robust and data-driven approach to optimizing trauma systems. Through the use of geospatial and mathematical models, we have modeled how potential future changes to trauma system characteristics may impact on the optimal configuration of the system, which will enable policy makers to make informed decisions about health service planning into the future.",,doi:https://doi.org/10.1097/SLA.0000000000004904
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Registration</h4>This review was registered on PROSPERO as CRD42020177714 .",,pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-021-05992-1; doi:https://doi.org/10.1186/s12879-021-05992-1; html:https://europepmc.org/articles/PMC8040367; pdf:https://europepmc.org/articles/PMC8040367?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 (h<sub>2</sub>SNP) 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,pdf:https://www.nature.com/articles/s41398-019-0635-y.pdf; doi:https://doi.org/10.1038/s41398-019-0635-y; html:https://europepmc.org/articles/PMC6892870; pdf:https://europepmc.org/articles/PMC6892870?pdf=render
-37562944,https://doi.org/10.1136/emermed-2023-213186,"Biases in the collection of blood alcohol data for adult major trauma patients in Victoria, Australia.","Lau G, Gabbe B, Mitra B, Dietze P, Reeder S, Cameron P, Read DJ, Symons E, Beck B.",,Emergency medicine journal : EMJ,2023,2023-08-10,N,epidemiology; wounds and injuries; toxicology; Alcohol Abuse,,,"<h4>Background</h4>In-hospital alcohol testing provides an opportunity to implement prevention strategies for patients with high risk of experiencing repeated alcohol-related injuries. However, barriers to alcohol testing in emergency settings can prevent patients from being tested. In this study, we aimed to understand potential biases in current data on the completion of blood alcohol tests for major trauma patients at hospitals in Victoria, Australia.<h4>Methods</h4>Victorian State Trauma Registry data on all adult major trauma patients from 1 January 2018 to 31 December 2021 were used. Characteristics associated with having a blood alcohol test recorded in the registry were assessed using logistic regression models.<h4>Results</h4>This study included 14 221 major trauma patients, of which 4563 (32.1%) had a blood alcohol test recorded. Having a blood alcohol test completed was significantly associated with age, socioeconomic disadvantage level, preferred language, having pre-existing mental health or substance use conditions, smoking status, presenting during times associated with heavy community alcohol consumption, injury cause and intent, and Glasgow Coma Scale scores (p<0.05). Restricting analyses to patients from a trauma centre where blood alcohol testing was part of routine clinical care mitigated most biases. However, relative to patients injured while driving a motor vehicle/motorcycle, lower odds of testing were still observed for patients with injuries from flames/scalds/contact burns (adjusted OR (aOR)=0.33, 95% CI 0.18 to 0.61) and low falls (aOR=0.17, 95% CI 0.12 to 0.25). Higher odds of testing were associated with pre-existing mental health (aOR=1.39, 95% CI 1.02 to 1.89) or substance use conditions (aOR=2.33, 95% CI to 1.47-3.70), and living in a more disadvantaged area (most disadvantaged quintile relative to least disadvantaged quintile: aOR=2.30, 95% CI 1.52 to 3.48).<h4>Conclusion</h4>Biases in the collection of blood alcohol data likely impact the surveillance of alcohol-related injuries. Routine alcohol testing after major trauma is needed to accurately inform epidemiology and the subsequent implementation of strategies for reducing alcohol-related injuries.",,doi:https://doi.org/10.1136/emermed-2023-213186
 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,,,"<h4>Aims/hypothesis</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions/interpretation</h4>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.",,pdf:https://link.springer.com/content/pdf/10.1007/s00125-021-05640-y.pdf; doi:https://doi.org/10.1007/s00125-021-05640-y; html:https://europepmc.org/articles/PMC8894164; pdf:https://europepmc.org/articles/PMC8894164?pdf=render
+37562944,https://doi.org/10.1136/emermed-2023-213186,"Biases in the collection of blood alcohol data for adult major trauma patients in Victoria, Australia.","Lau G, Gabbe B, Mitra B, Dietze P, Reeder S, Cameron P, Read DJ, Symons E, Beck B.",,Emergency medicine journal : EMJ,2023,2023-08-10,N,epidemiology; wounds and injuries; toxicology; Alcohol Abuse,,,"<h4>Background</h4>In-hospital alcohol testing provides an opportunity to implement prevention strategies for patients with high risk of experiencing repeated alcohol-related injuries. However, barriers to alcohol testing in emergency settings can prevent patients from being tested. In this study, we aimed to understand potential biases in current data on the completion of blood alcohol tests for major trauma patients at hospitals in Victoria, Australia.<h4>Methods</h4>Victorian State Trauma Registry data on all adult major trauma patients from 1 January 2018 to 31 December 2021 were used. Characteristics associated with having a blood alcohol test recorded in the registry were assessed using logistic regression models.<h4>Results</h4>This study included 14 221 major trauma patients, of which 4563 (32.1%) had a blood alcohol test recorded. Having a blood alcohol test completed was significantly associated with age, socioeconomic disadvantage level, preferred language, having pre-existing mental health or substance use conditions, smoking status, presenting during times associated with heavy community alcohol consumption, injury cause and intent, and Glasgow Coma Scale scores (p<0.05). Restricting analyses to patients from a trauma centre where blood alcohol testing was part of routine clinical care mitigated most biases. However, relative to patients injured while driving a motor vehicle/motorcycle, lower odds of testing were still observed for patients with injuries from flames/scalds/contact burns (adjusted OR (aOR)=0.33, 95% CI 0.18 to 0.61) and low falls (aOR=0.17, 95% CI 0.12 to 0.25). Higher odds of testing were associated with pre-existing mental health (aOR=1.39, 95% CI 1.02 to 1.89) or substance use conditions (aOR=2.33, 95% CI to 1.47-3.70), and living in a more disadvantaged area (most disadvantaged quintile relative to least disadvantaged quintile: aOR=2.30, 95% CI 1.52 to 3.48).<h4>Conclusion</h4>Biases in the collection of blood alcohol data likely impact the surveillance of alcohol-related injuries. Routine alcohol testing after major trauma is needed to accurately inform epidemiology and the subsequent implementation of strategies for reducing alcohol-related injuries.",,doi:https://doi.org/10.1136/emermed-2023-213186
 35637502,https://doi.org/10.1186/s12889-022-13453-w,Age within schoolyear and attention-deficit hyperactivity disorder in Scotland and Wales.,"Fleming M, Bandyopadhyay A, McLay JS, Clark D, King A, Mackay DF, Lyons RA, Sayal K, Brophy S, Pell JP.",,BMC public health,2022,2022-05-30,Y,Children; Education; Data Linkage; School; Attention-deficit Hyperactivity Disorder; Relative Age,,,"<h4>Background</h4>Previous studies suggest an association between age within schoolyear and attention-deficit hyperactivity disorder (ADHD). Scotland and Wales have different school entry cut-off dates (six months apart) and policies on holding back children. We aim to investigate the association between relative age and treated attention deficit hyperactivity disorder (ADHD) in two countries, accounting for held-back children.<h4>Methods</h4>Routine education and health records of 1,063,256 primary and secondary schoolchildren in Scotland (2009-2013) and Wales (2009-2016) were linked. Logistic regression was used to examine the relationships between age within schoolyear and treated ADHD, adjusting for child, maternity and obstetric confounders.<h4>Results</h4>Amongst children in their expected school year, 8,721 (0.87%) had treated ADHD (Scotland 0.84%; Wales 0.96%). In Wales, ADHD increased with decreasing age (youngest quartile, adjusted OR 1.32, 95% CI 1.19-1.46) but, in Scotland, it did not differ between the youngest and oldest quartiles. Including held-back children in analysis of their expected year, the overall prevalence of treated ADHD was 0.93%, and increased across age quartiles in both countries. More children were held back in Scotland (57,979; 7.66%) than Wales (2,401; 0.78%). Held-back children were more likely to have treated ADHD (Scotland OR 2.18, 95% CI 2.01-2.36; Wales OR 1.70, 95% CI 1.21-2.31) and 81.18% of held-back children would have been in the youngest quartile of their expected year.<h4>Conclusions</h4>Children younger within schoolyear are more likely to be treated for ADHD, suggesting immaturity may influence diagnosis. However, these children are more likely to be held back in countries that permit flexibility, attenuating the relative age effect.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-022-13453-w; doi:https://doi.org/10.1186/s12889-022-13453-w; html:https://europepmc.org/articles/PMC9150337; pdf:https://europepmc.org/articles/PMC9150337?pdf=render
 37794871,https://doi.org/10.1093/ehjdh/ztad044,An artificial intelligence tool for automated analysis of large-scale unstructured clinical cine cardiac magnetic resonance databases.,"Mariscal-Harana J, Asher C, Vergani V, Rizvi M, Keehn L, Kim RJ, Judd RM, Petersen SE, Razavi R, King AP, Ruijsink B, Puyol-Antón E.",,European heart journal. Digital health,2023,2023-07-13,Y,Artificial intelligence; Quality control; Cardiac function; Cardiac Segmentation; Cardiac Magnetic Resonance,,,"<h4>Aims</h4>Artificial intelligence (AI) techniques have been proposed for automating analysis of short-axis (SAX) cine cardiac magnetic resonance (CMR), but no CMR analysis tool exists to automatically analyse large (unstructured) clinical CMR datasets. We develop and validate a robust AI tool for start-to-end automatic quantification of cardiac function from SAX cine CMR in large clinical databases.<h4>Methods and results</h4>Our pipeline for processing and analysing CMR databases includes automated steps to identify the correct data, robust image pre-processing, an AI algorithm for biventricular segmentation of SAX CMR and estimation of functional biomarkers, and automated post-analysis quality control to detect and correct errors. The segmentation algorithm was trained on 2793 CMR scans from two NHS hospitals and validated on additional cases from this dataset (<i>n</i> = 414) and five external datasets (<i>n</i> = 6888), including scans of patients with a range of diseases acquired at 12 different centres using CMR scanners from all major vendors. Median absolute errors in cardiac biomarkers were within the range of inter-observer variability: <8.4 mL (left ventricle volume), <9.2 mL (right ventricle volume), <13.3 g (left ventricular mass), and <5.9% (ejection fraction) across all datasets. Stratification of cases according to phenotypes of cardiac disease and scanner vendors showed good performance across all groups.<h4>Conclusion</h4>We show that our proposed tool, which combines image pre-processing steps, a domain-generalizable AI algorithm trained on a large-scale multi-domain CMR dataset and quality control steps, allows robust analysis of (clinical or research) databases from multiple centres, vendors, and cardiac diseases. This enables translation of our tool for use in fully automated processing of large multi-centre databases.",,doi:https://doi.org/10.1093/ehjdh/ztad044; html:https://europepmc.org/articles/PMC10545512; pdf:https://europepmc.org/articles/PMC10545512?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,,,"<h4>Objective</h4>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.<h4>Materials and methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/jamiaopen/article-pdf/4/3/ooab001/40325375/ooab001.pdf; doi:https://doi.org/10.1093/jamiaopen/ooab001; html:https://europepmc.org/articles/PMC8423424; pdf:https://europepmc.org/articles/PMC8423424?pdf=render
@@ -729,8 +729,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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; doi:https://doi.org/10.1080/21645515.2022.2127572; html:https://europepmc.org/articles/PMC9746546; pdf:https://europepmc.org/articles/PMC9746546?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.",,pdf:https://www.nature.com/articles/s41467-022-35771-8.pdf; doi:https://doi.org/10.1038/s41467-022-35771-8; html:https://europepmc.org/articles/PMC9821346; pdf:https://europepmc.org/articles/PMC9821346?pdf=render
 32737300,https://doi.org/10.1038/s41467-020-17696-2,Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections.,"Sallah N, Miley W, Labo N, Carstensen T, Fatumo S, Gurdasani D, Pollard MO, Dilthey AT, Mentzer AJ, Marshall V, Cornejo Castro EM, Pomilla C, Young EH, Asiki G, Hibberd ML, Sandhu M, Kellam P, Newton R, Whitby D, Barroso I.",,Nature communications,2020,2020-07-31,Y,,,,"Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr Virus (EBV) establish life-long infections and are associated with malignancies. Striking geographic variation in incidence and the fact that virus alone is insufficient to cause disease, suggests other co-factors are involved. Here we present epidemiological analysis and genome-wide association study (GWAS) in 4365 individuals from an African population cohort, to assess the influence of host genetic and non-genetic factors on virus antibody responses. EBV/KSHV co-infection (OR = 5.71(1.58-7.12)), HIV positivity (OR = 2.22(1.32-3.73)) and living in a more rural area (OR = 1.38(1.01-1.89)) are strongly associated with immunogenicity. GWAS reveals associations with KSHV antibody response in the HLA-B/C region (p = 6.64 × 10<sup>-09</sup>). For EBV, associations are identified for VCA (rs71542439, p = 1.15 × 10<sup>-12</sup>). Human leucocyte antigen (HLA) and trans-ancestry fine-mapping substantiate that distinct variants in HLA-DQA1 (p = 5.24 × 10<sup>-44</sup>) are driving associations for EBNA-1 in Africa. This study highlights complex interactions between KSHV and EBV, in addition to distinct genetic architectures resulting in important differences in pathogenesis and transmission.",,pdf:https://www.nature.com/articles/s41467-020-17696-2.pdf; doi:https://doi.org/10.1038/s41467-020-17696-2; html:https://europepmc.org/articles/PMC7395761; pdf:https://europepmc.org/articles/PMC7395761?pdf=render
-33780550,https://doi.org/10.1111/anae.15457,Impact of a physician - critical care practitioner pre-hospital service in Wales on trauma survival: a retrospective analysis of linked registry data.,"Lyons J, Gabbe BJ, Rawlinson D, Lockey D, Fry RJ, Akbari A, Lyons RA.",,Anaesthesia,2021,2021-03-29,N,Trauma; Survival; Critical Care; Pre-hospital Care,,,"The Emergency Medical Retrieval and Transfer Service for Wales launched in 2015. This service delivers senior pre-hospital doctors and advanced critical care practitioners to the scene of time-critical life- and limb-threatening incidents to provide advanced decision-making and pre-hospital clinical care. The impact of the service on 30-day mortality was evaluated retrospectively using a data linkage system. The study included patients who sustained moderate-to-severe blunt traumatic injuries (injury severity score ≥ 9) between 27 April 2015 and 30 November 2018. The association between pre-hospital management by the Emergency Medical Retrieval and Transfer Service and 30-day mortality was assessed using multivariable logistic regression. In total, data from 4035 patients were analysed, of which 412 (10%) were treated by the Emergency Medical Retrieval and Transfer Service. A greater proportion of patients treated by the Emergency Medical Retrieval and Transfer Service had an injury severity score ≥ 16 and Glasgow coma scale ≤ 12 (288 (70%) vs. 1435 (40%) and 126 (31%) vs. 325 (9%), respectively). The unadjusted 30-day mortality rate was 11.7% for patients managed by the Emergency Medical Retrieval and Transfer Service compared with 9.6% for patients managed by standard pre-hospital care services. However, after adjustment for differences in case-mix, the 30-day mortality rate for patients treated by the Emergency Medical Retrieval and Transfer Service was 37% lower (adjusted odds ratio 0.63 (95%CI 0.41-0.97); p = 0.037). The introduction of an emergency medical retrieval service was associated with a reduction in 30-day mortality for patients with blunt traumatic injury.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa56616/Download/56616__19761__8c6edaf906b846a69c8b19bdb94d015d.pdf; doi:https://doi.org/10.1111/anae.15457
 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,,,"<h4>Background</h4>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.<h4>Case presentation</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcneurol.biomedcentral.com/track/pdf/10.1186/s12883-018-1058-8; doi:https://doi.org/10.1186/s12883-018-1058-8; html:https://europepmc.org/articles/PMC5930853; pdf:https://europepmc.org/articles/PMC5930853?pdf=render
+33780550,https://doi.org/10.1111/anae.15457,Impact of a physician - critical care practitioner pre-hospital service in Wales on trauma survival: a retrospective analysis of linked registry data.,"Lyons J, Gabbe BJ, Rawlinson D, Lockey D, Fry RJ, Akbari A, Lyons RA.",,Anaesthesia,2021,2021-03-29,N,Trauma; Survival; Critical Care; Pre-hospital Care,,,"The Emergency Medical Retrieval and Transfer Service for Wales launched in 2015. This service delivers senior pre-hospital doctors and advanced critical care practitioners to the scene of time-critical life- and limb-threatening incidents to provide advanced decision-making and pre-hospital clinical care. The impact of the service on 30-day mortality was evaluated retrospectively using a data linkage system. The study included patients who sustained moderate-to-severe blunt traumatic injuries (injury severity score ≥ 9) between 27 April 2015 and 30 November 2018. The association between pre-hospital management by the Emergency Medical Retrieval and Transfer Service and 30-day mortality was assessed using multivariable logistic regression. In total, data from 4035 patients were analysed, of which 412 (10%) were treated by the Emergency Medical Retrieval and Transfer Service. A greater proportion of patients treated by the Emergency Medical Retrieval and Transfer Service had an injury severity score ≥ 16 and Glasgow coma scale ≤ 12 (288 (70%) vs. 1435 (40%) and 126 (31%) vs. 325 (9%), respectively). The unadjusted 30-day mortality rate was 11.7% for patients managed by the Emergency Medical Retrieval and Transfer Service compared with 9.6% for patients managed by standard pre-hospital care services. However, after adjustment for differences in case-mix, the 30-day mortality rate for patients treated by the Emergency Medical Retrieval and Transfer Service was 37% lower (adjusted odds ratio 0.63 (95%CI 0.41-0.97); p = 0.037). The introduction of an emergency medical retrieval service was associated with a reduction in 30-day mortality for patients with blunt traumatic injury.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa56616/Download/56616__19761__8c6edaf906b846a69c8b19bdb94d015d.pdf; doi:https://doi.org/10.1111/anae.15457
 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,,,"<h4>Objectives</h4>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.<h4>Materials and methods</h4>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.<h4>Results</h4>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.<h4>Discussion and conclusion</h4>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.",,pdf:https://academic.oup.com/jamiaopen/article-pdf/3/4/545/36625793/ooaa047.pdf; doi:https://doi.org/10.1093/jamiaopen/ooaa047; html:https://europepmc.org/articles/PMC7717266; pdf:https://europepmc.org/articles/PMC7717266?pdf=render
 35039282,https://doi.org/10.1136/bmjopen-2021-049506,Development and external validation of prognostic models for COVID-19 to support risk stratification in secondary care.,"Adderley NJ, Taverner T, Price MJ, Sainsbury C, Greenwood D, Chandan JS, Takwoingi Y, Haniffa R, Hosier I, Welch C, Parekh D, Gallier S, Gokhale K, Denniston AK, Sapey E, Nirantharakumar K.",,BMJ open,2022,2022-01-17,Y,Public Health; Covid-19,,,"<h4>Objectives</h4>Existing UK prognostic models for patients admitted to the hospital with COVID-19 are limited by reliance on comorbidities, which are under-recorded in secondary care, and lack of imaging data among the candidate predictors. Our aims were to develop and externally validate novel prognostic models for adverse outcomes (death and intensive therapy unit (ITU) admission) in UK secondary care and externally validate the existing 4C score.<h4>Design</h4>Candidate predictors included demographic variables, symptoms, physiological measures, imaging and laboratory tests. Final models used logistic regression with stepwise selection.<h4>Setting</h4>Model development was performed in data from University Hospitals Birmingham (UHB). External validation was performed in the CovidCollab dataset.<h4>Participants</h4>Patients with COVID-19 admitted to UHB January-August 2020 were included.<h4>Main outcome measures</h4>Death and ITU admission within 28 days of admission.<h4>Results</h4>1040 patients with COVID-19 were included in the derivation cohort; 288 (28%) died and 183 (18%) were admitted to ITU within 28 days of admission. Area under the receiver operating characteristic curve (AUROC) for mortality was 0.791 (95% CI 0.761 to 0.822) in UHB and 0.767 (95% CI 0.754 to 0.780) in CovidCollab; AUROC for ITU admission was 0.906 (95% CI 0.883 to 0.929) in UHB and 0.811 (95% CI 0.795 to 0.828) in CovidCollab. Models showed good calibration. Addition of comorbidities to candidate predictors did not improve model performance. AUROC for the International Severe Acute Respiratory and Emerging Infection Consortium 4C score in the UHB dataset was 0.753 (95% CI 0.720 to 0.785).<h4>Conclusions</h4>The novel prognostic models showed good discrimination and calibration in derivation and external validation datasets, and performed at least as well as the existing 4C score using only routinely collected patient information. The models can be integrated into electronic medical records systems to calculate each individual patient's probability of death or ITU admission at the time of hospital admission. Implementation of the models and clinical utility should be evaluated.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/1/e049506.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049506; html:https://europepmc.org/articles/PMC8764710; pdf:https://europepmc.org/articles/PMC8764710?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,,,,"<h4>Objective</h4>To determine the risk factors for having diabetic retinopathy (DR) in children and young people (CYP) with type 1 diabetes (T1DM) at first screening.<h4>Methods</h4>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.<h4>Results</h4>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 HbA<sub>1c</sub>, 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).<h4>Conclusions</h4>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 HbA<sub>1c</sub> 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.",,pdf:https://www.nature.com/articles/s41433-020-01326-8.pdf; 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
@@ -742,20 +742,20 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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,,,"<h4>Purpose of review</h4>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.<h4>Recent findings</h4>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.",,pdf:https://link.springer.com/content/pdf/10.1007/s11892-018-1021-5.pdf; doi:https://doi.org/10.1007/s11892-018-1021-5; html:https://europepmc.org/articles/PMC6015804; pdf:https://europepmc.org/articles/PMC6015804?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,,,"<h4>Background</h4>This study aimed to identify novel associations between irritable bowel syndrome (IBS) and a broad range of outcomes.<h4>Methods</h4>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.<h4>Results</h4>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, <i>p</i> = 0.02), diverticular diseases of the intestine (OR: 1.13, 95%CI: 1.08-1.19, <i>p</i> = 3.00 × 10<sup>-6</sup>), gastro-esophageal reflux disease (OR: 1.09, 95%CI: 1.05-1.13, <i>p</i> = 3.72 × 10<sup>-5</sup>), dyspepsia (OR: 1.21, 95%CI: 1.13-1.30, <i>p</i> = 9.28 × 10<sup>-8</sup>), and diaphragmatic hernia (OR: 1.10, 95%CI: 1.05-1.15, <i>p</i> = 2.75 × 10<sup>-5</sup>). The causality of these associations was observed in female only, but not men.<h4>Conclusions</h4>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; doi:https://doi.org/10.3390/jcm12031106; html:https://europepmc.org/articles/PMC9918111; pdf:https://europepmc.org/articles/PMC9918111?pdf=render
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Discussion</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0243843&type=printable; doi:https://doi.org/10.1371/journal.pone.0243843; html:https://europepmc.org/articles/PMC7737962; pdf:https://europepmc.org/articles/PMC7737962?pdf=render
-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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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).<h4>Conclusions and relevance</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pds.5681; doi:https://doi.org/10.1002/pds.5681
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-022-07628-4; doi:https://doi.org/10.1186/s12879-022-07628-4; html:https://europepmc.org/articles/PMC9326417; pdf:https://europepmc.org/articles/PMC9326417?pdf=render
+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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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).<h4>Conclusions and relevance</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pds.5681; doi:https://doi.org/10.1002/pds.5681
 36525457,https://doi.org/10.1371/journal.pone.0279250,Undergoing radical treatment for prostate cancer and its impact on wellbeing: A qualitative study exploring men's experiences.,"Vyas N, Brunckhorst O, Fox L, Van Hemelrijck M, Muir G, Stewart R, Dasgupta P, Ahmed K.",,PloS one,2022,2022-12-16,Y,,,,"<h4>Introduction</h4>Quality of life in prostate cancer survivorship is becoming increasingly important, with mental and social wellbeing recognised as key components. However, limited global evaluation of psychosocial challenges experienced after treatment exists. Therefore, we aimed to explore the lived experiences of men who underwent radical treatment, and its psychosocial impact.<h4>Material and methods</h4>This qualitative study was conducted using 19 men who had undergone radical treatment (prostatectomy or radiotherapy) for their cancer. Semi-structured interviews were conducted exploring lived experiences of men after treatment. A Structured thematic analysis of collected data was undertaken, with an inductive co-construction of themes through the lens of the biopsychosocial model. Themes generated were considered within a psychological, social, and physical wellbeing framework.<h4>Results</h4>An initial knowledge gap meant mental wellbeing was strongly impacted initially leading to a 'Diagnostic Blow and the Search for Clarity'. Doubt over individuals' future resulted in 'An Uncertain Future' in many men. Once treatment was completed a 'Reflective journey' began, with men considering their outcomes and decisions made. Social wellbeing was also impacted with many identifying the 'Emotional Repercussions' on their relationships and the impact their diagnosis had on their partner and family. Many subsequently sought to increase their support through 'The Social Network and Advocacy', while physical changes led to an increased need for 'Social Planning'. Finally, physical wellbeing was highlighted by a continual acknowledgement of the 'Natural process of ageing' leading to a reluctancy to seek help, whilst simultaneously attempting to improve existing health via 'The Health Kick'.<h4>Conclusions</h4>Radical treatments have a considerable impact on mental and social wellbeing of individuals. Anxiety after diagnosis and significant uncertainty over individual futures exist, with physical complications of treatment leading to social repercussions. Future research should aim to identify forms of support to improve quality of life of these men.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279250&type=printable; doi:https://doi.org/10.1371/journal.pone.0279250; html:https://europepmc.org/articles/PMC9757548; pdf:https://europepmc.org/articles/PMC9757548?pdf=render
 36299367,https://doi.org/10.1183/23120541.00211-2022,Mortality associated with metabolic syndrome in people with COPD managed in primary care.,"Karsanji U, Evans RA, Quint JK, Khunti K, Lawson CA, Petherick E, Greening NJ, Singh SJ, Richardson M, Steiner MC.",,ERJ open research,2022,2022-10-24,Y,,,,"<h4>Objective</h4>The prevalence of metabolic syndrome (MetS) has been reported to be higher in selected populations of people with COPD. The impact of MetS on mortality in COPD is unknown. We used routinely collected healthcare data to estimate the prevalence of MetS in people with COPD managed in primary care and determine its impact on 5-year mortality.<h4>Methods</h4>Records from 103 955 patients with COPD from the Clinical Practice Research Datalink (CPRD-GOLD) between 2009 to 2017 were scrutinised. MetS was defined as the presence of three or more of: obesity, hypertension, lowered high-density lipoprotein cholesterol, elevated triglycerides or type 2 diabetes mellitus (T2DM). Univariate and multivariable Cox regression models were constructed to determine the prognostic impact of MetS on 5-year mortality. Similar univariate models were constructed for individual components of the definition of MetS.<h4>Results</h4>The prevalence of MetS in the COPD cohort was 10.1%. Univariate analyses showed the presence of MetS increased mortality (hazard ratio (HR) 1.19, 95% CI: 1.12-1.27, p<0.001), but this risk was substantially attenuated in the multivariable analysis (HR 1.06, 95% CI: 0.99-1.13, p<i>=</i>0.085). The presence of hypertension (HR 1.70, 95% CI: 1.63-1.77, p<0.001) and T2DM (HR 1.41, 95% CI: 1.34-1.48, p<0.001) increased and obesity (HR 0.74, 95% CI: 0.71-0.78, p<0.001) reduced mortality risk.<h4>Conclusion</h4>MetS in patients with COPD is associated with higher 5-year mortality, but this impact was minimal when adjusted for indices of COPD disease severity and other comorbidities. Individual components of the MetS definition exerted differential impacts on mortality suggesting limitation to the use of MetS as a multicomponent condition in predicting outcome in COPD.",,pdf:https://openres.ersjournals.com/content/erjor/8/4/00211-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00211-2022; html:https://europepmc.org/articles/PMC9589337; pdf:https://europepmc.org/articles/PMC9589337?pdf=render
 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.,"Gammall 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.",,pdf:https://www.nature.com/articles/s41698-022-00269-5.pdf; doi:https://doi.org/10.1038/s41698-022-00269-5; html:https://europepmc.org/articles/PMC9021198; pdf:https://europepmc.org/articles/PMC9021198?pdf=render
-36745557,https://doi.org/10.1093/bjd/ljac132,"Factors associated with depression, anxiety and severe mental illness among adults with atopic eczema or psoriasis: a systematic review and meta-analysis.","Adesanya EI, Matthewman J, Schonmann Y, Hayes JF, Henderson A, Mathur R, Mulick AR, Smith CH, Langan SM, Mansfield KE.",,The British journal of dermatology,2023,2023-03-01,N,,,,"<h4>Background</h4>Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear.<h4>Objectives</h4>To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis.<h4>Methods</h4>We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis.<h4>Results</h4>We included 21 studies (11 observational, 10 RCTs). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety - one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest that female sex and psoriatic arthritis were associated with depression [female sex: odds ratio (OR) 1.62, 95% confidence interval (CI) 1.09-2.40, 95% prediction intervals (PIs) 0.62-4.23, I2 = 24.90%, τ2 = 0.05; psoriatic arthritis: OR 2.26, 95% CI 1.56-3.25, 95% PI 0.21-24.23, I2 = 0.00%, τ2 = 0.00] and anxiety (female sex: OR 2.59, 95% CI 1.32-5.07, 95% PI 0.00-3956.27, I2 = 61.90%, τ2 = 0.22; psoriatic arthritis: OR 1.98, 95% CI 1.33-2.94, I2 = 0.00%, τ2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR 1.14, 95% CI 1.05-1.25, I2 0.00%, τ2 = 0.00), but not depression. Evidence from RCTs suggested that adults with AE or psoriasis given placebo had higher depression and anxiety scores compared with comparators given targeted treatment (e.g. biologic agents).<h4>Conclusions</h4>Our review highlights limited existing research on factors associated with depression, anxiety and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested that AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared with skin disease treated with targeted therapy; however, follow-up was limited. Therefore, long-term effects on mental health are unclear.",,pdf:https://academic.oup.com/bjd/article-pdf/188/4/460/51790111/ljac132.pdf; doi:https://doi.org/10.1093/bjd/ljac132
 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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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; doi:https://doi.org/10.2196/14306; html:https://europepmc.org/articles/PMC7199134
+36745557,https://doi.org/10.1093/bjd/ljac132,"Factors associated with depression, anxiety and severe mental illness among adults with atopic eczema or psoriasis: a systematic review and meta-analysis.","Adesanya EI, Matthewman J, Schonmann Y, Hayes JF, Henderson A, Mathur R, Mulick AR, Smith CH, Langan SM, Mansfield KE.",,The British journal of dermatology,2023,2023-03-01,N,,,,"<h4>Background</h4>Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear.<h4>Objectives</h4>To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis.<h4>Methods</h4>We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis.<h4>Results</h4>We included 21 studies (11 observational, 10 RCTs). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety - one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest that female sex and psoriatic arthritis were associated with depression [female sex: odds ratio (OR) 1.62, 95% confidence interval (CI) 1.09-2.40, 95% prediction intervals (PIs) 0.62-4.23, I2 = 24.90%, τ2 = 0.05; psoriatic arthritis: OR 2.26, 95% CI 1.56-3.25, 95% PI 0.21-24.23, I2 = 0.00%, τ2 = 0.00] and anxiety (female sex: OR 2.59, 95% CI 1.32-5.07, 95% PI 0.00-3956.27, I2 = 61.90%, τ2 = 0.22; psoriatic arthritis: OR 1.98, 95% CI 1.33-2.94, I2 = 0.00%, τ2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR 1.14, 95% CI 1.05-1.25, I2 0.00%, τ2 = 0.00), but not depression. Evidence from RCTs suggested that adults with AE or psoriasis given placebo had higher depression and anxiety scores compared with comparators given targeted treatment (e.g. biologic agents).<h4>Conclusions</h4>Our review highlights limited existing research on factors associated with depression, anxiety and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested that AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared with skin disease treated with targeted therapy; however, follow-up was limited. Therefore, long-term effects on mental health are unclear.",,pdf:https://academic.oup.com/bjd/article-pdf/188/4/460/51790111/ljac132.pdf; doi:https://doi.org/10.1093/bjd/ljac132
 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.",,pdf:https://academic.oup.com/brain/article-pdf/144/9/2670/40880367/awab253.pdf; 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
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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).<h4>Interpretation</h4>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.<h4>Clinical trial registration</h4>ClinicalTrials.gov Identifier: NCT01851538https://clinicaltrials.gov/ct2/show/NCT01851538.<h4>Funding</h4>EU/EFPIA IMI2JU BigData@Heart grant n°116074, Jaap Schouten Foundation and Noordwest Academie.",,pdf:http://www.thelancet.com/article/S2352396423002207/pdf; doi:https://doi.org/10.1016/j.ebiom.2023.104655; html:https://europepmc.org/articles/PMC10279550; pdf:https://europepmc.org/articles/PMC10279550?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.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009121&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009121; html:https://europepmc.org/articles/PMC8259985; pdf:https://europepmc.org/articles/PMC8259985?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,,,"<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>Interventions which target clusters of social and physical factors at home, especially among low-socioeconomic status families, are warranted.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa60257/Download/60257__24327__e83f9d0502424e5e9075c668a2672db1.pdf; doi:https://doi.org/10.1123/pes.2021-0174
 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.",,pdf:https://www.nature.com/articles/s41598-022-26141-x.pdf; doi:https://doi.org/10.1038/s41598-022-26141-x; html:https://europepmc.org/articles/PMC9789116; pdf:https://europepmc.org/articles/PMC9789116?pdf=render
-37190903,https://doi.org/10.1002/ijc.34548,Cancer incidence and mortality in 23 000 patients with type 1 diabetes in the UK: Long-term follow-up.,"Swerdlow AJ, Jones ME, Slater SD, Burden ACF, Botha JL, Waugh NR, Morris AD, Gatling W, Gillespie KM, Patterson CC, Schoemaker MJ.",,International journal of cancer,2023,2023-05-15,N,Cancer; type 1 diabetes; Cohort,,,"Type 2 diabetes is associated with raised risk of several cancers, but for type 1 diabetes risk data are fewer and inconsistent We assembled a cohort of 23 473 UK patients with insulin-treated diabetes diagnosed at ages <30, almost all of whom will have had type 1 diabetes, and for comparison 5058 diagnosed at ages 30 to 49, of whom we estimate two-thirds will have had type 2, and followed them for an average of 30 years for cancer incidence and mortality compared with general population rates. Patients aged <30 at diabetes diagnosis had significantly raised risks only for ovarian (standardised incidence ratio = 1.58; 95% confidence interval 1.16-2.11; P < .01) and vulval (3.55; 1.94-5.96; P < .001) cancers, with greatest risk when diabetes was diagnosed at ages 10-14. Risks of cancer overall (0.89; 0.84-0.95; P < .001) and sites including lung and larynx were significantly diminished. Patients diagnosed with diabetes at ages 30 to 49 had significantly raised risks of liver (1.76;1.08-2.72) and kidney (1.46;1.03-2.00) cancers, and reduced risk of cancer overall (0.89; 0.84-0.95). The raised ovarian and vulval cancer risks in patients with type 1 diabetes, especially with diabetes diagnosed around pubertal ages, suggest possible susceptibility of these organs at puberty to metabolic disruption at diabetes onset. Reduced risk of cancer overall, particularly smoking and alcohol-related sites, might reflect adoption of a healthy lifestyle.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.34548; doi:https://doi.org/10.1002/ijc.34548
 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; doi:https://doi.org/10.1177/17407745211069985; html:https://europepmc.org/articles/PMC9036147; pdf:https://europepmc.org/articles/PMC9036147?pdf=render
+37190903,https://doi.org/10.1002/ijc.34548,Cancer incidence and mortality in 23 000 patients with type 1 diabetes in the UK: Long-term follow-up.,"Swerdlow AJ, Jones ME, Slater SD, Burden ACF, Botha JL, Waugh NR, Morris AD, Gatling W, Gillespie KM, Patterson CC, Schoemaker MJ.",,International journal of cancer,2023,2023-05-15,N,Cancer; type 1 diabetes; Cohort,,,"Type 2 diabetes is associated with raised risk of several cancers, but for type 1 diabetes risk data are fewer and inconsistent We assembled a cohort of 23 473 UK patients with insulin-treated diabetes diagnosed at ages <30, almost all of whom will have had type 1 diabetes, and for comparison 5058 diagnosed at ages 30 to 49, of whom we estimate two-thirds will have had type 2, and followed them for an average of 30 years for cancer incidence and mortality compared with general population rates. Patients aged <30 at diabetes diagnosis had significantly raised risks only for ovarian (standardised incidence ratio = 1.58; 95% confidence interval 1.16-2.11; P < .01) and vulval (3.55; 1.94-5.96; P < .001) cancers, with greatest risk when diabetes was diagnosed at ages 10-14. Risks of cancer overall (0.89; 0.84-0.95; P < .001) and sites including lung and larynx were significantly diminished. Patients diagnosed with diabetes at ages 30 to 49 had significantly raised risks of liver (1.76;1.08-2.72) and kidney (1.46;1.03-2.00) cancers, and reduced risk of cancer overall (0.89; 0.84-0.95). The raised ovarian and vulval cancer risks in patients with type 1 diabetes, especially with diabetes diagnosed around pubertal ages, suggest possible susceptibility of these organs at puberty to metabolic disruption at diabetes onset. Reduced risk of cancer overall, particularly smoking and alcohol-related sites, might reflect adoption of a healthy lifestyle.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.34548; doi:https://doi.org/10.1002/ijc.34548
 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",,"<h4>Motivation</h4>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.<h4>Results</h4>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.<h4>Availability and implementation</h4>https://github.com/bio-ontology-research-group/phenogocon.",,pdf:https://academic.oup.com/bioinformatics/article-pdf/34/17/i857/25702307/bty605.pdf; doi:https://doi.org/10.1093/bioinformatics/bty605; html:https://europepmc.org/articles/PMC6129279; pdf:https://europepmc.org/articles/PMC6129279?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,,,"<h4>Introduction and aim</h4>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.<h4>Method</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.<h4>Conclusion</h4>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
 31616478,https://doi.org/10.3389/fgene.2019.00922,Machine Learning Predicts Accurately <i>Mycobacterium tuberculosis</i> 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,,"<b>Background:</b> Tuberculosis disease, caused by <i>Mycobacterium tuberculosis</i>, is a major public health problem. The emergence of <i>M. tuberculosis</i> 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. <b>Methods:</b> We applied machine learning approaches to 16,688 <i>M. tuberculosis</i> 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. <b>Results:</b> 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. <b>Conclusion:</b> 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.",,pdf:https://www.frontiersin.org/articles/10.3389/fgene.2019.00922/pdf; doi:https://doi.org/10.3389/fgene.2019.00922; html:https://europepmc.org/articles/PMC6775242; pdf:https://europepmc.org/articles/PMC6775242?pdf=render
@@ -766,12 +766,12 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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,,,"<b>Introduction</b>Patients 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.<b>Methods</b>We 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.<b>Results</b>Cases and controls had a median (25<sup>th</sup>-75<sup>th</sup>percentile) 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] <i>versus</i> 10.0 [7.0-14.4] cells/ml), although this difference was non-significant (<i>P</i> = 0.339). In controls, the mean cell concentration was significantly (<i>P</i> = 0.030) lower in post 30-day samples compared to samples collected within one day after index ACS: 10.1 (7.5-13.6) <i>versus</i> 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).<b>Conclusion</b>Despite 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; doi:https://doi.org/10.1080/1354750X.2022.2162966
 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,,,,"<h4>Context</h4>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.<h4>Objective</h4>To evaluate the available evidence on pubertal timing of boys and girls born to mothers with GDM.<h4>Data sources</h4>We searched MEDLINE, EMBASE, CINAHL Plus, Cochrane library and grey literature for observational studies up to October 2019.<h4>Study selection and extraction</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://eje.bioscientifica.com/downloadpdf/journals/eje/184/1/EJE-20-0296.pdf; doi:https://doi.org/10.1530/EJE-20-0296; html:https://europepmc.org/articles/PMC7707806; pdf:https://europepmc.org/articles/PMC7707806?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,,,,"<h4>Background</h4>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.<h4>Dataset/methods</h4>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.<h4>Results</h4>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/m<sup>2</sup> 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.<h4>Discussion</h4>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.",,pdf:https://www.nature.com/articles/s41366-021-00846-x.pdf; doi:https://doi.org/10.1038/s41366-021-00846-x; html:https://europepmc.org/articles/PMC8310793; pdf:https://europepmc.org/articles/PMC8310793?pdf=render
-37717030,https://doi.org/10.1186/s13756-023-01280-6,The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England.,"Yang YT, Zhong X, Fahmi A, Watts S, Ashcroft DM, Massey J, Fisher L, MacKenna B, Mehrkar A, Bacon SCJ, Goldacre B, Hand K, van Staa T, Palin V.",,Antimicrobial resistance and infection control,2023,2023-09-16,Y,Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic,,,"<h4>Background</h4>There is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes.<h4>Methods</h4>With the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated.<h4>Results</h4>Records from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36-0.53) for incident consultations and 0.43 (95% CI 0.33-0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07-0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022.<h4>Conclusions</h4>Changes to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.",,doi:https://doi.org/10.1186/s13756-023-01280-6; doi:https://doi.org/10.1186/s13756-023-01280-6; html:https://europepmc.org/articles/PMC10504725; pdf:https://europepmc.org/articles/PMC10504725?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,,,,"<h4>Importance</h4>Both epilepsy and enzyme-inducing antiseizure medications (eiASMs) having varying reports of an association with increased risks for osteoporosis.<h4>Objective</h4>To quantify and model the independent hazards for osteoporosis associated with incident epilepsy and eiASMS and non-eiASMs.<h4>Design, setting, and participants</h4>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.<h4>Exposure</h4>Incident adult-onset epilepsy using a 5-year washout and receipt of 4 consecutive ASMs.<h4>Main outcomes and measures</h4>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.<h4>Results</h4>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.<h4>Conclusions and relevance</h4>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
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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]).<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/ageing/article-pdf/50/4/1019/40971734/afab060.pdf; doi:https://doi.org/10.1093/ageing/afab060; html:https://europepmc.org/articles/PMC7989651; pdf:https://europepmc.org/articles/PMC7989651?pdf=render
+37717030,https://doi.org/10.1186/s13756-023-01280-6,The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England.,"Yang YT, Zhong X, Fahmi A, Watts S, Ashcroft DM, Massey J, Fisher L, MacKenna B, Mehrkar A, Bacon SCJ, Goldacre B, Hand K, van Staa T, Palin V.",,Antimicrobial resistance and infection control,2023,2023-09-16,Y,Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic,,,"<h4>Background</h4>There is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes.<h4>Methods</h4>With the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated.<h4>Results</h4>Records from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36-0.53) for incident consultations and 0.43 (95% CI 0.33-0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07-0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022.<h4>Conclusions</h4>Changes to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.",,doi:https://doi.org/10.1186/s13756-023-01280-6; doi:https://doi.org/10.1186/s13756-023-01280-6; html:https://europepmc.org/articles/PMC10504725; pdf:https://europepmc.org/articles/PMC10504725?pdf=render
 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; doi:https://doi.org/10.1016/j.socscimed.2022.115237; html:https://europepmc.org/articles/PMC9357441; pdf:https://europepmc.org/articles/PMC9357441?pdf=render
-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,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061849.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061849; html:https://europepmc.org/articles/PMC9709811; pdf:https://europepmc.org/articles/PMC9709811?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,,,,"<h4>Importance</h4>Both epilepsy and enzyme-inducing antiseizure medications (eiASMs) having varying reports of an association with increased risks for osteoporosis.<h4>Objective</h4>To quantify and model the independent hazards for osteoporosis associated with incident epilepsy and eiASMS and non-eiASMs.<h4>Design, setting, and participants</h4>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.<h4>Exposure</h4>Incident adult-onset epilepsy using a 5-year washout and receipt of 4 consecutive ASMs.<h4>Main outcomes and measures</h4>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.<h4>Results</h4>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.<h4>Conclusions and relevance</h4>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
 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.",,pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100356.full.pdf; doi:https://doi.org/10.1136/bmjhci-2021-100356; html:https://europepmc.org/articles/PMC8286765; pdf:https://europepmc.org/articles/PMC8286765?pdf=render
+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,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061849.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061849; html:https://europepmc.org/articles/PMC9709811; pdf:https://europepmc.org/articles/PMC9709811?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,,,"<h4>Background</h4>Inpatients experiencing homelessness are often discharged to unstable accommodation or the street, which may increase the risk of readmission.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://jech.bmj.com/content/jech/75/7/681.full.pdf; doi:https://doi.org/10.1136/jech-2020-215204; html:https://europepmc.org/articles/PMC8223662; pdf:https://europepmc.org/articles/PMC8223662?pdf=render
 37667866,https://doi.org/10.1111/cen.14966,Genetically predicted plasma cortisol and common chronic diseases: A Mendelian randomization study.,"Lee WH, Larsson SC, Wood A, Di Angelantonio E, Butterworth AS, Burgess S, Allara E.",,Clinical endocrinology,2023,2023-09-05,N,Hypertension; Cortisol; Osteoporosis; Type 2 diabetes; chronic diseases; Mendelian Randomization; Major Mental Illness,,,"<h4>Objective</h4>Cushing's syndrome is characterized by hypercortisolaemia and is frequently accompanied by comorbidities such as type 2 diabetes, hypertension, osteoporosis, depression and schizophrenia. It is unclear whether moderate but lifelong hypercortisolaemia is causally associated with these diseases in the general population. We aimed to address this research gap using a Mendelian randomization approach.<h4>Methods</h4>We used three cortisol-associated genetic variants in the SERPINA6/SERPINA1 region as genetic instruments in a two-sample, inverse-variance-weighted Mendelian randomization analysis. We obtained summary-level statistics for cortisol and disease outcomes from publicly available genetic consortia, and meta-analysed them as appropriate. We conducted a multivariable Mendelian randomization analysis to assess potential mediating effects.<h4>Results</h4>A 1 standard deviation higher genetically predicted plasma cortisol was associated with greater odds of hypertension (odds ratio: 1.12; 95% confidence interval [CI]: 1.05-1.18) as well as higher systolic blood pressure (mean difference [MD]: 0.03 SD change; 95% CI: 0.01-0.05) and diastolic blood pressure (MD: 0.03 SD change; 95% CI: 0.01-0.04). There was no evidence of association with type 2 diabetes, osteoporosis, depression and schizophrenia. The association with hypertension was attenuated upon adjustment for waist circumference, suggesting potential mediation through central obesity.<h4>Conclusion</h4>There is strong evidence for a causal association between plasma cortisol and greater risk for hypertension, potentially mediated by obesity.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cen.14966; doi:https://doi.org/10.1111/cen.14966
 33356394,https://doi.org/10.1161/hypertensionaha.120.16547,"Urate, Blood Pressure, and Cardiovascular Disease: Evidence From Mendelian Randomization and Meta-Analysis of Clinical Trials.","Gill D, Cameron AC, Burgess S, Li X, Doherty DJ, Karhunen V, Abdul-Rahim AH, Taylor-Rowan M, Zuber V, Tsao PS, Klarin D, VA Million Veteran Program, Evangelou E, Elliott P, Damrauer SM, Quinn TJ, Dehghan A, Theodoratou E, Dawson J, Tzoulaki I.",,"Hypertension (Dallas, Tex. : 1979)",2021,2020-12-28,Y,Cardiovascular diseases; Blood pressure; Uric acid; Systematic review; Odds Ratio,,,"Serum urate has been implicated in hypertension and cardiovascular disease, but it is not known whether it is exerting a causal effect. To investigate this, we performed Mendelian randomization analysis using data from UK Biobank, Million Veterans Program and genome-wide association study consortia, and meta-analysis of randomized controlled trials. The main Mendelian randomization analyses showed that every 1-SD increase in genetically predicted serum urate was associated with an increased risk of coronary heart disease (odds ratio, 1.19 [95% CI, 1.10-1.30]; <i>P</i>=4×10<sup>-5</sup>), peripheral artery disease (1.12 [95% CI, 1.03-1.21]; <i>P</i>=9×10<sup>-3</sup>), and stroke (1.11 [95% CI, 1.05-1.18]; <i>P</i>=2×10<sup>-4</sup>). In Mendelian randomization mediation analyses, elevated blood pressure was estimated to mediate approximately one-third of the effect of urate on cardiovascular disease risk. Systematic review and meta-analysis of randomized controlled trials showed a favorable effect of urate-lowering treatment on systolic blood pressure (mean difference, -2.55 mm Hg [95% CI, -4.06 to -1.05]; <i>P</i>=1×10<sup>-3</sup>) and major adverse cardiovascular events in those with previous cardiovascular disease (odds ratio, 0.40 [95% CI, 0.22-0.73]; <i>P</i>=3×10<sup>-3</sup>) but no significant effect on major adverse cardiovascular events in all individuals (odds ratio, 0.67 [95% CI, 0.44-1.03]; <i>P</i>=0.07). In summary, these Mendelian randomization and clinical trial data support an effect of higher serum urate on increasing blood pressure, which may mediate a consequent effect on cardiovascular disease risk. High-quality trials are necessary to provide definitive evidence on the specific clinical contexts where urate lowering may be of cardiovascular benefit.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.120.16547; doi:https://doi.org/10.1161/HYPERTENSIONAHA.120.16547; html:https://europepmc.org/articles/PMC7803439; pdf:https://europepmc.org/articles/PMC7803439?pdf=render
@@ -785,8 +785,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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,,,,"<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004204&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004204; html:https://europepmc.org/articles/PMC10047529; pdf:https://europepmc.org/articles/PMC10047529?pdf=render
 34481555,https://doi.org/10.1016/s2213-8587(21)00207-2,"Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records.","Katsoulis M, Lai AG, Diaz-Ordaz K, Gomes M, Pasea L, Banerjee A, Denaxas S, Tsilidis K, Lagiou P, Misirli G, Bhaskaran K, Wannamethee G, Dobson R, Batterham RL, Kipourou DK, Lumbers RT, Wen L, Wareham N, Langenberg C, Hemingway H.",,The lancet. Diabetes & endocrinology,2021,2021-09-02,Y,,,,"<h4>Background</h4>Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR).<h4>Methods</h4>In this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions.<h4>Findings</h4>We included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4·22 [95% CI 3·86-4·62]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a higher BMI category; OR 4·60 (4·06-5·22) and absolute risk (42% vs 18%) of transitioning from overweight to class 1 and 2 obesity, and OR 5·87 (5·23-6·59) and absolute risk (22% vs 5%) of transitioning from class 1 and 2 obesity to class 3 obesity. Other demographic factors were consistently less strongly associated with these transitions; for example, the OR of transitioning from normal weight to overweight or obesity in people living in the most socially deprived versus least deprived areas was 1·23 (1·18-1·27), for men versus women was 1·12 (1·08-1·16), and for Black individuals versus White individuals was 1·13 (1·04-1·24). We provide an open access online risk calculator, and present high-resolution obesity risk charts over a 1-year, 5-year, and 10-year follow-up period.<h4>Interpretation</h4>A radical shift in policy is required to focus on individuals at the highest risk of weight gain (ie, young adults aged 18-24 years) for individual-level and population-level prevention of obesity and its long-term consequences for health and health care.<h4>Funding</h4>The British Hearth Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2213858721002072/pdf; doi:https://doi.org/10.1016/S2213-8587(21)00207-2; html:https://europepmc.org/articles/PMC8440227; pdf:https://europepmc.org/articles/PMC8440227?pdf=render
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Department of Health and Social Care, England.",,pdf:http://www.thelancet.com/article/S2213260021005427/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00542-7; html:https://europepmc.org/articles/PMC8786320
-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.",,pdf:http://www.aginganddisease.org/EN/PDF/10.14336/AD.2022.1107; doi:https://doi.org/10.14336/AD.2022.1107; html:https://europepmc.org/articles/PMC10187689; pdf:https://europepmc.org/articles/PMC10187689?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.",,pdf:https://www.nature.com/articles/s41467-022-28517-z.pdf; doi:https://doi.org/10.1038/s41467-022-28517-z; html:https://europepmc.org/articles/PMC8927425; pdf:https://europepmc.org/articles/PMC8927425?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.",,pdf:http://www.aginganddisease.org/EN/PDF/10.14336/AD.2022.1107; doi:https://doi.org/10.14336/AD.2022.1107; html:https://europepmc.org/articles/PMC10187689; pdf:https://europepmc.org/articles/PMC10187689?pdf=render
 35781133,https://doi.org/10.3310/zyzc8514,Long-term impact of pre-incision antibiotics on children born by caesarean section: a longitudinal study based on 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.",,"Health technology assessment (Winchester, England)",2022,2022-06-01,N,Asthma; Caesarean section; Eczema; Child Health; Anti-bacterial Agents; Microbiome; Electronic Health Records; Interrupted Time Series Analysis,,,"<h4>Background</h4>Since changes in the national guidance in 2011, prophylactic antibiotics for women undergoing caesarean section are recommended prior to skin incision, rather than after the baby's umbilical cord has been clamped. Evidence from randomised controlled trials conducted outside the UK has shown that this reduces maternal infectious morbidity; however, the prophylactic antibiotics also cross the placenta, meaning that babies are exposed to them around the time of birth. Antibiotics are known to affect the gut microbiota of the babies, but the long-term effects of exposure to high-dose broad-spectrum antibiotics around the time of birth on allergy and immune-related diseases are unknown.<h4>Objectives</h4>We aimed to examine whether or not in-utero exposure to antibiotics immediately prior to birth compared with no pre-incisional antibiotic exposure increases the risk of (1) asthma and (2) eczema in children born by caesarean section.<h4>Design</h4>This was a controlled interrupted time series study.<h4>Setting</h4>The study took place in primary and secondary care.<h4>Participants</h4>Children born in the UK during 2006-18 delivered by caesarean section were compared with a control cohort delivered vaginally.<h4>Interventions</h4>In-utero exposure to antibiotics immediately prior to birth.<h4>Main outcome measures</h4>Asthma and eczema in children in the first 5 years of life. Additional secondary outcomes, including other allergy-related conditions, autoimmune diseases, infections, other immune system-related diseases and neurodevelopmental conditions, were also assessed.<h4>Data sources</h4>The Health Improvement Network (THIN) and the Clinical Practice Research Datalink (CPRD) primary care databases and the Hospital Episode Statistics (HES) database. Previously published linkage strategies were adapted to link anonymised data on mothers and babies in these databases. Duplicate practices contributing to both THIN and the CPRD databases were removed to create a THIN-CPRD data set.<h4>Results</h4>In the THIN-CPRD and HES data sets, records of 515,945 and 3,945,351 mother-baby pairs were analysed, respectively. The risk of asthma was not significantly higher in children born by caesarean section exposed to pre-incision antibiotics than in children whose mothers received post-cord clamping antibiotics, with an incidence rate ratio of 0.91 (95% confidence interval 0.78 to 1.05) for diagnosis of asthma in primary care and an incidence rate ratio of 1.05 (95% confidence interval 0.99 to 1.11) for asthma resulting in a hospital admission. We also did not find an increased risk of eczema, with an incidence rate ratio of 0.98 (95% confidence interval 0.94 to1.03) and an incidence rate ratio of 0.96 (95% confidence interval 0.71 to 1.29) for diagnosis in primary care and hospital admissions, respectively.<h4>Limitations</h4>It was not possible to ascertain the exposure to pre-incision antibiotics at an individual level. The maximum follow-up of children was 5 years.<h4>Conclusions</h4>There was no evidence that the policy change from post-cord clamping to pre-incision prophylactic antibiotics for caesarean sections during 2006-18 had an impact on the incidence of asthma and eczema in early childhood in the UK.<h4>Future work</h4>There is a need for further research to investigate if pre-incision antibiotics have any impact on developing asthma and other allergy and immune-related conditions in older children.<h4>Study registration</h4>This study is registered as researchregistry3736.<h4>Funding</h4>This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in <i>Health Technology Assessment</i>; Vol. 26, No. 30. See the NIHR Journals Library website for further project information.",,pdf:https://njl-admin.nihr.ac.uk/document/download/2039937; doi:https://doi.org/10.3310/ZYZC8514
 35055401,https://doi.org/10.3390/jpm12010086,Predicting Hospital Readmission for Campylobacteriosis from Electronic Health Records: A Machine Learning and Text Mining Perspective. ,"Zhou SM, Lyons RA, Rahman MA, Holborow A, Brophy S.",,Journal of personalized medicine,2022,2022-01-10,Y,,,,"(1) Background: This study investigates influential risk factors for predicting 30-day readmission to hospital for Campylobacter infections (CI). (2) Methods: We linked general practitioner and hospital admission records of 13,006 patients with CI in Wales (1990-2015). An approach called TF-zR (term frequency-zRelevance) technique was presented to evaluates how relevant a clinical term is to a patient in a cohort characterized by coded health records. The zR is a supervised term-weighting metric to assign weight to a term based on relative frequencies of the term across different classes. Cost-sensitive classifier with swarm optimization and weighted subset learning was integrated to identify influential clinical signals as predictors and optimal model for readmission prediction. (3) Results: From a pool of up to 17,506 variables, 33 most predictive factors were identified, including age, gender, Townsend deprivation quintiles, comorbidities, medications, and procedures. The predictive model predicted readmission with 73% sensitivity and 54% specificity. Variables associated with readmission included male gender, recurrent tonsillitis, non-healing open wounds, operation for in-gown toenails. Cystitis, paracetamol/codeine use, age (21-25), and heliclear triple pack use, were associated with a lower risk of readmission. (4) Conclusions: This study gives a profile of clustered variables that are predictive of readmission associated with campylobacteriosis.",,pdf:https://www.mdpi.com/2075-4426/12/1/86/pdf?version=1641832520; doi:https://doi.org/10.3390/jpm12010086; html:https://europepmc.org/articles/PMC8779953; pdf:https://europepmc.org/articles/PMC8779953?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,,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-021-05951-w; doi:https://doi.org/10.1186/s12879-021-05951-w; html:https://europepmc.org/articles/PMC7957446; pdf:https://europepmc.org/articles/PMC7957446?pdf=render
@@ -807,13 +807,13 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 35793336,https://doi.org/10.1371/journal.pone.0266521,"Spatiotemporal mapping of major trauma in Victoria, Australia.","Beck B, Zammit-Mangion A, Fry R, Smith K, Gabbe B.",,PloS one,2022,2022-07-06,Y,,,,"<h4>Background</h4>Spatiotemporal modelling techniques allow one to predict injury across time and space. However, such methods have been underutilised in injury studies. This study demonstrates the use of statistical spatiotemporal modelling in identifying areas of significantly high injury risk, and areas witnessing significantly increasing risk over time.<h4>Methods</h4>We performed a retrospective review of hospitalised major trauma patients from the Victorian State Trauma Registry, Australia, between 2007 and 2019. Geographical locations of injury events were mapped to the 79 local government areas (LGAs) in the state. We employed Bayesian spatiotemporal models to quantify spatial and temporal patterns, and analysed the results across a range of geographical remoteness and socioeconomic levels.<h4>Results</h4>There were 31,317 major trauma patients included. For major trauma overall, we observed substantial spatial variation in injury incidence and a significant 2.1% increase in injury incidence per year. Area-specific risk of injury by motor vehicle collision was higher in regional areas relative to metropolitan areas, while risk of injury by low fall was higher in metropolitan areas. Significant temporal increases were observed in injury by low fall, and the greatest increases were observed in the most disadvantaged LGAs.<h4>Conclusions</h4>These findings can be used to inform injury prevention initiatives, which could be designed to target areas with relatively high injury risk and with significantly increasing injury risk over time. Our finding that the greatest year-on-year increases in injury incidence were observed in the most disadvantaged areas highlights the need for a greater emphasis on reducing inequities in injury.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0266521&type=printable; doi:https://doi.org/10.1371/journal.pone.0266521; html:https://europepmc.org/articles/PMC9258853; pdf:https://europepmc.org/articles/PMC9258853?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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/intqhc/article-pdf/34/2/mzac031/43704475/mzac031.pdf; doi:https://doi.org/10.1093/intqhc/mzac031
 32997638,https://doi.org/10.1109/jbhi.2020.3027987,A Novel Intelligent Computational Approach to Model Epidemiological Trends and Assess the Impact of Non-Pharmacological Interventions for COVID-19.,"Ren J, Yan Y, Zhao H, Ma P, Zabalza J, Hussain Z, Luo S, Dai Q, Zhao S, Sheikh A, Hussain A, Li H.",,IEEE journal of biomedical and health informatics,2020,2020-12-04,Y,,,,"The novel coronavirus disease 2019 (COVID-19) pandemic has led to a worldwide crisis in public health. It is crucial we understand the epidemiological trends and impact of non-pharmacological interventions (NPIs), such as lockdowns for effective management of the disease and control of its spread. We develop and validate a novel intelligent computational model to predict epidemiological trends of COVID-19, with the model parameters enabling an evaluation of the impact of NPIs. By representing the number of daily confirmed cases (NDCC) as a time-series, we assume that, with or without NPIs, the pattern of the pandemic satisfies a series of Gaussian distributions according to the central limit theorem. The underlying pandemic trend is first extracted using a singular spectral analysis (SSA) technique, which decomposes the NDCC time series into the sum of a small number of independent and interpretable components such as a slow varying trend, oscillatory components and structureless noise. We then use a mixture of Gaussian fitting (GF) to derive a novel predictive model for the SSA extracted NDCC incidence trend, with the overall model termed SSA-GF. Our proposed model is shown to accurately predict the NDCC trend, peak daily cases, the length of the pandemic period, the total confirmed cases and the associated dates of the turning points on the cumulated NDCC curve. Further, the three key model parameters, specifically, the amplitude (alpha), mean (mu), and standard deviation (sigma) are linked to the underlying pandemic patterns, and enable a directly interpretable evaluation of the impact of NPIs, such as strict lockdowns and travel restrictions. The predictive model is validated using available data from China and South Korea, and new predictions are made, partially requiring future validation, for the cases of Italy, Spain, the UK and the USA. Comparative results demonstrate that the introduction of consistent control measures across countries can lead to development of similar parametric models, reflected in particular by relative variations in their underlying sigma, alpha and mu values. The paper concludes with a number of open questions and outlines future research directions.",,pdf:https://ieeexplore.ieee.org/ielx7/6221020/9281055/09210178.pdf; doi:https://doi.org/10.1109/JBHI.2020.3027987; html:https://europepmc.org/articles/PMC8545177; pdf:https://europepmc.org/articles/PMC8545177?pdf=render
-37008054,https://doi.org/10.14336/ad.2022.0829,Identifying Dynamic Patterns of Polypharmacy for Patients with Dementia from Primary Care Electronic Health Records: A Machine Learning Driven Longitudinal Study.,"Longo E, Burnett B, Bauermeister S, Zhou SM.",,Aging and disease,2023,2023-04-01,Y,Diagnosis; Dementia; Patient Safety; Machine Learning; Polypharmacy; Electronic Health Records; Exploratory Factor Analysis,,,"It is unclear how medication use evolved before diagnosis of dementia (DoD). This study aims to identify varied patterns of polypharmacy before DoD, their prevalence and possible complications. We collected primary care e-health records for 33,451 dementia patients in Wales from 1990 to 2015. The medication uses in every 5-year period along with 20-years prior to dementia diagnosis were considered. Exploratory factor analysis was used to identify clusters of medicines for every 5-year period. The prevalence of patients taking three or more medications was 82.16%, 69.7%, 41.1% and 5.5% in the Period 1 (0-5 years before DoD) ~ Period 4 (16-20 years before DoD) respectively. The Period 1 showed 3 clusters of polypharmacy - medicines for respiratory/urinary infections, arthropathies and rheumatism, and cardio-vascular disease (CVD) (66.55%); medicines for infections, arthropathies and rheumatism (AR), cardio-metabolic disease (CMD) and depression (22.02%); and medicines for arthropathies, rheumatism and osteoarthritis (2.6%). The Period 2 showed 4 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (69.7%); medicines for CVD and depression (3%); medicines for CMD and arthropathies (0.3%); and medicines for AR, and CVD (2,5%). The Period 3 showed 6 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (41.1%); medicines for CVD, acute-respiratory-infection (ARI), and arthropathies (1.25%); medicines for AR (1.16%); medicines for depression, anxiety (0.06%); medicines for CMD (1.4%); and medicines for dermatologic disorders (0.9%). The Period 4 showed 3 main clusters of polypharmacy - medicines for infections, arthropathy, and CVD (5.5%); medicines for anxiety, ARI (2.4%); and medicines for ARI and CVD (2.1%). As the development towards dementia progressed, the associative diseases tended to cluster with a larger prevalence in each cluster. Farther away before DoD, the clusters of polypharmacy tended to be clearly distinct between each other, resulting in an increasing number of patterns, but in a smaller prevalence.",,doi:https://doi.org/10.14336/ad.2022.0829; doi:https://doi.org/10.14336/AD.2022.0829; html:https://europepmc.org/articles/PMC10017143; pdf:https://europepmc.org/articles/PMC10017143?pdf=render
 37705832,https://doi.org/10.5837/bjc.2023.003,SGLT2 inhibitors in CKD and HFpEF: two new large trials and two new meta-analyses.,"Mayne KJ, Preiss D, Herrington WG.",,The British journal of cardiology,2023,2023-02-21,N,Cardiovascular disease; Heart Failure; Chronic Kidney Disease; Sodium-Glucose Co-Transporter 2 (Sglt2) Inhibitor,,,,,doi:https://doi.org/10.5837/bjc.2023.003; html:https://europepmc.org/articles/PMC10495762; pdf:https://europepmc.org/articles/PMC10495762?pdf=render; doi:https://doi.org/10.5837/bjc.2023.003
+37008054,https://doi.org/10.14336/ad.2022.0829,Identifying Dynamic Patterns of Polypharmacy for Patients with Dementia from Primary Care Electronic Health Records: A Machine Learning Driven Longitudinal Study.,"Longo E, Burnett B, Bauermeister S, Zhou SM.",,Aging and disease,2023,2023-04-01,Y,Diagnosis; Dementia; Patient Safety; Machine Learning; Polypharmacy; Electronic Health Records; Exploratory Factor Analysis,,,"It is unclear how medication use evolved before diagnosis of dementia (DoD). This study aims to identify varied patterns of polypharmacy before DoD, their prevalence and possible complications. We collected primary care e-health records for 33,451 dementia patients in Wales from 1990 to 2015. The medication uses in every 5-year period along with 20-years prior to dementia diagnosis were considered. Exploratory factor analysis was used to identify clusters of medicines for every 5-year period. The prevalence of patients taking three or more medications was 82.16%, 69.7%, 41.1% and 5.5% in the Period 1 (0-5 years before DoD) ~ Period 4 (16-20 years before DoD) respectively. The Period 1 showed 3 clusters of polypharmacy - medicines for respiratory/urinary infections, arthropathies and rheumatism, and cardio-vascular disease (CVD) (66.55%); medicines for infections, arthropathies and rheumatism (AR), cardio-metabolic disease (CMD) and depression (22.02%); and medicines for arthropathies, rheumatism and osteoarthritis (2.6%). The Period 2 showed 4 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (69.7%); medicines for CVD and depression (3%); medicines for CMD and arthropathies (0.3%); and medicines for AR, and CVD (2,5%). The Period 3 showed 6 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (41.1%); medicines for CVD, acute-respiratory-infection (ARI), and arthropathies (1.25%); medicines for AR (1.16%); medicines for depression, anxiety (0.06%); medicines for CMD (1.4%); and medicines for dermatologic disorders (0.9%). The Period 4 showed 3 main clusters of polypharmacy - medicines for infections, arthropathy, and CVD (5.5%); medicines for anxiety, ARI (2.4%); and medicines for ARI and CVD (2.1%). As the development towards dementia progressed, the associative diseases tended to cluster with a larger prevalence in each cluster. Farther away before DoD, the clusters of polypharmacy tended to be clearly distinct between each other, resulting in an increasing number of patterns, but in a smaller prevalence.",,doi:https://doi.org/10.14336/ad.2022.0829; doi:https://doi.org/10.14336/AD.2022.0829; html:https://europepmc.org/articles/PMC10017143; pdf:https://europepmc.org/articles/PMC10017143?pdf=render
 37140153,https://doi.org/10.1093/ehjci/jead093,Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation.,"Althunayyan AM, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.",,European heart journal. Cardiovascular Imaging,2023,2023-08-01,N,Surgery; Mitral regurgitation; Mitral Valve Prolapse; Global Longitudinal Strain; Lv Volumes,,,"<h4>Aims</h4>Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery.<h4>Methods and results</h4>Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01-1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00-2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment.<h4>Conclusion</h4>Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead093/50200028/jead093.pdf; doi:https://doi.org/10.1093/ehjci/jead093
 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.",,pdf:https://academic.oup.com/cercor/article-pdf/31/4/2071/36458400/bhaa345.pdf; doi:https://doi.org/10.1093/cercor/bhaa345; html:https://europepmc.org/articles/PMC7945030; pdf:https://europepmc.org/articles/PMC7945030?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.",,pdf:https://academic.oup.com/mbe/article-pdf/39/3/msac034/42692776/msac034.pdf; doi:https://doi.org/10.1093/molbev/msac034; html:https://europepmc.org/articles/PMC8892942; pdf:https://europepmc.org/articles/PMC8892942?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-acute Sequelae Of Sars-cov-2 Infection (Pasc); Post-Viral Syndromes,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Registration</h4>The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.",,pdf:https://www.mdpi.com/1660-4601/20/4/3477/pdf?version=1677135187; doi:https://doi.org/10.3390/ijerph20043477; html:https://europepmc.org/articles/PMC9967466; pdf:https://europepmc.org/articles/PMC9967466?pdf=render
 31000744,https://doi.org/10.1038/s41598-019-42036-w,"Measuring social, environmental and health inequalities using deep learning and street imagery.","Suel E, Polak JW, Bennett JE, Ezzati M.",,Scientific reports,2019,2019-04-18,Y,,"Applied Analytics, Improving Public Health",,"Cities are home to an increasing majority of the world's population. Currently, it is difficult to track social, economic, environmental and health outcomes in cities with high spatial and temporal resolution, needed to evaluate policies regarding urban inequalities. We applied a deep learning approach to street images for measuring spatial distributions of income, education, unemployment, housing, living environment, health and crime. Our model predicts different outcomes directly from raw images without extracting intermediate user-defined features. To evaluate the performance of the approach, we first trained neural networks on a subset of images from London using ground truth data at high spatial resolution from official statistics. We then compared how trained networks separated the best-off from worst-off deciles for different outcomes in images not used in training. The best performance was achieved for quality of the living environment and mean income. Allocation was least successful for crime and self-reported health (but not objectively measured health). We also evaluated how networks trained in London predict outcomes three other major cities in the UK: Birmingham, Manchester, and Leeds. The transferability analysis showed that networks trained in London, fine-tuned with only 1% of images in other cities, achieved performances similar to ones from trained on data from target cities themselves. Our findings demonstrate that street imagery has the potential complement traditional survey-based and administrative data sources for high-resolution urban surveillance to measure inequalities and monitor the impacts of policies that aim to address them.",,pdf:https://www.nature.com/articles/s41598-019-42036-w.pdf; doi:https://doi.org/10.1038/s41598-019-42036-w; html:https://europepmc.org/articles/PMC6473002; pdf:https://europepmc.org/articles/PMC6473002?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-acute Sequelae Of Sars-cov-2 Infection (Pasc); Post-Viral Syndromes,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Registration</h4>The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.",,pdf:https://www.mdpi.com/1660-4601/20/4/3477/pdf?version=1677135187; doi:https://doi.org/10.3390/ijerph20043477; html:https://europepmc.org/articles/PMC9967466; pdf:https://europepmc.org/articles/PMC9967466?pdf=render
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://jogh.org/wp-content/uploads/2022/06/jogh-12-04052.pdf; doi:https://doi.org/10.7189/jogh.12.04052; html:https://europepmc.org/articles/PMC9239324; pdf:https://europepmc.org/articles/PMC9239324?pdf=render
 35459745,https://doi.org/10.1136/thoraxjnl-2021-218374,Ambient heat exposure and COPD hospitalisations in England: a nationwide case-crossover study during 2007-2018.,"Konstantinoudis G, Minelli C, Vicedo-Cabrera AM, Ballester J, Gasparrini A, Blangiardo M.",,Thorax,2022,2022-04-22,Y,Copd Exacerbations; Copd Epidemiology; Copd Exacerbations Mechanisms,,,"<h4>Background</h4>There is emerging evidence suggesting a link between ambient heat exposure and chronic obstructive pulmonary disease (COPD) hospitalisations. Individual and contextual characteristics can affect population vulnerabilities to COPD hospitalisation due to heat exposure. This study quantifies the effect of ambient heat on COPD hospitalisations and examines population vulnerabilities by age, sex and contextual characteristics.<h4>Methods</h4>Individual data on COPD hospitalisation at high geographical resolution (postcodes) during 2007-2018 in England was retrieved from the small area health statistics unit. Maximum temperature at 1 km ×1 km resolution was available from the UK Met Office. We employed a case-crossover study design and fitted Bayesian conditional Poisson regression models. We adjusted for relative humidity and national holidays, and examined effect modification by age, sex, green space, average temperature, deprivation and urbanicity.<h4>Results</h4>After accounting for confounding, we found 1.47% (95% Credible Interval (CrI) 1.19% to 1.73%) increase in the hospitalisation risk for every 1°C increase in temperatures above 23.2°C (lags 0-2 days). We reported weak evidence of an effect modification by sex and age. We found a strong spatial determinant of the COPD hospitalisation risk due to heat exposure, which was alleviated when we accounted for contextual characteristics. 1851 (95% CrI 1 576 to 2 079) COPD hospitalisations were associated with temperatures above 23.2°C annually.<h4>Conclusion</h4>Our study suggests that resources should be allocated to support the public health systems, for instance, through developing or expanding heat-health alerts, to challenge the increasing future heat-related COPD hospitalisation burden.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/04/21/thoraxjnl-2021-218374.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-218374; html:https://europepmc.org/articles/PMC9606528; pdf:https://europepmc.org/articles/PMC9606528?pdf=render
 37662524,https://doi.org/10.1016/j.eclinm.2023.102172,Tafamidis treatment in patients with transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis.,"Wang J, Chen H, Tang Z, Zhang J, Xu Y, Wan K, Hussain K, Gkoutos GV, Han Y, Chen Y.",,EClinicalMedicine,2023,2023-08-24,Y,Prognosis; Tafamidis; Attr; Transthyretin Amyloid Cardiomyopathy,,,"<h4>Background</h4>Previous studies have reported that tafamidis treatment was associated with better outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with those without tafamidis treatment. Therefore, we aimed to systematically assess the association of tafamidis treatment with outcomes in patients with ATTR-CM.<h4>Methods</h4>The protocol for this systematic review and meta-analysis was registered in the PROSPERO (CRD42022381985). Pubmed, Ovid Embase, Scopus, Cochrane Library, and Web of Science were interrogated to identify studies that evaluated the impact of tafamidis on prognosis in ATTR-CM, from January 1, 2000 to June 1, 2023. A random-effects model was used to determine the pooled risk ratio (RR) for the adverse endpoints. In addition, the main outcomes included all-cause death or heart transplantation, the composite endpoints included all-cause death, heart transplantation, cardiac-assist device implantation, heart failure exacerbations, and hospitalization.<h4>Findings</h4>Fifteen studies comprising 2765 patients (mean age 75.9 ± 9.3 years; 83.7% male) with a mean follow-up duration of 18.7 ± 17.1 months were included in the meta-analysis. There was a decrease in left ventricular ejection fraction (LVEF) (standard mean differences (SMD: -0.17; 95% confidence interval (CI), -0.31 to -0.03; <i>P</i> = 0.02) but were no significant differences in intraventricular septum (IVS) thickness or global longitudinal strain (GLS) after tafamidis treatment. However, subgroup analysis showed no significant deterioration in LVEF in the patients with wild-type ATTR after tafamidis treatment (SMD: -0.11; 95% CI, -0.34 to 0.12, <i>P</i> = 0.34). In addition, the group with tafamidis treatment had a decreased risk for all-cause death or heart transplantation compared to patients without treatment (the pooled RR, 0.44; 95% CI, 0.31-0.65; <i>P</i> < 0.01). Subgroup analysis showed that there was no significant difference of tafamidis on the outcomes in patients with wild-type or hereditary ATTR (RR, 0.44; 95% CI, 0.27-0.73 <i>versus</i> 0.21, 95% CI, 0.11-0.40, <i>P</i> = 0.08). Furthermore, tafamidis treatment was associated with a lower risk of the composite endpoint (RR, 0.57; 95% CI, 0.42-0.77; <i>P</i> < 0.01).<h4>Interpretation</h4>Our findings suggested that there was no significant deterioration in LVEF in the patients with wild-type ATTR after tafamidis treatment. In addition, tafamidis treatment was associated with a low risk of all-cause death and adverse cardiovascular events.<h4>Funding</h4>This work was supported by grants from the Natural Science Foundation of Sichuan Province [Grant Number: 23NSFSC4589] and the National Natural Science Foundation of China [Grant Number: 82202248].",,doi:https://doi.org/10.1016/j.eclinm.2023.102172; html:https://europepmc.org/articles/PMC10474377; pdf:https://europepmc.org/articles/PMC10474377?pdf=render
@@ -822,13 +822,13 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 .",,The British journal of surgery,2021,2021-11-01,Y,,,,,,pdf:https://academic.oup.com/bjs/article-pdf/108/11/1274/47371055/znab183.pdf; doi:https://doi.org/10.1093/bjs/znab183; html:https://europepmc.org/articles/PMC8344569; pdf:https://europepmc.org/articles/PMC8344569?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<sup>®</sup> 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.",,pdf:https://www.nature.com/articles/s41467-021-27164-0.pdf; doi:https://doi.org/10.1038/s41467-021-27164-0; html:https://europepmc.org/articles/PMC8613205; pdf:https://europepmc.org/articles/PMC8613205?pdf=render
 37739596,https://doi.org/10.1016/j.jtha.2023.07.008,"""C1-inhibitor levels and venous thromboembolism: results from a Mendelian randomization study"": reply.","Cupido AJ, Petersen RS, Schmidt AF, Levi M, Cohn DM, Fijen LM.",,Journal of thrombosis and haemostasis : JTH,2023,2023-10-01,N,,,,,,doi:https://doi.org/10.1016/j.jtha.2023.07.008
+34571200,https://doi.org/10.1016/j.jaip.2021.09.026,Atopic Eczema-Associated Fracture Risk and Oral Corticosteroids: A Population-Based Cohort Study.,"Matthewman J, Mansfield KE, Prieto-Alhambra D, Mulick AR, Smeeth L, Lowe KE, Silverwood RJ, Langan SM.",,The journal of allergy and clinical immunology. In practice,2022,2021-09-24,Y,Fracture; Atopic Eczema; Atopic Dermatitis; osteoporotic fracture; Oral Corticosteroids,,,"<h4>Background</h4>Evidence suggests adults with atopic eczema have increased fracture risk. However, it is unclear whether oral corticosteroids explain the association.<h4>Objective</h4>To assess to what extent oral corticosteroids mediate the relationship between atopic eczema and fractures.<h4>Methods</h4>We conducted a cohort study using English primary care (Clinical Practice Research Datalink) and hospital admissions (Hospital Episode Statistics) records (1998-2016) including adults (18 years old and older) with atopic eczema matched (age, sex, and general practice) with up to 5 adults without atopic eczema. We used Cox regression to estimate hazard ratios (HRs) for specific major osteoporotic fractures (hip, spine, pelvis, or wrist) and for any-site fracture comparing individuals with atopic eczema with those without, adjusting for 6 different definitions of time-updated oral corticosteroid use (ever any prescription, ever high-dose, and recent, cumulative, current, or peak dose).<h4>Results</h4>We identified 526,808 individuals with atopic eczema and 2,569,030 without. We saw evidence of an association between atopic eczema and major osteoporotic fractures (eg, spine HR 1.15, 99% CI 1.08-1.22; hip HR 1.11, 99% CI 1.08-1.15) that remained after additionally adjusting for oral corticosteroids (eg, cumulative corticosteroid dose: spine HR 1.09, 99% CI 1.03-1.16; hip HR 1.09, 99% CI 1.06-1.12). Fracture rates were higher in people with severe atopic eczema than in people without even after adjusting for oral corticosteroids (eg, spine HR [99% CI]: confounder-adjusted 2.31 [1.91-2.81]; additionally adjusted for cumulative dose 1.71 [1.40-2.09]).<h4>Conclusions</h4>Our findings suggest that little of the association between atopic eczema and major osteoporotic fractures is explained by oral corticosteroid use.",,pdf:http://www.jaci-inpractice.org/article/S2213219821010187/pdf; doi:https://doi.org/10.1016/j.jaip.2021.09.026; html:https://europepmc.org/articles/PMC7612204; pdf:https://europepmc.org/articles/PMC7612204?pdf=render
 36593100,https://doi.org/10.1136/heartjnl-2022-322124,Response to: Correspondence on 'Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank' by Jolobe.,"Raisi-Estabragh Z, Harvey NC, Petersen SE.",,Heart (British Cardiac Society),2023,2023-01-02,N,epidemiology; acute coronary syndrome; Covid-19,,,,,doi:https://doi.org/10.1136/heartjnl-2022-322124
 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,2023,2023-10-01,Y,Cardiac function; Cardiac morphology; Mental health; Cardiovascular Magnetic Resonance; Neuroticism; Cardiovascular Remodelling,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead166/50880139/jead166.pdf; doi:https://doi.org/10.1093/ehjci/jead166; html:https://europepmc.org/articles/PMC10610755; pdf:https://europepmc.org/articles/PMC10610755?pdf=render
-34571200,https://doi.org/10.1016/j.jaip.2021.09.026,Atopic Eczema-Associated Fracture Risk and Oral Corticosteroids: A Population-Based Cohort Study.,"Matthewman J, Mansfield KE, Prieto-Alhambra D, Mulick AR, Smeeth L, Lowe KE, Silverwood RJ, Langan SM.",,The journal of allergy and clinical immunology. In practice,2022,2021-09-24,Y,Fracture; Atopic Eczema; Atopic Dermatitis; osteoporotic fracture; Oral Corticosteroids,,,"<h4>Background</h4>Evidence suggests adults with atopic eczema have increased fracture risk. However, it is unclear whether oral corticosteroids explain the association.<h4>Objective</h4>To assess to what extent oral corticosteroids mediate the relationship between atopic eczema and fractures.<h4>Methods</h4>We conducted a cohort study using English primary care (Clinical Practice Research Datalink) and hospital admissions (Hospital Episode Statistics) records (1998-2016) including adults (18 years old and older) with atopic eczema matched (age, sex, and general practice) with up to 5 adults without atopic eczema. We used Cox regression to estimate hazard ratios (HRs) for specific major osteoporotic fractures (hip, spine, pelvis, or wrist) and for any-site fracture comparing individuals with atopic eczema with those without, adjusting for 6 different definitions of time-updated oral corticosteroid use (ever any prescription, ever high-dose, and recent, cumulative, current, or peak dose).<h4>Results</h4>We identified 526,808 individuals with atopic eczema and 2,569,030 without. We saw evidence of an association between atopic eczema and major osteoporotic fractures (eg, spine HR 1.15, 99% CI 1.08-1.22; hip HR 1.11, 99% CI 1.08-1.15) that remained after additionally adjusting for oral corticosteroids (eg, cumulative corticosteroid dose: spine HR 1.09, 99% CI 1.03-1.16; hip HR 1.09, 99% CI 1.06-1.12). Fracture rates were higher in people with severe atopic eczema than in people without even after adjusting for oral corticosteroids (eg, spine HR [99% CI]: confounder-adjusted 2.31 [1.91-2.81]; additionally adjusted for cumulative dose 1.71 [1.40-2.09]).<h4>Conclusions</h4>Our findings suggest that little of the association between atopic eczema and major osteoporotic fractures is explained by oral corticosteroid use.",,pdf:http://www.jaci-inpractice.org/article/S2213219821010187/pdf; doi:https://doi.org/10.1016/j.jaip.2021.09.026; html:https://europepmc.org/articles/PMC7612204; pdf:https://europepmc.org/articles/PMC7612204?pdf=render
 37032516,https://doi.org/10.1111/aor.14537,Incidence and risk factors of late right heart failure in chronic mechanical circulatory support.,"Felix SEA, Numan L, Oerlemans MIF, Aarts E, Ramjankhan FZ, Gianoli M, Asselbergs FW, De Jonge N, Van Laake LW.",,Artificial organs,2023,2023-04-21,N,Risk factor; Mechanical Circulatory Support; Left Ventricular Assist Device; Late Right Heart Failure,,,"<h4>Background</h4>Late right heart failure (LRHF) is a common complication during long-term left ventricular assist device (LVAD) support. We aimed to identify risk factors for LRHF after LVAD implantation.<h4>Methods</h4>Patients undergoing primary LVAD implantation between 2006 and 2019 and surviving the perioperative period were included for this study (n = 261). Univariate Cox proportional hazards analysis was used to assess the association of clinical covariates and LRHF, stratified for device type. Variables with p < 0.10 entered the multivariable model. In a subset of patients with complete echocardiography or right catheterization data, this multivariable model was extended. Postoperative cardiopulmonary exercise test data were compared in patients with and without LRHF.<h4>Results</h4>Nineteen percentage of patients suffered from LRHF after a median of 12 months, of which 67% required hospitalization. A history of atrial fibrillation (AF) (HR: 2.06 [1.08-3.93], p = 0.029), a higher preoperative body mass index (BMI) (HR: 1.07 [1.01-1.13], p = 0.023), and intensive care unit (ICU) duration (HR: 1.03 [1.00-1.06], p = 0.025) were independent predictors of LHRF in the multivariable model. A significant relation between the severity of tricuspid regurgitation (TR) and LRHF (HR: 1.91 [1.13-3.21], p = 0.016) was found in patients with echocardiographic data. Patients with LRHF demonstrated a lower maximal workload and peak VO2 at 6 months postoperatively.<h4>Conclusion</h4>A history of AF, BMI, and longer ICU stay may help identify patients at high risk for LRHF. Severity of TR was significantly related to LRHF in a subset of patients.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aor.14537; doi:https://doi.org/10.1111/aor.14537
 33262239,https://doi.org/10.1128/msystems.00677-20,Investigating the Role of Diet and Exercise in Gut Microbe-Host Cometabolism. ,"Penney N, Barton W, Posma JM, Darzi A, Frost G, Cotter PD, Holmes E, Shanahan F, O'Sullivan O, Garcia-Perez I.",,mSystems,2020,2020-12-01,Y,,,,"We investigated the individual and combined effects of diet and physical exercise on metabolism and the gut microbiome to establish how these lifestyle factors influence host-microbiome cometabolism. Urinary and fecal samples were collected from athletes and less active controls. Individuals were further classified according to an objective dietary assessment score of adherence to healthy dietary habits according to WHO guidelines, calculated from their proton nuclear magnetic resonance (1H-NMR) urinary profiles. Subsequent models were generated comparing extremes of dietary habits, exercise, and the combined effect of both. Differences in metabolic phenotypes and gut microbiome profiles between the two groups were assessed. Each of the models pertaining to diet healthiness, physical exercise, or a combination of both displayed a metabolic and functional microbial signature, with a significant proportion of the metabolites identified as discriminating between the various pairwise comparisons resulting from gut microbe-host cometabolism. Microbial diversity was associated with a combination of high adherence to healthy dietary habits and exercise and was correlated with a distinct array of microbially derived metabolites, including markers of proteolytic activity. Improved control of dietary confounders, through the use of an objective dietary assessment score, has uncovered further insights into the complex, multifactorial relationship between diet, exercise, the gut microbiome, and metabolism. Furthermore, the observation of higher proteolytic activity associated with higher microbial diversity indicates that increased microbial diversity may confer deleterious as well as beneficial effects on the host.IMPORTANCE Improved control of dietary confounders, through the use of an objective dietary assessment score, has uncovered further insights into the complex, multifactorial relationship between diet, exercise, the gut microbiome, and metabolism. Each of the models pertaining to diet healthiness, physical exercise, or a combination of both, displayed a distinct metabolic and functional microbial signature. A significant proportion of the metabolites identified as discriminating between the various pairwise comparisons result from gut microbe-host cometabolism, and the identified interactions have expanded current knowledge in this area. Furthermore, although increased microbial diversity has previously been linked with health, our observation of higher microbial diversity being associated with increased proteolytic activity indicates that it may confer deleterious as well as beneficial effects on the host.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/85021/8/mSystems-2020-Penney-e00677-20.full.pdf; doi:https://doi.org/10.1128/mSystems.00677-20; html:https://europepmc.org/articles/PMC7716389; pdf:https://europepmc.org/articles/PMC7716389?pdf=render
-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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/ehjcimaging/article-pdf/23/11/1471/46583486/jeac101.pdf; doi:https://doi.org/10.1093/ehjci/jeac101; html:https://europepmc.org/articles/PMC9584621; pdf:https://europepmc.org/articles/PMC9584621?pdf=render
 31607513,https://doi.org/10.1016/j.cell.2019.08.051,"Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations.","Peterson RE, Kuchenbaecker K, Walters RK, Chen CY, Popejoy AB, Periyasamy S, Lam M, Iyegbe C, Strawbridge RJ, Brick L, Carey CE, Martin AR, Meyers JL, Su J, Chen J, Edwards AC, Kalungi A, Koen N, Majara L, Schwarz E, Smoller JW, Stahl EA, Sullivan PF, Vassos E, Mowry B, Prieto ML, Cuellar-Barboza A, Bigdeli TB, Edenberg HJ, Huang H, Duncan LE.",,Cell,2019,2019-10-10,N,Population genetics; Diversity; Psychiatry; complex disease; Gwas; Ancestry; Admixed Populations; Trans-ethnic; Trans-ancestry; Cross-ancestry,,,"Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.",,pdf:http://www.cell.com/article/S0092867419310025/pdf; doi:https://doi.org/10.1016/j.cell.2019.08.051; html:https://europepmc.org/articles/PMC6939869; pdf:https://europepmc.org/articles/PMC6939869?pdf=render; doi:https://doi.org/10.1016/j.cell.2019.08.051
+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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/ehjcimaging/article-pdf/23/11/1471/46583486/jeac101.pdf; doi:https://doi.org/10.1093/ehjci/jeac101; html:https://europepmc.org/articles/PMC9584621; pdf:https://europepmc.org/articles/PMC9584621?pdf=render
 34543272,https://doi.org/10.1371/journal.pcbi.1009324,Ten simple rules to make your computing more environmentally sustainable.,"Lannelongue L, Grealey J, Bateman A, Inouye M.",,PLoS computational biology,2021,2021-09-20,Y,,,,,,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009324&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009324; html:https://europepmc.org/articles/PMC8452068; pdf:https://europepmc.org/articles/PMC8452068?pdf=render
 35997594,https://doi.org/10.1099/mic.0.001223,Diagnostic MALDI-TOF MS can differentiate between high and low toxic <i>Staphylococcus aureus</i> 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,,,"<i>Staphylococcus aureus</i> 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.",,pdf:https://research-information.bris.ac.uk/ws/files/338315985/mic001223.pdf; doi:https://doi.org/10.1099/mic.0.001223; html:https://europepmc.org/articles/PMC10323763; pdf:https://europepmc.org/articles/PMC10323763?pdf=render
 37920183,https://doi.org/10.3389/fcvm.2023.1148931,Unraveling the relationships between alpha- and beta-adrenergic modulation and the risk of heart failure.,"Baudier C, Fougerousse F, Asselbergs FW, Guedj M, Komajda M, Kotecha D, Thomas Lumbers R, Schmidt AF, Tyl B.",,Frontiers in cardiovascular medicine,2023,2023-10-18,Y,"adrenergic receptors; Beta-blockers; Mendelian Randomization; Alpha-blockers; Target Validation, Drug",,,"<h4>Background</h4>The effects of α and ß adrenergic receptor modulation on the risk of developing heart failure (HF) remains uncertain due to a lack of randomized controlled trials. This study aimed to estimate the effects of α and ß adrenergic receptors modulation on the risk of HF and to provide proof of principle for genetic target validation studies in HF.<h4>Methods</h4>Genetic variants within the cis regions encoding the adrenergic receptors α1A, α2B, ß1, and ß2 associated with blood pressure in a 757,601-participant genome-wide association study (GWAS) were selected as instruments to perform a drug target Mendelian randomization study. Effects of these variants on HF risk were derived from the HERMES GWAS (542,362 controls; 40,805 HF cases).<h4>Results</h4>Lower α1A or ß1 activity was associated with reduced HF risk: odds ratio (OR) 0.83 (95% CI 0.74-0.93, <i>P</i> = 0.001) and 0.95 (95% CI 0.93-0.97, <i>P</i> = 8 × 10<sup>-6</sup>). Conversely, lower α2B activity was associated with increased HF risk: OR 1.09 (95% CI 1.05-1.12, <i>P</i> = 3 × 10<sup>-7</sup>). No evidence of an effect of lower ß2 activity on HF risk was found: OR 0.99 (95% CI 0.92-1.07, <i>P</i> = 0.95). Complementary analyses showed that these effects were consistent with those on left ventricular dimensions and acted independently of any potential effect on coronary artery disease.<h4>Conclusions</h4>This study provides genetic evidence that α1A or ß1 receptor inhibition will likely decrease HF risk, while lower α2B activity may increase this risk. Genetic variant analysis can assist with drug development for HF prevention.",,doi:https://doi.org/10.3389/fcvm.2023.1148931; html:https://europepmc.org/articles/PMC10619754; pdf:https://europepmc.org/articles/PMC10619754?pdf=render
@@ -859,8 +859,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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.",,
 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.",,pdf:https://discovery.ucl.ac.uk/10138810/1/ForUCLDiscovery.pdf; doi:https://doi.org/10.1101/cshperspect.a039230
 35322592,https://doi.org/10.1002/ehf2.13910,Cardiovascular outcomes associated with treatment of type 2 diabetes in patients with ischaemic heart failure.,"Godec TR, Bromage DI, Pujades-Rodriguez M, Cannatà A, Gonzalez-Izquierdo A, Denaxas S, Hemingway H, Shah AM, Yellon DM, McDonagh TA.",,ESC heart failure,2022,2022-03-23,Y,Type 2 diabetes; Metformin; Heart Failure; Outcomes; Ischaemic Cardiomyopathy; Antidiabetic Agents,,,"<h4>Aim</h4>The optimal strategy for diabetes control in patients with heart failure (HF) following myocardial infarction (MI) remains unknown. Metformin, a guideline-recommended therapy for patients with chronic HF and type 2 diabetes mellitus (T2DM), is associated with reduced mortality and HF hospitalizations. However, worse outcomes have been reported when used at the time of MI. We compared outcomes of patients with T2DM and HF of ischaemic aetiology according to antidiabetic treatment.<h4>Methods and results</h4>This study used linked data from primary care, hospital admissions, and death registries for 4.7 million inhabitants in England, as part of the CALIBER resource. The primary endpoint was a composite of cardiovascular mortality and HF hospitalization. The secondary endpoints were the individual components of the primary endpoint and all-cause mortality. To evaluate the effect of temporal changes in diabetes treatment, antidiabetic medication was included as time-dependent covariates in survival analyses. The study included 1172 patients with T2DM and prior MI and incident HF between 3 January 1998 and 26 February 2010. Five hundred and ninety-six patients had the primary outcome over median follow-up of 2.53 (IQR: 0.98-4.92) years. Adjusted analyses showed a reduced hazard of the composite endpoint for exposure to all antidiabetic medication with hazard ratios (HRs) of 0.50 [95% confidence interval (CI): 0.42-0.59], 0.66 (95% CI: 0.55-0.80), and 0.53 (95% CI: 0.43-0.65), respectively. A similar effect was seen for all-cause mortality [HRs of 0.43 (95% CI: 0.35-0.52), 0.57 (95% CI: 0.46-0.70), and 0.34 (95% CI: 0.27-0.43), respectively].<h4>Conclusions</h4>When considering changes in antidiabetic treatment over time, all drug classes were associated with reduced risk of cardiovascular mortality and HF hospitalization.",,pdf:https://kclpure.kcl.ac.uk/ws/files/173598342/ESC_Heart_Failure_2022_Godec_Cardiovascular_outcomes_associated_with_treatment_of_type_2_diabetes_in_patients_with.pdf; doi:https://doi.org/10.1002/ehf2.13910; html:https://europepmc.org/articles/PMC9065866; pdf:https://europepmc.org/articles/PMC9065866?pdf=render
-37703231,https://doi.org/10.1371/journal.pdig.0000334,A population-based study exploring phenotypic clusters and clinical outcomes in stroke using unsupervised machine learning approach.,"Akyea RK, Ntaios G, Kontopantelis E, Georgiopoulos G, Soria D, Asselbergs FW, Kai J, Weng SF, Qureshi N.",,PLOS digital health,2023,2023-09-13,Y,,,,"Individuals developing stroke have varying clinical characteristics, demographic, and biochemical profiles. This heterogeneity in phenotypic characteristics can impact on cardiovascular disease (CVD) morbidity and mortality outcomes. This study uses a novel clustering approach to stratify individuals with incident stroke into phenotypic clusters and evaluates the differential burden of recurrent stroke and other cardiovascular outcomes. We used linked clinical data from primary care, hospitalisations, and death records in the UK. A data-driven clustering analysis (kamila algorithm) was used in 48,114 patients aged ≥ 18 years with incident stroke, from 1-Jan-1998 to 31-Dec-2017 and no prior history of serious vascular events. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for subsequent adverse outcomes, for each of the generated clusters. Adverse outcomes included coronary heart disease (CHD), recurrent stroke, peripheral vascular disease (PVD), heart failure, CVD-related and all-cause mortality. Four distinct phenotypes with varying underlying clinical characteristics were identified in patients with incident stroke. Compared with cluster 1 (n = 5,201, 10.8%), the risk of composite recurrent stroke and CVD-related mortality was higher in the other 3 clusters (cluster 2 [n = 18,655, 38.8%]: hazard ratio [HR], 1.07; 95% CI, 1.02-1.12; cluster 3 [n = 10,244, 21.3%]: HR, 1.20; 95% CI, 1.14-1.26; and cluster 4 [n = 14,014, 29.1%]: HR, 1.44; 95% CI: 1.37-1.50). Similar trends in risk were observed for composite recurrent stroke and all-cause mortality outcome, and subsequent recurrent stroke outcome. However, results were not consistent for subsequent risk in CHD, PVD, heart failure, CVD-related mortality, and all-cause mortality. In this proof of principle study, we demonstrated how a heterogenous population of patients with incident stroke can be stratified into four relatively homogenous phenotypes with differential risk of recurrent and major cardiovascular outcomes. This offers an opportunity to revisit the stratification of care for patients with incident stroke to improve patient outcomes.",,doi:https://doi.org/10.1371/journal.pdig.0000334; html:https://europepmc.org/articles/PMC10499205; pdf:https://europepmc.org/articles/PMC10499205?pdf=render
 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.",,pdf:https://www.science.org/doi/pdf/10.1126/scitranslmed.abq4810?download=true; doi:https://doi.org/10.1126/scitranslmed.abq4810
+37703231,https://doi.org/10.1371/journal.pdig.0000334,A population-based study exploring phenotypic clusters and clinical outcomes in stroke using unsupervised machine learning approach.,"Akyea RK, Ntaios G, Kontopantelis E, Georgiopoulos G, Soria D, Asselbergs FW, Kai J, Weng SF, Qureshi N.",,PLOS digital health,2023,2023-09-13,Y,,,,"Individuals developing stroke have varying clinical characteristics, demographic, and biochemical profiles. This heterogeneity in phenotypic characteristics can impact on cardiovascular disease (CVD) morbidity and mortality outcomes. This study uses a novel clustering approach to stratify individuals with incident stroke into phenotypic clusters and evaluates the differential burden of recurrent stroke and other cardiovascular outcomes. We used linked clinical data from primary care, hospitalisations, and death records in the UK. A data-driven clustering analysis (kamila algorithm) was used in 48,114 patients aged ≥ 18 years with incident stroke, from 1-Jan-1998 to 31-Dec-2017 and no prior history of serious vascular events. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for subsequent adverse outcomes, for each of the generated clusters. Adverse outcomes included coronary heart disease (CHD), recurrent stroke, peripheral vascular disease (PVD), heart failure, CVD-related and all-cause mortality. Four distinct phenotypes with varying underlying clinical characteristics were identified in patients with incident stroke. Compared with cluster 1 (n = 5,201, 10.8%), the risk of composite recurrent stroke and CVD-related mortality was higher in the other 3 clusters (cluster 2 [n = 18,655, 38.8%]: hazard ratio [HR], 1.07; 95% CI, 1.02-1.12; cluster 3 [n = 10,244, 21.3%]: HR, 1.20; 95% CI, 1.14-1.26; and cluster 4 [n = 14,014, 29.1%]: HR, 1.44; 95% CI: 1.37-1.50). Similar trends in risk were observed for composite recurrent stroke and all-cause mortality outcome, and subsequent recurrent stroke outcome. However, results were not consistent for subsequent risk in CHD, PVD, heart failure, CVD-related mortality, and all-cause mortality. In this proof of principle study, we demonstrated how a heterogenous population of patients with incident stroke can be stratified into four relatively homogenous phenotypes with differential risk of recurrent and major cardiovascular outcomes. This offers an opportunity to revisit the stratification of care for patients with incident stroke to improve patient outcomes.",,doi:https://doi.org/10.1371/journal.pdig.0000334; html:https://europepmc.org/articles/PMC10499205; pdf:https://europepmc.org/articles/PMC10499205?pdf=render
 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.",,pdf:https://www.nature.com/articles/s41598-023-30369-6.pdf; doi:https://doi.org/10.1038/s41598-023-30369-6; html:https://europepmc.org/articles/PMC9981672; pdf:https://europepmc.org/articles/PMC9981672?pdf=render
 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.",,pdf:https://jamanetwork.com/journals/jamadermatology/articlepdf/2778389/jamadermatology_schmidt_2021_oi_210002_1623774349.64965.pdf; doi:https://doi.org/10.1001/jamadermatol.2021.0009; html:https://europepmc.org/articles/PMC8047754
 35667411,https://doi.org/10.1016/j.jamda.2022.05.003,Stroke in Older Adults Living in Care Homes: Results From a National Data Linkage Study in Wales.,"Harrison SL, Lip GYH, Akbari A, Torabi F, Ritchie LA, Akpan A, Halcox J, Rodgers S, Hollinghurst J, Harris D, Lane DA.",,Journal of the American Medical Directors Association,2022,2022-06-03,N,Anticoagulants; Cerebrovascular disease; Nursing Homes; Antiplatelets,,,"<h4>Objectives</h4>To determine the proportion of older people moving to care homes with a recent stroke, incidence of stroke after moving to a care home, mortality following stroke, and secondary stroke prevention management in older care home residents.<h4>Design</h4>Retrospective cohort study using population-scale individual-level linked data sources between 2003 and 2018 in the Secure Anonymized Information Linkage (SAIL) Databank.<h4>Setting and participants</h4>People aged ≥65 years residing in long-term care homes in Wales.<h4>Methods</h4>Competing risk models and logistic regression models were used to examine the association between prior stroke, incident stroke, and mortality following stroke.<h4>Results</h4>Of 86,602 individuals, 7.0% (n = 6055) experienced a stroke in the 12 months prior to care home entry. The incidence of stroke within 12 months after entry to a care home was 26.2 per 1000 person-years [95% confidence interval (CI) 25.0, 27.5]. Previous stroke was associated with higher risk of incident stroke after moving to a care home (subdistribution hazard ratio 1.83, 95% CI 1.57, 2.13) and 30-day mortality following stroke (odds ratio 2.18, 95% CI 1.59, 2.98). Severe frailty was not significantly associated with risk of stroke or 30-day mortality following stroke. Secondary stroke prevention included statins (51.0%), antiplatelets (61.2%), anticoagulants (52.4% of those with atrial fibrillation), and antihypertensives (92.1% of those with hypertension).<h4>Conclusions and implications</h4>At the time of care home entry, individuals with history of stroke in the previous 12 months are at a higher risk of incident stroke and mortality following an incident stroke. These individuals are frequently not prescribed medications for secondary stroke prevention. Further evidence is needed to determine the optimal care pathways for older people living in long-term care homes with history of stroke.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa60151/Download/60151__25104__e0e71818d5bd49acba048a3d98682425.pdf; doi:https://doi.org/10.1016/j.jamda.2022.05.003
@@ -868,26 +868,26 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 34969173,https://doi.org/10.1002/ejhf.2417,"A population-based study of 92 clinically recognized risk factors for heart failure: co-occurrence, prognosis and preventive potential.","Banerjee A, Pasea L, Chung SC, Direk K, Asselbergs FW, Grobbee DE, Kotecha D, Anker SD, Dyszynski T, Tyl B, Denaxas S, Lumbers RT, Hemingway H.",,European journal of heart failure,2022,2022-01-26,Y,Risk factor; epidemiology; Heart Failure; Primary Prevention,,,"<h4>Aims</h4>Primary prevention strategies for heart failure (HF) have had limited success, possibly due to a wide range of underlying risk factors (RFs). Systematic evaluations of the prognostic burden and preventive potential across this wide range of risk factors are lacking. We aimed at estimating evidence, prevalence and co-occurrence for primary prevention and impact on prognosis of RFs for incident HF.<h4>Methods and results</h4>We systematically reviewed trials and observational evidence of primary HF prevention across 92 putative aetiologic RFs for HF identified from US and European clinical practice guidelines. We identified 170 885 individuals aged ≥30 years with incident HF from 1997 to 2017, using linked primary and secondary care UK electronic health records (EHR) and rule-based phenotypes (ICD-10, Read Version 2, OPCS-4 procedure and medication codes) for each of 92 RFs. Only 10/92 factors had high quality observational evidence for association with incident HF; 7 had effective randomized controlled trial (RCT)-based interventions for HF prevention (RCT-HF), and 6 for cardiovascular disease prevention, but not HF (RCT-CVD), and the remainder had no RCT-based preventive interventions (RCT-0). We were able to map 91/92 risk factors to EHR using 5961 terms, and 88/91 factors were represented by at least one patient. In the 5 years prior to HF diagnosis, 44.3% had ≥4 RFs. By RCT evidence, the most common RCT-HF RFs were hypertension (48.5%), stable angina (34.9%), unstable angina (16.8%), myocardial infarction (15.8%), and diabetes (15.1%); RCT-CVD RFs were smoking (46.4%) and obesity (29.9%); and RCT-0 RFs were atrial arrhythmias (17.2%), cancer (16.5%), heavy alcohol intake (14.9%). Mortality at 1 year varied across all 91 factors (lowest: pregnancy-related hormonal disorder 4.2%; highest: phaeochromocytoma 73.7%). Among new HF cases, 28.5% had no RCT-HF RFs and 38.6% had no RCT-CVD RFs. 15.6% had either no RF or only RCT-0 RFs.<h4>Conclusion</h4>One in six individuals with HF have no recorded RFs or RFs without trials. We provide a systematic map of primary preventive opportunities across a wide range of RFs for HF, demonstrating a high burden of co-occurrence and the need for trials tackling multiple RFs.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.2417; doi:https://doi.org/10.1002/ejhf.2417; html:https://europepmc.org/articles/PMC9305958; pdf:https://europepmc.org/articles/PMC9305958?pdf=render
 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,,,"<b>Background</b>: 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. <b>Methods: </b>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. <b>Results:</b> Three key themes were identified from our Phase 1 findings: ' <i>Understanding and experiences of the potential benefits of sharing qualitative data from trials', 'Concerns about qualitative data sharing'</i>, and ' <i>Future guidance and funding</i>'. 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. <b>Conclusions:</b> 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
 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,,,"<h4>Objective</h4>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.<h4>Design</h4>Retrospective, descriptive cohort study, approved by NHS England.<h4>Setting</h4>Routine clinical data from 23.4 million people linked to data on covid-19 infection and treatment, within the OpenSAFELY-TPP database.<h4>Participants</h4>Outpatients with covid-19 at high risk of severe outcomes.<h4>Interventions</h4>Nirmatrelvir/ritonavir (paxlovid), sotrovimab, molnupiravir, casirivimab/imdevimab, or remdesivir, used in the community by covid-19 medicine delivery units.<h4>Results</h4>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%).<h4>Conclusions</h4>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.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000276.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000276; html:https://europepmc.org/articles/PMC9951378; pdf:https://europepmc.org/articles/PMC9951378?pdf=render
-36276403,https://doi.org/10.3389/fpubh.2022.875198,The mental health experiences of ethnic minorities in the UK during the Coronavirus pandemic: A qualitative exploration.,"Van Bortel T, Lombardo C, Guo L, Solomon S, Martin S, Hughes K, Weeks L, Crepaz-Keay D, McDaid S, Chantler O, Thorpe L, Morton A, Davidson G, John A, Kousoulis AA.",,Frontiers in public health,2022,2022-10-06,Y,Mental health; United Kingdom; Inequalities; Ethnic Minorities; Covid-19; Coronavirus Pandemic; Bame Ethnicity,,,"<h4>Background</h4>Worldwide, the Coronavirus pandemic has had a major impact on people's health, lives, and livelihoods. However, this impact has not been felt equally across various population groups. People from ethnic minority backgrounds in the UK have been more adversely affected by the pandemic, especially in terms of their physical health. Their mental health, on the other hand, has received less attention. This study aimed to explore the mental health experiences of UK adults from ethnic minorities during the Coronavirus pandemic. This work forms part of our wider long-term UK population study ""Mental Health in the Pandemic.""<h4>Methods</h4>We conducted an exploratory qualitative study with people from ethnic minority communities across the UK. A series of in-depth interviews were conducted with 15 women, 14 men and 1 non-binary person from ethnic minority backgrounds, aged between 18 and 65 years old (mean age = 40). We utilized purposefully selected maximum variation sampling in order to capture as wide a variety of views, perceptions and experiences as possible. Inclusion criteria: adults (18+) from ethnic minorities across the UK; able to provide full consent to participate; able to participate in a video- or phone-call interview. All interviews took place <i>via</i> MS Teams or Zoom. The gathered data were transcribed verbatim and underwent thematic analysis following Braun and Clarke carried out using NVivo 12 software.<h4>Results</h4>The qualitative data analysis yielded seven overarching themes: (1) pandemic-specific mental health and wellbeing experiences; (2) issues relating to the media; (3) coping mechanisms; (4) worries around and attitudes toward vaccination; (5) suggestions for support in moving forward; (6) best and worst experiences during pandemic and lockdowns; (7) biggest areas of change in personal life. Generally, participants' mental health experiences varied with some not being affected by the pandemic in a way related to their ethnicity, some sharing positive experiences and coping strategies (exercising more, spending more time with family, community cohesion), and some expressing negative experiences (eating or drinking more, feeling more isolated, or even racism and abuse, especially toward Asian communities). Concerns were raised around trust issues in relation to the media, the inadequate representation of ethnic minorities, and the spread of fake news especially on social media. Attitudes toward vaccinations varied too, with some people more willing to have the vaccine than others.<h4>Conclusion</h4>This study's findings highlight the diversity in the pandemic mental health experiences of ethnic minorities in the UK and has implications for policy, practice and further research. To enable moving forward beyond the pandemic, our study surfaced the need for culturally appropriate mental health support, financial support (as a key mental health determinant), accurate media representation, and clear communication messaging from the Governments of the UK.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.875198/pdf; doi:https://doi.org/10.3389/fpubh.2022.875198; html:https://europepmc.org/articles/PMC9582845; pdf:https://europepmc.org/articles/PMC9582845?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'.",,pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rstb.2018.0276; doi:https://doi.org/10.1098/rstb.2018.0276; html:https://europepmc.org/articles/PMC6558557; pdf:https://europepmc.org/articles/PMC6558557?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,,"<h4>Objectives</h4>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.<h4>Design</h4>Nationwide linked electronic cohort and nested case-control study.<h4>Setting</h4>Routinely collected data from primary care and hospital admissions in Wales, UK.<h4>Participants</h4>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.<h4>Main outcome measures</h4>Combined prevalence of JHS and EDS in Wales. Additional diagnosis and prescription data in those diagnosed with EDS or JHS compared with matched controls.<h4>Results</h4>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.<h4>Conclusions</h4>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.",pdf:https://bmjopen.bmj.com/content/bmjopen/9/11/e031365.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-031365; html:https://europepmc.org/articles/PMC6858200; pdf:https://europepmc.org/articles/PMC6858200?pdf=render
+36276403,https://doi.org/10.3389/fpubh.2022.875198,The mental health experiences of ethnic minorities in the UK during the Coronavirus pandemic: A qualitative exploration.,"Van Bortel T, Lombardo C, Guo L, Solomon S, Martin S, Hughes K, Weeks L, Crepaz-Keay D, McDaid S, Chantler O, Thorpe L, Morton A, Davidson G, John A, Kousoulis AA.",,Frontiers in public health,2022,2022-10-06,Y,Mental health; United Kingdom; Inequalities; Ethnic Minorities; Covid-19; Coronavirus Pandemic; Bame Ethnicity,,,"<h4>Background</h4>Worldwide, the Coronavirus pandemic has had a major impact on people's health, lives, and livelihoods. However, this impact has not been felt equally across various population groups. People from ethnic minority backgrounds in the UK have been more adversely affected by the pandemic, especially in terms of their physical health. Their mental health, on the other hand, has received less attention. This study aimed to explore the mental health experiences of UK adults from ethnic minorities during the Coronavirus pandemic. This work forms part of our wider long-term UK population study ""Mental Health in the Pandemic.""<h4>Methods</h4>We conducted an exploratory qualitative study with people from ethnic minority communities across the UK. A series of in-depth interviews were conducted with 15 women, 14 men and 1 non-binary person from ethnic minority backgrounds, aged between 18 and 65 years old (mean age = 40). We utilized purposefully selected maximum variation sampling in order to capture as wide a variety of views, perceptions and experiences as possible. Inclusion criteria: adults (18+) from ethnic minorities across the UK; able to provide full consent to participate; able to participate in a video- or phone-call interview. All interviews took place <i>via</i> MS Teams or Zoom. The gathered data were transcribed verbatim and underwent thematic analysis following Braun and Clarke carried out using NVivo 12 software.<h4>Results</h4>The qualitative data analysis yielded seven overarching themes: (1) pandemic-specific mental health and wellbeing experiences; (2) issues relating to the media; (3) coping mechanisms; (4) worries around and attitudes toward vaccination; (5) suggestions for support in moving forward; (6) best and worst experiences during pandemic and lockdowns; (7) biggest areas of change in personal life. Generally, participants' mental health experiences varied with some not being affected by the pandemic in a way related to their ethnicity, some sharing positive experiences and coping strategies (exercising more, spending more time with family, community cohesion), and some expressing negative experiences (eating or drinking more, feeling more isolated, or even racism and abuse, especially toward Asian communities). Concerns were raised around trust issues in relation to the media, the inadequate representation of ethnic minorities, and the spread of fake news especially on social media. Attitudes toward vaccinations varied too, with some people more willing to have the vaccine than others.<h4>Conclusion</h4>This study's findings highlight the diversity in the pandemic mental health experiences of ethnic minorities in the UK and has implications for policy, practice and further research. To enable moving forward beyond the pandemic, our study surfaced the need for culturally appropriate mental health support, financial support (as a key mental health determinant), accurate media representation, and clear communication messaging from the Governments of the UK.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.875198/pdf; doi:https://doi.org/10.3389/fpubh.2022.875198; html:https://europepmc.org/articles/PMC9582845; pdf:https://europepmc.org/articles/PMC9582845?pdf=render
 37740900,https://doi.org/10.1093/ageing/afad176,Interventions for reducing anticholinergic medication burden in older adults-a systematic review and meta-analysis.,"Braithwaite E, Todd OM, Atkin A, Hulatt R, Tadrous R, Alldred DP, Pirmohamed M, Walker L, Lawton R, Clegg A.",,Age and ageing,2023,2023-09-01,Y,Cognition; Meta-analysis; Systematic review; Falls; Older People; Older Adult; Anticholinergic Medication,,,"<h4>Introduction</h4>Anticholinergic medications block the neurotransmitter acetylcholine in the brain and peripheral nervous system. Many medications have anticholinergic properties, and the cumulative effect of these medications is termed anticholinergic burden. Increased anticholinergic burden can have short-term side effects such as dry mouth, blurred vision and urinary retention as well as long-term effects including dementia, worsening physical function and falls.<h4>Methods</h4>We carried out a systematic review (SR) with meta-analysis (MA) looking at randomised controlled trials addressing interventions to reduce anticholinergic burden in older adults.<h4>Results</h4>We identified seven papers suitable for inclusion in our SR and MA. Interventions included multi-disciplinary involvement in medication reviews and deprescribing of AC medications. Pooled data revealed no significant difference in outcomes between control and intervention group for falls (OR = 0.76, 95% CI: 0.52-1.11, n = 647), cognition (mean difference = 1.54, 95% CI: -0.04 to 3.13, n = 405), anticholinergic burden (mean difference = 0.04, 95% CI: -0.11 to 0.18, n = 710) or quality of life (mean difference = 0.04, 95% CI: -0.04 to 0.12, n = 461).<h4>Discussion</h4>Overall, there was no significant difference with interventions to reduce anticholinergic burden. As we did not see a significant change in anticholinergic burden scores following interventions, it is likely other outcomes would not change. Short follow-up time and lack of training and support surrounding successful deprescribing may have contributed.",,pdf:https://academic.oup.com/ageing/article-pdf/52/9/afad176/51729004/afad176.pdf; doi:https://doi.org/10.1093/ageing/afad176; html:https://europepmc.org/articles/PMC10517713; pdf:https://europepmc.org/articles/PMC10517713?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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:http://www.jacionline.org/article/S0091674920317127/pdf; 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
 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,,,"<h4>Objectives</h4>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.<h4>Study design</h4>The study design of this study is a retrospective cohort study and causal inference methods.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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; 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
 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,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5627; doi:https://doi.org/10.1002/gps.5627; html:https://europepmc.org/articles/PMC9292841; pdf:https://europepmc.org/articles/PMC9292841?pdf=render
 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.",,pdf:https://academic.oup.com/ageing/article-pdf/51/1/afab201/42083711/afab201.pdf; doi:https://doi.org/10.1093/ageing/afab201; html:https://europepmc.org/articles/PMC8753038; pdf:https://europepmc.org/articles/PMC8753038?pdf=render
 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,,,,"<h4>Objectives</h4>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.<h4>Design</h4>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).<h4>Setting</h4>Clinical academics in primary and secondary care in England.<h4>Participants</h4>Equivalent of 3200 full-time clinical academics in England.<h4>Interventions</h4>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.<h4>Main outcome measures</h4>Number of full-time clinical academics available to conduct clinical research during the pandemic in England.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0237298&type=printable; doi:https://doi.org/10.1371/journal.pone.0237298; html:https://europepmc.org/articles/PMC7425844; pdf:https://europepmc.org/articles/PMC7425844?pdf=render
-36719715,https://doi.org/10.2196/41248,Patterns in the Use of Heart Failure Telemonitoring: Post Hoc Analysis of the e-Vita Heart Failure Trial.,"Brons M, Ten Klooster I, van Gemert-Pijnen L, Jaarsma T, Asselbergs FW, Oerlemans MIFJ, Koudstaal S, Rutten FH.",,JMIR cardio,2023,2023-01-31,Y,Adherence; Heart Failure; Patient Monitoring; Remote Monitoring; Telemonitoring; Ehealth; Electronic Personal Health Record,,,"<h4>Background</h4>Research on the use of home telemonitoring data and adherence to it can provide new insights into telemonitoring for the daily management of patients with heart failure (HF).<h4>Objective</h4>We described the use of a telemonitoring platform-including remote patient monitoring of blood pressure, pulse, and weight-and the use of the electronic personal health record. Patient characteristics were assessed in both adherent and nonadherent patients to weight transmissions.<h4>Methods</h4>We used the data of the e-Vita HF study, a 3-arm parallel randomized trial performed in stable patients with HF managed in outpatient clinics in the Netherlands. In this study, data were analyzed from the participants in the intervention arm (ie, e-Vita HF platform). Adherence to weight transmissions was defined as transmitting weight ≥3 times per week for at least 42 weeks during a year.<h4>Results</h4>Data from 150 patients (mean age 67, SD 11 years; n=37, 25% female; n=123, 82% self-assessed New York Heart Association class I-II) were analyzed. One-year adherence to weight transmissions was 74% (n=111). Patients adherent to weight transmissions were less often hospitalized for HF in the 6 months before enrollment in the study compared to those who were nonadherent (n=9, 8% vs n=9, 23%; P=.02). The percentage of patients visiting the personal health record dropped steadily over time (n=140, 93% vs n=59, 39% at one year). With univariable analyses, there was no significant correlation between patient characteristics and adherence to weight transmissions.<h4>Conclusions</h4>Adherence to remote patient monitoring was high among stable patients with HF and best for weighing; however, adherence decreased over time. Clinical and demographic variables seem not related to adherence to transmitting weight.<h4>Trial registration</h4>ClinicalTrials.gov NCT01755988; https://clinicaltrials.gov/ct2/show/NCT01755988.",,pdf:https://cardio.jmir.org/2023/1/e41248/PDF; doi:https://doi.org/10.2196/41248; html:https://europepmc.org/articles/PMC9929726; pdf:https://europepmc.org/articles/PMC9929726?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.",,pdf:https://adc.bmj.com/content/archdischild/105/4/347.full.pdf; doi:https://doi.org/10.1136/archdischild-2019-317248; html:https://europepmc.org/articles/PMC7146921; pdf:https://europepmc.org/articles/PMC7146921?pdf=render
+36719715,https://doi.org/10.2196/41248,Patterns in the Use of Heart Failure Telemonitoring: Post Hoc Analysis of the e-Vita Heart Failure Trial.,"Brons M, Ten Klooster I, van Gemert-Pijnen L, Jaarsma T, Asselbergs FW, Oerlemans MIFJ, Koudstaal S, Rutten FH.",,JMIR cardio,2023,2023-01-31,Y,Adherence; Heart Failure; Patient Monitoring; Remote Monitoring; Telemonitoring; Ehealth; Electronic Personal Health Record,,,"<h4>Background</h4>Research on the use of home telemonitoring data and adherence to it can provide new insights into telemonitoring for the daily management of patients with heart failure (HF).<h4>Objective</h4>We described the use of a telemonitoring platform-including remote patient monitoring of blood pressure, pulse, and weight-and the use of the electronic personal health record. Patient characteristics were assessed in both adherent and nonadherent patients to weight transmissions.<h4>Methods</h4>We used the data of the e-Vita HF study, a 3-arm parallel randomized trial performed in stable patients with HF managed in outpatient clinics in the Netherlands. In this study, data were analyzed from the participants in the intervention arm (ie, e-Vita HF platform). Adherence to weight transmissions was defined as transmitting weight ≥3 times per week for at least 42 weeks during a year.<h4>Results</h4>Data from 150 patients (mean age 67, SD 11 years; n=37, 25% female; n=123, 82% self-assessed New York Heart Association class I-II) were analyzed. One-year adherence to weight transmissions was 74% (n=111). Patients adherent to weight transmissions were less often hospitalized for HF in the 6 months before enrollment in the study compared to those who were nonadherent (n=9, 8% vs n=9, 23%; P=.02). The percentage of patients visiting the personal health record dropped steadily over time (n=140, 93% vs n=59, 39% at one year). With univariable analyses, there was no significant correlation between patient characteristics and adherence to weight transmissions.<h4>Conclusions</h4>Adherence to remote patient monitoring was high among stable patients with HF and best for weighing; however, adherence decreased over time. Clinical and demographic variables seem not related to adherence to transmitting weight.<h4>Trial registration</h4>ClinicalTrials.gov NCT01755988; https://clinicaltrials.gov/ct2/show/NCT01755988.",,pdf:https://cardio.jmir.org/2023/1/e41248/PDF; doi:https://doi.org/10.2196/41248; html:https://europepmc.org/articles/PMC9929726; pdf:https://europepmc.org/articles/PMC9929726?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,,,,"<h4>Background</h4>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?<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://openres.ersjournals.com/content/erjor/early/2023/02/16/23120541.00591-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00591-2022; html:https://europepmc.org/articles/PMC10152257; pdf:https://europepmc.org/articles/PMC10152257?pdf=render
 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.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-022-00934-w.pdf; doi:https://doi.org/10.1007/s10654-022-00934-w; html:https://europepmc.org/articles/PMC9792414; pdf:https://europepmc.org/articles/PMC9792414?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
 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,,,"<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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
-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,,,"<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07944-8.pdf; doi:https://doi.org/10.1007/s00520-023-07944-8; html:https://europepmc.org/articles/PMC10444652; pdf:https://europepmc.org/articles/PMC10444652?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
 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.",,pdf:https://asa.scitation.org/doi/pdf/10.1121/1.5100272; 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
+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,,,"<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07944-8.pdf; doi:https://doi.org/10.1007/s00520-023-07944-8; html:https://europepmc.org/articles/PMC10444652; pdf:https://europepmc.org/articles/PMC10444652?pdf=render
 32864476,https://doi.org/10.23889/ijpds.v5i1.1157,"Prevalence of Down's Syndrome in England, 1998-2013: Comparison of linked surveillance data and electronic health records.","Doidge JC, Morris JK, Harron KL, Stevens S, Gilbert R.",,International journal of population data science,2020,2020-01-01,Y,Prevalence; Data Linkage; Disease Surveillance; Down’s Syndrome; Electronic Health Records; Linkage Error,,,"<h4>Introduction</h4>Disease registers and electronic health records are valuable resources for disease surveillance and research but can be limited by variation in data quality over time. Quality may be limited in terms of the accuracy of clinical information, of the internal linkage that supports person-based analysis of most administrative datasets, or by errors in linkage between multiple datasets.<h4>Objectives</h4>By linking the National Down Syndrome Cytogenetic Register (NDSCR) to Hospital Episode Statistics for England (HES), we aimed to assess the quality of each and establish a consistent approach for analysis of trends in prevalence of Down's syndrome among live births in England.<h4>Methods</h4>Probabilistic record linkage of NDSCR to HES for the period 1998-2013 was supported by linkage of babies to mothers within HES. Comparison of prevalence estimates in England were made using NDSCR only, HES data only, and linked data. Capture-recapture analysis and quantitative bias analysis were used to account for potential errors, including false positive diagnostic codes, unrecorded diagnoses, and linkage error.<h4>Results</h4>Analyses of single-source data indicated increasing live birth prevalence of Down's Syndrome, particularly in the analysis of HES. Linked data indicated a contrastingly stable prevalence of 12.3 (plausible range: 11.6-12.7) cases per 10 000 live births.<h4>Conclusion</h4>Case ascertainment in NDSCR improved slightly over time, creating a picture of slowly increasing prevalence. The emerging epidemic suggested by HES primarily reflects improving linkage within HES (assignment of unique patient identifiers to hospital episodes). Administrative data are valuable but trends should be interpreted with caution, and with assessment of data quality over time. Data linkage with quantitative bias analysis can provide more robust estimation and, in this case, stronger evidence that prevalence is not increasing. Routine linkage of administrative and register data can enhance the value of each.",,pdf:https://ijpds.org/article/download/1157/2531; doi:https://doi.org/10.23889/ijpds.v5i1.1157; html:https://europepmc.org/articles/PMC7115985; pdf:https://europepmc.org/articles/PMC7115985?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>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·<b>54, 0</b>·<b>95</b>-<b>2</b>·<b>49</b>).<h4>Interpretation</h4>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.<h4>Funding</h4>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.",,pdf:http://www.thelancet.com/article/S2665991322000984/pdf; 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
 31628383,https://doi.org/10.1038/s41598-019-51562-6,Whole genome sequencing of drug resistant Mycobacterium tuberculosis isolates from a high burden tuberculosis region of North West Pakistan.,"Jabbar A, Phelan JE, de Sessions PF, Khan TA, Rahman H, Khan SN, Cantillon DM, Wildner LM, Ali S, Campino S, Waddell SJ, Clark TG.",,Scientific reports,2019,2019-10-18,Y,,,,"Tuberculosis (TB), caused by Mycobacterium tuberculosis bacteria, is a leading infectious cause of mortality worldwide, including in Pakistan. Drug resistant M. tuberculosis is an emerging threat for TB control, making it important to detect the underlying genetic mutations, and thereby inform treatment decision making and prevent transmission. Whole genome sequencing has emerged as the new diagnostic to reliably predict drug resistance within a clinically relevant time frame, and its deployment will have the greatest impact on TB control in highly endemic regions. To evaluate the mutations leading to drug resistance and to assess for evidence of the transmission of resistant strains, 81 M. tuberculosis samples from Khyber Pakhtunkhwa province (North West Pakistan) were subjected to whole genome sequencing and standard drug susceptibility testing for eleven anti-TB drugs. We found the majority of M. tuberculosis isolates were the CAS/Delhi strain-type (lineage 3; n = 57; 70.4%) and multi-drug resistant (MDR; n = 62; 76.5%). The most frequent resistance mutations were observed in the katG and rpoB genes, conferring resistance to isoniazid and rifampicin respectively. Mutations were also observed in genes conferring resistance to other first and second-line drugs, including in pncA (pyrazinamide), embB (ethambutol), gyrA (fluoroquinolones), rrs (aminoglycosides), rpsL, rrs and giB (streptomycin) loci. Whilst the majority of mutations have been reported in global datasets, we describe unreported putative resistance markers in katG, ethA (ethionamide), gyrA and gyrB (fluoroquinolones), and pncA. Analysis of the mutations revealed that acquisition of rifampicin resistance often preceded isoniazid in our isolates. We also observed a high proportion (17.6%) of pre-MDR isolates with fluoroquinolone resistance markers, potentially due to unregulated anti-TB drug use. Our isolates were compared to previously sequenced strains from Pakistan in a combined phylogenetic tree analysis. The presence of lineage 2 was only observed in our isolates. Using a cut-off of less than ten genome-wide mutation differences between isolates, a transmission analysis revealed 18 M. tuberculosis isolates clustering within eight networks, thereby providing evidence of drug-resistant TB transmission in the Khyber Pakhtunkhwa province. Overall, we have demonstrated that drug-resistant TB isolates are circulating and transmitted in North West Pakistan. Further, we have shown the usefulness of whole genome sequencing as a diagnostic tool for characterizing M. tuberculosis isolates, which will assist future epidemiological studies and disease control activities in Pakistan.",,pdf:https://www.nature.com/articles/s41598-019-51562-6.pdf; doi:https://doi.org/10.1038/s41598-019-51562-6; html:https://europepmc.org/articles/PMC6802378; pdf:https://europepmc.org/articles/PMC6802378?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>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·<b>54, 0</b>·<b>95</b>-<b>2</b>·<b>49</b>).<h4>Interpretation</h4>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.<h4>Funding</h4>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.",,pdf:http://www.thelancet.com/article/S2665991322000984/pdf; 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
 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.",,pdf:https://www.rcpjournals.org/content/futurehosp/8/2/e243.full.pdf; 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
 31951005,https://doi.org/10.1093/jamia/ocz211,On classifying sepsis heterogeneity in the ICU: insight using machine learning.,"Ibrahim ZM, Wu H, Hamoud A, Stappen L, Dobson RJB, Agarossi A.",,Journal of the American Medical Informatics Association : JAMIA,2020,2020-03-01,Y,Sepsis; Machine Learning; Artificial Intelligence In Medicine; Sepsis Prediction; Sepsis Subtypes,Applied Analytics,,"<h4>Objectives</h4>Current machine learning models aiming to predict sepsis from electronic health records (EHR) do not account 20 for the heterogeneity of the condition despite its emerging importance in prognosis and treatment. This work demonstrates the added value of stratifying the types of organ dysfunction observed in patients who develop sepsis in the intensive care unit (ICU) in improving the ability to recognize patients at risk of sepsis from their EHR data.<h4>Materials and methods</h4>Using an ICU dataset of 13 728 records, we identify clinically significant sepsis subpopulations with distinct organ dysfunction patterns. We perform classification experiments with random forest, gradient boost trees, and support vector machines, using the identified subpopulations to distinguish patients who develop sepsis in the ICU from those who do not.<h4>Results</h4>The classification results show that features selected using sepsis subpopulations as background knowledge yield a superior performance in distinguishing septic from non-septic patients regardless of the classification model used. The improved performance is especially pronounced in specificity, which is a current bottleneck in sepsis prediction machine learning models.<h4>Conclusion</h4>Our findings can steer machine learning efforts toward more personalized models for complex conditions including sepsis.",Ibrahim et al. categorized patients in groups based on the type of organ failure. This categorization helped machine based algorithms to correctly identify those at high risk of sepsis.,pdf:https://academic.oup.com/jamia/article-pdf/27/3/437/34153319/ocz211.pdf; doi:https://doi.org/10.1093/jamia/ocz211; html:https://europepmc.org/articles/PMC7025363; pdf:https://europepmc.org/articles/PMC7025363?pdf=render
 31765395,https://doi.org/10.1371/journal.pone.0225625,Semantic computational analysis of anticoagulation use in atrial fibrillation from real world data.,"Bean DM, Teo J, Wu H, Oliveira R, Patel R, Bendayan R, Shah AM, Dobson RJB, Scott PA.",,PloS one,2019,2019-11-25,Y,,,,"Atrial fibrillation (AF) is the most common arrhythmia and significantly increases stroke risk. This risk is effectively managed by oral anticoagulation. Recent studies using national registry data indicate increased use of anticoagulation resulting from changes in guidelines and the availability of newer drugs. The aim of this study is to develop and validate an open source risk scoring pipeline for free-text electronic health record data using natural language processing. AF patients discharged from 1st January 2011 to 1st October 2017 were identified from discharge summaries (N = 10,030, 64.6% male, average age 75.3 ± 12.3 years). A natural language processing pipeline was developed to identify risk factors in clinical text and calculate risk for ischaemic stroke (CHA2DS2-VASc) and bleeding (HAS-BLED). Scores were validated vs two independent experts for 40 patients. Automatic risk scores were in strong agreement with the two independent experts for CHA2DS2-VASc (average kappa 0.78 vs experts, compared to 0.85 between experts). Agreement was lower for HAS-BLED (average kappa 0.54 vs experts, compared to 0.74 between experts). In high-risk patients (CHA2DS2-VASc ≥2) OAC use has increased significantly over the last 7 years, driven by the availability of DOACs and the transitioning of patients from AP medication alone to OAC. Factors independently associated with OAC use included components of the CHA2DS2-VASc and HAS-BLED scores as well as discharging specialty and frailty. OAC use was highest in patients discharged under cardiology (69%). Electronic health record text can be used for automatic calculation of clinical risk scores at scale. Open source tools are available today for this task but require further validation. Analysis of routinely collected EHR data can replicate findings from large-scale curated registries.","Bean et al. looked at using clinical notes to calculate risk scores: CHADSVASC and HASBLED for 10,030 AF patients from 2011 to October 2017), they’ve validated their natural language processing algorithm with getting clinicians to calculate the risk in conventional manner for 40 of cases, the two scores were in higher agreement for stroke risk compared to HAS-BLED They’ve concluded on usefulness of NLP method in risk calculation at the large scale.",pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0225625&type=printable; doi:https://doi.org/10.1371/journal.pone.0225625; html:https://europepmc.org/articles/PMC6876873; pdf:https://europepmc.org/articles/PMC6876873?pdf=render
@@ -902,47 +902,47 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Wellcome Trust Senior Fellowship, Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2589750021000170/pdf; 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
 32462176,https://doi.org/10.1093/ehjci/jeaa088,A head-to-head comparison of speckle tracking echocardiography and feature tracking cardiovascular magnetic resonance imaging in right ventricular deformation.,"Taha K, Bourfiss M, Te Riele ASJM, Cramer MM, van der Heijden JF, Asselbergs FW, Velthuis BK, Teske AJ.",,European heart journal. Cardiovascular Imaging,2021,2021-07-01,Y,Right Ventricle; Strain Imaging; Speckle Tracking; Arvc; Feature Tracking; Deformation Imaging,,,"<h4>Aims</h4>Speckle tracking echocardiography (STE) and feature tracking cardiovascular magnetic resonance imaging (FT-CMR) are advanced imaging techniques which are both used for quantification of global and regional myocardial strain. Direct comparisons of STE and FT-CMR regarding right ventricular (RV) strain analysis are limited. We aimed to study clinical performance, correlation and agreement of RV strain by these techniques, using arrhythmogenic right ventricular cardiomyopathy (ARVC) as a model for RV disease.<h4>Methods and results</h4>We enrolled 110 subjects, including 34 patients with definite ARVC, 30 preclinical relatives of ARVC patients, and 46 healthy control subjects. Global and regional RV longitudinal peak strain (PS) were measured by STE and FT-CMR. Both modalities showed reduced strain values in ARVC patients compared to ARVC relatives (STE global PS: P < 0.001; FT-CMR global PS: P < 0.001) and reduced strain values in ARVC relatives compared to healthy control subjects (STE global PS: P = 0.042; FT-CMR global PS: P = 0.084). There was a moderate, albeit significant correlation between RV strain values obtained by STE and FT-CMR [global PS r = 0.578 (95% confidence interval 0.427-0.697), P < 0.001]. Agreement between the techniques was weak (limits of agreement for global PS: ±11.8%). Correlation and agreement both deteriorated when regional strain was studied.<h4>Conclusion</h4>RV STE and FT-CMR show a similar trend within the spectrum of ARVC and have significant correlation, but inter-modality agreement is weak. STE and FT-CMR may therefore both individually have added value for assessment of RV function, but RV PS values obtained by these techniques currently cannot be used interchangeably in clinical practice.",,pdf:https://academic.oup.com/ehjcimaging/article-pdf/22/8/950/39199744/jeaa088.pdf; doi:https://doi.org/10.1093/ehjci/jeaa088; html:https://europepmc.org/articles/PMC8291671; pdf:https://europepmc.org/articles/PMC8291671?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,,,"<h4>Objectives</h4>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.<h4>Design</h4>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.<h4>Setting</h4>SW at a time considered early in the pandemic, where National Health Service authorities required evidence to guide localised planning and support decision-making.<h4>Participants</h4>Publicly available data on patients with COVID-19.<h4>Primary and secondary outcome measures</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e041536.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-041536; html:https://europepmc.org/articles/PMC7797241; pdf:https://europepmc.org/articles/PMC7797241?pdf=render
-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,,,,"<h4>Importance</h4>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.<h4>Objective</h4>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.<h4>Design, setting, and participants</h4>Two-sample 2 × 2 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.<h4>Exposures</h4>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.<h4>Main outcomes and measures</h4>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.<h4>Results</h4>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).<h4>Conclusions and relevance</h4>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
 33249608,https://doi.org/10.1111/opo.12765,Authors' Reply.,"Wright DM, O'Reilly D, Azuara-Blanco A, Curran R, McMullan M, Hogg RE.",,Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists),2021,2020-11-29,N,,,,,,doi:https://doi.org/10.1111/opo.12765
+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,,,,"<h4>Importance</h4>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.<h4>Objective</h4>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.<h4>Design, setting, and participants</h4>Two-sample 2 × 2 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.<h4>Exposures</h4>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.<h4>Main outcomes and measures</h4>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.<h4>Results</h4>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).<h4>Conclusions and relevance</h4>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
 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,,"<h4>Background</h4>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.<h4>Methods</h4>A machine learning algorithm (myocardial-ischemic-injury-index [MI<sup>3</sup>]) 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. MI<sup>3</sup> 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 MI<sup>3</sup> 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.<h4>Results</h4>Myocardial infarction occurred in 404 (13.4%) patients in the training set and 849 (10.6%) patients in the test set. MI<sup>3</sup> 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 MI<sup>3</sup> thresholds identifying low- and high-risk patients in the training set were 1.6 and 49.7, respectively. In the test set, MI<sup>3</sup> 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, MI<sup>3</sup> 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%]).<h4>Conclusions</h4>Using machine learning, MI<sup>3</sup> 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.<h4>Clinical trial registration</h4>URL: https://www.anzctr.org.au. Unique identifier: ACTRN12616001441404.",,doi:https://doi.org/10.1161/circulationaha.119.041980; doi:https://doi.org/10.1161/CIRCULATIONAHA.119.041980; html:https://europepmc.org/articles/PMC6749969; pdf:https://europepmc.org/articles/PMC6749969?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; doi:https://doi.org/10.1177/20552076221128677; html:https://europepmc.org/articles/PMC9834412; pdf:https://europepmc.org/articles/PMC9834412?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; doi:https://doi.org/10.7554/eLife.64827; html:https://europepmc.org/articles/PMC8064756; pdf:https://europepmc.org/articles/PMC8064756?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; doi:https://doi.org/10.1177/20552076221128677; html:https://europepmc.org/articles/PMC9834412; pdf:https://europepmc.org/articles/PMC9834412?pdf=render
 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 <sup>1</sup>H-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.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497842; 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
 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.",,pdf:https://www.mdpi.com/2075-4426/12/8/1230/pdf?version=1659687887; doi:https://doi.org/10.3390/jpm12081230; html:https://europepmc.org/articles/PMC9410389; pdf:https://europepmc.org/articles/PMC9410389?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,,,,"<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.<h4>Translational relevance</h4>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; doi:https://doi.org/10.1167/tvst.12.7.3; html:https://europepmc.org/articles/PMC10324418; pdf:https://europepmc.org/articles/PMC10324418?pdf=render
 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; doi:https://doi.org/10.1016/j.jpsychires.2022.12.015
+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,,,,"<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.<h4>Translational relevance</h4>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; doi:https://doi.org/10.1167/tvst.12.7.3; html:https://europepmc.org/articles/PMC10324418; pdf:https://europepmc.org/articles/PMC10324418?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,,,,,,pdf:https://journals.sagepub.com/doi/pdf/10.1177/1740774520976617; doi:https://doi.org/10.1177/1740774520976617; html:https://europepmc.org/articles/PMC8174009; pdf:https://europepmc.org/articles/PMC8174009?pdf=render
-35132056,https://doi.org/10.1038/s41467-022-28252-5,Genome-wide association meta-analysis identifies 29 new acne susceptibility loci.,"Mitchell BL, Saklatvala JR, Dand N, Hagenbeek FA, Li X, Min JL, Thomas L, Bartels M, Jan Hottenga J, Lupton MK, Boomsma DI, Dong X, Hveem K, Løset M, Martin NG, Barker JN, Han J, Smith CH, Rentería ME, Simpson MA.",,Nature communications,2022,2022-02-07,Y,,,,"Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial consequences. Here, we perform a GWAS meta-analysis comprising 20,165 individuals with acne from nine independent European ancestry cohorts. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches, we identify putative causal genes at several acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6% of the variance in acne liability in an independent cohort.",,pdf:https://www.nature.com/articles/s41467-022-28252-5.pdf; doi:https://doi.org/10.1038/s41467-022-28252-5; html:https://europepmc.org/articles/PMC8821634; pdf:https://europepmc.org/articles/PMC8821634?pdf=render
 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.",,pdf:https://f1000research.com/articles/9-1095/v2/pdf; doi:https://doi.org/10.12688/f1000research.25484.2; html:https://europepmc.org/articles/PMC8108552; pdf:https://europepmc.org/articles/PMC8108552?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1291; doi:https://doi.org/10.1002/ctm2.1291; html:https://europepmc.org/articles/PMC10280047; pdf:https://europepmc.org/articles/PMC10280047?pdf=render
-34435642,https://doi.org/10.1093/eurheartj/ehab350,Evidence to support magnetic resonance conditional labelling of all pacemaker and defibrillator leads in patients with cardiac implantable electronic devices.,"Bhuva AN, Moralee R, Brunker T, Lascelles K, Cash L, Patel KP, Lowe M, Sekhri N, Alpendurada F, Pennell DJ, Schilling R, Lambiase PD, Chow A, Moon JC, Litt H, Baksi AJ, Manisty CH.",,European heart journal,2022,2022-07-01,Y,Pacemaker; Magnetic Resonance Imaging; Defibrillator,,,"<h4>Aims</h4>Many cardiac pacemakers and defibrillators are not approved by regulators for magnetic resonance imaging (MRI). Even following generator exchange to an approved magnetic resonance (MR)-conditional model, many systems remain classified 'non-MR conditional' due to the leads. This classification makes patient access to MRI challenging, but there is no evidence of increased clinical risk. We compared the effect of MRI on non-MR conditional and MR-conditional pacemaker and defibrillator leads.<h4>Methods and results</h4>Patients undergoing clinical 1.5T MRI with pacemakers and defibrillators in three centres over 5 years were included. Magnetic resonance imaging protocols were similar for MR-conditional and non-MR conditional systems. Devices were interrogated pre- and immediately post-scan, and at follow-up, and adverse clinical events recorded. Lead parameter changes peri-scan were stratified by MR-conditional labelling. A total of 1148 MRI examinations were performed in 970 patients (54% non-MR conditional systems, 39% defibrillators, 15% pacing-dependent) with 2268 leads. There were no lead-related adverse clinical events, and no clinically significant immediate or late lead parameter changes following MRI in either MR-conditional or non-MR conditional leads. Small reductions in atrial and right ventricular sensed amplitudes and impedances were similar between groups, with no difference in the proportion of leads with parameter changes greater than pre-defined thresholds (7.1%, 95% confidence interval: 6.1-8.3).<h4>Conclusions</h4>There was no increased risk of MRI in patients with non-MR conditional pacemaker or defibrillator leads when following recommended protocols. Standardizing MR conditions for all leads would significantly improve access to MRI by enabling patients to be scanned in non-specialist centres, with no discernible incremental risk.",,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehab350/39932149/ehab350.pdf; doi:https://doi.org/10.1093/eurheartj/ehab350; html:https://europepmc.org/articles/PMC9259370; pdf:https://europepmc.org/articles/PMC9259370?pdf=render
+35132056,https://doi.org/10.1038/s41467-022-28252-5,Genome-wide association meta-analysis identifies 29 new acne susceptibility loci.,"Mitchell BL, Saklatvala JR, Dand N, Hagenbeek FA, Li X, Min JL, Thomas L, Bartels M, Jan Hottenga J, Lupton MK, Boomsma DI, Dong X, Hveem K, Løset M, Martin NG, Barker JN, Han J, Smith CH, Rentería ME, Simpson MA.",,Nature communications,2022,2022-02-07,Y,,,,"Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial consequences. Here, we perform a GWAS meta-analysis comprising 20,165 individuals with acne from nine independent European ancestry cohorts. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches, we identify putative causal genes at several acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6% of the variance in acne liability in an independent cohort.",,pdf:https://www.nature.com/articles/s41467-022-28252-5.pdf; doi:https://doi.org/10.1038/s41467-022-28252-5; html:https://europepmc.org/articles/PMC8821634; pdf:https://europepmc.org/articles/PMC8821634?pdf=render
 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,,,,"<h4>Objective</h4>To test for associations between SBP and BMI, with domain-specific cognitive abilities and examine which brain structural phenotypes mediate those associations.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>Our findings add to the body of evidence that addressing cardiovascular risk factors may also preserve cognitive function, via specific aspects of brain structure.",,html:https://journals.lww.com/jhypertension/Fulltext/2020/12000/Association_of_SBP_and_BMI_with_cognitive_and.22.aspx; doi:https://doi.org/10.1097/HJH.0000000000002579
-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,,,"<h4>Objective</h4>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.<h4>Design</h4>Registry based observational study.<h4>Setting</h4>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.<h4>Participants</h4>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).<h4>Main outcome measures</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000245.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render
+34435642,https://doi.org/10.1093/eurheartj/ehab350,Evidence to support magnetic resonance conditional labelling of all pacemaker and defibrillator leads in patients with cardiac implantable electronic devices.,"Bhuva AN, Moralee R, Brunker T, Lascelles K, Cash L, Patel KP, Lowe M, Sekhri N, Alpendurada F, Pennell DJ, Schilling R, Lambiase PD, Chow A, Moon JC, Litt H, Baksi AJ, Manisty CH.",,European heart journal,2022,2022-07-01,Y,Pacemaker; Magnetic Resonance Imaging; Defibrillator,,,"<h4>Aims</h4>Many cardiac pacemakers and defibrillators are not approved by regulators for magnetic resonance imaging (MRI). Even following generator exchange to an approved magnetic resonance (MR)-conditional model, many systems remain classified 'non-MR conditional' due to the leads. This classification makes patient access to MRI challenging, but there is no evidence of increased clinical risk. We compared the effect of MRI on non-MR conditional and MR-conditional pacemaker and defibrillator leads.<h4>Methods and results</h4>Patients undergoing clinical 1.5T MRI with pacemakers and defibrillators in three centres over 5 years were included. Magnetic resonance imaging protocols were similar for MR-conditional and non-MR conditional systems. Devices were interrogated pre- and immediately post-scan, and at follow-up, and adverse clinical events recorded. Lead parameter changes peri-scan were stratified by MR-conditional labelling. A total of 1148 MRI examinations were performed in 970 patients (54% non-MR conditional systems, 39% defibrillators, 15% pacing-dependent) with 2268 leads. There were no lead-related adverse clinical events, and no clinically significant immediate or late lead parameter changes following MRI in either MR-conditional or non-MR conditional leads. Small reductions in atrial and right ventricular sensed amplitudes and impedances were similar between groups, with no difference in the proportion of leads with parameter changes greater than pre-defined thresholds (7.1%, 95% confidence interval: 6.1-8.3).<h4>Conclusions</h4>There was no increased risk of MRI in patients with non-MR conditional pacemaker or defibrillator leads when following recommended protocols. Standardizing MR conditions for all leads would significantly improve access to MRI by enabling patients to be scanned in non-specialist centres, with no discernible incremental risk.",,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehab350/39932149/ehab350.pdf; doi:https://doi.org/10.1093/eurheartj/ehab350; html:https://europepmc.org/articles/PMC9259370; pdf:https://europepmc.org/articles/PMC9259370?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1291; doi:https://doi.org/10.1002/ctm2.1291; html:https://europepmc.org/articles/PMC10280047; pdf:https://europepmc.org/articles/PMC10280047?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,,,"<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Translational relevance</h4>Merged information from multimodal images improves segmentation performance of chorioretinal lesions.",,doi:https://doi.org/10.1167/tvst.9.9.38; doi:https://doi.org/10.1167/tvst.9.9.38; html:https://europepmc.org/articles/PMC7453042; pdf:https://europepmc.org/articles/PMC7453042?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,,,"<h4>Objective</h4>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.<h4>Design</h4>Registry based observational study.<h4>Setting</h4>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.<h4>Participants</h4>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).<h4>Main outcome measures</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000245.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render
 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,,,"<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://heart.bmj.com/content/heartjnl/107/11/902.full.pdf; doi:https://doi.org/10.1136/heartjnl-2020-318557; html:https://europepmc.org/articles/PMC8142420; pdf:https://europepmc.org/articles/PMC8142420?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,,,"<h4>Objectives</h4>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.<h4>Design</h4>Observational retrospective study examining cost of healthcare of patients receiving CRS surgery.<h4>Setting</h4>Linked electronic health records from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics databases in England.<h4>Participants</h4>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.<h4>Outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e055603.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055603; html:https://europepmc.org/articles/PMC8830221; pdf:https://europepmc.org/articles/PMC8830221?pdf=render
 35896705,https://doi.org/10.1038/s41598-022-16639-9,Estimation of biological heart age using cardiovascular magnetic resonance radiomics.,"Raisi-Estabragh Z, Salih A, Gkontra P, Atehortúa A, Radeva P, Boscolo Galazzo I, Menegaz G, Harvey NC, Lekadir K, Petersen SE.",,Scientific reports,2022,2022-07-27,Y,,,,"We developed a novel interpretable biological heart age estimation model using cardiovascular magnetic resonance radiomics measures of ventricular shape and myocardial character. We included 29,996 UK Biobank participants without cardiovascular disease. Images were segmented using an automated analysis pipeline. We extracted 254 radiomics features from the left ventricle, right ventricle, and myocardium of each study. We then used Bayesian ridge regression with tenfold cross-validation to develop a heart age estimation model using the radiomics features as the model input and chronological age as the model output. We examined associations of radiomics features with heart age in men and women, observing sex-differential patterns. We subtracted actual age from model estimated heart age to calculate a ""heart age delta"", which we considered as a measure of heart aging. We performed a phenome-wide association study of 701 exposures with heart age delta. The strongest correlates of heart aging were measures of obesity, adverse serum lipid markers, hypertension, diabetes, heart rate, income, multimorbidity, musculoskeletal health, and respiratory health. This technique provides a new method for phenotypic assessment relating to cardiovascular aging; further studies are required to assess whether it provides incremental risk information over current approaches.",,pdf:https://www.nature.com/articles/s41598-022-16639-9.pdf; doi:https://doi.org/10.1038/s41598-022-16639-9; html:https://europepmc.org/articles/PMC9329281; pdf:https://europepmc.org/articles/PMC9329281?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,,,,"<h4>Objective</h4>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.<h4>Setting</h4>Victoria, Australia.<h4>Participants</h4>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.<h4>Design</h4>Registry-based cohort study.<h4>Main measures</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>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
 32060159,https://doi.org/10.1136/bmjopen-2019-034396,Data-driven discovery of changes in clinical code usage over time: a case-study on changes in cardiovascular disease recording in two English electronic health records databases (2001-2015).,"Rockenschaub P, Nguyen V, Aldridge RW, Acosta D, García-Gómez JM, Sáez C.",,BMJ open,2020,2020-02-13,Y,Cardiovascular disease; Data Quality; Electronic Health Records; Clinical Coding; Statistics & Research Methods,The Human Phenome,,"<h4>Objectives</h4>To demonstrate how data-driven variability methods can be used to identify changes in disease recording in two English electronic health records databases between 2001 and 2015.<h4>Design</h4>Repeated cross-sectional analysis that applied data-driven temporal variability methods to assess month-by-month changes in routinely collected medical data. A measure of difference between months was calculated based on joint distributions of age, gender, socioeconomic status and recorded cardiovascular diseases. Distances between months were used to identify temporal trends in data recording.<h4>Setting</h4>400 English primary care practices from the Clinical Practice Research Datalink (CPRD GOLD) and 451 hospital providers from the Hospital Episode Statistics (HES).<h4>Main outcomes</h4>The proportion of patients (CPRD GOLD) and hospital admissions (HES) with a recorded cardiovascular disease (CPRD GOLD: coronary heart disease, heart failure, peripheral arterial disease, stroke; HES: International Classification of Disease codes I20-I69/G45).<h4>Results</h4>Both databases showed gradual changes in cardiovascular disease recording between 2001 and 2008. The recorded prevalence of included cardiovascular diseases in CPRD GOLD increased by 47%-62%, which partially reversed after 2008. For hospital records in HES, there was a relative decrease in angina pectoris (-34.4%) and unspecified stroke (-42.3%) over the same time period, with a concomitant increase in chronic coronary heart disease (+14.3%). Multiple abrupt changes in the use of myocardial infarction codes in hospital were found in March/April 2010, 2012 and 2014, possibly linked to updates of clinical coding guidelines.<h4>Conclusions</h4>Identified temporal variability could be related to potentially non-medical causes such as updated coding guidelines. These artificial changes may introduce temporal correlation among diagnoses inferred from routine data, violating the assumptions of frequently used statistical methods. Temporal variability measures provide an objective and robust technique to identify, and subsequently account for, those changes in electronic health records studies without any prior knowledge of the data collection process.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/2/e034396.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-034396; html:https://europepmc.org/articles/PMC7045100; pdf:https://europepmc.org/articles/PMC7045100?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,,,,"<h4>Objective</h4>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.<h4>Setting</h4>Victoria, Australia.<h4>Participants</h4>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.<h4>Design</h4>Registry-based cohort study.<h4>Main measures</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>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
 37827807,https://doi.org/10.1136/bmjresp-2023-001806,Observational cohort study protocol: neutrophil function and energetics in adults with pneumonia and sepsis - Pneumonia Metabolism in Ageing (PUMA).,"Grudzinska FS, Faniyi AA, Scott A, Sapey E, Thickett DR.",,BMJ open respiratory research,2023,2023-10-01,Y,Pneumonia; innate immunity; Bacterial Infection; respiratory infection; Neutrophil Biology,,,"<h4>Introduction</h4>Community-acquired pneumonia has high mortality and is associated with significant healthcare costs. In older adults with community-acquired pneumonia neutrophil dysfunction has been identified and is associated with poor outcomes for patients. Immunometabolism is a rapidly developing field which links immune cell function to metabolism. This study aims to explore neutrophil metabolism in community-acquired pneumonia.<h4>Methods and analysis</h4>Pneumonia Metabolism in Ageing study is a prospective observational study recruiting older adults hospitalised with community-acquired pneumonia to examine neutrophil function and metabolic status. Controls will be older adults with no acute illness. The primary endpoint is neutrophil chemotaxis.<h4>Ethics and dissemination</h4>The study has ethical approval from the Research Ethics Committee Wales, reference 19/WA/0299. This study involves participants who may lack the capacity to consent to research involvement, in this situation, personal or professional assent will be sought. The results from this study will be submitted for publication in peer-reviewed journals and disseminated at local and international conferences.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/10/1/e001806.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001806; html:https://europepmc.org/articles/PMC10582892; pdf:https://europepmc.org/articles/PMC10582892?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,,,,,,html:https://journals.lww.com/epidem/Fulltext/2022/01000/The_Authors_Respond.22.aspx; doi:https://doi.org/10.1097/EDE.0000000000001429
-37645022,https://doi.org/10.1183/20734735.0058-2023,The impact of poor housing and indoor air quality on respiratory health in children.,"Holden KA, Lee AR, Hawcutt DB, Sinha IP.",,"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.<h4>Educational aims</h4>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.",,doi:https://doi.org/10.1183/20734735.0058-2023; html:https://europepmc.org/articles/PMC10461733; pdf:https://europepmc.org/articles/PMC10461733?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 (<i>i</i>ECG) technique which estimates both endocardial and epicardial ventricular activation sequences. We aimed to quantitatively compare our <i>i</i>ECG 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 <i>i</i>ECG approach was improved by mimicking the effects of the His-Purkinje system on ventricular activation. EAM local activation timing (LAT) maps were compared with <i>i</i>ECG-LAT maps using absolute differences and Pearson's correlation coefficient, reported as mean ± standard deviation [95% confidence interval]. The correlation coefficient between <i>i</i>ECG-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 <i>i</i>ECG 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 <i>i</i>ECG 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 <i>i</i>ECG requires further refinements to facilitate clinical implementation and risk stratification.",,pdf:https://www.frontiersin.org/articles/10.3389/fphys.2021.730736/pdf; doi:https://doi.org/10.3389/fphys.2021.730736; html:https://europepmc.org/articles/PMC8521153; pdf:https://europepmc.org/articles/PMC8521153?pdf=render
+37645022,https://doi.org/10.1183/20734735.0058-2023,The impact of poor housing and indoor air quality on respiratory health in children.,"Holden KA, Lee AR, Hawcutt DB, Sinha IP.",,"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.<h4>Educational aims</h4>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.",,doi:https://doi.org/10.1183/20734735.0058-2023; html:https://europepmc.org/articles/PMC10461733; pdf:https://europepmc.org/articles/PMC10461733?pdf=render
 37532769,https://doi.org/10.1038/s42003-023-05171-9,Direct inference and control of genetic population structure from RNA sequencing data.,"Fachrul M, Karkey A, Shakya M, Judd LM, Harshegyi T, Sim KS, Tonks S, Dongol S, Shrestha R, Salim A, STRATAA study group, Baker S, Pollard AJ, Khor CC, Dolecek C, Basnyat B, Dunstan SJ, Holt KE, Inouye M.",,Communications biology,2023,2023-08-02,Y,,,,"RNAseq data can be used to infer genetic variants, yet its use for estimating genetic population structure remains underexplored. Here, we construct a freely available computational tool (RGStraP) to estimate RNAseq-based genetic principal components (RG-PCs) and assess whether RG-PCs can be used to control for population structure in gene expression analyses. Using whole blood samples from understudied Nepalese populations and the Geuvadis study, we show that RG-PCs had comparable results to paired array-based genotypes, with high genotype concordance and high correlations of genetic principal components, capturing subpopulations within the dataset. In differential gene expression analysis, we found that inclusion of RG-PCs as covariates reduced test statistic inflation. Our paper demonstrates that genetic population structure can be directly inferred and controlled for using RNAseq data, thus facilitating improved retrospective and future analyses of transcriptomic data.",,pdf:https://www.nature.com/articles/s42003-023-05171-9.pdf; doi:https://doi.org/10.1038/s42003-023-05171-9; html:https://europepmc.org/articles/PMC10397182; pdf:https://europepmc.org/articles/PMC10397182?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,,,,"<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004141&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004141; html:https://europepmc.org/articles/PMC9799317; pdf:https://europepmc.org/articles/PMC9799317?pdf=render
 35792838,https://doi.org/10.1093/bioinformatics/btac453,Flashfm-ivis: interactive visualization for fine-mapping of multiple quantitative traits.,"Zhou F, Butterworth AS, Asimit JL.",,"Bioinformatics (Oxford, England)",2022,2022-09-01,Y,,,,"<h4>Summary</h4>flashfm-ivis provides a suite of interactive visualization plots to view potential causal genetic variants that underlie associations that are shared or distinct between multiple quantitative traits and compares results between single- and multi-trait fine-mapping. Unique features include network diagrams that show joint effects between variants for each trait and regional association plots that integrate fine-mapping results, all with user-controlled zoom features for an interactive exploration of potential causal variants across traits.<h4>Availability and implementation</h4>flashfm-ivis is an open-source software under the MIT license. It is available as an interactive web-based tool (http://shiny.mrc-bsu.cam.ac.uk/apps/flashfm-ivis/) and as an R package. Code and documentation are available at https://github.com/fz-cambridge/flashfm-ivis and https://zenodo.org/record/6376244#.YjnarC-l2X0. Additional features can be downloaded as standalone R libraries to encourage reuse.<h4>Supplementary information</h4>Supplementary information are available at Bioinformatics online.",,pdf:https://academic.oup.com/bioinformatics/article-pdf/38/17/4238/49889636/btac453.pdf; doi:https://doi.org/10.1093/bioinformatics/btac453; html:https://europepmc.org/articles/PMC9438951; pdf:https://europepmc.org/articles/PMC9438951?pdf=render
 36369983,https://doi.org/10.1093/eurheartj/ehac650,Fit for the future: empowering clinical trials with digital technology.,"Kotecha D, DeVore AD, Asselbergs FW.",,European heart journal,2023,2023-01-01,N,,,,,,doi:https://doi.org/10.1093/eurheartj/ehac650
-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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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 &gt;45 ms (n = 63), and (iii) overt LV dysfunction, defined as reduced LVEF &lt;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)].<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeab178/40357499/jeab178.pdf; doi:https://doi.org/10.1093/ehjci/jeab178; html:https://europepmc.org/articles/PMC9584619; pdf:https://europepmc.org/articles/PMC9584619?pdf=render
 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,,,"<h4>Background</h4>home advice and modification interventions aim to promote independent living for those living in the community, but quantitative evidence of their effectiveness is limited.<h4>Aim</h4>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.<h4>Study design and setting</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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)].<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/ageing/article-pdf/49/6/1056/33993322/afaa158.pdf; doi:https://doi.org/10.1093/ageing/afaa158; html:https://europepmc.org/articles/PMC7583515; pdf:https://europepmc.org/articles/PMC7583515?pdf=render
-37751239,https://doi.org/10.2196/49438,Design and Evaluation of an Intensive Care Unit Dashboard Built in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Wac M, Craddock I, Chantziara S, Campbell T, Santos-Rodriguez R, Davidson B, McWilliams C.",,JMIR human factors,2023,2023-09-26,Y,Design; Health; ICU; EPR; intensive care unit; Interview; Intensive Care; Critical Care; Electronic Patient Record; Participatory Design; Ehr; Electronic Health Record; Software Engineering; Clinical Information System; Cis; Thematic Analysis; Dashboard; Human-centered Design; Covid-19; Interactive Display,,,"<h4>Background</h4>Dashboards and interactive displays are becoming increasingly prevalent in most health care settings and have the potential to streamline access to information, consolidate disparate data sources and deliver new insights. Our research focuses on intensive care units (ICUs) which are heavily instrumented, critical care environments that generate vast amounts of data and frequently require individualized support for each patient. Consequently, clinicians experience a high cognitive load, which can translate to suboptimal performance. The global COVID-19 pandemic exacerbated this problem by generating a large number of additional hospitalizations, which necessitated a new tool that would help manage ICUs' census. In a previous study, we interviewed clinicians at the University Hospitals Bristol and Weston National Health Service Foundation Trust to capture the requirements for bespoke dashboards that would alleviate this problem.<h4>Objective</h4>This study aims to design, implement, and evaluate an ICU dashboard to allow for monitoring of the high volume of patients in need of critical care, particularly tailored to high-demand situations, such as those seen during the COVID-19 pandemic.<h4>Methods</h4>Building upon the previously gathered requirements, we developed a dashboard, integrated it within the ICU of a National Health Service trust, and allowed all staff to access our tool. For evaluation purposes, participants were recruited and interviewed following a 25-day period during which they were able to use the dashboard clinically. The semistructured interviews followed a topic guide aimed at capturing the usability of the dashboard, supplemented with additional questions asked post hoc to probe themes established during the interview. Interview transcripts were analyzed using a thematic analysis framework that combined inductive and deductive approaches and integrated the Technology Acceptance Model.<h4>Results</h4>A total of 10 participants with 4 different roles in the ICU (6 consultants, 2 junior doctors, 1 nurse, and 1 advanced clinical practitioner) participated in the interviews. Our analysis generated 4 key topics that prevailed across the data: our dashboard met the usability requirements of the participants and was found useful and intuitive; participants perceived that it impacted their delivery of patient care by improving the access to the information and better equipping them to do their job; the tool was used in a variety of ways and for different reasons and tasks; and there were barriers to integration of our dashboard into practice, including familiarity with existing systems, which stifled the adoption of our tool.<h4>Conclusions</h4>Our findings show that the perceived utility of the dashboard had a positive impact on the clinicians' workflows in the ICU. Improving access to information translated into more efficient patient care and transformed some of the existing processes. The introduction of our tool was met with positive reception, but its integration during the COVID-19 pandemic limited its adoption into practice.",,doi:https://doi.org/10.2196/49438; html:https://europepmc.org/articles/PMC10565627
+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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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 &gt;45 ms (n = 63), and (iii) overt LV dysfunction, defined as reduced LVEF &lt;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)].<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeab178/40357499/jeab178.pdf; doi:https://doi.org/10.1093/ehjci/jeab178; html:https://europepmc.org/articles/PMC9584619; pdf:https://europepmc.org/articles/PMC9584619?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>International registered report identifier (irrid)</h4>DERR1-10.2196/18690.",,pdf:https://www.researchprotocols.org/2020/8/e18690/PDF; doi:https://doi.org/10.2196/18690; html:https://europepmc.org/articles/PMC7442945
+37751239,https://doi.org/10.2196/49438,Design and Evaluation of an Intensive Care Unit Dashboard Built in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Wac M, Craddock I, Chantziara S, Campbell T, Santos-Rodriguez R, Davidson B, McWilliams C.",,JMIR human factors,2023,2023-09-26,Y,Design; Health; ICU; EPR; intensive care unit; Interview; Intensive Care; Critical Care; Electronic Patient Record; Participatory Design; Ehr; Electronic Health Record; Software Engineering; Clinical Information System; Cis; Thematic Analysis; Dashboard; Human-centered Design; Covid-19; Interactive Display,,,"<h4>Background</h4>Dashboards and interactive displays are becoming increasingly prevalent in most health care settings and have the potential to streamline access to information, consolidate disparate data sources and deliver new insights. Our research focuses on intensive care units (ICUs) which are heavily instrumented, critical care environments that generate vast amounts of data and frequently require individualized support for each patient. Consequently, clinicians experience a high cognitive load, which can translate to suboptimal performance. The global COVID-19 pandemic exacerbated this problem by generating a large number of additional hospitalizations, which necessitated a new tool that would help manage ICUs' census. In a previous study, we interviewed clinicians at the University Hospitals Bristol and Weston National Health Service Foundation Trust to capture the requirements for bespoke dashboards that would alleviate this problem.<h4>Objective</h4>This study aims to design, implement, and evaluate an ICU dashboard to allow for monitoring of the high volume of patients in need of critical care, particularly tailored to high-demand situations, such as those seen during the COVID-19 pandemic.<h4>Methods</h4>Building upon the previously gathered requirements, we developed a dashboard, integrated it within the ICU of a National Health Service trust, and allowed all staff to access our tool. For evaluation purposes, participants were recruited and interviewed following a 25-day period during which they were able to use the dashboard clinically. The semistructured interviews followed a topic guide aimed at capturing the usability of the dashboard, supplemented with additional questions asked post hoc to probe themes established during the interview. Interview transcripts were analyzed using a thematic analysis framework that combined inductive and deductive approaches and integrated the Technology Acceptance Model.<h4>Results</h4>A total of 10 participants with 4 different roles in the ICU (6 consultants, 2 junior doctors, 1 nurse, and 1 advanced clinical practitioner) participated in the interviews. Our analysis generated 4 key topics that prevailed across the data: our dashboard met the usability requirements of the participants and was found useful and intuitive; participants perceived that it impacted their delivery of patient care by improving the access to the information and better equipping them to do their job; the tool was used in a variety of ways and for different reasons and tasks; and there were barriers to integration of our dashboard into practice, including familiarity with existing systems, which stifled the adoption of our tool.<h4>Conclusions</h4>Our findings show that the perceived utility of the dashboard had a positive impact on the clinicians' workflows in the ICU. Improving access to information translated into more efficient patient care and transformed some of the existing processes. The introduction of our tool was met with positive reception, but its integration during the COVID-19 pandemic limited its adoption into practice.",,doi:https://doi.org/10.2196/49438; html:https://europepmc.org/articles/PMC10565627
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://link.springer.com/content/pdf/10.1007/s11695-021-05493-9.pdf; doi:https://doi.org/10.1007/s11695-021-05493-9; html:https://europepmc.org/articles/PMC8323543; pdf:https://europepmc.org/articles/PMC8323543?pdf=render
-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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>National Institute for Health Research.",,doi:https://doi.org/10.1016/S2468-2667(23)00126-3
 34798287,https://doi.org/10.1016/j.jclinepi.2021.11.023,Missing data is poorly handled and reported in prediction model studies using machine learning: a literature review.,"Nijman S, Leeuwenberg AM, Beekers I, Verkouter I, Jacobs J, Bots ML, Asselbergs FW, Moons K, Debray T.",,Journal of clinical epidemiology,2022,2021-11-16,N,Prediction; Literature review; Reporting; Missing Data; Machine Learning,,,"<h4>Objectives</h4>Missing data is a common problem during the development, evaluation, and implementation of prediction models. Although machine learning (ML) methods are often said to be capable of circumventing missing data, it is unclear how these methods are used in medical research. We aim to find out if and how well prediction model studies using machine learning report on their handling of missing data.<h4>Study design and setting</h4>We systematically searched the literature on published papers between 2018 and 2019 about primary studies developing and/or validating clinical prediction models using any supervised ML methodology across medical fields. From the retrieved studies information about the amount and nature (e.g. missing completely at random, potential reasons for missingness) of missing data and the way they were handled were extracted.<h4>Results</h4>We identified 152 machine learning-based clinical prediction model studies. A substantial amount of these 152 papers did not report anything on missing data (n = 56/152). A majority (n = 96/152) reported details on the handling of missing data (e.g., methods used), though many of these (n = 46/96) did not report the amount of the missingness in the data. In these 96 papers the authors only sometimes reported possible reasons for missingness (n = 7/96) and information about missing data mechanisms (n = 8/96). The most common approach for handling missing data was deletion (n = 65/96), mostly via complete-case analysis (CCA) (n = 43/96). Very few studies used multiple imputation (n = 8/96) or built-in mechanisms such as surrogate splits (n = 7/96) that directly address missing data during the development, validation, or implementation of the prediction model.<h4>Conclusion</h4>Though missing values are highly common in any type of medical research and certainly in the research based on routine healthcare data, a majority of the prediction model studies using machine learning does not report sufficient information on the presence and handling of missing data. Strategies in which patient data are simply omitted are unfortunately the most often used methods, even though it is generally advised against and well known that it likely causes bias and loss of analytical power in prediction model development and in the predictive accuracy estimates. Prediction model researchers should be much more aware of alternative methodologies to address missing data.",,pdf:http://www.jclinepi.com/article/S0895435621003759/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.11.023
+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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>National Institute for Health Research.",,doi:https://doi.org/10.1016/S2468-2667(23)00126-3
 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,,,,"<h4>Objective</h4>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).<h4>Research design and methods</h4>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.<h4>Results</h4>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; <i>P</i> < 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; <i>P</i> = 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; <i>P</i> = 0.042), although again with evidence of pleiotropy.<h4>Conclusions</h4>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.",,pdf:https://diabetesjournals.org/care/article-pdf/44/7/1699/632992/dc202518.pdf; doi:https://doi.org/10.2337/dc20-2518; html:https://europepmc.org/articles/PMC8323186; pdf:https://europepmc.org/articles/PMC8323186?pdf=render
 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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e047101.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-047101; html:https://europepmc.org/articles/PMC7817800; pdf:https://europepmc.org/articles/PMC7817800?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-omics<sup>1</sup>. Here we examine a large cohort (the INTERVAL study<sup>2</sup>; 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 Biobank<sup>3</sup> 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.",,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; doi:https://doi.org/10.1038/s41586-023-05844-9; html:https://europepmc.org/articles/PMC10323211; pdf:https://europepmc.org/articles/PMC10323211?pdf=render; doi:https://doi.org/10.1038/s41586-023-05844-9
 37649471,https://doi.org/10.23889/ijpds.v6i3.1705,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 AB, Laing H.",,International journal of population data science,2021,2021-01-01,Y,"Colitis, ulcerative; Health Policy; Patient Reported Outcome Measure; Routinely Collected Health Data; Data Science; Value-based Health Care",,,"<h4>Introduction</h4>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.<h4>Objectives</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,doi:https://doi.org/10.23889/ijpds.v6i3.1705; html:https://europepmc.org/articles/PMC10464864; pdf:https://europepmc.org/articles/PMC10464864?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-omics<sup>1</sup>. Here we examine a large cohort (the INTERVAL study<sup>2</sup>; 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 Biobank<sup>3</sup> 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.",,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; doi:https://doi.org/10.1038/s41586-023-05844-9; html:https://europepmc.org/articles/PMC10323211; pdf:https://europepmc.org/articles/PMC10323211?pdf=render; doi:https://doi.org/10.1038/s41586-023-05844-9
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Discussion</h4>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.<h4>Systematic review registration</h4>PROSPERO CRD42022296113.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02173-w; doi:https://doi.org/10.1186/s13643-023-02173-w; html:https://europepmc.org/articles/PMC9883863; pdf:https://europepmc.org/articles/PMC9883863?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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0245636&type=printable; doi:https://doi.org/10.1371/journal.pone.0245636; html:https://europepmc.org/articles/PMC7840051; pdf:https://europepmc.org/articles/PMC7840051?pdf=render
 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,,,"<b>Background:</b> 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. <b>Methods:</b> 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 <b>Results:</b> 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) <b>Conclusions:</b> 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
@@ -952,9 +952,9 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 31711534,https://doi.org/10.1186/s13326-019-0216-2,Combining string and phonetic similarity matching to identify misspelt names of drugs in medical records written in Portuguese.,"Tissot H, Dobson R.",,Journal of biomedical semantics,2019,2019-11-12,Y,Similarity Search; Phonetic Similarity; Misspelt Names Of Drugs,,,"<h4>Background</h4>There is an increasing amount of unstructured medical data that can be analysed for different purposes. However, information extraction from free text data may be particularly inefficient in the presence of spelling errors. Existing approaches use string similarity methods to search for valid words within a text, coupled with a supporting dictionary. However, they are not rich enough to encode both typing and phonetic misspellings.<h4>Results</h4>Experimental results showed a joint string and language-dependent phonetic similarity is more accurate than traditional string distance metrics when identifying misspelt names of drugs in a set of medical records written in Portuguese.<h4>Conclusion</h4>We present a hybrid approach to efficiently perform similarity match that overcomes the loss of information inherit from using either exact match search or string based similarity search methods.",,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0216-2; doi:https://doi.org/10.1186/s13326-019-0216-2; html:https://europepmc.org/articles/PMC6849162; pdf:https://europepmc.org/articles/PMC6849162?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
 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.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa56833/Download/56833__19829__9b0bb77f67e84342b525fbccaba98e67.pdf; doi:https://doi.org/10.1080/02640414.2021.1928409
-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,,,"<h4>Background</h4>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.<h4>Methods</h4>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 (CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥4); (2) ERC and lower comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-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 (CHA<sub>2</sub>DS<sub>2</sub>-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.<h4>Results</h4>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]; <i>P</i>=0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63-0.94]; <i>P</i>=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]; <i>P</i>=0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83-1.06]; <i>P</i>=0.310). The comorbidity burden interacted with ERC in the UKB (interaction- <i>P</i>=0.027) but not in OptumLabs (interaction-<i>P</i>=0.720). ERC was not associated with an increased risk for the primary safety outcome.<h4>Conclusions</h4>ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥4).",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCEP.122.011585; doi:https://doi.org/10.1161/CIRCEP.122.011585
 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
 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,,,,,,pdf:https://discovery.ucl.ac.uk/10110375/1/Syed%20and%20Gilbert%20%282020%29.%20Are%20children%20who%20are%20home%20from%20school%20at%20an%20increased%20risk%20of%20child%20maltreatment.pdf; doi:https://doi.org/10.1093/pubmed/fdaa115
+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,,,"<h4>Background</h4>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.<h4>Methods</h4>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 (CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥4); (2) ERC and lower comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-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 (CHA<sub>2</sub>DS<sub>2</sub>-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.<h4>Results</h4>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]; <i>P</i>=0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63-0.94]; <i>P</i>=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]; <i>P</i>=0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83-1.06]; <i>P</i>=0.310). The comorbidity burden interacted with ERC in the UKB (interaction- <i>P</i>=0.027) but not in OptumLabs (interaction-<i>P</i>=0.720). ERC was not associated with an increased risk for the primary safety outcome.<h4>Conclusions</h4>ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥4).",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCEP.122.011585; doi:https://doi.org/10.1161/CIRCEP.122.011585
 31329239,https://doi.org/10.1093/jamia/ocz105,UK phenomics platform for developing and validating electronic health record phenotypes: CALIBER.,"Denaxas S, Gonzalez-Izquierdo A, Direk K, Fitzpatrick NK, Fatemifar G, Banerjee A, Dobson RJB, Howe LJ, Kuan V, Lumbers RT, Pasea L, Patel RS, Shah AD, Hingorani AD, Sudlow C, Hemingway H.",,Journal of the American Medical Informatics Association : JAMIA,2019,2019-12-01,Y,Phenotyping; Medical Informatics; Personalized Medicine; Electronic Health Records,The Human Phenome,,"<h4>Objective</h4>Electronic health records (EHRs) are a rich source of information on human diseases, but the information is variably structured, fragmented, curated using different coding systems, and collected for purposes other than medical research. We describe an approach for developing, validating, and sharing reproducible phenotypes from national structured EHR in the United Kingdom with applications for translational research.<h4>Materials and methods</h4>We implemented a rule-based phenotyping framework, with up to 6 approaches of validation. We applied our framework to a sample of 15 million individuals in a national EHR data source (population-based primary care, all ages) linked to hospitalization and death records in England. Data comprised continuous measurements (for example, blood pressure; medication information; coded diagnoses, symptoms, procedures, and referrals), recorded using 5 controlled clinical terminologies: (1) read (primary care, subset of SNOMED-CT [Systematized Nomenclature of Medicine Clinical Terms]), (2) International Classification of Diseases-Ninth Revision and Tenth Revision (secondary care diagnoses and cause of mortality), (3) Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures, Fourth Revision (hospital surgical procedures), and (4) DM+D prescription codes.<h4>Results</h4>Using the CALIBER phenotyping framework, we created algorithms for 51 diseases, syndromes, biomarkers, and lifestyle risk factors and provide up to 6 validation approaches. The EHR phenotypes are curated in the open-access CALIBER Portal (https://www.caliberresearch.org/portal) and have been used by 40 national and international research groups in 60 peer-reviewed publications.<h4>Conclusions</h4>We describe a UK EHR phenomics approach within the CALIBER EHR data platform with initial evidence of validity and use, as an important step toward international use of UK EHR data for health research.",,doi:https://doi.org/10.1093/jamia/ocz105; doi:https://doi.org/10.1093/jamia/ocz105; html:https://europepmc.org/articles/PMC6857510; pdf:https://europepmc.org/articles/PMC6857510?pdf=render
 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.",,pdf:https://academic.oup.com/braincomms/article-pdf/3/4/fcab241/41829863/fcab241.pdf; doi:https://doi.org/10.1093/braincomms/fcab241; html:https://europepmc.org/articles/PMC8688778; pdf:https://europepmc.org/articles/PMC8688778?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; Temporal Bipartite Network; Ehr Data Linkage,,,"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; doi:https://doi.org/10.1016/j.jbi.2022.104010; html:https://europepmc.org/articles/PMC8894882
@@ -966,33 +966,33 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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.",,pdf:https://www.nature.com/articles/s41467-022-35321-2.pdf; doi:https://doi.org/10.1038/s41467-022-35321-2; html:https://europepmc.org/articles/PMC9772225; pdf:https://europepmc.org/articles/PMC9772225?pdf=render
 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,,"<h4>Background and objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0220771&type=printable; doi:https://doi.org/10.1371/journal.pone.0220771; html:https://europepmc.org/articles/PMC6688802; pdf:https://europepmc.org/articles/PMC6688802?pdf=render
 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.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.1016032/pdf; doi:https://doi.org/10.3389/fcvm.2022.1016032; html:https://europepmc.org/articles/PMC9681217; pdf:https://europepmc.org/articles/PMC9681217?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,,,"<h4>Introduction</h4>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).<h4>Methods</h4>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).<h4>Results</h4>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).<h4>Conclusion</h4>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
 34506014,https://doi.org/10.1007/s11605-020-04612-8,"The Impact of a Centralised Pancreatic Cancer Service: a Case Study of Wales, UK.","Mowbray NG, Griffiths R, Akbari A, Hutchings H, Jenkins G, Al-Sarireh B.",,Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract,2022,2021-09-10,N,Pancreatic cancer; Pancreatic Surgery; Centralisation,,,"<h4>Introduction</h4>The centralisation of pancreatic cancer (PC) services still varies worldwide. This study aimed to assess the impact that a centralisation has had on patients in South Wales, UK.<h4>Methods</h4>A retrospective cohort analysis of patients in South Wales, UK, with PC prior to (2004-2009), and after (2010-2014) the formation of a specialist centre. Patients were identified using record linkage of electronic health records.<h4>Results</h4>The overall survival (OS) of all 3413 patients with PC increased from a median (IQR) 10 weeks (3-31) to 11 weeks (4-35), p = 0.038, after centralisation. The OS of patients undergoing surgical resection or chemotherapy alone did not improve (93 weeks (39-203) vs. 90 weeks (50-95), p = 0.764 and 33 weeks (20-57) vs. 33 weeks (19-58), p = 0.793). Surgical resection and chemotherapy rates increased (6.1% vs. 9.2%, p < 0.001 and 19.7% vs. 27.0%, p < 0.001). The 30-day mortality rate trended downwards (7.2% vs. 3.6%, p = 0.186). The percentage of patients who received no treatment reduced (75.2% vs. 69.6%, p < 0.001).<h4>Conclusion</h4>The centralisation of PC services in South Wales is associated with a small increase in OS and a larger increase in PC treatment utilisation. It is concerning that many patients still fail to receive any treatments.",,doi:https://doi.org/10.1007/s11605-020-04612-8
+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,,,"<h4>Introduction</h4>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).<h4>Methods</h4>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).<h4>Results</h4>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).<h4>Conclusion</h4>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
 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,,,"<h4>Background</h4>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.<h4>Aim</h4>To investigate the association between OACs and COVID-19 outcomes in those with atrial fibrillation and a CHA<sub>2</sub>DS<sub>2</sub>-VASc score of 2.<h4>Design and setting</h4>On behalf of NHS England, a population-based cohort study was conducted.<h4>Method</h4>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.<h4>Results</h4>Of 71 103 people with atrial fibrillation and a CHA<sub>2</sub>DS<sub>2</sub>-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.<h4>Conclusion</h4>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.",,pdf:https://bjgp.org/content/bjgp/early/2022/04/19/BJGP.2021.0689.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0689; html:https://europepmc.org/articles/PMC9037187; pdf:https://europepmc.org/articles/PMC9037187?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,,,"<b>Background:</b> 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. <b>Objective:</b> To define the CMR radiomics signatures for IHD and cerebrovascular disease and study their incremental value for disease discrimination over conventional CMR indices. <b>Methods:</b> We analysed CMR images of UK Biobank's subjects with pre-existing IHD, ischaemic cerebrovascular disease, myocardial infarction (MI), and ischaemic stroke (IS) (<i>n</i> = 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 <i>t</i>-test for statistical significance. A third model combining both radiomics and conventional indices was also evaluated. <b>Results:</b> 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. <b>Conclusions:</b> 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.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.716577/pdf; doi:https://doi.org/10.3389/fcvm.2021.716577; html:https://europepmc.org/articles/PMC8494975; pdf:https://europepmc.org/articles/PMC8494975?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,,,"<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-01940-7; doi:https://doi.org/10.1186/s12916-021-01940-7; html:https://europepmc.org/articles/PMC8022365; pdf:https://europepmc.org/articles/PMC8022365?pdf=render
 35188950,https://doi.org/10.1001/jamaneurol.2021.5420,Risk Factors and Prognosis of Early Posttraumatic Seizures in Moderate to Severe Traumatic Brain Injury.,"Laing J, Gabbe B, Chen Z, Perucca P, Kwan P, O'Brien TJ.",,JAMA neurology,2022,2022-04-01,N,,,,"<h4>Importance</h4>Early posttraumatic seizures (EPS) that may occur following a traumatic brain injury (TBI) are associated with poorer outcomes and development of posttraumatic epilepsy (PTE).<h4>Objective</h4>To evaluate risk factors for EPS, associated morbidity and mortality, and contribution to PTE.<h4>Design, setting, and participants</h4>Data were collected from an Australian registry-based cohort study of adults (age ≥18 years) with moderate to severe TBI from January 2005 to December 2019, with 2-year follow-up. The statewide trauma registry, conducted on an opt-out basis in Victoria (population 6.5 million), had 15 152 patients with moderate to severe TBI identified via Abbreviated Injury Scale (AIS) head severity score, with an opt-out rate less than 0.5% (opt-out n = 136).<h4>Main outcomes and measures</h4>EPS were identified via International Statistical Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM) codes recorded after the acute admission. Outcome measures also included in-hospital metrics, 2-year outcomes including PTE, and post-discharge mortality. Adaptive least absolute shrinkage and selection operator (LASSO) regression was used to build a prediction model for risk factors of EPS.<h4>Results</h4>Among the 15 152 participants (10 457 [69%] male; median [IQR] age, 60 [35-79] y), 416 (2.7%) were identified with EPS, including 27 (0.2%) with status epilepticus. Significant risk factors on multivariable analysis for developing EPS were younger age, higher Charlson Comorbidity Index, TBI sustained from a low fall, subdural hemorrhage, subarachnoid hemorrhage, higher Injury Severity Score, and greater head injury severity, measured using the AIS and Glasgow Coma Score. After adjustment for confounders, EPS were associated with increased ICU admission and ICU length of stay, ventilation and duration, hospital length of stay, and discharge to inpatient rehabilitation rather than home, but not in-hospital mortality. Outcomes in TBI admission survivors at 24 months, including mortality (relative risk [RR] = 2.14; 95% CI, 1.32-3.46; P = .002), development of PTE (RR = 2.91; 95% CI, 2.22-3.81; P < .001), and use of antiseizure medications (RR = 2.44; 95% CI, 1.98-3.02; P < .001), were poorer for cases with EPS after adjustment for confounders. The prediction model for EPS had an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.66-0.79), sensitivity of 66%, and specificity of 73% in the validation set.<h4>Discussion</h4>We identified important risk factors for EPS following moderate to severe TBI. Early posttraumatic seizures were associated with longer ICU and hospital admissions, ICU ventilation, and poorer 24-month outcomes including mortality and development of PTE.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861899; doi:https://doi.org/10.1001/jamaneurol.2021.5420; html:https://europepmc.org/articles/PMC8861899; doi:https://doi.org/10.1001/jamaneurol.2021.5420
 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,,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14444; doi:https://doi.org/10.1002/ehf2.14444; html:https://europepmc.org/articles/PMC10375103; pdf:https://europepmc.org/articles/PMC10375103?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,,,"<h4>Aims</h4>To determine differences in the management of diabetic kidney disease (DKD) relevant to patient sex, ethnicity and socio-economic group in UK primary care.<h4>Methods</h4>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.<h4>Results</h4>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), HbA<sub>1c</sub> : 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 HbA<sub>1c</sub> : 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).<h4>Conclusions</h4>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; doi:https://doi.org/10.1111/dme.15153
 35642867,https://doi.org/10.1111/bjhp.12606,"Perceived threat of COVID-19, attitudes towards vaccination, and vaccine hesitancy: A prospective longitudinal study in the UK.","Phillips R, Gillespie D, Hallingberg B, Evans J, Taiyari K, Torrens-Burton A, Cannings-John R, Williams D, Sheils E, Ashfield-Watt P, Akbari A, Hughes K, Thomas-Jones E, James D, Wood F.",,British journal of health psychology,2022,2022-06-01,Y,Risk Perception; Behaviour Change; Vaccine Hesitancy; Covid-19; Sars Cov2,,,"<h4>Objectives</h4>Using the Health Belief Model as a conceptual framework, we investigated the association between attitudes towards COVID-19, COVID-19 vaccinations, and vaccine hesitancy and change in these variables over a 9-month period in a UK cohort.<h4>Methods</h4>The COPE study cohort (n = 11,113) was recruited via an online survey at enrolment in March/April 2020. The study was advertised via the HealthWise Wales research registry and social media. Follow-up data were available for 6942 people at 3 months (June/July 2020) and 5037 at 12 months (March/April 2021) post-enrolment. Measures included demographics, perceived threat of COVID-19, perceived control, intention to accept or decline a COVID-19 vaccination, and attitudes towards vaccination. Logistic regression models were fitted cross-sectionally at 3 and 12 months to assess the association between motivational factors and vaccine hesitancy. Longitudinal changes in motivational variables for vaccine-hesitant and non-hesitant groups were examined using mixed-effect analysis of variance models.<h4>Results</h4>Fear of COVID-19, perceived susceptibility to COVID-19, and perceived personal control over COVID-19 infection transmission decreased between the 3- and 12-month surveys. Vaccine hesitancy at 12 months was independently associated with low fear of the disease and more negative attitudes towards COVID-19 vaccination. Specific barriers to COVID-19 vaccine uptake included concerns about safety and efficacy in light of its rapid development, mistrust of government and pharmaceutical companies, dislike of coercive policies, and perceived lack of relaxation in COVID-19-related restrictions as the vaccination programme progressed.<h4>Conclusions</h4>Decreasing fear of COVID-19, perceived susceptibility to the disease, and perceptions of personal control over reducing infection-transmission may impact future COVID-19 vaccination uptake.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa60128/Download/60128__24479__4d74009536e649b0b17180e2bfd80435.pdf; doi:https://doi.org/10.1111/bjhp.12606; html:https://europepmc.org/articles/PMC9347957; pdf:https://europepmc.org/articles/PMC9347957?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,,,"<h4>Aims</h4>To determine differences in the management of diabetic kidney disease (DKD) relevant to patient sex, ethnicity and socio-economic group in UK primary care.<h4>Methods</h4>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.<h4>Results</h4>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), HbA<sub>1c</sub> : 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 HbA<sub>1c</sub> : 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).<h4>Conclusions</h4>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; doi:https://doi.org/10.1111/dme.15153
 37669576,https://doi.org/10.1016/j.schres.2023.08.024,Unraveling ethnic disparities in antipsychotic prescribing among patients with psychosis: A retrospective cohort study based on electronic clinical records.,"Wang T, Codling D, Bhugra D, Msosa Y, Broadbent M, Patel R, Roberts A, McGuire P, Stewart R, Dobson R, Harland R.",,Schizophrenia research,2023,2023-09-03,N,Psychopharmacology; Psychosis; Ethnicity; Electronic Health Records; Healthcare Inequality; Antipsychotic Prescription,,,"<h4>Background</h4>Previous studies have shown mixed evidence on ethnic disparities in antipsychotic prescribing among patients with psychosis in the UK, partly due to small sample sizes. This study aimed to examine the current state of antipsychotic prescription with respect to patient ethnicity among the entire population known to a large UK mental health trust with non-affective psychosis, adjusting for multiple potential risk factors.<h4>Methods</h4>This retrospective cohort study included all patients (N = 19,291) who were aged 18 years or over at their first diagnoses of non-affective psychosis (identified with the ICD-10 codes of F20-F29) recorded in electronic health records (EHRs) at the South London and Maudsley NHS Trust until March 2021. The most recently recorded antipsychotic treatments and patient attributes were extracted from EHRs, including both structured fields and free-text fields processed using natural language processing applications. Multivariable logistic regression models were used to calculate the odds ratios (OR) for antipsychotic prescription according to patient ethnicity, adjusted for multiple potential contributing factors, including demographic (age and gender), clinical (diagnoses, duration of illness, service use and history of cannabis use), socioeconomic factors (level of deprivation and own-group ethnic density in the area of residence) and temporal changes in clinical guidelines (date of prescription).<h4>Results</h4>The cohort consisted of 43.10 % White, 8.31 % Asian, 40.80 % Black, 2.64 % Mixed, and 5.14 % of patients from Other ethnicity. Among them, 92.62 % had recorded antipsychotic receipt, where 24.05 % for depot antipsychotics and 81.72 % for second-generation antipsychotic (SGA) medications. Most ethnic minority groups were not significantly different from White patients in receiving any antipsychotic. Among those receiving antipsychotic prescribing, Black patients were more likely to be prescribed depot (adjusted OR 1.29, 95 % confidence interval (CI) 1.14-1.47), but less likely to receive SGA (adjusted OR 0.85, 95 % CI 0.74-0.97), olanzapine (OR 0.82, 95 % CI 0.73-0.92) and clozapine (adjusted OR 0.71, 95 % CI 0.6-0.85) than White patients. All the ethnic minority groups were less likely to be prescribed olanzapine than the White group.<h4>Conclusions</h4>Black patients with psychosis had a distinct pattern in antipsychotic prescription, with less use of SGA, including olanzapine and clozapine, but more use of depot antipsychotics, even when adjusting for the effects of multiple demographic, clinical and socioeconomic factors. Further research is required to understand the sources of these ethnic disparities and eliminate care inequalities.",,doi:https://doi.org/10.1016/j.schres.2023.08.024
 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,,,"<h4>Purpose</h4>This study aimed to characterise recovery from pain and mental health symptoms, and identify whether treatment use facilitates recovery.<h4>Methods</h4>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 (<i>n</i> = 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.<h4>Results</h4>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.<h4>Conclusions</h4>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
+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.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127079; 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
 37658971,https://doi.org/10.1007/s11897-023-00626-w,Multimorbidity in Heart Failure: Leveraging Cluster Analysis to Guide Tailored Treatment Strategies.,"van de Veerdonk MC, Savarese G, Handoko ML, Beulens JWJ, Asselbergs F, Uijl A.",,Current heart failure reports,2023,2023-09-02,Y,Clustering; Phenotyping; Heart Failure; Machine Learning; Treatment Response; Precision Medicine,,,"<h4>Review purpose</h4>This review summarises key findings on treatment effects within phenotypical clusters of patients with heart failure (HF), making a distinction between patients with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF).<h4>Findings</h4>Treatment response differed among clusters; ACE inhibitors were beneficial in all HFrEF phenotypes, while only some studies show similar beneficial prognostic effects in HFpEF patients. Beta-blockers had favourable effects in all HFrEF patients but not in HFpEF phenotypes and tended to worsen prognosis in older, cardiorenal patients. Mineralocorticoid receptor antagonists had more favourable prognostic effects in young, obese males and metabolic HFpEF patients. While a phenotype-guided approach is a promising solution for individualised treatment strategies, there are several aspects that still require improvements before such an approach could be implemented in clinical practice. Stronger evidence from clinical trials and real-world data may assist in establishing a phenotype-guided treatment approach for patient with HF in the future.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00626-w.pdf; doi:https://doi.org/10.1007/s11897-023-00626-w; html:https://europepmc.org/articles/PMC10589138; pdf:https://europepmc.org/articles/PMC10589138?pdf=render
 37884627,https://doi.org/10.1038/s41591-023-02608-w,The value of standards for health datasets in artificial intelligence-based applications.,"Arora A, Alderman JE, Palmer J, Ganapathi S, Laws E, McCradden MD, Oakden-Rayner L, Pfohl SR, Ghassemi M, McKay F, Treanor D, Rostamzadeh N, Mateen B, Gath J, Adebajo AO, Kuku S, Matin R, Heller K, Sapey E, Sebire NJ, Cole-Lewis H, Calvert M, Denniston A, Liu X.",,Nature medicine,2023,2023-10-26,N,,,,"Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative).",,doi:https://doi.org/10.1038/s41591-023-02608-w
-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.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127079; 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
 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.",,pdf:https://www.ajtmh.org/downloadpdf/journals/tpmd/105/3/article-p561.pdf; doi:https://doi.org/10.4269/ajtmh.21-0482; html:https://europepmc.org/articles/PMC8592367; pdf:https://europepmc.org/articles/PMC8592367?pdf=render
 37679551,https://doi.org/10.1038/s41590-023-01635-6,Author Correction: Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.,"Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman ÅK, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, Võsa U, Esko T, Hayward C, Johansson Å, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Landén M, Wilson JF, Siegbahn A, Wallentin L, Mälarstig A, Butterworth AS, Peters JE.",,Nature immunology,2023,2023-11-01,Y,,,,,,doi:https://doi.org/10.1038/s41590-023-01635-6; html:https://europepmc.org/articles/PMC10602847; pdf:https://europepmc.org/articles/PMC10602847?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopengastro.bmj.com/content/bmjgast/10/1/e001139.full.pdf; doi:https://doi.org/10.1136/bmjgast-2023-001139; html:https://europepmc.org/articles/PMC10230891; pdf:https://europepmc.org/articles/PMC10230891?pdf=render
 31477110,https://doi.org/10.1186/s12913-019-4286-8,Weekend admissions and mortality for major acute disorders across England and Wales: record linkage cohort studies.,"Roberts SE, John A, Lewis KE, Brown J, Lyons RA, Williams JG.",,BMC health services research,2019,2019-09-02,Y,Mortality; Weekend Admissions; Acute Disorders,Improving Public Health,,"<h4>Background</h4>To establish which major disorders are susceptible to increased mortality following acute admissions on weekends, compared with week days, and how this may be explained.<h4>Methods</h4>Cohorts based on national administrative inpatient and mortality data for 14,168,443 hospitalised patients in England and 913,068 in Wales who were admitted for 66 disorders that were associated with at least 200 deaths within 30 days of acute admission. The main outcome measure was the weekend mortality effect (defined as the conventional mortality odds ratio for admissions on weekends compared with week days).<h4>Results</h4>There were large, statistically significant weekend mortality effects (> 20%) in England for 22 of the 66 conditions and in both countries for 14. These 14 were 4 of 13 cancers (oesophageal, colorectal, lung and lymphomas); 4 of 13 circulatory disorders (angina, abdominal aortic aneurysm, peripheral vascular disease and arterial embolism & thrombosis); one of 8 respiratory disorders (pleural effusion); 2 of 12 gastrointestinal disorders (alcoholic and other liver disease); 2 of 3 ageing-related disorders (Alzheimer's disease and dementia); none of 7 trauma conditions; and one of 10 other disorders (acute renal failure). Across the disorders, 64% of the variation in weekend mortality effects in England and Wales was explained by reductions in admission rates at weekends and the medical disease category.<h4>Conclusions</h4>The effect of weekend admission on 30 day mortality is seen mainly for cancers, some circulatory disorders, liver disease and a few other conditions which are mainly ageing- or cancer-related. Most of the increased mortality is associated with reduced admission rates at weekends and the medical disease category.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-019-4286-8; doi:https://doi.org/10.1186/s12913-019-4286-8; html:https://europepmc.org/articles/PMC6720086; pdf:https://europepmc.org/articles/PMC6720086?pdf=render
-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,,,,"<h4>Background</h4>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.<h4>Materials and methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>This global study found no significant difference in the 30-day morbidity and mortality of SG, RYGB, and OAGB in propensity score-matched cohorts.",,pdf:https://www.nature.com/articles/s41366-021-01048-1.pdf; doi:https://doi.org/10.1038/s41366-021-01048-1; html:https://europepmc.org/articles/PMC8671878; pdf:https://europepmc.org/articles/PMC8671878?pdf=render
 32908284,https://doi.org/10.1038/s41591-020-1037-7,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, SPIRIT-AI and CONSORT-AI Steering Group, SPIRIT-AI and CONSORT-AI Consensus Group.",,Nature medicine,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.",,pdf:https://www.nature.com/articles/s41591-020-1037-7.pdf; doi:https://doi.org/10.1038/s41591-020-1037-7; html:https://europepmc.org/articles/PMC7598944; pdf:https://europepmc.org/articles/PMC7598944?pdf=render
+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,,,,"<h4>Background</h4>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.<h4>Materials and methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>This global study found no significant difference in the 30-day morbidity and mortality of SG, RYGB, and OAGB in propensity score-matched cohorts.",,pdf:https://www.nature.com/articles/s41366-021-01048-1.pdf; doi:https://doi.org/10.1038/s41366-021-01048-1; html:https://europepmc.org/articles/PMC8671878; pdf:https://europepmc.org/articles/PMC8671878?pdf=render
 32908283,https://doi.org/10.1038/s41591-020-1034-x,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.",,Nature medicine,2020,2020-09-09,Y,,,,"The CONSORT 2010 statement provides minimum guidelines for reporting randomized 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.",,pdf:https://www.nature.com/articles/s41591-020-1034-x.pdf; doi:https://doi.org/10.1038/s41591-020-1034-x; html:https://europepmc.org/articles/PMC7598943; pdf:https://europepmc.org/articles/PMC7598943?pdf=render
-36932161,https://doi.org/10.1038/s41433-023-02478-z,Evaluating patient-reported outcome measures (PROMs) for future clinical trials in adult patients with optic neuritis.,"Panthagani J, O'Donovan C, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston AK, Moore DJ, Braithwaite T.",,"Eye (London, England)",2023,2023-03-17,Y,,,,"<h4>Objective</h4>To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.<h4>Methods</h4>We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).<h4>Results</h4>From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.<h4>Conclusion</h4>There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.",,pdf:https://www.nature.com/articles/s41433-023-02478-z.pdf; doi:https://doi.org/10.1038/s41433-023-02478-z; html:https://europepmc.org/articles/PMC10022552; pdf:https://europepmc.org/articles/PMC10022552?pdf=render
 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.",,pdf:http://www.thelancet.com/article/S2589750020303174/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30317-4
+36932161,https://doi.org/10.1038/s41433-023-02478-z,Evaluating patient-reported outcome measures (PROMs) for future clinical trials in adult patients with optic neuritis.,"Panthagani J, O'Donovan C, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston AK, Moore DJ, Braithwaite T.",,"Eye (London, England)",2023,2023-03-17,Y,,,,"<h4>Objective</h4>To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.<h4>Methods</h4>We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).<h4>Results</h4>From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.<h4>Conclusion</h4>There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.",,pdf:https://www.nature.com/articles/s41433-023-02478-z.pdf; doi:https://doi.org/10.1038/s41433-023-02478-z; html:https://europepmc.org/articles/PMC10022552; pdf:https://europepmc.org/articles/PMC10022552?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 <i>trendbreaker</i>. 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; doi:https://doi.org/10.1098/rstb.2020.0266; html:https://europepmc.org/articles/PMC8165581; pdf:https://europepmc.org/articles/PMC8165581?pdf=render
 33344049,https://doi.org/10.1167/tvst.9.13.5,Automated Segmentation of Optical Coherence Tomography Angiography Images: Benchmark Data and Clinically Relevant Metrics.,"Giarratano Y, Bianchi E, Gray C, Morris A, MacGillivray T, Dhillon B, Bernabeu MO.",,Translational vision science & technology,2020,2020-12-03,Y,Automated Segmentation; Retinal Vasculature; Optical Coherence Tomography Angiography,,,"<h4>Purpose</h4>To generate the first open dataset of retinal parafoveal optical coherence tomography angiography (OCTA) images with associated ground truth manual segmentations, and to establish a standard for OCTA image segmentation by surveying a broad range of state-of-the-art vessel enhancement and binarization procedures.<h4>Methods</h4>Handcrafted filters and neural network architectures were used to perform vessel enhancement. Thresholding methods and machine learning approaches were applied to obtain the final binarization. Evaluation was performed by using pixelwise metrics and newly proposed topological metrics. Finally, we compare the error in the computation of clinically relevant vascular network metrics (e.g., foveal avascular zone area and vessel density) across segmentation methods.<h4>Results</h4>Our results show that, for the set of images considered, deep learning architectures (U-Net and CS-Net) achieve the best performance (Dice = 0.89). For applications where manually segmented data are not available to retrain these approaches, our findings suggest that optimally oriented flux (OOF) is the best handcrafted filter (Dice = 0.86). Moreover, our results show up to 25% differences in vessel density accuracy depending on the segmentation method used.<h4>Conclusions</h4>In this study, we derive and validate the first open dataset of retinal parafoveal OCTA images with associated ground truth manual segmentations. Our findings should be taken into account when comparing the results of clinical studies and performing meta-analyses. Finally, we release our data and source code to support standardization efforts in OCTA image segmentation.<h4>Translational relevance</h4>This work establishes a standard for OCTA retinal image segmentation and introduces the importance of evaluating segmentation performance in terms of clinically relevant metrics.",,doi:https://doi.org/10.1167/tvst.9.13.5; doi:https://doi.org/10.1167/tvst.9.13.5; html:https://europepmc.org/articles/PMC7718823; pdf:https://europepmc.org/articles/PMC7718823?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,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/edm2.309; doi:https://doi.org/10.1002/edm2.309; html:https://europepmc.org/articles/PMC8754243; pdf:https://europepmc.org/articles/PMC8754243?pdf=render
 31748543,https://doi.org/10.1038/s41398-019-0613-4,Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5.,"Johnston KJA, Adams MJ, Nicholl BI, Ward J, Strawbridge RJ, McIntosh AM, Smith DJ, Bailey MES.",,Translational psychiatry,2019,2019-11-20,Y,,Understanding the Causes of Disease,,"Chronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the conditional false discovery rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located within SLC16A7 on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouring LINC01360, LRRIQ3, FPGT and FPGT-TNNI3K, or within/close to LRFN5 on chromosome 14. The SNPs associated with both outcomes were also located within LRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain.","This study aimed to identify parts of the genome that cause chronic pain (self-reported as lasting 3+ months), or major depressive disorder (MDD) and to investigate if these two conditions share common genetic causes. They identified 11 different parts of the genome where a specific change (SNP) was linked to chronic pain (6 parts of the genome), MDD (9 parts), or symptoms shared by both conditions (4 parts). The results also suggest that one of parts of the genome that causes chronic pain may influence the development of MDD (but not vice versa), including through lifestyle factors.",pdf:https://www.nature.com/articles/s41398-019-0613-4.pdf; doi:https://doi.org/10.1038/s41398-019-0613-4; html:https://europepmc.org/articles/PMC6868167; pdf:https://europepmc.org/articles/PMC6868167?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,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/edm2.309; doi:https://doi.org/10.1002/edm2.309; html:https://europepmc.org/articles/PMC8754243; pdf:https://europepmc.org/articles/PMC8754243?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,,,,,,pdf:https://europepmc.org/articles/pmc7592804?pdf=render; doi:https://doi.org/10.7326/M20-4986; html:https://europepmc.org/articles/PMC7592804; pdf:https://europepmc.org/articles/PMC7592804?pdf=render
 32575372,https://doi.org/10.3390/genes11060668,A Knowledge-Based Machine Learning Approach to Gene Prioritisation in Amyotrophic Lateral Sclerosis.,"Bean DM, Al-Chalabi A, Dobson RJB, Iacoangeli A.",,Genes,2020,2020-06-19,Y,Amyotrophic Lateral Sclerosis; Motor Neurone Disease; Machine Learning; Gene Discovery; Gene Prioritisation; Knowledge Graph,,,"Amyotrophic lateral sclerosis is a neurodegenerative disease of the upper and lower motor neurons resulting in death from neuromuscular respiratory failure, typically within two to five years of first symptoms. Several rare disruptive gene variants have been associated with ALS and are responsible for about 15% of all cases. Although our knowledge of the genetic landscape of this disease is improving, it remains limited. Machine learning models trained on the available protein-protein interaction and phenotype-genotype association data can use our current knowledge of the disease genetics for the prediction of novel candidate genes. Here, we describe a knowledge-based machine learning method for this purpose. We trained our model on protein-protein interaction data from IntAct, gene function annotation from Gene Ontology, and known disease-gene associations from DisGeNet. Using several sets of known ALS genes from public databases and a manual review as input, we generated a list of new candidate genes for each input set. We investigated the relevance of the predicted genes in ALS by using the available summary statistics from the largest ALS genome-wide association study and by performing functional and phenotype enrichment analysis. The predicted sets were enriched for genes associated with other neurodegenerative diseases known to overlap with ALS genetically and phenotypically, as well as for biological processes associated with the disease. Moreover, using ALS genes from ClinVar and our manual review as input, the predicted sets were enriched for ALS-associated genes (ClinVar <i>p</i> = 0.038 and manual review <i>p</i> = 0.060) when used for gene prioritisation in a genome-wide association study.",,pdf:https://www.mdpi.com/2073-4425/11/6/668/pdf?version=1592549363; doi:https://doi.org/10.3390/genes11060668; html:https://europepmc.org/articles/PMC7349022; pdf:https://europepmc.org/articles/PMC7349022?pdf=render
 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,,,"<h4>Objectives</h4>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.<h4>Design</h4>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.<h4>Setting</h4>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.<h4>Participants</h4>Patients with any CHD procedure recorded in NCHDA between April 2000 and March 2017 from public hospitals.<h4>Primary and secondary outcome measures</h4>Primary: number of linked records, number of unique patients and number of generated spells of care. Secondary: quality and completeness of linkage.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e057343.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057343; html:https://europepmc.org/articles/PMC9121475; pdf:https://europepmc.org/articles/PMC9121475?pdf=render
@@ -1005,8 +1005,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 37798805,https://doi.org/10.1186/s13063-023-07576-7,"Medicines and Healthcare products Regulatory Agency's ""Consultation on proposals for legislative changes for clinical trials"": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.","Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.",,Trials,2023,2023-10-05,Y,Legislation; data sharing; Consultation,,,"In the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals ""to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines"". The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research. Two topics arose frequently in the discussion: the emphasis on legislation, and the absence of questions on data sharing. It is our opinion that the proposals rely heavily on legislation to change practice. However, clinical trials are heterogeneous, and as a result some trials will struggle to comply with all of the proposed legislation. Furthermore, adaptive design clinical trials are even more heterogeneous than their non-adaptive counterparts, and face more challenges. Consequently, it is possible that increased legislation could have a greater negative impact on adaptive designs than non-adaptive designs. Overall, we are sceptical that the introduction of legislation will achieve the desired outcomes, with some exceptions. Meanwhile the topic of data sharing - making anonymised individual-level clinical trial data available to other investigators for further use - is entirely absent from the proposals and the consultation in general. However, as an aspect of the wider concept of open science and reproducible research, data sharing is an increasingly important aspect of clinical trials. The benefits of data sharing include faster innovation, improved surveillance of drug safety and effectiveness and decreasing participant exposure to unnecessary risk. There are already a number of UK-focused documents that discuss and encourage data sharing, for example, the Concordat on Open Research Data and the Medical Research Council's Data Sharing Policy. We strongly suggest that data sharing should be the norm rather than the exception, and hope that the forthcoming proposals on clinical trials invite discussion on this important topic.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07576-7; doi:https://doi.org/10.1186/s13063-023-07576-7; html:https://europepmc.org/articles/PMC10552399; pdf:https://europepmc.org/articles/PMC10552399?pdf=render
 35616501,https://doi.org/10.1177/14791641221088824,Sleep behaviours and associated habits and the progression of pre-diabetes to type 2 diabetes mellitus in adults: A systematic review and meta-analysis.,"Mostafa SA, Mena SC, Antza C, Balanos G, Nirantharakumar K, Tahrani AA.",,Diabetes & vascular disease research,2022,2022-05-01,Y,Type 2 diabetes mellitus; Sleep disorders; Systematic review; Pre-diabetes,,,"<h4>Introduction</h4>Certain sleep behaviours increase risk of type 2 diabetes mellitus (T2DM) in the general population, but whether they contribute to the progression from pre-diabetes to T2DM is uncertain. We conducted a systematic review to assess this.<h4>Methods</h4>Structured searches were performed on bibliographic databases (MEDLINE, EMBASE and CINAHL) from inception to 26/04/2021 for longitudinal studies/trials consisting of adults⩾18 years with pre-diabetes and sleep behaviours (short or long sleep duration (SD), late chronotype, insomnia, obstructive sleep apnoea, daytime napping and/or night-shift employment) that reported on incident T2DM or glycaemic changes. The Newcastle-Ottawa Scale was used for quality assessment.<h4>Results</h4>Six studies were included. Meta-analysis of three studies (<i>n</i> = 20,139) demonstrated that short SD was associated with greater risk of progression to T2DM, hazard ratio (HR) 1.59 (95% CI 1.29-1.97), I<sup>2</sup> heterogeneity score 0%, <i>p</i> < 0.0001, but not for long SD, HR 1.50 (0.86-2.62), I<sup>2</sup> heterogeneity 77%, <i>p</i> = 0.15. The systematic review showed insomnia and night-shift duty were associated with higher progression to T2DM. Studies were rated as moderate-to-high quality.<h4>Conclusions</h4>Progression from pre-diabetes to T2DM increases with short SD, but only limited data exists for insomnia and night-shift duty. Whether manipulating sleep could reduce progression from pre-diabetes to T2DM needs to be examined.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152198; doi:https://doi.org/10.1177/14791641221088824; html:https://europepmc.org/articles/PMC9152198; pdf:https://europepmc.org/articles/PMC9152198?pdf=render
 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.",,pdf:http://www.thelancet.com/article/S2589750020302193/pdf; 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
-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,,,"<h4>Objective</h4>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).<h4>Design</h4>National observational study of administrative hospital data.<h4>Setting</h4>National Health Service hospitals in England.<h4>Study population</h4>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).<h4>Main exposure</h4>Procedure date (2020/2021 vs 2019/2020).<h4>Main outcomes</h4>Numbers and timing (age in months) of first primary CLP procedures.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/6/e071973.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-071973; html:https://europepmc.org/articles/PMC10276964; pdf:https://europepmc.org/articles/PMC10276964?pdf=render
 35271547,https://doi.org/10.1097/ta.0000000000003592,Does patient preference for online or telephone follow-up impact on response rates and data completeness following injury?,"Gabbe BJ, Hart MJ, Brown A, McLellan S, Morgan MJ, Beck B, de Steiger RS, Cameron PA.",,The journal of trauma and acute care surgery,2022,2022-03-08,N,,,,"<h4>Background</h4>Routine collection of patient-reported outcomes is needed to better understand recovery, benchmark between trauma centers and systems, and monitor outcomes over time. A key component of follow-up methodology is the mode of administration of outcome measures with multiple options available. We aimed to quantify patient preference and compare the response rates and data completeness for telephone and online completion in trauma patients.<h4>Methods</h4>A registry-based cohort study of adult (16 years and older) patients registered to the Victorian State Trauma Registry and Victorian Orthopedic Trauma Outcomes Registry from April 2020 to December 2020 was undertaken. Survivors to discharge were contacted by telephone and offered the option of telephone or online completion of 6-month follow-up using the five-level EuroQol five-dimension (EQ-5D-5L) questionnaire and the 12-item World Health Organization Disability Assessment Schedule (WHODAS). The online and telephone groups were compared for differences in characteristics, follow-up rates, and data completeness. Multivariable logistic regression was used to identify predictors of choosing online completion.<h4>Results</h4>Of the 3,886 patients, 51% (n = 1,994) chose online follow-up, and the follow-up rates were lower for online (77%), compared with telephone (89%), follow-up. Younger age, higher socioeconomic status, and preferred language other than English were associated with higher adjusted odds of choosing online completion. Admission to intensive care was associated with lower adjusted odds of choosing online completion. Completion rate for the EQ-5D-5L utility score was 97% for both groups. A valid total 12-WHODAS score could be calculated for 63% of online respondents compared with 86% for the telephone group.<h4>Conclusion</h4>More than half of trauma patients opted for online completion. Completion rates did differ depending on the questionnaire and telephone follow-up rates were higher. Nevertheless, given the wide diversity of the trauma population, the high rate of online uptake, and potential resource constraints, the study findings largely support the use of dual methods for follow-up.<h4>Level of evidence</h4>Prognostic/Epidemiological, Level III.",,doi:https://doi.org/10.1097/TA.0000000000003592
+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,,,"<h4>Objective</h4>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).<h4>Design</h4>National observational study of administrative hospital data.<h4>Setting</h4>National Health Service hospitals in England.<h4>Study population</h4>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).<h4>Main exposure</h4>Procedure date (2020/2021 vs 2019/2020).<h4>Main outcomes</h4>Numbers and timing (age in months) of first primary CLP procedures.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/6/e071973.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-071973; html:https://europepmc.org/articles/PMC10276964; pdf:https://europepmc.org/articles/PMC10276964?pdf=render
 37118525,https://doi.org/10.1038/s43587-022-00328-3,Strong peak immunogenicity but rapid antibody waning following third vaccine dose in older residents of care homes.,"Tut G, Lancaster T, Krutikov M, Sylla P, Bone D, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Kaur N, Tut E, Bruton R, Wu MY, Harvey R, Carr EJ, Crick COVID Immunity Pipeline, Beale R, Stirrup O, Shrotri M, Azmi B, Fuller C, Baynton V, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,Nature aging,2023,2023-01-20,Y,,,,"Third-dose coronavirus disease 2019 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable older people who exhibit suboptimal responses after primary vaccination series. This observational study, which was carried out by the VIVALDI study based in England, looked at spike-specific immune responses in 341 staff and residents in long-term care facilities who received an mRNA vaccine following dual primary series vaccination with BNT162b2 or ChAdOx1. Third-dose vaccination strongly increased antibody responses with preferential relative enhancement in older people and was required to elicit neutralization of Omicron. Cellular immune responses were also enhanced with strong cross-reactive recognition of Omicron. However, antibody titers fell 21-78% within 100 d after vaccine and 27% of participants developed a breakthrough Omicron infection. These findings reveal strong immunogenicity of a third vaccine in one of the most vulnerable population groups and endorse an approach for widespread delivery across this population. Ongoing assessment will be required to determine the stability of immune protection.",,pdf:https://www.nature.com/articles/s43587-022-00328-3.pdf; doi:https://doi.org/10.1038/s43587-022-00328-3; html:https://europepmc.org/articles/PMC10154221; pdf:https://europepmc.org/articles/PMC10154221?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.",,pdf:https://www.nature.com/articles/s41598-018-32876-3.pdf; doi:https://doi.org/10.1038/s41598-018-32876-3; html:https://europepmc.org/articles/PMC6168481; pdf:https://europepmc.org/articles/PMC6168481?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,Apoptosis; Genetic Variants; Antibody-dependent Cell-mediated Cytotoxicity (Adcc); Multi-omic; Autoimmune Thyroid Diseases (Aitd); Anti-thyroid Peroxidase Antibody (Tpoab),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<sup>-</sup> CD314<sup>+</sup> CD158b<sup>+</sup> 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.",,pdf:https://www.mdpi.com/2073-4409/9/3/665/pdf?version=1584361130; doi:https://doi.org/10.3390/cells9030665; html:https://europepmc.org/articles/PMC7140647; pdf:https://europepmc.org/articles/PMC7140647?pdf=render
@@ -1015,19 +1015,19 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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
 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,,"<h4>Background</h4>Atopic dermatitis is characterized by chronic inflammation, which is a risk factor for atrial fibrillation.<h4>Objective</h4>To examine the association between hospital-diagnosed atopic dermatitis and atrial fibrillation.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Limitations</h4>Analyses were limited to persons with moderate-to-severe atopic dermatitis, and we had no lifestyle data.<h4>Conclusion</h4>Patients with hospital-diagnosed atopic dermatitis have a 20% increased long-term risk of atrial fibrillation, but the absolute risk remains low.",,pdf:http://www.jaad.org/article/S0190962219326143/pdf; 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
 34726481,https://doi.org/10.1126/science.abl9551,"Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant.","Elliott P, Haw D, Wang H, Eales O, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, Trotter AJ, Prosolek SJ, COVID-19 Genomics UK (COG-UK) Consortium11‡, Ashby D, Donnelly CA, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S.",,"Science (New York, N.Y.)",2021,2021-12-17,N,,,,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.",,pdf:https://www.science.org/history/7d0b03b2-b465-410e-a40d-7300157d8b54/science.abl9551.v1.pdf; doi:https://doi.org/10.1126/science.abl9551
-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,,,"<h4>Aim</h4>This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.<h4>Methods</h4>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.<h4>Results</h4>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)].<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf; doi:https://doi.org/10.1093/ehjqcco/qcad029
 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,,,"<h4>Objective</h4>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.<h4>Design</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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 ( <i>www.UC-CaRE.uk</i> ) can support treatment decision-making.",,pdf:https://gut.bmj.com/content/gutjnl/71/4/705.full.pdf; doi:https://doi.org/10.1136/gutjnl-2020-323546; html:https://europepmc.org/articles/PMC8921573; pdf:https://europepmc.org/articles/PMC8921573?pdf=render
+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,,,"<h4>Aim</h4>This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.<h4>Methods</h4>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.<h4>Results</h4>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)].<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf; doi:https://doi.org/10.1093/ehjqcco/qcad029
 35650647,https://doi.org/10.1186/s41512-022-00124-y,A scoping methodological review of simulation studies comparing statistical and machine learning approaches to risk prediction for time-to-event data.,"Smith H, Sweeting M, Morris T, Crowther MJ.",,Diagnostic and prognostic research,2022,2022-06-02,Y,Survival analysis; Machine Learning; Simulation Studies; Clinical Risk Prediction; Prognostic Modelling,,,"<h4>Background</h4>There is substantial interest in the adaptation and application of so-called machine learning approaches to prognostic modelling of censored time-to-event data. These methods must be compared and evaluated against existing methods in a variety of scenarios to determine their predictive performance. A scoping review of how machine learning methods have been compared to traditional survival models is important to identify the comparisons that have been made and issues where they are lacking, biased towards one approach or misleading.<h4>Methods</h4>We conducted a scoping review of research articles published between 1 January 2000 and 2 December 2020 using PubMed. Eligible articles were those that used simulation studies to compare statistical and machine learning methods for risk prediction with a time-to-event outcome in a medical/healthcare setting. We focus on data-generating mechanisms (DGMs), the methods that have been compared, the estimands of the simulation studies, and the performance measures used to evaluate them.<h4>Results</h4>A total of ten articles were identified as eligible for the review. Six of the articles evaluated a method that was developed by the authors, four of which were machine learning methods, and the results almost always stated that this developed method's performance was equivalent to or better than the other methods compared. Comparisons were often biased towards the novel approach, with the majority only comparing against a basic Cox proportional hazards model, and in scenarios where it is clear it would not perform well. In many of the articles reviewed, key information was unclear, such as the number of simulation repetitions and how performance measures were calculated.<h4>Conclusion</h4>It is vital that method comparisons are unbiased and comprehensive, and this should be the goal even if realising it is difficult. Fully assessing how newly developed methods perform and how they compare to a variety of traditional statistical methods for prognostic modelling is imperative as these methods are already being applied in clinical contexts. Evaluations of the performance and usefulness of recently developed methods for risk prediction should be continued and reporting standards improved as these methods become increasingly popular.",,pdf:https://diagnprognres.biomedcentral.com/track/pdf/10.1186/s41512-022-00124-y; doi:https://doi.org/10.1186/s41512-022-00124-y; html:https://europepmc.org/articles/PMC9161606; pdf:https://europepmc.org/articles/PMC9161606?pdf=render
 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,,,,,,pdf:https://gh.bmj.com/content/bmjgh/7/3/e008099.full.pdf; doi:https://doi.org/10.1136/bmjgh-2021-008099; html:https://europepmc.org/articles/PMC8905410; pdf:https://europepmc.org/articles/PMC8905410?pdf=render
 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; Roc, Receiver Operating Curve; Severe Acute Respiratory Syndrome‐Related Coronavirus 2 (Sars-Cov-2); Bmem, Bayesian Mixed-effect Model; Css, Covid Symptoms Study; Di, Data Invalid; Kcl, King's College London; Lfat, Lateral Flow Antigen Test; Nhs Uk, National Health Service Of The United Kingdom; 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; Auc, Area Under The Curve; Bmi, Body Mass Index; Ci, Confidence Interval; Lr, Logistic Regression; Iqr, Inter Quartile Range; Rf, Random Forest; Covid-19, Coronavirus Disease 2019; Covid-19 Detection; Rtpcr, Reverse Transcription Polymerase Chain Reaction",,,"<h4>Background</h4>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.<h4>Methods</h4>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 <i>per se</i> 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.<h4>Findings</h4>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).<h4>Interpretation</h4>Post-vaccination symptoms <i>per se</i> 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.<h4>Funding</h4>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; doi:https://doi.org/10.1016/j.eclinm.2021.101212; html:https://europepmc.org/articles/PMC8635464; pdf:https://europepmc.org/articles/PMC8635464?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,,,"<h4>Background</h4>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.<h4>Objective</h4>Investigate whether incorporating additional related disorders in the classification model development process can lead to the discovery of an AD-specific gene expression signature.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://content.iospress.com:443/download/journal-of-alzheimers-disease/jad191163?id=journal-of-alzheimers-disease%2Fjad191163; doi:https://doi.org/10.3233/JAD-191163; html:https://europepmc.org/articles/PMC7175937; pdf:https://europepmc.org/articles/PMC7175937?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.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/8/1/e000967.full.pdf; doi:https://doi.org/10.1136/bmjresp-2021-000967; html:https://europepmc.org/articles/PMC8261886; pdf:https://europepmc.org/articles/PMC8261886?pdf=render
-35471746,https://doi.org/10.1186/s13613-022-01011-x,The resilient intensive care unit.,"Salluh JIF, Kurtz P, Bastos LSL, Quintairos A, Zampieri FG, Bozza FA.",,Annals of intensive care,2022,2022-04-26,Y,,,,"<h4>Background</h4>The COVID-19 pandemic tested the capacity of intensive care units (ICU) to respond to a crisis and demonstrated their fragility. Unsurprisingly, higher than usual mortality rates, lengths of stay (LOS), and ICU-acquired complications occurred during the pandemic. However, worse outcomes were not universal nor constant across ICUs and significant variation in outcomes was reported, demonstrating that some ICUs could adequately manage the surge of COVID-19.<h4>Methods</h4>In the present editorial, we discuss the concept of a resilient Intensive Care Unit, including which metrics can be used to address the capacity to respond, sustain results and incorporate new practices that lead to improvement.<h4>Results</h4>We believe that a resiliency analysis adds a component of preparedness to the usual ICU performance evaluation and outcomes metrics to be used during the crisis and in regular times.<h4>Conclusions</h4>The COVID-19 pandemic demonstrated the need for a resilient health system. Although this concept has been discussed for health systems, it was not tested in intensive care. Future studies should evaluate this concept to improve ICU organization for standard and pandemic times.",,pdf:https://annalsofintensivecare.springeropen.com/track/pdf/10.1186/s13613-022-01011-x; doi:https://doi.org/10.1186/s13613-022-01011-x; html:https://europepmc.org/articles/PMC9038989; pdf:https://europepmc.org/articles/PMC9038989?pdf=render
 32046816,https://doi.org/10.2807/1560-7917.es.2020.25.5.2000080,Effectiveness of airport screening at detecting travellers infected with novel coronavirus (2019-nCoV).,"Quilty BJ, Clifford S, CMMID nCoV working group2, Flasche S, Eggo RM.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2020,2020-02-01,Y,Surveillance; Effectiveness; Interventions; Emerging Infections; 2019-Ncov; Airport Screening; Thermal Scanning,,,"We evaluated effectiveness of thermal passenger screening for 2019-nCoV infection at airport exit and entry to inform public health decision-making. In our baseline scenario, we estimated that 46% (95% confidence interval: 36 to 58) of infected travellers would not be detected, depending on incubation period, sensitivity of exit and entry screening, and proportion of asymptomatic cases. Airport screening is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers to avoid entry of infected travellers.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/5/eurosurv-25-5-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.5.2000080&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.5.2000080; html:https://europepmc.org/articles/PMC7014668; pdf:https://europepmc.org/articles/PMC7014668?pdf=render
-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<sup>-11</sup>) 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.",,pdf:https://www.nature.com/articles/s41591-022-02046-0.pdf; doi:https://doi.org/10.1038/s41591-022-02046-0; html:https://europepmc.org/articles/PMC9671801; pdf:https://europepmc.org/articles/PMC9671801?pdf=render
+35471746,https://doi.org/10.1186/s13613-022-01011-x,The resilient intensive care unit.,"Salluh JIF, Kurtz P, Bastos LSL, Quintairos A, Zampieri FG, Bozza FA.",,Annals of intensive care,2022,2022-04-26,Y,,,,"<h4>Background</h4>The COVID-19 pandemic tested the capacity of intensive care units (ICU) to respond to a crisis and demonstrated their fragility. Unsurprisingly, higher than usual mortality rates, lengths of stay (LOS), and ICU-acquired complications occurred during the pandemic. However, worse outcomes were not universal nor constant across ICUs and significant variation in outcomes was reported, demonstrating that some ICUs could adequately manage the surge of COVID-19.<h4>Methods</h4>In the present editorial, we discuss the concept of a resilient Intensive Care Unit, including which metrics can be used to address the capacity to respond, sustain results and incorporate new practices that lead to improvement.<h4>Results</h4>We believe that a resiliency analysis adds a component of preparedness to the usual ICU performance evaluation and outcomes metrics to be used during the crisis and in regular times.<h4>Conclusions</h4>The COVID-19 pandemic demonstrated the need for a resilient health system. Although this concept has been discussed for health systems, it was not tested in intensive care. Future studies should evaluate this concept to improve ICU organization for standard and pandemic times.",,pdf:https://annalsofintensivecare.springeropen.com/track/pdf/10.1186/s13613-022-01011-x; doi:https://doi.org/10.1186/s13613-022-01011-x; html:https://europepmc.org/articles/PMC9038989; pdf:https://europepmc.org/articles/PMC9038989?pdf=render
 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,,"<i>Background:</i> 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. <i>Method:</i> 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. <i>Results:</i> 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. <i>Contribution:</i> 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.",,pdf:https://bdj.pensoft.net/article/29232/download/pdf/; doi:https://doi.org/10.3897/BDJ.6.e29232; html:https://europepmc.org/articles/PMC6281706; pdf:https://europepmc.org/articles/PMC6281706?pdf=render
-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,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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).",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088280; doi:https://doi.org/10.1016/j.ufug.2023.127934; html:https://europepmc.org/articles/PMC10088280; pdf:https://europepmc.org/articles/PMC10088280?pdf=render
+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<sup>-11</sup>) 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.",,pdf:https://www.nature.com/articles/s41591-022-02046-0.pdf; doi:https://doi.org/10.1038/s41591-022-02046-0; html:https://europepmc.org/articles/PMC9671801; pdf:https://europepmc.org/articles/PMC9671801?pdf=render
 32301135,https://doi.org/10.1111/opo.12685,Delayed attendance at routine eye examinations is associated with increased probability of general practitioner referral: a record linkage study in Northern Ireland.,"Wright DM, O'Reilly D, Azuara-Blanco A, Curran R, McMullan M, Hogg RE.",,Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists),2020,2020-04-16,N,epidemiology; Public Health; Optometry Services,,,"<h4>Purpose</h4>To investigate relationships between health and socio-economic status with delayed attendance at routine eye examinations and risk of subsequent general practitioner (GP) referral in Northern Ireland.<h4>Methods</h4>We constructed a cohort of 132 046 community dwelling individuals aged ≥60 years, drawing contextual information from the 2011 Northern Ireland Census. Using linked administrative records of routine eye examinations between 2009 and 2014, we calculated 311 999 examination intervals. Multinomial models were used to estimate associations between contextual factors and examination interval (classified into three groups: early recall, on-time, delayed attendance). Associations between examination interval and referral risk were estimated using logistic regression.<h4>Results</h4>Delayed attendance was recorded for 129 857 (41.6%) examination intervals, 53 759 (17.2%) delayed by ≥6 months. Female sex, poor general or mental health were each associated with delay, as were longer distances to optometry services among those aged ≥70 years (longest vs shortest: Relative Risk Ratio = 1.21 [1.14, 1.28]). Low income and residence in social housing were associated with reduced delay risk. There were 3347 (3.5%) and 11 401 (5.3%) GP referrals in the 60-69 and ≥70 years age groups respectively. Delayed attendance was associated with increased referral risk in both groups (Odds Ratios: 60-69 years = 1.30 [1.04, 1.61]; ≥70 years = 1.07 [1.01, 1.13]).<h4>Conclusions</h4>Poor health and longer distances to optometry services were associated with delayed attendance at routine eye examinations but low income was not. Delayed attendance was associated with increased GP referral risk, indicative of missed opportunities to detect potentially serious eye conditions.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/opo.12685; doi:https://doi.org/10.1111/opo.12685
+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,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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).",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088280; doi:https://doi.org/10.1016/j.ufug.2023.127934; html:https://europepmc.org/articles/PMC10088280; pdf:https://europepmc.org/articles/PMC10088280?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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://medinform.jmir.org/2023/1/e45534/PDF; doi:https://doi.org/10.2196/45534; html:https://europepmc.org/articles/PMC10193205
 35487738,https://doi.org/10.1136/bmjopen-2021-057017,Variation in the estimated prevalence of multimorbidity: systematic review and meta-analysis of 193 international studies.,"Ho IS, Azcoaga-Lorenzo A, Akbari A, Davies J, Hodgins P, Khunti K, Kadam U, Lyons R, McCowan C, Mercer SW, Nirantharakumar K, Guthrie B.",,BMJ open,2022,2022-04-29,Y,epidemiology; Geriatric Medicine; General Medicine (See Internal Medicine),,,"<h4>Objective</h4>(1) To estimate the pooled prevalence of multimorbidity in all age groups, globally. (2) To examine how measurement of multimorbidity impacted the estimated prevalence.<h4>Methods</h4>In this systematic review and meta-analysis, we conducted searches in nine bibliographic databases (PsycINFO, Embase, Global Health, Medline, Scopus, Web of Science, Cochrane Library, CINAHL and ProQuest Dissertations and Theses Global) for prevalence studies published between database inception and 21 January 2020. Studies reporting the prevalence of multimorbidity (in all age groups and in community, primary care, care home and hospital settings) were included. Studies with an index condition or those that did not include people with no long-term conditions in the denominator were excluded. Retrieved studies were independently reviewed by two reviewers, and relevant data were extracted using predesigned pro forma. We used meta-analysis to pool the estimated prevalence of multimorbidity across studies, and used random-effects meta-regression and subgroup analysis to examine the association of heterogeneous prevalence estimates with study and measure characteristics.<h4>Results</h4>13 807 titles were screened, of which 193 met inclusion criteria for meta-analysis. The pooled prevalence of multimorbidity was 42.4% (95% CI 38.9% to 46.0%) with high heterogeneity (I<sup>2</sup> >99%). In adjusted meta-regression models, participant mean age and the number of conditions included in a measure accounted for 47.8% of heterogeneity in effect sizes. The estimated prevalence of multimorbidity was significantly higher in studies with older adults and those that included larger numbers of conditions. There was no significant difference in estimated prevalence between low-income or middle-income countries (36.8%) and high-income countries (44.3%), or between self-report (40.0%) and administrative/clinical databases (52.7%).<h4>Conclusions</h4>The pooled prevalence of multimorbidity was significantly higher in older populations and when studies included a larger number of baseline conditions. The findings suggest that, to improve study comparability and quality of reporting, future studies should use a common core conditions set for multimorbidity measurement and report multimorbidity prevalence stratified by sociodemographics.<b>PROSPERO registration number</b>CRD42020172409.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057017.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057017; html:https://europepmc.org/articles/PMC9058768; pdf:https://europepmc.org/articles/PMC9058768?pdf=render
 37712381,https://doi.org/10.7189/jogh.13.04101,Understanding and reporting odds ratios as rate-ratio estimates in case-control studies.,"Kerr S, Greenland S, Jeffrey K, Millington T, Bedston S, Ritchie L, Simpson CR, Fagbamigbe AF, Kurdi A, Robertson C, Sheikh A, Rudan I.",,Journal of global health,2023,2023-09-15,Y,,,,"<h4>Background</h4>We noted that there remains some confusion in the health-science literature on reporting sample odds ratios as estimated rate ratios in case-control studies.<h4>Methods</h4>We recap historical literature that definitively answered the question of when sample odds ratios (ORs) from a case-control study are consistent estimators for population rate ratios. We use numerical examples to illustrate the magnitude of the disparity between sample ORs in a case-control study and population rate ratios when sufficient conditions for them to be equal are not satisfied.<h4>Results</h4>We stress that in a case-control study, sampling controls from those still at risk at the time of outcome event of the index case is not sufficient for a sample OR to be a consistent estimator for an intelligible rate ratio. In such studies, constancy of the exposure prevalence together with constancy of the hazard ratio (HR) (i.e., the instantaneous rate ratio) over time is sufficient for this result if sampling time is not controlled; if time is controlled, constancy of the HR will suffice. We present numerical examples to illustrate how failure to satisfy these conditions adds a small systematic error to sample ORs as estimates of population rate ratios.<h4>Conclusions</h4>We recommend that researchers understand and critically evaluate all conditions used to interpret their estimates as consistent for a population parameter in case-control studies.",,pdf:https://jogh.org/wp-content/uploads/2023/09/jogh-13-04101.pdf; doi:https://doi.org/10.7189/jogh.13.04101; html:https://europepmc.org/articles/PMC10502767; pdf:https://europepmc.org/articles/PMC10502767?pdf=render
@@ -1038,17 +1038,17 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 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.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/C1E5FCC67F1D627908A5495EED02577B/S2056469422000833a.pdf/div-class-title-edify-eating-disorders-delineating-illness-and-recovery-trajectories-to-inform-personalised-prevention-and-early-intervention-in-young-people-project-outline-div.pdf; doi:https://doi.org/10.1192/bjb.2022.83
 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,,,"<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.karger.com/Article/Pdf/520674; doi:https://doi.org/10.1159/000520674; html:https://europepmc.org/articles/PMC8985014; doi:https://doi.org/10.1159/000520674
 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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e064586.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064586; html:https://europepmc.org/articles/PMC9511592; pdf:https://europepmc.org/articles/PMC9511592?pdf=render
-37284234,https://doi.org/10.1140/epjds/s13688-023-00391-9,"The shock, the coping, the resilience: smartphone application use reveals Covid-19 lockdown effects on human behaviors.","Liu XF, Wang ZZ, Xu XK, Wu Y, Zhao Z, Deng H, Wang P, Chao N, Huang YC.",,EPJ data science,2023,2023-06-05,Y,Human behaviors; Natural Experiment; Lockdown; Smartphone Apps; Covid-19,,,"Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming ""digital residents."" This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9.",,doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?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,,,"<h4>Objective</h4>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.<h4>Design</h4>Data linkage between a longitudinal birth cohort and routinely collected electronic health records.<h4>Setting</h4>Consenting Millennium Cohort Study (MCS) participants residing in Wales and Scotland.<h4>Patients</h4>3119 children who participated in the age 5 MCS interview.<h4>Main outcome measures</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://adc.bmj.com/content/archdischild/105/3/282.full.pdf; doi:https://doi.org/10.1136/archdischild-2019-317271; html:https://europepmc.org/articles/PMC7041499; pdf:https://europepmc.org/articles/PMC7041499?pdf=render
 32128788,https://doi.org/10.1111/bjd.18889,The association between partner bereavement and melanoma: cohort studies in the U.K. and Denmark.,"Wong AYS, Frøslev T, Dearing L, Forbes HJ, Mulick A, Mansfield KE, Silverwood RJ, Kjaersgaard A, Sørensen HT, Smeeth L, Lewin A, Schmidt SAJ, Langan SM.",,The British journal of dermatology,2020,2020-03-03,Y,,,,"<h4>Background</h4>Psychological stress is commonly cited as a risk factor for melanoma, but clinical evidence is limited.<h4>Objectives</h4>This study aimed to evaluate the association between partner bereavement and (i) first-time melanoma diagnosis and (ii) mortality in patients with melanoma.<h4>Methods</h4>We conducted two cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). In study 1, we compared the risk of first melanoma diagnosis in bereaved vs. matched nonbereaved people using stratified Cox regression. In study 2 we estimated hazard ratios (HRs) for death from melanoma in bereaved compared with nonbereaved individuals with melanoma using Cox regression. We estimated HRs separately for the U.K. and for Denmark, and then pooled the data to perform a random-effects meta-analysis.<h4>Results</h4>In study 1, the pooled adjusted HR for the association between partner bereavement and melanoma diagnosis was 0·88 [95% confidence interval (CI) 0·84-0·92] across the entire follow-up period. In study 2, we observed increased melanoma-specific mortality in people experiencing partner bereavement across the entire follow-up period (HR 1·17, 95% CI 1·06-1·30), with the peak occurring during the first year of follow-up (HR 1·31, 95% CI 1·07-1·60).<h4>Conclusions</h4>We found decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. These findings may be partly explained by delayed detection resulting from the loss of a partner who could notice skin changes. Stress may play a role in melanoma progression. Our findings indicate the need for a low threshold for skin examination in individuals whose partners have died. What is already known about this topic? Psychological stress has been proposed as a risk factor for the development and progression of cancer, including melanoma, but evidence is conflicting. Clinical evidence is limited by small sample sizes, potential recall bias associated with self-report, and heterogeneous stress definitions. What does this study add? We found a decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. While stress might play a role in the progression of melanoma, an alternative explanation is that bereaved people no longer have a close person to help notice skin changes, leading to delayed melanoma detection. Linked Comment: Talaganis et al. Br J Dermatol 2020; 183:607-608.",,doi:https://doi.org/10.1111/bjd.18889; doi:https://doi.org/10.1111/bjd.18889; html:https://europepmc.org/articles/PMC7587014; pdf:https://europepmc.org/articles/PMC7587014?pdf=render
+37284234,https://doi.org/10.1140/epjds/s13688-023-00391-9,"The shock, the coping, the resilience: smartphone application use reveals Covid-19 lockdown effects on human behaviors.","Liu XF, Wang ZZ, Xu XK, Wu Y, Zhao Z, Deng H, Wang P, Chao N, Huang YC.",,EPJ data science,2023,2023-06-05,Y,Human behaviors; Natural Experiment; Lockdown; Smartphone Apps; Covid-19,,,"Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming ""digital residents."" This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9.",,doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?pdf=render
 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,,,"<h4>Background and objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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, <i>p</i><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, <i>p<</i>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.<h4>Conclusions</h4>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.",,pdf:https://publinestorage.blob.core.windows.net/journals/JCTP.2022.2(1).23.00003.pdf; doi:https://doi.org/10.14218/jctp.2022.00003; html:https://europepmc.org/articles/PMC8994161; pdf:https://europepmc.org/articles/PMC8994161?pdf=render
 33168126,https://doi.org/10.1192/bjo.2020.42,Impact of schizophrenia genetic liability on the association between schizophrenia and physical illness: data-linkage study.,"Kendall KM, John A, Lee SC, Rees E, Pardiñas AF, Banos MDP, Owen MJ, O'Donovan MC, Kirov G, Lloyd K, Jones I, Legge SE, Walters JTR.",,BJPsych open,2020,2020-11-10,Y,Genetics; Schizophrenia; Physical Health; Psychotic Disorders,,,"<h4>Background</h4>Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.<h4>Aims</h4>To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.<h4>Method</h4>We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.<h4>Results</h4>Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015-0.017), with carriers being 7.5-7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.<h4>Conclusions</h4>This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A00360A347FCC91E2E9D0B39FBDCE887/S2056472420000423a.pdf/div-class-title-impact-of-schizophrenia-genetic-liability-on-the-association-between-schizophrenia-and-physical-illness-data-linkage-study-div.pdf; doi:https://doi.org/10.1192/bjo.2020.42; html:https://europepmc.org/articles/PMC7745237; pdf:https://europepmc.org/articles/PMC7745237?pdf=render
 33475522,https://doi.org/10.2196/18229,Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: Protocol for a Systematic Review.,"Fundikira LS, Chillo P, van Laake LW, Mutagaywa RK, Schmidt AF, Kamuhabwa A, Kwesigabo G, Asselbergs FW.",,JMIR research protocols,2021,2021-01-21,Y,Dilated cardiomyopathy; Sub-Saharan Africa; Cardiomyopathy; Cardiovascular risk factors; Heart Failure,,,"<h4>Background</h4>Cardiomyopathies, defined as diseases involving mainly the heart muscles, are linked to an estimated 5.9 of 100,000 deaths globally. In sub-Saharan Africa, cardiomyopathies constitute 21.4% of heart failure cases, with dilated cardiomyopathy (DCM) being the most common form. The etiology of DCM is heterogeneous and is broadly categorized as genetic or nongenetic, as well as a mixed disease in which genetics interact with intrinsic and environmental factors. Factors such as age, gender, family history, and ethnicity are nonmodifiable, whereas modifiable risk factors include poor nutrition, physical inactivity, and excessive alcohol consumption, among others. However, the relative contribution of the different risk factors to the etiology of DCM is not known in sub-Saharan Africa, and the prevalence of DCM among heart failure patients has not been systematically studied in the region.<h4>Objective</h4>The aim of this review is to synthesize available literature from sub-Saharan Africa on the prevalence of DCM among patients with heart failure, as well as the literature on factors associated with DCM. This paper outlines the protocol that will be followed to conduct the systematic review.<h4>Methods</h4>A limited search of the PubMed database will be performed to identify relevant keywords contained in the title, abstract, and subject descriptors using initial search terms ""heart failure,"" ""cardiomyopathy,"" and ""sub-Saharan Africa."" These search terms and their synonyms will then be used in an extensive search in PubMed, and will address the first research question on prevalence. To address the second research question on risk factors, the terms ""heart failure,"" ""cardiomyopathy,"" and ""cardiovascular risk factors"" in ""Sub-Saharan Africa"" will be used, listing them one by one. Articles published from 2000 and in the English language will be included. Indexed articles in PubMed and Embase will be included, as well as the first 300 articles retrieved from a Google Scholar search. Collected data will be organized in Endnote and then uploaded to the Rayyan web app for systematic reviews. Two reviewers will independently select articles against the inclusion criteria. Discrepancies in reviewer selections will be resolved by an arbitrator. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for reporting systematic reviews will be applied. A map of sub-Saharan Africa with colors to show disease prevalence in each country will be included. For quantitative data, where possible, odds ratios (for categorical outcome data) or standardized mean differences (for continuous data) and their 95% CIs will be calculated.<h4>Results</h4>The primary outcomes will be the prevalence of DCM among patients with heart failure and cardiovascular risk factors associated with DCM in sub-Saharan Africa. The literature search will begin on January 1, 2021, and data analysis is expected to be completed by April 30, 2021.<h4>Conclusions</h4>This review will provide information on the current status of the prevalence and associated factors of DCM, and possibly identify gaps, including paucity of data or conflicting results that need to be addressed to improve our understanding of DCM in sub-Saharan Africa.<h4>International registered report identifier (irrid)</h4>PRR1-10.2196/18229.",,pdf:https://jmir.org/api/download?alt_name=resprot_v10i1e18229_app1.pdf&filename=7e28e6f3581cda60eb7faa74a1bb7968.pdf; doi:https://doi.org/10.2196/18229; html:https://europepmc.org/articles/PMC7862000
 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,,"<h4>Background</h4>Few studies have examined health service utilization of children with overweight or obesity by using linked electronic health records (EHRs).<h4>Objective/methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ijpo.12505; doi:https://doi.org/10.1111/ijpo.12505; html:https://europepmc.org/articles/PMC6563186; pdf:https://europepmc.org/articles/PMC6563186?pdf=render
 31504435,https://doi.org/10.1093/eurheartj/ehz569,Obesity causes cardiovascular diseases: adding to the weight of evidence.,"Hingorani AD, Finan C, Schmidt AF.",,European heart journal,2020,2020-01-01,N,,,,,,pdf:https://academic.oup.com/eurheartj/article-pdf/41/2/227/31731687/ehz569.pdf; doi:https://doi.org/10.1093/eurheartj/ehz569
 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,,"<h4>Background</h4>Previous studies have identified an inverse association between melanoma and smoking; however, data from population-based studies are scarce.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.18526; doi:https://doi.org/10.1111/bjd.18526; html:https://europepmc.org/articles/PMC7383980; pdf:https://europepmc.org/articles/PMC7383980?pdf=render
-37805492,https://doi.org/10.1186/s12864-023-09663-0,Mapping the epigenomic landscape of human monocytes following innate immune activation reveals context-specific mechanisms driving endotoxin tolerance.,"Amarasinghe HE, Zhang P, Whalley JP, Allcock A, Migliorini G, Brown AC, Scozzafava G, Knight JC.",,BMC genomics,2023,2023-10-07,Y,Chromatin Accessibility; Expression Quantitative Trait Loci; Endotoxin Tolerance; Human Monocytes; Enhancer Rna; Context-specificity,,,"<h4>Background</h4>Monocytes are key mediators of innate immunity to infection, undergoing profound and dynamic changes in epigenetic state and immune function which are broadly protective but may be dysregulated in disease. Here, we aimed to advance understanding of epigenetic regulation following innate immune activation, acutely and in endotoxin tolerant states.<h4>Methods</h4>We exposed human primary monocytes from healthy donors (n = 6) to interferon-γ or differing combinations of endotoxin (lipopolysaccharide), including acute response (2 h) and two models of endotoxin tolerance: repeated stimulations (6 + 6 h) and prolonged exposure to endotoxin (24 h). Another subset of monocytes was left untreated (naïve). We identified context-specific regulatory elements based on epigenetic signatures for chromatin accessibility (ATAC-seq) and regulatory non-coding RNAs from total RNA sequencing.<h4>Results</h4>We present an atlas of differential gene expression for endotoxin and interferon response, identifying widespread context specific changes. Across assayed states, only 24-29% of genes showing differential exon usage are also differential at the gene level. Overall, 19.9% (6,884 of 34,616) of repeatedly observed ATAC peaks were differential in at least one condition, the majority upregulated on stimulation and located in distal regions (64.1% vs 45.9% of non-differential peaks) within which sequences were less conserved than non-differential peaks. We identified enhancer-derived RNA signatures specific to different monocyte states that correlated with chromatin accessibility changes. The endotoxin tolerance models showed distinct chromatin accessibility and transcriptomic signatures, with integrated analysis identifying genes and pathways involved in the inflammatory response, detoxification, metabolism and wound healing. We leveraged eQTL mapping for the same monocyte activation states to link potential enhancers with specific genes, identifying 1,946 unique differential ATAC peaks with 1,340 expression associated genes. We further use this to inform understanding of reported GWAS, for example involving FCHO1 and coronary artery disease.<h4>Conclusion</h4>This study reports context-specific regulatory elements based on transcriptomic profiling and epigenetic signatures for enhancer-derived RNAs and chromatin accessibility in immune tolerant monocyte states, and demonstrates the informativeness of linking such elements and eQTL to inform future mechanistic studies aimed at defining therapeutic targets of immunosuppression and diseases.",,doi:https://doi.org/10.1186/s12864-023-09663-0; html:https://europepmc.org/articles/PMC10559536; pdf:https://europepmc.org/articles/PMC10559536?pdf=render
 34194954,https://doi.org/10.1002/advs.202100707,Green Algorithms: Quantifying the Carbon Footprint of Computation.,"Lannelongue L, Grealey J, Inouye M.",,"Advanced science (Weinheim, Baden-Wurttemberg, Germany)",2021,2021-05-02,Y,Climate change; Green Computing; Computational Research,,,"Climate change is profoundly affecting nearly all aspects of life on earth, including human societies, economies, and health. Various human activities are responsible for significant greenhouse gas (GHG) emissions, including data centers and other sources of large-scale computation. Although many important scientific milestones are achieved thanks to the development of high-performance computing, the resultant environmental impact is underappreciated. In this work, a methodological framework to estimate the carbon footprint of any computational task in a standardized and reliable way is presented and metrics to contextualize GHG emissions are defined. A freely available online tool, Green Algorithms (www.green-algorithms.org) is developed, which enables a user to estimate and report the carbon footprint of their computation. The tool easily integrates with computational processes as it requires minimal information and does not interfere with existing code, while also accounting for a broad range of hardware configurations. Finally, the GHG emissions of algorithms used for particle physics simulations, weather forecasts, and natural language processing are quantified. Taken together, this study develops a simple generalizable framework and freely available tool to quantify the carbon footprint of nearly any computation. Combined with recommendations to minimize unnecessary CO<sub>2</sub> emissions, the authors hope to raise awareness and facilitate greener computation.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202100707; doi:https://doi.org/10.1002/advs.202100707; html:https://europepmc.org/articles/PMC8224424; pdf:https://europepmc.org/articles/PMC8224424?pdf=render
+37805492,https://doi.org/10.1186/s12864-023-09663-0,Mapping the epigenomic landscape of human monocytes following innate immune activation reveals context-specific mechanisms driving endotoxin tolerance.,"Amarasinghe HE, Zhang P, Whalley JP, Allcock A, Migliorini G, Brown AC, Scozzafava G, Knight JC.",,BMC genomics,2023,2023-10-07,Y,Chromatin Accessibility; Expression Quantitative Trait Loci; Endotoxin Tolerance; Human Monocytes; Enhancer Rna; Context-specificity,,,"<h4>Background</h4>Monocytes are key mediators of innate immunity to infection, undergoing profound and dynamic changes in epigenetic state and immune function which are broadly protective but may be dysregulated in disease. Here, we aimed to advance understanding of epigenetic regulation following innate immune activation, acutely and in endotoxin tolerant states.<h4>Methods</h4>We exposed human primary monocytes from healthy donors (n = 6) to interferon-γ or differing combinations of endotoxin (lipopolysaccharide), including acute response (2 h) and two models of endotoxin tolerance: repeated stimulations (6 + 6 h) and prolonged exposure to endotoxin (24 h). Another subset of monocytes was left untreated (naïve). We identified context-specific regulatory elements based on epigenetic signatures for chromatin accessibility (ATAC-seq) and regulatory non-coding RNAs from total RNA sequencing.<h4>Results</h4>We present an atlas of differential gene expression for endotoxin and interferon response, identifying widespread context specific changes. Across assayed states, only 24-29% of genes showing differential exon usage are also differential at the gene level. Overall, 19.9% (6,884 of 34,616) of repeatedly observed ATAC peaks were differential in at least one condition, the majority upregulated on stimulation and located in distal regions (64.1% vs 45.9% of non-differential peaks) within which sequences were less conserved than non-differential peaks. We identified enhancer-derived RNA signatures specific to different monocyte states that correlated with chromatin accessibility changes. The endotoxin tolerance models showed distinct chromatin accessibility and transcriptomic signatures, with integrated analysis identifying genes and pathways involved in the inflammatory response, detoxification, metabolism and wound healing. We leveraged eQTL mapping for the same monocyte activation states to link potential enhancers with specific genes, identifying 1,946 unique differential ATAC peaks with 1,340 expression associated genes. We further use this to inform understanding of reported GWAS, for example involving FCHO1 and coronary artery disease.<h4>Conclusion</h4>This study reports context-specific regulatory elements based on transcriptomic profiling and epigenetic signatures for enhancer-derived RNAs and chromatin accessibility in immune tolerant monocyte states, and demonstrates the informativeness of linking such elements and eQTL to inform future mechanistic studies aimed at defining therapeutic targets of immunosuppression and diseases.",,doi:https://doi.org/10.1186/s12864-023-09663-0; html:https://europepmc.org/articles/PMC10559536; pdf:https://europepmc.org/articles/PMC10559536?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 shown<sup>1</sup> to be highly efficient for discovery of genetic associations<sup>2</sup>. 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 group<sup>3</sup>. 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).",,pdf:https://www.nature.com/articles/s41586-023-06034-3.pdf; doi:https://doi.org/10.1038/s41586-023-06034-3; html:https://europepmc.org/articles/PMC10208981; pdf:https://europepmc.org/articles/PMC10208981?pdf=render
 34639458,https://doi.org/10.3390/ijerph181910156,Health-Related Quality of Life (HRQoL) Outcomes Following Injury in Childhood and Adolescence Using EuroQol (EQ-5D) Responses with Pooled Longitudinal Data. ,"Dipnall JF, Rivara FP, Lyons RA, Ameratunga S, Brussoni M, Lecky FE, Bradley C, Beck B, Lyons J, Schneeberg A, Harrison JE, Gabbe BJ.",,International journal of environmental research and public health,2021,2021-09-27,Y,,,,"Injury is a leading contributor to the global disease burden in children, affecting their health-related quality of life (HRQoL)-yet valid estimates of burden are absent. This study pooled longitudinal data from five cohort studies of pediatric injury survivors (5-17 years) at baseline, 1-, 4-, 6-, 12-, and 24- months (n = 2334). HRQoL post-injury was measured using the 3-level EQ-5D utility score (EQ-5D) and five health states (mobility, self-care, activity, pain, anxiety and depression (anxiety)). Mean EQ-5D post-injury did not return to baseline level (0.95) by 24 months (0.88) and was lower for females over time (-0.04, 95%CI -0.05, -0.02). A decreased adjusted risk ratio over time (ARR) was observed for intentional injuries (pain: 0.85, 95%CI 0.73,0.98; anxiety: 0.62, 95%CI 0.49,0.78); spinal cord injuries (mobility: 0.61, 95%CI 0.45,0.83), self-care: 0.76, 95%CI 0.63,0.91, activity: 0.64, 95%CI 0.47,0.88); moderate/severe traumatic brain injury (activity: 0.83, 95%CI 0.71,0.96). ARRs were also low for certain fractures, with various health states affected. HRQoL outcomes over time for children and adolescents post-injury differed across key demographic and injury related attributes. HRQoL did not reach levels consistent with full health by 24 months with recovery plateauing from 6 to 24 months. Tailored interventions are required to respond to the varying post-injury recovery trajectories in this population.",,doi:https://doi.org/10.3390/ijerph181910156; html:https://europepmc.org/articles/PMC8507627; pdf:https://europepmc.org/articles/PMC8507627?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,,,,"<h4>Importance</h4>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.<h4>Objective</h4>To provide contemporary quantitative data synthesis of the diagnostic accuracy and prognostic value of stress CMR in stable chest pain.<h4>Data sources</h4>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.<h4>Study selection</h4>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.<h4>Data extraction and synthesis</h4>This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.<h4>Main outcomes and measures</h4>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.<h4>Results</h4>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%.<h4>Conclusion and relevance</h4>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
@@ -1077,26 +1077,26 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 35508365,https://doi.org/10.1136/injuryprev-2021-044513,Prevalence of alcohol and other drug use in patients presenting to hospital for fall-related injuries: a systematic review.,"Lau G, Ang JY, Kim N, Gabbe BJ, Mitra B, Dietze PM, Reeder S, Beck B.",,Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention,2022,2022-05-04,N,Drugs; Alcohol; Fall; Systematic review; Metanalysis,,,"<h4>Background</h4>Alcohol and other drug (AOD) use is a key preventable risk factor for serious injuries. Prevention strategies to date have largely focused on transport injuries, despite AOD use being a significant risk factor for other injury causes, including falls. This systematic review aimed to report the prevalence of AOD use in patients presenting to hospital for fall-related injuries.<h4>Methods</h4>This systematic review includes studies published in English after the year 2010 that objectively measured the prevalence of AOD use in patients presenting to hospital for a fall-related injury. Screening, data extraction and risk of bias assessments were completed by two independent reviewers. Data were presented using narrative synthesis and, where appropriate, meta-analyses.<h4>Results</h4>A total of 12 707 records were screened. Full texts were retrieved for 2042 records, of which 29 were included. Four studies reported the combined prevalence of any alcohol and/or drug use, generating a pooled prevalence estimate of 37% (95% CI 25% to 49%). Twenty-two records reported on the prevalence of acute alcohol use alone and nine reported specifically on the prevalence of drugs other than alcohol, with prevalence ranging from 2% to 57% and 7% to 46%, respectively. The variation in prevalence estimates likely resulted from differences in toxicology testing methods across studies.<h4>Conclusions</h4>AOD exposure was common in hospitalised fall-related injuries. However, research addressing prevalence across different types of falls and the use of drugs other than alcohol was limited. Future research should address these areas to improve our understanding of which populations should be targeted in AOD and injury prevention strategies .<h4>Prospero registration number</h4>CRD42020188746.",,doi:https://doi.org/10.1136/injuryprev-2021-044513
 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; doi:https://doi.org/10.1016/j.media.2022.102678
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.<h4>Systematic review registration</h4>PROSPERO CRD42020216205.",,doi:https://doi.org/10.1186/s13643-023-02261-x; 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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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 (<i>P</i> < 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.<h4>Conclusion</h4>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
 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,,,,,,pdf:http://www.thelancet.com/article/S0140673620319668/pdf; 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
-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; doi:https://doi.org/10.1093/nar/gkab449; html:https://europepmc.org/articles/PMC8262728; pdf:https://europepmc.org/articles/PMC8262728?pdf=render
 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,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0213435&type=printable; doi:https://doi.org/10.1371/journal.pone.0213435; html:https://europepmc.org/articles/PMC6457613; pdf:https://europepmc.org/articles/PMC6457613?pdf=render
+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; doi:https://doi.org/10.1093/nar/gkab449; html:https://europepmc.org/articles/PMC8262728; pdf:https://europepmc.org/articles/PMC8262728?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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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 (<i>P</i> < 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.<h4>Conclusion</h4>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
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.<h4>Level of evidence</h4>Prognostic, level III.",,doi:https://doi.org/10.1097/TA.0000000000003317
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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].<h4>Conclusion</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0261142&type=printable; doi:https://doi.org/10.1371/journal.pone.0261142; html:https://europepmc.org/articles/PMC8757902; pdf:https://europepmc.org/articles/PMC8757902?pdf=render
 35776955,https://doi.org/10.1093/ehjqcco/qcac039,One step closer to quantifying 'clinical likelihood' in pre-test probability.,"Weir-McCall JR, Williams MC, Wood A.",,European heart journal. Quality of care & clinical outcomes,2022,2022-09-01,N,,,,,,doi:https://doi.org/10.1093/ehjqcco/qcac039; html:https://europepmc.org/articles/PMC9442847; pdf:https://europepmc.org/articles/PMC9442847?pdf=render; doi:https://doi.org/10.1093/ehjqcco/qcac039
-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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Discussion</h4>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.<h4>Trial registration</h4>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
 32894757,https://doi.org/10.1093/ageing/afaa138,Short physical performance battery as a practical tool to assess mortality risk in chronic obstructive pulmonary disease.,"Fermont JM, Mohan D, Fisk M, Bolton CE, Macnee W, Cockcroft JR, McEniery C, Fuld J, Cheriyan J, Tal-Singer R, Müllerova H, Wood AM, Wilkinson IB, Polkey MI, ERICA consortium.",,Age and ageing,2021,2021-05-01,Y,Mortality; Skeletal muscle; Biomarkers; Older People; chronic obstructive pulmonary disease,,,"<h4>Rationale</h4>chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and common in older adults. The BODE Index is the most recognised mortality risk score in COPD but includes a 6-minute walk test (6MWT) that is seldom available in practise; the BODE Index may be better adopted if the 6MWT was replaced.<h4>Objectives</h4>we investigated whether a modified BODE Index in which 6MWT was replaced by an alternative measure of physical capacity, specifically the short physical performance battery (SPPB) or components, retained its predictive ability for mortality in individuals with COPD.<h4>Methods</h4>we analysed 630 COPD patients from the ERICA cohort study for whom UK Office for National Statistics verified mortality data were available. Variables tested at baseline included spirometry, 6MWT, SPPB and its components (4-m gait speed test [4MGS], chair stand and balance). Predictive models were developed using stratified multivariable Cox regression, and assessed by C-indices and calibration plots with 10-fold cross-validation and replication.<h4>Results</h4>during median 2 years of follow-up, 60 (10%) individuals died. There was no significant difference between the discriminative ability of BODE6MWT (C-index 0.709, 95% confidence interval [CI], 0.680-0.737), BODESPPB (C-index 0.683, 95% CI, 0.647-0.712), BODE4MGS (C-index 0.676, 95% CI, 0.643-0.700) and BODEBALANCE (C-index 0.686, 95% CI, 0.651-0.713) for predicting mortality.<h4>Conclusions</h4>the SPPB, and its 4MGS and balance components, can potentially be used as an alternative to the 6MWT in the BODE Index without significant loss of predictive ability in all-cause mortality.",,pdf:https://academic.oup.com/ageing/article-pdf/50/3/795/37807880/afaa138.pdf; doi:https://doi.org/10.1093/ageing/afaa138; html:https://europepmc.org/articles/PMC8098797; pdf:https://europepmc.org/articles/PMC8098797?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Discussion</h4>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.<h4>Trial registration</h4>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
 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.",,pdf:http://insight.jci.org/articles/view/156643/files/pdf; doi:https://doi.org/10.1172/jci.insight.156643; html:https://europepmc.org/articles/PMC9977494; pdf:https://europepmc.org/articles/PMC9977494?pdf=render
 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,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0805-0; doi:https://doi.org/10.1186/s12911-019-0805-0; html:https://europepmc.org/articles/PMC6472089; pdf:https://europepmc.org/articles/PMC6472089?pdf=render
-37730605,https://doi.org/10.1186/s12889-023-16523-9,Inequalities and mental health during the Coronavirus pandemic in the UK: a mixed-methods exploration.,"Lombardo C, Guo L, Solomon S, Crepaz-Keay D, McDaid S, Thorpe L, Martin S, John A, Morton A, Davidson G, Kousoulis AA, Van Bortel T.",,BMC public health,2023,2023-09-20,Y,Coronavirus; Mental health; Pandemic; United Kingdom; Inequalities; Social Determinants; Inequity; Adult Population; Covid-19,,,"<h4>Background</h4>The World Health Organisation declared the novel Coronavirus disease (COVID-19) a global pandemic on 11th March 2020. Since then, the world has been firmly in its grip. At the time of writing, there were more than 767,972,961 million confirmed cases and over 6,950,655 million deaths. While the main policy focus has been on controlling the virus and ensuring vaccine roll-out and uptake, the population mental health impacts of the pandemic are expected to be long-term, with certain population groups affected more than others.<h4>Methods</h4>The overall objectives of our 'Coronavirus: Mental Health and the Pandemic' study were to explore UK adults' experiences of the Coronavirus pandemic and to gain insights into the mental health impacts, population-level changes over time, current and future mental health needs, and how these can best be addressed. The wider mixed-methods study consisted of repeated cross-sectional surveys and embedded qualitative sub-studies including in-depth interviews and focus group discussions with the wider UK adult population. For this particular inequalities and mental health sub-study, we used mixed methods data from our cross-sectional surveys and we carried out three Focus Group Discussions with a maximum variation sample from across the UK adult population. The discussions covered the broader topic of 'Inequalities and mental health during the Coronavirus pandemic in the UK' and took place online between April and August 2020. Focus Groups transcripts were analysed using thematic analysis in NVIVO. Cross-sectional survey data were analysed using STATA for descriptive statistics.<h4>Results</h4>Three broad main themes emerged, each supporting a number of sub-themes: (1) Impacts of the pandemic; (2) Moving forward: needs and recommendations; (3) Coping mechanisms and resilience. Findings showed that participants described their experiences of the pandemic in relation to its impact on themselves and on different groups of people. Their experiences illustrated how the pandemic and subsequent measures had exacerbated existing inequalities and created new ones, and triggered various emotional responses. Participants also described their coping strategies and what worked and did not work for them, as well as support needs and recommendations for moving forward through, and out of, the pandemic; all of which are valuable learnings to be considered in policy making for improving mental health and for ensuring future preparedness.<h4>Conclusions</h4>The pandemic is taking a long-term toll on the nations' mental health which will continue to have impacts for years to come. It is therefore crucial to learn the vital lessons learned from this pandemic. Specific as well as whole-government policies need to respond to this, address inequalities and the different needs across the life-course and across society, and take a holistic approach to mental health improvement across the UK.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-16523-9; doi:https://doi.org/10.1186/s12889-023-16523-9; html:https://europepmc.org/articles/PMC10510114; pdf:https://europepmc.org/articles/PMC10510114?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,,,,"<h4>Background</h4>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.<h4>Objectives</h4>To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660846/7/Mulick_etal_2021_Four-childhood-atopic-dermatitis-subtypes.pdf; 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
+37730605,https://doi.org/10.1186/s12889-023-16523-9,Inequalities and mental health during the Coronavirus pandemic in the UK: a mixed-methods exploration.,"Lombardo C, Guo L, Solomon S, Crepaz-Keay D, McDaid S, Thorpe L, Martin S, John A, Morton A, Davidson G, Kousoulis AA, Van Bortel T.",,BMC public health,2023,2023-09-20,Y,Coronavirus; Mental health; Pandemic; United Kingdom; Inequalities; Social Determinants; Inequity; Adult Population; Covid-19,,,"<h4>Background</h4>The World Health Organisation declared the novel Coronavirus disease (COVID-19) a global pandemic on 11th March 2020. Since then, the world has been firmly in its grip. At the time of writing, there were more than 767,972,961 million confirmed cases and over 6,950,655 million deaths. While the main policy focus has been on controlling the virus and ensuring vaccine roll-out and uptake, the population mental health impacts of the pandemic are expected to be long-term, with certain population groups affected more than others.<h4>Methods</h4>The overall objectives of our 'Coronavirus: Mental Health and the Pandemic' study were to explore UK adults' experiences of the Coronavirus pandemic and to gain insights into the mental health impacts, population-level changes over time, current and future mental health needs, and how these can best be addressed. The wider mixed-methods study consisted of repeated cross-sectional surveys and embedded qualitative sub-studies including in-depth interviews and focus group discussions with the wider UK adult population. For this particular inequalities and mental health sub-study, we used mixed methods data from our cross-sectional surveys and we carried out three Focus Group Discussions with a maximum variation sample from across the UK adult population. The discussions covered the broader topic of 'Inequalities and mental health during the Coronavirus pandemic in the UK' and took place online between April and August 2020. Focus Groups transcripts were analysed using thematic analysis in NVIVO. Cross-sectional survey data were analysed using STATA for descriptive statistics.<h4>Results</h4>Three broad main themes emerged, each supporting a number of sub-themes: (1) Impacts of the pandemic; (2) Moving forward: needs and recommendations; (3) Coping mechanisms and resilience. Findings showed that participants described their experiences of the pandemic in relation to its impact on themselves and on different groups of people. Their experiences illustrated how the pandemic and subsequent measures had exacerbated existing inequalities and created new ones, and triggered various emotional responses. Participants also described their coping strategies and what worked and did not work for them, as well as support needs and recommendations for moving forward through, and out of, the pandemic; all of which are valuable learnings to be considered in policy making for improving mental health and for ensuring future preparedness.<h4>Conclusions</h4>The pandemic is taking a long-term toll on the nations' mental health which will continue to have impacts for years to come. It is therefore crucial to learn the vital lessons learned from this pandemic. Specific as well as whole-government policies need to respond to this, address inequalities and the different needs across the life-course and across society, and take a holistic approach to mental health improvement across the UK.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-16523-9; doi:https://doi.org/10.1186/s12889-023-16523-9; html:https://europepmc.org/articles/PMC10510114; pdf:https://europepmc.org/articles/PMC10510114?pdf=render
 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,,,"<h4>Introduction</h4>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).<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>ISRCTN80103507.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e063199.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063199; html:https://europepmc.org/articles/PMC9453996; pdf:https://europepmc.org/articles/PMC9453996?pdf=render
 36264615,https://doi.org/10.1161/circgen.122.003704,Prevalence and Disease Expression of Pathogenic and Likely Pathogenic Variants Associated With Inherited Cardiomyopathies in the General Population.,"Bourfiss M, van Vugt M, Alasiri AI, Ruijsink B, van Setten J, Schmidt AF, Dooijes D, Puyol-Antón E, Velthuis BK, van Tintelen JP, Te Riele ASJM, Baas AF, Asselbergs FW.",,Circulation. Genomic and precision medicine,2022,2022-10-20,Y,Genetics; Dilated cardiomyopathy; hypertrophic cardiomyopathy; Arrhythmogenic Right Ventricular Cardiomyopathy; Whole Exome Sequencing,,,"<h4>Background</h4>Pathogenic and likely pathogenic variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM) are recommended to be reported as secondary findings in genome sequencing studies. This provides opportunities for early diagnosis, but also fuels uncertainty in variant carriers (G+), since disease penetrance is incomplete. We assessed the prevalence and disease expression of G+ in the general population.<h4>Methods</h4>We identified pathogenic and likely pathogenic variants associated with ARVC, DCM and/or HCM in 200 643 UK Biobank individuals, who underwent whole exome sequencing. We calculated the prevalence of G+ and analyzed the frequency of cardiomyopathy/heart failure diagnosis. In undiagnosed individuals, we analyzed early signs of disease expression using available electrocardiography and cardiac magnetic resonance imaging data.<h4>Results</h4>We found a prevalence of 1:578, 1:251, and 1:149 for pathogenic and likely pathogenic variants associated with ARVC, DCM and HCM respectively. Compared with controls, cardiovascular mortality was higher in DCM G+ (odds ratio 1.67 [95% CI 1.04; 2.59], <i>P</i>=0.030), but similar in ARVC and HCM G+ (<i>P</i>≥0.100). Cardiomyopathy or heart failure diagnosis were more frequent in DCM G+ (odds ratio 3.66 [95% CI 2.24; 5.81], <i>P</i>=4.9×10<sup>-7</sup>) and HCM G+ (odds ratio 3.03 [95% CI 1.98; 4.56], <i>P</i>=5.8×10<sup>-7</sup>), but comparable in ARVC G+ (<i>P</i>=0.172). In contrast, ARVC G+ had more ventricular arrhythmias (<i>P</i>=3.3×10<sup>-4</sup>). In undiagnosed individuals, left ventricular ejection fraction was reduced in DCM G+ (<i>P</i>=0.009).<h4>Conclusions</h4>In the general population, pathogenic and likely pathogenic variants associated with ARVC, DCM, or HCM are not uncommon. Although G+ have increased mortality and morbidity, disease penetrance in these carriers from the general population remains low (1.2-3.1%). Follow-up decisions in case of incidental findings should not be based solely on a variant, but on multiple factors, including family history and disease expression.",,pdf:https://discovery.ucl.ac.uk/10160737/3/Asselbergs_hcg-15-e003704.pdf; doi:https://doi.org/10.1161/CIRCGEN.122.003704; html:https://europepmc.org/articles/PMC9770140; pdf:https://europepmc.org/articles/PMC9770140?pdf=render
 36529028,https://doi.org/10.1016/j.ijmedinf.2022.104942,Defining clinical subtypes of adult asthma using electronic health records: Analysis of a large UK primary care database with external validation.,"Horne EMF, McLean S, Alsallakh MA, Davies GA, Price DB, Sheikh A, Tsanas A.",,International journal of medical informatics,2023,2022-12-07,N,Cluster analysis; Asthma; Electronic Health Records,,,"<h4>Introduction</h4>Asthma is one of the commonest chronic conditions in the world. Subtypes of asthma have been defined, typically from clinical datasets on small, well-characterised subpopulations of asthma patients. We sought to define asthma subtypes from large longitudinal primary care electronic health records (EHRs) using cluster analysis.<h4>Methods</h4>In this retrospective cohort study, we extracted asthma subpopulations from the Optimum Patient Care Research Database (OPCRD) to robustly train and test algorithms, and externally validated findings in the Secure Anonymised Information Linkage (SAIL) Databank. In both databases, we identified adults with an asthma diagnosis code recorded in the three years prior to an index date. Train and test datasets were selected from OPCRD using an index date of Jan 1, 2016. Two internal validation datasets were selected from OPCRD using index dates of Jan 1, 2017 and 2018. Three external validation datasets were selected from SAIL using index dates of Jan 1, 2016, 2017 and 2018. Each dataset comprised 50,000 randomly selected non-overlapping patients. Subtypes were defined by applying multiple correspondence analysis and k-means cluster analysis to the train dataset, and were validated in the internal and external validation datasets.<h4>Results</h4>We defined six asthma subtypes with clear clinical interpretability: low inhaled corticosteroid (ICS) use and low healthcare utilisation (30% of patients); low-to-medium ICS use (36%); low-to-medium ICS use and comorbidities (12%); varied ICS use and comorbid chronic obstructive pulmonary disease (4%); high (10%) and very high ICS use (7%). The subtypes were replicated with high accuracy in internal (91-92%) and external (84-86%) datasets.<h4>Conclusion</h4>Asthma subtypes derived and validated in large independent EHR databases were primarily defined by level of ICS use, level of healthcare use, and presence of comorbidities. This has important clinical implications towards defining asthma subtypes, facilitating patient stratification, and developing more personalised monitoring and treatment strategies.",,doi:https://doi.org/10.1016/j.ijmedinf.2022.104942; doi:https://doi.org/10.1016/j.ijmedinf.2022.104942
 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,,,"<h4>Background</h4>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.<h4>Objectives</h4>We aimed to investigate potential associations between diet and periodontitis using novel statistical techniques for dietary pattern analysis.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/ajcn/article-pdf/112/6/1485/34844146/nqaa266.pdf; doi:https://doi.org/10.1093/ajcn/nqaa266
 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),,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/ehjdh/article-pdf/2/4/635/41972750/ztab082.pdf; doi:https://doi.org/10.1093/ehjdh/ztab082; html:https://europepmc.org/articles/PMC9707970; pdf:https://europepmc.org/articles/PMC9707970?pdf=render
-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.",,pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render
 29457906,https://doi.org/10.1021/acs.jproteome.7b00879,Optimized Phenotypic Biomarker Discovery and Confounder Elimination via Covariate-Adjusted Projection to Latent Structures from Metabolic Spectroscopy Data.,"Posma JM, Garcia-Perez I, Ebbels TMD, Lindon JC, Stamler J, Elliott P, Holmes E, Nicholson JK.",,Journal of proteome research,2018,2018-02-27,Y,Chemometrics; multivariate data analysis; Biomarker Discovery; Sampling Bias; Covariate Adjustment; Metabolic Phenotyping; Random Matrix Theory; Reanalysis; Monte Carlo Cross-validation; Confounder Elimination,Applied Analytics,,"Metabolism is altered by genetics, diet, disease status, environment, and many other factors. Modeling either one of these is often done without considering the effects of the other covariates. Attributing differences in metabolic profile to one of these factors needs to be done while controlling for the metabolic influence of the rest. We describe here a data analysis framework and novel confounder-adjustment algorithm for multivariate analysis of metabolic profiling data. Using simulated data, we show that similar numbers of true associations and significantly less false positives are found compared to other commonly used methods. Covariate-adjusted projections to latent structures (CA-PLS) are exemplified here using a large-scale metabolic phenotyping study of two Chinese populations at different risks for cardiovascular disease. Using CA-PLS, we find that some previously reported differences are actually associated with external factors and discover a number of previously unreported biomarkers linked to different metabolic pathways. CA-PLS can be applied to any multivariate data where confounding may be an issue and the confounder-adjustment procedure is translatable to other multivariate regression techniques.",,pdf:https://pubs.acs.org/doi/pdf/10.1021/acs.jproteome.7b00879; doi:https://doi.org/10.1021/acs.jproteome.7b00879; html:https://europepmc.org/articles/PMC5891819; pdf:https://europepmc.org/articles/PMC5891819?pdf=render
+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.",,pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?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,,,,"<h4>Importance</h4>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.<h4>Objective</h4>To systematically review the susceptibility to and transmission of SARS-CoV-2 among children and adolescents compared with adults.<h4>Data sources</h4>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.<h4>Study selection</h4>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.<h4>Data extraction and synthesis</h4>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.<h4>Main outcomes and measures</h4>Secondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population screening studies) among children and adolescents compared with adults.<h4>Results</h4>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.<h4>Conclusions and relevance</h4>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.",,pdf:https://jamanetwork.com/journals/jamapediatrics/articlepdf/2771181/jamapediatrics_viner_2020_oi_200071_1611604170.25358.pdf; doi:https://doi.org/10.1001/jamapediatrics.2020.4573; html:https://europepmc.org/articles/PMC7519436; doi:https://doi.org/10.1001/jamapediatrics.2020.4573
 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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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).<h4>Conclusion</h4>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; doi:https://doi.org/10.1002/ejhf.2868
 36809311,https://doi.org/10.1093/ejendo/lvad024,The ultra-acute steroid response to traumatic injury: a cohort study.,"Bentley C, Hazeldine J, Bravo L, Taylor AE, Gilligan LC, Shaheen F, Acharjee A, Gkoutos G, Foster MA, Arlt W, Lord JM.",,European journal of endocrinology,2023,2023-03-01,N,Steroids; Mass spectrometry; Glucocorticoids; Major Trauma; 11-Oxygenated Androgens,,,"<h4>Objective</h4>Trauma-induced steroid changes have been studied post-hospital admission, resulting in a lack of understanding of the speed and extent of the immediate endocrine response to injury. The Golden Hour study was designed to capture the ultra-acute response to traumatic injury.<h4>Design</h4>We conducted an observational cohort study including adult male trauma patients <60 years, with blood samples drawn ≤1 h of major trauma by pre-hospital emergency responders.<h4>Methods</h4>We recruited 31 adult male trauma patients (mean age 28 [range 19-59] years) with a mean injury severity score (ISS) of 16 (IQR 10-21). The median time to first sample was 35 (range 14-56) min, with follow-up samples collected 4-12 and 48-72 h post-injury. Serum steroids in patients and age- and sex-matched healthy controls (HCs) (n = 34) were analysed by tandem mass spectrometry.<h4>Results</h4>Within 1 h of injury, we observed an increase in glucocorticoid and adrenal androgen biosynthesis. Cortisol and 11-hydroxyandrostendione increased rapidly, whilst cortisone and 11-ketoandrostenedione decreased, reflective of increased cortisol and 11-oxygenated androgen precursor biosynthesis by 11β-hydroxylase and increased cortisol activation by 11β-hydroxysteroid dehydrogenase type 1. Active classic gonadal androgens testosterone and 5α-dihydrotestosterone decreased, whilst the active 11-oxygenated androgen 11-ketotestosterone maintained pre-injury levels.<h4>Conclusions</h4>Changes in steroid biosynthesis and metabolism occur within minutes of traumatic injury. Studies that address whether ultra-early changes in steroid metabolism are associated with patient outcomes are now required.",,pdf:https://academic.oup.com/ejendo/article-pdf/188/3/290/49630912/lvad024.pdf; doi:https://doi.org/10.1093/ejendo/lvad024
@@ -1110,16 +1110,16 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 37408046,https://doi.org/10.1186/s40545-023-00590-9,Delivering the precision oncology paradigm: reduced R&D costs and greater return on investment through a companion diagnostic informed precision oncology medicines approach.,"Henderson RH, French D, Stewart E, Smart D, Idica A, Redmond S, Eckstein M, Clark J, Sullivan R, Keeling P, Lawler M.",,Journal of pharmaceutical policy and practice,2023,2023-07-05,Y,,,,"<h4>Background</h4>Precision oncology medicines represent a paradigm shift compared to non-precision oncology medicines in cancer therapy, in some situations delivering more clinical benefit, and potentially lowering healthcare costs. We determined whether employing a companion diagnostic (CDx) approach during oncology medicines development delivers effective therapies that are within the cost constraints of current health systems. R&D costs of developing a medicine are subject to debate, with average estimates ranging from $765 million (m) to $4.6 billion (b). Our aim was to determine whether precision oncology medicines are cheaper to bring from R&D to market; a secondary goal was to determine whether precision oncology medicines have a greater return on investment (ROI).<h4>Method</h4>Data on oncology medicines approved between 1997 and 2020 by the US Food and Drug Administration (FDA) were analysed from the Securities and Exchange Commission (SEC) filings. Data were compiled from 10-K, 10-Q, and 20-F financial performance filings on medicines' development costs through their R&D lifetime. Clinical trial data were split into clinical trial phases 1-3 and probability of success (POS) of trials was calculated, along with preclinical costs. Cost-of-capital (CoC) approach was applied and, if appropriate, a tax rebate was subtracted from the total.<h4>Results</h4>Data on 42 precision and 29 non-precision oncology medicines from 56 companies listed by the National Cancer Institute which had complete data available were analysed. Estimated mean cost to deliver a new oncology medicine was $4.4b (95% CI, $3.6-5.2b). Costs to bring a precision oncology medicine to market were $1.1b less ($3.5b; 95% CI, $2.7-4.5b) compared to non-precision oncology medicines ($4.6b; 95% CI, $3.5-6.1b). The key driver of costs was POS of clinical trials, accounting for a difference of $591.3 m. Additional data analysis illustrated that there was a 27% increase in return on investment (ROI) of precision oncology medicines over non-precision oncology medicines.<h4>Conclusion</h4>Our results provide an accurate estimate of the R&D spend required to bring an oncology medicine to market. Deployment of a CDx at the earliest stage substantially lowers the cost associated with oncology medicines development, potentially making them available to more patients, while staying within the cost constraints of cancer health systems.",,pdf:https://joppp.biomedcentral.com/counter/pdf/10.1186/s40545-023-00590-9; doi:https://doi.org/10.1186/s40545-023-00590-9; html:https://europepmc.org/articles/PMC10320864; pdf:https://europepmc.org/articles/PMC10320864?pdf=render
 35264566,https://doi.org/10.1038/s41467-022-28729-3,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,2022,2022-03-09,Y,,,,"Many individual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal the molecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism (VTE) risk. We identify PROCR-p.Ser219Gly as the likely causal variant at the locus and protein C as a causal factor. Using genetic analyses, human recall-by-genotype and in vitro experimentation, we demonstrate that PROCR-219Gly increases plasma levels of (activated) protein C through endothelial protein C receptor (EPCR) ectodomain shedding in endothelial cells, attenuating leukocyte-endothelial cell adhesion and vascular inflammation. We also associate PROCR-219Gly with an increased pro-thrombotic state via coagulation factor VII, a ligand of EPCR. Our study, which links PROCR-219Gly to CAD through anti-inflammatory mechanisms and to VTE through pro-thrombotic mechanisms, provides a framework to reveal the mechanisms underlying similar cross-phenotype associations.",,pdf:https://www.nature.com/articles/s41467-022-28729-3.pdf; doi:https://doi.org/10.1038/s41467-022-28729-3; html:https://europepmc.org/articles/PMC8907312; pdf:https://europepmc.org/articles/PMC8907312?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>International registered report identifier (irrid)</h4>PRR1-10.2196/42965.",,pdf:https://www.researchprotocols.org/2023/1/e42965/PDF; doi:https://doi.org/10.2196/42965; html:https://europepmc.org/articles/PMC9936366
-37813531,https://doi.org/10.1136/bmjopen-2023-073162,Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.,"Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMJ open,2023,2023-10-09,Y,Obstetrics; epidemiology; Maternal Medicine,,,"<h4>Introduction</h4>Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.<h4>Methods and analysis</h4>Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.<h4>Ethics and dissemination</h4>Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.",,doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render
 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
+37813531,https://doi.org/10.1136/bmjopen-2023-073162,Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.,"Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMJ open,2023,2023-10-09,Y,Obstetrics; epidemiology; Maternal Medicine,,,"<h4>Introduction</h4>Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.<h4>Methods and analysis</h4>Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.<h4>Ethics and dissemination</h4>Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.",,doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?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
 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
 36289925,https://doi.org/10.3390/biomedicines10102662,"Temporal Evolution of Multiday, Epileptic Functional Networks Prior to Seizure Occurrence.","Laiou P, Biondi A, Bruno E, Viana PF, Winston JS, Rashid Z, Ranjan Y, Conde P, Stewart C, Sun S, Zhang Y, Folarin A, Dobson RJB, Schulze-Bonhage A, Dümpelmann M, Richardson MP, Radar-Cns Consortium.",,Biomedicines,2022,2022-10-21,Y,Epilepsy; EEG; Graph theory; ECG; Functional Network; Seizure Lateralization; Evolving Network,,,"Epilepsy is one of the most common neurological disorders, characterized by the occurrence of repeated seizures. Given that epilepsy is considered a network disorder, tools derived from network neuroscience may confer the valuable ability to quantify the properties of epileptic brain networks. In this study, we use well-established brain network metrics (i.e., mean strength, variance of strength, eigenvector centrality, betweenness centrality) to characterize the temporal evolution of epileptic functional networks over several days prior to seizure occurrence. We infer the networks using long-term electroencephalographic recordings from 12 people with epilepsy. We found that brain network metrics are variable across days and show a circadian periodicity. In addition, we found that in 9 out of 12 patients the distribution of the variance of strength in the day (or even two last days) prior to seizure occurrence is significantly different compared to the corresponding distributions on all previous days. Our results suggest that brain network metrics computed fromelectroencephalographic recordings could potentially be used to characterize brain network changes that occur prior to seizures, and ultimately contribute to seizure warning systems.",,pdf:https://www.mdpi.com/2227-9059/10/10/2662/pdf?version=1666684470; doi:https://doi.org/10.3390/biomedicines10102662; html:https://europepmc.org/articles/PMC9599905; pdf:https://europepmc.org/articles/PMC9599905?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,,,,,,pdf:https://biblio.ugent.be/publication/8757812/file/8757816.pdf; doi:https://doi.org/10.1111/bjd.21042; html:https://europepmc.org/articles/PMC9545500; pdf:https://europepmc.org/articles/PMC9545500?pdf=render
 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,,,"<h4>Background</h4>Biological heart age estimation can provide insights into cardiac aging. However, existing studies do not consider differential aging across cardiac regions.<h4>Purpose</h4>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.<h4>Study type</h4>Cross-sectional.<h4>Population</h4>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).<h4>Field strength/sequence</h4>A 1.5 T/balanced steady-state free precession.<h4>Assessment</h4>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).<h4>Statistical test</h4>Multiple testing correction with false discovery method (threshold = 5%).<h4>Results</h4>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<sup>-26</sup> ). 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<sup>-6</sup> ).<h4>Data conclusion</h4>This work demonstrates image-based heart age estimation as a novel method for understanding cardiac aging.<h4>Evidence level</h4>1.<h4>Technical efficacy</h4>Stage 1.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmri.28675; doi:https://doi.org/10.1002/jmri.28675
 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,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cea.13741; doi:https://doi.org/10.1111/cea.13741
-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,,,"<h4>Objectives</h4>To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.",,pdf:https://heart.bmj.com/content/heartjnl/early/2023/03/21/heartjnl-2022-321888.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321888; html:https://europepmc.org/articles/PMC10314020; pdf:https://europepmc.org/articles/PMC10314020?pdf=render
 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.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008164&type=printable; doi:https://doi.org/10.1371/journal.pgen.1008164; html:https://europepmc.org/articles/PMC6592570; pdf:https://europepmc.org/articles/PMC6592570?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,,,"<h4>Objectives</h4>To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.",,pdf:https://heart.bmj.com/content/heartjnl/early/2023/03/21/heartjnl-2022-321888.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321888; html:https://europepmc.org/articles/PMC10314020; pdf:https://europepmc.org/articles/PMC10314020?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,,,"<h4>Aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Over one in six children (17.2%, <i>n</i> = 85,792) were currently or previously in contact with social services, and almost one child in every 20 (4.8%, <i>n</i> = 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.<h4>Conclusion</h4>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.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A60E6D761449A937DCE08F3A075B236D/S2045796023000276a.pdf/div-class-title-the-mental-health-of-all-children-in-contact-with-social-services-a-population-wide-record-linkage-study-in-northern-ireland-div.pdf; doi:https://doi.org/10.1017/S2045796023000276; html:https://europepmc.org/articles/PMC10227534; pdf:https://europepmc.org/articles/PMC10227534?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.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/20552076211048654; doi:https://doi.org/10.1177/20552076211048654; html:https://europepmc.org/articles/PMC8637703; pdf:https://europepmc.org/articles/PMC8637703?pdf=render
 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,,,"<h4>Aims</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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: <i>Bone Joint J</i> 2021;103-B(4):769-774.",,doi:https://doi.org/10.1302/0301-620X.103B4.BJJ-2020-1647.R1
@@ -1133,8 +1133,8 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI
 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),,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Prospero registration number</h4>CRD42019140361 and CRD42019161764.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e048008.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-048008; html:https://europepmc.org/articles/PMC8273461; pdf:https://europepmc.org/articles/PMC8273461?pdf=render
 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.",,pdf:https://www.nature.com/articles/s41398-018-0236-1.pdf; doi:https://doi.org/10.1038/s41398-018-0236-1; html:https://europepmc.org/articles/PMC6123450; pdf:https://europepmc.org/articles/PMC6123450?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,,,,,html:http://hdl.handle.net/20.500.11820/885f92d9-96bd-467c-893a-d5eb23d109e9; doi:https://doi.org/10.1136/thoraxjnl-2020-215566
-37519214,https://doi.org/10.1177/09622802231188518,Multiple imputation approaches for epoch-level accelerometer data in trials.,"Tackney MS, Williamson E, Cook DG, Limb E, Harris T, Carpenter J.",,Statistical methods in medical research,2023,2023-07-31,Y,Missing Data; Accelerometer; Multiple Imputation; Wearables; Physical Activity Trial,,,"Clinical trials that investigate physical activity interventions often use accelerometers to measure step count at a very granular level, for example in 5-second epochs. Participants typically wear the accelerometer for a week-long period at baseline, and for one or more week-long follow-up periods after the intervention. The data is aggregated to provide daily or weekly step counts for the primary analysis. Missing data are common as participants may not wear the device as per protocol. Approaches to handling missing data in the literature have defined missingness on the day level using a threshold on daily weartime, which leads to loss of information on the time of day when data are missing. We propose an approach to identifying and classifying missingness at the finer epoch-level and present two approaches to handling missingness using multiple imputation. Firstly, we present a parametric approach which accounts for the number of missing epochs per day. Secondly, we describe a non-parametric approach where missing periods during the day are replaced by donor data from the same person where possible, or data from a different person who is matched on demographic and physical activity-related variables. Our simulation studies show that the non-parametric approach leads to estimates of the effect of treatment that are least biased while maintaining small standard errors. We illustrate the application of these different multiple imputation strategies to the analysis of the 2017 PACE-UP trial. The proposed framework is likely to be applicable to other digital health outcomes and to other wearable devices.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/09622802231188518; doi:https://doi.org/10.1177/09622802231188518; html:https://europepmc.org/articles/PMC10563375; pdf:https://europepmc.org/articles/PMC10563375?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,,,,"<h4>Objective</h4>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.<h4>Design</h4>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.<h4>Setting</h4>Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data.<h4>Population</h4>Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021.<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.bmj.com/content/bmj/376/bmj-2021-067519.full.pdf; doi:https://doi.org/10.1136/bmj-2021-067519; html:https://europepmc.org/articles/PMC8753487; pdf:https://europepmc.org/articles/PMC8753487?pdf=render
+37519214,https://doi.org/10.1177/09622802231188518,Multiple imputation approaches for epoch-level accelerometer data in trials.,"Tackney MS, Williamson E, Cook DG, Limb E, Harris T, Carpenter J.",,Statistical methods in medical research,2023,2023-07-31,Y,Missing Data; Accelerometer; Multiple Imputation; Wearables; Physical Activity Trial,,,"Clinical trials that investigate physical activity interventions often use accelerometers to measure step count at a very granular level, for example in 5-second epochs. Participants typically wear the accelerometer for a week-long period at baseline, and for one or more week-long follow-up periods after the intervention. The data is aggregated to provide daily or weekly step counts for the primary analysis. Missing data are common as participants may not wear the device as per protocol. Approaches to handling missing data in the literature have defined missingness on the day level using a threshold on daily weartime, which leads to loss of information on the time of day when data are missing. We propose an approach to identifying and classifying missingness at the finer epoch-level and present two approaches to handling missingness using multiple imputation. Firstly, we present a parametric approach which accounts for the number of missing epochs per day. Secondly, we describe a non-parametric approach where missing periods during the day are replaced by donor data from the same person where possible, or data from a different person who is matched on demographic and physical activity-related variables. Our simulation studies show that the non-parametric approach leads to estimates of the effect of treatment that are least biased while maintaining small standard errors. We illustrate the application of these different multiple imputation strategies to the analysis of the 2017 PACE-UP trial. The proposed framework is likely to be applicable to other digital health outcomes and to other wearable devices.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/09622802231188518; doi:https://doi.org/10.1177/09622802231188518; html:https://europepmc.org/articles/PMC10563375; pdf:https://europepmc.org/articles/PMC10563375?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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; doi:https://doi.org/10.1093/ije/dyaa216; html:https://europepmc.org/articles/PMC8271202; pdf:https://europepmc.org/articles/PMC8271202?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,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016330; 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
 32616598,https://doi.org/10.1183/13993003.01809-2020,Using imaging to combat a pandemic: rationale for developing the UK National COVID-19 Chest Imaging Database. ,"Jacob J, Alexander D, Baillie JK, Berka R, Bertolli O, Blackwood J, Buchan I, Bloomfield C, Cushnan D, Docherty A, Edey A, Favaro A, Gleeson F, Halling-Brown M, Hare S, Jefferson E, Johnstone A, Kirby M, McStay R, Nair A, Openshaw PJM, Parker G, Reilly G, Robinson G, Roditi G, Rodrigues JCL, Sebire N, Semple MG, Sudlow C, Woznitza N, Joshi I.",,The European respiratory journal,2020,2020-08-13,Y,,,,"The National COVID-19 Chest Imaging Database (NCCID) is a repository of chest radiographs, CT and MRI images and clinical data from COVID-19 patients across the UK, to support research and development of AI technology and give insight into COVID-19 disease https://bit.ly/3eQeuha",,pdf:https://erj.ersjournals.com/content/erj/56/2/2001809.full.pdf; doi:https://doi.org/10.1183/13993003.01809-2020; html:https://europepmc.org/articles/PMC7331656; pdf:https://europepmc.org/articles/PMC7331656?pdf=render
@@ -1152,13 +1152,13 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI
 34598995,https://doi.org/10.1136/bmjopen-2021-055219,"wEight chanGes, caRdio-mEtabolic risks and morTality in patients with hyperthyroidism (EGRET): a protocol for a CPRD-HES linked cohort study.","Torlinska B, Hazlehurst JM, Nirantharakumar K, Thomas GN, Priestley JR, Finnikin SJ, Saunders P, Abrams KR, Boelaert K.",,BMJ open,2021,2021-10-01,Y,Thyroid disease; epidemiology; Cardiac Epidemiology,,,"<h4>Introduction</h4>Hyperthyroidism is a common condition affecting up to 3% of the UK population. Treatment improves symptoms and reduces the risk of atrial fibrillation and stroke that contribute to increased mortality. The most common symptom is weight loss, which is reversed during treatment. However, the weight regain may be excessive, contributing to increased risk of obesity. Current treatment options include antithyroid drugs, radioiodine and thyroidectomy. Whether there are differences in either weight change or the long-term cardiometabolic risk between the three treatments is unclear.<h4>Methods and analysis</h4>The study will establish the natural history of weight change in hyperthyroidism, investigate the risk of obesity and risks of cardiometabolic conditions and death relative to the treatment. The data on patients diagnosed with hyperthyroidism between 1 January 1996 and 31 December 2015 will come from Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office of National Statistics Death Registry. The weight changes will be modelled using a flexible joint modelling, accounting for mortality. Obesity prevalence in the general population will be sourced from Health Survey for England and compared with the post-treatment prevalence of obesity in patients with hyperthyroidism. The incidence and time-to-event of major adverse cardiovascular events, other cardiometabolic outcomes and mortality will be compared between the treatments using the inverse propensity weighting model. Incidence rate ratios of outcomes will be modelled with Poisson regression. Time to event will be analysed using Cox proportional hazards model. A competing risks approach will be adopted to estimate comparative incidences to allow for the impact of mortality.<h4>Ethics and dissemination</h4>The study will bring new knowledge on the risk of developing obesity, cardiometabolic morbidity and mortality following treatment for hyperthyroidism to inform clinical practice and public health policies. The results will be disseminated via open-access peer-reviewed publications and directly to the patients and public groups (Independent Scientific Advisory Committee protocol approval #20_000185).",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e055219.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055219; html:https://europepmc.org/articles/PMC8488707; pdf:https://europepmc.org/articles/PMC8488707?pdf=render
 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,,,"<h4>Background</h4>No single study contrasts the extent and consequences of inequity of kidney care across the clinical course of kidney disease.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfac224/45505736/gfac224.pdf; doi:https://doi.org/10.1093/ndt/gfac224; html:https://europepmc.org/articles/PMC10157789; pdf:https://europepmc.org/articles/PMC10157789?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.",,pdf:https://discovery.ucl.ac.uk/10149151/1/Dobson_The%20COPILOT%20Raw%20Illumina%20Genotyping%20QC%20Protocol_VoR.pdf; doi:https://doi.org/10.1002/cpz1.373
-37477360,https://doi.org/10.1097/ypg.0000000000000349,Schizophrenia polygenic risk score and type 2 diabetes onset in older adults with no schizophrenia diagnosis.,"Shamsutdinova D, Ajnakina O, Roberts A, Stahl D.",,Psychiatric genetics,2023,2023-07-04,Y,,,,"<h4>Objectives</h4>An association between type 2 diabetes (T2DM) and schizophrenia has long been observed, and recent research revealed presence of shared genetic factors. However, epidemiological evidence was inconsistent, some reported insignificant contribution of genetic factors to T2DM-schizophrenia comorbidity. Prior works studied people with schizophrenia, particularly, antipsychotic-naive patients, or those during the first psychotic experience to limit schizophrenia-related environmental factors. In contrast, we controlled such factors by utilizing a general population sample of individuals undiagnosed with schizophrenia. We hypothesized that if schizophrenia genetics impact T2DM development and such impact is not fully mediated by schizophrenia-related environment, people with high polygenic schizophrenia risk would exhibit elevated T2DM incidence.<h4>Methods</h4>Using a population-representative sample of adults aged ≥50 from English Longitudinal Study of Ageing ( n  = 5968, 493 T2DM cases, average follow-up 8.7 years), we investigated if schizophrenia polygenic risk score (PGS-SZ) is associated with T2DM onset. A proportional hazards model with interval censoring was adjusted for age and sex (Model 1), and age, sex, BMI, hypertension, cardiovascular diseases, exercise, smoking, depressive symptoms and T2DM polygenic risk score (Model 2). According to the power calculations, hazard rates > 1.14 per standard deviation in PGS-SZ could be detected.<h4>Results</h4>We did not observe a significant association between PGS-SZ and T2DM incidence (hazard ratio 1.04; 95% CI 0.93-1.15; and 1.01, 95% CI 0.94-1.09).<h4>Conclusion</h4>Our results suggest low contribution of the intrinsic biological mechanisms driven by the polygenic risk of schizophrenia on future T2DM onset. Further research is needed.",,doi:https://doi.org/10.1097/YPG.0000000000000349; html:https://europepmc.org/articles/PMC10501355; pdf:https://europepmc.org/articles/PMC10501355?pdf=render
 32717063,https://doi.org/10.1093/cvr/cvaa233,Gene expression profiling of hypertrophic cardiomyocytes identifies new players in pathological remodelling.,"Vigil-Garcia M, Demkes CJ, Eding JEC, Versteeg D, de Ruiter H, Perini I, Kooijman L, Gladka MM, Asselbergs FW, Vink A, Harakalova M, Bossu A, van Veen TAB, Boogerd CJ, van Rooij E.",,Cardiovascular research,2021,2021-05-01,Y,Cardiomyocyte; hypertrophy; Heart Failure; Rna Sequencing; Pfkp; Pathological Remodelling,,,"<h4>Aims</h4>Pathological cardiac remodelling is characterized by cardiomyocyte (CM) hypertrophy and fibroblast activation, which can ultimately lead to maladaptive hypertrophy and heart failure (HF). Genome-wide expression analysis on heart tissue has been instrumental for the identification of molecular mechanisms at play. However, these data were based on signals derived from all cardiac cell types. Here, we aimed for a more detailed view on molecular changes driving maladaptive CM hypertrophy to aid in the development of therapies to reverse pathological remodelling.<h4>Methods and results</h4>Utilizing CM-specific reporter mice exposed to pressure overload by transverse aortic banding and CM isolation by flow cytometry, we obtained gene expression profiles of hypertrophic CMs in the more immediate phase after stress, and CMs showing pathological hypertrophy. We identified subsets of genes differentially regulated and specific for either stage. Among the genes specifically up-regulated in the CMs during the maladaptive phase we found known stress markers, such as Nppb and Myh7, but additionally identified a set of genes with unknown roles in pathological hypertrophy, including the platelet isoform of phosphofructokinase (PFKP). Norepinephrine-angiotensin II treatment of cultured human CMs induced the secretion of N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) and recapitulated the up-regulation of these genes, indicating conservation of the up-regulation in failing CMs. Moreover, several genes induced during pathological hypertrophy were also found to be increased in human HF, with their expression positively correlating to the known stress markers NPPB and MYH7. Mechanistically, suppression of Pfkp in primary CMs attenuated stress-induced gene expression and hypertrophy, indicating that Pfkp is an important novel player in pathological remodelling of CMs.<h4>Conclusion</h4>Using CM-specific transcriptomic analysis, we identified novel genes induced during pathological hypertrophy that are relevant for human HF, and we show that PFKP is a conserved failure-induced gene that can modulate the CM stress response.",,doi:https://doi.org/10.1093/cvr/cvaa233; doi:https://doi.org/10.1093/cvr/cvaa233; html:https://europepmc.org/articles/PMC8152696; pdf:https://europepmc.org/articles/PMC8152696?pdf=render
+37477360,https://doi.org/10.1097/ypg.0000000000000349,Schizophrenia polygenic risk score and type 2 diabetes onset in older adults with no schizophrenia diagnosis.,"Shamsutdinova D, Ajnakina O, Roberts A, Stahl D.",,Psychiatric genetics,2023,2023-07-04,Y,,,,"<h4>Objectives</h4>An association between type 2 diabetes (T2DM) and schizophrenia has long been observed, and recent research revealed presence of shared genetic factors. However, epidemiological evidence was inconsistent, some reported insignificant contribution of genetic factors to T2DM-schizophrenia comorbidity. Prior works studied people with schizophrenia, particularly, antipsychotic-naive patients, or those during the first psychotic experience to limit schizophrenia-related environmental factors. In contrast, we controlled such factors by utilizing a general population sample of individuals undiagnosed with schizophrenia. We hypothesized that if schizophrenia genetics impact T2DM development and such impact is not fully mediated by schizophrenia-related environment, people with high polygenic schizophrenia risk would exhibit elevated T2DM incidence.<h4>Methods</h4>Using a population-representative sample of adults aged ≥50 from English Longitudinal Study of Ageing ( n  = 5968, 493 T2DM cases, average follow-up 8.7 years), we investigated if schizophrenia polygenic risk score (PGS-SZ) is associated with T2DM onset. A proportional hazards model with interval censoring was adjusted for age and sex (Model 1), and age, sex, BMI, hypertension, cardiovascular diseases, exercise, smoking, depressive symptoms and T2DM polygenic risk score (Model 2). According to the power calculations, hazard rates > 1.14 per standard deviation in PGS-SZ could be detected.<h4>Results</h4>We did not observe a significant association between PGS-SZ and T2DM incidence (hazard ratio 1.04; 95% CI 0.93-1.15; and 1.01, 95% CI 0.94-1.09).<h4>Conclusion</h4>Our results suggest low contribution of the intrinsic biological mechanisms driven by the polygenic risk of schizophrenia on future T2DM onset. Further research is needed.",,doi:https://doi.org/10.1097/YPG.0000000000000349; html:https://europepmc.org/articles/PMC10501355; pdf:https://europepmc.org/articles/PMC10501355?pdf=render
 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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeab266/41764801/jeab266.pdf; doi:https://doi.org/10.1093/ehjci/jeab266; html:https://europepmc.org/articles/PMC9365306; pdf:https://europepmc.org/articles/PMC9365306?pdf=render
 34139439,https://doi.org/10.1016/j.compbiomed.2021.104542,Development and application of the ocular immune-mediated inflammatory diseases ontology enhanced with synonyms from online patient support forum conversation.,"Pendleton SC, Slater LT, Karwath A, Gilbert RM, Davis N, Pesudovs K, Liu X, Denniston AK, Gkoutos GV, Braithwaite T.",,Computers in biology and medicine,2021,2021-06-08,Y,Inflammation; Uveitis; Ontology; Patient Voice; Sentiment,,,"<h4>Background</h4>Unstructured text created by patients represents a rich, but relatively inaccessible resource for advancing patient-centred care. This study aimed to develop an ontology for ocular immune-mediated inflammatory diseases (OcIMIDo), as a tool to facilitate data extraction and analysis, illustrating its application to online patient support forum data.<h4>Methods</h4>We developed OcIMIDo using clinical guidelines, domain expertise, and cross-references to classes from other biomedical ontologies. We developed an approach to add patient-preferred synonyms text-mined from oliviasvision.org online forum, using statistical ranking. We validated the approach with split-sampling and comparison to manual extraction. Using OcIMIDo, we then explored the frequency of OcIMIDo classes and synonyms, and their potential association with natural language sentiment expressed in each online forum post.<h4>Findings</h4>OcIMIDo (version 1.2) includes 661 classes, describing anatomy, clinical phenotype, disease activity status, complications, investigations, interventions and functional impacts. It contains 1661 relationships and axioms, 2851 annotations, including 1131 database cross-references, and 187 patient-preferred synonyms. To illustrate OcIMIDo's potential applications, we explored 9031 forum posts, revealing frequent mention of different clinical phenotypes, treatments, and complications. Language sentiment analysis of each post was generally positive (median 0.12, IQR 0.01-0.24). In multivariable logistic regression, the odds of a post expressing negative sentiment were significantly associated with first posts as compared to replies (OR 3.3, 95% CI 2.8 to 3.9, p < 0.001).<h4>Conclusion</h4>We report the development and validation of a new ontology for inflammatory eye diseases, which includes patient-preferred synonyms, and can be used to explore unstructured patient or physician-reported text data, with many potential applications.",,doi:https://doi.org/10.1016/j.compbiomed.2021.104542; doi:https://doi.org/10.1016/j.compbiomed.2021.104542; html:https://europepmc.org/articles/PMC8404035
+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.",,pdf:https://www.mdpi.com/2077-0383/10/5/921/pdf?version=1615467325; doi:https://doi.org/10.3390/jcm10050921; html:https://europepmc.org/articles/PMC7956169; pdf:https://europepmc.org/articles/PMC7956169?pdf=render
 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
 37477803,https://doi.org/10.1007/s11897-023-00615-z,Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review.,"Meijs C, Handoko ML, Savarese G, Vernooij RWM, Vaartjes I, Banerjee A, Koudstaal S, Brugts JJ, Asselbergs FW, Uijl A.",,Current heart failure reports,2023,2023-07-21,Y,Clustering; Phenotyping; Heart Failure; Machine Learning; Precision Medicine,,,"<h4>Review purpose</h4>This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice.<h4>Findings</h4>34 studies were identified (n = 19 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. HF = heart failure, EF = ejection fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, CKD = chronic kidney disease, AF = atrial fibrillation, IHD = ischaemic heart disease, CAD = coronary artery disease, ICD = implantable cardioverter-defibrillator, CRT = cardiac resynchronization therapy, NT-proBNP = N-terminal pro b-type natriuretic peptide, BMI = Body Mass Index, COPD = Chronic obstructive pulmonary disease.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00615-z.pdf; doi:https://doi.org/10.1007/s11897-023-00615-z; html:https://europepmc.org/articles/PMC10589200; pdf:https://europepmc.org/articles/PMC10589200?pdf=render
-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.",,pdf:https://www.mdpi.com/2077-0383/10/5/921/pdf?version=1615467325; doi:https://doi.org/10.3390/jcm10050921; html:https://europepmc.org/articles/PMC7956169; pdf:https://europepmc.org/articles/PMC7956169?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,,,,,,pdf:https://www.bmj.com/content/bmj/380/bmj-2022-073149.full.pdf; doi:https://doi.org/10.1136/bmj-2022-073149; html:https://europepmc.org/articles/PMC9973128
 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; doi:https://doi.org/10.1016/S2589-7500(22)00249-7
 37735103,https://doi.org/10.1136/bmjresp-2023-001895,"Preterm birth, birth weight, infant weight gain and their associations with childhood asthma and spirometry: a cross-sectional observational study in Nairobi, Kenya.","Meme H, Amukoye E, Bowyer C, Chakaya J, Dobson R, Fuld J, Gray CM, Kiplimo R, Lesosky M, Mortimer K, Ndombi A, Obasi A, Orina F, Quint JK, Semple S, West SE, Zurba L, Devereux G.",,BMJ open respiratory research,2023,2023-09-01,Y,Asthma; Paediatric Lung Disaese; Asthma Epidemiology,,,"<h4>Background</h4>In sub-Saharan Africa, the origins of asthma and high prevalence of abnormal lung function remain unclear. In high-income countries (HICs), associations between birth measurements and childhood asthma and lung function highlight the importance of antenatal and early life factors in the aetiology of asthma and abnormal lung function in children. We present here the first study in sub-Saharan Africa to relate birth characteristics to both childhood respiratory symptoms and lung function.<h4>Methods</h4>Children attending schools in two socioeconomically contrasting but geographically close areas of Nairobi, Kenya, were recruited to a cross-sectional study of childhood asthma and lung function. Questionnaires quantified respiratory symptoms and preterm birth; lung function was measured by spirometry; and parents were invited to bring the child's immunisation booklet containing records of birth weight and serial weights in the first year.<h4>Results</h4>2373 children participated, 52% girls, median age (IQR), 10 years (8-13). Spirometry data were available for 1622. Child immunisation booklets were available for 500 and birth weight and infant weight gain data were available for 323 and 494 children, respectively. In multivariable analyses, preterm birth was associated with the childhood symptoms 'wheeze in the last 12 months'; OR 1.64, (95% CI 1.03 to 2.62), p=0.038; and 'trouble breathing' 3.18 (95% CI 2.27 to 4.45), p<0.001. Birth weight (kg) was associated with forced expiratory volume in 1 s z-score, regression coefficient (β) 0.30 (0.08, 0.52), p=0.008, FVC z-score 0.29 (95% CI 0.08 to 0.51); p=0.008 and restricted spirometry, OR 0.11 (95% CI 0.02 to 0.78), p=0.027.<h4>Conclusion</h4>These associations are in keeping with those in HICs and highlight antenatal factors in the aetiology of asthma and lung function abnormalities in sub-Saharan Africa.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/10/1/e001895.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001895; html:https://europepmc.org/articles/PMC10514609; pdf:https://europepmc.org/articles/PMC10514609?pdf=render
@@ -1176,8 +1176,8 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI
 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,,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0240902&type=printable; doi:https://doi.org/10.1371/journal.pone.0240902; html:https://europepmc.org/articles/PMC7660485; pdf:https://europepmc.org/articles/PMC7660485?pdf=render
 35048949,https://doi.org/10.1093/eurjpc/zwac008,Light to moderate coffee consumption is associated with lower risk of death: a UK Biobank study.,"Simon J, Fung K, Raisi-Estabragh Z, Aung N, Khanji MY, Kolossváry M, Merkely B, Munroe PB, Harvey NC, Piechnik SK, Neubauer S, Petersen SE, Maurovich-Horvat P.",,European journal of preventive cardiology,2022,2022-05-01,N,Cardiac Magnetic Resonance; Cardiovascular Health; Coffee Consumption,,,"<h4>Aims</h4>To study the association of daily coffee consumption with all-cause and cardiovascular (CV) mortality and major CV outcomes. In a subgroup of participants who underwent cardiovascular magnetic resonance (CMR) imaging, we evaluated the association between regular coffee intake and cardiac structure and function.<h4>Methods and results</h4>UK Biobank participants without clinically manifested heart disease at the time of recruitment were included. Regular coffee intake was categorized into three groups: zero, light-to-moderate (0.5-3 cups/day), and high (>3 cups/day). In the multivariate analysis, we adjusted for the main CV risk factors. We included 468 629 individuals (56.2 ± 8.1 years, 44.2% male), of whom 22.1% did not consume coffee regularly, 58.4% had 0.5-3 cups per day, and 19.5% had >3 cups per day. Compared to non-coffee drinkers, light-to-moderate (0.5-3 cups per day) coffee drinking was associated with lower risk of all-cause mortality [multivariate hazard ratio (HR) = 0.88, 95% confidence interval (CI): 0.83-0.92; P < 0.001] and CV mortality (multivariate HR = 0.83, 95% CI: 0.74-0.94; P = 0.006), and incident stroke (multivariate HR = 0.79, 95% CI: 0.63-0.99 P = 0.037) after a median follow-up of 11 years. CMR data were available in 30 650 participants. Both light-to-moderate and high coffee consuming categories were associated with dose-dependent increased left and right ventricular end-diastolic, end-systolic and stroke volumes, and greater left ventricular mass.<h4>Conclusion</h4>Coffee consumption of up to three cups per day was associated with favourable CV outcomes. Regular coffee consumption was also associated with a likely healthy pattern of CMR metrics in keeping with the reverse of age-related cardiac alterations.",,pdf:https://academic.oup.com/eurjpc/article-pdf/29/6/982/43589594/zwac008.pdf; doi:https://doi.org/10.1093/eurjpc/zwac008
 29944675,https://doi.org/10.1371/journal.pone.0199026,"The diagnosis, burden and prognosis of dementia: A record-linkage cohort study in England.","Pujades-Rodriguez M, Assi V, Gonzalez-Izquierdo A, Wilkinson T, Schnier C, Sudlow C, Hemingway H, Whiteley WN.",,PloS one,2018,2018-06-26,Y,,The Human Phenome,,"<h4>Objectives</h4>Electronic health records (EHR) might be a useful resource to study the risk factors and clinical care of people with dementia. We sought to determine the diagnostic validity of dementia captured in linked EHR.<h4>Methods and findings</h4>A cohort of adults in linked primary care, hospital, disease registry and mortality records in England, [CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records)]. The proportion of individuals with dementia, Alzheimer's disease, vascular and rare dementia in each data source was determined. A comparison was made of symptoms and care between people with dementia and age-, sex- and general practice-matched controls, using conditional logistic regression. The lifetime risk and prevalence of dementia and mortality rates in people with and without dementia were estimated with random-effects Poisson models. There were 47,386 people with dementia: 12,633 with Alzheimer's disease, 9540 with vascular and 1539 with rare dementia. Seventy-four percent of cases had corroborating evidence of dementia. People with dementia were more likely to live in a deprived area (conditional OR 1.26;95%CI:1.20-1.31 most vs least deprived), have documented memory impairment (cOR = 11.97;95%CI:11.24-12.75), falls (cOR = 2.36;95%CI:2.31-2.41), depression (cOR = 2.03; 95%CI:1.98-2.09) or anxiety (cOR = 1.27; 95%CI:1.23-1.32). The lifetime risk of dementia at age 65 was 9.2% (95%CI:9.0%-9.4%), in men and 14.9% (95%CI:14.7%-15.1%) in women. The population prevalence of recorded dementia increased from 0.3% in 2000 to 0.7% in 2010. A higher mortality rate was observed in people with than without dementia (IRR = 1.56;95%CI:1.54-1.58).<h4>Conclusions</h4>Most people with a record of dementia in linked UK EHR had some corroborating evidence for diagnosis. The estimated 10-year risk of dementia was higher than published population-based estimations. EHR are therefore a promising source of data for dementia research.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199026&type=printable; doi:https://doi.org/10.1371/journal.pone.0199026; html:https://europepmc.org/articles/PMC6019102; pdf:https://europepmc.org/articles/PMC6019102?pdf=render
-35435219,https://doi.org/10.1093/ehjqcco/qcac016,Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.,"Raisi-Estabragh Z, Kobo O, Freeman P, Petersen SE, Kolman L, Miller RJH, Roguin A, Van Spall HGC, Vuong J, Yang EH, Mamas MA.",,European heart journal. Quality of care & clinical outcomes,2022,2022-12-01,Y,Cancer; Cardiovascular disease; epidemiology; Cardiovascular Mortality; Mortality Trends; Cardio-oncology,,,"<h4>Aims</h4>We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.<h4>Methods and results</h4>We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629 308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).<h4>Conclusion</h4>We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.",,pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcac016/43887262/qcac016.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac016; html:https://europepmc.org/articles/PMC9745666; pdf:https://europepmc.org/articles/PMC9745666?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,,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.19122; doi:https://doi.org/10.1111/bjd.19122
+35435219,https://doi.org/10.1093/ehjqcco/qcac016,Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.,"Raisi-Estabragh Z, Kobo O, Freeman P, Petersen SE, Kolman L, Miller RJH, Roguin A, Van Spall HGC, Vuong J, Yang EH, Mamas MA.",,European heart journal. Quality of care & clinical outcomes,2022,2022-12-01,Y,Cancer; Cardiovascular disease; epidemiology; Cardiovascular Mortality; Mortality Trends; Cardio-oncology,,,"<h4>Aims</h4>We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.<h4>Methods and results</h4>We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629 308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).<h4>Conclusion</h4>We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.",,pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcac016/43887262/qcac016.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac016; html:https://europepmc.org/articles/PMC9745666; pdf:https://europepmc.org/articles/PMC9745666?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.",pdf:https://www.nature.com/articles/s41598-019-54849-w.pdf; doi:https://doi.org/10.1038/s41598-019-54849-w; html:https://europepmc.org/articles/PMC6906499; pdf:https://europepmc.org/articles/PMC6906499?pdf=render
 35765237,https://doi.org/10.1111/1747-0080.12746,An investigation of early enteral nutrition provision in major burn patients in Australia and New Zealand.,"Kurmis R, Nicholls C, Singer Y, Edgar DW, Wood FM, Gabbe BJ, Tracy LM.",,Nutrition & dietetics: the journal of the Dietitians Association of Australia,2022,2022-06-28,Y,Burns; Parenteral nutrition; enteral nutrition,,,"<h4>Aims</h4>Early enteral nutrition (provided within 24 h of admission) is the optimal form of nutritional support for major burn injuries. The aim of this study was to (i) audit early enteral nutrition practices, (ii) identify characteristics of patients who received early enteral nutrition, and (iii) investigate whether early enteral nutrition was associated with in-hospital outcomes.<h4>Methods</h4>An analysis of prospectively collected data from the Burns Registry of Australia and New Zealand was conducted. Specifically, this study focused on major burns patients (defined as burns affecting more than 20% and 15% total body surface area for adult paediatric patients, respectively) admitted to a specialist burn service between 1 July 2016 and 30 June 2019.<h4>Results</h4>Data from 474 major burns patients (88 paediatric patients) revealed 69% received early enteral nutrition. Paediatric patients who received early enteral nutrition were younger than their counterparts who did not receive the same support (p = 0.04). Adult patients who received early enteral nutrition sustained larger burns (p < 0.001). Early enteral nutrition was not associated with in-hospital mortality following major burn injury in adult patients in either unadjusted (p = 0.77) or confounder-adjusted (p = 0.69) analyses.<h4>Conclusions</h4>Approximately two-thirds of patients with major burn injuries received early enteral nutrition. Early enteral nutrition was not associated with in-hospital mortality following major burn injury. Further research should focus on modifiable reasons why major burns patients do not receive enteral nutrition within 24 h of admission.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796319; doi:https://doi.org/10.1111/1747-0080.12746; html:https://europepmc.org/articles/PMC9796319; pdf:https://europepmc.org/articles/PMC9796319?pdf=render
 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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14308; doi:https://doi.org/10.1002/ehf2.14308; html:https://europepmc.org/articles/PMC10192248; pdf:https://europepmc.org/articles/PMC10192248?pdf=render
@@ -1188,10 +1188,10 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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).<h4>Interpretation</h4>The survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older.<h4>Funding</h4>NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative.",,pdf:http://www.thelancet.com/article/S0140673620309302/pdf; 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
 34642218,https://doi.org/10.1136/bcr-2021-243424,Neurological injury from virtual reality mishap. ,"Warner N, Teo JT.",,BMJ case reports,2021,2021-10-12,Y,,,,"Consumer virtual reality systems are becoming increasingly popular with the increasing availability of devices and gamified technologies. Self-sustained injury risks exist with the use of this technology in the uncontrolled home environment, however, the public awareness of these risks may not be recognised. We present a case of a low- impact virtual reality fall resulting in spinal cord injury, hypoglossal nerve injury, vertebral artery dissection and traumatic brain injury.",,pdf:https://casereports.bmj.com/content/bmjcr/14/10/e243424.full.pdf; doi:https://doi.org/10.1136/bcr-2021-243424; html:https://europepmc.org/articles/PMC8513217; pdf:https://europepmc.org/articles/PMC8513217?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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://medinform.jmir.org/2022/11/e38168/PDF; doi:https://doi.org/10.2196/38168; html:https://europepmc.org/articles/PMC9682451
-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
 34304930,https://doi.org/10.1016/j.burns.2021.06.007,Trends in Victorian burn injuries 2008-2017.,"Cleland H, Fernando DT, Gabbe BJ.",,Burns : journal of the International Society for Burn Injuries,2022,2021-07-07,N,Burns Mortality; Burns Epidemiology; Burns Australia,,,"<h4>Objectives</h4>To describe incidence and characteristics of hospital presentations and deaths due to burn injury in the Australian state of Victoria from 2008 to 2017 and identify trends in incidence and patterns.<h4>Methods</h4>Three population-based datasets were used to ascertain burn-related hospital admissions, emergency department presentations, and deaths. These were the Victorian Admitted Episodes Dataset (VAED), Victorian Emergency Minimum Dataset (VEMD), and the Cause of Death-Unit Record File (COD-URF), respectively. Descriptive statistics on demographics (age and gender), burn injury characteristics (intent, cause, burn size and body region) and hospital burden (length of stay (LOS) and costs) were used to present the profile of patients. Incidence rates by age, gender and intent were calculated. Trend analysis on incidence was carried out using forced Poisson Regression models with the natural logarithm of the annual populations as an offset. Incident rate ratios were used to interpret the models. Risk ratios were used to compare the risk differences between population sub-groups. A negative binomial model was used to test the association between LOS and age and the total body surface area (TBSA) of the burn.<h4>Results</h4>Overall males had higher rates of death, admission and ED presentation. For adults, the elderly had the highest rates of deaths and admissions while for children, the very young had highest rates for admissions and presentations. Exposure to smoke, fire and flames was the most common cause of deaths, and contact with heat and hot substances was most common among ED presentations. The elderly and those with Total Body Surface Area (TBSA) burn ≥20% had a higher risk of longer hospital stay. Rates of severe burns and deaths from burns remained stable during the study period in the setting of an annual 2% increase in population. Paediatric hospital admission rates decreased over time.<h4>Conclusion</h4>The risk of sustaining burn injury, the types of burn and outcomes, varied by age and gender. We found evidence of a limited decrease in burn injury rates in some sub-groups: appropriate and effective targeted prevention strategies for burns are needed to avoid the significant short and long-term suffering experienced.",,doi:https://doi.org/10.1016/j.burns.2021.06.007
-36692937,https://doi.org/10.2196/42866,The Feasibility of Implementing Remote Measurement Technologies in Psychological Treatment for Depression: Mixed Methods Study on Engagement.,"de Angel V, Adeleye F, Zhang Y, Cummins N, Munir S, Lewis S, Laporta Puyal E, Matcham F, Sun S, Folarin AA, Ranjan Y, Conde P, Rashid Z, Dobson R, Hotopf M.",,JMIR mental health,2023,2023-01-24,Y,Depression; Mobile phone; Anxiety; Smartphone; Mhealth; Mobile Health; Wearable Devices; Digital Health; Digital Phenotyping; Passive Sensing,,,"<h4>Background</h4>Remote measurement technologies (RMTs) such as smartphones and wearables can help improve treatment for depression by providing objective, continuous, and ecologically valid insights into mood and behavior. Engagement with RMTs is varied and highly context dependent; however, few studies have investigated their feasibility in the context of treatment.<h4>Objective</h4>A mixed methods design was used to evaluate engagement with active and passive data collection via RMT in people with depression undergoing psychotherapy. We evaluated the effects of treatment on 2 different types of engagement: study attrition (engagement with study protocol) and patterns of missing data (engagement with digital devices), which we termed data availability. Qualitative interviews were conducted to help interpret the differences in engagement.<h4>Methods</h4>A total of 66 people undergoing psychological therapy for depression were followed up for 7 months. Active data were gathered from weekly questionnaires and speech and cognitive tasks, and passive data were gathered from smartphone sensors and a Fitbit (Fitbit Inc) wearable device.<h4>Results</h4>The overall retention rate was 60%. Higher-intensity treatment (χ<sup>2</sup><sub>1</sub>=4.6; P=.03) and higher baseline anxiety (t<sub>56.28</sub>=-2.80, 2-tailed; P=.007) were associated with attrition, but depression severity was not (t<sub>50.4</sub>=-0.18; P=.86). A trend toward significance was found for the association between longer treatments and increased attrition (U=339.5; P=.05). Data availability was higher for active data than for passive data initially but declined at a sharper rate (90%-30% drop in 7 months). As for passive data, wearable data availability fell from a maximum of 80% to 45% at 7 months but showed higher overall data availability than smartphone-based data, which remained stable at the range of 20%-40% throughout. Missing data were more prevalent among GPS location data, followed by among Bluetooth data, then among accelerometry data. As for active data, speech and cognitive tasks had lower completion rates than clinical questionnaires. The participants in treatment provided less Fitbit data but more active data than those on the waiting list.<h4>Conclusions</h4>Different data streams showed varied patterns of missing data, despite being gathered from the same device. Longer and more complex treatments and clinical characteristics such as higher baseline anxiety may reduce long-term engagement with RMTs, and different devices may show opposite patterns of missingness during treatment. This has implications for the scalability and uptake of RMTs in health care settings, the generalizability and accuracy of the data collected by these methods, feature construction, and the appropriateness of RMT use in the long term.",,pdf:https://mental.jmir.org/2023/1/e42866/PDF; doi:https://doi.org/10.2196/42866; html:https://europepmc.org/articles/PMC9906314
+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
 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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/9/e033013.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-033013; html:https://europepmc.org/articles/PMC6773283; pdf:https://europepmc.org/articles/PMC6773283?pdf=render
+36692937,https://doi.org/10.2196/42866,The Feasibility of Implementing Remote Measurement Technologies in Psychological Treatment for Depression: Mixed Methods Study on Engagement.,"de Angel V, Adeleye F, Zhang Y, Cummins N, Munir S, Lewis S, Laporta Puyal E, Matcham F, Sun S, Folarin AA, Ranjan Y, Conde P, Rashid Z, Dobson R, Hotopf M.",,JMIR mental health,2023,2023-01-24,Y,Depression; Mobile phone; Anxiety; Smartphone; Mhealth; Mobile Health; Wearable Devices; Digital Health; Digital Phenotyping; Passive Sensing,,,"<h4>Background</h4>Remote measurement technologies (RMTs) such as smartphones and wearables can help improve treatment for depression by providing objective, continuous, and ecologically valid insights into mood and behavior. Engagement with RMTs is varied and highly context dependent; however, few studies have investigated their feasibility in the context of treatment.<h4>Objective</h4>A mixed methods design was used to evaluate engagement with active and passive data collection via RMT in people with depression undergoing psychotherapy. We evaluated the effects of treatment on 2 different types of engagement: study attrition (engagement with study protocol) and patterns of missing data (engagement with digital devices), which we termed data availability. Qualitative interviews were conducted to help interpret the differences in engagement.<h4>Methods</h4>A total of 66 people undergoing psychological therapy for depression were followed up for 7 months. Active data were gathered from weekly questionnaires and speech and cognitive tasks, and passive data were gathered from smartphone sensors and a Fitbit (Fitbit Inc) wearable device.<h4>Results</h4>The overall retention rate was 60%. Higher-intensity treatment (χ<sup>2</sup><sub>1</sub>=4.6; P=.03) and higher baseline anxiety (t<sub>56.28</sub>=-2.80, 2-tailed; P=.007) were associated with attrition, but depression severity was not (t<sub>50.4</sub>=-0.18; P=.86). A trend toward significance was found for the association between longer treatments and increased attrition (U=339.5; P=.05). Data availability was higher for active data than for passive data initially but declined at a sharper rate (90%-30% drop in 7 months). As for passive data, wearable data availability fell from a maximum of 80% to 45% at 7 months but showed higher overall data availability than smartphone-based data, which remained stable at the range of 20%-40% throughout. Missing data were more prevalent among GPS location data, followed by among Bluetooth data, then among accelerometry data. As for active data, speech and cognitive tasks had lower completion rates than clinical questionnaires. The participants in treatment provided less Fitbit data but more active data than those on the waiting list.<h4>Conclusions</h4>Different data streams showed varied patterns of missing data, despite being gathered from the same device. Longer and more complex treatments and clinical characteristics such as higher baseline anxiety may reduce long-term engagement with RMTs, and different devices may show opposite patterns of missingness during treatment. This has implications for the scalability and uptake of RMTs in health care settings, the generalizability and accuracy of the data collected by these methods, feature construction, and the appropriateness of RMT use in the long term.",,pdf:https://mental.jmir.org/2023/1/e42866/PDF; doi:https://doi.org/10.2196/42866; html:https://europepmc.org/articles/PMC9906314
 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,,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jdv.17450; doi:https://doi.org/10.1111/jdv.17450; html:https://europepmc.org/articles/PMC8447018; pdf:https://europepmc.org/articles/PMC8447018?pdf=render
 37393610,https://doi.org/10.1016/j.xpro.2023.102392,Protocol for the automatic extraction of epidemiological information via a pre-trained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wang Z, Cao Y, Wong ZSY, Xu XK, Sun Y.",,STAR protocols,2023,2023-07-01,Y,Health Sciences; Clinical Protocol; Computer Sciences,,,"The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model.<sup>1</sup> We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE. For complete details on the use and execution of this protocol, please refer to Wang et al.<sup>2</sup>.",,doi:https://doi.org/10.1016/j.xpro.2023.102392; doi:https://doi.org/10.1016/j.xpro.2023.102392; html:https://europepmc.org/articles/PMC10328978; pdf:https://europepmc.org/articles/PMC10328978?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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dom.14203; doi:https://doi.org/10.1111/dom.14203; html:https://europepmc.org/articles/PMC7537530; pdf:https://europepmc.org/articles/PMC7537530?pdf=render
@@ -1207,16 +1207,16 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI
 36701266,https://doi.org/10.1371/journal.pmed.1004036,"Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.","Vinther JL, Cadman T, Avraam D, Ekstrøm CT, Sørensen TIA, Elhakeem A, Santos AC, Pinot de Moira A, Heude B, Iñiguez C, Pizzi C, Simons E, Voerman E, Corpeleijn E, Zariouh F, Santorelli G, Inskip HM, Barros H, Carson J, Harris JR, Nader JL, Ronkainen J, Strandberg-Larsen K, Santa-Marina L, Calas L, Cederkvist L, Popovic M, Charles MA, Welten M, Vrijheid M, Azad M, Subbarao P, Burton P, Mandhane PJ, Huang RC, Wilson RC, Haakma S, Fernández-Barrés S, Turvey S, Santos S, Tough SC, Sebert S, Moraes TJ, Salika T, Jaddoe VWV, Lawlor DA, Nybo Andersen AM.",,PLoS medicine,2023,2023-01-26,Y,,,,"<h4>Background</h4>Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence.<h4>Methods and findings</h4>We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries.<h4>Conclusions</h4>This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004036&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004036; html:https://europepmc.org/articles/PMC9879424; pdf:https://europepmc.org/articles/PMC9879424?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,,,,"<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://downloads.hindawi.com/journals/jhe/2021/6663884.pdf; doi:https://doi.org/10.1155/2021/6663884; html:https://europepmc.org/articles/PMC8285182; pdf:https://europepmc.org/articles/PMC8285182?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,,"<h4>Background</h4>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.<h4>Method</h4>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.<h4>Result</h4>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.<h4>Conclusion</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0202359&type=printable; doi:https://doi.org/10.1371/journal.pone.0202359; html:https://europepmc.org/articles/PMC6124703; pdf:https://europepmc.org/articles/PMC6124703?pdf=render
-35796550,https://doi.org/10.1093/hmg/ddac153,The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study.,"Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.",,Human molecular genetics,2022,2022-11-01,N,,,,"Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD endpoints in up to 1 153 768 European (maximum 123 668 cases) and 212 453 East Asian (maximum 29 319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple CVDs, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL) cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk.",,pdf:https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac153/45277324/ddac153.pdf; doi:https://doi.org/10.1093/hmg/ddac153
 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,,,"<h4>Objectives</h4>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.<h4>Design</h4>A cross-sectional population study and a long-term CVD decision model.<h4>Setting</h4>Primary care, UK.<h4>Participants</h4>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.<h4>Interventions</h4>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.<h4>Outcomes</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Optimising cardiovascular treatments can cost-effectively reduce cardiovascular risk and improve life expectancy.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/12/e052884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052884; html:https://europepmc.org/articles/PMC8719215; pdf:https://europepmc.org/articles/PMC8719215?pdf=render
+35796550,https://doi.org/10.1093/hmg/ddac153,The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study.,"Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.",,Human molecular genetics,2022,2022-11-01,N,,,,"Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD endpoints in up to 1 153 768 European (maximum 123 668 cases) and 212 453 East Asian (maximum 29 319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple CVDs, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL) cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk.",,pdf:https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac153/45277324/ddac153.pdf; doi:https://doi.org/10.1093/hmg/ddac153
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>An increase in body mass index (β -2.81; 95% CI -3.98; -1.63 per 5 kg/m<sup>2</sup> ) 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.<h4>Conclusions</h4>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.",,pdf:https://discovery.ucl.ac.uk/10151289/1/Asselbergs_Lifestyle%20changes%20and%20kidney%20function_AOP.pdf; doi:https://doi.org/10.1111/eci.13814; html:https://europepmc.org/articles/PMC9540114; pdf:https://europepmc.org/articles/PMC9540114?pdf=render
 34143303,https://doi.org/10.1007/s00787-021-01817-3,National record-linkage study of hospital admissions for schizophrenia in childhood and adolescence in England.,"Seminog O, Hoang U, Goldacre M, James A.",,European child & adolescent psychiatry,2022,2021-06-18,Y,Schizophrenia; Children; epidemiology; Electronic Records; Childhood Onset,,,"<h4>Background</h4>There is a lack of information on changes in hospital admission rates for childhood-onset schizophrenia (COS), or on patient characteristics, to inform clinical research and health service provision.<h4>Aims</h4>To report age- and sex-specific incidence rates of hospital admissions and day patient care for schizophrenia (ICD-10 F20) and non-affective psychosis (ICD-10 F20-29), by year of occurrence and age, in childhood and adolescence.<h4>Methods</h4>Population-based study using person-linked data for England (available 2001-2016); time-periods in single years and 4-year groups.<h4>Results</h4>Hospitalised incidence for schizophrenia increased with increasing age, from 0.03 (95% confidence interval (CI) 0.02-0.05) and 0.01 (0-0.01) per 100,000 in, respectively, males and females aged 5-12 years, to 3.67 (3.44-3.91) in males and 1.58 (1.43-1.75) in females aged 13-17 years. There was no gender difference in hospitalised incidence rates in children aged 5-12, but in 13-17 years old, there was a male excess. Rates for schizophrenia were stable over time in 5-12 years old. In ages 13-17, rates for schizophrenia decreased between 2001-2004 and 2013-2016 in males, from 6.65 (6.04-7.31) down to 1.40 (1.13-1.73), and in females from 2.42 (2.05-2.83) to 1.18 (0.92-1.48). The hospitalisation rates for schizophrenia and non-affective psychosis, combined, in 13-17 years old decreased in males from 14.20 (13.30-15.14) in 2001-2004 to 10.77 (9.97-11.60) in 2013-2016, but increased in females from 7.49 (6.83-8.20) to 10.16 (9.38-11.00).<h4>Conclusions</h4>The study confirms that childhood-onset schizophrenia is extremely rare, with only 32 cases identified over a 15-year period in the whole of England. The incidence of schizophrenia and non-affective psychosis increased substantially in adolescence; however, the marked reduction in the proportion of those diagnosed with schizophrenia in this age group suggests a possible change in diagnostic practice.",,pdf:https://link.springer.com/content/pdf/10.1007/s00787-021-01817-3.pdf; doi:https://doi.org/10.1007/s00787-021-01817-3; html:https://europepmc.org/articles/PMC9663394; pdf:https://europepmc.org/articles/PMC9663394?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.",,pdf:https://www.mdpi.com/1660-4601/18/24/13304/pdf?version=1639728813; doi:https://doi.org/10.3390/ijerph182413304; html:https://europepmc.org/articles/PMC8707886; pdf:https://europepmc.org/articles/PMC8707886?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,,,"<h4>Objectives</h4>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.<h4>Design</h4>Cohort study using linked trauma registry and health administrative datasets.<h4>Setting</h4>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).<h4>Participants</h4>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.<h4>Intervention</h4>Not applicable.<h4>Main outcome measure</h4>Prevalence of chronic physical health conditions.<h4>Results</h4>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.<h4>Conclusions</h4>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
 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,,,"<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%).<h4>Conclusions</h4>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
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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/1.73m<sup>2</sup>, 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·1.73m<sup>2</sup>) considered evidence of glomerular hyperfiltration.<h4>Results</h4>21 623 participants had CKD: 7781 with reduced eGFR and 15 500 with albuminuria. 1828 participants had an eGFR ≥120 mL/min/1.73m<sup>2</sup>. 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/1.73m<sup>2</sup> 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.<h4>Conclusions</h4>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.",,pdf:https://ora.ox.ac.uk/objects/uuid:aefe90da-8a81-4cfa-981a-bb36eca6faa3/files/r6w924c60k; doi:https://doi.org/10.1161/HYPERTENSIONAHA.122.19354; html:https://europepmc.org/articles/PMC9640248; pdf:https://europepmc.org/articles/PMC9640248?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; Attenuated Wavy Fibers; Canine Induced Pluripotent Stem Cells,,,"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.",,pdf:https://www.mdpi.com/2076-2615/12/13/1679/pdf?version=1656561768; doi:https://doi.org/10.3390/ani12131679; html:https://europepmc.org/articles/PMC9265105; pdf:https://europepmc.org/articles/PMC9265105?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,,,"<h4>Introduction</h4>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.<h4>Materials and methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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
+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; Attenuated Wavy Fibers; Canine Induced Pluripotent Stem Cells,,,"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.",,pdf:https://www.mdpi.com/2076-2615/12/13/1679/pdf?version=1656561768; doi:https://doi.org/10.3390/ani12131679; html:https://europepmc.org/articles/PMC9265105; pdf:https://europepmc.org/articles/PMC9265105?pdf=render
 37670953,https://doi.org/10.23889/ijpds.v8i1.2113,Lessons learned from using linked administrative data to evaluate the Family Nurse Partnership in England and Scotland.,"Cavallaro FL, Cannings-John R, Lugg-Widger F, Gilbert R, Kennedy E, Kendall S, Robling M, Harron KL.",,International journal of population data science,2023,2023-05-11,Y,Evaluation; Early Years; Administrative Data; Adolescent Motherhood; Cross-Sectoral Linkage,,,"<h4>Introduction</h4>""Big data"" - including linked administrative data - can be exploited to evaluate interventions for maternal and child health, providing time- and cost-effective alternatives to randomised controlled trials. However, using these data to evaluate population-level interventions can be challenging.<h4>Objectives</h4>We aimed to inform future evaluations of complex interventions by describing sources of bias, lessons learned, and suggestions for improvements, based on two observational studies using linked administrative data from health, education and social care sectors to evaluate the Family Nurse Partnership (FNP) in England and Scotland.<h4>Methods</h4>We first considered how different sources of potential bias within the administrative data could affect results of the evaluations. We explored how each study design addressed these sources of bias using maternal confounders captured in the data. We then determined what additional information could be captured at each step of the complex intervention to enable analysts to minimise bias and maximise comparability between intervention and usual care groups, so that any observed differences can be attributed to the intervention.<h4>Results</h4>Lessons learned include the need for i) detailed data on intervention activity (dates/geography) and usual care; ii) improved information on data linkage quality to accurately characterise control groups; iii) more efficient provision of linked data to ensure timeliness of results; iv) better measurement of confounding characteristics affecting who is eligible, approached and enrolled.<h4>Conclusions</h4>Linked administrative data are a valuable resource for evaluations of the FNP national programme and other complex population-level interventions. However, information on local programme delivery and usual care are required to account for biases that characterise those who receive the intervention, and to inform understanding of mechanisms of effect. National, ongoing, robust evaluations of complex public health evaluations would be more achievable if programme implementation was integrated with improved national and local data collection, and robust quasi-experimental designs.",,doi:https://doi.org/10.23889/ijpds.v8i1.2113; html:https://europepmc.org/articles/PMC10476150; pdf:https://europepmc.org/articles/PMC10476150?pdf=render
 PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’ lived experiences of the impacts of COVID-19 policies and guidelines on maternal and reproductive healthcare services in the United Kingdom,"Chaloner J, Qureshi I, Gogoi M, Ekezie W, Al-Oraibi A, Wobi F, Agbonmwandolor J, Nellums L, Pareek M.",,European journal of midwifery,2023,2023-01-01,Y,Healthcare Workers; Vaccine Hesitancy; Redeployment; Infection Controls; Covid-19; Policies And Guidelines,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630987/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630987/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC10630987; pdf:https://europepmc.org/articles/PMC10630987?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.",,pdf:https://academic.oup.com/dote/article-pdf/35/1/doab058/42098674/doab058.pdf; doi:https://doi.org/10.1093/dote/doab058
@@ -1246,8 +1246,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 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.",,pdf:http://arxiv.org/pdf/2010.01165; doi:https://doi.org/10.1016/j.artmed.2021.102083
 34253559,https://doi.org/10.1136/jech-2021-216689,"Long-term trends in population-based hospitalisation rates for myocardial infarction in England: a national database study of 3.5 million admissions, 1968-2016.","Wright FL, Townsend N, Greenland M, Goldacre MJ, Smolina K, Lacey B, Nedkoff L.",,Journal of epidemiology and community health,2022,2021-07-12,Y,epidemiology; Ischaemic Heart Disease; Record Linkage,,,"<h4>Aim</h4>To analyse the timing and scale of temporal changes in rates of hospitalised myocardial infarction (MI) in England by age and sex from 1968 to 2016.<h4>Methods</h4>MI admissions for adults aged 15-84 years were identified from electronic hospital data. We calculated age-standardised and age-specific rates, and examined trends using joinpoint.<h4>Results</h4>From 1968 to 2016, there were 3.5 million admissions for MI in England (68% men). Rates increased in the early years of the study in both men and women, peaked in the mid-1980s (355 per 100 000 population in men; 127 in women) and declined by 38.8% in men and 37.4% in women from 1990 to 2011. From 2012, however, modest increases were observed in both sexes. Long-term trends in rates over the study period varied by age and sex, with those aged 70 years and older having the greatest and most sustained increases in the early years (1968-1985). During subsequent years, rates decreased in most age groups until 2010-2011. The exception was younger women (35-49 years) and men (15-34 years) who experienced significant increases from the mid-1990s to 2007 (range +2.1%/year to 4.7%/year). From 2012 onwards, rates increased in all age groups except the oldest, with the most marked increases in men aged 15-34 years (7.2%/year) and women aged 40-49 (6.9%-7.3%/year) .<h4>Conclusion</h4>Despite substantial declines in hospital admission rates for MI in England since 1990, the burden of annual admissions remains high. Continued surveillance of trends and coronary disease preventive strategies are warranted.",,pdf:https://jech.bmj.com/content/jech/76/1/45.full.pdf; doi:https://doi.org/10.1136/jech-2021-216689; html:https://europepmc.org/articles/PMC8666807; pdf:https://europepmc.org/articles/PMC8666807?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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://mhealth.jmir.org/2022/1/e28095/PDF; doi:https://doi.org/10.2196/28095; html:https://europepmc.org/articles/PMC8838593
-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,,,"<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Stakeholders recognized that any PRO data collection after treatment discontinuation should have clearly defined objectives to ensure that data can be analyzed and reported.<h4>Conclusions</h4>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
 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.",,pdf:https://www.mdpi.com/2075-4426/12/6/958/pdf?version=1655284846; doi:https://doi.org/10.3390/jpm12060958; html:https://europepmc.org/articles/PMC9225330; pdf:https://europepmc.org/articles/PMC9225330?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,,,"<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Stakeholders recognized that any PRO data collection after treatment discontinuation should have clearly defined objectives to ensure that data can be analyzed and reported.<h4>Conclusions</h4>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
 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,,,"<h4>Objective</h4>In this study, we describe the pattern of bed occupancy across England during the peak of the first wave of the COVID-19 pandemic.<h4>Design</h4>Descriptive survey.<h4>Setting</h4>All non-specialist secondary care providers in England from 27 March27to 5 June 2020.<h4>Participants</h4>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).<h4>Main outcome measures</h4>Two thresholds for 'safe occupancy' were used: 85% as per the Royal College of Emergency Medicine and 92% as per NHS Improvement.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e042945.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042945; html:https://europepmc.org/articles/PMC7843315; pdf:https://europepmc.org/articles/PMC7843315?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.",,pdf:https://academic.oup.com/ije/article-pdf/52/1/132/49127281/dyac105.pdf; doi:https://doi.org/10.1093/ije/dyac105; html:https://europepmc.org/articles/PMC9908051; pdf:https://europepmc.org/articles/PMC9908051?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09363-1; doi:https://doi.org/10.1186/s12913-023-09363-1; html:https://europepmc.org/articles/PMC10096103; pdf:https://europepmc.org/articles/PMC10096103?pdf=render
@@ -1271,8 +1271,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 37722858,https://doi.org/10.3399/bjgp.2023.0077,Inequities in hypertension management: observational cross-sectional study in North East London using electronic health records.,"Rison S, Redfern O, Dostal I, Carvalho C, Mathur R, Raisi-Estabragh Z, Robson J.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-10-26,Y,Hypertension; Cardiovascular diseases; Blood pressure; General Practice; Antihypertensives; Health Inequities,,,"<h4>Background</h4>Hypertension is a key modifiable risk factor for cardiovascular disease - the leading cause of death in the UK. Good blood pressure (BP) control reduces mortality. However, health inequities may lead to variability in hypertension monitoring and control.<h4>Aim</h4>To investigate health inequities related to ethnicity, sex, age, and socioeconomic status in the monitoring, treatment, and control of BP in a large cohort of adult patients with hypertension.<h4>Design and setting</h4>A cross-sectional cohort study of adults with hypertension registered with general practices in North East London on 1 April 2019.<h4>Method</h4>Multivariable logistic regression was used to estimate associations of demographics and treatment intensity for the following hypertension management indicators: a) BP recording in past 12 months; b) BP on age- adjusted target; and c) BP on age-adjusted target and BP recorded in past 12 months.<h4>Results</h4>In total, 156 296 adults were included. The Black ethnicity group was less likely to have controlled BP than the White ethnicity group (odds ratio [OR] 0.87, 95% [confidence interval] CI = 0.84 to 0.91). The Asian ethnicity group was more likely to have controlled BP (OR 1.28, 95% CI = 1.23 to 1.32). Ethnicity differences in control could not be explained by the likelihood of having a recent BP recording, nor by treatment intensity differences. Older adults (aged ≥50 years) were more likely to have controlled hypertension than younger patients.<h4>Conclusion</h4>Individuals of Black ethnicity and younger people are less likely to have controlled hypertension and may warrant targeted interventions. Possible explanations for these findings are presented but further research is needed about reasons for ethnic differences.",,doi:https://doi.org/10.3399/BJGP.2023.0077; html:https://europepmc.org/articles/PMC10523336; pdf:https://europepmc.org/articles/PMC10523336?pdf=render
 32571619,https://doi.org/10.1016/j.schres.2020.05.007,Real-world implementation of precision psychiatry: Transdiagnostic risk calculator for the automatic detection of individuals at-risk of psychosis.,"Oliver D, Spada G, Colling C, Broadbent M, Baldwin H, Patel R, Stewart R, Stahl D, Dobson R, McGuire P, Fusar-Poli P.",,Schizophrenia research,2021,2020-06-19,Y,Feasibility; Implementation; Risk Calculator; Precision Psychiatry; Psychosis;transdiagnostic,,,"<h4>Background</h4>Risk estimation models integrated into Electronic Health Records (EHRs) can deliver innovative approaches in psychiatry, but clinicians' endorsement and their real-world usability are unknown. This study aimed to investigate the real-world feasibility of implementing an individualised, transdiagnostic risk calculator to automatically screen EHRs and detect individuals at-risk for psychosis.<h4>Methods</h4>Feasibility implementation study encompassing an in-vitro phase (March 2018 to May 2018) and in-vivo phase (May 2018 to April 2019). The in-vitro phase addressed implementation barriers and embedded the risk calculator (predictors: age, gender, ethnicity, index cluster diagnosis, age*gender) into the local EHR. The in-vivo phase investigated the real-world feasibility of screening individuals accessing secondary mental healthcare at the South London and Maudsley NHS Trust. The primary outcome was adherence of clinicians to automatic EHR screening, defined by the proportion of clinicians who responded to alerts from the risk calculator, over those contacted.<h4>Results</h4>In-vitro phase: implementation barriers were identified/overcome with clinician and service user engagement, and the calculator was successfully integrated into the local EHR through the CogStack platform. In-vivo phase: 3722 individuals were automatically screened and 115 were detected. Clinician adherence was 74% without outreach and 85% with outreach. One-third of clinicians responded to the first email (37.1%) or phone calls (33.7%). Among those detected, cumulative risk of developing psychosis was 12% at six-month follow-up.<h4>Conclusion</h4>This is the first implementation study suggesting that combining precision psychiatry and EHR methods to improve detection of individuals with emerging psychosis is feasible. Future psychiatric implementation research is urgently needed.",,doi:https://doi.org/10.1016/j.schres.2020.05.007; doi:https://doi.org/10.1016/j.schres.2020.05.007; html:https://europepmc.org/articles/PMC7875179
 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.",,pdf:https://bjgpopen.org/content/bjgpoa/4/5/bjgpopen20X101109.full.pdf; doi:https://doi.org/10.3399/bjgpopen20X101109; html:https://europepmc.org/articles/PMC7880177; pdf:https://europepmc.org/articles/PMC7880177?pdf=render
-36298714,https://doi.org/10.3390/v14102159,Production and Characterisation of Stabilised PV-3 Virus-like Particles Using <i>Pichia pastoris</i>.,"Sherry L, Grehan K, Swanson JJ, Bahar MW, Porta C, Fry EE, Stuart DI, Rowlands DJ, Stonehouse NJ.",,Viruses,2022,2022-09-30,Y,Poliovirus; Vaccine; virus-like particle; Pichia pastoris,,,"Following the success of global vaccination programmes using the live-attenuated oral and inactivated poliovirus vaccines (OPV and IPV), wild poliovirus (PV) is now only endemic in Afghanistan and Pakistan. However, the continued use of these vaccines poses potential risks to the eradication of PV. The production of recombinant PV virus-like particles (VLPs), which lack the viral genome offer great potential as next-generation vaccines for the post-polio world. We have previously reported production of PV VLPs using <i>Pichia pastoris</i>, however, these VLPs were in the non-native conformation (C Ag), which would not produce effective protection against PV. Here, we build on this work and show that it is possible to produce wt PV-3 and thermally stabilised PV-3 (referred to as PV-3 SC8) VLPs in the native conformation (D Ag) using <i>Pichia pastoris</i>. We show that the PV-3 SC8 VLPs provide a much-improved D:C antigen ratio as compared to wt PV-3, whilst exhibiting greater thermostability than the current IPV vaccine. Finally, we determine the cryo-EM structure of the yeast-derived PV-3 SC8 VLPs and compare this to previously published PV-3 D Ag structures, highlighting the similarities between these recombinantly expressed VLPs and the infectious virus, further emphasising their potential as a next-generation vaccine candidate for PV.",,pdf:https://www.mdpi.com/1999-4915/14/10/2159/pdf?version=1665465973; doi:https://doi.org/10.3390/v14102159; html:https://europepmc.org/articles/PMC9611624; pdf:https://europepmc.org/articles/PMC9611624?pdf=render
 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,,,"<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>Development of systematic recording methods of animal-vehicle collisions will improve reporting of these crash types to assist future studies in implementing effective countermeasures.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.13361; doi:https://doi.org/10.1111/1742-6723.13361
+36298714,https://doi.org/10.3390/v14102159,Production and Characterisation of Stabilised PV-3 Virus-like Particles Using <i>Pichia pastoris</i>.,"Sherry L, Grehan K, Swanson JJ, Bahar MW, Porta C, Fry EE, Stuart DI, Rowlands DJ, Stonehouse NJ.",,Viruses,2022,2022-09-30,Y,Poliovirus; Vaccine; virus-like particle; Pichia pastoris,,,"Following the success of global vaccination programmes using the live-attenuated oral and inactivated poliovirus vaccines (OPV and IPV), wild poliovirus (PV) is now only endemic in Afghanistan and Pakistan. However, the continued use of these vaccines poses potential risks to the eradication of PV. The production of recombinant PV virus-like particles (VLPs), which lack the viral genome offer great potential as next-generation vaccines for the post-polio world. We have previously reported production of PV VLPs using <i>Pichia pastoris</i>, however, these VLPs were in the non-native conformation (C Ag), which would not produce effective protection against PV. Here, we build on this work and show that it is possible to produce wt PV-3 and thermally stabilised PV-3 (referred to as PV-3 SC8) VLPs in the native conformation (D Ag) using <i>Pichia pastoris</i>. We show that the PV-3 SC8 VLPs provide a much-improved D:C antigen ratio as compared to wt PV-3, whilst exhibiting greater thermostability than the current IPV vaccine. Finally, we determine the cryo-EM structure of the yeast-derived PV-3 SC8 VLPs and compare this to previously published PV-3 D Ag structures, highlighting the similarities between these recombinantly expressed VLPs and the infectious virus, further emphasising their potential as a next-generation vaccine candidate for PV.",,pdf:https://www.mdpi.com/1999-4915/14/10/2159/pdf?version=1665465973; doi:https://doi.org/10.3390/v14102159; html:https://europepmc.org/articles/PMC9611624; pdf:https://europepmc.org/articles/PMC9611624?pdf=render
 35259281,https://doi.org/10.1111/acel.13524,Biological mechanisms of aging predict age-related disease co-occurrence in patients.,"Fraser HC, Kuan V, Johnen R, Zwierzyna M, Hingorani AD, Beyer A, Partridge L.",,Aging cell,2022,2022-03-08,Y,Aging; Genetics; Age-related Disease; Multimorbidity; Aging Hallmarks,,,"Genetic, environmental, and pharmacological interventions into the aging process can confer resistance to multiple age-related diseases in laboratory animals, including rhesus monkeys. These findings imply that individual mechanisms of aging might contribute to the co-occurrence of age-related diseases in humans and could be targeted to prevent these conditions simultaneously. To address this question, we text mined 917,645 literature abstracts followed by manual curation and found strong, non-random associations between age-related diseases and aging mechanisms in humans, confirmed by gene set enrichment analysis of GWAS data. Integration of these associations with clinical data from 3.01 million patients showed that age-related diseases associated with each of five aging mechanisms were more likely than chance to be present together in patients. Genetic evidence revealed that innate and adaptive immunity, the intrinsic apoptotic signaling pathway and activity of the ERK1/2 pathway were associated with multiple aging mechanisms and diverse age-related diseases. Mechanisms of aging hence contribute both together and individually to age-related disease co-occurrence in humans and could potentially be targeted accordingly to prevent multimorbidity.",,pdf:https://discovery.ucl.ac.uk/10145565/1/Hignorani_Biological%20mechanisms%20of%20aging%20predict%20age-related%20disease%20co-occurrence%20in%20patients_AOP.pdf; doi:https://doi.org/10.1111/acel.13524; html:https://europepmc.org/articles/PMC9009120; pdf:https://europepmc.org/articles/PMC9009120?pdf=render
 36331190,https://doi.org/10.1056/nejmoa2204233,Empagliflozin in Patients with Chronic Kidney Disease.,"The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R.",,The New England journal of medicine,2023,2022-11-04,Y,,,,"<h4>Background</h4>The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients.<h4>Methods</h4>We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m<sup>2</sup> of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m<sup>2</sup> with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to <10 ml per minute per 1.73 m<sup>2</sup>, a sustained decrease in eGFR of ≥40% from baseline, or death from renal causes) or death from cardiovascular causes.<h4>Results</h4>A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P<0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P = 0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups.<h4>Conclusions</h4>Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EudraCT number, 2017-002971-24.).",,pdf:https://ora.ox.ac.uk/objects/uuid:f91f9722-f207-4d97-aa64-58636b323acc/files/r6969z144v; doi:https://doi.org/10.1056/NEJMoa2204233; html:https://europepmc.org/articles/PMC7614055; pdf:https://europepmc.org/articles/PMC7614055?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,,,"<h4>Purpose</h4>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.<h4>Design</h4>Retrospective analysis of electronic health records from 27 National Health Service secondary care healthcare providers in the UK.<h4>Participants</h4>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.<h4>Methods</h4>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.<h4>Main outcome measures</h4>Visual acuity (VA), number of injections, and number of visits.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165682; 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
@@ -1280,12 +1280,12 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 31757515,https://doi.org/10.1016/j.jaci.2019.09.015,Atopic eczema and fracture risk in adults: A population-based cohort study.,"Lowe KE, Mansfield KE, Delmestri A, Smeeth L, Roberts A, Abuabara K, Prieto-Alhambra D, Langan SM.",,The Journal of allergy and clinical immunology,2020,2019-11-19,Y,Osteoporosis; Fracture; Atopic Eczema; Severity; Population Based,Understanding the Causes of Disease,,"<h4>Background</h4>Limited evidence suggests increased fracture risk in people with atopic eczema. Any link could have substantial effect; atopic eczema is common, and fractures have associated morbidity and mortality.<h4>Objective</h4>We sought to examine whether atopic eczema is associated with fracture and whether fracture risk varies with eczema severity.<h4>Methods</h4>We performed a matched cohort study set in primary care (Clinical Practice Research Datalink GOLD 1998-2016) and linked hospital admissions data (Hospital Episode Statistics), including adults (≥18 years old) with atopic eczema matched (by age, sex, general practice, and cohort entry date) with up to 5 individuals without eczema. We estimated hazard ratios (HRs) from stratified Cox regression comparing risk of major osteoporotic (hip, pelvis, spine, wrist, and proximal humerus) fractures individually and any fracture in those with and without atopic eczema.<h4>Results</h4>We identified 526,808 people with atopic eczema and 2,569,030 people without atopic eczema. Those with eczema had increased risk of hip (HR, 1.10; 99% CI, 1.06-1.14), pelvic (HR, 1.10; 99% CI, 1.02-1.19), spinal (HR, 1.18; 99% CI, 1.10-1.27), and wrist (HR, 1.07; 99% CI, 1.03,-1.11) fractures. We found no evidence of increased proximal humeral (HR, 1.06; 99% CI, 0.97-1.15) fracture risk. Fracture risk increased with increasing eczema severity, with the strongest associations in people with severe eczema (compared with those without) for spinal (HR, 2.09; 99% CI, 1.66-2.65), pelvic (HR, 1.66; 99% CI, 1.26-2.20), and hip (HR, 1.50; 99% CI, 1.30-1.74) fractures. Associations persisted after oral glucocorticoid adjustment.<h4>Conclusions</h4>People with atopic eczema have increased fracture risk, particularly major osteoporotic fractures.",This population-wide study used datalinkage methods to create a matched cohort study between 1998-2016. The study estimated hazard ratios and compared the risk of major fractures and any fracture in people with and without atopic eczema. Findings suggest that people with atopic eczema have an increased fracture risk.,pdf:http://www.jacionline.org/article/S0091674919312515/pdf; doi:https://doi.org/10.1016/j.jaci.2019.09.015; html:https://europepmc.org/articles/PMC7014587; pdf:https://europepmc.org/articles/PMC7014587?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
 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,,,"<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://respiratory-research.biomedcentral.com/counter/pdf/10.1186/s12931-022-02130-6; doi:https://doi.org/10.1186/s12931-022-02130-6; html:https://europepmc.org/articles/PMC9367123; pdf:https://europepmc.org/articles/PMC9367123?pdf=render
-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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https://gbmdeconvoluter.leeds.ac.uk.",,pdf:https://academic.oup.com/neuro-oncology/advance-article-pdf/doi/10.1093/neuonc/noad021/49522012/noad021.pdf; doi:https://doi.org/10.1093/neuonc/noad021; html:https://europepmc.org/articles/PMC10326489; pdf:https://europepmc.org/articles/PMC10326489?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Health and Medical Research Fund, Hong Kong.",,pdf:https://www.repository.cam.ac.uk/bitstreams/bb5465bd-c08f-4c3d-ab0e-87fee39fc92b/download; doi:https://doi.org/10.1016/S2214-109X(22)00358-8; html:https://europepmc.org/articles/PMC9573849
 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,,,,"<h4>Background</h4>There is a known shortfall in hepatology service resources across England and Wales.<h4>Aim</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/apt.15232; doi:https://doi.org/10.1111/apt.15232; html:https://europepmc.org/articles/PMC6519290; pdf:https://europepmc.org/articles/PMC6519290?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Health and Medical Research Fund, Hong Kong.",,pdf:https://www.repository.cam.ac.uk/bitstreams/bb5465bd-c08f-4c3d-ab0e-87fee39fc92b/download; doi:https://doi.org/10.1016/S2214-109X(22)00358-8; html:https://europepmc.org/articles/PMC9573849
+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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https://gbmdeconvoluter.leeds.ac.uk.",,pdf:https://academic.oup.com/neuro-oncology/advance-article-pdf/doi/10.1093/neuonc/noad021/49522012/noad021.pdf; doi:https://doi.org/10.1093/neuonc/noad021; html:https://europepmc.org/articles/PMC10326489; pdf:https://europepmc.org/articles/PMC10326489?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.",,pdf:https://link.springer.com/content/pdf/10.1007/s12265-023-10398-2.pdf; doi:https://doi.org/10.1007/s12265-023-10398-2
-35504525,https://doi.org/10.1016/j.jclinepi.2022.04.025,How traditional informed consent impairs inclusivity in a learning healthcare system: lessons learned from the Utrecht Cardiovascular Cohort.,"Groenhof TKJ, Mostert M, Lea NC, Haitjema S, de Vries MC, van Dijk WB, Grobbee DE, Asselbergs FW, Bots ML, van der Graaf R.",,Journal of clinical epidemiology,2022,2022-04-30,N,,,,,,doi:https://doi.org/10.1016/j.jclinepi.2022.04.025
 34426417,https://doi.org/10.1136/bmjhci-2021-100385,Review of study reporting guidelines for clinical studies using artificial intelligence in healthcare. ,"Shelmerdine SC, Arthurs OJ, Denniston A, Sebire NJ.",,BMJ health & care informatics,2021,2021-08-01,Y,,,,"High-quality research is essential in guiding evidence-based care, and should be reported in a way that is reproducible, transparent and where appropriate, provide sufficient detail for inclusion in future meta-analyses. Reporting guidelines for various study designs have been widely used for clinical (and preclinical) studies, consisting of checklists with a minimum set of points for inclusion. With the recent rise in volume of research using artificial intelligence (AI), additional factors need to be evaluated, which do not neatly conform to traditional reporting guidelines (eg, details relating to technical algorithm development). In this review, reporting guidelines are highlighted to promote awareness of essential content required for studies evaluating AI interventions in healthcare. These include published and in progress extensions to well-known reporting guidelines such as Standard Protocol Items: Recommendations for Interventional Trials-AI (study protocols), Consolidated Standards of Reporting Trials-AI (randomised controlled trials), Standards for Reporting of Diagnostic Accuracy Studies-AI (diagnostic accuracy studies) and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis-AI (prediction model studies). Additionally there are a number of guidelines that consider AI for health interventions more generally (eg, Checklist for Artificial Intelligence in Medical Imaging (CLAIM), minimum information (MI)-CLAIM, MI for Medical AI Reporting) or address a specific element such as the 'learning curve' (Developmental and Exploratory Clinical Investigation of Decision-AI) . Economic evaluation of AI health interventions is not currently addressed, and may benefit from extension to an existing guideline. In the face of a rapid influx of studies of AI health interventions, reporting guidelines help ensure that investigators and those appraising studies consider both the well-recognised elements of good study design and reporting, while also adequately addressing new challenges posed by AI-specific elements.",,pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100385.full.pdf; doi:https://doi.org/10.1136/bmjhci-2021-100385; html:https://europepmc.org/articles/PMC8383863; pdf:https://europepmc.org/articles/PMC8383863?pdf=render
+35504525,https://doi.org/10.1016/j.jclinepi.2022.04.025,How traditional informed consent impairs inclusivity in a learning healthcare system: lessons learned from the Utrecht Cardiovascular Cohort.,"Groenhof TKJ, Mostert M, Lea NC, Haitjema S, de Vries MC, van Dijk WB, Grobbee DE, Asselbergs FW, Bots ML, van der Graaf R.",,Journal of clinical epidemiology,2022,2022-04-30,N,,,,,,doi:https://doi.org/10.1016/j.jclinepi.2022.04.025
 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,,,"<h4>Context</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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 (PRS<sub>T2D</sub>) 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.<h4>Results</h4>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 PRS<sub>T2D</sub> with each outcome in each category of BMI or first-degree family history of diabetes. Those in the highest quintile of PRS<sub>T2D</sub> 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 PRS<sub>T2D</sub> 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 PRS<sub>T2D</sub>.<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/jes/article-pdf/7/4/bvad020/49229172/bvad020.pdf; doi:https://doi.org/10.1210/jendso/bvad020; html:https://europepmc.org/articles/PMC9933896; pdf:https://europepmc.org/articles/PMC9933896?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,,,"<h4>Background</h4>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.<h4>Methods</h4>(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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/jpubhealth/article-pdf/42/4/e516/34469316/fdz172.pdf; doi:https://doi.org/10.1093/pubmed/fdz172
 37751444,https://doi.org/10.1371/journal.pone.0290583,Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.,"Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.",,PloS one,2023,2023-09-26,Y,,,,"<h4>Background</h4>Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.<h4>Aims</h4>To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.<h4>Methods</h4>We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.<h4>Results</h4>We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.<h4>Conclusions</h4>Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0290583&type=printable; doi:https://doi.org/10.1371/journal.pone.0290583; html:https://europepmc.org/articles/PMC10521988; pdf:https://europepmc.org/articles/PMC10521988?pdf=render
@@ -1298,8 +1298,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.8556; doi:https://doi.org/10.1002/sim.8556; html:https://europepmc.org/articles/PMC8432147; pdf:https://europepmc.org/articles/PMC8432147?pdf=render
 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,,,,"<h4>Introduction</h4>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.<h4>Aims and objectives</h4>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.<h4>Methods</h4>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.<h4>Conclusion</h4>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.",,pdf:https://ijpds.org/article/download/581/2923; doi:https://doi.org/10.23889/ijpds.v4i1.581; html:https://europepmc.org/articles/PMC8142962; pdf:https://europepmc.org/articles/PMC8142962?pdf=render
 32142356,https://doi.org/10.1164/rccm.201902-0286oc,"Prenatal, Early-Life, and Childhood Exposure to Air Pollution and Lung Function: The ALSPAC Cohort.","Cai Y, Hansell AL, Granell R, Blangiardo M, Zottoli M, Fecht D, Gulliver J, Henderson AJ, Elliott P.",,American journal of respiratory and critical care medicine,2020,2020-07-01,N,Air pollution; Children; Traffic; Alspac; Respiratory Health,,,"<b>Rationale</b>: Exposure to air pollution during intrauterine development and through childhood may have lasting effects on respiratory health.<b>Objectives</b>: To investigate lung function at ages 8 and 15 years in relation to air pollution exposures during pregnancy, infancy, and childhood in a UK population-based birth cohort.<b>Methods</b>: Individual exposures to source-specific particulate matter ≤10 μm in aerodynamic diameter (PM<sub>10</sub>) during each trimester, 0-6 months, 7-12 months (1990-1993), and up to age 15 years (1991-2008) were examined in relation to FEV<sub>1</sub>% predicted and FVC% predicted at ages 8 (<i>n</i> = 5,276) and 15 (<i>n</i> = 3,446) years using linear regression models adjusted for potential confounders. A profile regression model was used to identify sensitive time periods.<b>Measurements and Main Results</b>: We did not find clear evidence of a sensitive exposure period for PM<sub>10</sub> from road traffic. At age 8 years, 1 μg/m<sup>3</sup> higher exposure during the first trimester was associated with lower FEV<sub>1</sub>% predicted (-0.826; 95% confidence interval [CI], -1.357 to -0.296) and FVC% predicted (-0.817; 95% CI, -1.357 to -0.276), but similar associations were seen for exposures for other trimesters, 0-6 months, 7-12 months, and 0-7 years. Associations were stronger among boys, as well as children whose mother had a lower education level or smoked during pregnancy. For PM<sub>10</sub> from all sources, the third trimester was associated with lower FVC% predicted (-1.312; 95% CI, -2.100 to -0.525). At age 15 years, no adverse associations with lung function were seen.<b>Conclusions</b>: Exposure to road-traffic PM<sub>10</sub> during pregnancy may result in small but significant reductions in lung function at age 8 years.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328307; doi:https://doi.org/10.1164/rccm.201902-0286OC; html:https://europepmc.org/articles/PMC7328307; pdf:https://europepmc.org/articles/PMC7328307?pdf=render; doi:https://doi.org/10.1164/rccm.201902-0286oc
-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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0270668&type=printable; doi:https://doi.org/10.1371/journal.pone.0270668; html:https://europepmc.org/articles/PMC9269978; pdf:https://europepmc.org/articles/PMC9269978?pdf=render
 32651323,https://doi.org/10.3233/jad-200338,"Alzheimer's Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N = 395,769).","Ferguson AC, Tank R, Lyall LM, Ward J, Celis-Morales C, Strawbridge R, Ho F, Whelan CD, Gill J, Welsh P, Anderson JJ, Mark PB, Mackay DF, Smith DJ, Pell JP, Cavanagh J, Sattar N, Lyall DM.",,Journal of Alzheimer's disease : JAD,2020,2020-01-01,N,Cholesterol; apoE; Alzheimer’s disease; Dementia; Uk Biobank,,,"<h4>Background</h4>Alzheimer's disease (AD) is a neurodegenerative condition where the underlying etiology is still unclear. Investigating the potential influence of apolipoprotein E (APOE), a major genetic risk factor, on common blood biomarkers could provide a greater understanding of the mechanisms of AD and dementia risk.<h4>Objective</h4>Our objective was to conduct the largest (to date) single-protocol investigation of blood biomarkers in the context of APOE genotype, in UK Biobank.<h4>Methods</h4>After quality control and exclusions, data on 395,769 participants of White European ancestry were available for analysis. Linear regressions were used to test potential associations between APOE genotypes and biomarkers.<h4>Results</h4>Several biomarkers significantly associated with APOEɛ4 'risk' and ɛ2 'protective' genotypes (versus neutral ɛ3/ɛ3). Most associations supported previous data: for example, ɛ4 genotype was associated with elevated low-density lipoprotein cholesterol (LDL) (standardized beta [b] = 0.150 standard deviations [SDs] per allele, p < 0.001) and ɛ2 with lower LDL (b = -0.456 SDs, p < 0.001). There were however instances of associations found in unexpected directions: e.g., ɛ4 and increased insulin-like growth factor (IGF-1) (b = 0.017, p < 0.001) where lower levels have been previously suggested as an AD risk factor.<h4>Conclusion</h4>These findings highlight biomarker differences in non-demented people at genetic risk for dementia. The evidence herein supports previous hypotheses of involvement from cardiometabolic and neuroinflammatory pathways.",,pdf:https://eprints.gla.ac.uk/217500/1/217500.pdf; doi:https://doi.org/10.3233/JAD-200338
+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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0270668&type=printable; doi:https://doi.org/10.1371/journal.pone.0270668; html:https://europepmc.org/articles/PMC9269978; pdf:https://europepmc.org/articles/PMC9269978?pdf=render
 37814896,https://doi.org/10.1161/circgen.123.004181,Cardiovascular Disease Knowledge Portal: A Community Resource for Cardiovascular Disease Research.,"Costanzo MC, Roselli C, Brandes M, Duby M, Hoang Q, Jang D, Koesterer R, Kudtarkar P, Moriondo A, Nguyen T, Ruebenacker O, Smadbeck P, Sun Y, Butterworth AS, Aragam KG, Thomas Lumbers R, Khera AV, Lubitz SA, Ellinor PT, Gaulton KJ, Flannick J, Burtt NP.",,Circulation. Genomic and precision medicine,2023,2023-10-10,N,Phenotype; Myocardial infarction; Biomarker; Cardiovascular disease; epigenomics,,,,,doi:https://doi.org/10.1161/CIRCGEN.123.004181
 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,,,"<h4>Background and objectives</h4>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).<h4>Research design and methods</h4>Respondents were from English Longitudinal Study of Ageing (ELSA) (<i>N</i> = 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.<h4>Results</h4>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.<h4>Discussion and implications</h4>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.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/13607863.2021.1893270?needAccess=true; doi:https://doi.org/10.1080/13607863.2021.1893270
 37270201,https://doi.org/10.1136/heartjnl-2023-322616,Reliability of major bleeding events in UK routine data versus clinical trial adjudicated follow-up data.,"Harper C, Mafham M, Herrington W, Staplin N, Stevens W, Wallendszus K, Haynes R, Landray MJ, Parish S, Bowman L, Armitage J.",,Heart (British Cardiac Society),2023,2023-09-13,Y,"Atherosclerosis; Research Design; Electronic Health Records; Outcome Assessment, Health Care",,,"<h4>Objective</h4>To assess how reliable UK routine data are for ascertaining major bleeding events compared with adjudicated follow-up.<h4>Methods</h4>The ASCEND (A Study of Cardiovascular Events iN Diabetes) primary prevention trial randomised 15 480 UK people with diabetes to aspirin versus matching placebo. The primary safety outcome was major bleeding (including intracranial haemorrhage, sight-threatening eye bleeding, serious gastrointestinal bleeding and other major bleeding (epistaxis, haemoptysis, haematuria, vaginal and other bleeding)) ascertained by direct-participant mail-based follow-up, with >90% of outcomes undergoing adjudication. Nearly all participants were linked to routinely collected hospitalisation and death data (ie, routine data). An algorithm categorised bleeding events from routine data as major/minor. Kappa statistics were used to assess agreement between data sources, and randomised comparisons were re-run using routine data.<h4>Results</h4>When adjudicated follow-up and routine data were compared, there was agreement for 318 major bleeding events, with routine data identifying 281 additional-potential events, and not identifying 241 participant-reported events (kappa 0.53, 95% CI 0.49 to 0.57). Repeating ASCEND's randomised comparisons using routine data only found estimated relative and absolute effects of allocation to aspirin versus placebo on major bleeding similar to adjudicated follow-up (adjudicated follow-up: aspirin 314 (4.1%) vs placebo 245 (3.2%); rate ratio (RR) 1.29, 95% CI 1.09 to 1.52; absolute excess +6.3/5000 person-years (mean SE±2.1); vs routine data: 327 (4.2%) vs 272 (3.5%); RR 1.21, 95% CI 1.03 to 1.41; absolute excess +5.0/5000 (±2.2)).<h4>Conclusions</h4>Analyses of the ASCEND randomised trial found that major bleeding events ascertained via UK routine data sources provided relative and absolute treatment effects similar to adjudicated follow-up.<h4>Trial registration number</h4>ISRCTN60635500; NCT00135226.",,pdf:https://heart.bmj.com/content/heartjnl/early/2023/06/02/heartjnl-2023-322616.full.pdf; doi:https://doi.org/10.1136/heartjnl-2023-322616; html:https://europepmc.org/articles/PMC10511984; pdf:https://europepmc.org/articles/PMC10511984?pdf=render
@@ -1308,23 +1308,23 @@ 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCEP.121.010221; doi:https://doi.org/10.1161/CIRCEP.121.010221
 30648344,https://doi.org/10.1002/cnm.3180,A semi-active human digital twin model for detecting severity of carotid stenoses from head vibration-A coupled computational mechanics and computer vision method.,"Chakshu NK, Carson J, Sazonov I, Nithiarasu P.",,International journal for numerical methods in biomedical engineering,2019,2019-02-20,Y,Computer vision; Blood flow; Systemic Circulation; Carotid Stenoses; Digital Twin; Biomechanical Vibrations; Face Video,Applied Analytics,,"In this work, we propose a methodology to detect the severity of carotid stenosis from a video of a human face with the help of a coupled blood flow and head vibration model. This semi-active digital twin model is an attempt to link noninvasive video of a patient face to the percentage of carotid occlusion. The pulsatile nature of blood flow through the carotid arteries induces a subtle head vibration. This vibration is a potential indicator of carotid stenosis severity, and it is exploited in the present study. A head vibration model has been proposed in the present work that is linked to the forces generated by blood flow with or without occlusion. The model is used to generate a large number of virtual head vibration data for different degrees of occlusion. In order to determine the in vivo head vibration, a computer vision algorithm is adopted to use human face videos. The in vivo vibrations are compared against the virtual vibration data generated from the coupled computational blood flow/vibration model. A comparison of the in vivo vibration is made against the virtual data to find the best fit between in vivo and virtual data. The preliminary results on healthy subjects and a patient clearly indicate that the model is accurate and it possesses the potential for detecting approximate severity of carotid artery stenoses.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3180; doi:https://doi.org/10.1002/cnm.3180; html:https://europepmc.org/articles/PMC6593817; pdf:https://europepmc.org/articles/PMC6593817?pdf=render
 33824583,https://doi.org/10.2147/copd.s298585,There is No Fast Track to Identify Fast Decliners in Alpha-1 Antitrypsin Deficiency by Spirometry: A Longitudinal Study of Repeated Measurements.,"Stockley JA, Stockley RA, Sapey E.",,International journal of chronic obstructive pulmonary disease,2021,2021-03-29,Y,Lung function; decline; Alpha-1 Antitrypsin Deficiency; Obstructive Airways Disease,,,"<h4>Background</h4>It is known that lung function decline in Alpha-1 Antitrypsin Deficiency (AATD) varies. Those with a rapid decline are at highest risk of poorer outcomes but may benefit most from targeted treatments including augmentation therapy. Current evidence suggests rapid decliners can be identified after 3 years of serial follow-up. It would be advantageous to identify these patients over a shorter time period, especially in mild disease.<h4>Methods</h4>Post-bronchodilator spirometry was performed every 6 months for a total of 18 months (4 measurements) by PiZZ AATD patients (ex- or never-smokers) either without spirometric COPD or with mild COPD. Where possible, retrospective spirometry data were included. Decline was assessed using 2 (baseline and 6 month) or four measurements (including baseline, 6, 12 and 18 months) and compared to retrospective decline rates using annual measurements over 3 years.<h4>Results</h4>Seventy-two PiZZ AATD patients were included, with 27 having at least three years of retrospective, annual spirometry. 18-month progression obtained by linear regression showed variable degrees of change with 29 showing no decline, 8 showing slow decline and 35 showing rapid decline. Bland-Altman plots showed that there was no overall agreement between predicted rate of decline using data obtained over 6 months and that obtained over 18 months. Furthermore, there was no agreement between rate of decline from either 6 or 18 months' data when compared to data collected over 3 years. The positive predictive value for rapid decline with 18 months of data compared to 3 years was only 50.0%.<h4>Conclusion</h4>This study suggests serial lung function over 18 months cannot identify AATD patients who have rapidly declining lung function. There is an urgent need for different biomarkers to help identify these patients at the earliest opportunity.",,pdf:https://www.dovepress.com/getfile.php?fileID=68078; doi:https://doi.org/10.2147/COPD.S298585; html:https://europepmc.org/articles/PMC8018552; pdf:https://europepmc.org/articles/PMC8018552?pdf=render
-35355205,https://doi.org/10.1007/s11897-022-00544-3,LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review.,"Printezi MI, Yousif LIE, Kamphuis JAM, van Laake LW, Cramer MJ, Hobbelink MGG, Asselbergs FW, Teske AJ.",,Current heart failure reports,2022,2022-03-30,Y,Cardiotoxicity; Echocardiography; Left ventricular ejection fraction; Cardiac Magnetic Resonance Imaging; Cardio-oncology; Multigated Acquisition Scan,,,"<h4>Purpose of review</h4>The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably.<h4>Recent findings</h4>In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-022-00544-3.pdf; doi:https://doi.org/10.1007/s11897-022-00544-3; html:https://europepmc.org/articles/PMC9177497; pdf:https://europepmc.org/articles/PMC9177497?pdf=render
 33735069,https://doi.org/10.1016/s2589-7500(20)30240-5,"A global review of publicly available datasets for ophthalmological imaging: barriers to access, usability, and generalisability.","Khan SM, Liu X, Nath S, Korot E, Faes L, Wagner SK, Keane PA, Sebire NJ, Burton MJ, Denniston AK.",,The Lancet. Digital health,2021,2020-10-01,N,,,,"Health data that are publicly available are valuable resources for digital health research. Several public datasets containing ophthalmological imaging have been frequently used in machine learning research; however, the total number of datasets containing ophthalmological health information and their respective content is unclear. This Review aimed to identify all publicly available ophthalmological imaging datasets, detail their accessibility, describe which diseases and populations are represented, and report on the completeness of the associated metadata. With the use of MEDLINE, Google's search engine, and Google Dataset Search, we identified 94 open access datasets containing 507 724 images and 125 videos from 122 364 patients. Most datasets originated from Asia, North America, and Europe. Disease populations were unevenly represented, with glaucoma, diabetic retinopathy, and age-related macular degeneration disproportionately overrepresented in comparison with other eye diseases. The reporting of basic demographic characteristics such as age, sex, and ethnicity was poor, even at the aggregate level. This Review provides greater visibility for ophthalmological datasets that are publicly available as powerful resources for research. Our paper also exposes an increasing divide in the representation of different population and disease groups in health data repositories. The improved reporting of metadata would enable researchers to access the most appropriate datasets for their needs and maximise the potential of such resources.",,pdf:http://www.thelancet.com/article/S2589750020302405/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30240-5
+35355205,https://doi.org/10.1007/s11897-022-00544-3,LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review.,"Printezi MI, Yousif LIE, Kamphuis JAM, van Laake LW, Cramer MJ, Hobbelink MGG, Asselbergs FW, Teske AJ.",,Current heart failure reports,2022,2022-03-30,Y,Cardiotoxicity; Echocardiography; Left ventricular ejection fraction; Cardiac Magnetic Resonance Imaging; Cardio-oncology; Multigated Acquisition Scan,,,"<h4>Purpose of review</h4>The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably.<h4>Recent findings</h4>In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-022-00544-3.pdf; doi:https://doi.org/10.1007/s11897-022-00544-3; html:https://europepmc.org/articles/PMC9177497; pdf:https://europepmc.org/articles/PMC9177497?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/ ).",,pdf:https://www.nature.com/articles/s41467-020-19996-z.pdf; doi:https://doi.org/10.1038/s41467-020-19996-z; html:https://europepmc.org/articles/PMC7744536; pdf:https://europepmc.org/articles/PMC7744536?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; Inverse Electrocardiography; Equivalent Dipole Layer; His-purkinje System; 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.",,pdf:https://link.springer.com/content/pdf/10.1007/s10439-022-02905-4.pdf; doi:https://doi.org/10.1007/s10439-022-02905-4; html:https://europepmc.org/articles/PMC8847268; pdf:https://europepmc.org/articles/PMC8847268?pdf=render
 35275087,https://doi.org/10.2196/34898,Longitudinal Relationships Between Depressive Symptom Severity and Phone-Measured Mobility: Dynamic Structural Equation Modeling Study.,"Zhang Y, Folarin AA, Sun S, Cummins N, Vairavan S, Bendayan R, Ranjan Y, Rashid Z, Conde P, Stewart C, Laiou P, Sankesara H, Matcham F, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Vilella E, Simblett S, Rintala A, Bruce S, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BW, Narayan VA, Annas P, Hotopf M, Dobson RJ, RADAR-CNS consortium.",,JMIR mental health,2022,2022-03-11,Y,Modeling; Mobility; Depression; Mental health; Medical Informatics; Mhealth; Mobile Health; Dynamic Structural Equation Modeling; Location Data,,,"<h4>Background</h4>The mobility of an individual measured by phone-collected location data has been found to be associated with depression; however, the longitudinal relationships (the temporal direction of relationships) between depressive symptom severity and phone-measured mobility have yet to be fully explored.<h4>Objective</h4>We aimed to explore the relationships and the direction of the relationships between depressive symptom severity and phone-measured mobility over time.<h4>Methods</h4>Data used in this paper came from a major EU program, called the Remote Assessment of Disease and Relapse-Major Depressive Disorder, which was conducted in 3 European countries. Depressive symptom severity was measured with the 8-item Patient Health Questionnaire (PHQ-8) through mobile phones every 2 weeks. Participants' location data were recorded by GPS and network sensors in mobile phones every 10 minutes, and 11 mobility features were extracted from location data for the 2 weeks prior to the PHQ-8 assessment. Dynamic structural equation modeling was used to explore the longitudinal relationships between depressive symptom severity and phone-measured mobility.<h4>Results</h4>This study included 2341 PHQ-8 records and corresponding phone-collected location data from 290 participants (age: median 50.0 IQR 34.0, 59.0) years; of whom 215 (74.1%) were female, and 149 (51.4%) were employed. Significant negative correlations were found between depressive symptom severity and phone-measured mobility, and these correlations were more significant at the within-individual level than the between-individual level. For the direction of relationships over time, Homestay (time at home) (φ=0.09, P=.01), Location Entropy (time distribution on different locations) (φ=-0.04, P=.02), and Residential Location Count (reflecting traveling) (φ=0.05, P=.02) were significantly correlated with the subsequent changes in the PHQ-8 score, while changes in the PHQ-8 score significantly affected (φ=-0.07, P<.001) the subsequent periodicity of mobility.<h4>Conclusions</h4>Several phone-derived mobility features have the potential to predict future depression, which may provide support for future clinical applications, relapse prevention, and remote mental health monitoring practices in real-world settings.",,pdf:https://mental.jmir.org/2022/3/e34898/PDF; doi:https://doi.org/10.2196/34898; html:https://europepmc.org/articles/PMC8957008
 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,,,"<h4>Background</h4>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.<h4>Methods and results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://hal.univ-lorraine.fr/hal-03320880/file/1-s2.0-S1071916421002025-main.pdf; doi:https://doi.org/10.1016/j.cardfail.2021.05.012
+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,,,"<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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)).<h4>Conclusions</h4>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.",,pdf:https://heart.bmj.com/content/heartjnl/108/1/37.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-319566
 36224602,https://doi.org/10.1186/s12916-022-02544-5,Early onset of immune-mediated diseases in minority ethnic groups in the UK. ,"Sharma-Oates A, Zemedikun DT, Kumar K, Reynolds JA, Jain A, Raza K, Williams JA, Bravo L, Cardoso VR, Gkoutos G, Nirantharakumar K, Lord JM.",,BMC medicine,2022,2022-10-13,Y,,,,"The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis. This was a population-based retrospective primary care study. Linear regression provided unadjusted and adjusted estimates of age at diagnosis for common IMDs within the following ethnic groups: White, South Asian, African-Caribbean and Mixed-race/Other. Potential disease risk confounders in the association between ethnicity and diagnosis age including sex, smoking, body mass index and social deprivation (Townsend quintiles) were adjusted for. The analysis was replicated using data from UK Biobank (UKB). After adjusting for risk confounders, we observed that individuals from South Asian, African-Caribbean and Mixed-race/Other ethnicities were diagnosed with IMDs at a significantly younger age than their White counterparts for almost all IMDs. The difference in the diagnosis age (ranging from 2 to 30 years earlier) varied for each disease and by ethnicity. For example, rheumatoid arthritis was diagnosed at age 49, 48 and 47 years in individuals of African-Caribbean, South Asian and Mixed-race/Other ethnicities respectively, compared to 56 years in White ethnicities. The earlier diagnosis of most IMDs observed was validated in UKB although with a smaller effect size. Individuals from non-White ethnic groups in the UK had an earlier age at diagnosis for several IMDs than White adults.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02544-5; doi:https://doi.org/10.1186/s12916-022-02544-5; html:https://europepmc.org/articles/PMC9558944; pdf:https://europepmc.org/articles/PMC9558944?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,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Outcomes</h4>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 (r<sub>g</sub> 0·81).<h4>Interpretation</h4>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).",,pdf:http://www.thelancet.com/article/S2352396419300775/pdf; 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
 37206266,https://doi.org/10.1002/jha2.698,Biallelic deleterious germline <i>SH2B3</i> variants cause a novel syndrome of myeloproliferation and multi-organ autoimmunity.,"Blombery P, Pazhakh V, Albuquerque AS, Maimaris J, Tu L, Briones Miranda B, Evans F, Thompson ER, Carpenter B, Proctor I, Curtin JA, Lambert J, Burns SO, Lieschke GJ.",,EJHaem,2023,2023-04-30,Y,Genetics; Molecular diagnosis; Myeloid Function And Development,,,"<i>SH2B3</i> is a negative regulator of multiple cytokine receptor signalling pathways in haematopoietic tissue. To date, a single kindred has been described with germline biallelic loss-of-function <i>SH2B3</i> variants characterized by early onset developmental delay, hepatosplenomegaly and autoimmune thyroiditis/hepatitis. Herein, we described two further unrelated kindreds with germline biallelic loss-of-function <i>SH2B3</i> variants that show striking phenotypic similarity to each other as well as to the previous kindred of myeloproliferation and multi-organ autoimmunity. One proband also suffered severe thrombotic complications. CRISPR-Cas9 gene editing of zebrafish <i>sh2b3</i> created assorted deleterious variants in F0 crispants, which manifest significantly increased number of macrophages and thrombocytes, partially replicating the human phenotype. Treatment of the <i>sh2b3</i> crispant fish with ruxolitinib intercepted this myeloproliferative phenotype. Skin-derived fibroblasts from one patient demonstrated increased phosphorylation of JAK2 and STAT5 after stimulation with IL-3, GH, GM-CSF and EPO compared to healthy controls. In conclusion, these additional probands and functional data in combination with the previous kindred provide sufficient evidence for biallelic homozygous deleterious variants in <i>SH2B3</i> to be considered a valid gene-disease association for a clinical syndrome of bone marrow myeloproliferation and multi-organ autoimmune manifestations.",,doi:https://doi.org/10.1002/jha2.698; doi:https://doi.org/10.1002/jha2.698; html:https://europepmc.org/articles/PMC10188477; pdf:https://europepmc.org/articles/PMC10188477?pdf=render
-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,,,"<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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)).<h4>Conclusions</h4>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.",,pdf:https://heart.bmj.com/content/heartjnl/108/1/37.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-319566
 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,,,"<h4>Background and objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>LCA achieved higher aRI than other clustering algorithms.",,doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; 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
-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,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Outcomes</h4>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 (r<sub>g</sub> 0·81).<h4>Interpretation</h4>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).",,pdf:http://www.thelancet.com/article/S2352396419300775/pdf; 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
 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,,,,"<h4>Importance</h4>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.<h4>Objective</h4>To investigate whether atopic eczema is associated with cancer.<h4>Design, setting, and participants</h4>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.<h4>Exposure</h4>Atopic eczema.<h4>Main outcomes and measures</h4>Overall cancer risk and risk of specific cancers were compared in people with and without atopic eczema.<h4>Results</h4>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.<h4>Conclusions and relevance</h4>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.",,pdf:https://jamanetwork.com/journals/jamadermatology/articlepdf/2767601/jamadermatology_mansfield_2020_oi_200037_1602515656.45058.pdf; doi:https://doi.org/10.1001/jamadermatol.2020.1948; html:https://europepmc.org/articles/PMC7315391
 35477354,https://doi.org/10.1186/s12877-022-03077-5,Performance of the SarQoL quality of life tool in a UK population of older people with probable sarcopenia and implications for use in clinical trials: findings from the SarcNet registry.,"Witham MD, Heslop P, Dodds RM, Clegg AP, Hope SV, McDonald C, Smithard D, Storey B, Tan AL, Thornhill A, Sayer AA.",,BMC geriatrics,2022,2022-04-27,Y,Quality of life; Validity; Sarcopenia; Responsiveness; Minimum Clinical Important Difference,,,"<h4>Background</h4>The Sarcopenia Quality of Life (SarQoL) questionnaire is a disease-specific sarcopenia quality of life tool. We aimed to independently assess SarQoL with a particular focus on its suitability as a clinical trial outcome measure.<h4>Methods</h4>We analysed data from the UK Sarcopenia Network and Registry. Measures of physical performance and lean mass were collected at baseline. SarQoL and the Strength, Assistance, Rise, Climb - Falls (SARC-F) questionnaire (to assess functional ability) were collected at both baseline and six-month follow-up. Global changes in fitness and quality of life at 6 months were elicited on seven-point Likert scales. Internal consistency was assessed using Cronbach's alpha. Responsiveness (Cohen's d and Guyatt coefficients) and minimum clinically important differences were calculated for participants reporting slight improvement or worsening in their global scores. Concurrent validity was assessed by correlating baseline SarQoL scores with measures of physical performance and functional ability.<h4>Results</h4>We analysed data from 147 participants, 125 of whom underwent follow up assessment; mean age 78 years; 72 (49%) were women. Internal consistency was good; Cronbach's alpha was 0.944 at baseline and 0.732 at telephone follow-up. Correlation between baseline and follow-up SarQoL was weak (r = 0.27; p = 0.03). The minimum clinically important improvement ranged from 5 to 21 points giving trial sample size estimates of 25-100 participants. SarQoL scores were moderately correlated with handgrip (r = 0.37; p < 0.001), SARC-F (r = - 0.45; p < 0.001), short physical performance battery (r = 0.48; p < 0.001) and 4-m walk speed (r = 0.48; p < 0.001).<h4>Conclusions</h4>SarQoL has acceptable performance in older UK participants with probable sarcopenia and is sufficiently responsive for use in clinical trials for sarcopenia.",,pdf:https://bmcgeriatr.biomedcentral.com/track/pdf/10.1186/s12877-022-03077-5; doi:https://doi.org/10.1186/s12877-022-03077-5; html:https://europepmc.org/articles/PMC9043890; pdf:https://europepmc.org/articles/PMC9043890?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.",,pdf:https://www.nature.com/articles/s41467-022-32219-x.pdf; doi:https://doi.org/10.1038/s41467-022-32219-x; html:https://europepmc.org/articles/PMC9349177; pdf:https://europepmc.org/articles/PMC9349177?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,,,,"<h4>Objective</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Interpretation</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ana.25642; doi:https://doi.org/10.1002/ana.25642; html:https://europepmc.org/articles/PMC6944510; pdf:https://europepmc.org/articles/PMC6944510?pdf=render
-36828655,https://doi.org/10.1136/bmjopen-2022-068718,Maternal and child outcomes for pregnant women with pre-existing multiple long-term conditions: protocol for an observational study in the UK.,"Lee SI, Hope H, O'Reilly D, Kent L, Santorelli G, Subramanian A, Moss N, Azcoaga-Lorenzo A, Fagbamigbe AF, Nelson-Piercy C, Yau C, McCowan C, Kennedy JI, Phillips K, Singh M, Mhereeg M, Cockburn N, Brocklehurst P, Plachcinski R, Riley RD, Thangaratinam S, Brophy S, Hemali Sudasinghe SPB, Agrawal U, Vowles Z, Abel KM, Nirantharakumar K, Black M, Eastwood KA, MuM-PreDiCT.",,BMJ open,2023,2023-02-24,Y,Obstetrics; epidemiology; Maternal Medicine,,,"<h4>Introduction</h4>One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions).<h4>Methods and analysis</h4>Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses.<h4>Ethics and dissemination</h4>Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e068718.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-068718; html:https://europepmc.org/articles/PMC9972454; pdf:https://europepmc.org/articles/PMC9972454?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>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; doi:https://doi.org/10.1016/j.lanepe.2021.100267; html:https://europepmc.org/articles/PMC8629724; pdf:https://europepmc.org/articles/PMC8629724?pdf=render
+36828655,https://doi.org/10.1136/bmjopen-2022-068718,Maternal and child outcomes for pregnant women with pre-existing multiple long-term conditions: protocol for an observational study in the UK.,"Lee SI, Hope H, O'Reilly D, Kent L, Santorelli G, Subramanian A, Moss N, Azcoaga-Lorenzo A, Fagbamigbe AF, Nelson-Piercy C, Yau C, McCowan C, Kennedy JI, Phillips K, Singh M, Mhereeg M, Cockburn N, Brocklehurst P, Plachcinski R, Riley RD, Thangaratinam S, Brophy S, Hemali Sudasinghe SPB, Agrawal U, Vowles Z, Abel KM, Nirantharakumar K, Black M, Eastwood KA, MuM-PreDiCT.",,BMJ open,2023,2023-02-24,Y,Obstetrics; epidemiology; Maternal Medicine,,,"<h4>Introduction</h4>One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions).<h4>Methods and analysis</h4>Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses.<h4>Ethics and dissemination</h4>Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e068718.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-068718; html:https://europepmc.org/articles/PMC9972454; pdf:https://europepmc.org/articles/PMC9972454?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Objective</h4>To characterize infant entries to care in England.<h4>Participants and setting</h4>All children in England who first entered care during infancy, between April 2006 and March 2014 (n = 42,000).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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; doi:https://doi.org/10.1016/j.chiabu.2020.104760; html:https://europepmc.org/articles/PMC7718112
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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; doi:https://doi.org/10.1111/ans.17985; html:https://europepmc.org/articles/PMC9804322; pdf:https://europepmc.org/articles/PMC9804322?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13219-4; doi:https://doi.org/10.1186/s12889-022-13219-4; html:https://europepmc.org/articles/PMC9115545; pdf:https://europepmc.org/articles/PMC9115545?pdf=render
@@ -1333,14 +1333,14 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/ibdjournal/article-pdf/27/11/1719/40784408/izab059.pdf; doi:https://doi.org/10.1093/ibd/izab059; html:https://europepmc.org/articles/PMC8528147; pdf:https://europepmc.org/articles/PMC8528147?pdf=render
 31413164,https://doi.org/10.1183/13993003.00476-2019,Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis. ,"Krishna MT, Subramanian A, Adderley NJ, Zemedikun DT, Gkoutos GV, Nirantharakumar K.",,The European respiratory journal,2019,2019-11-14,N,,,,"The association between allergic diseases and autoimmune disorders is not well established. Our objective was to determine incidence rates of autoimmune disorders in allergic rhinitis/conjunctivitis (ARC), atopic eczema and asthma, and to investigate for co-occurring patterns. This was a retrospective cohort study (1990-2018) employing data extracted from The Health Improvement Network (UK primary care database). The exposure group comprised ARC, atopic eczema and asthma (all ages). For each exposed patient, up to two randomly selected age- and sex-matched controls with no documented allergic disease were used. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters. 782 320, 1 393 570 and 1 049 868 patients with ARC, atopic eczema and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sjögren's syndrome, vitiligo, rheumatoid arthritis, psoriasis, pernicious anaemia, inflammatory bowel disease, coeliac disease and autoimmune thyroiditis were uniformly higher in the three allergic diseases compared with controls. Specifically, aIRRs of SLE (1.45) and Sjögren's syndrome (1.88) were higher in ARC; aIRRs of SLE (1.44), Sjögren's syndrome (1.61) and myasthenia (1.56) were higher in asthma; and aIRRs of SLE (1.86), Sjögren's syndrome (1.48), vitiligo (1.54) and psoriasis (2.41) were higher in atopic eczema. There was no significant effect of the three allergic diseases on multiple sclerosis or of ARC and atopic eczema on myasthenia. Using ARM, allergic diseases clustered with multiple autoimmune disorders. Three age- and sex-related clusters were identified, with a relatively complex pattern in females ≥55 years old. The long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns.",,pdf:https://erj.ersjournals.com/content/erj/54/5/1900476.full.pdf; doi:https://doi.org/10.1183/13993003.00476-2019
 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
-35087703,https://doi.org/10.5334/aogh.3465,Household Air Pollution and Respiratory Symptoms a Month Before and During the Stringent COVID-19 Lockdown Levels 5 and 4 in South Africa.,"Wright CY, Kapwata T, Abdelatif N, Batini C, Wernecke B, Kunene Z, Millar DA, Mathee A, Street R, Panchal R, Hansell A, Cordell R, Hey JV.",,Annals of global health,2022,2022-01-10,Y,,,,"<h4>Background</h4>Household air pollution (HAP) is associated with adverse human health impacts. During COVID-19 Lockdown Levels 5 and 4 (the most stringent levels), South Africans remained at home, potentially increasing their exposure to HAP.<h4>Objectives</h4>To investigate changes in fuel use behaviours/patterns of use affecting HAP exposure and associated HAP-related respiratory health outcomes during COVID-19 Lockdown Levels 5 and 4.<h4>Methods</h4>This was a cross-sectional online and telephonic survey of participants from an existing database. Logistic regression and McNemar's test were used to analyse household-level data.<h4>Results</h4>Among 2 505 participants, while electricity was the main energy source for cooking and heating the month before and during Lockdown Levels 5 and 4, some households used less electricity during Lockdown Levels 5 and 4 or switched to ""dirty fuels."" One third of participants reported presence of environmental tobacco smoke in the home, a source of HAP associated with respiratory illnesses. Prevalence of HAP-related respiratory health outcomes were <10% (except dry cough). Majority of households reported cooking more, cleaning more and spending more time indoors during Lockdown Levels 5 and 4 - potentially exposed to HAP.<h4>Conclusion</h4>Should South Africa return to Lockdown Levels 5 or 4, awareness raising about the risks associated with HAP as well as messaging information for prevention of exposure to HAP, including environmental tobacco smoke, and associated adverse health impacts will be necessary.",,pdf:http://www.annalsofglobalhealth.org/articles/10.5334/aogh.3465/galley/3414/download/; doi:https://doi.org/10.5334/aogh.3465; html:https://europepmc.org/articles/PMC8757382; pdf:https://europepmc.org/articles/PMC8757382?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,,"<h4>Background</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0214-4; doi:https://doi.org/10.1186/s13326-019-0214-4; html:https://europepmc.org/articles/PMC6849160; pdf:https://europepmc.org/articles/PMC6849160?pdf=render
+35087703,https://doi.org/10.5334/aogh.3465,Household Air Pollution and Respiratory Symptoms a Month Before and During the Stringent COVID-19 Lockdown Levels 5 and 4 in South Africa.,"Wright CY, Kapwata T, Abdelatif N, Batini C, Wernecke B, Kunene Z, Millar DA, Mathee A, Street R, Panchal R, Hansell A, Cordell R, Hey JV.",,Annals of global health,2022,2022-01-10,Y,,,,"<h4>Background</h4>Household air pollution (HAP) is associated with adverse human health impacts. During COVID-19 Lockdown Levels 5 and 4 (the most stringent levels), South Africans remained at home, potentially increasing their exposure to HAP.<h4>Objectives</h4>To investigate changes in fuel use behaviours/patterns of use affecting HAP exposure and associated HAP-related respiratory health outcomes during COVID-19 Lockdown Levels 5 and 4.<h4>Methods</h4>This was a cross-sectional online and telephonic survey of participants from an existing database. Logistic regression and McNemar's test were used to analyse household-level data.<h4>Results</h4>Among 2 505 participants, while electricity was the main energy source for cooking and heating the month before and during Lockdown Levels 5 and 4, some households used less electricity during Lockdown Levels 5 and 4 or switched to ""dirty fuels."" One third of participants reported presence of environmental tobacco smoke in the home, a source of HAP associated with respiratory illnesses. Prevalence of HAP-related respiratory health outcomes were <10% (except dry cough). Majority of households reported cooking more, cleaning more and spending more time indoors during Lockdown Levels 5 and 4 - potentially exposed to HAP.<h4>Conclusion</h4>Should South Africa return to Lockdown Levels 5 or 4, awareness raising about the risks associated with HAP as well as messaging information for prevention of exposure to HAP, including environmental tobacco smoke, and associated adverse health impacts will be necessary.",,pdf:http://www.annalsofglobalhealth.org/articles/10.5334/aogh.3465/galley/3414/download/; doi:https://doi.org/10.5334/aogh.3465; html:https://europepmc.org/articles/PMC8757382; pdf:https://europepmc.org/articles/PMC8757382?pdf=render
 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,,,"<h4>Introduction</h4>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.<h4>Aims</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Prospero registration number</h4>The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057885.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?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,,,"<h4>Introduction</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa50163/Download/0050163-25062019060819.pdf; doi:https://doi.org/10.1136/injuryprev-2018-043085
 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,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755653; 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
 36960327,https://doi.org/10.2147/clep.s384605,Severe Mental Illness Among Adults with Atopic Eczema or Psoriasis: Population-Based Matched Cohort Studies within UK Primary Care.,"Adesanya EI, Henderson AD, Matthewman J, Bhate K, Hayes JF, Mulick A, Mathur R, Smith C, Carreira H, Rathod SD, Langan SM, Mansfield KE.",,Clinical epidemiology,2023,2023-03-17,Y,Psychology; epidemiology; Dermatology,,,"<h4>Background</h4>Existing research exploring associations between atopic eczema (AE) or psoriasis, and severe mental illness (SMI - ie, schizophrenia, bipolar disorder, other psychoses) is limited, with longitudinal evidence particularly scarce. Therefore, temporal directions of associations are unclear. We aimed to investigate associations between AE or psoriasis and incident SMI among adults.<h4>Methods</h4>We conducted matched cohort studies using primary care electronic health records (January 1997 to January 2020) from the UK Clinical Practice Research Datalink GOLD. We identified two cohorts: 1) adults (≥18 years) with and without AE and 2) adults with and without psoriasis. We matched (on age, sex, general practice) adults with AE or psoriasis with up to five adults without. We used Cox regression, stratified by matched set, to estimate hazard ratios (HRs) comparing incident SMI among adults with and without AE or psoriasis.<h4>Results</h4>We identified 1,023,232 adults with AE and 4,908,059 without, and 363,210 with psoriasis and 1,801,875 without. After adjusting for matching variables (age, sex, general practice) and potential confounders (deprivation, calendar period) both AE and psoriasis were associated with at least a 17% increased hazard of SMI (AE: HR=1.17,95% CI=1.12-1.22; psoriasis: HR=1.26,95% CI=1.18-1.35). After additionally adjusting for potential mediators (comorbidity burden, harmful alcohol use, smoking status, body mass index, and, in AE only, sleep problems and high-dose glucocorticoids), associations with SMI did not persist for AE (HR=0.98,95% CI=0.93-1.04), and were attenuated for psoriasis (HR=1.14,95% CI=1.05-1.23).<h4>Conclusion</h4>Our findings suggest adults with AE or psoriasis are at increased risk of SMI compared to matched comparators. After adjusting for potential mediators, associations with SMI did not persist for AE, and were attenuated for psoriasis, suggesting that the increased risk may be explained by mediating factors (eg, sleep problems). Our research highlights the importance of monitoring mental health in adults with AE or psoriasis.",,pdf:https://www.dovepress.com/getfile.php?fileID=88236; doi:https://doi.org/10.2147/CLEP.S384605; html:https://europepmc.org/articles/PMC10030004; pdf:https://europepmc.org/articles/PMC10030004?pdf=render
-37407123,https://doi.org/10.1016/j.jcmg.2023.01.016,Ischemic Heart Disease and Vascular Risk Factors Are Associated With Accelerated Brain Aging.,"Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE.",,JACC. Cardiovascular imaging,2023,2023-04-12,Y,brain aging; ischemic heart disease; Cognitive Decline; Vascular Risk Factors; Brain Health,,,"<h4>Background</h4>Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.<h4>Objectives</h4>The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.<h4>Methods</h4>Brain age was estimated in subjects with prevalent IHD (n = 1,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n = 35,237).<h4>Results</h4>Prevalent IHD was linked to significantly accelerated brain aging (P < 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13 [95% CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.<h4>Conclusions</h4>Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.",,doi:https://doi.org/10.1016/j.jcmg.2023.01.016; html:https://europepmc.org/articles/PMC10317841; pdf:https://europepmc.org/articles/PMC10317841?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.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010093&type=printable; doi:https://doi.org/10.1371/journal.pgen.1010093; html:https://europepmc.org/articles/PMC9022822; pdf:https://europepmc.org/articles/PMC9022822?pdf=render
+37407123,https://doi.org/10.1016/j.jcmg.2023.01.016,Ischemic Heart Disease and Vascular Risk Factors Are Associated With Accelerated Brain Aging.,"Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE.",,JACC. Cardiovascular imaging,2023,2023-04-12,Y,brain aging; ischemic heart disease; Cognitive Decline; Vascular Risk Factors; Brain Health,,,"<h4>Background</h4>Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.<h4>Objectives</h4>The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.<h4>Methods</h4>Brain age was estimated in subjects with prevalent IHD (n = 1,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n = 35,237).<h4>Results</h4>Prevalent IHD was linked to significantly accelerated brain aging (P < 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13 [95% CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.<h4>Conclusions</h4>Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.",,doi:https://doi.org/10.1016/j.jcmg.2023.01.016; html:https://europepmc.org/articles/PMC10317841; pdf:https://europepmc.org/articles/PMC10317841?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05033.pdf; doi:https://doi.org/10.7189/jogh.12.05033; html:https://europepmc.org/articles/PMC9304921; pdf:https://europepmc.org/articles/PMC9304921?pdf=render
 36253349,https://doi.org/10.1038/s41467-022-33675-1,Systematic Mendelian randomization using the human plasma proteome to discover potential therapeutic targets for stroke.,"Chen L, Peters JE, Prins B, Persyn E, Traylor M, Surendran P, Karthikeyan S, Yonova-Doing E, Di Angelantonio E, Roberts DJ, Watkins NA, Ouwehand WH, Danesh J, Lewis CM, Bronson PG, Markus HS, Burgess S, Butterworth AS, Howson JMM.",,Nature communications,2022,2022-10-17,Y,,,,"Stroke is the second leading cause of death with substantial unmet therapeutic needs. To identify potential stroke therapeutic targets, we estimate the causal effects of 308 plasma proteins on stroke outcomes in a two-sample Mendelian randomization framework and assess mediation effects by stroke risk factors. We find associations between genetically predicted plasma levels of six proteins and stroke (P ≤ 1.62 × 10<sup>-4</sup>). The genetic associations with stroke colocalize (Posterior Probability >0.7) with the genetic associations of four proteins (TFPI, TMPRSS5, CD6, CD40). Mendelian randomization supports atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes as stroke risk factors (P ≤ 0.0071). Body mass index, white matter hyperintensity and atrial fibrillation appear to mediate the TFPI, IL6RA, TMPRSS5 associations with stroke. Furthermore, thirty-six proteins are associated with one or more of these risk factors using Mendelian randomization. Our results highlight causal pathways and potential therapeutic targets for stroke.",,pdf:https://www.nature.com/articles/s41467-022-33675-1.pdf; doi:https://doi.org/10.1038/s41467-022-33675-1; html:https://europepmc.org/articles/PMC9576777; pdf:https://europepmc.org/articles/PMC9576777?pdf=render
 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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/ehjdh/article-pdf/2/1/154/37807088/ztaa016.pdf; doi:https://doi.org/10.1093/ehjdh/ztaa016; html:https://europepmc.org/articles/PMC9707891; pdf:https://europepmc.org/articles/PMC9707891?pdf=render
@@ -1349,8 +1349,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 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,,,,"<h4>Objective</h4>To explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer disease (AD).<h4>Methods</h4>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.<h4>Results</h4>We found that higher risk of AD was significantly associated with being a ""morning person"" (odds ratio [OR] 1.01, <i>p</i> = 0.001), shorter sleep duration (self-reported: β = -0.006, <i>p</i> = 1.9 × 10<sup>-4</sup>; accelerometer based: β = -0.015, <i>p</i> = 6.9 × 10<sup>-5</sup>), less likely to report long sleep (β = -0.003, <i>p</i> = 7.3 × 10<sup>-7</sup>), earlier timing of the least active 5 hours (β = -0.024, <i>p</i> = 1.7 × 10<sup>-13</sup>), and a smaller number of sleep episodes (β = -0.025, <i>p</i> = 5.7 × 10<sup>-14</sup>) after adjustment for multiple comparisons. We also found that higher risk of AD was associated with lower risk of insomnia (OR 0.99, <i>p</i> = 7 × 10<sup>-13</sup>). 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.<h4>Conclusion</h4>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.",,pdf:https://n.neurology.org/content/neurology/95/14/e1963.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000010463; html:https://europepmc.org/articles/PMC7682841; pdf:https://europepmc.org/articles/PMC7682841?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),,,"<h4>Objectives</h4>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.<h4>Design</h4>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.<h4>Setting</h4>Five UK centres interested in COPD.<h4>Participants</h4>Population-based sample including 714 individuals with spirometry-defined COPD, smoked at least 10 pack years and who were clinically stable for >4 weeks.<h4>Interventions</h4>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.<h4>Primary and secondary outcome measures</h4>New occurrence (first event) of fatal or non-fatal hospitalised CVD, and all-cause and cause-specific mortality.<h4>Results</h4>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).<h4>Conclusion</h4>Poor physical performance defined by the 6MWT improves prediction of CV hospitalisation in individuals with COPD.<h4>Trial registration number</h4>ID 11101.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/12/e038360.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038360; html:https://europepmc.org/articles/PMC7772292; pdf:https://europepmc.org/articles/PMC7772292?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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).<h4>Interpretation</h4>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.<h4>Funding</h4>US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.",,doi:https://doi.org/10.1016/s2352-3018(23)00028-0; 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
-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,2023,2023-09-01,Y,,,,"<h4>Importance</h4>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.<h4>Objective</h4>To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes.<h4>Design, setting, and participants</h4>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.<h4>Exposure</h4>LTL.<h4>Main outcomes and measures</h4>Cardiovascular imaging traits and HF.<h4>Results</h4>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.<h4>Conclusions and relevance</h4>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.",,pdf:https://jamanetwork.com/journals/jamacardiology/articlepdf/2807386/jamacardiology_aung_2023_oi_230032_1689092909.06174.pdf; doi:https://doi.org/10.1001/jamacardio.2023.2167; html:https://europepmc.org/articles/PMC10372756
 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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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).<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeac030/42506545/jeac030.pdf; doi:https://doi.org/10.1093/ehjci/jeac030; html:https://europepmc.org/articles/PMC9762936; pdf:https://europepmc.org/articles/PMC9762936?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,2023,2023-09-01,Y,,,,"<h4>Importance</h4>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.<h4>Objective</h4>To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes.<h4>Design, setting, and participants</h4>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.<h4>Exposure</h4>LTL.<h4>Main outcomes and measures</h4>Cardiovascular imaging traits and HF.<h4>Results</h4>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.<h4>Conclusions and relevance</h4>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.",,pdf:https://jamanetwork.com/journals/jamacardiology/articlepdf/2807386/jamacardiology_aung_2023_oi_230032_1689092909.06174.pdf; doi:https://doi.org/10.1001/jamacardio.2023.2167; html:https://europepmc.org/articles/PMC10372756
 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,,,,,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
 36066609,https://doi.org/10.1007/s00392-022-02088-x,Towards automatic classification of cardiovascular magnetic resonance Task Force Criteria for diagnosis of arrhythmogenic right ventricular cardiomyopathy.,"Bourfiss M, Sander J, de Vos BD, Te Riele ASJM, Asselbergs FW, Išgum I, Velthuis BK.",,Clinical research in cardiology : official journal of the German Cardiac Society,2023,2022-09-06,Y,Cardiac Magnetic Resonance Imaging; Arrhythmogenic Right Ventricular Cardiomyopathy; Automatic Segmentation; Deep Learning,,,"<h4>Background</h4>Arrhythmogenic right ventricular cardiomyopathy (ARVC) is diagnosed according to the Task Force Criteria (TFC) in which cardiovascular magnetic resonance (CMR) imaging plays an important role. Our study aims to apply an automatic deep learning-based segmentation for right and left ventricular CMR assessment and evaluate this approach for classification of the CMR TFC.<h4>Methods</h4>We included 227 subjects suspected of ARVC who underwent CMR. Subjects were classified into (1) ARVC patients fulfilling TFC; (2) at-risk family members; and (3) controls. To perform automatic segmentation, a Bayesian Dilated Residual Neural Network was trained and tested. Performance of automatic versus manual segmentation was assessed using Dice-coefficient and Hausdorff distance. Since automatic segmentation is most challenging in basal slices, manual correction of the automatic segmentation in the most basal slice was simulated (automatic<sup>-basal</sup>). CMR TFC calculated using manual and automatic<sup>-basal</sup> segmentation were compared using Cohen's Kappa (κ).<h4>Results</h4>Automatic segmentation was trained on CMRs of 70 subjects (39.6 ± 18.1 years, 47% female) and tested on 157 subjects (36.9 ± 17.6 years, 59% female). Dice-coefficient and Hausdorff distance showed good agreement between manual and automatic segmentations (≥ 0.89 and ≤ 10.6 mm, respectively) which further improved after simulated correction of the most basal slice (≥ 0.92 and ≤ 9.2 mm, p < 0.001). Pearson correlation of volumetric and functional CMR measurements was good to excellent (automatic (r = 0.78-0.99, p < 0.001) and automatic<sup>-basal</sup> (r = 0.88-0.99, p < 0.001) measurements). CMR TFC classification using automatic<sup>-basal</sup> segmentations was comparable to manual segmentations (κ 0.98 ± 0.02) with comparable diagnostic performance.<h4>Conclusions</h4>Combining automatic segmentation of CMRs with correction of the most basal slice results in accurate CMR TFC classification of subjects suspected of ARVC.",,pdf:https://link.springer.com/content/pdf/10.1007/s00392-022-02088-x.pdf; doi:https://doi.org/10.1007/s00392-022-02088-x; html:https://europepmc.org/articles/PMC9998324; pdf:https://europepmc.org/articles/PMC9998324?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Netherlands Lung Foundation, HDRUK, Asthma UK center for Applied Research and NIHR Global Respiratory Health Unit (RESPIRE).",,pdf:http://www.thelancet.com/article/S2589537020303047/pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100560; html:https://europepmc.org/articles/PMC7533363; pdf:https://europepmc.org/articles/PMC7533363?pdf=render
@@ -1358,8 +1358,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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.",,pdf:https://diabetesjournals.org/diabetes/article-pdf/71/2/359/640867/db210320.pdf; 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
 36609282,https://doi.org/10.1186/s13063-022-06967-6,A comparison of covariate adjustment approaches under model misspecification in individually randomized trials.,"Tackney MS, Morris T, White I, Leyrat C, Diaz-Ordaz K, Williamson E.",,Trials,2023,2023-01-06,Y,Randomized controlled trials; Iptw; G-computation; Tmle; Covariate Adjustment; Ancova; Misspecification; Aiptw,,,"Adjustment for baseline covariates in randomized trials has been shown to lead to gains in power and can protect against chance imbalances in covariates. For continuous covariates, there is a risk that the the form of the relationship between the covariate and outcome is misspecified when taking an adjusted approach. Using a simulation study focusing on individually randomized trials with small sample sizes, we explore whether a range of adjustment methods are robust to misspecification, either in the covariate-outcome relationship or through an omitted covariate-treatment interaction. Specifically, we aim to identify potential settings where G-computation, inverse probability of treatment weighting (IPTW), augmented inverse probability of treatment weighting (AIPTW) and targeted maximum likelihood estimation (TMLE) offer improvement over the commonly used analysis of covariance (ANCOVA). Our simulations show that all adjustment methods are generally robust to model misspecification if adjusting for a few covariates, sample size is 100 or larger, and there are no covariate-treatment interactions. When there is a non-linear interaction of treatment with a skewed covariate and sample size is small, all adjustment methods can suffer from bias; however, methods that allow for interactions (such as G-computation with interaction and IPTW) show improved results compared to ANCOVA. When there are a high number of covariates to adjust for, ANCOVA retains good properties while other methods suffer from under- or over-coverage. An outstanding issue for G-computation, IPTW and AIPTW in small samples is that standard errors are underestimated; they should be used with caution without the availability of small-sample corrections, development of which is needed. These findings are relevant for covariate adjustment in interim analyses of larger trials.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-022-06967-6; doi:https://doi.org/10.1186/s13063-022-06967-6; html:https://europepmc.org/articles/PMC9817411; pdf:https://europepmc.org/articles/PMC9817411?pdf=render
 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.",,pdf:https://academic.oup.com/cid/article-pdf/72/Supplement_3/S172/38618862/ciab192.pdf; doi:https://doi.org/10.1093/cid/ciab192; html:https://europepmc.org/articles/PMC8201574; pdf:https://europepmc.org/articles/PMC8201574?pdf=render
-36732776,https://doi.org/10.1186/s13040-023-00321-5,LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes.,"Alasiri A, Karczewski KJ, Cole B, Loza BL, Moore JH, van der Laan SW, Asselbergs FW, Keating BJ, van Setten J.",,BioData mining,2023,2023-02-02,Y,Human Genetic; Loss-of-function Variants; Compound Heterozygotes; Knockout Genes,,,"<h4>Background</h4>Loss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. The association of LoF variants with complex diseases and traits may lead to the discovery and validation of novel therapeutic targets. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect. Moreover, there is a lack of methods for detecting knockout genes caused by compound heterozygous (CH) LoF variants.<h4>Results</h4>We have developed the Loss-of-Function ToolKit (LoFTK), which allows efficient and automated prediction of LoF variants from genotyped, imputed and sequenced genomes. LoFTK enables the identification of genes that are inactive in one or two copies and provides summary statistics for downstream analyses. LoFTK can identify CH LoF variants, which result in LoF genes with two copies lost. Using data from parents and offspring we show that 96% of CH LoF genes predicted by LoFTK in the offspring have the respective alleles donated by each parent.<h4>Conclusions</h4>LoFTK is a command-line based tool that provides a reliable computational workflow for predicting LoF variants from genotyped and sequenced genomes, identifying genes that are inactive in 1 or 2 copies. LoFTK is an open software and is freely available to non-commercial users at https://github.com/CirculatoryHealth/LoFTK .",,pdf:https://biodatamining.biomedcentral.com/counter/pdf/10.1186/s13040-023-00321-5; doi:https://doi.org/10.1186/s13040-023-00321-5; html:https://europepmc.org/articles/PMC9893534; pdf:https://europepmc.org/articles/PMC9893534?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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; t<sub>37</sub>=-0.19, P=.85). However, 82% (14/17) of the participants were satisfied with using the app.<h4>Conclusions</h4>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.",,pdf:https://diabetes.jmir.org/2020/4/e19650/PDF; doi:https://doi.org/10.2196/19650; html:https://europepmc.org/articles/PMC7710444; pdf:https://europepmc.org/articles/PMC7710444?pdf=render
+36732776,https://doi.org/10.1186/s13040-023-00321-5,LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes.,"Alasiri A, Karczewski KJ, Cole B, Loza BL, Moore JH, van der Laan SW, Asselbergs FW, Keating BJ, van Setten J.",,BioData mining,2023,2023-02-02,Y,Human Genetic; Loss-of-function Variants; Compound Heterozygotes; Knockout Genes,,,"<h4>Background</h4>Loss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. The association of LoF variants with complex diseases and traits may lead to the discovery and validation of novel therapeutic targets. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect. Moreover, there is a lack of methods for detecting knockout genes caused by compound heterozygous (CH) LoF variants.<h4>Results</h4>We have developed the Loss-of-Function ToolKit (LoFTK), which allows efficient and automated prediction of LoF variants from genotyped, imputed and sequenced genomes. LoFTK enables the identification of genes that are inactive in one or two copies and provides summary statistics for downstream analyses. LoFTK can identify CH LoF variants, which result in LoF genes with two copies lost. Using data from parents and offspring we show that 96% of CH LoF genes predicted by LoFTK in the offspring have the respective alleles donated by each parent.<h4>Conclusions</h4>LoFTK is a command-line based tool that provides a reliable computational workflow for predicting LoF variants from genotyped and sequenced genomes, identifying genes that are inactive in 1 or 2 copies. LoFTK is an open software and is freely available to non-commercial users at https://github.com/CirculatoryHealth/LoFTK .",,pdf:https://biodatamining.biomedcentral.com/counter/pdf/10.1186/s13040-023-00321-5; doi:https://doi.org/10.1186/s13040-023-00321-5; html:https://europepmc.org/articles/PMC9893534; pdf:https://europepmc.org/articles/PMC9893534?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,,,,"<h4>Objective</h4>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.<h4>Research design and methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://care.diabetesjournals.org/content/diacare/43/8/1868.full.pdf; doi:https://doi.org/10.2337/dc19-2116
 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",,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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; doi:https://doi.org/10.1016/j.lanepe.2021.100248; html:https://europepmc.org/articles/PMC8672041; pdf:https://europepmc.org/articles/PMC8672041?pdf=render
 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,,,"<h4>Introduction</h4>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).<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>ISRCTN11811602; Pre-results.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/9/e050647.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-050647; html:https://europepmc.org/articles/PMC8450967; pdf:https://europepmc.org/articles/PMC8450967?pdf=render
@@ -1370,8 +1370,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 37817277,https://doi.org/10.1186/s13063-023-07656-8,"e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.","Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.",,Trials,2023,2023-10-10,Y,Consent; Clinical Trial; E-consent,,,"<h4>Background</h4>During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.<h4>Methods</h4>A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.<h4>Results</h4>Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.<h4>Conclusion</h4>e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.",,doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render
 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.",,pdf:https://www.nature.com/articles/s41467-023-36439-7.pdf; doi:https://doi.org/10.1038/s41467-023-36439-7; html:https://europepmc.org/articles/PMC9922305; pdf:https://europepmc.org/articles/PMC9922305?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,,,"<h4>Objectives</h4>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.<h4>Design</h4>Longitudinal study using primary care electronic health records.<h4>Setting</h4>285 general practices in North East London.<h4>Participants</h4>Children born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort).<h4>Main outcome measure</h4>Receipt of timely MMR vaccination between 12 and 18 months of age.<h4>Methods</h4>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.<h4>Results</h4>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 (<i>n</i>=33 226; 51.3% boys) and pandemic (<i>n</i>=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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e066288.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?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,,,"<h4>Background</h4>A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.<h4>Objective</h4>We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1017337/pdf; doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?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",,,"<h4>Objectives</h4>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.<h4>Design</h4>Review of prospectively collected Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) data.<h4>Setting, participants</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>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%).<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50485; doi:https://doi.org/10.5694/mja2.50485
+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,,,"<h4>Background</h4>A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.<h4>Objective</h4>We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1017337/pdf; doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?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, Li Y, Sperrin M, Ashcroft DM, van Staa TP.",,BMJ (Clinical research ed.),2020,2020-11-04,Y,,,,"<h4>Objective</h4>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.<h4>Design</h4>Longitudinal cohort study from 1 January 1998 to 31 December 2018.<h4>Setting and participants</h4>3.6 million patients from the Clinical Practice Research Datalink registered at 391 general practices in England with linked hospital admission and mortality records.<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.bmj.com/content/bmj/371/bmj.m3919.full.pdf; doi:https://doi.org/10.1136/bmj.m3919; html:https://europepmc.org/articles/PMC7610202
 36060542,https://doi.org/10.3389/fdgth.2022.939292,Clinical deployment environments: Five pillars of translational machine learning for health.,"Harris S, Bonnici T, Keen T, Lilaonitkul W, White MJ, Swanepoel N.",,Frontiers in digital health,2022,2022-08-19,Y,Safety; Artificial intelligence; Machine Learning; Health Informatics; Translational Medicine; Ml-ops,,,"Machine Learning for Health (ML4H) has demonstrated efficacy in computer imaging and other self-contained digital workflows, but has failed to substantially impact routine clinical care. This is no longer because of poor adoption of Electronic Health Records Systems (EHRS), but because ML4H needs an infrastructure for development, deployment and evaluation within the healthcare institution. In this paper, we propose a design pattern called a Clinical Deployment Environment (CDE). We sketch the five pillars of the CDE: (1) real world development supported by live data where ML4H teams can iteratively build and test at the bedside (2) an ML-Ops platform that brings the rigour and standards of continuous deployment to ML4H (3) design and supervision by those with expertise in AI safety (4) the methods of implementation science that enable the algorithmic insights to influence the behaviour of clinicians and patients and (5) continuous evaluation that uses randomisation to avoid bias but in an agile manner. The CDE is intended to answer the same requirements that bio-medicine articulated in establishing the translational medicine domain. It envisions a transition from ""real-world"" data to ""real-world"" development.",,pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2022.939292/pdf; doi:https://doi.org/10.3389/fdgth.2022.939292; html:https://europepmc.org/articles/PMC9437594; pdf:https://europepmc.org/articles/PMC9437594?pdf=render
 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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/7/e036099.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-036099; html:https://europepmc.org/articles/PMC7380838; pdf:https://europepmc.org/articles/PMC7380838?pdf=render
@@ -1387,33 +1387,33 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 34032955,https://doi.org/10.1007/s11136-021-02876-4,"Health status after penetrating major trauma in Victoria, Australia: a registry-based cohort study.","Giummarra MJ, Dipnall JF, Gibson G, Beck B, Gabbe BJ.",,"Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation",2021,2021-05-25,N,Recovery; Health Status; Health-related Quality Of Life; Gunshot Wounds; Penetrating Trauma; Stab Wounds,,,"<h4>Purpose</h4>As few studies have examined long-term health after penetrating injury, this population-based registry study sought to assess health outcomes up to 24 months post-injury.<h4>Methods</h4>Major trauma patients with penetrating trauma (2009-2017) were included from the Victorian State Trauma Registry (N = 1,067; 102 died, 208 were lost to follow-up). The EQ-5D-3L was used to measure health status at 6, 12 and 24-months. Mixed linear and logistic regressions were used to examine predictors of summary scores, and problems versus no problems on each health dimension.<h4>Results</h4>Average health status summary scores were 0.70 (sd = 0.26) at 6 and 12 months, and 0.72 (sd = 0.26) at 24 months post-injury. Prevalence of problems was consistent over time: mobility (24-26%), self-care (17-20%), usual activities (47-50%), pain/discomfort (44-49%), and anxiety/depression (54-56%). Lower health status and reporting problems was associated with middle-older age, female sex, unemployment; pre-injury disability, comorbid conditions; and assault and firearm injury versus cutting/piercing.<h4>Conclusion</h4>Problems with usual activities, pain/discomfort and anxiety or depression are common after penetrating major trauma. Risk factor screening in hospital could be used to identify people at risk of poor health outcomes, and to link people at risk with services in hospital or early post-discharge to improve their longer-term health outcomes.",,doi:https://doi.org/10.1007/s11136-021-02876-4
 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; doi:https://doi.org/10.1016/j.xgen.2021.100086; html:https://europepmc.org/articles/PMC8758502; pdf:https://europepmc.org/articles/PMC8758502?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,html:https://journals.lww.com/epidem/Fulltext/2021/09000/Weight_Change_and_the_Onset_of_Cardiovascular.19.aspx; doi:https://doi.org/10.1097/EDE.0000000000001393; html:https://europepmc.org/articles/PMC8318567; pdf:https://europepmc.org/articles/PMC8318567?pdf=render
-37750555,https://doi.org/10.1161/jaha.123.030766,Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.,"Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B, REVEAL Collaborative Group.",,Journal of the American Heart Association,2023,2023-09-26,N,Cardiovascular diseases; Quality of life; United States; United Kingdom; Secondary Prevention; Health Care Costs,,,"Background Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention. Methods and Results Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21 820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (£5830 [United Kingdom], $14 133 [US Medicare]), of myocardial infarction with urgent CRV procedure (£5614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (£4674/£4651 and $15 251/$17 539). Conclusions Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",,doi:https://doi.org/10.1161/JAHA.123.030766; html:https://europepmc.org/articles/PMC7615160; pdf:https://europepmc.org/articles/PMC7615160?pdf=render; doi:https://doi.org/10.1161/jaha.123.030766
 31109684,https://doi.org/10.1016/j.injury.2019.05.004,Agreement between medical record and administrative coding of common comorbidities in orthopaedic trauma patients.,"Daly S, Nguyen TQ, Gabbe BJ, Braaf S, Simpson P, Ekegren CL.",,Injury,2019,2019-05-08,N,Trauma; Comorbidity; Agreement; Orthopaedic; Icd-10-am,,,"OBJECTIVE:To i) quantify the agreement between comorbidities documented within medical records and an orthopaedic trauma dataset; and ii) compare agreement between these sources before and after the introduction of new comorbidity coding rules in Australian hospitals. STUDY DESIGN AND SETTING:A random sample of adult (≥ 16 years) orthopaedic trauma patients (n = 400) were extracted from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR). Diagnoses of obesity, arthritis, diabetes and cardiac conditions documented within patients' medical records were compared to ICD-10-AM comorbidity codes (provided by hospitals) for the same admission. Agreement was calculated (Cohen's kappa) before and after the introduction of new coding rules. RESULTS:All comorbidities had the same or higher prevalence in medical record data compared to coded data. Kappa values ranged from <0.001 (poor agreement) for coronary artery disease to 0.94 (excellent agreement) for type 2 diabetes. There was improvement in agreement between sources for most conditions following the introduction of new coding rules. CONCLUSION:There has been improvement in the coding of certain comorbidities since the introduction of new coding rules, suggesting that, since 2015, administrative data has improved capacity to capture patients' comorbidity profiles. Consideration must be taken when using the ICD-10-AM data due to its limitations.",,doi:https://doi.org/10.1016/j.injury.2019.05.004
 32478737,https://doi.org/10.3791/60794,Implementation of a Real-Time Psychosis Risk Detection and Alerting System Based on Electronic Health Records using CogStack.,"Wang T, Oliver D, Msosa Y, Colling C, Spada G, Roguski Ł, Folarin A, Stewart R, Roberts A, Dobson RJB, Fusar-Poli P.",,Journal of visualized experiments : JoVE,2020,2020-05-15,N,,,,"Recent studies have shown that an automated, lifespan-inclusive, transdiagnostic, and clinically based, individualized risk calculator provides a powerful system for supporting the early detection of individuals at-risk of psychosis at a large scale, by leveraging electronic health records (EHRs). This risk calculator has been externally validated twice and is undergoing feasibility testing for clinical implementation. Integration of this risk calculator in clinical routine should be facilitated by prospective feasibility studies, which are required to address pragmatic challenges, such as missing data, and the usability of this risk calculator in a real-world and routine clinical setting. Here, we present an approach for a prospective implementation of a real-time psychosis risk detection and alerting service in a real-world EHR system. This method leverages the CogStack platform, which is an open-source, lightweight, and distributed information retrieval and text extraction system. The CogStack platform incorporates a set of services that allow for full-text search of clinical data, lifespan-inclusive, real-time calculation of psychosis risk, early risk-alerting to clinicians, and the visual monitoring of patients over time. Our method includes: 1) ingestion and synchronization of data from multiple sources into the CogStack platform, 2) implementation of a risk calculator, whose algorithm was previously developed and validated, for timely computation of a patient's risk of psychosis, 3) creation of interactive visualizations and dashboards to monitor patients' health status over time, and 4) building automated alerting systems to ensure that clinicians are notified of patients at-risk, so that appropriate actions can be pursued. This is the first ever study that has developed and implemented a similar detection and alerting system in clinical routine for early detection of psychosis.",,pdf:https://www.jove.com/pdf/60794/implementation-real-time-psychosis-risk-detection-alerting-system; doi:https://doi.org/10.3791/60794; html:https://europepmc.org/articles/PMC7272223; pdf:https://europepmc.org/articles/PMC7272223?pdf=render; doi:https://doi.org/10.3791/60794
+37750555,https://doi.org/10.1161/jaha.123.030766,Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.,"Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B, REVEAL Collaborative Group.",,Journal of the American Heart Association,2023,2023-09-26,N,Cardiovascular diseases; Quality of life; United States; United Kingdom; Secondary Prevention; Health Care Costs,,,"Background Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention. Methods and Results Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21 820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (£5830 [United Kingdom], $14 133 [US Medicare]), of myocardial infarction with urgent CRV procedure (£5614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (£4674/£4651 and $15 251/$17 539). Conclusions Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",,doi:https://doi.org/10.1161/JAHA.123.030766; html:https://europepmc.org/articles/PMC7615160; pdf:https://europepmc.org/articles/PMC7615160?pdf=render; doi:https://doi.org/10.1161/jaha.123.030766
 33959646,https://doi.org/10.3389/fcvm.2021.658915,"Common Variants Associated With <i>OSMR</i> Expression Contribute to Carotid Plaque Vulnerability, but Not to Cardiovascular Disease in Humans.","van Keulen D, van Koeverden ID, Boltjes A, Princen HMG, van Gool AJ, de Borst GJ, Asselbergs FW, Tempel D, Pasterkamp G, van der Laan SW.",,Frontiers in cardiovascular medicine,2021,2021-04-20,Y,Genetics; Atherosclerosis; Cardiovascular disease; Plaque; Osm; Osmr; Lifr,,,"<b>Background and Aims:</b> Oncostatin M (OSM) signaling is implicated in atherosclerosis, however the mechanism remains unclear. We investigated the impact of common genetic variants in <i>OSM</i> and its receptors, <i>OSMR</i> and <i>LIFR</i>, on overall plaque vulnerability, plaque phenotype, intraplaque <i>OSMR</i> and <i>LIFR</i> expression, coronary artery calcification burden and cardiovascular disease susceptibility. <b>Methods and Results:</b> We queried Genotype-Tissue Expression data and found that rs13168867 (C allele) was associated with decreased <i>OSMR</i> expression and that rs10491509 (A allele) was associated with increased <i>LIFR</i> expression in arterial tissues. No variant was significantly associated with <i>OSM</i> expression. We associated these two variants with plaque characteristics from 1,443 genotyped carotid endarterectomy patients in the Athero-Express Biobank Study. After correction for multiple testing, rs13168867 was significantly associated with an increased overall plaque vulnerability (β = 0.118 ± s.e. = 0.040, <i>p</i> = 3.00 × 10<sup>-3</sup>, C allele). Looking at individual plaque characteristics, rs13168867 showed strongest associations with intraplaque fat (β = 0.248 ± s.e. = 0.088, <i>p</i> = 4.66 × 10<sup>-3</sup>, C allele) and collagen content (β = -0.259 ± s.e. = 0.095, <i>p</i> = 6.22 × 10<sup>-3</sup>, C allele), but these associations were not significant after correction for multiple testing. rs13168867 was not associated with intraplaque <i>OSMR</i> expression. Neither was intraplaque <i>OSMR</i> expression associated with plaque vulnerability and no known <i>OSMR</i> eQTLs were associated with coronary artery calcification burden, or cardiovascular disease susceptibility. No associations were found for rs10491509 in the <i>LIFR</i> locus. <b>Conclusions:</b> Our study suggests that rs1316887 in the OSMR locus is associated with increased plaque vulnerability, but not with coronary calcification or cardiovascular disease risk. It remains unclear through which precise biological mechanisms OSM signaling exerts its effects on plaque morphology. However, the OSM-OSMR/LIFR pathway is unlikely to be causally involved in lifetime cardiovascular disease susceptibility.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.658915/pdf; doi:https://doi.org/10.3389/fcvm.2021.658915; html:https://europepmc.org/articles/PMC8093786; pdf:https://europepmc.org/articles/PMC8093786?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
 34957541,https://doi.org/10.1111/bjh.18013,A novel algorithmic approach to generate consensus treatment guidelines in adult acute myeloid leukaemia.,"Coats T, Bean D, Basset A, Sirkis T, Brammeld J, Johnson S, Thomas I, Gilkes A, Raj K, Dennis M, Knapper S, Mehta P, Khwaja A, Hunter H, Tauro S, Bowen D, Jones G, Dobson R, Russell N, Dillon R.",,British journal of haematology,2022,2021-12-26,N,Myeloid Leukaemia; Classifications; Diagnostic Haematology; Clinical Haematology,,,"Induction therapy for acute myeloid leukaemia (AML) has changed with the approval of a number of new agents. Clinical guidelines can struggle to keep pace with an evolving treatment and evidence landscape and therefore identifying the most appropriate front-line treatment is challenging for clinicians. Here, we combined drug eligibility criteria and genetic risk stratification into a digital format, allowing the full range of possible treatment eligibility scenarios to be defined. Using exemplar cases representing each of the 22 identified scenarios, we sought to generate consensus on treatment choice from a panel of nine aUK AML experts. We then analysed >2500 real-world cases using the same algorithm, confirming the existence of 21/22 of these scenarios and demonstrating that our novel approach could generate a consensus AML induction treatment in 98% of cases. Our approach, driven by the use of decision trees, is an efficient way to develop consensus guidance rapidly and could be applied to other disease areas. It has the potential to be updated frequently to capture changes in eligibility criteria, novel therapies and emerging trial data. An interactive digital version of the consensus guideline is available.",,pdf:https://discovery.dundee.ac.uk/files/71382229/Br_J_Haematol_2022_Coats_A_novel_algorithmic_approach_to_generate_consensus_treatment_guidelines_in_adult_acute.pdf; doi:https://doi.org/10.1111/bjh.18013
 32685698,https://doi.org/10.12688/wellcomeopenres.15842.3,Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China.,"Endo A, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Abbott S, Kucharski AJ, Funk S.",,Wellcome open research,2020,2020-07-10,Y,Branching Process; Overdispersion; Novel Coronavirus; Superspreading; Covid-19; Sars-cov-2,,,"<b>Background:</b> A novel coronavirus disease (COVID-19) outbreak has now spread to a number of countries worldwide. While sustained transmission chains of human-to-human transmission suggest high basic reproduction number <i>R</i> <sub>0</sub>, variation in the number of secondary transmissions (often characterised by so-called superspreading events) may be large as some countries have observed fewer local transmissions than others. <b>Methods:</b> We quantified individual-level variation in COVID-19 transmission by applying a mathematical model to observed outbreak sizes in affected countries. We extracted the number of imported and local cases in the affected countries from the World Health Organization situation report and applied a branching process model where the number of secondary transmissions was assumed to follow a negative-binomial distribution. <b>Results:</b> Our model suggested a high degree of individual-level variation in the transmission of COVID-19. Within the current consensus range of <i>R</i> <sub>0</sub> (2-3), the overdispersion parameter <i>k</i> of a negative-binomial distribution was estimated to be around 0.1 (median estimate 0.1; 95% CrI: 0.05-0.2 for R0 = 2.5), suggesting that 80% of secondary transmissions may have been caused by a small fraction of infectious individuals (~10%). A joint estimation yielded likely ranges for <i>R</i> <sub>0</sub> and <i>k</i> (95% CrIs: <i>R</i> <sub>0</sub> 1.4-12; <i>k</i> 0.04-0.2); however, the upper bound of <i>R</i> <sub>0</sub> was not well informed by the model and data, which did not notably differ from that of the prior distribution. <b>Conclusions:</b> Our finding of a highly-overdispersed offspring distribution highlights a potential benefit to focusing intervention efforts on superspreading. As most infected individuals do not contribute to the expansion of an epidemic, the effective reproduction number could be drastically reduced by preventing relatively rare superspreading events.",,doi:https://doi.org/10.12688/wellcomeopenres.15842.3; html:https://europepmc.org/articles/PMC7338915; pdf:https://europepmc.org/articles/PMC7338915?pdf=render
 37699620,https://doi.org/10.1136/bmjopen-2023-074626,Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline.,"Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne J, Sharp MK, Stuart EA, Hernan MA, Lee H, McAuley JH.",,BMJ open,2023,2023-09-12,Y,Retrospective studies; epidemiology; Statistics & Research Methods,,,"<h4>Background</h4>Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline.<h4>Methods/design</h4>The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses.<h4>Ethics and dissemination</h4>Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.",,doi:https://doi.org/10.1136/bmjopen-2023-074626; html:https://europepmc.org/articles/PMC10503363; pdf:https://europepmc.org/articles/PMC10503363?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,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.26104; doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render
 31671849,https://doi.org/10.3390/ijerph16214178,Associations between the Home Physical Environment and Children's Home-Based Physical Activity and Sitting. ,"Sheldrick MP, Maitland C, Mackintosh KA, Rosenberg M, Griffiths LJ, Fry R, Stratton G.",,International journal of environmental research and public health,2019,2019-10-29,Y,,,,"It is important to understand the correlates of children's physical activity (PA) and sitting at home, where children spend significant time. The home social environment has an important influence; however, much less is known about the home physical environment. Therefore, the study aimed to assess relationships between the physical environment and children's sitting and PA at home. In total, 235 child-parent dyads were included in the analyses. Children spent 67% of their time at home sitting. Linear regression analyses examined associations between physical home environmental factors obtained via an audit and children's (55% girl, 10.2 ± 0.7) objective PA and sitting at home. Following adjustment for socio-demographics and social environmental factors, an open plan living area (OPLA), musical instrument accessibility and availability, and perceived house size were negatively and positively associated, whereas media equipment accessibility and availability was positively and negatively associated with sitting and standing, respectively. Additionally, an OPLA was positively associated with total and moderate-to-vigorous PA. Furthermore, sitting breaks were positively associated with objective garden size and negatively associated with digital TV. The physical home environment may have an important influence on children's sitting, standing and PA at home; therefore, interventions that target this environment are needed.",,pdf:https://www.mdpi.com/1660-4601/16/21/4178/pdf?version=1573119054; doi:https://doi.org/10.3390/ijerph16214178; html:https://europepmc.org/articles/PMC6862192; pdf:https://europepmc.org/articles/PMC6862192?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,,,"<h4>Background & aims</h4>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.<h4>Methods</h4>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).<h4>Results</h4>A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m<sup>2</sup>, 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).<h4>Conclusion</h4>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.<h4>Impact and implications</h4>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.",,pdf:https://discovery.ucl.ac.uk/id/eprint/10175737/1/1-s2.0-S0168827823004208-main.pdf; doi:https://doi.org/10.1016/j.jhep.2023.05.046
+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,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.26104; doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render
 33591280,https://doi.org/10.2196/16348,A Social Media Campaign (#datasaveslives) to Promote the Benefits of Using Health Data for Research Purposes: Mixed Methods Analysis.,"Hassan L, Nenadic G, Tully MP.",,Journal of medical Internet research,2021,2021-02-16,Y,Medical research; Public Engagement; Social Network Analysis; Social Media,,,"<h4>Background</h4>Social media provides the potential to engage a wide audience about scientific research, including the public. However, little empirical research exists to guide health scientists regarding what works and how to optimize impact. We examined the social media campaign #datasaveslives established in 2014 to highlight positive examples of the use and reuse of health data in research.<h4>Objective</h4>This study aims to examine how the #datasaveslives hashtag was used on social media, how often, and by whom; thus, we aim to provide insights into the impact of a major social media campaign in the UK health informatics research community and further afield.<h4>Methods</h4>We analyzed all publicly available posts (tweets) that included the hashtag #datasaveslives (N=13,895) on the microblogging platform Twitter between September 1, 2016, and August 31, 2017. Using a combination of qualitative and quantitative analyses, we determined the frequency and purpose of tweets. Social network analysis was used to analyze and visualize tweet sharing (retweet) networks among hashtag users.<h4>Results</h4>Overall, we found 4175 original posts and 9720 retweets featuring #datasaveslives by 3649 unique Twitter users. In total, 66.01% (2756/4175) of the original posts were retweeted at least once. Higher frequencies of tweets were observed during the weeks of prominent policy publications, popular conferences, and public engagement events. Cluster analysis based on retweet relationships revealed an interconnected series of groups of #datasaveslives users in academia, health services and policy, and charities and patient networks. Thematic analysis of tweets showed that #datasaveslives was used for a broader range of purposes than indexing information, including event reporting, encouraging participation and action, and showing personal support for data sharing.<h4>Conclusions</h4>This study shows that a hashtag-based social media campaign was effective in encouraging a wide audience of stakeholders to disseminate positive examples of health research. Furthermore, the findings suggest that the campaign supported community building and bridging practices within and between the interdisciplinary sectors related to the field of health data science and encouraged individuals to demonstrate personal support for sharing health data.",,pdf:https://www.jmir.org/2021/2/e16348/PDF; doi:https://doi.org/10.2196/16348; html:https://europepmc.org/articles/PMC7925154
 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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Prospero registration number</h4>CRD42020163941.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/12/e038324.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038324; html:https://europepmc.org/articles/PMC7772326; pdf:https://europepmc.org/articles/PMC7772326?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,,,"<h4>Background & aims</h4>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.<h4>Methods</h4>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).<h4>Results</h4>A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m<sup>2</sup>, 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).<h4>Conclusion</h4>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.<h4>Impact and implications</h4>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.",,pdf:https://discovery.ucl.ac.uk/id/eprint/10175737/1/1-s2.0-S0168827823004208-main.pdf; doi:https://doi.org/10.1016/j.jhep.2023.05.046
 37748493,https://doi.org/10.1016/s2213-2600(23)00262-x,"Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study.",C-MORE/PHOSP-COVID Collaborative Group.,,The Lancet. Respiratory medicine,2023,2023-09-22,Y,,,,"<h4>Introduction</h4>The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.<h4>Methods</h4>In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025.<h4>Findings</h4>Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2-6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5-5·8]; p<sub>adjusted</sub>=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4-10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32-4·82]; p<sub>adjusted</sub>=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23-11·88]; p<sub>adjusted</sub>=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.<h4>Interpretation</h4>After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification.<h4>Funding</h4>UK Research and Innovation and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S221326002300262X/pdf; doi:https://doi.org/10.1016/S2213-2600(23)00262-X; html:https://europepmc.org/articles/PMC7615263; pdf:https://europepmc.org/articles/PMC7615263?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Aims</h4>To explore the relationship between metformin use and development of AMD among patients with type 2 diabetes in the UK.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>We found no evidence that metformin was associated with risk of AMD in primary care patients requiring treatment for type 2 diabetes.",,pdf:https://discovery.ucl.ac.uk/10143945/1/Keane_T2DM%20metformin%20and%20risk%20of%20AMD%20BJO%2020220111%20clean.pdf; doi:https://doi.org/10.1136/bjophthalmol-2021-319641
 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.",,pdf:https://www.nature.com/articles/s41467-019-11451-y.pdf; doi:https://doi.org/10.1038/s41467-019-11451-y; html:https://europepmc.org/articles/PMC6692500; pdf:https://europepmc.org/articles/PMC6692500?pdf=render
-37755828,https://doi.org/10.1001/jamanetworkopen.2023.36023,Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials: A Systematic Review.,"Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Douglas SRG, Rizzo RRN, Devonshire JJ, Williams SA, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne JAC, Sharp MK, Stuart EA, Hernán MA, Lee H, McAuley JH.",,JAMA network open,2023,2023-09-05,Y,,,,"<h4>Importance</h4>Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice.<h4>Objective</h4>To assess the reporting of observational studies that explicitly aimed to emulate a target trial.<h4>Evidence review</h4>We searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation.<h4>Findings</h4>A total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation.<h4>Conclusion and relevance</h4>In this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.",,doi:https://doi.org/10.1001/jamanetworkopen.2023.36023; html:https://europepmc.org/articles/PMC10534275
 33788869,https://doi.org/10.1371/journal.pone.0249258,Using graphic modelling to identify modifiable mediators of the association between area-based deprivation at birth and offspring unemployment.,"Bogie J, Fleming M, Cullen B, Mackay D, Pell JP.",,PloS one,2021,2021-03-31,Y,,,,"<h4>Background</h4>Deprivation can perpetuate across generations; however, the causative pathways are not well understood. Directed acyclic graphs (DAG) with mediation analysis can help elucidate and quantify complex pathways in order to identify modifiable factors at which to target interventions.<h4>Methods and findings</h4>We linked ten Scotland-wide databases (six health and four education) to produce a cohort of 217,226 pupils who attended Scottish schools between 2009 and 2013. The DAG comprised 23 potential mediators of the association between area deprivation at birth and subsequent offspring 'not in education, employment or training' status, covering maternal, antenatal, perinatal and child health, school engagement, and educational factors. Analyses were performed using modified g-computation. Deprivation at birth was associated with a 7.3% increase in offspring 'not in education, employment or training'. The principal mediators of this association were smoking during pregnancy (natural indirect effect of 0·016, 95% CI 0·013, 0·019) and school absences (natural indirect effect of 0·021, 95% CI 0·018, 0·024), explaining 22% and 30% of the total effect respectively. The proportion of the association potentially eliminated by addressing these factors was 19% (controlled direct effect when set to non-smoker 0·058; 95% CI 0·053, 0·063) for smoking during pregnancy and 38% (controlled direct effect when set to no absences 0·043; 95% CI 0·037, 0·049) for school absences.<h4>Conclusions</h4>Combining a DAG with mediation analysis helped disentangle a complex public health problem and quantified the modifiable factors of maternal smoking and school absence that could be targeted for intervention. This study also demonstrates the general utility of DAGs in understanding complex public health problems.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0249258&type=printable; doi:https://doi.org/10.1371/journal.pone.0249258; html:https://europepmc.org/articles/PMC8011734; pdf:https://europepmc.org/articles/PMC8011734?pdf=render
 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,,,"<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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 <i>MC4R</i> (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.<h4>Conclusions</h4>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.",,pdf:https://nutrition.bmj.com/content/bmjnph/3/2/247.full.pdf; doi:https://doi.org/10.1136/bmjnph-2020-000107; html:https://europepmc.org/articles/PMC7841812; pdf:https://europepmc.org/articles/PMC7841812?pdf=render
+37755828,https://doi.org/10.1001/jamanetworkopen.2023.36023,Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials: A Systematic Review.,"Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Douglas SRG, Rizzo RRN, Devonshire JJ, Williams SA, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne JAC, Sharp MK, Stuart EA, Hernán MA, Lee H, McAuley JH.",,JAMA network open,2023,2023-09-05,Y,,,,"<h4>Importance</h4>Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice.<h4>Objective</h4>To assess the reporting of observational studies that explicitly aimed to emulate a target trial.<h4>Evidence review</h4>We searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation.<h4>Findings</h4>A total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation.<h4>Conclusion and relevance</h4>In this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.",,doi:https://doi.org/10.1001/jamanetworkopen.2023.36023; html:https://europepmc.org/articles/PMC10534275
 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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e067254.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-067254; html:https://europepmc.org/articles/PMC9923317; pdf:https://europepmc.org/articles/PMC9923317?pdf=render
-33836256,https://doi.org/10.1016/j.jclinepi.2021.03.025,Internal-external cross-validation helped to evaluate the generalizability of prediction models in large clustered datasets.,"Takada T, Nijman S, Denaxas S, Snell KIE, Uijl A, Nguyen TL, Asselbergs FW, Debray TPA.",,Journal of clinical epidemiology,2021,2021-04-06,N,Heterogeneity; Discrimination; Validation; Prediction model; calibration; Model Comparison,,,"<h4>Objective</h4>To illustrate how to evaluate the need of complex strategies for developing generalizable prediction models in large clustered datasets.<h4>Study design and setting</h4>We developed eight Cox regression models to estimate the risk of heart failure using a large population-level dataset. These models differed in the number of predictors, the functional form of the predictor effects (non-linear effects and interaction) and the estimation method (maximum likelihood and penalization). Internal-external cross-validation was used to evaluate the models' generalizability across the included general practices.<h4>Results</h4>Among 871,687 individuals from 225 general practices, 43,987 (5.5%) developed heart failure during a median follow-up time of 5.8 years. For discrimination, the simplest prediction model yielded a good concordance statistic, which was not much improved by adopting complex strategies. Between-practice heterogeneity in discrimination was similar in all models. For calibration, the simplest model performed satisfactorily. Although accounting for non-linear effects and interaction slightly improved the calibration slope, it also led to more heterogeneity in the observed/expected ratio. Similar results were found in a second case study involving patients with stroke.<h4>Conclusion</h4>In large clustered datasets, prediction model studies may adopt internal-external cross-validation to evaluate the generalizability of competing models, and to identify promising modelling strategies.",,pdf:http://www.jclinepi.com/article/S0895435621001074/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.03.025
 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,,,"<h4>Objectives</h4>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.<h4>Design</h4>Systematic review and quality assessment using the appraisal of guidelines for research and evaluation (AGREE) II methodology.<h4>Data sources</h4>PubMed and EMBASE (27 October 2016), two Chinese academic databases, eight guideline databases, and Google and Google scholar (July 2017).<h4>Eligibility criteria</h4>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.<h4>Data extraction and synthesis</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Prospero registration number</h4>CRD42016046104.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/8/e026677.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-026677; html:https://europepmc.org/articles/PMC6720466; pdf:https://europepmc.org/articles/PMC6720466?pdf=render
+33836256,https://doi.org/10.1016/j.jclinepi.2021.03.025,Internal-external cross-validation helped to evaluate the generalizability of prediction models in large clustered datasets.,"Takada T, Nijman S, Denaxas S, Snell KIE, Uijl A, Nguyen TL, Asselbergs FW, Debray TPA.",,Journal of clinical epidemiology,2021,2021-04-06,N,Heterogeneity; Discrimination; Validation; Prediction model; calibration; Model Comparison,,,"<h4>Objective</h4>To illustrate how to evaluate the need of complex strategies for developing generalizable prediction models in large clustered datasets.<h4>Study design and setting</h4>We developed eight Cox regression models to estimate the risk of heart failure using a large population-level dataset. These models differed in the number of predictors, the functional form of the predictor effects (non-linear effects and interaction) and the estimation method (maximum likelihood and penalization). Internal-external cross-validation was used to evaluate the models' generalizability across the included general practices.<h4>Results</h4>Among 871,687 individuals from 225 general practices, 43,987 (5.5%) developed heart failure during a median follow-up time of 5.8 years. For discrimination, the simplest prediction model yielded a good concordance statistic, which was not much improved by adopting complex strategies. Between-practice heterogeneity in discrimination was similar in all models. For calibration, the simplest model performed satisfactorily. Although accounting for non-linear effects and interaction slightly improved the calibration slope, it also led to more heterogeneity in the observed/expected ratio. Similar results were found in a second case study involving patients with stroke.<h4>Conclusion</h4>In large clustered datasets, prediction model studies may adopt internal-external cross-validation to evaluate the generalizability of competing models, and to identify promising modelling strategies.",,pdf:http://www.jclinepi.com/article/S0895435621001074/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.03.025
 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 Confounder Data; Missing Indicator,,,"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.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4655332/1/Estimating-treatment-effects-with-partially-observed-covariates-using-outcome-regression-with-missing-indicators.pdf; doi:https://doi.org/10.1002/bimj.201900041
 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,,,"<h4>Aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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; doi:https://doi.org/10.1111/bcp.15191; html:https://europepmc.org/articles/PMC9303316; pdf:https://europepmc.org/articles/PMC9303316?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; doi:https://doi.org/10.1056/NEJMc2113864; html:https://europepmc.org/articles/PMC8552534; pdf:https://europepmc.org/articles/PMC8552534?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.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010726&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010726; html:https://europepmc.org/articles/PMC9744322; pdf:https://europepmc.org/articles/PMC9744322?pdf=render
 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.",,pdf:https://www.mdpi.com/1660-4601/17/17/6139/pdf?version=1598511551; doi:https://doi.org/10.3390/ijerph17176139; html:https://europepmc.org/articles/PMC7504024; pdf:https://europepmc.org/articles/PMC7504024?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.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010726&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010726; html:https://europepmc.org/articles/PMC9744322; pdf:https://europepmc.org/articles/PMC9744322?pdf=render
 36512045,https://doi.org/10.1007/s00330-022-09323-z,Prediction of incident cardiovascular events using machine learning and CMR radiomics.,"Pujadas ER, Raisi-Estabragh Z, Szabo L, McCracken C, Morcillo CI, Campello VM, Martín-Isla C, Atehortua AM, Vago H, Merkely B, Maurovich-Horvat P, Harvey NC, Neubauer S, Petersen SE, Lekadir K.",,European radiology,2023,2022-12-13,Y,Atrial fibrillation; Heart Failure; Preventive Medicine; Machine Learning; Radiomics,,,"<h4>Objectives</h4>Evaluation of the feasibility of using cardiovascular magnetic resonance (CMR) radiomics in the prediction of incident atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), and stroke using machine learning techniques.<h4>Methods</h4>We identified participants from the UK Biobank who experienced incident AF, HF, MI, or stroke during the continuous longitudinal follow-up. The CMR indices and the vascular risk factors (VRFs) as well as the CMR images were obtained for each participant. Three-segmented regions of interest (ROIs) were computed: right ventricle cavity, left ventricle (LV) cavity, and LV myocardium in end-systole and end-diastole phases. Radiomics features were extracted from the 3D volumes of the ROIs. Seven integrative models were built for each incident cardiovascular disease (CVD) as an outcome. Each model was built with VRF, CMR indices, and radiomics features and a combination of them. Support vector machine was used for classification. To assess the model performance, the accuracy, sensitivity, specificity, and AUC were reported.<h4>Results</h4>AF prediction model using the VRF+CMR+Rad model (accuracy: 0.71, AUC 0.76) obtained the best result. However, the AUC was similar to the VRF+Rad model. HF showed the most significant improvement with the inclusion of CMR metrics (VRF+CMR+Rad: 0.79, AUC 0.84). Moreover, adding only the radiomics features to the VRF reached an almost similarly good performance (VRF+Rad: accuracy 0.77, AUC 0.83). Prediction models looking into incident MI and stroke reached slightly smaller improvement.<h4>Conclusions</h4>Radiomics features may provide incremental predictive value over VRF and CMR indices in the prediction of incident CVDs.<h4>Key points</h4>• Prediction of incident atrial fibrillation, heart failure, stroke, and myocardial infarction using machine learning techniques. • CMR radiomics, vascular risk factors, and standard CMR indices will be considered in the machine learning models. • The experiments show that radiomics features can provide incremental predictive value over VRF and CMR indices in the prediction of incident cardiovascular diseases.",,pdf:https://link.springer.com/content/pdf/10.1007/s00330-022-09323-z.pdf; doi:https://doi.org/10.1007/s00330-022-09323-z; html:https://europepmc.org/articles/PMC10121487; pdf:https://europepmc.org/articles/PMC10121487?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.",,pdf:https://www.nature.com/articles/s41598-021-86266-3.pdf; doi:https://doi.org/10.1038/s41598-021-86266-3; html:https://europepmc.org/articles/PMC8007605; pdf:https://europepmc.org/articles/PMC8007605?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,,,,,,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/05/23/2020.05.20.20108217.full.pdf; doi:https://doi.org/10.1038/s41588-021-00783-5
@@ -1423,8 +1423,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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/m<sup>2</sup> 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; <i>P</i><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.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.120.020246; doi:https://doi.org/10.1161/JAHA.120.020246; html:https://europepmc.org/articles/PMC8403301; pdf:https://europepmc.org/articles/PMC8403301?pdf=render
 36415305,https://doi.org/10.1093/ehjopen/oeac066,"Identifying unmet antithrombotic therapeutic need, and implications for stroke and systemic embolism in atrial fibrillation patients: a population-scale longitudinal study.","Torabi F, Harris DE, Bodger O, Akbari A, Lyons RA, Gravenor M, Halcox JP.",,European heart journal open,2022,2022-11-21,Y,Anticoagulation; Atrial fibrillation; Electronic Health Records; Stroke And Systemic Embolism,,,"<h4>Aims</h4>Guidelines recommend anticoagulation (AC) in atrial fibrillation (AF) to reduce stroke and systemic embolism (SSE) risk; however, implementation has been slow across many populations. This study aimed to quantify the potential impact of changing prevalence of AF, associated risk, and AC prescribing on SSE hospitalizations and death.<h4>Methods and results</h4>We evaluated temporal trends of AF, CHA<sub>2</sub>DS<sub>2</sub>-VASc, antithrombotic prescriptions, SSE hospitalizations, death, and their associations between 2012 and 2018 in a longitudinal cohort of AF patients in Wales UK. Multi-state Markov models were used to estimate expected SSE rates given the AC coverage, adjusting for CHA<sub>2</sub>DS<sub>2</sub>-VASc scores. SSE rates were modelled for various past and future AC scenarios. A total of 107 137 AF patients were evaluated (mean age = 74 years, 45% female). AF prevalence increased from 1.75 to 2.22% (<i>P</i>-value <0.001). SSE hospitalizations decreased by 18% (2.34-1.92%, <i>P</i>-value <0.001). Increased AC coverage from 50 to 70% was associated with a 37% lower SSE rate, after adjustment for individual time-dependent CHA<sub>2</sub>DS<sub>2</sub>VASc scores. The observed AC increase accounted for approximately 80 fewer SSE hospitalizations per 100 000/year. If 90% AC coverage had been achieved since 2012, an estimated 279 SSE per 100 000/year may have been prevented. Our model also predicts that improving AC coverage to 90% over the next 9 years could reduce annual SSE rates by 9%.<h4>Conclusion</h4>We quantified the relationship between observed AC coverage, estimating the potential impact of variation in the timing of large-scale implementation. These data emphasize the importance of timely implementation and the considerable opportunity to improve clinical outcomes in the Wales-AF population.",,pdf:https://academic.oup.com/ehjopen/article-pdf/2/6/oeac066/48439565/oeac066.pdf; doi:https://doi.org/10.1093/ehjopen/oeac066; html:https://europepmc.org/articles/PMC9678205; pdf:https://europepmc.org/articles/PMC9678205?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,,,"<h4>Introduction</h4>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.<h4>Methods</h4>We used data from The National Joint Registry for England, Wales, Northern Ireland and the Isle of Man on the volume of primary THRs (<i>n</i>=94,936) and TKRs (<i>n</i>=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.<h4>Results</h4>By 2060, THR and TKR volume would increase from 2018 levels by an estimated 37.7% (<i>n</i>=130,766) and 36.6% (<i>n</i>=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).<h4>Conclusion</h4>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
-36869930,https://doi.org/10.1007/s00520-023-07633-6,Cost consequences of unscheduled emergency admissions in cancer patients in the last year of life.,"McFerran E, Cairnduff V, Elder R, Gavin A, Lawler M.",,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,2023,2023-03-04,Y,Neoplasms; Death; Palliative care; Emergency Care; Cost Consequences,,,"<h4>Objectives</h4>Cancer is a leading cause of death. This paper examines the utilisation of unscheduled emergency end-of-life healthcare and estimates expenditure in this domain. We explore care patterns and quantify the likely benefits from service reconfigurations which may influence rates of hospital admission and deaths.<h4>Methods</h4>Using prevalence-based retrospective data from the Northern Ireland General Registrar's Office linked by cancer diagnosis to Patient Administration episode data for unscheduled emergency care (1st January 2014 to 31st December 2015), we estimate unscheduled-emergency-care costs in the last year of life. We model potential resources released by reductions in length-of-stay for cancer patients. Linear regression examined patient characteristics affecting length of stay.<h4>Results</h4>A total of 3134 cancer patients used 60,746 days of unscheduled emergency care (average 19.5 days). Of these, 48.9% had ≥1 admission during their last 28 days of life. Total estimated cost was £28,684,261, averaging £9200 per person. Lung cancer patients had the highest proportion of admissions (23.2%, mean length of stay = 17.9 days, mean cost=£7224). The highest service use and total cost was in those diagnosed at stage IV (38.4%), who required 22,099 days of care, costing £9,629,014. Palliative care support, identified in 25.5% of patients, contributed £1,322,328. A 3-day reduction in the mean length of stay with a 10% reduction in admissions, could reduce costs by £7.37 million. Regression analyses explained 41% of length-of-stay variability.<h4>Conclusions</h4>The cost burden from unscheduled care use in the last year of life of cancer patients is significant. Opportunities to prioritise service reconfiguration for high-costing users emphasized lung and colorectal cancers as offering the greatest potential to influence outcomes.",,pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07633-6.pdf; doi:https://doi.org/10.1007/s00520-023-07633-6; html:https://europepmc.org/articles/PMC9985568; pdf:https://europepmc.org/articles/PMC9985568?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,,"<h4>Importance</h4>Cardiovascular disease (CVD) risk has not been previously evaluated in a large matched cohort study in idiopathic intracranial hypertension (IIH).<h4>Objectives</h4>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.<h4>Design, setting, and participants</h4>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.<h4>Main outcomes and measures</h4>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.<h4>Results</h4>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.<h4>Conclusions and relevance</h4>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.",,pdf:https://jamanetwork.com/journals/jamaneurology/articlepdf/2737044/jamaneurology_adderley_2019_oi_190046.pdf; doi:https://doi.org/10.1001/jamaneurol.2019.1812; html:https://europepmc.org/articles/PMC6618853
+36869930,https://doi.org/10.1007/s00520-023-07633-6,Cost consequences of unscheduled emergency admissions in cancer patients in the last year of life.,"McFerran E, Cairnduff V, Elder R, Gavin A, Lawler M.",,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,2023,2023-03-04,Y,Neoplasms; Death; Palliative care; Emergency Care; Cost Consequences,,,"<h4>Objectives</h4>Cancer is a leading cause of death. This paper examines the utilisation of unscheduled emergency end-of-life healthcare and estimates expenditure in this domain. We explore care patterns and quantify the likely benefits from service reconfigurations which may influence rates of hospital admission and deaths.<h4>Methods</h4>Using prevalence-based retrospective data from the Northern Ireland General Registrar's Office linked by cancer diagnosis to Patient Administration episode data for unscheduled emergency care (1st January 2014 to 31st December 2015), we estimate unscheduled-emergency-care costs in the last year of life. We model potential resources released by reductions in length-of-stay for cancer patients. Linear regression examined patient characteristics affecting length of stay.<h4>Results</h4>A total of 3134 cancer patients used 60,746 days of unscheduled emergency care (average 19.5 days). Of these, 48.9% had ≥1 admission during their last 28 days of life. Total estimated cost was £28,684,261, averaging £9200 per person. Lung cancer patients had the highest proportion of admissions (23.2%, mean length of stay = 17.9 days, mean cost=£7224). The highest service use and total cost was in those diagnosed at stage IV (38.4%), who required 22,099 days of care, costing £9,629,014. Palliative care support, identified in 25.5% of patients, contributed £1,322,328. A 3-day reduction in the mean length of stay with a 10% reduction in admissions, could reduce costs by £7.37 million. Regression analyses explained 41% of length-of-stay variability.<h4>Conclusions</h4>The cost burden from unscheduled care use in the last year of life of cancer patients is significant. Opportunities to prioritise service reconfiguration for high-costing users emphasized lung and colorectal cancers as offering the greatest potential to influence outcomes.",,pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07633-6.pdf; doi:https://doi.org/10.1007/s00520-023-07633-6; html:https://europepmc.org/articles/PMC9985568; pdf:https://europepmc.org/articles/PMC9985568?pdf=render
 35861678,https://doi.org/10.2196/36989,Developing a Long COVID Phenotype for Postacute COVID-19 in a National Primary Care Sentinel Cohort: Observational Retrospective Database Analysis.,"Mayor N, Meza-Torres B, Okusi C, Delanerolle G, Chapman M, Wang W, Anand S, Feher M, Macartney J, Byford R, Joy M, Gatenby P, Curcin V, Greenhalgh T, Delaney B, de Lusignan S.",,JMIR public health and surveillance,2022,2022-08-11,Y,Phenotype; Surveillance; epidemiology; Public Health; Hospitalization; Social Class; Disease Management; General Practitioners; Ethnicity; Electronic Health Record; Medical Record Systems; Systematized Nomenclature Of Medicine; Computerized; Bioportal; Biomedical Ontologies; Data Accuracy; Digital Tool; Covid-19; Sars-cov-2; Long Covid; Postacute Covid-19 Syndrome; Data Extracts,,,"<h4>Background</h4>Following COVID-19, up to 40% of people have ongoing health problems, referred to as postacute COVID-19 or long COVID (LC). LC varies from a single persisting symptom to a complex multisystem disease. Research has flagged that this condition is underrecorded in primary care records, and seeks to better define its clinical characteristics and management. Phenotypes provide a standard method for case definition and identification from routine data and are usually machine-processable. An LC phenotype can underpin research into this condition.<h4>Objective</h4>This study aims to develop a phenotype for LC to inform the epidemiology and future research into this condition. We compared clinical symptoms in people with LC before and after their index infection, recorded from March 1, 2020, to April 1, 2021. We also compared people recorded as having acute infection with those with LC who were hospitalized and those who were not.<h4>Methods</h4>We used data from the Primary Care Sentinel Cohort (PCSC) of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database. This network was recruited to be nationally representative of the English population. We developed an LC phenotype using our established 3-step ontological method: (1) ontological step (defining the reasoning process underpinning the phenotype, (2) coding step (exploring what clinical terms are available, and (3) logical extract model (testing performance). We created a version of this phenotype using Protégé in the ontology web language for BioPortal and using PhenoFlow. Next, we used the phenotype to compare people with LC (1) with regard to their symptoms in the year prior to acquiring COVID-19 and (2) with people with acute COVID-19. We also compared hospitalized people with LC with those not hospitalized. We compared sociodemographic details, comorbidities, and Office of National Statistics-defined LC symptoms between groups. We used descriptive statistics and logistic regression.<h4>Results</h4>The long-COVID phenotype differentiated people hospitalized with LC from people who were not and where no index infection was identified. The PCSC (N=7.4 million) includes 428,479 patients with acute COVID-19 diagnosis confirmed by a laboratory test and 10,772 patients with clinically diagnosed COVID-19. A total of 7471 (1.74%, 95% CI 1.70-1.78) people were coded as having LC, 1009 (13.5%, 95% CI 12.7-14.3) had a hospital admission related to acute COVID-19, and 6462 (86.5%, 95% CI 85.7-87.3) were not hospitalized, of whom 2728 (42.2%) had no COVID-19 index date recorded. In addition, 1009 (13.5%, 95% CI 12.73-14.28) people with LC were hospitalized compared to 17,993 (4.5%, 95% CI 4.48-4.61; P<.001) with uncomplicated COVID-19.<h4>Conclusions</h4>Our LC phenotype enables the identification of individuals with the condition in routine data sets, facilitating their comparison with unaffected people through retrospective research. This phenotype and study protocol to explore its face validity contributes to a better understanding of LC.",,pdf:https://publichealth.jmir.org/2022/8/e36989/PDF; doi:https://doi.org/10.2196/36989; html:https://europepmc.org/articles/PMC9374163
 35410184,https://doi.org/10.1186/s12889-022-13069-0,The local burden of disease during the first wave of the COVID-19 epidemic in England: estimation using different data sources from changing surveillance practices.,"Nightingale ES, Abbott S, Russell TW, CMMID Covid-19 Working Group, Lowe R, Medley GF, Brady OJ.",,BMC public health,2022,2022-04-11,Y,,,,"<h4>Background</h4>The COVID-19 epidemic has differentially impacted communities across England, with regional variation in rates of confirmed cases, hospitalisations and deaths. Measurement of this burden changed substantially over the first months, as surveillance was expanded to accommodate the escalating epidemic. Laboratory confirmation was initially restricted to clinical need (""pillar 1"") before expanding to community-wide symptomatics (""pillar 2""). This study aimed to ascertain whether inconsistent measurement of case data resulting from varying testing coverage could be reconciled by drawing inference from COVID-19-related deaths.<h4>Methods</h4>We fit a Bayesian spatio-temporal model to weekly COVID-19-related deaths per local authority (LTLA) throughout the first wave (1 January 2020-30 June 2020), adjusting for the local epidemic timing and the age, deprivation and ethnic composition of its population. We combined predictions from this model with case data under community-wide, symptomatic testing and infection prevalence estimates from the ONS infection survey, to infer the likely trajectory of infections implied by the deaths in each LTLA.<h4>Results</h4>A model including temporally- and spatially-correlated random effects was found to best accommodate the observed variation in COVID-19-related deaths, after accounting for local population characteristics. Predicted case counts under community-wide symptomatic testing suggest a total of 275,000-420,000 cases over the first wave - a median of over 100,000 additional to the total confirmed in practice under varying testing coverage. This translates to a peak incidence of around 200,000 total infections per week across England. The extent to which estimated total infections are reflected in confirmed case counts was found to vary substantially across LTLAs, ranging from 7% in Leicester to 96% in Gloucester with a median of 23%.<h4>Conclusions</h4>Limitations in testing capacity biased the observed trajectory of COVID-19 infections throughout the first wave. Basing inference on COVID-19-related mortality and higher-coverage testing later in the time period, we could explore the extent of this bias more explicitly. Evidence points towards substantial under-representation of initial growth and peak magnitude of infections nationally, to which different parts of the country contribute unequally.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13069-0; doi:https://doi.org/10.1186/s12889-022-13069-0; html:https://europepmc.org/articles/PMC8996221; pdf:https://europepmc.org/articles/PMC8996221?pdf=render
 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,,,,,,pdf:http://www.thelancet.com/article/S2589537020302133/pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100469; html:https://europepmc.org/articles/PMC7385442; pdf:https://europepmc.org/articles/PMC7385442?pdf=render
@@ -1433,8 +1433,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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.",pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/18/eurosurv-25-18-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.18.2000632&mimeType=pdf&containerItemId=content/eurosurveillance; 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
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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 .",,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-021-00249-x; doi:https://doi.org/10.1186/s13326-021-00249-x; html:https://europepmc.org/articles/PMC8383460; pdf:https://europepmc.org/articles/PMC8383460?pdf=render
 36947103,https://doi.org/10.1093/molbev/msad070,An Assessment of Quaternary Structure Functionality in Homomer Protein Complexes.,"Abrusán G, Foguet C.",,Molecular biology and evolution,2023,2023-04-01,Y,Protein complexes; Coevolution; Neutral evolution; Ligand binding; Homomers,,,"It has been recently suggested that a significant fraction of homomer protein-protein interfaces evolve neutrally, without contributing to function, due to a hydrophobic bias in missense mutations. However, the fraction of such gratuitous complexes is currently unknown. Here, we quantified the fraction of homodimers where multimerization is unlikely to contribute to their biochemical function. We show that: 1) ligand binding-site structure predicts whether a homomer is functional or not; the vast majority of homodimers with multichain binding-sites (MBS) are likely to be functional, while in homodimers with single-chain binding-sites (SBS) and small to medium interfaces, quaternary structure is unlikely to be functional in a significant fraction-35%, even up to 42%-of complexes; 2) the hydrophobicity of interfaces changes little with the strength of selection, and the amino acid composition of interfaces is shaped by the ""hydrophobic ratchet"" in both types, but they are not in a strict equilibrium with mutations; particularly cysteines are much more abundant in mutations than in interfaces or surfaces; 3) in MBS homomers, the interfaces are conserved, while in a high fraction of SBS homomers, the interface is not more conserved than the solvent-accessible surface; and 4) MBS homomer interfaces coevolve more strongly with ligand binding sites than the interfaces of SBS homomers, and MBS complexes have higher capacity to transfer information from ligands across the interfaces than SBS homomers, explaining the enrichment of allostery in the former.",,pdf:https://academic.oup.com/mbe/advance-article-pdf/doi/10.1093/molbev/msad070/49594873/msad070.pdf; doi:https://doi.org/10.1093/molbev/msad070; html:https://europepmc.org/articles/PMC10118308; pdf:https://europepmc.org/articles/PMC10118308?pdf=render
-36482104,https://doi.org/10.1038/s41591-022-02100-x,Association of wearable device-measured vigorous intermittent lifestyle physical activity with mortality.,"Stamatakis E, Ahmadi MN, Gill JMR, Thøgersen-Ntoumani C, Gibala MJ, Doherty A, Hamer M.",,Nature medicine,2022,2022-12-08,Y,,,,"Wearable devices can capture unexplored movement patterns such as brief bursts of vigorous intermittent lifestyle physical activity (VILPA) that is embedded into everyday life, rather than being done as leisure time exercise. Here, we examined the association of VILPA with all-cause, cardiovascular disease (CVD) and cancer mortality in 25,241 nonexercisers (mean age 61.8 years, 14,178 women/11,063 men) in the UK Biobank. Over an average follow-up of 6.9 years, during which 852 deaths occurred, VILPA was inversely associated with all three of these outcomes in a near-linear fashion. Compared with participants who engaged in no VILPA, participants who engaged in VILPA at the sample median VILPA frequency of 3 length-standardized bouts per day (lasting 1 or 2 min each) showed a 38%-40% reduction in all-cause and cancer mortality risk and a 48%-49% reduction in CVD mortality risk. Moreover, the sample median VILPA duration of 4.4 min per day was associated with a 26%-30% reduction in all-cause and cancer mortality risk and a 32%-34% reduction in CVD mortality risk. We obtained similar results when repeating the above analyses for vigorous physical activity (VPA) in 62,344 UK Biobank participants who exercised (1,552 deaths, 35,290 women/27,054 men). These results indicate that small amounts of vigorous nonexercise physical activity are associated with substantially lower mortality. VILPA in nonexercisers appears to elicit similar effects to VPA in exercisers, suggesting that VILPA may be a suitable physical activity target, especially in people not able or willing to exercise.",,pdf:https://www.nature.com/articles/s41591-022-02100-x.pdf; doi:https://doi.org/10.1038/s41591-022-02100-x; html:https://europepmc.org/articles/PMC9800274; pdf:https://europepmc.org/articles/PMC9800274?pdf=render
 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; doi:https://doi.org/10.1016/j.xpro.2021.100334; html:https://europepmc.org/articles/PMC7881265; pdf:https://europepmc.org/articles/PMC7881265?pdf=render
+36482104,https://doi.org/10.1038/s41591-022-02100-x,Association of wearable device-measured vigorous intermittent lifestyle physical activity with mortality.,"Stamatakis E, Ahmadi MN, Gill JMR, Thøgersen-Ntoumani C, Gibala MJ, Doherty A, Hamer M.",,Nature medicine,2022,2022-12-08,Y,,,,"Wearable devices can capture unexplored movement patterns such as brief bursts of vigorous intermittent lifestyle physical activity (VILPA) that is embedded into everyday life, rather than being done as leisure time exercise. Here, we examined the association of VILPA with all-cause, cardiovascular disease (CVD) and cancer mortality in 25,241 nonexercisers (mean age 61.8 years, 14,178 women/11,063 men) in the UK Biobank. Over an average follow-up of 6.9 years, during which 852 deaths occurred, VILPA was inversely associated with all three of these outcomes in a near-linear fashion. Compared with participants who engaged in no VILPA, participants who engaged in VILPA at the sample median VILPA frequency of 3 length-standardized bouts per day (lasting 1 or 2 min each) showed a 38%-40% reduction in all-cause and cancer mortality risk and a 48%-49% reduction in CVD mortality risk. Moreover, the sample median VILPA duration of 4.4 min per day was associated with a 26%-30% reduction in all-cause and cancer mortality risk and a 32%-34% reduction in CVD mortality risk. We obtained similar results when repeating the above analyses for vigorous physical activity (VPA) in 62,344 UK Biobank participants who exercised (1,552 deaths, 35,290 women/27,054 men). These results indicate that small amounts of vigorous nonexercise physical activity are associated with substantially lower mortality. VILPA in nonexercisers appears to elicit similar effects to VPA in exercisers, suggesting that VILPA may be a suitable physical activity target, especially in people not able or willing to exercise.",,pdf:https://www.nature.com/articles/s41591-022-02100-x.pdf; doi:https://doi.org/10.1038/s41591-022-02100-x; html:https://europepmc.org/articles/PMC9800274; pdf:https://europepmc.org/articles/PMC9800274?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.",,pdf:https://joii-journal.springeropen.com/counter/pdf/10.1186/s12348-022-00304-3; doi:https://doi.org/10.1186/s12348-022-00304-3; html:https://europepmc.org/articles/PMC9443634; pdf:https://europepmc.org/articles/PMC9443634?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; doi:https://doi.org/10.1016/j.xgen.2021.100004; html:https://europepmc.org/articles/PMC9451133; pdf:https://europepmc.org/articles/PMC9451133?pdf=render
 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; doi:https://doi.org/10.1016/j.jnutbio.2021.108929
@@ -1451,8 +1451,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 33174528,https://doi.org/10.3310/hta24570,Antimicrobial-impregnated central venous catheters for preventing neonatal bloodstream infection: the PREVAIL RCT.,"Gilbert R, Brown M, Faria R, Fraser C, Donohue C, Rainford N, Grosso A, Sinha AK, Dorling J, Gray J, Muller-Pebody B, Harron K, Moitt T, McGuire W, Bojke L, Gamble C, Oddie SJ.",,"Health technology assessment (Winchester, England)",2020,2020-11-01,Y,Infant; Newborn; Economic analysis; Central Venous Catheter; Bloodstream Infection; Randomised Controlled Trial; Generalisability; Antimicrobial-impregnated Catheter,,,"<h4>Background</h4>Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies.<h4>Objectives</h4>The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS.<h4>Design</h4>Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England.<h4>Setting</h4>The randomised controlled trial was conducted in 18 neonatal intensive care units in England.<h4>Participants</h4>Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size).<h4>Interventions</h4>The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation.<h4>Main outcome measure</h4>Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data.<h4>Results</h4>Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, <i>n</i> = 430; standard peripherally inserted central venous catheter, <i>n</i> = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; <i>p</i> = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; <i>p</i> = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days.<h4>Limitations</h4>The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance.<h4>Conclusions</h4>No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care.<h4>Trial registration</h4>Current Controlled Trials ISRCTN81931394.<h4>Funding</h4>This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in <i>Health Technology Assessment</i>; Vol. 24, No. 57. See the NIHR Journals Library website for further project information.",,pdf:https://njl-admin.nihr.ac.uk/document/download/2034745; html:http://europepmc.org/books/NBK563908; doi:https://doi.org/10.3310/hta24570
 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.",,pdf:https://www.mdpi.com/1660-4601/17/3/892/pdf?version=1580475934; doi:https://doi.org/10.3390/ijerph17030892; html:https://europepmc.org/articles/PMC7037699; pdf:https://europepmc.org/articles/PMC7037699?pdf=render
 36688706,https://doi.org/10.1093/rheumatology/kead038,Classification of patients with osteoarthritis through clusters of comorbidities using 633 330 individuals from Spain.,"Pineda-Moncusí M, Dernie F, Dell'Isola A, Kamps A, Runhaar J, Swain S, Zhang W, Englund M, Pitsillidou I, Strauss VY, Robinson DE, Prieto-Alhambra D, Khalid S.",,"Rheumatology (Oxford, England)",2023,2023-11-01,Y,Clustering; epidemiology; Comorbidities; Oa,,,"<h4>Objectives</h4>To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster.<h4>Methods</h4>This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥1% of the individuals (n = 35) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards.<h4>Results</h4>We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95% CI: 1.09, 1.15]).<h4>Conclusion</h4>Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.",,pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead038/49101708/kead038.pdf; doi:https://doi.org/10.1093/rheumatology/kead038; html:https://europepmc.org/articles/PMC10629784; pdf:https://europepmc.org/articles/PMC10629784?pdf=render
-37730620,https://doi.org/10.1186/s13643-023-02333-y,What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.,"Rahtz E, Bell SL, Nurse A, Wheeler BW, Guell C, Elliott LR, Thompson CW, McDougall CW, Lovell R.",,Systematic reviews,2023,2023-09-20,Y,,,,"<h4>Background</h4>There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits.<h4>Methods</h4>An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed.<h4>Discussion</h4>The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02333-y; doi:https://doi.org/10.1186/s13643-023-02333-y; html:https://europepmc.org/articles/PMC10512649; pdf:https://europepmc.org/articles/PMC10512649?pdf=render
 34002035,https://doi.org/10.1038/s41366-021-00807-4,Risk factors mediating the effect of body mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis.,"Gill D, Zuber V, Dawson J, Pearson-Stuttard J, Carter AR, Sanderson E, Karhunen V, Levin MG, Wootton RE, Klarin D, Tsao PS, Tsilidis KK, Damrauer SM, Burgess S, Elliott P.",,International journal of obesity (2005),2021,2021-05-17,Y,,,,"<h4>Background</h4>Higher body mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits, and smoking is not fully understood.<h4>Methods</h4>Using consortia and UK Biobank genetic association summary data from 140,595 to 898,130 participants predominantly of European ancestry, Mendelian randomization mediation analysis was performed to investigate the degree to which systolic blood pressure (SBP), diabetes, lipid traits, and smoking mediated an effect of BMI and WHR on the risk of coronary artery disease (CAD), peripheral artery disease (PAD) and stroke.<h4>Results</h4>The odds ratio of CAD per 1-standard deviation increase in genetically predicted BMI was 1.49 (95% CI 1.39 to 1.60). This attenuated to 1.34 (95% CI 1.24 to 1.45) after adjusting for genetically predicted SBP (proportion mediated 27%, 95% CI 3% to 50%), to 1.27 (95% CI 1.17 to 1.37) after adjusting for genetically predicted diabetes (41% mediated, 95% CI 18% to 63%), to 1.47 (95% CI 1.36 to 1.59) after adjusting for genetically predicted lipids (3% mediated, 95% -23% to 29%), and to 1.46 (95% CI 1.34 to 1.58) after adjusting for genetically predicted smoking (6% mediated, 95% CI -20% to 32%). Adjusting for all the mediators together, the estimate attenuated to 1.14 (95% CI 1.04 to 1.26; 66% mediated, 95% CI 42% to 91%). A similar pattern was observed when considering genetically predicted WHR as the exposure, and PAD or stroke as the outcome.<h4>Conclusions</h4>Measures to reduce obesity will lower the risk of cardiovascular disease primarily by impacting downstream metabolic risk factors, particularly diabetes and hypertension. Reduction of obesity prevalence alongside control and management of its mediators is likely to be most effective for minimizing the burden of obesity.",,pdf:https://www.nature.com/articles/s41366-021-00807-4.pdf; doi:https://doi.org/10.1038/s41366-021-00807-4; html:https://europepmc.org/articles/PMC8236409; pdf:https://europepmc.org/articles/PMC8236409?pdf=render
+37730620,https://doi.org/10.1186/s13643-023-02333-y,What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.,"Rahtz E, Bell SL, Nurse A, Wheeler BW, Guell C, Elliott LR, Thompson CW, McDougall CW, Lovell R.",,Systematic reviews,2023,2023-09-20,Y,,,,"<h4>Background</h4>There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits.<h4>Methods</h4>An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed.<h4>Discussion</h4>The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02333-y; doi:https://doi.org/10.1186/s13643-023-02333-y; html:https://europepmc.org/articles/PMC10512649; pdf:https://europepmc.org/articles/PMC10512649?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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; <i>p</i> = 0.006).<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/burnstrauma/article-pdf/doi/10.1093/burnst/tkaa044/37307900/tkaa044.pdf; doi:https://doi.org/10.1093/burnst/tkaa044; html:https://europepmc.org/articles/PMC7901708; pdf:https://europepmc.org/articles/PMC7901708?pdf=render
 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.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/39/eurosurv-26-39-5.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.39.2001440&mimeType=pdf&containerItemId=content/eurosurveillance; 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
 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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Design</h4>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.<h4>Discussion</h4>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.",,pdf:https://eprints.whiterose.ac.uk/197084/1/26335565221145493.pdf; doi:https://doi.org/10.1177/26335565221145493; html:https://europepmc.org/articles/PMC9761229; pdf:https://europepmc.org/articles/PMC9761229?pdf=render
@@ -1460,24 +1460,24 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 37538810,https://doi.org/10.1016/j.ekir.2023.05.008,Impact of outcome adjudication in kidney disease trials: observations from the Study of Heart and Renal Protection (SHARP).,"Herrington WG, Harper C, Staplin N, Haynes R, Emberson J, Reith C, Hooi LS, Levin A, Wanner C, Baigent C, Landray M, SHARP Collaborative Group.",,Kidney international reports,2023,2023-08-01,Y,Transplantation; Dialysis; Chronic Kidney Disease; Clinical Trials; Adjudication,,,"<h4>Introduction</h4>We aimed to assess opportunities for trial streamlining and the scientific impact of adjudication on kidney and cardiovascular outcomes in CKD.<h4>Methods</h4>We analysed the effects of adjudication of ~2100 maintenance kidney replacement therapy (KRT) and ~1300 major atherosclerotic events (MAEs) recorded in SHARP. We first compared outcome classification before versus after adjudication, and then re-ran randomised comparisons using pre-adjudicated follow-up data.<h4>Results</h4>For maintenance KRT, adjudication had little impact with only 1% of events being refuted (28/2115). Consequently, randomised comparisons using pre-adjudication reports found almost identical results (pre-adjudication: simvastatin/ezetimibe 1038 vs placebo 1077; risk ratio [RR] 0.95, 95%CI 0.88-1.04; post-adjudicated: 1057 vs 1084; RR=0.97, 95%CI 0.89-1.05). For MAEs, about one-quarter of patient reports were refuted (324/1275 [25%]), and reviewing 3538 other potential vascular events and death reports identified only 194 additional MAEs. Nevertheless, randomised analyses using SHARP's pre-adjudicated data alone found similar results to analyses based on adjudicated outcomes (pre-adjudication: 573 vs 702; RR=0.80, 95%CI 0.72-0.89; adjudicated: 526 vs 619; RR=0.83, 95%CI 0.74- 0.94), and also suggested refuted MAEs were likely to represent atherosclerotic disease (RR for refuted MAEs=0.80, 95%CI 0.65-1.00).<h4>Conclusions</h4>These analyses provide three key insights. First, they provide a rationale for nephrology trials not to adjudicate maintenance KRT. Secondly, when an event that mimics an atherosclerotic outcome is not expected to be influenced by the treatment under study (e.g. heart failure), the aim of adjudicating atherosclerotic outcomes should be to remove such events. Lastly, restrictive definitions for the remaining suspected atherosclerotic outcomes may reduce statistical power.",,doi:https://doi.org/10.1016/j.ekir.2023.05.008; html:https://europepmc.org/articles/PMC7614871; pdf:https://europepmc.org/articles/PMC7614871?pdf=render
 35385889,https://doi.org/10.1515/dmpt-2021-0104,Prevalence of <i>CYP2C19*2</i> 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,,,"<h4>Objectives</h4>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 <i>CYP2C19*2</i> carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.<h4>Methods</h4>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 <i>CYP2C19</i> assay.<h4>Results</h4>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 <i>CYP2C19*2</i> 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 <i>CYP2C19*2</i> allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele.<h4>Conclusions</h4>This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.",,pdf:https://discovery.ucl.ac.uk/10135735/1/Asselbergs_10.1515_dmdi-2021-0104.pdf; doi:https://doi.org/10.1515/dmpt-2021-0104
 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,,,"<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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). <b>Conclusion:</b> 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.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364733; doi:https://doi.org/10.1080/20008066.2022.2105577; html:https://europepmc.org/articles/PMC9364733; pdf:https://europepmc.org/articles/PMC9364733?pdf=render
-34535985,https://doi.org/10.1002/hep4.1805,Genome-Wide Association Study of NAFLD Using Electronic Health Records.,"Fairfield CJ, Drake TM, Pius R, Bretherick AD, Campbell A, Clark DW, Fallowfield JA, Hayward C, Henderson NC, Joshi PK, Mills NL, Porteous DJ, Ramachandran P, Semple RK, Shaw CA, Sudlow CLM, Timmers PRHJ, Wilson JF, Wigmore SJ, Harrison EM, Spiliopoulou A.",,Hepatology communications,2022,2021-09-17,Y,,,,"Genome-wide association studies (GWAS) have identified several risk loci for nonalcoholic fatty liver disease (NAFLD). Previous studies have largely relied on small sample sizes and have assessed quantitative traits. We performed a case-control GWAS in the UK Biobank using recorded diagnosis of NAFLD based on diagnostic codes recommended in recent consensus guidelines. We performed a GWAS of 4,761 cases of NAFLD and 373,227 healthy controls without evidence of NAFLD. Sensitivity analyses were performed excluding other co-existing hepatic pathology, adjusting for body mass index (BMI) and adjusting for alcohol intake. A total of 9,723,654 variants were assessed by logistic regression adjusted for age, sex, genetic principal components, and genotyping batch. We performed a GWAS meta-analysis using available summary association statistics. Six risk loci were identified (P < 5*10<sup>-8</sup> ) (apolipoprotein E [APOE], patatin-like phospholipase domain containing 3 [PNPLA3, transmembrane 6 superfamily member 2 [TM6SF2], glucokinase regulator [GCKR], mitochondrial amidoxime reducing component 1 [MARC1], and tribbles pseudokinase 1 [TRIB1]). All loci retained significance in sensitivity analyses without co-existent hepatic pathology and after adjustment for BMI. PNPLA3 and TM6SF2 remained significant after adjustment for alcohol (alcohol intake was known in only 158,388 individuals), with others demonstrating consistent direction and magnitude of effect. All six loci were significant on meta-analysis. Rs429358 (P = 2.17*10<sup>-11</sup> ) is a missense variant within the APOE gene determining ϵ4 versus ϵ2/ϵ3 alleles. The ϵ4 allele of APOE offered protection against NAFLD (odds ratio for heterozygotes 0.84 [95% confidence interval 0.78-0.90] and homozygotes 0.64 [0.50-0.79]). Conclusion: This GWAS replicates six known NAFLD-susceptibility loci and confirms that the ϵ4 allele of APOE is associated with protection against NAFLD. The results are consistent with published GWAS using histological and radiological measures of NAFLD, confirming that NAFLD identified through diagnostic codes from consensus guidelines is a valid alternative to more invasive and costly approaches.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep4.1805; doi:https://doi.org/10.1002/hep4.1805; html:https://europepmc.org/articles/PMC8793997; pdf:https://europepmc.org/articles/PMC8793997?pdf=render
 31756303,https://doi.org/10.1161/circgen.119.002711,Genetic Determinants of Lipids and Cardiovascular Disease Outcomes: A Wide-Angled Mendelian Randomization Investigation.,"Allara E, Morani G, Carter P, Gkatzionis A, Zuber V, Foley CN, Rees JMB, Mason AM, Bell S, Gill D, Lindström S, Butterworth AS, Di Angelantonio E, Peters J, Burgess S, INVENT consortium.",,Circulation. Genomic and precision medicine,2019,2019-11-22,Y,Lipids; Aortic valve stenosis; epidemiology; Venous Thromboembolism; Mendelian Randomization,,,"<h4>Background</h4>Evidence from randomized trials has shown that therapies that lower LDL (low-density lipoprotein)-cholesterol and triglycerides reduce coronary artery disease (CAD) risk. However, there is still uncertainty about their effects on other cardiovascular outcomes. We therefore performed a systematic investigation of causal relationships between circulating lipids and cardiovascular outcomes using a Mendelian randomization approach.<h4>Methods</h4>In the primary analysis, we performed 2-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188 577 participants, and genetic associations with cardiovascular outcomes from 367 703 participants in UK Biobank.<h4>Results</h4>For LDL-cholesterol, in addition to the expected positive associations with CAD risk (odds ratio [OR] per 1 SD increase, 1.45 [95% CI, 1.35-1.57]) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically predicted LDL-cholesterol with abdominal aortic aneurysm (OR, 1.75 [95% CI, 1.40-2.17]) and aortic valve stenosis (OR, 1.46 [95% CI, 1.25-1.70]). Genetically predicted triglyceride levels were positively associated with CAD (OR, 1.25 [95% CI, 1.12-1.40]), aortic valve stenosis (OR, 1.29 [95% CI, 1.04-1.61]), and hypertension (OR, 1.17 [95% CI, 1.07-1.27]), but inversely associated with venous thromboembolism (OR, 0.79 [95% CI, 0.67-0.93]) and hemorrhagic stroke (OR, 0.78 [95% CI, 0.62-0.98]). We also found positive associations of genetically predicted LDL-cholesterol and triglycerides with heart failure that appeared to be mediated by CAD.<h4>Conclusions</h4>Lowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis but may increase thromboembolic risk.",,doi:https://doi.org/10.1161/CIRCGEN.119.002711; html:https://europepmc.org/articles/PMC6922071; pdf:https://europepmc.org/articles/PMC6922071?pdf=render; pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.119.002711
-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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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; doi:https://doi.org/10.1093/europace/euac022; html:https://europepmc.org/articles/PMC9326851; pdf:https://europepmc.org/articles/PMC9326851?pdf=render
+34535985,https://doi.org/10.1002/hep4.1805,Genome-Wide Association Study of NAFLD Using Electronic Health Records.,"Fairfield CJ, Drake TM, Pius R, Bretherick AD, Campbell A, Clark DW, Fallowfield JA, Hayward C, Henderson NC, Joshi PK, Mills NL, Porteous DJ, Ramachandran P, Semple RK, Shaw CA, Sudlow CLM, Timmers PRHJ, Wilson JF, Wigmore SJ, Harrison EM, Spiliopoulou A.",,Hepatology communications,2022,2021-09-17,Y,,,,"Genome-wide association studies (GWAS) have identified several risk loci for nonalcoholic fatty liver disease (NAFLD). Previous studies have largely relied on small sample sizes and have assessed quantitative traits. We performed a case-control GWAS in the UK Biobank using recorded diagnosis of NAFLD based on diagnostic codes recommended in recent consensus guidelines. We performed a GWAS of 4,761 cases of NAFLD and 373,227 healthy controls without evidence of NAFLD. Sensitivity analyses were performed excluding other co-existing hepatic pathology, adjusting for body mass index (BMI) and adjusting for alcohol intake. A total of 9,723,654 variants were assessed by logistic regression adjusted for age, sex, genetic principal components, and genotyping batch. We performed a GWAS meta-analysis using available summary association statistics. Six risk loci were identified (P < 5*10<sup>-8</sup> ) (apolipoprotein E [APOE], patatin-like phospholipase domain containing 3 [PNPLA3, transmembrane 6 superfamily member 2 [TM6SF2], glucokinase regulator [GCKR], mitochondrial amidoxime reducing component 1 [MARC1], and tribbles pseudokinase 1 [TRIB1]). All loci retained significance in sensitivity analyses without co-existent hepatic pathology and after adjustment for BMI. PNPLA3 and TM6SF2 remained significant after adjustment for alcohol (alcohol intake was known in only 158,388 individuals), with others demonstrating consistent direction and magnitude of effect. All six loci were significant on meta-analysis. Rs429358 (P = 2.17*10<sup>-11</sup> ) is a missense variant within the APOE gene determining ϵ4 versus ϵ2/ϵ3 alleles. The ϵ4 allele of APOE offered protection against NAFLD (odds ratio for heterozygotes 0.84 [95% confidence interval 0.78-0.90] and homozygotes 0.64 [0.50-0.79]). Conclusion: This GWAS replicates six known NAFLD-susceptibility loci and confirms that the ϵ4 allele of APOE is associated with protection against NAFLD. The results are consistent with published GWAS using histological and radiological measures of NAFLD, confirming that NAFLD identified through diagnostic codes from consensus guidelines is a valid alternative to more invasive and costly approaches.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep4.1805; doi:https://doi.org/10.1002/hep4.1805; html:https://europepmc.org/articles/PMC8793997; pdf:https://europepmc.org/articles/PMC8793997?pdf=render
 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.",,pdf:https://discovery.ucl.ac.uk/10135735/1/Asselbergs_10.1515_dmdi-2021-0104.pdf; doi:https://doi.org/10.1515/dmdi-2021-0104
+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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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; doi:https://doi.org/10.1093/europace/euac022; html:https://europepmc.org/articles/PMC9326851; pdf:https://europepmc.org/articles/PMC9326851?pdf=render
 33072403,https://doi.org/10.1186/s40959-020-00079-3,Early- and late anthracycline-induced cardiac dysfunction: echocardiographic characterization and response to heart failure therapy.,"Kamphuis JAM, Linschoten M, Cramer MJ, Doevendans PA, Asselbergs FW, Teske AJ.",,"Cardio-oncology (London, England)",2020,2020-10-13,Y,Heart Failure; Anthracyclines; Cardiac Dysfunction; Cardiac Effects Of Cancer Treatment,,,"<h4>Background</h4>Anthracycline-induced cardiac dysfunction (ACD) is a notorious side effect of anticancer treatment. It has been described as a phenomenon of a continuous progressive decline of cardiac function, eventually leading to dilated cardiomyopathy (DCM). This progressive nature suggests that patients with a delayed ACD diagnosis have greater compromise of cardiac function and more adverse remodeling, with a poor response to heart failure (HF) treatment. This study aimed to delineate the impact of a delayed ACD diagnosis on echocardiographic characteristics and response to HF treatment.<h4>Methods and results</h4>From the population of our cardio-oncology outpatient clinic, 92 ACD patients were included in this study (age 51.6 ± 16.2 years, median cumulative anthracycline dose 329 [200-329] mg/m<sup>2</sup>), and a median follow-up of 25.0 [9.6-37.2] months after ACD diagnosis. Median time to ACD diagnosis for patients diagnosed early (< 1 year) and late (> 1 year) was 4.0 vs. 47.7 months respectively. There were no echocardiographic differences between patients diagnosed early vs. late (LVEF 43.6 ± 4.9% vs. 43.0 ± 6.2% and iEDV 63.6 vs. 62.9 mL/m<sup>2</sup>). Eighty-three percent of patients presented with mild LV dysfunction and in 79% the LV was not dilated. Patients diagnosed early were more likely to have (partial) recovery of cardiac function upon HF treatment initiation (<i>p</i> = 0.015).<h4>Conclusions</h4>In the setting of a cardio-oncology outpatient clinic, patients with ACD presented with a hypokinetic non-dilated cardiomyopathy, rather than typical DCM. Timing of ACD diagnosis did not impact HF disease severity. However, in patients receiving an early diagnosis, cardiac function was more likely to recover upon HF treatment.",,pdf:https://cardiooncologyjournal.biomedcentral.com/track/pdf/10.1186/s40959-020-00079-3; doi:https://doi.org/10.1186/s40959-020-00079-3; html:https://europepmc.org/articles/PMC7557080; pdf:https://europepmc.org/articles/PMC7557080?pdf=render
 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,,,"<h4>Objective</h4>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.<h4>Design/setting/participants</h4>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.<h4>Results</h4>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&lt;0.0001) and being of black ethnicity (6.21 (95% CI 2.69 to 14.3); p&lt;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&lt;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).<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e063159.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063159; html:https://europepmc.org/articles/PMC9644078; pdf:https://europepmc.org/articles/PMC9644078?pdf=render
 37671353,https://doi.org/10.23889/ijpds.v5i3.2133,Public Involvement & Engagement in health inequalities research on COVID-19 pandemic: a case study of CIDACS/FIOCRUZ BAHIA.,"Dos Anjos Fonseca A, Pimenta DM, de Almeida MRS, Lima RT, Barreto ML, Ichihara MYT.",,International journal of population data science,2020,2020-01-01,Y,Brazil; Pandemic; Policymakers; Social Inequalities; Public Engagement; Community Groups; Public Involvement,,,"<h4>Introduction</h4>Health inequalities in Brazil have deepened on Covid-19 pandemic, and the most vulnerable people were the more affected. A multidisciplinary team from Cidacs/Fiocruz Bahia developed a Social Disparities Index for Covid-19 (IDS-COVID-19) to support the evaluation of effects of health inequalities on the pandemic in Brazil. Public Involvement and Engagement were the pillars of this research because they allowed us to access first hand experiences about the social context in our country.<h4>Objectives</h4>This paper aims to describe our Public Involvement and Engagement experience by analysing our challenges, strategies, activities, results, and lessons learned during the construction of IDS-COVID-19.<h4>Methods</h4>The basis of the IDS-Covid-19 public engagement model was the participation of different social groups through methods and techniques that allow dialogue. Several activities and communication products supported the continuous interactions. Another guideline was the inclusion and the welcoming of participants from the beginning of the project to ensure that the participant's contributions could drive decision-making about the research.<h4>Results</h4>Participants made several contributions to the research as a new layer of information to the Index, and improvements were made to the interactive panel. They also compromised to support the dissemination and use of the product. Eight representatives of community groups and 29 policymakers participated in our engagement activities during the project. More than 500 people were in our open webinars. In addition, more than 140 news items about IDS-Covid-19 were published in national and international media.<h4>Conclusions</h4>We highlight as lessons learned the adaptation of some dissemination formats to the public, and the necessity of being flexible and accessible to participants. We strengthened the relationship with relevant stakeholders by exploring individual conversations by phone, WhatsApp, email, and interviews to produce a documentary that registered this whole experience. Cidacs/Fiocruz Bahia has also embedded public engagement and involvement in the study agenda.",,doi:https://doi.org/10.23889/ijpds.v5i3.2133; html:https://europepmc.org/articles/PMC10476697; pdf:https://europepmc.org/articles/PMC10476697?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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 m<sup>2</sup>). 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.<h4>Interpretation</h4>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.<h4>Funding</h4>UK Medical Research Council and Kidney Research UK.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613836; doi:https://doi.org/10.1016/S0140-6736(22)02074-8; html:https://europepmc.org/articles/PMC7613836
 37719788,https://doi.org/10.1093/noajnl/vdad096,Development of a core outcome set for use in adult primary glioma phase III interventional trials: A mixed methods study.,"Retzer A, Baddeley E, Sivell S, Scott H, Nelson A, Bulbeck H, Seddon K, Grant R, Adams R, Watts C, Aiyegbusi OL, Kearns P, Rivera SC, Dirven L, Calvert M, Byrne A.",,Neuro-oncology advances,2023,2023-01-01,Y,trials; Outcomes; Neuro-oncology; Delphi; Primary Glioma,,,"<h4>Background</h4>Glioma interventional studies should collect data aligned with patient priorities, enabling treatment benefit assessment and informed decision-making. This requires effective data synthesis and meta-analyses, underpinned by consistent trial outcome measurement, analysis, and reporting. Development of a core outcome set (COS) may contribute to a solution.<h4>Methods</h4>A 5-stage process was used to develop a COS for glioma trials from the UK perspective. Outcome lists were generated in stages 1: a trial registry review and systematic review of qualitative studies and 2: interviews with glioma patients and caregivers. In stage 3, the outcome lists were de-duplicated with accessible terminology, in stage 4 outcomes were rated via a 2-round Delphi process, and stage 5 comprised a consensus meeting to finalize the COS. Patient-reportable COS outcomes were identified.<h4>Results</h4>In Delphi round 1, 96 participants rated 35 outcomes identified in stages 1 and 2, to which a further 10 were added. Participants (77/96) rated the resulting 45 outcomes in round 2. Of these, 22 outcomes met a priori threshold for inclusion in the COS. After further review, a COS consisting of 19 outcomes grouped into 7 outcome domains (survival, adverse events, activities of daily living, health-related quality of life, seizure activity, cognitive function, and physical function) was finalized by 13 participants at the consensus meeting.<h4>Conclusions</h4>A COS for glioma trials was developed, comprising 7 outcome domains. Additional research will identify appropriate measurement tools and further validate this COS.",,pdf:https://academic.oup.com/noa/advance-article-pdf/doi/10.1093/noajnl/vdad096/51026152/vdad096.pdf; doi:https://doi.org/10.1093/noajnl/vdad096; html:https://europepmc.org/articles/PMC10503650; pdf:https://europepmc.org/articles/PMC10503650?pdf=render
 37025302,https://doi.org/10.1093/jacamr/dlad039,Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in <i>Mycobacterium tuberculosis</i>.,"Brankin AE, Fowler PW.",,JAC-antimicrobial resistance,2023,2023-04-04,Y,,,,"<h4>Objectives</h4>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.<h4>Methods</h4>We analysed the Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) dataset of globally diverse WGS <i>Mycobacterium tuberculosis</i> isolates, with matched MICs for two fluoroquinolone drugs and allowed putative minor alleles to contribute to resistance prediction.<h4>Results</h4>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 <i>M. tuberculosis</i> population containing a resistance-conferring allele and the magnitude of resistance.<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/jacamr/article-pdf/5/2/dlad039/49747584/dlad039.pdf; doi:https://doi.org/10.1093/jacamr/dlad039; html:https://europepmc.org/articles/PMC10072237; pdf:https://europepmc.org/articles/PMC10072237?pdf=render
-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.",,pdf:https://academic.oup.com/eurheartj/article-pdf/43/31/2921/45333809/ehac238.pdf; doi:https://doi.org/10.1093/eurheartj/ehac238; html:https://europepmc.org/articles/PMC9443991; pdf:https://europepmc.org/articles/PMC9443991?pdf=render
 32810544,https://doi.org/10.1016/j.ijcard.2020.08.030,The relation between VLDL-cholesterol and risk of cardiovascular events in patients with manifest cardiovascular disease.,"Heidemann BE, Koopal C, Bots ML, Asselbergs FW, Westerink J, Visseren FLJ.",,International journal of cardiology,2021,2020-08-15,N,Inflammation; Vascular disease; Major Adverse Cardiovascular Events; Non-hdl-c; Vldl-c; Triglyceride Rich Lipoproteins,,,"<h4>Introduction</h4>Apolipoprotein B containing lipoproteins are atherogenic. There is evidence that with low plasma low density lipoprotein cholesterol (LDL-C) levels residual vascular risk might be caused by triglyceride rich lipoproteins such as very-low density lipoproteins (VLDL), chylomicrons and their remnants. We investigated the relationship between VLDL-cholesterol (VLDL-C) and recurrent major adverse cardiovascular events (MACE), major adverse limb events (MALE) and all-cause mortality in a cohort of patients with cardiovascular disease.<h4>Methods</h4>Prospective cohort study in 8057 patients with cardiovascular disease from the UCC-SMART study. The relation between calculated VLDL-C levels and the occurrence of MACE, MALE and all-cause mortality was analyzed with Cox regression models.<h4>Results</h4>Patients mean age was 60 ± 10 years, 74% were male, 4894 (61%) had coronary artery disease, 2445 (30%) stroke, 1425 (18%) peripheral arterial disease and 684 (8%) patients had an abdominal aorta aneurysm at baseline. A total of 1535 MACE, 571 MALE and 1792 deaths were observed during a median follow up of 8.2 years (interquartile range 4.512.2). VLDL-C was not associated with risk of MACE or all-cause mortality. In the highest quartile of VLDL-C the risk was higher for major adverse limb events (MALE) (HR 1.49; 95%CI 1.16-1.93) compared to the lowest quartile, after adjustment for confounders including LDL-C and lipid lowering medication.<h4>Conclusion</h4>In patients with clinically manifest cardiovascular disease plasma VLDL-C confers an increased risk for MALE, but not for MACE and all-cause mortality, independent of established risk factors including LDL-C and lipid-lowering medication.",,pdf:http://www.internationaljournalofcardiology.com/article/S0167527320335579/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.08.030
+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.",,pdf:https://academic.oup.com/eurheartj/article-pdf/43/31/2921/45333809/ehac238.pdf; doi:https://doi.org/10.1093/eurheartj/ehac238; html:https://europepmc.org/articles/PMC9443991; pdf:https://europepmc.org/articles/PMC9443991?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-021-03210-9; doi:https://doi.org/10.1186/s12967-021-03210-9; html:https://europepmc.org/articles/PMC8722174; pdf:https://europepmc.org/articles/PMC8722174?pdf=render
 32763829,https://doi.org/10.1016/j.ebiom.2020.102932,Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk: An IMI DIRECT study.,"Eriksen R, Perez IG, Posma JM, Haid M, Sharma S, Prehn C, Thomas LE, Koivula RW, Bizzotto R, Prehn C, Mari A, Giordano GN, Pavo I, Schwenk JM, De Masi F, Tsirigos KD, Brunak S, Viñuela A, Mahajan A, McDonald TJ, Kokkola T, Rutter F, Teare H, Hansen TH, Fernandez J, Jones A, Jennison C, Walker M, McCarthy MI, Pedersen O, Ruetten H, Forgie I, Bell JD, Pearson ER, Franks PW, Adamski J, Holmes E, Frost G.",,EBioMedicine,2020,2020-08-04,Y,Type 2 diabetes; metabolic profiling; Dietary Patterns; Cardiometabolic Health,,,"<h4>Background</h4>Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D.<h4>Methods</h4>We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite profile model (T<sub>pred</sub>) was constructed using multivariable regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous T<sub>pred</sub> score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models.<h4>Findings</h4>A higher T<sub>pred</sub> score was associated with healthier diets high in wholegrain (β=3.36 g, 95% CI 0.31, 6.40 and β=2.82 g, 95% CI 0.06, 5.57) and lower energy intake (β=-75.53 kcal, 95% CI -144.71, -2.35 and β=-122.51 kcal, 95% CI -186.56, -38.46), and saturated fat (β=-0.92 g, 95% CI -1.56, -0.28 and β=-0.98 g, 95% CI -1.53, -0.42 g), respectively for cohort 1 and 2. In both cohorts a higher T<sub>pred</sub> score was also associated with lower total body adiposity and favourable lipid profiles HDL-cholesterol (β=0.07 mmol/L, 95% CI 0.03, 0.1), (β=0.08 mmol/L, 95% CI 0.04, 0.1), and triglycerides (β=-0.1 mmol/L, 95% CI -0.2, -0.03), (β=-0.2 mmol/L, 95% CI -0.3, -0.09), respectively for cohort 1 and 2. In cohort 2, the T<sub>pred</sub> score was negatively associated with liver fat (β=-0.74%, 95% CI -0.67, -0.81), and lower fasting concentrations of HbA1c (β=-0.9 mmol/mol, 95% CI -1.5, -0.1), glucose (β=-0.2 mmol/L, 95% CI -0.4, -0.05) and insulin (β=-11.0 pmol/mol, 95% CI -19.5, -2.6). Longitudinal analysis showed at 18-month follow up a higher T<sub>pred</sub> score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, 95% CI -0.3, -0.01) and insulin (β=-9.2 pmol/mol, 95% CI -17.9, -0.4) concentrations in cohort 2.<h4>Interpretation</h4>Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health.<h4>Funding</h4>This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115,317 (DIRECT), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies.",,pdf:http://www.thelancet.com/article/S235239642030308X/pdf; doi:https://doi.org/10.1016/j.ebiom.2020.102932; html:https://europepmc.org/articles/PMC7406914; pdf:https://europepmc.org/articles/PMC7406914?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.",,pdf:https://www.nature.com/articles/s41598-022-16375-0.pdf; doi:https://doi.org/10.1038/s41598-022-16375-0; html:https://europepmc.org/articles/PMC9307565; pdf:https://europepmc.org/articles/PMC9307565?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.",,pdf:https://www.nature.com/articles/s41533-022-00280-0.pdf; doi:https://doi.org/10.1038/s41533-022-00280-0; html:https://europepmc.org/articles/PMC9156666; pdf:https://europepmc.org/articles/PMC9156666?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
 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.",,pdf:https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bcp.14458; doi:https://doi.org/10.1111/bcp.14458
+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
 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/m<sup>2</sup>/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; 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
 32247548,https://doi.org/10.1016/j.tips.2020.03.003,Electronic Health Records to Predict Gestational Diabetes Risk.,"Mateen BA, David AL, Denaxas S.",,Trends in pharmacological sciences,2020,2020-04-01,N,Artificial intelligence; Gestational Diabetes Mellitus; Machine Learning; Risk Prediction; Electronic Health Records,,,"Gestational diabetes mellitus is a common pregnancy complication associated with significant adverse health outcomes for both women and infants. Effective screening and early prediction tools as part of routine clinical care are needed to reduce the impact of the disease on the baby and mother. Using large-scale electronic health records, Artzi and colleagues developed and evaluated a machine learning driven tool to identify women at high and low risk of GDM. Their findings showcase how artificial intelligence approaches can potentially be embedded in clinical care to enable accurate and rapid risk stratification.",,pdf:https://discovery.ucl.ac.uk/10097090/3/Denaxas_Electronic%20Health%20Records%20to%20Predict%20Gestational%20Diabetes%20Risk_AAM.pdf; doi:https://doi.org/10.1016/j.tips.2020.03.003
 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; doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render
@@ -1486,23 +1486,23 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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.",,pdf:https://www.bmj.com/content/bmj/370/bmj.m3210.full.pdf; doi:https://doi.org/10.1136/bmj.m3210; html:https://europepmc.org/articles/PMC7490785
 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,,,,,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-020-01754-z; doi:https://doi.org/10.1186/s12916-020-01754-z; html:https://europepmc.org/articles/PMC7487816; pdf:https://europepmc.org/articles/PMC7487816?pdf=render
 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. <i>Having a support network</i> included social supports such as family and friends, and receiving other funded/non-funded assistance towards improving independence and participation. <i>Being positive and engaged</i> included being able to participate, being positive, using compensatory strategies, and becoming fit, healthy and happy. <i>Getting good care</i> 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
-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
 30554166,https://doi.org/10.1136/injuryprev-2018-043019,"Work absence due to compensable RTCs in Victoria, Australia.","Gray SE, Gabbe BJ, Collie A.",,Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention,2020,2018-12-15,N,Functional Outcome; Burden Of Disease; Descriptive Epidemiology; Occupational Injury; Motor Vehicle Occupant,,,"<h4>Introduction</h4>RTC burden is commonly measured using fatality or hospitalisation statistics. However, non-fatal and less severe injuries contribute substantial economic and human costs, including work absence. In Victoria, Australia, two major compensation systems provide income support to employed people injured in RTCs; workers' compensation (if RTC occurred during work) and an RTC-specific compensation system. This study aimed to describe the number and rate of episodes of work absence due to compensable RTC and determine factors associated with work-related RTC resulting in work absence.<h4>Methods</h4>Administrative data for working-age people (15-65 years) with accepted compensation claims between 1 July 2003 and 30 June 2013 were extracted from Victoria's Compensation Research Database and analysed. Injured people receiving at least one day of income support were retained. Rate calculations used Victoria's labour force as the denominator and negative binomial regression determined any time-based trend changes. Multivariable logistic regression was used to determine odds of the RTC being work-related.<h4>Results</h4>There were 40 677 claims made by workers with an RTC injury that consequently missed work, averaging 4068 claims per year at a rate of 12.9 per 100 000 working population. Work-related cases contributed 17.4% (N=7061). Males, older adults and RTCs involving heavy vehicles, buses, trains and trams had higher odds of a work-related RTC resulting in work absence. More severe injuries tended not to be work-related.<h4>Conclusions</h4>Work absence due to RTC injury constitutes a substantial burden, and this measure could provide a valuable addition to conventional RTC statistics.",,doi:https://doi.org/10.1136/injuryprev-2018-043019
+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
 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.",,pdf:https://www.nature.com/articles/s41467-021-26280-1.pdf; doi:https://doi.org/10.1038/s41467-021-26280-1; html:https://europepmc.org/articles/PMC8688480; pdf:https://europepmc.org/articles/PMC8688480?pdf=render
 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,,,"<h4>Background</h4>Bariatric surgery is the most effective treatment for severe obesity. However, without recommended follow-up it has long-term risks.<h4>Aim</h4>To investigate whether nutritional and weight monitoring in primary care meets current clinical guidance, after patients are discharged from specialist bariatric care.<h4>Design and setting</h4>Retrospective cohort study in primary care practices contributing to IQVIA Medical Research Data in the UK (1 January 2000 to 17 January 2018).<h4>Method</h4>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.<h4>Results</h4>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% (<i>n</i> = 629/1400) and 61.2% (<i>n</i> = 653/1067). Annual proportions of blood tests specific to bariatric surgery were low, for example, recorded copper measurement varied between 1.2% (<i>n</i> = 10/818) and 1.5% (<i>n</i> = 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.<h4>Conclusion</h4>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.",,pdf:https://bjgp.org/content/bjgp/71/707/e441.full.pdf; doi:https://doi.org/10.3399/bjgp20X714161; html:https://europepmc.org/articles/PMC8041293; pdf:https://europepmc.org/articles/PMC8041293?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.<h4>Study registration number</h4>NCT04330599.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render
 32238333,https://doi.org/10.2196/16400,Low-Density Lipoprotein Cholesterol Target Attainment in Patients With Established Cardiovascular Disease: Analysis of Routine Care Data.,"Groenhof TKJ, Kofink D, Bots ML, Nathoe HM, Hoefer IE, Van Solinge WW, Lely AT, Asselbergs FW, Haitjema S.",,JMIR medical informatics,2020,2020-04-02,Y,LDL-C; Cardiovascular Risk Management; Learning Health Care System; Routine Clinical Data,Better Care,cardiovascular,"<h4>Background</h4>Direct feedback on quality of care is one of the key features of a learning health care system (LHS), enabling health care professionals to improve upon the routine clinical care of their patients during practice.<h4>Objective</h4>This study aimed to evaluate the potential of routine care data extracted from electronic health records (EHRs) in order to obtain reliable information on low-density lipoprotein cholesterol (LDL-c) management in cardiovascular disease (CVD) patients referred to a tertiary care center.<h4>Methods</h4>We extracted all LDL-c measurements from the EHRs of patients with a history of CVD referred to the University Medical Center Utrecht. We assessed LDL-c target attainment at the time of referral and per year. In patients with multiple measurements, we analyzed LDL-c trajectories, truncated at 6 follow-up measurements. Lastly, we performed a logistic regression analysis to investigate factors associated with improvement of LDL-c at the next measurement.<h4>Results</h4>Between February 2003 and December 2017, 250,749 LDL-c measurements were taken from 95,795 patients, of whom 23,932 had a history of CVD. At the time of referral, 51% of patients had not reached their LDL-c target. A large proportion of patients (55%) had no follow-up LDL-c measurements. Most of the patients with repeated measurements showed no change in LDL-c levels over time: the transition probability to remain in the same category was up to 0.84. Sequence clustering analysis showed more women (odds ratio 1.18, 95% CI 1.07-1.10) in the cluster with both most measurements off target and the most LDL-c measurements furthest from the target. Timing of drug prescription was difficult to determine from our data, limiting the interpretation of results regarding medication management.<h4>Conclusions</h4>Routine care data can be used to provide feedback on quality of care, such as LDL-c target attainment. These routine care data show high off-target prevalence and little change in LDL-c over time. Registrations of diagnosis; follow-up trajectory, including primary and secondary care; and medication use need to be improved in order to enhance usability of the EHR system for adequate feedback.",,pdf:https://medinform.jmir.org/2020/4/e16400/PDF; doi:https://doi.org/10.2196/16400; html:https://europepmc.org/articles/PMC7163416
 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.",,pdf:https://www.nature.com/articles/s41591-020-0916-2.pdf; 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
+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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.<h4>Study registration number</h4>NCT04330599.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render
 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).",,pdf:https://www.frontiersin.org/articles/10.3389/fpsyt.2021.627996/pdf; doi:https://doi.org/10.3389/fpsyt.2021.627996; html:https://europepmc.org/articles/PMC8141616; pdf:https://europepmc.org/articles/PMC8141616?pdf=render
 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,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081749; 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
 31168069,https://doi.org/10.1038/s41380-019-0439-8,"The genomic basis of mood instability: identification of 46 loci in 363,705 UK Biobank participants, genetic correlation with psychiatric disorders, and association with gene expression and function.","Ward J, Tunbridge EM, Sandor C, Lyall LM, Ferguson A, Strawbridge RJ, Lyall DM, Cullen B, Graham N, Johnston KJA, Webber C, Escott-Price V, O'Donovan M, Pell JP, Bailey MES, Harrison PJ, Smith DJ.",,Molecular psychiatry,2020,2019-06-05,Y,,,,"Genome-wide association studies (GWAS) of psychiatric phenotypes have tended to focus on categorical diagnoses, but to understand the biology of mental illness it may be more useful to study traits which cut across traditional boundaries. Here, we report the results of a GWAS of mood instability as a trait in a large population cohort (UK Biobank, n = 363,705). We also assess the clinical and biological relevance of the findings, including whether genetic associations show enrichment for nervous system pathways. Forty six unique loci associated with mood instability were identified with a SNP heritability estimate of 9%. Linkage Disequilibrium Score Regression (LDSR) analyses identified genetic correlations with Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizophrenia, anxiety, and Post Traumatic Stress Disorder (PTSD). Gene-level and gene set analyses identified 244 significant genes and 6 enriched gene sets. Tissue expression analysis of the SNP-level data found enrichment in multiple brain regions, and eQTL analyses highlighted an inversion on chromosome 17 plus two brain-specific eQTLs. In addition, we used a Phenotype Linkage Network (PLN) analysis and community analysis to assess for enrichment of nervous system gene sets using mouse orthologue databases. The PLN analysis found enrichment in nervous system PLNs for a community containing serotonin and melatonin receptors. In summary, this work has identified novel loci, tissues and gene sets contributing to mood instability. These findings may be relevant for the identification of novel trans-diagnostic drug targets and could help to inform future stratified medicine innovations in mental health.",,pdf:https://eprints.gla.ac.uk/185493/1/185493.pdf; doi:https://doi.org/10.1038/s41380-019-0439-8; html:https://europepmc.org/articles/PMC7116257; pdf:https://europepmc.org/articles/PMC7116257?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.",,pdf:https://www.jmir.org/2020/8/e20169/PDF; doi:https://doi.org/10.2196/20169; html:https://europepmc.org/articles/PMC7450371
+33605084,https://doi.org/10.1111/jcmm.16388,P62-positive aggregates are homogenously distributed in the myocardium and associated with the type of mutation in genetic cardiomyopathy.,"van der Klooster ZJ, Sepehrkhouy S, Dooijes D, Te Rijdt WP, Schuiringa FSAM, Lingeman J, van Tintelen JP, Harakalova M, Goldschmeding R, Suurmeijer AJH, Asselbergs FW, Vink A.",,Journal of cellular and molecular medicine,2021,2021-02-18,Y,Histology; Pathology; Senescence; Genetic; Cardiomyopathy; Autophagy; P62; Phospholamban; Desminopathy; Sequestosome-1,,,"Genetic cardiomyopathy is caused by mutations in various genes. The accumulation of potentially proteotoxic mutant protein aggregates due to insufficient autophagy is a possible mechanism of disease development. The objective of this study was to investigate the distribution in the myocardium of such aggregates in relation to specific pathogenic genetic mutations in cardiomyopathy hearts. Hearts from 32 genetic cardiomyopathy patients, 4 non-genetic cardiomyopathy patients and 5 controls were studied. Microscopic slices from an entire midventricular heart slice were stained for p62 (sequestosome-1, marker for aggregated proteins destined for autophagy). The percentage of cardiomyocytes with p62 accumulation was higher in cardiomyopathy hearts (median 3.3%) than in healthy controls (0.3%; P < .0001). p62 accumulation was highest in the desmin (15.6%) and phospholamban (7.2%) groups. P62 accumulation was homogeneously distributed in the myocardium. Fibrosis was not associated with p62 accumulation in subgroup analysis of phospholamban hearts. In conclusion, accumulation of p62-positive protein aggregates is homogeneously distributed in the myocardium independently of fibrosis distribution and associated with desmin and phospholamban cardiomyopathy. Proteotoxic protein accumulation is a diffuse process in the myocardium while a more localized second hit, such as local strain during exercise, might determine whether this leads to regional myocyte decay.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.16388; doi:https://doi.org/10.1111/jcmm.16388; html:https://europepmc.org/articles/PMC7957157; pdf:https://europepmc.org/articles/PMC7957157?pdf=render
 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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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).<h4>Conclusion</h4>Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS.<h4>Clinical trial registration</h4>The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.",,pdf:https://academic.oup.com/ehjacc/advance-article-pdf/doi/10.1093/ehjacc/zuad042/50087609/zuad042.pdf; doi:https://doi.org/10.1093/ehjacc/zuad042; html:https://europepmc.org/articles/PMC10328437; pdf:https://europepmc.org/articles/PMC10328437?pdf=render
 36256701,https://doi.org/10.1093/eurjcn/zvac098,Bed rest duration and complications after transfemoral cardiac catheterization: a network meta-analysis.,"Busca E, Airoldi C, Bertoncini F, Buratti G, Casarotto R, Gaboardi S, Faggiano F, Barisone M, White IR, Allara E, Dal Molin A.",,European journal of cardiovascular nursing,2023,2023-07-01,Y,Cardiac catheterization; Percutaneous coronary intervention; Systematic review; Network Meta-analysis; Femoral Access,,,"<h4>Aims</h4>To assess the effects of bed rest duration on short-term complications following transfemoral catheterization.<h4>Methods and results</h4>A systematic search was carried out in MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, Scopus, SciELO and in five registries of grey literature. Randomized controlled trials and quasi-experimental studies comparing different durations of bed rest after transfemoral catheterization were included. Primary outcomes were haematoma and bleeding near the access site. Secondary outcomes were arteriovenous fistula, pseudoaneurysm, back pain, general patient discomfort and urinary discomfort. Study findings were summarized using a network meta-analysis (NMA). Twenty-eight studies and 9217 participants were included (mean age 60.4 years). In NMA, bed rest duration was not consistently associated with either primary outcome, and this was confirmed in sensitivity analyses. There was no evidence of associations with secondary outcomes, except for two effects related to back pain. A bed rest duration of 2-2.9 h was associated with lower risk of back pain [risk ratio (RR) 0.33, 95% confidence interval (CI) 0.17-0.62] and a duration over 12 h with greater risk of back pain (RR 1.94, 95% CI 1.16-3.24), when compared with the 4-5.9 h interval. Post hoc analysis revealed an increased risk of back pain per hour of bed rest (RR 1.08, 95% CI 1.04-1.11).<h4>Conclusion</h4>A short bed rest was not associated with complications in patients undergoing transfemoral catheterization; the greater the duration of bed rest, the more likely the patients were to experience back pain. Ambulation as early as 2 h after transfemoral catheterization can be safely implemented.<h4>Registration</h4>PROSPERO: CRD42014014222.",,pdf:https://academic.oup.com/eurjcn/advance-article-pdf/doi/10.1093/eurjcn/zvac098/47022353/zvac098.pdf; doi:https://doi.org/10.1093/eurjcn/zvac098; html:https://europepmc.org/articles/PMC10353909; pdf:https://europepmc.org/articles/PMC10353909?pdf=render
-33605084,https://doi.org/10.1111/jcmm.16388,P62-positive aggregates are homogenously distributed in the myocardium and associated with the type of mutation in genetic cardiomyopathy.,"van der Klooster ZJ, Sepehrkhouy S, Dooijes D, Te Rijdt WP, Schuiringa FSAM, Lingeman J, van Tintelen JP, Harakalova M, Goldschmeding R, Suurmeijer AJH, Asselbergs FW, Vink A.",,Journal of cellular and molecular medicine,2021,2021-02-18,Y,Histology; Pathology; Senescence; Genetic; Cardiomyopathy; Autophagy; P62; Phospholamban; Desminopathy; Sequestosome-1,,,"Genetic cardiomyopathy is caused by mutations in various genes. The accumulation of potentially proteotoxic mutant protein aggregates due to insufficient autophagy is a possible mechanism of disease development. The objective of this study was to investigate the distribution in the myocardium of such aggregates in relation to specific pathogenic genetic mutations in cardiomyopathy hearts. Hearts from 32 genetic cardiomyopathy patients, 4 non-genetic cardiomyopathy patients and 5 controls were studied. Microscopic slices from an entire midventricular heart slice were stained for p62 (sequestosome-1, marker for aggregated proteins destined for autophagy). The percentage of cardiomyocytes with p62 accumulation was higher in cardiomyopathy hearts (median 3.3%) than in healthy controls (0.3%; P < .0001). p62 accumulation was highest in the desmin (15.6%) and phospholamban (7.2%) groups. P62 accumulation was homogeneously distributed in the myocardium. Fibrosis was not associated with p62 accumulation in subgroup analysis of phospholamban hearts. In conclusion, accumulation of p62-positive protein aggregates is homogeneously distributed in the myocardium independently of fibrosis distribution and associated with desmin and phospholamban cardiomyopathy. Proteotoxic protein accumulation is a diffuse process in the myocardium while a more localized second hit, such as local strain during exercise, might determine whether this leads to regional myocyte decay.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.16388; doi:https://doi.org/10.1111/jcmm.16388; html:https://europepmc.org/articles/PMC7957157; pdf:https://europepmc.org/articles/PMC7957157?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,,,"<h4>Background</h4>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.<h4>Objectives</h4>The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives.<h4>Methods</h4>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]).<h4>Results</h4>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).<h4>Conclusions</h4>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
 34785789,https://doi.org/10.1038/s41591-021-01546-9,Patient-reported outcomes in the regulatory approval of medical devices.,"Cruz Rivera S, Dickens AP, Aiyegbusi OL, Flint R, Fleetcroft C, McPherson D, Collis P, Calvert MJ.",,Nature medicine,2021,2021-12-01,N,,,,,,pdf:http://pure-oai.bham.ac.uk/ws/files/149366889/The_role_of_PROs_MedicalDevices_NatMed_FINAL_Sep_REVISED_CLEANCOPY2.pdf; doi:https://doi.org/10.1038/s41591-021-01546-9
+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,,,"<h4>Background</h4>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.<h4>Objectives</h4>The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives.<h4>Methods</h4>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]).<h4>Results</h4>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).<h4>Conclusions</h4>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
 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; doi:https://doi.org/10.7189/jogh.11.01011; html:https://europepmc.org/articles/PMC8763337; pdf:https://europepmc.org/articles/PMC8763337?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; Enterovirus Structure; Echovirus E11,,,"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.",,pdf:https://www.mdpi.com/1999-4915/14/12/2625/pdf?version=1669703629; doi:https://doi.org/10.3390/v14122625; html:https://europepmc.org/articles/PMC9781616; pdf:https://europepmc.org/articles/PMC9781616?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; doi:https://doi.org/10.7189/jogh.11.01010; html:https://europepmc.org/articles/PMC8763336; pdf:https://europepmc.org/articles/PMC8763336?pdf=render
@@ -1514,8 +1514,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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.",,pdf:https://www.mdpi.com/2077-0383/9/2/545/pdf?version=1581938622; doi:https://doi.org/10.3390/jcm9020545; html:https://europepmc.org/articles/PMC7073517; pdf:https://europepmc.org/articles/PMC7073517?pdf=render
 36100927,https://doi.org/10.28920/dhm52.3.164-174,Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multi-centre randomised clinical trial.,"Millar IL, Lind FG, Jansson KÅ, Hájek M, Smart DR, Fernandes TD, McGinnes RA, Williamson OD, Miller RK, Martin CA, Gabbe BJ, Myles PS, Cameron PA, HOLLT investigator group.",,Diving and hyperbaric medicine,2022,2022-09-01,N,Injuries; Wounds; Fractures; Orthopaedics; Outcome; Hyperbaric Oxygen Treatment; Musculo-skeletal,,,"<h4>Introduction</h4>Hyperbaric oxygen treatment (HBOT) is sometimes used in the management of open fractures and severe soft tissue crush injury, aiming to reduce complications and improve outcomes.<h4>Methods</h4>Patients with open tibial fractures were randomly assigned within 48 hours of injury to receive standard trauma care or standard care plus 12 sessions of HBOT. The primary outcome was the incidence of necrosis or infection or both occurring within 14 days of injury.<h4>Results</h4>One-hundred and twenty patients were enrolled. Intention to treat primary outcome occurred in 25/58 HBOT assigned patients and 34/59 controls (43% vs 58%, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25 to 1.18, P = 0.12). Tissue necrosis occurred in 29% of HBOT patients and 53% of controls (OR 0.35, 95% CI 0.16 to 0.78, P = 0.01). There were fewer late complications in patients receiving HBOT (6/53 vs 18/52, OR 0.22, 95% CI 0.08 to 0.64, P = 0.007) including delayed fracture union (5/53 vs 13/52, OR 0.31, 95% CI 0.10 to 0.95, P = 0.04). Quality of life measures at one and two years were superior in HBOT patients. The mean score difference in short form 36 was 2.90, 95% CI 1.03 to 4.77, P = 0.002, in the short musculoskeletal function assessment (SMFA) was 2.54, 95% CI 0.62 to 4.46, P = 0.01; and in SMFA daily activities was 19.51, 95% CI 0.06 to 21.08, P = 0.05.<h4>Conclusions</h4>In severe lower limb trauma, early HBOT reduces tissue necrosis and the likelihood of long-term complications, and improves functional outcomes. Future research should focus on optimal dosage and whether HBOT has benefits for other injury types.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536848; doi:https://doi.org/10.28920/dhm52.3.164-174; html:https://europepmc.org/articles/PMC9536848; pdf:https://europepmc.org/articles/PMC9536848?pdf=render; doi:https://doi.org/10.28920/dhm52.3.164-174
 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,,,,"<h4>Aims</h4>To assess whether glycaemic control is associated with a lifelong increased risk of fracture in people with newly diagnosed Type 1 diabetes.<h4>Methods</h4>People with newly diagnosed Type 1 diabetes between 1 January 1995 and 10 May 2016 were identified in The Health Improvement Network database. Longitudinal HbA<sub>1c</sub> measurements from diagnosis to fracture or study end or loss to follow-up were collected. A Cox proportional hazards model with HbA<sub>1c</sub> included as a time-dependent variable was fitted to these data.<h4>Results</h4>Some 5368 people with newly diagnosed Type 1 diabetes were included. The estimated adjusted hazard ratio (aHR) for HbA<sub>1c</sub> 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 HbA<sub>1c</sub> .<h4>Conclusions</h4>In people with newly diagnosed Type 1 diabetes, higher HbA<sub>1c</sub> is associated with an increased risk for fractures.",,doi:https://doi.org/10.1111/dme.13945
-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<sup>-6</sup>, 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.",,pdf:https://www.nature.com/articles/s41598-022-22218-9.pdf; doi:https://doi.org/10.1038/s41598-022-22218-9; html:https://europepmc.org/articles/PMC9637114; pdf:https://europepmc.org/articles/PMC9637114?pdf=render
 34173614,https://doi.org/10.1016/s2666-7568(20)30012-x,Evolution and effects of COVID-19 outbreaks in care homes: a population analysis in 189 care homes in one geographical region of the UK.,"Burton JK, Bayne G, Evans C, Garbe F, Gorman D, Honhold N, McCormick D, Othieno R, Stevenson JE, Swietlik S, Templeton KE, Tranter M, Willocks L, Guthrie B.",,The lancet. Healthy longevity,2020,2020-10-20,Y,,,,"<h4>Background</h4>COVID-19 has affected care home residents internationally, but detailed information on outbreaks is scarce. We aimed to describe the evolution of outbreaks of COVID-19 in all care homes in one large health region in Scotland.<h4>Methods</h4>We did a population analysis of testing, cases, and deaths in care homes in the National Health Service (NHS) Lothian health region of the UK. We obtained data for COVID-19 testing (PCR testing of nasopharyngeal swabs for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) and deaths (COVID-19-related and non-COVID-19-related), and we analysed data by several variables including type of care home, number of beds, and locality. Outcome measures were timing of outbreaks, number of confirmed cases of COVID-19 in care home residents, care home characteristics associated with the presence of an outbreak, and deaths of residents in both care homes and hospitals. We calculated excess deaths (both COVID-19-related and non-COVID-19-related), which we defined as the sum of deaths over and above the historical average in the same period over the past 5 years.<h4>Findings</h4>Between March 10 and Aug 2, 2020, residents at 189 care homes (5843 beds) were tested for COVID-19 when symptomatic. A COVID-19 outbreak was confirmed at 69 (37%) care homes, of which 66 (96%) were care homes for older people. The size of care homes for older people was strongly associated with a COVID-19 outbreak (odds ratio per 20-bed increase 3·35, 95% CI 1·99-5·63). 907 confirmed cases of SARS-CoV-2 infection were recorded during the study period, and 432 COVID-19-related deaths. 229 (25%) COVID-19-related cases and 99 (24%) COVID-related deaths occurred in five (3%) of 189 care homes, and 441 (49%) cases and 207 (50%) deaths were in 13 (7%) care homes. 411 (95%) COVID-19-related deaths occurred in the 69 care homes with a confirmed COVID-19 outbreak, 19 (4%) deaths were in hospital, and two (<1%) were in one of the 120 care homes without a confirmed COVID-19 outbreak. At the 69 care homes with a confirmed COVID-19 outbreak, 74 excess non-COVID-19-related deaths were reported, whereas ten non-COVID-19-related excess deaths were observed in the 120 care homes without a confirmed COVID-19 outbreak. 32 fewer non-COVID-19-related deaths than expected were reported among care home residents in hospital.<h4>Interpretation</h4>The effect of COVID-19 on care homes has been substantial but concentrated in care homes with known outbreaks. A key implication from our findings is that, if community incidence of COVID-19 increases again, many care home residents will be susceptible. Shielding care home residents from potential sources of SARS-CoV-2 infection, and ensuring rapid action to minimise outbreak size if infection is introduced, will be important for any second wave.<h4>Funding</h4>None.",,doi:https://doi.org/10.1016/s2666-7568(20)30012-x; doi:https://doi.org/10.1016/S2666-7568(20)30012-X; html:https://europepmc.org/articles/PMC7574931; pdf:https://europepmc.org/articles/PMC7574931?pdf=render
+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<sup>-6</sup>, 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.",,pdf:https://www.nature.com/articles/s41598-022-22218-9.pdf; doi:https://doi.org/10.1038/s41598-022-22218-9; html:https://europepmc.org/articles/PMC9637114; pdf:https://europepmc.org/articles/PMC9637114?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; 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
 31312209,https://doi.org/10.3389/fgene.2019.00567,Use of Pharmacogenetic Drugs by the Dutch Population.,"Alshabeeb MA, Deneer VHM, Khan A, Asselbergs FW.",,Frontiers in genetics,2019,2019-07-02,Y,CYP2C19; CYP2D6; Pharmacogenetics; Adrs; Slco1b1; Preemptive Genetic Testing,Better Care,,"<h4>Introduction</h4>The Dutch Pharmacogenetics Working Group (DPWG) indicated a list of actionable genotypes that affect patients' response to more 50 drugs; these drugs which show variable effects based on patients' genetic traits were named as pharmacogenetics (PGX) drugs. Preemptive genetic testing before using these drugs may protect certain patients from serious adverse reactions and could help in avoiding treatment failures. The objectives of this study include identifying the rate of PGX drug usage among Dutch population, estimating the level of users who carry the actionable genotypes and determining the main genes involved in drug's effect variability.<h4>Methods</h4>Usage of PGX drugs over 2011-2017 by the insured population (an average of 11.4 million) in outpatient clinics in Netherlands was obtained from the publically available GIP databank. The data of 45 drugs were analyzed and their interactions with selected pharmacogenes were estimated. Frequency of actionable genotypes of 249 Dutch parents was obtained from the public database: Genome of Netherlands (GoNL), to identify the pattern of genetic characteristics of Dutch population.<h4>Results</h4>Over a 7 year period, 51.3 million exposures of patients to PGX drugs were reported with an average of 5.3 exposures per each drug user. One quarterof the exposures (12.4 million) are predicted to be experienced by individuals with actionable genotypes (risky exposures). Up to 60% of the risky exposures (around 7.5 million) were related to drugs metabolized by CYP2D6. SLCO1B1, and CYP2C19 were also identified among the top genes affecting response of drugs users (involved in about 22 and 12.4% of the risky exposures, respectively). Cardiovascular medications were the top prescribed PGX drug class (43%), followed by gastroenterology (29%) and psychiatry/neurology medications (15%). Women use more PGX drugs than men (55.8 vs. 44.2%, respectively) with the majority (84%) of users in both sexes are above 45 years.<h4>Conclusion</h4>PGX drugs are commonly used in Netherlands. Preemptive panel testing for CYP2D6, SLCO1B1, and CYP2C19 only could be useful to predict 95% of vulnerable patients' exposures to PGX drugs. Future studies to assess the economic impact of preemptive panel testing on patients of older age are suggested.",,pdf:https://www.frontiersin.org/articles/10.3389/fgene.2019.00567/pdf; doi:https://doi.org/10.3389/fgene.2019.00567; html:https://europepmc.org/articles/PMC6614185; pdf:https://europepmc.org/articles/PMC6614185?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,,,,,,pdf:http://www.ijidonline.com/article/S1201971220325297/pdf; 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
@@ -1530,22 +1530,22 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 37104291,https://doi.org/10.1371/journal.pmed.1004221,A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study.,"Sobiecki JG, Imamura F, Davis CR, Sharp SJ, Koulman A, Hodgson JM, Guevara M, Schulze MB, Zheng JS, Agnoli C, Bonet C, Colorado-Yohar SM, Fagherazzi G, Franks PW, Gundersen TE, Jannasch F, Kaaks R, Katzke V, Molina-Montes E, Nilsson PM, Palli D, Panico S, Papier K, Rolandsson O, Sacerdote C, Tjønneland A, Tong TYN, van der Schouw YT, Danesh J, Butterworth AS, Riboli E, Murphy KJ, Wareham NJ, Forouhi NG.",,PLoS medicine,2023,2023-04-27,Y,,,,"<h4>Background</h4>Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet.<h4>Methods and findings</h4>We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding.<h4>Conclusions</h4>These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully.<h4>Trial registration</h4>Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004221&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004221; html:https://europepmc.org/articles/PMC10138823; pdf:https://europepmc.org/articles/PMC10138823?pdf=render
 31242963,https://doi.org/10.1016/j.vaccine.2019.06.019,An online decision tree for vaccine efficacy trial design during infectious disease epidemics: The InterVax-Tool.,"Bellan SE, Eggo RM, Gsell PS, Kucharski AJ, Dean NE, Donohue R, Zook M, Edmunds WJ, Odhiambo F, Longini IM, Brisson M, Mahon BE, Henao-Restrepo AM.",,Vaccine,2019,2019-06-24,Y,Vaccines; Decision support system; epidemics; Outbreaks; Emerging Infectious Diseases; Phase Iii Trial; Scientific Communication; Public Health Emergency; Vaccine Trial Design,"Applied Analytics, Better Care, Better, Faster and More Efficient Clinical Trials",,"<h4>Background</h4>Licensed vaccines are urgently needed for emerging infectious diseases, but the nature of these epidemics causes challenges for the design of phase III trials to evaluate vaccine efficacy. Designing and executing rigorous, fast, and ethical, vaccine efficacy trials is difficult, and the decisions and limitations in the design of these trials encompass epidemiological, logistical, regulatory, statistical, and ethical dimensions.<h4>Results</h4>Trial design decisions are complex and interrelated, but current guidance documents do not lend themselves to efficient decision-making. We created InterVax-Tool (http://vaxeval.com), an online, interactive decision-support tool, to help diverse stakeholders navigate the decisions in the design of phase III vaccine trials. InterVax-Tool offers high-level visual and interactive assistance through a set of four decision trees, guiding users through selection of the: (1) Primary Endpoint, (2) Target Population, (3) Randomization Scheme, and, (4) Comparator. We provide guidance on how key considerations - grouped as Epidemiological, Vaccine-related, Infrastructural, or Sociocultural - inform each decision in the trial design process.<h4>Conclusions</h4>InterVax-Tool facilitates structured, transparent, and collaborative discussion of trial design, while recording the decision-making process. Users can save and share their decisions, which is useful both for comparing proposed trial designs, and for justifying particular design choices. Here, we describe the goals and features of InterVax-Tool as well as its application to the design of a Zika vaccine efficacy trial.",,doi:https://doi.org/10.1016/j.vaccine.2019.06.019; doi:https://doi.org/10.1016/j.vaccine.2019.06.019; html:https://europepmc.org/articles/PMC6620503
 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,,,"<h4>Background</h4>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.<h4>Objective</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.jmir.org/2020/6/e18185/PDF; doi:https://doi.org/10.2196/18185; html:https://europepmc.org/articles/PMC7381072
-37808344,https://doi.org/10.1016/j.jacadv.2023.100573,<i>CYP2C19</i> Genotype Prevalence and Association With Recurrent Myocardial Infarction in British-South Asians Treated With Clopidogrel.,"Magavern EF, Jacobs B, Warren H, Finocchiaro G, Finer S, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",,JACC. Advances,2023,2023-09-01,Y,Pharmacogenomics; ischemic heart disease; Pharmacotherapy; Preventive Cardiology,,,"<h4>Background</h4>Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in <i>CYP2C19</i> and their relationship with clinical efficacy have not included South Asian populations.<h4>Objectives</h4>The objective of this study was to assess prevalence of common <i>CYP2C19</i> genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.<h4>Methods</h4>The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. <i>CYP2C19</i> diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification.<h4>Results</h4>Genes & Health cohort participants (N = 44,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function <i>CYP2C19</i> allele. The prevalence of poor metabolizers carrying 2 <i>CYP2C19</i> loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; <i>P</i> = 0.019).<h4>Conclusions</h4>A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry.",,doi:https://doi.org/10.1016/j.jacadv.2023.100573; html:https://europepmc.org/articles/PMC10550831; pdf:https://europepmc.org/articles/PMC10550831?pdf=render
 32935062,https://doi.org/10.23889/ijpds.v5i2.1383,Prospective data linkage to facilitate COVID-19 trials - A call to action.,"Paprica PA, Sydes MR, McGrail KM, Morris AD, Schull MJ, Walker R.",,International journal of population data science,2020,2020-08-11,Y,,,,,,pdf:https://ijpds.org/article/download/1383/2566; doi:https://doi.org/10.23889/ijpds.v5i2.1383; html:https://europepmc.org/articles/PMC7473253; pdf:https://europepmc.org/articles/PMC7473253?pdf=render
+37808344,https://doi.org/10.1016/j.jacadv.2023.100573,<i>CYP2C19</i> Genotype Prevalence and Association With Recurrent Myocardial Infarction in British-South Asians Treated With Clopidogrel.,"Magavern EF, Jacobs B, Warren H, Finocchiaro G, Finer S, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",,JACC. Advances,2023,2023-09-01,Y,Pharmacogenomics; ischemic heart disease; Pharmacotherapy; Preventive Cardiology,,,"<h4>Background</h4>Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in <i>CYP2C19</i> and their relationship with clinical efficacy have not included South Asian populations.<h4>Objectives</h4>The objective of this study was to assess prevalence of common <i>CYP2C19</i> genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.<h4>Methods</h4>The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. <i>CYP2C19</i> diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification.<h4>Results</h4>Genes & Health cohort participants (N = 44,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function <i>CYP2C19</i> allele. The prevalence of poor metabolizers carrying 2 <i>CYP2C19</i> loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; <i>P</i> = 0.019).<h4>Conclusions</h4>A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry.",,doi:https://doi.org/10.1016/j.jacadv.2023.100573; html:https://europepmc.org/articles/PMC10550831; pdf:https://europepmc.org/articles/PMC10550831?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.",,pdf:https://www.bmj.com/content/bmj/370/bmj.m3164.full.pdf; doi:https://doi.org/10.1136/bmj.m3164; html:https://europepmc.org/articles/PMC7490784
 32878619,https://doi.org/10.1186/s12916-020-01726-3,COVID-19 length of hospital stay: a systematic review and data synthesis.,"Rees EM, Nightingale ES, Jafari Y, Waterlow NR, Clifford S, B Pearson CA, Group CW, Jombart T, Procter SR, Knight GM.",,BMC medicine,2020,2020-09-03,Y,Length Of Stay; Hospitalisation; Icu Capacity; Covid-19; Sars-cov-2; Bed Demand,,,"<h4>Background</h4>The COVID-19 pandemic has placed an unprecedented strain on health systems, with rapidly increasing demand for healthcare in hospitals and intensive care units (ICUs) worldwide. As the pandemic escalates, determining the resulting needs for healthcare resources (beds, staff, equipment) has become a key priority for many countries. Projecting future demand requires estimates of how long patients with COVID-19 need different levels of hospital care.<h4>Methods</h4>We performed a systematic review of early evidence on length of stay (LoS) of patients with COVID-19 in hospital and in ICU. We subsequently developed a method to generate LoS distributions which combines summary statistics reported in multiple studies, accounting for differences in sample sizes. Applying this approach, we provide distributions for total hospital and ICU LoS from studies in China and elsewhere, for use by the community.<h4>Results</h4>We identified 52 studies, the majority from China (46/52). Median hospital LoS ranged from 4 to 53 days within China, and 4 to 21 days outside of China, across 45 studies. ICU LoS was reported by eight studies-four each within and outside China-with median values ranging from 6 to 12 and 4 to 19 days, respectively. Our summary distributions have a median hospital LoS of 14 (IQR 10-19) days for China, compared with 5 (IQR 3-9) days outside of China. For ICU, the summary distributions are more similar (median (IQR) of 8 (5-13) days for China and 7 (4-11) days outside of China). There was a visible difference by discharge status, with patients who were discharged alive having longer LoS than those who died during their admission, but no trend associated with study date.<h4>Conclusion</h4>Patients with COVID-19 in China appeared to remain in hospital for longer than elsewhere. This may be explained by differences in criteria for admission and discharge between countries, and different timing within the pandemic. In the absence of local data, the combined summary LoS distributions provided here can be used to model bed demands for contingency planning and then updated, with the novel method presented here, as more studies with aggregated statistics emerge outside China.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01726-3; doi:https://doi.org/10.1186/s12916-020-01726-3; html:https://europepmc.org/articles/PMC7467845; pdf:https://europepmc.org/articles/PMC7467845?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,,,,"<h4>Background</h4>To compare health, educational and employment outcomes of schoolchildren receiving medication for a skin disorder with peers.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0243383&type=printable; 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>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; 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
-36357634,https://doi.org/10.1007/s00467-022-05789-7,Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.,"Downie ML, Gupta S, Chan MMY, Sadeghi-Alavijeh O, Cao J, Parekh RS, Diz CB, Bierzynska A, Levine AP, Pepper RJ, Stanescu H, Saleem MA, Kleta R, Bockenhauer D, Koziell AB, Gale DP.",,"Pediatric nephrology (Berlin, Germany)",2023,2022-11-10,Y,Paediatrics; Minimal Change Disease; Focal Segmental Glomerulosclerosis; Monogenic; Genetic Risk Score; Steroid-resistant Nephrotic Syndrome; Steroid-sensitive Nephrotic Syndrome,,,"<h4>Background</h4>Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways.<h4>Methods</h4>We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls.<h4>Results</h4>The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS.<h4>Conclusions</h4>The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. A higher resolution version of the Graphical abstract is available as Supplementary information.",,pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05789-7.pdf; doi:https://doi.org/10.1007/s00467-022-05789-7; html:https://europepmc.org/articles/PMC10154254; pdf:https://europepmc.org/articles/PMC10154254?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",,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>World Health Organization.",,doi:https://doi.org/10.1016/j.lanepe.2022.100381; doi:https://doi.org/10.1016/j.lanepe.2022.100381; html:https://europepmc.org/articles/PMC8996067; pdf:https://europepmc.org/articles/PMC8996067?pdf=render
+36357634,https://doi.org/10.1007/s00467-022-05789-7,Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.,"Downie ML, Gupta S, Chan MMY, Sadeghi-Alavijeh O, Cao J, Parekh RS, Diz CB, Bierzynska A, Levine AP, Pepper RJ, Stanescu H, Saleem MA, Kleta R, Bockenhauer D, Koziell AB, Gale DP.",,"Pediatric nephrology (Berlin, Germany)",2023,2022-11-10,Y,Paediatrics; Minimal Change Disease; Focal Segmental Glomerulosclerosis; Monogenic; Genetic Risk Score; Steroid-resistant Nephrotic Syndrome; Steroid-sensitive Nephrotic Syndrome,,,"<h4>Background</h4>Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways.<h4>Methods</h4>We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls.<h4>Results</h4>The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS.<h4>Conclusions</h4>The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. A higher resolution version of the Graphical abstract is available as Supplementary information.",,pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05789-7.pdf; doi:https://doi.org/10.1007/s00467-022-05789-7; html:https://europepmc.org/articles/PMC10154254; pdf:https://europepmc.org/articles/PMC10154254?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,,,,"<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003290&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003290; html:https://europepmc.org/articles/PMC7553326; pdf:https://europepmc.org/articles/PMC7553326?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Observationally, BMI was associated with 1576 proteins (P < 1.4 × 10<sup>-5</sup>), 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<sup>-15</sup>), FABP4 (0.64 SD per SD BMI, 95% CI 0.46-0.83, P = 6.7 × 10<sup>-12</sup>) and SHBG (-0.45 SD per SD BMI, 95% CI -0.65 to -0.25, P = 1.4 × 10<sup>-5</sup>). There was agreement in the magnitude of observational and MR estimates (R<sup>2</sup> = 0.33) and evidence that proteins most strongly altered by BMI were enriched for genes involved in cardiovascular disease.<h4>Conclusions</h4>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.",,pdf:https://www.nature.com/articles/s41366-021-00896-1.pdf; doi:https://doi.org/10.1038/s41366-021-00896-1; html:https://europepmc.org/articles/PMC8455324; pdf:https://europepmc.org/articles/PMC8455324?pdf=render
-35365070,https://doi.org/10.1186/s12879-022-07268-8,Impact of non-pharmaceutical interventions on SARS-CoV-2 outbreaks in English care homes: a modelling study.,"Rosello A, Barnard RC, Smith DRM, Evans S, Grimm F, Davies NG, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Modelling Working Group, Deeny SR, Knight GM, Edmunds WJ.",,BMC infectious diseases,2022,2022-04-01,Y,PCR; Testing; mathematical model; Long-term Care Facility; Care Home; Non-pharmaceutical Interventions; Covid-19; Sars-cov-2,,,"<h4>Background</h4>COVID-19 outbreaks still occur in English care homes despite the interventions in place.<h4>Methods</h4>We developed a stochastic compartmental model to simulate the spread of SARS-CoV-2 within an English care home. We quantified the outbreak risk with baseline non-pharmaceutical interventions (NPIs) already in place, the role of community prevalence in driving outbreaks, and the relative contribution of all importation routes into a fully susceptible care home. We also considered the potential impact of additional control measures in care homes with and without immunity, namely: increasing staff and resident testing frequency, using lateral flow antigen testing (LFD) tests instead of polymerase chain reaction (PCR), enhancing infection prevention and control (IPC), increasing the proportion of residents isolated, shortening the delay to isolation, improving the effectiveness of isolation, restricting visitors and limiting staff to working in one care home. We additionally present a Shiny application for users to apply this model to their facility of interest, specifying care home, outbreak and intervention characteristics.<h4>Results</h4>The model suggests that importation of SARS-CoV-2 by staff, from the community, is the main driver of outbreaks, that importation by visitors or from hospitals is rare, and that the past testing strategy (monthly testing of residents and daily testing of staff by PCR) likely provides negligible benefit in preventing outbreaks. Daily staff testing by LFD was 39% (95% 18-55%) effective in preventing outbreaks at 30 days compared to no testing.<h4>Conclusions</h4>Increasing the frequency of testing in staff and enhancing IPC are important to preventing importations to the care home. Further work is needed to understand the impact of vaccination in this population, which is likely to be very effective in preventing outbreaks.",,pdf:https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/s12879-022-07268-8; doi:https://doi.org/10.1186/s12879-022-07268-8; html:https://europepmc.org/articles/PMC8972713; pdf:https://europepmc.org/articles/PMC8972713?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<sup>-4</sup>) and downregulated genes in adult schizophrenia brains (fold change = 1.51, false discovery rate = 4 × 10<sup>-10</sup>). 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, <i>PCDHA2, PCDHA3</i> and <i>PCDHA5</i>, 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.",,pdf:https://academic.oup.com/braincomms/article-pdf/3/4/fcab275/41365065/fcab275.pdf; doi:https://doi.org/10.1093/braincomms/fcab275; html:https://europepmc.org/articles/PMC8633770; pdf:https://europepmc.org/articles/PMC8633770?pdf=render
+35365070,https://doi.org/10.1186/s12879-022-07268-8,Impact of non-pharmaceutical interventions on SARS-CoV-2 outbreaks in English care homes: a modelling study.,"Rosello A, Barnard RC, Smith DRM, Evans S, Grimm F, Davies NG, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Modelling Working Group, Deeny SR, Knight GM, Edmunds WJ.",,BMC infectious diseases,2022,2022-04-01,Y,PCR; Testing; mathematical model; Long-term Care Facility; Care Home; Non-pharmaceutical Interventions; Covid-19; Sars-cov-2,,,"<h4>Background</h4>COVID-19 outbreaks still occur in English care homes despite the interventions in place.<h4>Methods</h4>We developed a stochastic compartmental model to simulate the spread of SARS-CoV-2 within an English care home. We quantified the outbreak risk with baseline non-pharmaceutical interventions (NPIs) already in place, the role of community prevalence in driving outbreaks, and the relative contribution of all importation routes into a fully susceptible care home. We also considered the potential impact of additional control measures in care homes with and without immunity, namely: increasing staff and resident testing frequency, using lateral flow antigen testing (LFD) tests instead of polymerase chain reaction (PCR), enhancing infection prevention and control (IPC), increasing the proportion of residents isolated, shortening the delay to isolation, improving the effectiveness of isolation, restricting visitors and limiting staff to working in one care home. We additionally present a Shiny application for users to apply this model to their facility of interest, specifying care home, outbreak and intervention characteristics.<h4>Results</h4>The model suggests that importation of SARS-CoV-2 by staff, from the community, is the main driver of outbreaks, that importation by visitors or from hospitals is rare, and that the past testing strategy (monthly testing of residents and daily testing of staff by PCR) likely provides negligible benefit in preventing outbreaks. Daily staff testing by LFD was 39% (95% 18-55%) effective in preventing outbreaks at 30 days compared to no testing.<h4>Conclusions</h4>Increasing the frequency of testing in staff and enhancing IPC are important to preventing importations to the care home. Further work is needed to understand the impact of vaccination in this population, which is likely to be very effective in preventing outbreaks.",,pdf:https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/s12879-022-07268-8; doi:https://doi.org/10.1186/s12879-022-07268-8; html:https://europepmc.org/articles/PMC8972713; pdf:https://europepmc.org/articles/PMC8972713?pdf=render
 33986429,https://doi.org/10.1038/s41598-021-89743-x,Predicting sex from retinal fundus photographs using automated deep learning.,"Korot E, Pontikos N, Liu X, Wagner SK, Faes L, Huemer J, Balaskas K, Denniston AK, Khawaja A, Keane PA.",,Scientific reports,2021,2021-05-13,Y,,,,"Deep learning may transform health care, but model development has largely been dependent on availability of advanced technical expertise. Herein we present the development of a deep learning model by clinicians without coding, which predicts reported sex from retinal fundus photographs. A model was trained on 84,743 retinal fundus photos from the UK Biobank dataset. External validation was performed on 252 fundus photos from a tertiary ophthalmic referral center. For internal validation, the area under the receiver operating characteristic curve (AUROC) of the code free deep learning (CFDL) model was 0.93. Sensitivity, specificity, positive predictive value (PPV) and accuracy (ACC) were 88.8%, 83.6%, 87.3% and 86.5%, and for external validation were 83.9%, 72.2%, 78.2% and 78.6% respectively. Clinicians are currently unaware of distinct retinal feature variations between males and females, highlighting the importance of model explainability for this task. The model performed significantly worse when foveal pathology was present in the external validation dataset, ACC: 69.4%, compared to 85.4% in healthy eyes, suggesting the fovea is a salient region for model performance OR (95% CI): 0.36 (0.19, 0.70) p = 0.0022. Automated machine learning (AutoML) may enable clinician-driven automated discovery of novel insights and disease biomarkers.",,pdf:https://www.nature.com/articles/s41598-021-89743-x.pdf; doi:https://doi.org/10.1038/s41598-021-89743-x; html:https://europepmc.org/articles/PMC8119673; pdf:https://europepmc.org/articles/PMC8119673?pdf=render
 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.",,pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000292&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000292; html:https://europepmc.org/articles/PMC10021216; pdf:https://europepmc.org/articles/PMC10021216?pdf=render
-36210800,https://doi.org/10.1038/s43856-022-00189-2,Feasibility and ethics of using data from the Scottish newborn blood spot archive for research.,"Cunningham-Burley S, McCartney DL, Campbell A, Flaig R, Orange CEL, Porteous C, Aitken M, Mulholland C, Davidson S, McCafferty SM, Murphy L, Wrobel N, McCafferty S, Wallace K, StClair D, Kerr S, Hayward C, McIntosh AM, Sudlow C, Marioni RE, Pell J, Miedzybrodzka Z, Porteous DJ.",,Communications medicine,2022,2022-10-06,Y,epigenomics; epidemiology,,,"<h4>Background</h4>Newborn heel prick blood spots are routinely used to screen for inborn errors of metabolism and life-limiting inherited disorders. The potential value of secondary data from newborn blood spot archives merits ethical consideration and assessment of feasibility for public benefit. Early life exposures and behaviours set health trajectories in childhood and later life. The newborn blood spot is potentially well placed to create an unbiased and cost-effective population-level retrospective birth cohort study. Scotland has retained newborn blood spots for all children born since 1965, around 3 million in total. However, a moratorium on research access is currently in place, pending public consultation.<h4>Methods</h4>We conducted a Citizens' Jury as a first step to explore whether research use of newborn blood spots was in the public interest. We also assessed the feasibility and value of extracting research data from dried blood spots for predictive medicine.<h4>Results</h4>Jurors delivered an agreed verdict that conditional research access to the newborn blood spots was in the public interest. The Chief Medical Officer for Scotland authorised restricted lifting of the current research moratorium to allow a feasibility study. Newborn blood spots from consented Generation Scotland volunteers were retrieved and their potential for both epidemiological and biological research demonstrated.<h4>Conclusions</h4>Through the Citizens' Jury, we have begun to identify under what conditions, if any, should researchers in Scotland be granted access to the archive. Through the feasibility study, we have demonstrated the potential value of research access for health data science and predictive medicine.",,pdf:https://www.nature.com/articles/s43856-022-00189-2.pdf; doi:https://doi.org/10.1038/s43856-022-00189-2; html:https://europepmc.org/articles/PMC9537278; pdf:https://europepmc.org/articles/PMC9537278?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,,"<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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; doi:https://doi.org/10.1371/journal.pmed.1002833; html:https://europepmc.org/articles/PMC6586257; pdf:https://europepmc.org/articles/PMC6586257?pdf=render
+36210800,https://doi.org/10.1038/s43856-022-00189-2,Feasibility and ethics of using data from the Scottish newborn blood spot archive for research.,"Cunningham-Burley S, McCartney DL, Campbell A, Flaig R, Orange CEL, Porteous C, Aitken M, Mulholland C, Davidson S, McCafferty SM, Murphy L, Wrobel N, McCafferty S, Wallace K, StClair D, Kerr S, Hayward C, McIntosh AM, Sudlow C, Marioni RE, Pell J, Miedzybrodzka Z, Porteous DJ.",,Communications medicine,2022,2022-10-06,Y,epigenomics; epidemiology,,,"<h4>Background</h4>Newborn heel prick blood spots are routinely used to screen for inborn errors of metabolism and life-limiting inherited disorders. The potential value of secondary data from newborn blood spot archives merits ethical consideration and assessment of feasibility for public benefit. Early life exposures and behaviours set health trajectories in childhood and later life. The newborn blood spot is potentially well placed to create an unbiased and cost-effective population-level retrospective birth cohort study. Scotland has retained newborn blood spots for all children born since 1965, around 3 million in total. However, a moratorium on research access is currently in place, pending public consultation.<h4>Methods</h4>We conducted a Citizens' Jury as a first step to explore whether research use of newborn blood spots was in the public interest. We also assessed the feasibility and value of extracting research data from dried blood spots for predictive medicine.<h4>Results</h4>Jurors delivered an agreed verdict that conditional research access to the newborn blood spots was in the public interest. The Chief Medical Officer for Scotland authorised restricted lifting of the current research moratorium to allow a feasibility study. Newborn blood spots from consented Generation Scotland volunteers were retrieved and their potential for both epidemiological and biological research demonstrated.<h4>Conclusions</h4>Through the Citizens' Jury, we have begun to identify under what conditions, if any, should researchers in Scotland be granted access to the archive. Through the feasibility study, we have demonstrated the potential value of research access for health data science and predictive medicine.",,pdf:https://www.nature.com/articles/s43856-022-00189-2.pdf; doi:https://doi.org/10.1038/s43856-022-00189-2; html:https://europepmc.org/articles/PMC9537278; pdf:https://europepmc.org/articles/PMC9537278?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://qualitysafety.bmj.com/content/qhc/early/2022/03/02/bmjqs-2020-012108.full.pdf; 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,,,,,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000151.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000151; html:https://europepmc.org/articles/PMC9951363; pdf:https://europepmc.org/articles/PMC9951363?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>We used genetic association testing and Mendelian randomization to predict the effect of ivabradine and heart rate lowering on cardiovascular outcomes.<h4>Results</h4>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).<h4>Conclusion</h4>Genetic modelling of ivabradine recapitulates its benefits in heart failure, promotion of atrial fibrillation, and neutral effect on myocardial infarction.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0236193&type=printable; doi:https://doi.org/10.1371/journal.pone.0236193; html:https://europepmc.org/articles/PMC7373274; pdf:https://europepmc.org/articles/PMC7373274?pdf=render
@@ -1554,8 +1554,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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.",pdf:https://www.science.org/cms/asset/fb31d61b-4be3-483a-b040-2ee970dfb432/pap.pdf; doi:https://doi.org/10.1126/science.abc0473; html:https://europepmc.org/articles/PMC7200009; pdf:https://europepmc.org/articles/PMC7200009?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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
 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,,,"<h4>Background</h4>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.<h4>Objective</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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 (R<sup>2</sup>=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 (R<sup>2</sup>=0.338, RMSE=4.547).<h4>Conclusions</h4>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.",,pdf:https://mhealth.jmir.org/2021/7/e29840/PDF; doi:https://doi.org/10.2196/29840; html:https://europepmc.org/articles/PMC8367113
-35568032,https://doi.org/10.1016/j.ajhg.2022.04.009,Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites.,"Bomba L, Walter K, Guo Q, Surendran P, Kundu K, Nongmaithem S, Karim MA, Stewart ID, Langenberg C, Danesh J, Di Angelantonio E, Roberts DJ, Ouwehand WH, INTERVAL study, Dunham I, Butterworth AS, Soranzo N.",,American journal of human genetics,2022,2022-05-13,Y,Sequencing; Proteomics; drug targets; Metabolomics; Endophenotypes; Loss-of-function; Metabolon; Wgs; Wes; Rare Genetic Variant,,,"Metabolite levels measured in the human population are endophenotypes for biological processes. We combined sequencing data for 3,924 (whole-exome sequencing, WES, discovery) and 2,805 (whole-genome sequencing, WGS, replication) donors from a prospective cohort of blood donors in England. We used multiple approaches to select and aggregate rare genetic variants (minor allele frequency [MAF] < 0.1%) in protein-coding regions and tested their associations with 995 metabolites measured in plasma by using ultra-high-performance liquid chromatography-tandem mass spectrometry. We identified 40 novel associations implicating rare coding variants (27 genes and 38 metabolites), of which 28 (15 genes and 28 metabolites) were replicated. We developed algorithms to prioritize putative driver variants at each locus and used mediation and Mendelian randomization analyses to test directionality at associations of metabolite and protein levels at the ACY1 locus. Overall, 66% of reported associations implicate gene targets of approved drugs or bioactive drug-like compounds, contributing to drug targets' validating efforts.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/337646/3/1-s2.0-S0002929722001574-main.pdf; doi:https://doi.org/10.1016/j.ajhg.2022.04.009; html:https://europepmc.org/articles/PMC9247822; pdf:https://europepmc.org/articles/PMC9247822?pdf=render
 34796724,https://doi.org/10.1161/jaha.120.019814,"Dietary Fatty Acids, Macronutrient Substitutions, Food Sources and Incidence of Coronary Heart Disease: Findings From the EPIC-CVD Case-Cohort Study Across Nine European Countries.","Steur M, Johnson L, Sharp SJ, Imamura F, Sluijs I, Key TJ, Wood A, Chowdhury R, Guevara M, Jakobsen MU, Johansson I, Koulman A, Overvad K, Sánchez MJ, van der Schouw YT, Trichopoulou A, Weiderpass E, Wennberg M, Zheng JS, Boeing H, Boer JMA, Boutron-Ruault MC, Ericson U, Heath AK, Huybrechts I, Imaz L, Kaaks R, Krogh V, Kühn T, Kyrø C, Masala G, Melander O, Moreno-Iribas C, Panico S, Quirós JR, Rodríguez-Barranco M, Sacerdote C, Santiuste C, Skeie G, Tjønneland A, Tumino R, Verschuren WMM, Zamora-Ros R, Dahm CC, Perez-Cornago A, Schulze MB, Tong TYN, Riboli E, Wareham NJ, Danesh J, Butterworth AS, Forouhi NG.",,Journal of the American Heart Association,2021,2021-11-19,Y,Coronary Heart Disease; Primary Prevention; Dietary Guidelines; Nutritional Epidemiology; Saturated Fat,,,"Background There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain. Methods and Results We conducted a case-cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country-specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice-weighted Cox regression models and pooled results using random-effects meta-analysis. We found no evidence for associations of the consumption of total or fatty acid classes with CHD, regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was lower per 1% higher energy intake of SFAs from yogurt (HR, 0.93 [95% CI, 0.88-0.99]), cheese (HR, 0.98 [95% CI, 0.96-1.00]), and fish (HR, 0.87 [95% CI, 0.75-1.00]), but higher for SFAs from red meat (HR, 1.07 [95% CI, 1.02-1.12]) and butter (HR, 1.02 [95% CI, 1.00-1.04]). Conclusions This observational study found no strong associations of total fatty acids, SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, with incident CHD. By contrast, we found associations of SFAs with CHD in opposite directions dependent on the food source. These findings should be further confirmed, but support public health recommendations to consider food sources alongside the macronutrients they contain, and suggest the importance of the overall food matrix.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.120.019814; doi:https://doi.org/10.1161/JAHA.120.019814; html:https://europepmc.org/articles/PMC9075396; pdf:https://europepmc.org/articles/PMC9075396?pdf=render
+35568032,https://doi.org/10.1016/j.ajhg.2022.04.009,Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites.,"Bomba L, Walter K, Guo Q, Surendran P, Kundu K, Nongmaithem S, Karim MA, Stewart ID, Langenberg C, Danesh J, Di Angelantonio E, Roberts DJ, Ouwehand WH, INTERVAL study, Dunham I, Butterworth AS, Soranzo N.",,American journal of human genetics,2022,2022-05-13,Y,Sequencing; Proteomics; drug targets; Metabolomics; Endophenotypes; Loss-of-function; Metabolon; Wgs; Wes; Rare Genetic Variant,,,"Metabolite levels measured in the human population are endophenotypes for biological processes. We combined sequencing data for 3,924 (whole-exome sequencing, WES, discovery) and 2,805 (whole-genome sequencing, WGS, replication) donors from a prospective cohort of blood donors in England. We used multiple approaches to select and aggregate rare genetic variants (minor allele frequency [MAF] < 0.1%) in protein-coding regions and tested their associations with 995 metabolites measured in plasma by using ultra-high-performance liquid chromatography-tandem mass spectrometry. We identified 40 novel associations implicating rare coding variants (27 genes and 38 metabolites), of which 28 (15 genes and 28 metabolites) were replicated. We developed algorithms to prioritize putative driver variants at each locus and used mediation and Mendelian randomization analyses to test directionality at associations of metabolite and protein levels at the ACY1 locus. Overall, 66% of reported associations implicate gene targets of approved drugs or bioactive drug-like compounds, contributing to drug targets' validating efforts.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/337646/3/1-s2.0-S0002929722001574-main.pdf; doi:https://doi.org/10.1016/j.ajhg.2022.04.009; html:https://europepmc.org/articles/PMC9247822; pdf:https://europepmc.org/articles/PMC9247822?pdf=render
 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,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.nature.com/articles/s41416-018-0365-6.pdf; doi:https://doi.org/10.1038/s41416-018-0365-6; html:https://europepmc.org/articles/PMC6354010; pdf:https://europepmc.org/articles/PMC6354010?pdf=render
 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 <i>P</i><0.01), but not between IAB versus AF (<i>P</i>=0.999). This association remained statistically significant in the multivariable model (IAB: HR, 4.8 (1.4-16.1), <i>P</i>=0.013; AF: HR, 6.4 (1.7-24.0), <i>P</i>=0.007). In the external validation cohort, the survival distribution was also significantly worse for IAB or AF versus no IAB (<i>P</i>=0.037; <i>P</i>=0.005), but not for IAB versus AF (<i>P</i>=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.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025473; 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.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010294&type=printable; doi:https://doi.org/10.1371/journal.pgen.1010294; html:https://europepmc.org/articles/PMC9436054; pdf:https://europepmc.org/articles/PMC9436054?pdf=render
@@ -1564,19 +1564,19 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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; doi:https://doi.org/10.1098/rspb.2020.1405; html:https://europepmc.org/articles/PMC7575516; pdf:https://europepmc.org/articles/PMC7575516?pdf=render
 37075078,https://doi.org/10.1371/journal.pmed.1004223,The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.,"Sheppard JP, Koshiaris C, Stevens R, Lay-Flurrie S, Banerjee A, Bellows BK, Clegg A, Hobbs FDR, Payne RA, Swain S, Usher-Smith JA, McManus RJ.",,PLoS medicine,2023,2023-04-19,Y,,,,"<h4>Background</h4>Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data.<h4>Methods and findings</h4>This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out.<h4>Conclusions</h4>Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004223&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004223; html:https://europepmc.org/articles/PMC10155987; pdf:https://europepmc.org/articles/PMC10155987?pdf=render
 34347787,https://doi.org/10.1371/journal.pone.0253809,Developing a Natural Language Processing tool to identify perinatal self-harm in electronic healthcare records.,"Ayre K, Bittar A, Kam J, Verma S, Howard LM, Dutta R.",,PloS one,2021,2021-08-04,Y,,,,"<h4>Background</h4>Self-harm occurring within pregnancy and the postnatal year (""perinatal self-harm"") is a clinically important yet under-researched topic. Current research likely under-estimates prevalence due to methodological limitations. Electronic healthcare records (EHRs) provide a source of clinically rich data on perinatal self-harm.<h4>Aims</h4>(1) To create a Natural Language Processing (NLP) tool that can, with acceptable precision and recall, identify mentions of acts of perinatal self-harm within EHRs. (2) To use this tool to identify service-users who have self-harmed perinatally, based on their EHRs.<h4>Methods</h4>We used the Clinical Record Interactive Search system to extract de-identified EHRs of secondary mental healthcare service-users at South London and Maudsley NHS Foundation Trust. We developed a tool that applied several layers of linguistic processing based on the spaCy NLP library for Python. We evaluated mention-level performance in the following domains: span, status, temporality and polarity. Evaluation was done against a manually coded reference standard. Mention-level performance was reported as precision, recall, F-score and Cohen's kappa for each domain. Performance was also assessed at 'service-user' level and explored whether a heuristic rule improved this. We report per-class statistics for service-user performance, as well as likelihood ratios and post-test probabilities.<h4>Results</h4>Mention-level performance: micro-averaged F-score, precision and recall for span, polarity and temporality >0.8. Kappa for status 0.68, temporality 0.62, polarity 0.91. Service-user level performance with heuristic: F-score, precision, recall of minority class 0.69, macro-averaged F-score 0.81, positive LR 9.4 (4.8-19), post-test probability 69.0% (53-82%). Considering the task difficulty, the tool performs well, although temporality was the attribute with the lowest level of annotator agreement.<h4>Conclusions</h4>It is feasible to develop an NLP tool that identifies, with acceptable validity, mentions of perinatal self-harm within EHRs, although with limitations regarding temporality. Using a heuristic rule, it can also function at a service-user-level.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0253809&type=printable; doi:https://doi.org/10.1371/journal.pone.0253809; html:https://europepmc.org/articles/PMC8336818; pdf:https://europepmc.org/articles/PMC8336818?pdf=render
-35238940,https://doi.org/10.1093/ndt/gfac040,"Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial.",EMPA-KIDNEY Collaborative Group.,,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2022,2022-06-01,Y,"Cardiovascular disease; Empagliflozin; Sodium-glucose Co-transporter 2 Inhibitor; Ckd, Clinical Trial",,,"<h4>Background</h4>The effects of the sodium-glucose co-transporter 2 inhibitor empagliflozin on renal and cardiovascular disease have not been tested in a dedicated population of people with chronic kidney disease (CKD).<h4>Methods</h4>The EMPA-KIDNEY trial is an international randomized, double-blind, placebo-controlled trial assessing whether empagliflozin 10 mg daily decreases the risk of kidney disease progression or cardiovascular death in people with CKD. People with or without diabetes mellitus (DM) were eligible provided they had an estimated glomerular filtration rate (eGFR) ≥20 but <45 mL/min/1.73 m2 or an eGFR ≥45 but <90 mL/min/1.73 m2 with a urinary albumin:creatinine ratio (uACR) ≥200 mg/g. The trial design is streamlined, as extra work for collaborating sites is kept to a minimum and only essential information is collected.<h4>Results</h4>Between 15 May 2019 and 16 April 2021, 6609 people from eight countries in Europe, North America and East Asia were randomized. The mean age at randomization was 63.8 years [standard deviation (SD) 13.9)], 2192 (33%) were female and 3570 (54%) had no prior history of DM. The mean eGFR was 37.5 mL/min/1.73 m2 (SD 14.8), including 5185 (78%) with an eGFR <45 mL/min/1.73 m2. The median uACR was 412 mg/g) (quartile 1-quartile 3 94-1190), with a uACR <300 mg/g in 3194 (48%). The causes of kidney disease included diabetic kidney disease [n = 2057 (31%)], glomerular disease [n = 1669 (25%)], hypertensive/renovascular disease [n = 1445 (22%)], other [n = 808 (12%)] and unknown causes [n = 630 (10%)].<h4>Conclusions</h4>EMPA-KIDNEY will evaluate the efficacy and safety of empagliflozin in a widely generalizable population of people with CKD at risk of kidney disease progression. Results are anticipated in 2022.",,pdf:https://academic.oup.com/ndt/article-pdf/37/7/1317/44138360/gfac040.pdf; doi:https://doi.org/10.1093/ndt/gfac040; html:https://europepmc.org/articles/PMC9217655; pdf:https://europepmc.org/articles/PMC9217655?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,,,"<h4>Context</h4>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.<h4>Design</h4>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.<h4>Patients</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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
+35238940,https://doi.org/10.1093/ndt/gfac040,"Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial.",EMPA-KIDNEY Collaborative Group.,,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2022,2022-06-01,Y,"Cardiovascular disease; Empagliflozin; Sodium-glucose Co-transporter 2 Inhibitor; Ckd, Clinical Trial",,,"<h4>Background</h4>The effects of the sodium-glucose co-transporter 2 inhibitor empagliflozin on renal and cardiovascular disease have not been tested in a dedicated population of people with chronic kidney disease (CKD).<h4>Methods</h4>The EMPA-KIDNEY trial is an international randomized, double-blind, placebo-controlled trial assessing whether empagliflozin 10 mg daily decreases the risk of kidney disease progression or cardiovascular death in people with CKD. People with or without diabetes mellitus (DM) were eligible provided they had an estimated glomerular filtration rate (eGFR) ≥20 but <45 mL/min/1.73 m2 or an eGFR ≥45 but <90 mL/min/1.73 m2 with a urinary albumin:creatinine ratio (uACR) ≥200 mg/g. The trial design is streamlined, as extra work for collaborating sites is kept to a minimum and only essential information is collected.<h4>Results</h4>Between 15 May 2019 and 16 April 2021, 6609 people from eight countries in Europe, North America and East Asia were randomized. The mean age at randomization was 63.8 years [standard deviation (SD) 13.9)], 2192 (33%) were female and 3570 (54%) had no prior history of DM. The mean eGFR was 37.5 mL/min/1.73 m2 (SD 14.8), including 5185 (78%) with an eGFR <45 mL/min/1.73 m2. The median uACR was 412 mg/g) (quartile 1-quartile 3 94-1190), with a uACR <300 mg/g in 3194 (48%). The causes of kidney disease included diabetic kidney disease [n = 2057 (31%)], glomerular disease [n = 1669 (25%)], hypertensive/renovascular disease [n = 1445 (22%)], other [n = 808 (12%)] and unknown causes [n = 630 (10%)].<h4>Conclusions</h4>EMPA-KIDNEY will evaluate the efficacy and safety of empagliflozin in a widely generalizable population of people with CKD at risk of kidney disease progression. Results are anticipated in 2022.",,pdf:https://academic.oup.com/ndt/article-pdf/37/7/1317/44138360/gfac040.pdf; doi:https://doi.org/10.1093/ndt/gfac040; html:https://europepmc.org/articles/PMC9217655; pdf:https://europepmc.org/articles/PMC9217655?pdf=render
 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,,,"<b>Background:</b> 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). <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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
-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<sup>-3</sup> mm<sup>2</sup> s<sup>-1</sup> 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.",,pdf:https://www.nature.com/articles/s41598-021-82214-3.pdf; doi:https://doi.org/10.1038/s41598-021-82214-3; html:https://europepmc.org/articles/PMC7862387; pdf:https://europepmc.org/articles/PMC7862387?pdf=render
 30120083,https://doi.org/10.1016/j.ebiom.2018.08.004,"Genome-Wide Association Study of Circadian Rhythmicity in 71,500 UK Biobank Participants and Polygenic Association with Mood Instability.","Ferguson A, Lyall LM, Ward J, Strawbridge RJ, Cullen B, Graham N, Niedzwiedz CL, Johnston KJA, MacKay D, Biello SM, Pell JP, Cavanagh J, McIntosh AM, Doherty A, Bailey MES, Lyall DM, Wyse CA, Smith DJ.",,EBioMedicine,2018,2018-08-14,Y,Mood Instability; Gwas; Polygenic Risk Score; Circadian Rhythmicity; Relative Amplitude,Understanding the Causes of Disease,,"<h4>Background</h4>Circadian rhythms are fundamental to health and are particularly important for mental wellbeing. Disrupted rhythms of rest and activity are recognised as risk factors for major depressive disorder and bipolar disorder.<h4>Methods</h4>We conducted a genome-wide association study (GWAS) of low relative amplitude (RA), an objective measure of rest-activity cycles derived from the accelerometer data of 71,500 UK Biobank participants. Polygenic risk scores (PRS) for low RA were used to investigate potential associations with psychiatric phenotypes.<h4>Outcomes</h4>Two independent genetic loci were associated with low RA, within genomic regions for Neurofascin (NFASC) and Solute Carrier Family 25 Member 17 (SLC25A17). A secondary GWAS of RA as a continuous measure identified a locus within Meis Homeobox 1 (MEIS1). There were no significant genetic correlations between low RA and any of the psychiatric phenotypes assessed. However, PRS for low RA was significantly associated with mood instability across multiple PRS thresholds (at PRS threshold 0·05: OR = 1·02, 95% CI = 1·01-1·02, p = 9·6 × 10<sup>-5</sup>), and with major depressive disorder (at PRS threshold 0·1: OR = 1·03, 95% CI = 1·01-1·05, p = 0·025) and neuroticism (at PRS threshold 0·5: Beta = 0·02, 95% CI = 0·007-0·04, p = 0·021).<h4>Interpretation</h4>Overall, our findings contribute new knowledge on the complex genetic architecture of circadian rhythmicity and suggest a putative biological link between disrupted circadian function and mood disorder phenotypes, particularly mood instability, but also major depressive disorder and neuroticism.<h4>Funding</h4>Medical Research Council (MR/K501335/1).",,pdf:http://www.thelancet.com/article/S2352396418302925/pdf; doi:https://doi.org/10.1016/j.ebiom.2018.08.004; html:https://europepmc.org/articles/PMC6154782; pdf:https://europepmc.org/articles/PMC6154782?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<sup>-3</sup> mm<sup>2</sup> s<sup>-1</sup> 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.",,pdf:https://www.nature.com/articles/s41598-021-82214-3.pdf; doi:https://doi.org/10.1038/s41598-021-82214-3; html:https://europepmc.org/articles/PMC7862387; pdf:https://europepmc.org/articles/PMC7862387?pdf=render
 35762393,https://doi.org/10.1093/oncolo/oyac117,Using Patient-Reported Outcomes in Dose-Finding Oncology Trials: Surveys of Key Stakeholders and the National Cancer Research Institute Consumer Forum.,"Lai-Kwon J, Vanderbeek AM, Minchom A, Lee Aiyegbusi O, Ogunleye D, Stephens R, Calvert M, Yap C.",,The oncologist,2022,2022-09-01,Y,Cancer; Quality of life; Clinical Trials; Drug Development; Adverse Events; Patient-reported Outcomes,,,"<h4>Background</h4>Patient-reported adverse events may be a useful adjunct for assessing a drug's tolerability in dose-finding oncology trials (DFOT). We conducted surveys of international stakeholders and the National Cancer Research Institute (NCRI) Consumer Forum to understand attitudes about patient-reported outcome (PRO) use in DFOT.<h4>Methods</h4>A 35-question survey of clinicians, trial managers, statisticians, funders, and regulators of DFOT was distributed via professional bodies examining experience using PROs, benefits/barriers, and their potential role in defining tolerable doses. An 8-question survey of the NCRI Consumer Forum explored similar themes.<h4>Results</h4>International survey: 112 responses from 15 September-30 November 2020; 103 trialists [48 clinicians (42.9%), 38 statisticians (34.0%), 17 trial managers (15.2%)], 7 regulators (6.3%), 2 funders (1.8%)]. Most trialists had no experience designing (73, 70.9%), conducting (52, 50.5%), or reporting (88, 85.4%) PROs in DFOT. Most agreed that PROs could identify new toxicities (75, 67.0%) and provide data on the frequency (86, 76.8%) and duration (81, 72.3%) of toxicities. The top 3 barriers were lack of guidance regarding PRO selection (73/103, 70.9%), missing PRO data (71/103, 68.9%), and overburdening staff (68/103, 66.0%). NCRI survey: 57 responses on 21 March 2021. A total of 28 (49.1%) were willing to spend &lt;15 min/day completing PROs. Most (55, 96.5%) preferred to complete PROs online. 61 (54.5%) trialists and 57 (100%) consumers agreed that patient-reported adverse events should be used to inform dose-escalation decisions.<h4>Conclusion</h4>Stakeholders reported minimal experience using PROs in DFOT but broadly supported their use. Guidelines are needed to standardize PRO selection, analysis, and reporting in DFOT.",,pdf:https://academic.oup.com/oncolo/article-pdf/27/9/768/45667678/oyac117.pdf; doi:https://doi.org/10.1093/oncolo/oyac117; html:https://europepmc.org/articles/PMC9438918; pdf:https://europepmc.org/articles/PMC9438918?pdf=render
-36408685,https://doi.org/10.1161/circheartfailure.122.009526,"Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure.","Gürgöze MT, van Vark LC, Baart SJ, Kardys I, Akkerhuis KM, Manintveld OC, Postmus D, Hillege HL, Lesman-Leegte I, Asselbergs FW, Brunner-la-Rocca HP, van den Bos EJ, Orsel JG, de Ridder SPJ, Pinto YM, Boersma E.",,Circulation. Heart failure,2023,2022-11-21,Y,Prognosis; Biomarkers; Heart Failure; Growth Differentiation Factor 15,,,"<h4>Background</h4>Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk.<h4>Methods</h4>TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling.<h4>Results</h4>Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785).<h4>Conclusions</h4>Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice.<h4>Registration</h4>URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.122.009526; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.122.009526; html:https://europepmc.org/articles/PMC9833118; pdf:https://europepmc.org/articles/PMC9833118?pdf=render
-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,,,"<h4>Objective</h4>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.<h4>Design, setting, participants</h4>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.<h4>Analysis</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e053884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053884; html:https://europepmc.org/articles/PMC8867374; pdf:https://europepmc.org/articles/PMC8867374?pdf=render
 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,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/burnstrauma/article-pdf/doi/10.1093/burnst/tkz004/33423529/tkz004.pdf; doi:https://doi.org/10.1093/burnst/tkz004; html:https://europepmc.org/articles/PMC7175773; pdf:https://europepmc.org/articles/PMC7175773?pdf=render
+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,,,"<h4>Objective</h4>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.<h4>Design, setting, participants</h4>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.<h4>Analysis</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e053884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053884; html:https://europepmc.org/articles/PMC8867374; pdf:https://europepmc.org/articles/PMC8867374?pdf=render
+36408685,https://doi.org/10.1161/circheartfailure.122.009526,"Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure.","Gürgöze MT, van Vark LC, Baart SJ, Kardys I, Akkerhuis KM, Manintveld OC, Postmus D, Hillege HL, Lesman-Leegte I, Asselbergs FW, Brunner-la-Rocca HP, van den Bos EJ, Orsel JG, de Ridder SPJ, Pinto YM, Boersma E.",,Circulation. Heart failure,2023,2022-11-21,Y,Prognosis; Biomarkers; Heart Failure; Growth Differentiation Factor 15,,,"<h4>Background</h4>Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk.<h4>Methods</h4>TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling.<h4>Results</h4>Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785).<h4>Conclusions</h4>Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice.<h4>Registration</h4>URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.122.009526; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.122.009526; html:https://europepmc.org/articles/PMC9833118; pdf:https://europepmc.org/articles/PMC9833118?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,,,"<h4>Objectives</h4>In clinical practice, many prediction models cannot be used when predictor values are missing. We, therefore, propose and evaluate methods for real-time imputation.<h4>Study design and setting</h4>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.<h4>Results</h4>-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.<h4>Conclusion</h4>Multiple imputations using either CMI or JMI is recommended when dealing with missing predictor values in real-time settings.",,pdf:http://www.jclinepi.com/article/S0895435621000056/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.01.003
 35835762,https://doi.org/10.1038/s41467-022-31626-4,"Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity.","Gilchrist JJ, Makino S, Naranbhai V, Sharma PK, Koturan S, Tong O, Taylor CA, Watson RA, de Los Aires AV, Cooper R, Lau E, Danielli S, Hameiri-Bowen D, Lee W, Ng E, Whalley J, Knight JC, Fairfax BP.",,Nature communications,2022,2022-07-14,Y,,,,"Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect Natural Killer cell gene expression is poorly understood. Here we perform expression quantitative trait locus mapping of negatively selected Natural Killer cells from a population of healthy Europeans (n = 245). We find a significant subset of genes demonstrate expression quantitative trait loci specific to Natural Killer cells and these are highly informative of human disease, in particular autoimmunity. A Natural Killer cell transcriptome-wide association study across five common autoimmune diseases identifies further novel associations at 27 genes. In addition to these cis observations, we find novel master-regulatory regions impacting expression of trans gene networks at regions including 19q13.4, the Killer cell Immunoglobulin-like Receptor region, GNLY, MC1R and UVSSA. Our findings provide new insights into the unique biology of Natural Killer cells, demonstrating markedly different expression quantitative trait loci from other immune cells, with implications for disease mechanisms.",,pdf:https://www.nature.com/articles/s41467-022-31626-4.pdf; doi:https://doi.org/10.1038/s41467-022-31626-4; html:https://europepmc.org/articles/PMC9283523; pdf:https://europepmc.org/articles/PMC9283523?pdf=render
-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).",,pdf:https://research-information.bris.ac.uk/files/341783442/J_of_Bone_Mineral_Res_2022_Curtis_Telomere_Length_and_Risk_of_Incident_Fracture_and_Arthroplasty_Findings_From_UK_1_.pdf; doi:https://doi.org/10.1002/jbmr.4664; html:https://europepmc.org/articles/PMC9826022; pdf:https://europepmc.org/articles/PMC9826022?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; doi:https://doi.org/10.1016/j.bbih.2021.100286; html:https://europepmc.org/articles/PMC8261829; pdf:https://europepmc.org/articles/PMC8261829?pdf=render
+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).",,pdf:https://research-information.bris.ac.uk/files/341783442/J_of_Bone_Mineral_Res_2022_Curtis_Telomere_Length_and_Risk_of_Incident_Fracture_and_Arthroplasty_Findings_From_UK_1_.pdf; doi:https://doi.org/10.1002/jbmr.4664; html:https://europepmc.org/articles/PMC9826022; pdf:https://europepmc.org/articles/PMC9826022?pdf=render
 35099396,https://doi.org/10.2196/21341,"Collaborative Research and Development of a Novel, Patient-Centered Digital Platform (MyEyeSite) for Rare Inherited Retinal Disease Data: Acceptability and Feasibility Study.","Gilbert RM, Sumodhee D, Pontikos N, Hollyhead C, Patrick A, Scarles S, Van Der Smissen S, Young RM, Nettleton N, Webster AR, Cammack J.",,JMIR formative research,2022,2022-01-31,Y,Genetics; Mobile phone; Ophthalmology; Rare Diseases; Digital Health; Gdpr; Eye Data; Inherited Retinal Diseases (Ird); Myeyesite; Subject Access Request (Sar),,,"<h4>Background</h4>Inherited retinal diseases (IRDs) are a leading cause of blindness in children and working age adults in the United Kingdom and other countries, with an appreciable socioeconomic impact. However, by definition, IRD data are individually rare, and as a result, this patient group has been underserved by research. Researchers need larger amounts of these rare data to make progress in this field, for example, through the development of gene therapies. The challenge has been how to find and make these data available to researchers in the most productive way. MyEyeSite is a research collaboration aiming to design and develop a digital platform (the MyEyeSite platform) for people with rare IRDs that will enable patients, doctors, and researchers to aggregate and share specialist eye health data. A crucial component of this platform is the MyEyeSite patient application, which will provide the means for patients with IRD to interact with the system and, in particular, to collate, manage, and share their personal specialist IRD data both for research and their own health care.<h4>Objective</h4>This study aims to test the acceptability and feasibility of the MyEyeSite platform in the target IRD population through a collaborative patient-centered study.<h4>Methods</h4>Qualitative data were generated through focus groups and workshops, and quantitative data were obtained through a survey of patients with IRD. Participants were recruited through clinics at Moorfields Eye Hospital National Health Service (NHS) Foundation Trust and the National Institute for Health Research (NIHR) Moorfields Biomedical Research Centre through their patient and public involvement databases.<h4>Results</h4>Our IRD focus group sample (n=50) highlighted the following themes: frustration with the current system regarding data sharing within the United Kingdom's NHS; positive expectations of the potential benefits of the MyEyeSite patient application, resulting from increased access to this specialized data; and concerns regarding data security, including potentially unethical use of the data outside the NHS. Of the surveyed 80 participants, 68 (85%) were motivated to have a more active role in their eye care and share their data for research purposes using a secure technology, such as a web application or mobile app.<h4>Conclusions</h4>This study demonstrates that patients with IRD are highly motivated to be actively involved in managing their own data for research and their own eye care. It demonstrates the feasibility of involving patients with IRD in the detailed design of the MyEyeSite platform exemplar, with input from the patient with IRD workshops playing a key role in determining both the functionality and accessibility of the designs and prototypes. The development of a user-centered technological solution to the problem of rare health data has the potential to benefit not only the patient with IRD community but also others with rare diseases.",,pdf:https://formative.jmir.org/2022/1/e21341/PDF; doi:https://doi.org/10.2196/21341; html:https://europepmc.org/articles/PMC8845013; pdf:https://europepmc.org/articles/PMC8845013?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,,,"<h4>Introduction</h4>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.<h4>Materials and methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa50368/Download/0050368-25062019091637.pdf; doi:https://doi.org/10.1016/j.burns.2019.04.006
 32637892,https://doi.org/10.1016/j.eclinm.2020.100392,The association between exposure to childhood maltreatment and the subsequent development of functional somatic and visceral pain syndromes.,"Chandan JS, Keerthy D, Zemedikun DT, Okoth K, Gokhale KM, Raza K, Bandyopadhyay S, Taylor J, Nirantharakumar K.",,EClinicalMedicine,2020,2020-06-06,Y,epidemiology; Primary Care; Childhood Maltreatment; Central Sensitivity Syndromes,,,"BACKGROUND:Childhood maltreatment is a global public health issue linked to a vast mortality and morbidity burden. This study builds on current literature to explore the risk of developing central sensitivity syndromes (CSS) (consisting of somatic and visceral pain syndromes) subsequent to childhood maltreatment exposure. METHODS:A retrospective population based open cohort study using the UK primary care database, 'The Health Improvement Network,' between 1st January 1995-31st December 2018. 80,657 adult patients who had experienced childhood maltreatment or maltreatment related concerns (exposed patients) were matched to 161,314 unexposed patients by age and sex. Outcomes of interest were the development of CSS: either somatic (Fibromyalgia, chronic fatigue syndrome, temporomandibular joint disorder, chronic lower back pain, chronic headache, myofascial pain syndrome and restless leg syndrome) or visceral (Interstitial cystitis, vulvodynia, chronic prostatitis and irritable bowel syndrome) in nature. Effect sizes are presented as adjusted incidence rate ratios (aIRR) with confidence intervals (CI). Models were adjusted for the following covariates at cohort entry: age, sex, deprivation, anxiety, depression and serious mental ill health. RESULTS:The average age at cohort entry was 23.4 years and the median follow was 2.2 years. There was an increased risk of developing fibromyalgia (aIRR 2.06; 95% CI 1.71-2.48), chronic fatigue syndrome (1.47; 1.08-2.00), chronic lower back pain (1.99; 1.68-2.35), restless leg syndrome (1.82; 1.41-2.35) and irritable bowel syndrome (1.15; 1.08-1.22) when compared to the unexposed group, whereas no statistical association was seen with the development of temporomandibular joint disorder (1.00; 0.88-1.13), chronic headache (1.04; 0.59-1.86), interstitial cystitis (1.19; 0.51-2.74), vulvodynia (0.65; 0.34-1.26), chronic prostatitis (0.34; 0.07-1.77) and myofascial pain syndrome (0.88; 0.36-2.14). Outcome numbers were low, most likely, due to the rarity of visceral conditions (aside from irritable bowel syndrome). The association between a history of childhood maltreatment and CSS were mainly observed in somatic CSS. INTERPRETATION:The debilitating effects of CSS carry a substantial physical, psychological and economic burden to both the individuals who are diagnosed with them and the health services who serve them. Primary prevention approaches targeting childhood maltreatment as well as secondary preventative approaches should be considered to minimise the associated burden of CSS.",,pdf:http://www.thelancet.com/article/S258953702030136X/pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100392; html:https://europepmc.org/articles/PMC7329705; pdf:https://europepmc.org/articles/PMC7329705?pdf=render
@@ -1602,9 +1602,9 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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; doi:https://doi.org/10.1016/j.cels.2020.05.012; html:https://europepmc.org/articles/PMC7264033
 35189884,https://doi.org/10.1186/s12913-022-07607-0,Factors influencing follow-up care post-TIA and minor stroke: a qualitative study using the theoretical domains framework.,"Turner GM, Aquino MRJV, Atkins L, Foy R, Mant J, Calvert M.",,BMC health services research,2022,2022-02-21,Y,Follow-up; Transient Ischaemic Attack; Tia; Minor Stroke; Theoretical Domains Framework,,,"<h4>Background</h4>Follow-up care after transient ischaemic attack (TIA) and minor stroke has been found to be sub-optimal, with individuals often feeling abandoned. We aimed to explore factors influencing holistic follow-up care after TIA and minor stroke.<h4>Methods</h4>Qualitative semi-structured interviews with 24 healthcare providers (HCPs): 5 stroke doctors, 4 nurses, 9 allied health professionals and 6 general practitioners. Participants were recruited from three TIA clinics, seven general practices and one community care trust in the West Midlands, England. Interview transcripts were deductively coded using the Theoretical Domains Framework and themes were generated from coded data.<h4>Results</h4>There was no clear pathway for supporting people with TIA or minor stroke after rapid specialist review in hospital; consequently, these patients had limited access to HCPs from all settings ('Environmental context and resources'). There was lack of understanding of potential needs post-TIA/minor stroke, in particular residual problems such as anxiety/fatigue ('Knowledge'). Identification and management of needs was largely influenced by HCPs' perceived role, professional training ('Social professional role and identity') and time constraints ('Environmental context and resources'). Follow-up was often passive - with onerous on patients to seek support - and predominantly focused on acute medical management ('Intentions'/'Goal').<h4>Conclusions</h4>Follow-up care post-TIA/minor stroke is currently sub-optimal. Through identifying factors which influence follow-up, we can inform guidelines and practical strategies to improve holistic healthcare.",,pdf:https://bmchealthservres.biomedcentral.com/track/pdf/10.1186/s12913-022-07607-0; doi:https://doi.org/10.1186/s12913-022-07607-0; html:https://europepmc.org/articles/PMC8859903; pdf:https://europepmc.org/articles/PMC8859903?pdf=render
 35193920,https://doi.org/10.1136/bmjopen-2021-055773,Investigating the optimal handling of uncertain pregnancy episodes in the CPRD GOLD Pregnancy Register: a methodological study using UK primary care data.,"Campbell J, Bhaskaran K, Thomas S, Williams R, McDonald HI, Minassian C.",,BMJ open,2022,2022-02-22,Y,epidemiology; Public Health; Maternal Medicine,,,"<h4>Objectives</h4>To investigate why episodes of pregnancy identified from electronic health records may be incomplete or conflicting (overlapping), and provide guidance on how to handle them.<h4>Setting</h4>Pregnancy Register generated from the Clinical Practice Research Datalink (CPRD) GOLD UK primary care database.<h4>Participants</h4>Female patients with at least one pregnancy episode in the Register (01 January 1937-31 December 2017) which had no recorded outcome or conflicted with another episode.<h4>Design</h4>We identified multiple scenarios potentially explaining why uncertain episodes occur. Criteria were established and systematically applied to determine whether episodes had evidence of each scenario. Linked Hospital Episode Statistics were used to identify pregnancy events not captured in primary care.<h4>Results</h4>Of 5.8 million pregnancy episodes in the Register, 932 604 (16%) had no recorded outcome, and 478 341 (8.5%) conflicted with another episode (251 026 distinct conflicting pairs of episodes among 210 593 women). 826 146 (89%) of the episodes without outcome recorded in primary care and 215 577 (86%) of the conflicting pairs were consistent with one or more of our proposed scenarios. For 689 737 (74%) episodes with recorded outcome missing and 215 544 (86%) of the conflicting pairs (at least one episode), supportive evidence (eg, antenatal records, linked hospital records) suggested they were true and current pregnancies. Furthermore, 516 818 (55 %) and 160 936 (64%), respectively, were during research quality follow-up time. For a sizeable proportion of uncertain episode, there is evidence to suggest that historical outcomes being recorded by the general practitioner during an ongoing pregnancy may offer explanation (73 208 (29.2%) and 349 874 (37.5%)).<h4>Conclusions</h4>This work provides insight to users of the CPRD Pregnancy Register on why uncertain pregnancy episodes exist and indicates that most of these episodes are likely to be real pregnancies. Guidance is given to help researchers consider whether to include/exclude uncertain pregnancies from their studies, and how to tailor approaches to minimise underestimation and bias.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e055773.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055773; html:https://europepmc.org/articles/PMC8867343; pdf:https://europepmc.org/articles/PMC8867343?pdf=render
-36005401,https://doi.org/10.3390/jcdd9080237,The Relationship of Maternal Gestational Mass Spectrometry-Derived Metabolites with Offspring Congenital Heart Disease: Results from Multivariable and Mendelian Randomization Analyses.,"Taylor K, McBride N, Zhao J, Oddie S, Azad R, Wright J, Andreassen OA, Stewart ID, Langenberg C, Magnus MC, Borges MC, Caputo M, Lawlor DA.",,Journal of cardiovascular development and disease,2022,2022-07-27,Y,Metabolites; Congenital heart disease; Alspac; Moba; Born In Bradford,,,"Background: It is plausible that maternal pregnancy metabolism influences the risk of offspring congenital heart disease (CHD). We sought to explore this through a systematic approach using different methods and data. Methods: We undertook multivariable logistic regression of the odds of CHD for 923 mass spectrometry (MS)-derived metabolites in a sub-sample of a UK birth cohort (Born in Bradford (BiB); N = 2605, 46 CHD cases). We considered metabolites reaching a p-value threshold <0.05 to be suggestively associated with CHD. We sought validation of our findings, by repeating the multivariable regression analysis within the BiB cohort for any suggestively associated metabolite that was measured by nuclear magnetic resonance (NMR) or clinical chemistry (N = 7296, 87 CHD cases), and by using genetic risk scores (GRS: weighted genetic risk scores of single nucleotide polymorphisms (SNPs) that were associated with any suggestive metabolite) in Mendelian randomization (MR) analyses. The MR analyses were performed in BiB and two additional European birth cohorts (N = 38,662, 319 CHD cases). Results: In the main multivariable analyses, we identified 44 metabolites suggestively associated with CHD, including those from the following super pathways: amino acids, lipids, co-factors and vitamins, xenobiotics, nucleotides, energy, and several unknown molecules. Of these 44, isoleucine and leucine were available in the larger BiB cohort (NMR), and for these the results were validated. The MR analyses were possible for 27/44 metabolites and for 11 there was consistency with the multivariable regression results. Conclusions: In summary, we have used complimentary data sources and statistical techniques to construct layers of evidence. We found that pregnancy amino acid metabolism, androgenic steroid lipids, and levels of succinylcarnitine could be important contributing factors for CHD.",,pdf:https://www.mdpi.com/2308-3425/9/8/237/pdf?version=1658976309; doi:https://doi.org/10.3390/jcdd9080237; html:https://europepmc.org/articles/PMC9410051; pdf:https://europepmc.org/articles/PMC9410051?pdf=render
 31443926,https://doi.org/10.1016/s0140-6736(19)31674-5,Medium and long-term risks of specific cardiovascular diseases in survivors of 20 adult cancers: a population-based cohort study using multiple linked UK electronic health records databases.,"Strongman H, Gadd S, Matthews A, Mansfield KE, Stanway S, Lyon AR, Dos-Santos-Silva I, Smeeth L, Bhaskaran K.",,"Lancet (London, England)",2019,2019-08-20,Y,,Understanding the Causes of Disease,,"<h4>Background</h4>The past few decades have seen substantial improvements in cancer survival, but concerns exist about long-term cardiovascular disease risk in survivors. Evidence is scarce on the risks of specific cardiovascular diseases in survivors of a wide range of cancers to inform prevention and management. In this study, we used large-scale electronic health records data from multiple linked UK databases to address these evidence gaps.<h4>Methods</h4>For this population-based cohort study, we used linked primary care, hospital, and cancer registry data from the UK Clinical Practice Research Datalink to identify cohorts of survivors of the 20 most common cancers who were 18 years or older and alive 12 months after diagnosis and controls without history of cancer, matched for age, sex, and general practice. We compared risks for a range of cardiovascular disease outcomes using crude and adjusted Cox models. We fitted interactions to investigate effect modification, and flexible parametric survival models to estimate absolute excess risks over time.<h4>Findings</h4>Between Jan 1, 1990, and Dec 31, 2015, 126 120 individuals with a diagnosis of a cancer of interest still being followed up at least 1 year later were identified and matched to 630 144 controls. After exclusions, 108 215 cancer survivors and 523 541 controls were included in the main analyses. Venous thromboembolism risk was elevated in survivors of 18 of 20 site-specific cancers compared with that of controls; adjusted hazard ratios (HRs) ranged from 1·72 (95% CI 1·57-1·89) in patients after prostate cancer to 9·72 (5·50-17·18) after pancreatic cancer. HRs decreased over time, but remained elevated more than 5 years after diagnosis. We observed increased risks of heart failure or cardiomyopathy in patients after ten of 20 cancers, including haematological (adjusted HR 1·94, 1·66-2·25, with non-Hodgkin lymphoma; 1·77, 1·50-2·09, with leukaemia; and 3·29, 2·59-4·18, with multiple myeloma), oesophageal (1·96, 1·46-2·64), lung (1·82, 1·52-2·17) kidney (1·73, 1·38-2·17) and ovarian (1·59, 1·19-2·12). Elevated risks of arrhythmia, pericarditis, coronary artery disease, stroke, and valvular heart disease were also observed for multiple cancers, including haematological malignancies. HRs for heart failure or cardiomyopathy and venous thromboembolism were greater in patients without previous cardiovascular disease and in younger patients. However, absolute excess risks were generally greater with increasing age. Increased risks of these outcomes seemed most pronounced in patients who had received chemotherapy.<h4>Interpretation</h4>Survivors of most site-specific cancers had increased medium-term to long-term risk for one or more cardiovascular diseases compared with that for the general population, with substantial variations between cancer sites.<h4>Funding</h4>Wellcome Trust and Royal Society.",,pdf:http://www.thelancet.com/article/S0140673619316745/pdf; doi:https://doi.org/10.1016/S0140-6736(19)31674-5; html:https://europepmc.org/articles/PMC6857444; pdf:https://europepmc.org/articles/PMC6857444?pdf=render
 33724919,https://doi.org/10.2196/26627,Artificial Intelligence-Enabled Analysis of Public Attitudes on Facebook and Twitter Toward COVID-19 Vaccines in the United Kingdom and the United States: Observational Study.,"Hussain A, Tahir A, Hussain Z, Sheikh Z, Gogate M, Dashtipour K, Ali A, Sheikh A.",,Journal of medical Internet research,2021,2021-04-05,Y,Artificial intelligence; Vaccination; Public Health; Health Informatics; Natural Language Processing; Twitter; Sentiment Analysis; Deep Learning; Covid-19; Infodemiology; Facebook; Social Media,,,"<h4>Background</h4>Global efforts toward the development and deployment of a vaccine for COVID-19 are rapidly advancing. To achieve herd immunity, widespread administration of vaccines is required, which necessitates significant cooperation from the general public. As such, it is crucial that governments and public health agencies understand public sentiments toward vaccines, which can help guide educational campaigns and other targeted policy interventions.<h4>Objective</h4>The aim of this study was to develop and apply an artificial intelligence-based approach to analyze public sentiments on social media in the United Kingdom and the United States toward COVID-19 vaccines to better understand the public attitude and concerns regarding COVID-19 vaccines.<h4>Methods</h4>Over 300,000 social media posts related to COVID-19 vaccines were extracted, including 23,571 Facebook posts from the United Kingdom and 144,864 from the United States, along with 40,268 tweets from the United Kingdom and 98,385 from the United States from March 1 to November 22, 2020. We used natural language processing and deep learning-based techniques to predict average sentiments, sentiment trends, and topics of discussion. These factors were analyzed longitudinally and geospatially, and manual reading of randomly selected posts on points of interest helped identify underlying themes and validated insights from the analysis.<h4>Results</h4>Overall averaged positive, negative, and neutral sentiments were at 58%, 22%, and 17% in the United Kingdom, compared to 56%, 24%, and 18% in the United States, respectively. Public optimism over vaccine development, effectiveness, and trials as well as concerns over their safety, economic viability, and corporation control were identified. We compared our findings to those of nationwide surveys in both countries and found them to correlate broadly.<h4>Conclusions</h4>Artificial intelligence-enabled social media analysis should be considered for adoption by institutions and governments alongside surveys and other conventional methods of assessing public attitude. Such analyses could enable real-time assessment, at scale, of public confidence and trust in COVID-19 vaccines, help address the concerns of vaccine sceptics, and help develop more effective policies and communication strategies to maximize uptake.",,pdf:https://www.jmir.org/2021/4/e26627/PDF; doi:https://doi.org/10.2196/26627; html:https://europepmc.org/articles/PMC8023383
+36005401,https://doi.org/10.3390/jcdd9080237,The Relationship of Maternal Gestational Mass Spectrometry-Derived Metabolites with Offspring Congenital Heart Disease: Results from Multivariable and Mendelian Randomization Analyses.,"Taylor K, McBride N, Zhao J, Oddie S, Azad R, Wright J, Andreassen OA, Stewart ID, Langenberg C, Magnus MC, Borges MC, Caputo M, Lawlor DA.",,Journal of cardiovascular development and disease,2022,2022-07-27,Y,Metabolites; Congenital heart disease; Alspac; Moba; Born In Bradford,,,"Background: It is plausible that maternal pregnancy metabolism influences the risk of offspring congenital heart disease (CHD). We sought to explore this through a systematic approach using different methods and data. Methods: We undertook multivariable logistic regression of the odds of CHD for 923 mass spectrometry (MS)-derived metabolites in a sub-sample of a UK birth cohort (Born in Bradford (BiB); N = 2605, 46 CHD cases). We considered metabolites reaching a p-value threshold <0.05 to be suggestively associated with CHD. We sought validation of our findings, by repeating the multivariable regression analysis within the BiB cohort for any suggestively associated metabolite that was measured by nuclear magnetic resonance (NMR) or clinical chemistry (N = 7296, 87 CHD cases), and by using genetic risk scores (GRS: weighted genetic risk scores of single nucleotide polymorphisms (SNPs) that were associated with any suggestive metabolite) in Mendelian randomization (MR) analyses. The MR analyses were performed in BiB and two additional European birth cohorts (N = 38,662, 319 CHD cases). Results: In the main multivariable analyses, we identified 44 metabolites suggestively associated with CHD, including those from the following super pathways: amino acids, lipids, co-factors and vitamins, xenobiotics, nucleotides, energy, and several unknown molecules. Of these 44, isoleucine and leucine were available in the larger BiB cohort (NMR), and for these the results were validated. The MR analyses were possible for 27/44 metabolites and for 11 there was consistency with the multivariable regression results. Conclusions: In summary, we have used complimentary data sources and statistical techniques to construct layers of evidence. We found that pregnancy amino acid metabolism, androgenic steroid lipids, and levels of succinylcarnitine could be important contributing factors for CHD.",,pdf:https://www.mdpi.com/2308-3425/9/8/237/pdf?version=1658976309; doi:https://doi.org/10.3390/jcdd9080237; html:https://europepmc.org/articles/PMC9410051; pdf:https://europepmc.org/articles/PMC9410051?pdf=render
 37789377,https://doi.org/10.1186/s12943-023-01863-2,Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures.,"Figiel S, Yin W, Doultsinos D, Erickson A, Poulose N, Singh R, Magnussen A, Anbarasan T, Teague R, He M, Lundeberg J, Loda M, Verrill C, Colling R, Gill PS, Bryant RJ, Hamdy FC, Woodcock DJ, Mills IG, Cussenot O, Lamb AD.",,Molecular cancer,2023,2023-10-03,Y,prostate cancer; Virtual Biopsy; Spatial Transcriptomics; Prognostic Genetic Signatures,,,"Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx®, Decipher®, Prostadiag®) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.",,pdf:https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-023-01863-2; doi:https://doi.org/10.1186/s12943-023-01863-2; html:https://europepmc.org/articles/PMC10546768; pdf:https://europepmc.org/articles/PMC10546768?pdf=render
 37814053,https://doi.org/10.1038/s41588-023-01522-8,Age-dependent topic modeling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk.,"Jiang X, Zhang MJ, Zhang Y, Durvasula A, Inouye M, Holmes C, Price AL, McVean G.",,Nature genetics,2023,2023-10-09,N,,,,"The analysis of longitudinal data from electronic health records (EHRs) has the potential to improve clinical diagnoses and enable personalized medicine, motivating efforts to identify disease subtypes from patient comorbidity information. Here we introduce an age-dependent topic modeling (ATM) method that provides a low-rank representation of longitudinal records of hundreds of distinct diseases in large EHR datasets. We applied ATM to 282,957 UK Biobank samples, identifying 52 diseases with heterogeneous comorbidity profiles; analyses of 211,908 All of Us samples produced concordant results. We defined subtypes of the 52 heterogeneous diseases based on their comorbidity profiles and compared genetic risk across disease subtypes using polygenic risk scores (PRSs), identifying 18 disease subtypes whose PRS differed significantly from other subtypes of the same disease. We further identified specific genetic variants with subtype-dependent effects on disease risk. In conclusion, ATM identifies disease subtypes with differential genome-wide and locus-specific genetic risk profiles.",,doi:https://doi.org/10.1038/s41588-023-01522-8
 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.",,pdf:https://www.frontiersin.org/articles/10.3389/fgene.2022.818574/pdf; doi:https://doi.org/10.3389/fgene.2022.818574; html:https://europepmc.org/articles/PMC8894758; pdf:https://europepmc.org/articles/PMC8894758?pdf=render
@@ -1615,30 +1615,30 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 33184391,https://doi.org/10.1038/s41598-020-76816-6,Prediction of vascular aging based on smartphone acquired PPG signals.,"Dall'Olio L, Curti N, Remondini D, Safi Harb Y, Asselbergs FW, Castellani G, Uh HW.",,Scientific reports,2020,2020-11-12,Y,,,,"Photoplethysmography (PPG) measured by smartphone has the potential for a large scale, non-invasive, and easy-to-use screening tool. Vascular aging is linked to increased arterial stiffness, which can be measured by PPG. We investigate the feasibility of using PPG to predict healthy vascular aging (HVA) based on two approaches: machine learning (ML) and deep learning (DL). We performed data preprocessing, including detrending, demodulating, and denoising on the raw PPG signals. For ML, ridge penalized regression has been applied to 38 features extracted from PPG, whereas for DL several convolutional neural networks (CNNs) have been applied to the whole PPG signals as input. The analysis has been conducted using the crowd-sourced Heart for Heart data. The prediction performance of ML using two features (AUC of 94.7%) - the a wave of the second derivative PPG and tpr, including four covariates, sex, height, weight, and smoking - was similar to that of the best performing CNN, 12-layer ResNet (AUC of 95.3%). Without having the heavy computational cost of DL, ML might be advantageous in finding potential biomarkers for HVA prediction. The whole workflow of the procedure is clearly described, and open software has been made available to facilitate replication of the results.",,pdf:https://www.nature.com/articles/s41598-020-76816-6.pdf; doi:https://doi.org/10.1038/s41598-020-76816-6; html:https://europepmc.org/articles/PMC7661535; pdf:https://europepmc.org/articles/PMC7661535?pdf=render
 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,,,,,,pdf:https://journals.sagepub.com/doi/pdf/10.1177/0141076820961776; doi:https://doi.org/10.1177/0141076820961776; html:https://europepmc.org/articles/PMC7809339; pdf:https://europepmc.org/articles/PMC7809339?pdf=render
 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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>NCT05240742.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e065142.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-065142; html:https://europepmc.org/articles/PMC9709810; pdf:https://europepmc.org/articles/PMC9709810?pdf=render
-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; doi:https://doi.org/10.1038/s41598-023-33391-w; html:https://europepmc.org/articles/PMC10199085; pdf:https://europepmc.org/articles/PMC10199085?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; <i>P</i><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; <i>P</i>=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.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.119.013684; doi:https://doi.org/10.1161/JAHA.119.013684; html:https://europepmc.org/articles/PMC7428631; pdf:https://europepmc.org/articles/PMC7428631?pdf=render
+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; doi:https://doi.org/10.1038/s41598-023-33391-w; html:https://europepmc.org/articles/PMC10199085; pdf:https://europepmc.org/articles/PMC10199085?pdf=render
 34632432,https://doi.org/10.1016/s2666-5247(21)00128-2,Epidemiology of <i>Mycobacterium abscessus</i> 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,,,,"<h4>Background</h4><i>Mycobacterium abscessus</i> 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.<h4>Methods</h4>In this retrospective observational study, we analysed consecutive <i>M abscessus</i> 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]).<h4>Findings</h4>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.<h4>Interpretation</h4>Previously identified widely disseminated dominant clones of <i>M abscessus</i> 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 <i>M abscessus</i> 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.<h4>Funding</h4>The National Institute for Health Research, Health Data Research UK, The Wellcome Trust, The Medical Research Council, and Public Health England.",,pdf:http://www.thelancet.com/article/S2666524721001282/pdf; doi:https://doi.org/10.1016/S2666-5247(21)00128-2; html:https://europepmc.org/articles/PMC8481905
 34581777,https://doi.org/10.1182/bloodadvances.2021005453,G protein-coupled receptor kinase 5 regulates thrombin signaling in platelets via PAR-1.,"Downes K, Zhao X, Gleadall NS, McKinney H, Kempster C, Batista J, Thomas PL, Cooper M, Michael JV, Kreuzhuber R, Wedderburn K, Waller K, Varney B, Verdier H, Kriek N, Ashford SE, Stirrups KE, Dunster JL, McKenzie SE, Ouwehand WH, Gibbins JM, Yang J, Astle WJ, Ma P.",,Blood advances,2022,2022-04-01,Y,,,,"The interindividual variation in the functional response of platelets to activation by agonists is heritable. Genome-wide association studies (GWASs) of quantitative measures of platelet function have identified fewer than 20 distinctly associated variants, some with unknown mechanisms. Here, we report GWASs of pathway-specific functional responses to agonism by adenosine 5'-diphosphate, a glycoprotein VI-specific collagen mimetic, and thrombin receptor-agonist peptides, each specific to 1 of the G protein-coupled receptors PAR-1 and PAR-4, in subsets of 1562 individuals. We identified an association (P = 2.75 × 10-40) between a common intronic variant, rs10886430, in the G protein-coupled receptor kinase 5 gene (GRK5) and the sensitivity of platelets to activate through PAR-1. The variant resides in a megakaryocyte-specific enhancer that is bound by the transcription factors GATA1 and MEIS1. The minor allele (G) is associated with fewer GRK5 transcripts in platelets and the greater sensitivity of platelets to activate through PAR-1. We show that thrombin-mediated activation of human platelets causes binding of GRK5 to PAR-1 and that deletion of the mouse homolog Grk5 enhances thrombin-induced platelet activation sensitivity and increases platelet accumulation at the site of vascular injury. This corroborates evidence that the human G allele of rs10886430 is associated with a greater risk for cardiovascular disease. In summary, by combining the results of pathway-specific GWASs and expression quantitative trait locus studies in humans with the results from platelet function studies in Grk5-/- mice, we obtain evidence that GRK5 regulates the human platelet response to thrombin via the PAR-1 pathway.",,pdf:https://ashpublications.org/bloodadvances/article-pdf/6/7/2319/1886257/advancesadv2021005453.pdf; doi:https://doi.org/10.1182/bloodadvances.2021005453; html:https://europepmc.org/articles/PMC9006276; pdf:https://europepmc.org/articles/PMC9006276?pdf=render
 34468736,https://doi.org/10.1093/europace/euab162,Comparing clinical performance of current implantable cardioverter-defibrillator implantation recommendations in arrhythmogenic right ventricular cardiomyopathy.,"Bosman LP, Bosman LP, Nielsen Gerlach CL, Cadrin-Tourigny J, Orgeron G, Tichnell C, Murray B, Bourfiss M, van der Heijden JF, Yap SC, Zeppenfeld K, van den Berg MP, Wilde AAM, Asselbergs FW, Tandri H, Calkins H, van Tintelen JP, 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",2022,2022-02-01,Y,Prognosis; Risk stratification; Ventricular Arrhythmias; Implantable Cardioverter-defibrillator; Arrhythmogenic Right Ventricular Cardiomyopathy,,,"<h4>Aims</h4>Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have an increased risk of ventricular arrhythmias (VA). Four implantable cardioverter-defibrillator (ICD) recommendation algorithms are available The International Task Force Consensus ('ITFC'), an ITFC modification by Orgeron et al. ('mITFC'), the AHA/HRS/ACC guideline for VA management ('AHA'), and the HRS expert consensus statement ('HRS'). This study aims to validate and compare the performance of these algorithms in ARVC.<h4>Methods and results</h4>We classified 617 definite ARVC patients (38.5 ± 15.1 years, 52.4% male, 39.2% prior sustained VA) according to four algorithms. Clinical performance was evaluated by sensitivity, specificity, ROC-analysis, and decision curve analysis for any sustained VA and for fast VA (>250 b.p.m.). During 6.4 [2.8-11.5] years follow-up, 282 (45.7%) patients experienced any sustained VA, and 63 (10.2%) fast VA. For any sustained VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (94.0-97.8% vs. 76.7-83.5%), but lower specificity (15.9-32.0% vs. 42.7%-60.1%). Similarly, for fast VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (95.2-97.1% vs. 76.7-78.4%) but lower specificity (42.7-43.1 vs. 76.7-78.4%). Decision curve analysis showed ITFC and mITFC to be superior for a 5-year sustained VA risk ICD indication threshold between 5-25% or 2-9% for fast VA.<h4>Conclusion</h4>The ITFC and mITFC provide the highest protection rates, whereas AHA and HRS decrease unnecessary ICD placements. ITFC or mITFC should be used if we consider the 5-year threshold for ICD indication to lie within 5-25% for sustained VA or 2-9% for fast VA. These data will inform decision-making for ICD placement in ARVC.",,pdf:https://academic.oup.com/europace/article-pdf/24/2/296/42370389/euab162.pdf; doi:https://doi.org/10.1093/europace/euab162; html:https://europepmc.org/articles/PMC8824519; pdf:https://europepmc.org/articles/PMC8824519?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
-35144751,https://doi.org/10.1016/j.jacc.2021.11.045,Echocardiographic Deformation Imaging for Early Detection of Genetic Cardiomyopathies: JACC Review Topic of the Week.,"Taha K, Kirkels FP, Teske AJ, Asselbergs FW, van Tintelen JP, Doevendans PA, Kutty S, Haugaa KH, Cramer MJ.",,Journal of the American College of Cardiology,2022,2022-02-01,N,Early Detection; Speckle Tracking; Family Screening; Deformation Imaging; Genetic Cardiomyopathy,,,"Clinical screening of the relatives of patients with genetic cardiomyopathies is challenging, as they often lack detectable cardiac abnormalities at presentation. Life-threatening adverse events can already occur in these early stages of disease, so sensitive tools to reveal the earliest signs of disease are needed. The utility of echocardiographic deformation imaging for early detection has been explored for this population in multiple studies but has not been broadly implemented in clinical practice. The authors discuss contemporary evidence on the utility of deformation imaging in relatives of patients with genetic cardiomyopathies. The available body of data shows that deformation imaging reveals early disease-specific abnormalities in dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic cardiomyopathy. Deformation imaging seems promising to enhance the screening and follow-up protocols in relatives, and the authors propose measures to accelerate its implementation in clinical care.",,doi:https://doi.org/10.1016/j.jacc.2021.11.045; doi:https://doi.org/10.1016/j.jacc.2021.11.045
 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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>PCAT and PAAT density was measured in coronary (<i>n</i> = 1016) and aortic (<i>n</i> = 108) segments from 108 subjects [TAK + coronary artery disease (CAD), <i>n</i> = 36; TAK, <i>n</i> = 18; atherosclerotic CAD, <i>n</i> = 32; matched controls, <i>n</i> = 22]. Median PCAT and PAAT densities varied between groups (mPCAT: <i>P</i> < 0.0001; PAAT: <i>P</i> = 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 (<i>P</i> = 0.0002), and 8.20 ± SEM 2.04 HU higher in TAK patients without CAD than controls (<i>P</i> = 0.0001). mPCAT density was correlated with Indian Takayasu Clinical Activity Score (<i>r</i> = 0.43, <i>P</i> = 0.001) and C-reactive protein (<i>r</i> = 0.41, <i>P</i> < 0.0001) and was higher in active vs. inactive TAK (<i>P</i> = 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 <sup>68</sup>Ga-DOTATATE positron emission tomography (PET) equated to an increase of 2.44 ± SEM 0.77 HU in PCAT density for each unit increase in <sup>68</sup>Ga-DOTATATE maximum tissue-to-blood ratio (<i>P</i> = 0.002). These findings remained in multivariable sensitivity analyses adjusted for potential confounders.<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/ehjopen/article-pdf/1/2/oeab019/41727950/oeab019.pdf; doi:https://doi.org/10.1093/ehjopen/oeab019; html:https://europepmc.org/articles/PMC8508012; pdf:https://europepmc.org/articles/PMC8508012?pdf=render
+35144751,https://doi.org/10.1016/j.jacc.2021.11.045,Echocardiographic Deformation Imaging for Early Detection of Genetic Cardiomyopathies: JACC Review Topic of the Week.,"Taha K, Kirkels FP, Teske AJ, Asselbergs FW, van Tintelen JP, Doevendans PA, Kutty S, Haugaa KH, Cramer MJ.",,Journal of the American College of Cardiology,2022,2022-02-01,N,Early Detection; Speckle Tracking; Family Screening; Deformation Imaging; Genetic Cardiomyopathy,,,"Clinical screening of the relatives of patients with genetic cardiomyopathies is challenging, as they often lack detectable cardiac abnormalities at presentation. Life-threatening adverse events can already occur in these early stages of disease, so sensitive tools to reveal the earliest signs of disease are needed. The utility of echocardiographic deformation imaging for early detection has been explored for this population in multiple studies but has not been broadly implemented in clinical practice. The authors discuss contemporary evidence on the utility of deformation imaging in relatives of patients with genetic cardiomyopathies. The available body of data shows that deformation imaging reveals early disease-specific abnormalities in dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic cardiomyopathy. Deformation imaging seems promising to enhance the screening and follow-up protocols in relatives, and the authors propose measures to accelerate its implementation in clinical care.",,doi:https://doi.org/10.1016/j.jacc.2021.11.045; doi:https://doi.org/10.1016/j.jacc.2021.11.045
 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,,,"<h4>Background and aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>From &gt;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).<h4>Conclusions</h4>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.",,pdf:https://biblio.ugent.be/publication/01GTEZMFA3PQ4FR2HWVVMJE1PP/file/01GTEZP5YQ68PC7TFPP52TS6QR.pdf; 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
-37770476,https://doi.org/10.1038/s41467-023-41249-y,Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration.,"Austin-Zimmerman I, Levey DF, Giannakopoulou O, Deak JD, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Million Veteran Program, Concato J, Buysse DJ, Gaziano JM, Gottlieb DJ, Polimanti R, Stein MB, Bramon E, Gelernter J.",,Nature communications,2023,2023-09-28,Y,,,,"Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (r<sub>g</sub> = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.",,doi:https://doi.org/10.1038/s41467-023-41249-y; html:https://europepmc.org/articles/PMC10539313; pdf:https://europepmc.org/articles/PMC10539313?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,,,"<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> Pre-symptomatic transmission may be essential to consider for containment and mitigation strategies for COVID-19.",,pdf:https://wellcomeopenresearch.org/articles/5-58/v1/pdf; doi:https://doi.org/10.12688/wellcomeopenres.15788.1; html:https://europepmc.org/articles/PMC7324944; pdf:https://europepmc.org/articles/PMC7324944?pdf=render
+37770476,https://doi.org/10.1038/s41467-023-41249-y,Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration.,"Austin-Zimmerman I, Levey DF, Giannakopoulou O, Deak JD, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Million Veteran Program, Concato J, Buysse DJ, Gaziano JM, Gottlieb DJ, Polimanti R, Stein MB, Bramon E, Gelernter J.",,Nature communications,2023,2023-09-28,Y,,,,"Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (r<sub>g</sub> = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.",,doi:https://doi.org/10.1038/s41467-023-41249-y; html:https://europepmc.org/articles/PMC10539313; pdf:https://europepmc.org/articles/PMC10539313?pdf=render
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities.<h4>Results</h4>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.<h4>Conclusions</h4>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; doi:https://doi.org/10.7189/jogh.11.15003; html:https://europepmc.org/articles/PMC8542376; pdf:https://europepmc.org/articles/PMC8542376?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: <i>N</i> <sub>Cases</sub> = 42, <i>N</i> <sub>Control</sub> = 40 490; UK Biobank: <i>N</i> <sub>Cases</sub> = 2091, <i>N</i> <sub>Control</sub> = 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-<i>R</i> <sup>2</sup> 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.",,pdf:https://academic.oup.com/braincomms/article-pdf/5/2/fcad041/49521070/fcad041.pdf; doi:https://doi.org/10.1093/braincomms/fcad041; html:https://europepmc.org/articles/PMC10053643; pdf:https://europepmc.org/articles/PMC10053643?pdf=render
 31863937,https://doi.org/10.1016/j.aap.2019.105333,A systematic review of the association between fault or blame-related attributions and procedures after transport injury and health and work-related outcomes.,"Giummarra MJ, Lau G, Grant G, Gabbe BJ.",,Accident; analysis and prevention,2020,2019-12-19,N,Depression; Recovery; Pain; Anxiety; Mental health; Ptsd; Fault; Road Trauma; Transport Injury,,,"Attributions of fault are often associated with worse injury outcomes; however, the consistency and magnitude of these impacts is not known. This review examined the prognostic role of fault on health, mental health, pain and work outcomes after transport injury. A systematic search of five electronic databases (Medline, Embase, CINAHL, PsycINFO, Cochrane Library) yielded 16,324 records published between 2000 and January 2018. Eligibility criteria were: adult transport injury survivors; prospective design; multivariable analysis; fault-related factor analysed; pain, mental health, general health or work-related outcome. Citations (n = 10,558, excluding duplicates) and full text articles (n = 555) were screened manually (Reviewer 1), and using concurrent machine learning and text mining (Reviewer 2; using Abstrackr, WordStat and QDA miner). Data from 55 papers that met all inclusion criteria were extracted, papers were evaluated for risk of bias using the QUIPS tool, and overall level of evidence was assessed using the GRADE tool. There were six main fault-related factors classified as: fault or responsibility, fault-based compensation, lawyer involvement or litigation, blame or guilt, road user or position in vehicle, and impact direction. Overall there were inconsistent associations between fault and transport injury outcomes, and 60% of papers had high risk of bias. There was moderate evidence that fault-based compensation claims were associated with poorer health-related outcomes, and that lawyer involvement was associated with poorer work outcomes beyond 12 months post-injury. However, the evidence of negative associations between fault-based compensation claims and work-related outcomes was limited. Lawyer involvement and fault-based compensation claims were associated with adverse mental health outcomes six months post-injury, but not beyond 12 months. The most consistent associations between fault and negative outcomes were not for fault attributions, per se, but were related to fault-related procedures (e.g., lawyer engagement, fault-based compensation claims).",,doi:https://doi.org/10.1016/j.aap.2019.105333
+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: <i>N</i> <sub>Cases</sub> = 42, <i>N</i> <sub>Control</sub> = 40 490; UK Biobank: <i>N</i> <sub>Cases</sub> = 2091, <i>N</i> <sub>Control</sub> = 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-<i>R</i> <sup>2</sup> 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.",,pdf:https://academic.oup.com/braincomms/article-pdf/5/2/fcad041/49521070/fcad041.pdf; doi:https://doi.org/10.1093/braincomms/fcad041; html:https://europepmc.org/articles/PMC10053643; pdf:https://europepmc.org/articles/PMC10053643?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,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.",,pdf:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1070340/pdf; doi:https://doi.org/10.3389/fmicb.2023.1070340; html:https://europepmc.org/articles/PMC10043416; pdf:https://europepmc.org/articles/PMC10043416?pdf=render
 32255392,https://doi.org/10.1080/09273948.2019.1709650,Non-invasive Instrument-Based Tests for Quantifying Anterior Chamber Flare in Uveitis: A Systematic Review.,"Liu X, McNally TW, Beese S, Downie LE, Solebo AL, Faes L, Husain S, Keane PA, Moore DJ, Denniston AK.",,Ocular immunology and inflammation,2021,2020-04-07,N,"Diagnostic test; Systematic review; Uveitis; optical coherence tomography; Laser Flare Photometry; Anterior Chamber Flare; Aqueous Humor, Aqueous Humour; Aqueous Protein Concentration; Tyndall Effect",,,"<b>Purpose</b>: Anterior chamber (AC) flare is a key sign for anterior uveitis. New instrument-based techniques for measuring AC flare can offer automation and objectivity. This review aims to identify objective instrument-based measures for AC flare.<b>Methods</b>: In this systematic review, we identified studies reporting correlation between instrument-based tests versus clinician AC flare grading, and/or aqueous protein concentration, as well as test reliability.<b>Results</b>: Four index tests were identified in 11 studies: laser-flare photometry (LFP), optical coherence tomography, ocular flare analysis meter (OFAM) and the double-pass technique. The correlation between LFP and clinician grading was 0.40-0.93 and 0.87-0.94 for LFP and protein concentration. The double-pass technique showed no correlation with clinician grading and insufficient information was available for OFAM.<b>Conclusion</b>: LFP shows moderate to strong correlation with clinician grading and aqueous protein concentration. LFP could be a superior reference test compared to clinician AC flare grading for validating new index tests.",,pdf:https://discovery.ucl.ac.uk/10097154/3/Solebo_Liu%20AC%20Flare%20SR%20290919.pdf; doi:https://doi.org/10.1080/09273948.2019.1709650
-37575973,https://doi.org/10.2147/clep.s417176,Anxiety and Depression in People with Eczema or Psoriasis: A Comparison of Associations in UK Biobank and Linked Primary Care Data.,"Matthewman J, Mansfield KE, Hayes JF, Adesanya EI, Smith CH, Roberts A, Langan SM, Henderson AD.",,Clinical epidemiology,2023,2023-08-07,Y,Depression; Psoriasis; Anxiety; Eczema; Cross-sectional study; Data Linkage; Electronic Health Records; Ascertainment; Uk Biobank,,,"<h4>Introduction</h4>Previous research has shown associations between eczema and psoriasis and anxiety and depression. We investigated whether associations are consistent across different settings of ascertainment for depression and anxiety, including interview and survey responses from UK Biobank (a large longitudinal cohort recruiting individuals aged 40-69 years between 2006-2010), and linked primary care data, with the aim of drawing more reliable conclusions through triangulation.<h4>Methods</h4>In cross-sectional studies, we estimated associations between eczema or psoriasis and anxiety or depression, defining anxiety or depression as 1) self-reported previous diagnosis at UK Biobank recruitment interview; 2) PHQ-9/GAD-7 score indicating depression or anxiety from a UK Biobank mental health follow-up survey in 2016; and 3) diagnosis in linked primary care electronic health record data.<h4>Results</h4>We analysed 230,047 people with linked Biobank and primary care data. We found poor agreement between the data sources for eczema, psoriasis, anxiety, and depression. Eg, 9474 had a previous eczema diagnosis in primary care data, 4069 self-reported previous eczema diagnosis at the UK biobank interview, and 1536 had eczema in both data sources (for depression 40,455; 13,320; and 9588 respectively). Having eczema or psoriasis (recorded in primary care or baseline interview) was associated with higher odds of anxiety and depression. Eg, the adjusted odds ratio for depression comparing those with eczema to those without was greater than 1 when defining the outcome from 1) the recruitment interview (1.36, 95% confidence interval 1.27-1.45); 2) the follow-up survey (1.24, 1.09-1.39), and 3) primary care records (1.56, 1.50-1.62).<h4>Discussion</h4>Our findings support increased prevalence of mental illness in people with psoriasis and eczema across multiple data sources, which should be considered in planning of mental health services. However, we found poor agreement in disease ascertainment between settings, with implications for data interpretation in electronic health records.",,pdf:https://www.dovepress.com/getfile.php?fileID=91773; doi:https://doi.org/10.2147/CLEP.S417176; html:https://europepmc.org/articles/PMC10421744; pdf:https://europepmc.org/articles/PMC10421744?pdf=render
 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,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>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; 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
+37575973,https://doi.org/10.2147/clep.s417176,Anxiety and Depression in People with Eczema or Psoriasis: A Comparison of Associations in UK Biobank and Linked Primary Care Data.,"Matthewman J, Mansfield KE, Hayes JF, Adesanya EI, Smith CH, Roberts A, Langan SM, Henderson AD.",,Clinical epidemiology,2023,2023-08-07,Y,Depression; Psoriasis; Anxiety; Eczema; Cross-sectional study; Data Linkage; Electronic Health Records; Ascertainment; Uk Biobank,,,"<h4>Introduction</h4>Previous research has shown associations between eczema and psoriasis and anxiety and depression. We investigated whether associations are consistent across different settings of ascertainment for depression and anxiety, including interview and survey responses from UK Biobank (a large longitudinal cohort recruiting individuals aged 40-69 years between 2006-2010), and linked primary care data, with the aim of drawing more reliable conclusions through triangulation.<h4>Methods</h4>In cross-sectional studies, we estimated associations between eczema or psoriasis and anxiety or depression, defining anxiety or depression as 1) self-reported previous diagnosis at UK Biobank recruitment interview; 2) PHQ-9/GAD-7 score indicating depression or anxiety from a UK Biobank mental health follow-up survey in 2016; and 3) diagnosis in linked primary care electronic health record data.<h4>Results</h4>We analysed 230,047 people with linked Biobank and primary care data. We found poor agreement between the data sources for eczema, psoriasis, anxiety, and depression. Eg, 9474 had a previous eczema diagnosis in primary care data, 4069 self-reported previous eczema diagnosis at the UK biobank interview, and 1536 had eczema in both data sources (for depression 40,455; 13,320; and 9588 respectively). Having eczema or psoriasis (recorded in primary care or baseline interview) was associated with higher odds of anxiety and depression. Eg, the adjusted odds ratio for depression comparing those with eczema to those without was greater than 1 when defining the outcome from 1) the recruitment interview (1.36, 95% confidence interval 1.27-1.45); 2) the follow-up survey (1.24, 1.09-1.39), and 3) primary care records (1.56, 1.50-1.62).<h4>Discussion</h4>Our findings support increased prevalence of mental illness in people with psoriasis and eczema across multiple data sources, which should be considered in planning of mental health services. However, we found poor agreement in disease ascertainment between settings, with implications for data interpretation in electronic health records.",,pdf:https://www.dovepress.com/getfile.php?fileID=91773; doi:https://doi.org/10.2147/CLEP.S417176; html:https://europepmc.org/articles/PMC10421744; pdf:https://europepmc.org/articles/PMC10421744?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,,,,"<h4>Background</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-022-02702-1; doi:https://doi.org/10.1186/s13059-022-02702-1; html:https://europepmc.org/articles/PMC9229144; pdf:https://europepmc.org/articles/PMC9229144?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,,,,"<h4>Objective</h4>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.<h4>Research design and methods</h4>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.<h4>Results</h4>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; <i>P</i> < 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]; <i>P</i> = 0.005), being prescribed insulin in the last 60 days (1.58 [1.42-1.75]; <i>P</i> < 0.001), male sex (2.27 [2.09-2.46]; <i>P</i> < 0.001), being overweight (2.02 [1.54-2.64]; <i>P</i> < 0.001) or obese (8.29 [6.42-10.69]; <i>P</i> < 0.001), heart failure (1.41 [1.18-1.70]; <i>P</i> < 0.001), ischemic heart disease (1.22 [1.11-1.34]; <i>P</i> < 0.001), atrial fibrillation (1.23 [1.04-1.46]; <i>P</i> = 0.015), hypertension (1.32 [1.23-1.43]; <i>P</i> < 0.001), and depression (1.75 [1.61-1.91]; <i>P</i> < 0.001).<h4>Conclusions</h4>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.",,pdf:https://care.diabetesjournals.org/content/diacare/42/5/954.full.pdf; doi:https://doi.org/10.2337/dc18-2004
 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,,,"<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>Retinal photography and OCT are able to detect and measure vitreous inflammation. Both techniques are reliable, automatable, and warrant further evaluation.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/09273948.2020.1799038?needAccess=true; doi:https://doi.org/10.1080/09273948.2020.1799038; html:https://europepmc.org/articles/PMC8935946; pdf:https://europepmc.org/articles/PMC8935946?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02948-x; doi:https://doi.org/10.1186/s12916-023-02948-x; html:https://europepmc.org/articles/PMC10403838; pdf:https://europepmc.org/articles/PMC10403838?pdf=render
 30102210,https://doi.org/10.1016/s1470-2045(18)30425-x,A roadmap for restoring trust in Big Data.,"Lawler M, Morris AD, Sullivan R, Birney E, Middleton A, Makaroff L, Knoppers BM, Horgan D, Eggermont A.",,The Lancet. Oncology,2018,2018-08-01,N,,,,,,doi:https://doi.org/10.1016/S1470-2045(18)30425-X
 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.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.119.14302; doi:https://doi.org/10.1161/HYPERTENSIONAHA.119.14302
+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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02948-x; doi:https://doi.org/10.1186/s12916-023-02948-x; html:https://europepmc.org/articles/PMC10403838; pdf:https://europepmc.org/articles/PMC10403838?pdf=render
 37723491,https://doi.org/10.1186/s13073-023-01221-3,Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human.,"Niskanen JE, Ohlsson Å, Ljungvall I, Drögemüller M, Ernst RF, Dooijes D, van Deutekom HWM, van Tintelen JP, Snijders Blok CJB, van Vugt M, van Setten J, Asselbergs FW, Petrič AD, Salonen M, Hundi S, Hörtenhuber M, DoGA consortium, Kere J, Pyle WG, Donner J, Postma AV, Leeb T, Andersson G, Hytönen MK, Häggström J, Wiberg M, Friederich J, Eberhard J, Harakalova M, van Steenbeek FG, Wess G, Lohi H.",,Genome medicine,2023,2023-09-18,Y,Genetics; Cardiac; Arrhythmia; Cardiology; Gwas; Transcriptomics; Complex Trait; Companion Animal,,,"<h4>Background</h4>Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis.<h4>Methods</h4>We performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts.<h4>Results</h4>Our results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes.<h4>Conclusions</h4>Collectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies.",,pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-023-01221-3; doi:https://doi.org/10.1186/s13073-023-01221-3; html:https://europepmc.org/articles/PMC10506233; pdf:https://europepmc.org/articles/PMC10506233?pdf=render
 35520099,https://doi.org/10.23889/ijpds.v6i1.1718,"What makes administrative data ""research-ready""? A systematic review and thematic analysis of published literature.","Grath-Lone LM, Jay MA, Blackburn R, Gordon E, Zylbersztejn A, Wiljaars L, Gilbert R.",,International journal of population data science,2022,2022-04-27,Y,Systematic review; Administrative Data; Thematic Analysis; Research-ready,,,"<h4>Introduction</h4>Administrative data are a valuable research resource, but are under-utilised in the UK due to governance, technical and other barriers (e.g., the time and effort taken to gain secure data access). In recent years, there has been considerable government investment in making administrative data ""research-ready"", but there is no definition of what this term means. A common understanding of what constitutes research-ready administrative data is needed to establish clear principles and frameworks for their development and the realisation of their full research potential.<h4>Objective</h4>To define the characteristics of research-ready administrative data based on a systematic review and synthesis of existing literature.<h4>Methods</h4>On 29<sup>th</sup> June 2021, we systematically searched seven electronic databases for (1) peer-reviewed literature (2) related to research-ready administrative data (3) written in the English language. Following supplementary searches and snowball screening, we conducted a thematic analysis of the identified relevant literature.<h4>Results</h4>Overall, we screened 2,375 records and identified 38 relevant studies published between 2012 and 2021. Most related to administrative data from the UK and US and particularly to health data. The term research-ready was used inconsistently in the literature and there was some conflation with the concept of data being ready for statistical analysis. From the thematic analysis, we identified five defining characteristics of research-ready administrative data: (a) accessible, (b) broad, (c) curated, (d) documented and (e) enhanced for research purposes.<h4>Conclusions</h4>Our proposed characteristics of research-ready administrative data could act as a starting point to help data owners and researchers develop common principles and standards. In the more immediate term, the proposed characteristics are a useful framework for cataloguing existing research-ready administrative databases and relevant resources that can support their development.",,doi:https://doi.org/10.23889/ijpds.v6i1.1718; html:https://europepmc.org/articles/PMC9052961; pdf:https://europepmc.org/articles/PMC9052961?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,,,"<h4>Background</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/s12859-022-04838-0; doi:https://doi.org/10.1186/s12859-022-04838-0; html:https://europepmc.org/articles/PMC9338519; pdf:https://europepmc.org/articles/PMC9338519?pdf=render
@@ -1656,8 +1656,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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 ∼1.8×1.8×10mm<sup>3</sup>). 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; doi:https://doi.org/10.1016/j.media.2021.102228
 33493433,https://doi.org/10.1016/s1470-2045(20)30743-9,"The impact of the COVID-19 pandemic on radiotherapy services in England, UK: a population-based study.","Spencer K, Jones CM, Girdler R, Roe C, Sharpe M, Lawton S, Miller L, Lewis P, Evans M, Sebag-Montefiore D, Roques T, Smittenaar R, Morris E.",,The Lancet. Oncology,2021,2021-01-22,Y,,,,"<h4>Background</h4>The indirect impact of the COVID-19 pandemic on cancer outcomes is of increasing concern. However, the extent to which key treatment modalities have been affected is unclear. We aimed to assess the impact of the pandemic on radiotherapy activity in England.<h4>Methods</h4>In this population-based study, data relating to all radiotherapy delivered for cancer in the English NHS, between Feb 4, 2019, and June 28, 2020, were extracted from the National Radiotherapy Dataset. Changes in mean weekly radiotherapy courses, attendances (reflecting fractions), and fractionation patterns following the start of the UK lockdown were compared with corresponding months in 2019 overall, for specific diagnoses, and across age groups. The significance of changes in radiotherapy activity during lockdown was examined using interrupted time-series (ITS) analysis.<h4>Findings</h4>In 2020, mean weekly radiotherapy courses fell by 19·9% in April, 6·2% in May, and 11·6% in June compared with corresponding months in 2019. A relatively greater fall was observed for attendances (29·1% in April, 31·4% in May, and 31·5% in June). These changes were significant on ITS analysis (p<0·0001). A greater reduction in treatment courses between 2019 and 2020 was seen for patients aged 70 years or older compared with those aged younger than 70 years (34·4% vs 7·3% in April). By diagnosis, the largest reduction from 2019 to 2020 in treatment courses was for prostate cancer (77·0% in April) and non-melanoma skin cancer (72·4% in April). Conversely, radiotherapy courses in April, 2020, compared with April, 2019, increased by 41·2% in oesophageal cancer, 64·2% in bladder cancer, and 36·3% in rectal cancer. Increased use of ultra-hypofractionated (26 Gy in five fractions) breast radiotherapy as a percentage of all courses (0·2% in April, 2019, to 60·6% in April, 2020; ITS p<0·0001) contributed to the substantial reduction in attendances.<h4>Interpretation</h4>Radiotherapy activity fell significantly, but use of hypofractionated regimens rapidly increased in the English NHS during the first peak of the COVID-19 pandemic. An increase in treatments for some cancers suggests that radiotherapy compensated for reduced surgical activity. These data will assist health-care providers in understanding the indirect consequences of the pandemic and the role of radiotherapy services in minimising these consequences.<h4>Funding</h4>None.",,pdf:http://www.thelancet.com/article/S1470204520307439/pdf; doi:https://doi.org/10.1016/S1470-2045(20)30743-9; html:https://europepmc.org/articles/PMC7825861; pdf:https://europepmc.org/articles/PMC7825861?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,,,,"<h4>Background</h4>Atopic eczema is a common chronic inflammatory skin disease. Research suggests an association between atopic eczema and obesity, with inconsistent evidence from European populations.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4658151/1/Ascott-etal-2020_Atopic_eczema_and-obesity.pdf; doi:https://doi.org/10.1111/bjd.19597
-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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedresmethodol.biomedcentral.com/track/pdf/10.1186/s12874-020-01163-z; doi:https://doi.org/10.1186/s12874-020-01163-z; html:https://europepmc.org/articles/PMC7694355; pdf:https://europepmc.org/articles/PMC7694355?pdf=render
 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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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%).<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/europace/article-pdf/22/5/787/33178222/euaa039.pdf; doi:https://doi.org/10.1093/europace/euaa039; html:https://europepmc.org/articles/PMC7203633; pdf:https://europepmc.org/articles/PMC7203633?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedresmethodol.biomedcentral.com/track/pdf/10.1186/s12874-020-01163-z; doi:https://doi.org/10.1186/s12874-020-01163-z; html:https://europepmc.org/articles/PMC7694355; pdf:https://europepmc.org/articles/PMC7694355?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 (<i>R<sub>t</sub></i>: 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 <i>R<sub>t</sub></i> 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 <i>R<sub>t</sub></i> using a model that mapped unobserved infections to each data source. We then compared differences in <i>R<sub>t</sub></i> 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. <i>R<sub>t</sub></i> 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 <i>R<sub>t</sub></i> estimates. Further work should clarify the best way to combine and interpret <i>R<sub>t</sub></i> 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; doi:https://doi.org/10.1098/rstb.2020.0283; html:https://europepmc.org/articles/PMC8165604; pdf:https://europepmc.org/articles/PMC8165604?pdf=render
 31653530,https://doi.org/10.1016/j.echo.2019.08.015,A Practical Guide to Assess the Reproducibility of Echocardiographic Measurements.,"Bunting KV, Steeds RP, Slater LT, Rogers JK, Gkoutos GV, Kotecha D.",,Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography,2019,2019-10-22,N,Reproducibility; Echocardiography; Repeatability; reliability,,,"Echocardiography plays an essential role in the diagnosis and assessment of cardiovascular disease. Measurements derived from echocardiography are also used to determine the severity of disease, its progression over time, and to aid in the choice of optimal therapy. It is therefore clinically important that echocardiographic measurements be reproducible, repeatable, and reliable. There are a variety of statistical tests available to assess these parameters, and in this article the authors summarize those available for use by echocardiographers to improve their clinical practice. Correlation coefficients, linear regression, Bland-Altman plots, and the coefficient of variation are explored, along with their limitations. The authors also provide an online tool for the easy calculation of these statistics in the clinical environment (www.birmingham.ac.uk/echo). Quantifying and enhancing the reproducibility of echocardiography has important potential to improve the value of echocardiography as the basis for good clinical decision-making.",,pdf:http://www.onlinejase.com/article/S0894731719309460/pdf; doi:https://doi.org/10.1016/j.echo.2019.08.015
 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; <i>P</i>=0.046; I<sup>2</sup>=0%) but a comparable risk of major bleeding (adjusted cause-specific HR, 0.93; 95% CI, 0.62-1.39; <i>P</i>=0.73; I<sup>2</sup>=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; <i>P</i>=0.06; I<sup>2</sup>=0%) and 0.75 (95% CI, 0.61-0.92; <i>P</i>=0.007; I<sup>2</sup>=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.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.120.021115; doi:https://doi.org/10.1161/JAHA.120.021115; html:https://europepmc.org/articles/PMC8649290; pdf:https://europepmc.org/articles/PMC8649290?pdf=render
@@ -1672,9 +1672,9 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 34648354,https://doi.org/10.1126/science.abj1541,Mapping the proteo-genomic convergence of human diseases.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Cortes A, Koprulu M, Wörheide MA, Oerton E, Cook J, Stewart ID, Kerrison ND, Luan J, Raffler J, Arnold M, Arlt W, O'Rahilly S, Kastenmüller G, Gamazon ER, Hingorani AD, Scott RA, Wareham NJ, Langenberg C.",,"Science (New York, N.Y.)",2021,2021-11-12,N,,,,"Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3892 plasma proteins to create a cis-anchored gene-protein-disease map of 1859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to connect etiologically related diseases, to provide biological context for new or emerging disorders, and to integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at loci identified in genome-wide association studies, thereby addressing a major barrier to experimental validation and clinical translation of genetic discoveries.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904207; doi:https://doi.org/10.1126/science.abj1541; html:https://europepmc.org/articles/PMC9904207; pdf:https://europepmc.org/articles/PMC9904207?pdf=render; doi:https://doi.org/10.1126/science.abj1541
 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,,,,"<h4>Objective</h4>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.<h4>Design</h4>Population based cohort study.<h4>Setting</h4>The UK Clinical Practice Research Datalink.<h4>Participants</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>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 <i>v</i> 17.65 per 1000, adjusted risk ratio 1.55, 95% confidence interval 1.19 to 2.03) and specifically cardiovascular malformations (10.60 <i>v</i> 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 <i>v</i> 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 <i>v</i> 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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>ClinicalTrials.gov NCT03948620.",,pdf:https://www.bmj.com/content/bmj/368/bmj.m331.full.pdf; doi:https://doi.org/10.1136/bmj.m331; html:https://europepmc.org/articles/PMC7190043
 33391794,https://doi.org/10.1098/rsos.200958,"ACE inhibition and cardiometabolic risk factors, lung <i>ACE2</i> and <i>TMPRSS2</i> 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, Di Angelantonio E, Engelhardt BE, Peters JE, Sin DD, Burgess S.",,Royal Society open science,2020,2020-11-18,Y,Genetic epidemiology; Angiotensin-converting enzyme inhibitors; Mendelian Randomization; Covid-19,,,"Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of <i>ACE2</i> and <i>TMPRSS2</i> in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung <i>ACE2</i> and <i>TMPRSS2</i> gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with <i>ACE2</i> gene expression in the Lung eQTL Consortium (<i>p</i> = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung <i>ACE2</i> gene expression in the Gene-Tissue Expression (GTEx) study (<i>p</i> = 4 × 10<sup>-4</sup>) and with circulating plasma ACE2 levels in the INTERVAL study (<i>p</i> = 0.03), but not with lung <i>ACE2</i> expression in the Lung eQTL Consortium study (<i>p</i> = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung <i>ACE2</i> and <i>TMPRSS2</i> expression or plasma ACE2 levels.",,pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.200958; doi:https://doi.org/10.1098/rsos.200958; html:https://europepmc.org/articles/PMC7735342; pdf:https://europepmc.org/articles/PMC7735342?pdf=render
-36717723,https://doi.org/10.1038/s41590-022-01380-2,A patient-centric modeling framework captures recovery from SARS-CoV-2 infection.,"Ruffieux H, Hanson AL, Lodge S, Lawler NG, Whiley L, Gray N, Nolan TH, Bergamaschi L, Mescia F, Turner L, de Sa A, Pelly VS, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) BioResource COVID-19 Collaboration, Kotagiri P, Kingston N, Bradley JR, Holmes E, Wist J, Nicholson JK, Lyons PA, Smith KGC, Richardson S, Bantug GR, Hess C.",,Nature immunology,2023,2023-01-30,Y,,,,"The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct 'systemic recovery' profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app , designed to test our findings prospectively.",,pdf:https://www.nature.com/articles/s41590-022-01380-2.pdf; doi:https://doi.org/10.1038/s41590-022-01380-2; html:https://europepmc.org/articles/PMC9892000; pdf:https://europepmc.org/articles/PMC9892000?pdf=render
-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; doi:https://doi.org/10.1016/j.cmet.2022.03.002; html:https://europepmc.org/articles/PMC9097589
 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,,,"<b>Background:</b> 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. <b>Methods:</b> 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). <b>Results:</b> 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 (<i>p</i> < 0.001), whereas the baseline method reduced it to 15.8±15.6 (<i>p</i> < 0.001). MOCOnet was significantly better than the baseline method in suppressing motion artefacts and more consistently (<i>p</i> = 0.007). <b>Conclusion:</b> 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.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.768245/pdf; doi:https://doi.org/10.3389/fcvm.2021.768245; html:https://europepmc.org/articles/PMC8649951; pdf:https://europepmc.org/articles/PMC8649951?pdf=render
+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; doi:https://doi.org/10.1016/j.cmet.2022.03.002; html:https://europepmc.org/articles/PMC9097589
+36717723,https://doi.org/10.1038/s41590-022-01380-2,A patient-centric modeling framework captures recovery from SARS-CoV-2 infection.,"Ruffieux H, Hanson AL, Lodge S, Lawler NG, Whiley L, Gray N, Nolan TH, Bergamaschi L, Mescia F, Turner L, de Sa A, Pelly VS, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) BioResource COVID-19 Collaboration, Kotagiri P, Kingston N, Bradley JR, Holmes E, Wist J, Nicholson JK, Lyons PA, Smith KGC, Richardson S, Bantug GR, Hess C.",,Nature immunology,2023,2023-01-30,Y,,,,"The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct 'systemic recovery' profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app , designed to test our findings prospectively.",,pdf:https://www.nature.com/articles/s41590-022-01380-2.pdf; doi:https://doi.org/10.1038/s41590-022-01380-2; html:https://europepmc.org/articles/PMC9892000; pdf:https://europepmc.org/articles/PMC9892000?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.",,pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000843&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000843; html:https://europepmc.org/articles/PMC10021875; pdf:https://europepmc.org/articles/PMC10021875?pdf=render
 32150548,https://doi.org/10.1371/journal.pgen.1008605,The influence of rare variants in circulating metabolic biomarkers.,"Riveros-Mckay F, Oliver-Williams C, Karthikeyan S, Walter K, Kundu K, Ouwehand WH, Roberts D, Di Angelantonio E, Soranzo N, Danesh J, INTERVAL Study, Wheeler E, Zeggini E, Butterworth AS, Barroso I.",,PLoS genetics,2020,2020-03-09,Y,,Understanding the Causes of Disease,cardiovascular,"Circulating metabolite levels are biomarkers for cardiovascular disease (CVD). Here we studied, association of rare variants and 226 serum lipoproteins, lipids and amino acids in 7,142 (discovery plus follow-up) healthy participants. We leveraged the information from multiple metabolite measurements on the same participants to improve discovery in rare variant association analyses for gene-based and gene-set tests by incorporating correlated metabolites as covariates in the validation stage. Gene-based analysis corrected for the effective number of tests performed, confirmed established associations at APOB, APOC3, PAH, HAL and PCSK (p<1.32x10-7) and identified novel gene-trait associations at a lower stringency threshold with ACSL1, MYCN, FBXO36 and B4GALNT3 (p<2.5x10-6). Regulation of the pyruvate dehydrogenase (PDH) complex was associated for the first time, in gene-set analyses also corrected for effective number of tests, with IDL and LDL parameters, as well as circulating cholesterol (pMETASKAT<2.41x10-6). In conclusion, using an approach that leverages metabolite measurements obtained in the same participants, we identified novel loci and pathways involved in the regulation of these important metabolic biomarkers. As large-scale biobanks continue to amass sequencing and phenotypic information, analytical approaches such as ours will be useful to fully exploit the copious amounts of biological data generated in these efforts.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008605&type=printable; doi:https://doi.org/10.1371/journal.pgen.1008605; html:https://europepmc.org/articles/PMC7108731; pdf:https://europepmc.org/articles/PMC7108731?pdf=render
 33713332,https://doi.org/10.1007/s40620-021-00996-1,End-stage kidney disease in patients with clinically manifest vascular disease; incidence and risk factors: results from the UCC-SMART cohort study.,"Østergaard HB, Westerink J, Verhaar MC, Bots ML, Asselbergs FW, de Borst GJ, Kappelle LJ, Visseren FLJ, van der Leeuw J, UCC-SMART studygroup.",,Journal of nephrology,2021,2021-03-13,Y,Cardiovascular disease; incidence; End-stage Kidney Disease; Modifiable Risk Factors,,,"<h4>Background</h4>Patients with cardiovascular disease (CVD) are at increased risk of end-stage kidney disease (ESKD). Insights into the incidence and role of modifiable risk factors for end-stage kidney disease may provide means for prevention in patients with cardiovascular disease.<h4>Methods</h4>We included 8402 patients with stable cardiovascular disease. Incidence rates (IRs) for end-stage kidney disease were determined stratified according to vascular disease location. Cox proportional hazard models were used to assess the risk of end-stage kidney disease for the different determinants.<h4>Results</h4>Sixty-five events were observed with a median follow-up of 8.6 years. The overall incidence rate of end-stage kidney disease was 0.9/1000 person-years. Patients with polyvascular disease had the highest incidence rate (1.8/1000 person-years). Smoking (Hazard ratio (HR) 1.87; 95% CI 1.10-3.19), type 2 diabetes (HR 1.81; 95% CI 1.05-3.14), higher systolic blood pressure (HR 1.37; 95% CI 1.24-1.52/10 mmHg), lower estimated glomerular filtration rate (eGFR) (HR 2.86; 95% CI 2.44-3.23/10 mL/min/1.73 m<sup>2</sup>) and higher urine albumin/creatinine ratio (uACR) (HR 1.19; 95% CI 1.15-1.23/10 mg/mmol) were independently associated with elevated risk of end-stage kidney disease. Body mass index (BMI), waist circumference, non-HDL-cholesterol and exercise were not independently associated with risk of end-stage kidney disease.<h4>Conclusions</h4>Incidence of end-stage kidney disease in patients with cardiovascular disease varies according to vascular disease location. Several modifiable risk factors for end-stage kidney disease were identified in patients with cardiovascular disease. These findings highlight the potential of risk factor management in patients with manifest cardiovascular disease.",,pdf:https://link.springer.com/content/pdf/10.1007/s40620-021-00996-1.pdf; doi:https://doi.org/10.1007/s40620-021-00996-1; html:https://europepmc.org/articles/PMC8494654; pdf:https://europepmc.org/articles/PMC8494654?pdf=render
@@ -1692,8 +1692,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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,,,,"<h4>Objectives</h4>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.<h4>Design</h4>Population based study.<h4>Setting</h4>1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database.<h4>Participants</h4>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).<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.bmj.com/content/bmj/375/bmj-2021-065834.full.pdf; doi:https://doi.org/10.1136/bmj-2021-065834; html:https://europepmc.org/articles/PMC8715128; pdf:https://europepmc.org/articles/PMC8715128?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.",pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0228940&type=printable; doi:https://doi.org/10.1371/journal.pone.0228940; html:https://europepmc.org/articles/PMC7010290; pdf:https://europepmc.org/articles/PMC7010290?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; doi:https://doi.org/10.1038/s41588-023-01379-x; html:https://europepmc.org/articles/PMC10181934; pdf:https://europepmc.org/articles/PMC10181934?pdf=render
-35482474,https://doi.org/10.1111/bjd.21627,Biomarkers of disease progression in people with psoriasis: a scoping review.,"Ramessur R, Corbett M, Marshall D, Acencio ML, Barbosa IA, Dand N, Di Meglio P, Haddad S, Jensen AHM, Koopmann W, Mahil SK, Ostaszewski M, Rahmatulla S, Rastrick J, Saklatvala J, Weidinger S, Wright K, Eyerich K, Ndlovu M, Barker JN, Skov L, Conrad C, Smith CH, BIOMAP consortium.",,The British journal of dermatology,2022,2022-07-11,Y,,,,"<h4>Background</h4>Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice.<h4>Objectives</h4>To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community.<h4>Methods</h4>A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with disease progression. The main outcomes were any measure of skin severity or any prespecified psoriasis comorbidity. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (longitudinal design and/or use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise, and mapped to relevant cellular and molecular pathways.<h4>Results</h4>Of 181 included studies, most investigated genomic or proteomic biomarkers associated with disease severity (n = 145) or psoriatic arthritis (n = 30). Methodological and reporting limitations compromised interpretation of findings, most notably a lack of longitudinal studies, and inadequate control for key prognostic factors. The following candidate biomarkers with future potential utility were identified for predicting disease severity: LCE3D, interleukin (IL)23R, IL23A, NFKBIL1 loci, HLA-C*06:02 (genomic), IL-17A, IgG aHDL, GlycA, I-FABP and kallikrein 8 (proteomic), tyramine (metabolomic); psoriatic arthritis: HLA-C*06:02, HLA-B*27, HLA-B*38, HLA-B*08, and variation at the IL23R and IL13 loci (genomic); IL-17A, CXCL10, Mac-2 binding protein, integrin b5, matrix metalloproteinase-3 and macrophage-colony stimulating factor (proteomic) and tyramine and mucic acid (metabolomic); and type 2 diabetes mellitus: variation in IL12B and IL23R loci (genomic). No biomarkers were supported by sufficient evidence for clinical use without further validation.<h4>Conclusions</h4>This review provides a comprehensive catalogue of investigated biomarkers of disease progression in psoriasis. Future studies must address the common methodological limitations identified herein to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic? The current treatment paradigm in psoriasis is reactive. There is a need to develop effective risk-stratified management approaches that can proactively attenuate the substantial burden of disease. Prognostic biomarkers of disease progression have therefore been the focus of intense research. What does this study add? This review is the first to scope, collate and catalogue research investigating biomarkers of disease progression in psoriasis. The review identifies potentially promising candidate biomarkers for further investigation and highlights common important limitations that should be considered when designing and conducting future studies in this area.",,pdf:https://kclpure.kcl.ac.uk/ws/files/177671246/Br_J_Dermatol_2022_Ramessur_Biomarkers_of_disease_progression_in_people_with_psoriasis_a_scoping_review.pdf; doi:https://doi.org/10.1111/bjd.21627; html:https://europepmc.org/articles/PMC9796834; pdf:https://europepmc.org/articles/PMC9796834?pdf=render
 35103484,https://doi.org/10.1161/circgen.121.003553,Genetically Predicted Neutrophil-to-Lymphocyte Ratio and Coronary Artery Disease: Evidence From Mendelian Randomization. ,"Cupido AJ, Kraaijenhof JM, Burgess S, Asselbergs FW, Hovingh GK, Gill D.",,Circulation. Genomic and precision medicine,2022,2022-02-01,Y,,,,,,pdf:https://discovery.ucl.ac.uk/10145750/1/CIRCGEN.121.003553.pdf; doi:https://doi.org/10.1161/CIRCGEN.121.003553; html:https://europepmc.org/articles/PMC7612391; pdf:https://europepmc.org/articles/PMC7612391?pdf=render
+35482474,https://doi.org/10.1111/bjd.21627,Biomarkers of disease progression in people with psoriasis: a scoping review.,"Ramessur R, Corbett M, Marshall D, Acencio ML, Barbosa IA, Dand N, Di Meglio P, Haddad S, Jensen AHM, Koopmann W, Mahil SK, Ostaszewski M, Rahmatulla S, Rastrick J, Saklatvala J, Weidinger S, Wright K, Eyerich K, Ndlovu M, Barker JN, Skov L, Conrad C, Smith CH, BIOMAP consortium.",,The British journal of dermatology,2022,2022-07-11,Y,,,,"<h4>Background</h4>Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice.<h4>Objectives</h4>To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community.<h4>Methods</h4>A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with disease progression. The main outcomes were any measure of skin severity or any prespecified psoriasis comorbidity. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (longitudinal design and/or use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise, and mapped to relevant cellular and molecular pathways.<h4>Results</h4>Of 181 included studies, most investigated genomic or proteomic biomarkers associated with disease severity (n = 145) or psoriatic arthritis (n = 30). Methodological and reporting limitations compromised interpretation of findings, most notably a lack of longitudinal studies, and inadequate control for key prognostic factors. The following candidate biomarkers with future potential utility were identified for predicting disease severity: LCE3D, interleukin (IL)23R, IL23A, NFKBIL1 loci, HLA-C*06:02 (genomic), IL-17A, IgG aHDL, GlycA, I-FABP and kallikrein 8 (proteomic), tyramine (metabolomic); psoriatic arthritis: HLA-C*06:02, HLA-B*27, HLA-B*38, HLA-B*08, and variation at the IL23R and IL13 loci (genomic); IL-17A, CXCL10, Mac-2 binding protein, integrin b5, matrix metalloproteinase-3 and macrophage-colony stimulating factor (proteomic) and tyramine and mucic acid (metabolomic); and type 2 diabetes mellitus: variation in IL12B and IL23R loci (genomic). No biomarkers were supported by sufficient evidence for clinical use without further validation.<h4>Conclusions</h4>This review provides a comprehensive catalogue of investigated biomarkers of disease progression in psoriasis. Future studies must address the common methodological limitations identified herein to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic? The current treatment paradigm in psoriasis is reactive. There is a need to develop effective risk-stratified management approaches that can proactively attenuate the substantial burden of disease. Prognostic biomarkers of disease progression have therefore been the focus of intense research. What does this study add? This review is the first to scope, collate and catalogue research investigating biomarkers of disease progression in psoriasis. The review identifies potentially promising candidate biomarkers for further investigation and highlights common important limitations that should be considered when designing and conducting future studies in this area.",,pdf:https://kclpure.kcl.ac.uk/ws/files/177671246/Br_J_Dermatol_2022_Ramessur_Biomarkers_of_disease_progression_in_people_with_psoriasis_a_scoping_review.pdf; doi:https://doi.org/10.1111/bjd.21627; html:https://europepmc.org/articles/PMC9796834; pdf:https://europepmc.org/articles/PMC9796834?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",,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/8/8/e024755.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-024755; html:https://europepmc.org/articles/PMC6078268; pdf:https://europepmc.org/articles/PMC6078268?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; doi:https://doi.org/10.1080/09537104.2021.2003317
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>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; doi:https://doi.org/10.1016/j.lana.2022.100335; html:https://europepmc.org/articles/PMC9381845; pdf:https://europepmc.org/articles/PMC9381845?pdf=render
@@ -1702,14 +1702,14 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 34910136,https://doi.org/10.1093/eurheartj/ehab863,Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.,"HPS3/TIMI55-REVEAL Collaborative Group, Writing Committee, Sammons E, Hopewell JC, Chen F, Stevens W, Wallendszus K, Valdes-Marquez E, Dayanandan R, Knott C, Murphy K, Wincott E, Baxter A, Goodenough R, Lay M, Hill M, Macdonnell S, Fabbri G, Lucci D, Fajardo-Moser M, Brenner S, Hao D, Zhang H, Liu J, Wuhan B, Mosegaard S, Herrington W, Wanner C, Angermann C, Ertl G, Maggioni A, Barter P, Mihaylova B, Mitchel Y, Blaustein R, Goto S, Tobert J, DeLucca P, Chen Y, Chen Z, Gray A, Haynes R, Armitage J, Baigent C, Wiviott S, Cannon C, Braunwald E, Collins R, Bowman L, Landray M, REVEAL Collaborative Group.",,European heart journal,2022,2022-04-01,Y,Randomized Trial; Cetp Inhibitor Therapy,,,"<h4>Aims</h4>REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period.<h4>Methods and results</h4>A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3-15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10-29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7-17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0-2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants.<h4>Conclusion</h4>The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms.<h4>Trial registration</h4>International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.",,pdf:https://academic.oup.com/eurheartj/article-pdf/43/14/1416/43292041/ehab863.pdf; doi:https://doi.org/10.1093/eurheartj/ehab863; html:https://europepmc.org/articles/PMC8986460; pdf:https://europepmc.org/articles/PMC8986460?pdf=render
 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,,,,,,pdf:https://www.nature.com/articles/s41467-022-29641-6.pdf; doi:https://doi.org/10.1038/s41467-022-29641-6; html:https://europepmc.org/articles/PMC8986867; pdf:https://europepmc.org/articles/PMC8986867?pdf=render
 29966429,https://doi.org/10.1177/2047487318785228,"Clinically recorded heart rate and incidence of 12 coronary, cardiac, cerebrovascular and peripheral arterial diseases in 233,970 men and women: A linked electronic health record study.","Archangelidi O, Pujades-Rodriguez M, Timmis A, Jouven X, Denaxas S, Hemingway H.",,European journal of preventive cardiology,2018,2018-07-02,N,Heart rate; Sudden death; Heart Failure; cardiovascular; Linked Electronic Health Records,,,"Background In healthy population cohorts, resting heart rate above 90 bpm is associated with mortality from coronary heart disease, but it is not clear whether associations are present at lower heart rates or whether these associations differ between women. Methods The CALIBER resource of linked electronic health records from primary care, hospitalisations, myocardial infarction registry and cause-specific mortality in the UK was used to assess associations between resting heart rate and 12 fatal and non-fatal coronary, cardiac, cerebral and peripheral vascular cardiovascular diseases and death using Cox proportional hazard models. Results Among 233,970 patients, 29,690 fatal and non-fatal events occurred. Fully adjusted models showed that resting heart rate was not associated in men or women with cerebrovascular events. In men a resting heart rate of 70-79 bpm (29.1% of all men) versus less than 60 bpm was associated with an increased risk of heart failure (hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.26-2.16), unheralded coronary death (HR 1.65, 95% CI 1.13-2.41), total cardiovascular events (HR 1.22, 95% CI 1.15-1.28) and all-cause mortality (HR 1.39, 95% CI 1.22-1.58). Women with a higher resting heart rate level of 80-89 bpm versus 60 bpm had a higher risk of total cardiovascular disease events (HR 1.17, 95% CI 1.07-1.24) and all-cause mortality (HR 1.21, 95% CI 1.07-1.35) compared to a resting heart rate less than 60 bpm. The risk was also present at higher heart rates (>90 bpm) for heart failure and sudden cardiac death. Conclusions A resting heart rate that clinicians currently consider as 'normal' in the general population is specifically associated with the incidence of certain major cardiovascular diseases and death, with the risk starting at lower resting heart rate levels in men compared to women. Further research is required to evaluate whether interventions to lower resting heart rate are warranted to prevent disease. The study is registered at: clinicaltrials.gov (ID: NCT01947361).",,pdf:http://eprints.whiterose.ac.uk/134568/7/OArchangelidi_EJPC_accepted.pdf; doi:https://doi.org/10.1177/2047487318785228
-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,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.25697; doi:https://doi.org/10.1002/jia2.25697; html:https://europepmc.org/articles/PMC8022092; pdf:https://europepmc.org/articles/PMC8022092?pdf=render
 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
+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,,,"<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.25697; doi:https://doi.org/10.1002/jia2.25697; html:https://europepmc.org/articles/PMC8022092; pdf:https://europepmc.org/articles/PMC8022092?pdf=render
 33367483,https://doi.org/10.1093/bioinformatics/btaa1079,A non-linear regression method for estimation of gene-environment heritability.,"Kerin M, Marchini J.",,"Bioinformatics (Oxford, England)",2021,2021-04-01,Y,,,,"<h4>Motivation</h4>Gene-environment (GxE) interactions are one of the least studied aspects of the genetic architecture of human traits and diseases. The environment of an individual is inherently high dimensional, evolves through time and can be expensive and time consuming to measure. The UK Biobank study, with all 500 000 participants having undergone an extensive baseline questionnaire, represents a unique opportunity to assess GxE heritability for many traits and diseases in a well powered setting.<h4>Results</h4>We have developed a randomized Haseman-Elston non-linear regression method applicable when many environmental variables have been measured on each individual. The method (GPLEMMA) simultaneously estimates a linear environmental score (ES) and its GxE heritability. We compare the method via simulation to a whole-genome regression approach (LEMMA) for estimating GxE heritability. We show that GPLEMMA is more computationally efficient than LEMMA on large datasets, and produces results highly correlated with those from LEMMA when applied to simulated data and real data from the UK Biobank.<h4>Availability and implementation</h4>Software implementing the GPLEMMA method is available from https://jmarchini.org/gplemma/.<h4>Supplementary information</h4>Supplementary data are available at Bioinformatics online.",,pdf:https://academic.oup.com/bioinformatics/article-pdf/36/24/5632/36899551/btaa1079.pdf; doi:https://doi.org/10.1093/bioinformatics/btaa1079; html:https://europepmc.org/articles/PMC8023682; pdf:https://europepmc.org/articles/PMC8023682?pdf=render
 34437535,https://doi.org/10.1371/journal.pgen.1009723,The impact of age on genetic risk for common diseases.,"Jiang X, Holmes C, McVean G.",,PLoS genetics,2021,2021-08-26,Y,,,,"Inherited genetic variation contributes to individual risk for many complex diseases and is increasingly being used for predictive patient stratification. Previous work has shown that genetic factors are not equally relevant to human traits across age and other contexts, though the reasons for such variation are not clear. Here, we introduce methods to infer the form of the longitudinal relationship between genetic relative risk for disease and age and to test whether all genetic risk factors behave similarly. We use a proportional hazards model within an interval-based censoring methodology to estimate age-varying individual variant contributions to genetic relative risk for 24 common diseases within the British ancestry subset of UK Biobank, applying a Bayesian clustering approach to group variants by their relative risk profile over age and permutation tests for age dependency and multiplicity of profiles. We find evidence for age-varying relative risk profiles in nine diseases, including hypertension, skin cancer, atherosclerotic heart disease, hypothyroidism and calculus of gallbladder, several of which show evidence, albeit weak, for multiple distinct profiles of genetic relative risk. The predominant pattern shows genetic risk factors having the greatest relative impact on risk of early disease, with a monotonic decrease over time, at least for the majority of variants, although the magnitude and form of the decrease varies among diseases. As a consequence, for diseases where genetic relative risk decreases over age, genetic risk factors have stronger explanatory power among younger populations, compared to older ones. We show that these patterns cannot be explained by a simple model involving the presence of unobserved covariates such as environmental factors. We discuss possible models that can explain our observations and the implications for genetic risk prediction.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009723&type=printable; doi:https://doi.org/10.1371/journal.pgen.1009723; html:https://europepmc.org/articles/PMC8389405; pdf:https://europepmc.org/articles/PMC8389405?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-022-01842-5; doi:https://doi.org/10.1186/s12911-022-01842-5; html:https://europepmc.org/articles/PMC9009062; pdf:https://europepmc.org/articles/PMC9009062?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,,,"<h4>Objective</h4>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.<h4>Method</h4>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 (<i>n</i> = 40).<h4>Results</h4>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.<h4>Conclusion</h4>Remote administration of cognitive tasks successfully captured the difficulties with response inhibition and regulation of attention, supporting the feasibility and validity of remote assessments.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/10870547231172763; doi:https://doi.org/10.1177/10870547231172763; html:https://europepmc.org/articles/PMC10291103; pdf:https://europepmc.org/articles/PMC10291103?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://cardiab.biomedcentral.com/track/pdf/10.1186/s12933-019-0972-4; doi:https://doi.org/10.1186/s12933-019-0972-4; html:https://europepmc.org/articles/PMC6900858; pdf:https://europepmc.org/articles/PMC6900858?pdf=render
 33493066,https://doi.org/10.1161/strokeaha.120.031659,"Sex, Age, and Socioeconomic Differences in Nonfatal Stroke Incidence and Subsequent Major Adverse Outcomes.","Akyea RK, Vinogradova Y, Qureshi N, Patel RS, Kontopantelis E, Ntaios G, Asselbergs FW, Kai J, Weng SF.",,Stroke,2021,2021-01-25,Y,Population; Cardiovascular diseases; epidemiology; incidence; Secondary Prevention,,,"<h4>Background and purpose</h4>Data about variations in stroke incidence and subsequent major adverse outcomes are essential to inform secondary prevention and prioritizing resources to those at the greatest risk of major adverse end points. We aimed to describe the age, sex, and socioeconomic differences in the rates of first nonfatal stroke and subsequent major adverse outcomes.<h4>Methods</h4>The cohort study used linked Clinical Practice Research Datalink and Hospital Episode Statistics data from the United Kingdom. The incidence rate (IR) ratio of first nonfatal stroke and subsequent major adverse outcomes (composite major adverse cardiovascular events, recurrent stroke, cardiovascular disease-related, and all-cause mortality) were calculated and presented by year, sex, age group, and socioeconomic status based on an individual's location of residence, in adults with incident nonfatal stroke diagnosis between 1998 and 2017.<h4>Results</h4>A total of 82 774 first nonfatal stroke events were recorded in either primary care or hospital data-an IR of 109.20 per 100 000 person-years (95% CI, 108.46-109.95). Incidence was significantly higher in women compared with men (IR ratio, 1.13 [95% CI, 1.12-1.15]; <i>P</i><0.001). Rates adjusted for age and sex were higher in the lowest compared with the highest socioeconomic status group (IR ratio, 1.10 [95% CI, 1.08-1.13]; <i>P</i><0.001). For subsequent major adverse outcomes, the overall incidence for major adverse cardiovascular event was 38.05 per 100 person-years (95% CI, 37.71-38.39) with a slightly higher incidence in women compared with men (38.42 versus 37.62; IR ratio, 1.02 [95% CI, 1.00-1.04]; <i>P</i>=0.0229). Age and socioeconomic status largely accounted for the observed higher incidence of adverse outcomes in women.<h4>Conclusions</h4>In the United Kingdom, incidence of initial stroke and subsequent major adverse outcomes are higher in women, older populations, and people living in socially deprived areas.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.031659; doi:https://doi.org/10.1161/STROKEAHA.120.031659; html:https://europepmc.org/articles/PMC7834661; pdf:https://europepmc.org/articles/PMC7834661?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,,,"<h4>Objective</h4>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.<h4>Method</h4>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 (<i>n</i> = 40).<h4>Results</h4>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.<h4>Conclusion</h4>Remote administration of cognitive tasks successfully captured the difficulties with response inhibition and regulation of attention, supporting the feasibility and validity of remote assessments.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/10870547231172763; doi:https://doi.org/10.1177/10870547231172763; html:https://europepmc.org/articles/PMC10291103; pdf:https://europepmc.org/articles/PMC10291103?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Method</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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
 33472714,https://doi.org/10.1017/s1368980021000197,Diet and risk of gastro-oesophageal reflux disease in the Melbourne Collaborative Cohort Study.,"Wang SE, Hodge AM, Dashti SG, Dixon-Suen SC, Mitchell H, Thomas RJ, Williamson EM, Makalic E, Boussioutas A, Haydon AM, Giles GG, Milne RL, Kendall BJ, English DR.",,Public health nutrition,2021,2021-01-21,N,Fat; Diet; Prospective Cohort Study; Gastro-oesophageal Reflux Disease; Carbonated Beverages,,,"<h4>Objective</h4>To examine associations between diet and risk of developing gastro-oesophageal reflux disease (GERD).<h4>Design</h4>Prospective cohort with a median follow-up of 15·8 years. Baseline diet was measured using a FFQ. GERD was defined as self-reported current or history of daily heartburn or acid regurgitation beginning at least 2 years after baseline. Sex-specific logistic regressions were performed to estimate OR for GERD associated with diet quality scores and intakes of nutrients, food groups and individual foods and beverages. The effect of substituting saturated fat for monounsaturated or polyunsaturated fat on GERD risk was examined.<h4>Setting</h4>Melbourne, Australia.<h4>Participants</h4>A cohort of 20 926 participants (62 % women) aged 40-59 years at recruitment between 1990 and 1994.<h4>Results</h4>For men, total fat intake was associated with increased risk of GERD (OR 1·05 per 5 g/d; 95 % CI 1·01, 1·09; P = 0·016), whereas total carbohydrate (OR 0·89 per 30 g/d; 95 % CI 0·82, 0·98; P = 0·010) and starch intakes (OR 0·84 per 30 g/d; 95 % CI 0·75, 0·94; P = 0·005) were associated with reduced risk. Nutrients were not associated with risk for women. For both sexes, substituting saturated fat for polyunsaturated or monounsaturated fat did not change risk. For both sexes, fish, chicken, cruciferous vegetables and carbonated beverages were associated with increased risk, whereas total fruit and citrus were associated with reduced risk. No association was observed with diet quality scores.<h4>Conclusions</h4>Diet is a possible risk factor for GERD, but food considered as triggers of GERD symptoms might not necessarily contribute to disease development. Potential differential associations for men and women warrant further investigation.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/274F1A424FA99A10625C3447D256A318/S1368980021000197a.pdf/div-class-title-diet-and-risk-of-gastro-oesophageal-reflux-disease-in-the-melbourne-collaborative-cohort-study-div.pdf; doi:https://doi.org/10.1017/S1368980021000197
 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,,,,,,pdf:http://www.clinicaloncologyonline.net/article/S0936655521005161/pdf; doi:https://doi.org/10.1016/j.clon.2021.12.017
@@ -1734,8 +1734,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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,,"<h4>Summary</h4>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.<h4>Availability and implementation</h4>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.,pdf:https://academic.oup.com/bioinformatics/article-pdf/35/22/4851/30706861/btz469.pdf; doi:https://doi.org/10.1093/bioinformatics/btz469; html:https://europepmc.org/articles/PMC6853652; pdf:https://europepmc.org/articles/PMC6853652?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://bmjpaedsopen.bmj.com/content/bmjpo/5/1/e001049.full.pdf; doi:https://doi.org/10.1136/bmjpo-2021-001049; html:https://europepmc.org/articles/PMC8111870; pdf:https://europepmc.org/articles/PMC8111870?pdf=render
 32285648,https://doi.org/10.1002/ehf2.12689,Predicting sustained ventricular arrhythmias in dilated cardiomyopathy: a meta-analysis and systematic review.,"Sammani A, Kayvanpour E, Bosman LP, Sedaghat-Hamedani F, Proctor T, Gi WT, Broezel A, Jensen K, Katus HA, Te Riele ASJM, Meder B, Asselbergs FW.",,ESC heart failure,2020,2020-04-14,Y,Prognosis; Dilated cardiomyopathy; risk; Sudden Cardiac Death; Implantable Cardiac-defibrillator,,,"<h4>Aims</h4>Patients with non-ischaemic dilated cardiomyopathy (DCM) are at increased risk of sudden cardiac death. Identification of patients that may benefit from implantable cardioverter-defibrillator implantation remains challenging. In this study, we aimed to determine predictors of sustained ventricular arrhythmias in patients with DCM.<h4>Methods and results</h4>We searched MEDLINE/Embase for studies describing predictors of sustained ventricular arrhythmias in patients with DCM. Quality and bias were assessed using the Quality in Prognostic Studies tool, articles with high risk of bias in ≥2 areas were excluded. Unadjusted hazard ratios (HRs) of uniformly defined predictors were pooled, while all other predictors were evaluated in a systematic review. We included 55 studies (11 451 patients and 3.7 ± 2.3 years follow-up). Crude annual event rate was 4.5%. Younger age [HR 0.82; 95% CI (0.74-1.00)], hypertension [HR 1.95; 95% CI (1.26-3.00)], prior sustained ventricular arrhythmia [HR 4.15; 95% CI (1.32-13.02)], left ventricular ejection fraction on ultrasound [HR 1.45; 95% CI (1.19-1.78)], left ventricular dilatation (HR 1.10), and presence of late gadolinium enhancement [HR 5.55; 95% CI (4.02-7.67)] were associated with arrhythmic outcome in pooled analyses. Prior non-sustained ventricular arrhythmia and several genotypes [mutations in Phospholamban (PLN), Lamin A/C (LMNA), and Filamin-C (FLNC)] were associated with arrhythmic outcome in non-pooled analyses. Quality of evidence was moderate, and heterogeneity among studies was moderate to high.<h4>Conclusions</h4>In patients with DCM, the annual event rate of sustained ventricular arrhythmias is approximately 4.5%. This risk is considerably higher in younger patients with hypertension, prior (non-)sustained ventricular arrhythmia, decreased left ventricular ejection fraction, left ventricular dilatation, late gadolinium enhancement, and genetic mutations (PLN, LMNA, and FLNC). These results may help determine appropriate candidates for implantable cardioverter-defibrillator implantation.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.12689; doi:https://doi.org/10.1002/ehf2.12689; html:https://europepmc.org/articles/PMC7373946; pdf:https://europepmc.org/articles/PMC7373946?pdf=render
-36470992,https://doi.org/10.1038/s41375-022-01773-0,Continuous Indexing of Fibrosis (CIF): improving the assessment and classification of MPN patients.,"Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D.",,Leukemia,2023,2022-12-05,Y,,,,"The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to fully capture sample heterogeneity. To improve the quantitation of reticulin fibrosis, we developed a machine learning approach using bone marrow trephine (BMT) samples (n = 107) from patients diagnosed with MPN or a reactive marrow. The resulting Continuous Indexing of Fibrosis (CIF) enhances the detection and monitoring of fibrosis within BMTs, and aids MPN subtyping. When combined with megakaryocyte feature analysis, CIF discriminates between the frequently challenging differential diagnosis of essential thrombocythemia (ET) and pre-fibrotic myelofibrosis with high predictive accuracy [area under the curve = 0.94]. CIF also shows promise in the identification of MPN patients at risk of disease progression; analysis of samples from 35 patients diagnosed with ET and enrolled in the Primary Thrombocythemia-1 trial identified features predictive of post-ET myelofibrosis (area under the curve = 0.77). In addition to these clinical applications, automated analysis of fibrosis has clear potential to further refine disease classification boundaries and inform future studies of the micro-environmental factors driving disease initiation and progression in MPN and other stem cell disorders.",,pdf:https://www.nature.com/articles/s41375-022-01773-0.pdf; doi:https://doi.org/10.1038/s41375-022-01773-0; html:https://europepmc.org/articles/PMC9898027; pdf:https://europepmc.org/articles/PMC9898027?pdf=render
 32680743,https://doi.org/10.1016/j.jphys.2020.06.008,"Adaptation, self-motivation and support services are key to physical activity participation three to five years after major trauma: a qualitative study.","Ekegren CL, Braaf S, Ameratunga S, Ponsford J, Nunn A, Cameron P, Lyons RA, Gabbe BJ.",,Journal of physiotherapy,2020,2020-07-14,N,Trauma; Recovery; Exercise; wounds and injuries; Sedentary Lifestyle,,,"<h4>Questions</h4>What are the perceived long-term impacts of major trauma on physical activity participation over time? What factors influence physical activity participation in people recovering from major trauma?<h4>Design</h4>Longitudinal qualitative study.<h4>Participants</h4>Sixty-six people aged ≥ 16 years with non-neurological major trauma.<h4>Methods</h4>Participants were interviewed 3 years (n = 66), 4 years (n = 63) and 5 years (n = 57) after their injury. A thematic analysis was performed.<h4>Results</h4>Despite wanting to be physically active, many participants experienced significant, long-term physical activity restriction after their injury, which persisted over time. Restrictions were often related to a fear of re-injury or of exacerbating pain and fatigue levels. These restrictions were a source of distress and frustration for many participants, given the perceived impacts on their social life, family roles and enjoyment of life. Participants were also concerned about weight gain, health decline and reduced physical fitness. Participants valued the support of insurers and specialised services in facilitating access to modified activities, such as clinical Pilates and hydrotherapy. Many participants also recognised the importance of adaptation, goal-setting, self-motivation and determination to be physically active despite limitations.<h4>Conclusion</h4>People recovering from major trauma experienced significant and persistent physical activity restriction after their injury. Given the high prevalence of activity restrictions, distress and health concerns that were reported, there is an urgent need to develop and evaluate support strategies to improve physical activity participation in this group.",,doi:https://doi.org/10.1016/j.jphys.2020.06.008; doi:https://doi.org/10.1016/j.jphys.2020.06.008
+36470992,https://doi.org/10.1038/s41375-022-01773-0,Continuous Indexing of Fibrosis (CIF): improving the assessment and classification of MPN patients.,"Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D.",,Leukemia,2023,2022-12-05,Y,,,,"The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to fully capture sample heterogeneity. To improve the quantitation of reticulin fibrosis, we developed a machine learning approach using bone marrow trephine (BMT) samples (n = 107) from patients diagnosed with MPN or a reactive marrow. The resulting Continuous Indexing of Fibrosis (CIF) enhances the detection and monitoring of fibrosis within BMTs, and aids MPN subtyping. When combined with megakaryocyte feature analysis, CIF discriminates between the frequently challenging differential diagnosis of essential thrombocythemia (ET) and pre-fibrotic myelofibrosis with high predictive accuracy [area under the curve = 0.94]. CIF also shows promise in the identification of MPN patients at risk of disease progression; analysis of samples from 35 patients diagnosed with ET and enrolled in the Primary Thrombocythemia-1 trial identified features predictive of post-ET myelofibrosis (area under the curve = 0.77). In addition to these clinical applications, automated analysis of fibrosis has clear potential to further refine disease classification boundaries and inform future studies of the micro-environmental factors driving disease initiation and progression in MPN and other stem cell disorders.",,pdf:https://www.nature.com/articles/s41375-022-01773-0.pdf; doi:https://doi.org/10.1038/s41375-022-01773-0; html:https://europepmc.org/articles/PMC9898027; pdf:https://europepmc.org/articles/PMC9898027?pdf=render
 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.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609771; 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
 33678251,https://doi.org/10.1016/j.jaci.2020.08.026,"The intersect of genetics, environment, and microbiota in asthma-perspectives and challenges.","Tang HHF, Teo SM, Sly PD, Holt PG, Inouye M.",,The Journal of allergy and clinical immunology,2021,2021-03-01,N,Environment; Genomics; Asthma; Microbiota; systems biology; Gene-environment Interaction; Allergy And Immunology,,,"In asthma, a significant portion of the interaction between genetics and environment occurs through microbiota. The proposed mechanisms behind this interaction are complex and at times contradictory. This review covers recent developments in our understanding of this interaction: the ""microbial hypothesis"" and the ""farm effect""; the role of endotoxin and genetic variation in pattern recognition systems; the interaction with allergen exposure; the additional involvement of host gut and airway microbiota; the role of viral respiratory infections in interaction with the 17q21 and CDHR3 genetic loci; and the importance of in utero and early-life timing of exposures. We propose a unified framework for understanding how all these phenomena interact to drive asthma pathogenesis. Finally, we point out some future challenges for continued research in this field, in particular the need for multiomic integration, as well as the potential utility of asthma endotyping.",,doi:https://doi.org/10.1016/j.jaci.2020.08.026
 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,,,"<h4>Aims</h4>To determine the frequency and pattern of cardiac complications in patients hospitalised with coronavirus disease (COVID-19).<h4>Methods and results</h4>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 (<i>n</i>=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 (<i>n</i>=142, 4.7%) being most common. The incidence of other cardiac complications was 1.8% for heart failure (<i>n</i>=55), 0.5% for acute coronary syndrome (<i>n</i>=15), 0.5% for ventricular arrhythmia (<i>n</i>=14), 0.1% for bacterial endocarditis (<i>n</i>=4) and myocarditis (<i>n</i>=3), respectively, and 0.03% for pericarditis (<i>n</i>=1). Pulmonary embolism was diagnosed in 198 (6.6%) patients.<h4>Conclusion</h4>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.",,pdf:https://academic.oup.com/ehjacc/article-pdf/9/8/817/49790126/ehjacc0817.pdf; doi:https://doi.org/10.1177/2048872620974605; html:https://europepmc.org/articles/PMC7734244; pdf:https://europepmc.org/articles/PMC7734244?pdf=render
@@ -1753,8 +1753,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 37918923,https://doi.org/10.1136/bmjopen-2023-072531,Evaluation of variation in special educational needs provision and its impact on health and education using administrative records for England: umbrella protocol for a mixed-methods research programme.,"Zylbersztejn A, Lewis K, Nguyen V, Matthews J, Winterburn I, Karwatowska L, Barnes S, Lilliman M, Saxton J, Stone A, Boddy K, Downs J, Logan S, Rahi J, Black-Hawkins K, Dearden L, Ford T, Harron K, De Stavola B, Gilbert R.",,BMJ open,2023,2023-11-02,Y,epidemiology; Public Health; Qualitative Research; Health Informatics; Statistics & Research Methods; Health Equity,,,"<h4>Introduction</h4>One-third of children in England have special educational needs (SEN) provision recorded during their school career. The proportion of children with SEN provision varies between schools and demographic groups, which may reflect variation in need, inequitable provision and/or systemic factors. There is scant evidence on whether SEN provision improves health and education outcomes.<h4>Methods</h4>The Health Outcomes of young People in Education (HOPE) research programme uses administrative data from the Education and Child Health Insights from Linked Data-ECHILD-which contains data from all state schools, and contacts with National Health Service hospitals in England, to explore variation in SEN provision and its impact on health and education outcomes. This umbrella protocol sets out analyses across four work packages (WP). WP1 defined a range of 'health phenotypes', that is health conditions expected to need SEN provision in primary school. Next, we describe health and education outcomes (WP1) and individual, school-level and area-level factors affecting variation in SEN provision across different phenotypes (WP2). WP3 assesses the impact of SEN provision on health and education outcomes for specific health phenotypes using a range of causal inference methods to account for confounding factors and possible selection bias. In WP4 we review local policies and synthesise findings from surveys, interviews and focus groups of service users and providers to understand factors associated with variation in and experiences of identification, assessment and provision for SEN. Triangulation of findings on outcomes, variation and impact of SEN provision for different health phenotypes in ECHILD, with experiences of SEN provision will inform interpretation of findings for policy, practice and families and methods for future evaluation.<h4>Ethics and dissemination</h4>Research ethics committees have approved the use of the ECHILD database and, separately, the survey, interviews and focus groups of young people, parents and service providers. These stakeholders will contribute to the design, interpretation and communication of findings.",,doi:https://doi.org/10.1136/bmjopen-2023-072531; html:https://europepmc.org/articles/PMC10626865; pdf:https://europepmc.org/articles/PMC10626865?pdf=render
 33782396,https://doi.org/10.1038/s41467-021-22213-0,Implications of the school-household network structure on SARS-CoV-2 transmission under school reopening strategies in England.,"Munday JD, Sherratt K, Meakin S, Endo A, Pearson CAB, Hellewell J, Abbott S, Bosse NI, CMMID COVID-19 Working Group, Atkins KE, Wallinga J, Edmunds WJ, van Hoek AJ, Funk S.",,Nature communications,2021,2021-03-29,Y,,,,"In early 2020 many countries closed schools to mitigate the spread of SARS-CoV-2. Since then, governments have sought to relax the closures, engendering a need to understand associated risks. Using address records, we construct a network of schools in England connected through pupils who share households. We evaluate the risk of transmission between schools under different reopening scenarios. We show that whilst reopening select year-groups causes low risk of large-scale transmission, reopening secondary schools could result in outbreaks affecting up to 2.5 million households if unmitigated, highlighting the importance of careful monitoring and within-school infection control to avoid further school closures or other restrictions.",,pdf:https://www.nature.com/articles/s41467-021-22213-0.pdf; doi:https://doi.org/10.1038/s41467-021-22213-0; html:https://europepmc.org/articles/PMC8007691; pdf:https://europepmc.org/articles/PMC8007691?pdf=render
 33939619,https://doi.org/10.2196/29072,Predicting Risk of Hospital Admission in Patients With Suspected COVID-19 in a Community Setting: Protocol for Development and Validation of a Multivariate Risk Prediction Tool.,"Espinosa-Gonzalez AB, Neves AL, Fiorentino F, Prociuk D, 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,2021,2021-05-25,Y,Primary Care; Hospital Admission; Electronic Health Records; Early Warning Score; Risk Prediction Tool; Covid-19 Severity,,,"<h4>Background</h4>During the pandemic, remote consultations have become the norm for assessing patients with signs and symptoms of COVID-19 to decrease the risk of transmission. This has intensified the clinical uncertainty already experienced by primary care clinicians when assessing patients with suspected COVID-19 and has prompted the use of risk prediction scores, such as the National Early Warning Score (NEWS2), to assess severity and guide treatment. However, the risk prediction tools available have not been validated in a community setting and are not designed to capture the idiosyncrasies of COVID-19 infection.<h4>Objective</h4>The objective of this study is to produce a multivariate risk prediction tool, RECAP-V1 (Remote COVID-19 Assessment in Primary Care), to support primary care clinicians in the identification of those patients with COVID-19 that are at higher risk of deterioration and facilitate the early escalation of their treatment with the aim of improving patient outcomes.<h4>Methods</h4>The study follows a prospective cohort observational design, whereby patients presenting in primary care with signs and symptoms suggestive of COVID-19 will be followed and their data linked to hospital outcomes (hospital admission and death). Data collection will be carried out by primary care clinicians in four arms: North West London Clinical Commissioning Groups (NWL CCGs), Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), Covid Clinical Assessment Service (CCAS), and South East London CCGs (Doctaly platform). The study involves the use of an electronic template that incorporates a list of items (known as RECAP-V0) thought to be associated with disease outcome according to previous qualitative work. Data collected will be linked to patient outcomes in highly secure environments. We will then use multivariate logistic regression analyses for model development and validation.<h4>Results</h4>Recruitment of participants started in October 2020. Initially, only the NWL CCGs and RCGP RSC arms were active. As of March 24, 2021, we have recruited a combined sample of 3827 participants in these two arms. CCAS and Doctaly joined the study in February 2021, with CCAS starting the recruitment process on March 15, 2021. The first part of the analysis (RECAP-V1 model development) is planned to start in April 2021 using the first half of the NWL CCGs and RCGP RSC combined data set. Posteriorly, the model will be validated with the rest of the NWL CCGs and RCGP RSC data as well as the CCAS and Doctaly data sets. The study was approved by the Research Ethics Committee on May 27, 2020 (Integrated Research Application System number: 283024, Research Ethics Committee reference number: 20/NW/0266) and badged as National Institute of Health Research Urgent Public Health Study on October 14, 2020.<h4>Conclusions</h4>We believe the validated RECAP-V1 early warning score will be a valuable tool for the assessment of severity in patients with suspected COVID-19 in the community, either in face-to-face or remote consultations, and will facilitate the timely escalation of treatment with the potential to improve patient outcomes.<h4>Trial registration</h4>ISRCTN registry ISRCTN13953727; https://www.isrctn.com/ISRCTN13953727.<h4>International registered report identifier (irrid)</h4>DERR1-10.2196/29072.",,pdf:https://jmir.org/api/download?alt_name=resprot_v10i5e29072_app1.pdf&filename=e079f888f9036dd40808005eb7b49b6f.pdf; doi:https://doi.org/10.2196/29072; html:https://europepmc.org/articles/PMC8153031
-34173574,https://doi.org/10.1016/j.puhip.2020.100039,Schools and COVID-19: Reopening Pandora's box?,"Ziauddeen N, Woods-Townsend K, Saxena S, Gilbert R, Alwan NA.",,"Public health in practice (Oxford, England)",2020,2020-11-01,Y,Safety; Covid-19; School Re-Opening,,,"Schools in countries across the world are reopening as lockdown to slow progression of COVID-19 is eased. The UK government ordered school closures in England from March 20, 2020, later than the rest of Europe. A temporary and limited return for some year groups was trialled from June 2020. Teachers, school governors, the public and doctors have openly challenged the decision. The UK government has struggled to provide enough detailed information to convince the public, teachers and health practitioners, that effective systems for protection, including test, trace and isolate, are in place to prevent and manage outbreaks in schools. Risks of infection on reopening to children, staff and families must be weighed against the harms of closure to children's education and social development. The potential consequences, if the re-opening of schools is managed badly, is subsequent waves of COVID-19 infection leading to more deaths, further school closures and prolonged restrictions, losing any ground gained thus far. This article weighs the evidence for risks and benefits of reopening schools during the pandemic.",,doi:https://doi.org/10.1016/j.puhip.2020.100039; doi:https://doi.org/10.1016/j.puhip.2020.100039; html:https://europepmc.org/articles/PMC7486860; pdf:https://europepmc.org/articles/PMC7486860?pdf=render
 30887727,https://doi.org/10.1002/ppul.24314,Physical activity among children with asthma: Cross-sectional analysis in the UK millennium cohort.,"Pike KC, Griffiths LJ, Dezateux C, Pearce A.",,Pediatric pulmonology,2019,2019-03-18,Y,Children; Cohort study; epidemiology; Physical Activity; Asthma And Early Wheeze,Improving Public Health,,"<h4>Background</h4>Although beneficial for health and well-being, most children do not achieve recommended levels of physical activity. Evidence for children with asthma is mixed, with symptom severity rarely considered. This paper aimed to address this gap.<h4>Methods</h4>We analyzed cross-sectional associations between physical activity and parent-reported asthma symptoms and severity for 6497 UK Millennium Cohort Study 7-year-old participants (3321, [49%] girls). Primary outcomes were daily moderate-to-vigorous physical activity (MVPA, minutes) and proportion of children achieving recommended minimum daily levels of 60 minutes of MVPA. Daily steps, sedentary time, and total activity counts per minute (cpm) were recorded, as were parent-reported asthma symptoms, medications, and recent hospital admissions. Associations were investigated using quantile (continuous outcomes) and Poisson (binary outcomes) regression, adjusting for demographic, socioeconomic, health, and environmental factors.<h4>Results</h4>Neither asthma status nor severity was associated with MVPA; children recently hospitalized for asthma were less likely to achieve recommended daily MVPA (risk ratio [95% confidence interval [CI]]: 0.67 [0.44, 1.03]). Recent wheeze, current asthma, and severe asthma symptoms were associated with fewer sedentary hours (difference in medians [95% CI]: -0.18 [-0.27, -0.08]; -0.14 [-0.24, -0.05]; -0.15, [-0.28, -0.02], respectively) and hospital admission with lower total activity (-48 cpm [-68, -28]).<h4>Conclusion</h4>Children with asthma are as physically active as their asthma-free counterparts, while those recently hospitalized for asthma are less active. Qualitative studies are needed to understand the perceptions of children and families about physical activity following hospital admission and to inform support and advice needed to maintain active lifestyles for children with asthma.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ppul.24314; doi:https://doi.org/10.1002/ppul.24314; html:https://europepmc.org/articles/PMC6617805; pdf:https://europepmc.org/articles/PMC6617805?pdf=render
+34173574,https://doi.org/10.1016/j.puhip.2020.100039,Schools and COVID-19: Reopening Pandora's box?,"Ziauddeen N, Woods-Townsend K, Saxena S, Gilbert R, Alwan NA.",,"Public health in practice (Oxford, England)",2020,2020-11-01,Y,Safety; Covid-19; School Re-Opening,,,"Schools in countries across the world are reopening as lockdown to slow progression of COVID-19 is eased. The UK government ordered school closures in England from March 20, 2020, later than the rest of Europe. A temporary and limited return for some year groups was trialled from June 2020. Teachers, school governors, the public and doctors have openly challenged the decision. The UK government has struggled to provide enough detailed information to convince the public, teachers and health practitioners, that effective systems for protection, including test, trace and isolate, are in place to prevent and manage outbreaks in schools. Risks of infection on reopening to children, staff and families must be weighed against the harms of closure to children's education and social development. The potential consequences, if the re-opening of schools is managed badly, is subsequent waves of COVID-19 infection leading to more deaths, further school closures and prolonged restrictions, losing any ground gained thus far. This article weighs the evidence for risks and benefits of reopening schools during the pandemic.",,doi:https://doi.org/10.1016/j.puhip.2020.100039; doi:https://doi.org/10.1016/j.puhip.2020.100039; html:https://europepmc.org/articles/PMC7486860; pdf:https://europepmc.org/articles/PMC7486860?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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>ISRCTN39864003.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/6/e060280.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060280; html:https://europepmc.org/articles/PMC9207897; pdf:https://europepmc.org/articles/PMC9207897?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.",,pdf:https://erj.ersjournals.com/content/erj/54/3/1802309.full.pdf; doi:https://doi.org/10.1183/13993003.02309-2018; html:https://europepmc.org/articles/PMC6727030; pdf:https://europepmc.org/articles/PMC6727030?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.",,pdf:https://academic.oup.com/oncolo/article-pdf/26/1/e182/41923952/oncolo_26_1_n_a.pdf; doi:https://doi.org/10.1634/theoncologist.2020-0572; html:https://europepmc.org/articles/PMC7460944; pdf:https://europepmc.org/articles/PMC7460944?pdf=render
@@ -1779,8 +1779,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 35614427,https://doi.org/10.1186/s12889-022-13457-6,"The association between childhood hearing loss and self-reported peer victimisation, depressive symptoms, and self-harm: longitudinal analyses of a prospective, nationally representative cohort study.","Butcher E, Cortina-Borja M, Dezateux C, Knowles R.",,BMC public health,2022,2022-05-25,Y,Child; Hearing loss; Cohort studies; Mental health; Self-harm; Depressive Symptoms; Peer Victimisation,,,"<h4>Background</h4>Childhood hearing loss (HL) predicts poor mental health and is associated with a higher risk of communication difficulties. The relationship of childhood HL with specific types of poor mental health (such as depressive symptoms or self-harm) and peer victimisation remains unclear.<h4>Methods</h4>We analysed data from the Millennium Cohort Study (MCS), a prospective observational cohort study of children living in the UK at age 9 months and born between 2000 to 2002. Data were available on the children and their families at ages 9 months, then at 3, 5, 7, 11, and 14 years. Participants were 10,858 singleton children with self-reported data on peer victimisation, depressive symptoms, and self-harm at age 14 years. Multivariable logistic regression models were fitted to estimate odds ratios (OR) for HL with peer victimisation, depressive symptoms, and self-harm. HL presence was examined in terms of any HL between ages 9 months and 14 years, as well as by HL trajectory type (defined by onset and persistence). Analyses were adjusted for potential sources of confounding, survey design, and attrition at age 14 years. Interactions between sex and HL were examined in each model and multiple imputation procedures used to address missing data.<h4>Results</h4>Children with any HL had increased odds of depressive symptoms (OR: 1.32, 95% CI: 1.09-1.60), self-harm (1.41, 1.12-1.78) and, in girls only, peer victimisation (girls: 1.81, 1.29-2.55; boys: 1.05, 0.73-1.51), compared to those without HL. HL with later age at onset and persistence to age 14 years was the only trajectory associated with all outcomes.<h4>Conclusions</h4>Childhood HL may predict peer victimisation (in girls), depressive symptoms, and self-harm. Further research is needed to identify HL trajectories and methods to facilitate good mental health in children with HL.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-022-13457-6; doi:https://doi.org/10.1186/s12889-022-13457-6; html:https://europepmc.org/articles/PMC9131522; pdf:https://europepmc.org/articles/PMC9131522?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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<sup>-10</sup>) 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.<h4>Findings</h4>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.<h4>Interpretation</h4>Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth.<h4>Funding</h4>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; doi:https://doi.org/10.1016/j.ebiom.2023.104441; html:https://europepmc.org/articles/PMC9879767; pdf:https://europepmc.org/articles/PMC9879767?pdf=render
 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.",,pdf:https://www.nature.com/articles/s41598-021-00748-y.pdf; doi:https://doi.org/10.1038/s41598-021-00748-y; html:https://europepmc.org/articles/PMC8560804; pdf:https://europepmc.org/articles/PMC8560804?pdf=render
-37221222,https://doi.org/10.1038/s41397-023-00307-w,SLCO1B1*5 is protective against non-senile cataracts in cohort prescribed statins: analysis in a British-South Asian cohort.,"Magavern EF, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",,The pharmacogenomics journal,2023,2023-05-23,Y,,,,"<h4>Background</h4>Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity.<h4>Methods</h4>The Genes & Health cohort consists of British-Bangladeshi and British-Pakistani participants from East London, Manchester and Bradford, UK. SLCO1B1*5 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B1*5 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not.<h4>Results</h4>Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5-0.9, p 0.007)).<h4>Conclusions</h4>Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.",,pdf:https://www.nature.com/articles/s41397-023-00307-w.pdf; doi:https://doi.org/10.1038/s41397-023-00307-w; html:https://europepmc.org/articles/PMC10506906; pdf:https://europepmc.org/articles/PMC10506906?pdf=render
 36541441,https://doi.org/10.1002/hbm.26182,"Predicting sex, age, general cognition and mental health with machine learning on brain structural connectomes.","Yeung HW, Stolicyn A, Buchanan CR, Tucker-Drob EM, Bastin ME, Luz S, McIntosh AM, Whalley HC, Cox SR, Smith K.",,Human brain mapping,2023,2022-12-21,Y,Cognition; Diffusion Tensor Imaging; General Psychopathology; Deep Learning; Structural Connectomes,,,"There is an increasing expectation that advanced, computationally expensive machine learning (ML) techniques, when applied to large population-wide neuroimaging datasets, will help to uncover key differences in the human brain in health and disease. We take a comprehensive approach to explore how multiple aspects of brain structural connectivity can predict sex, age, general cognitive function and general psychopathology, testing different ML algorithms from deep learning (DL) model (BrainNetCNN) to classical ML methods. We modelled N = 8183 structural connectomes from UK Biobank using six different structural network weightings obtained from diffusion MRI. Streamline count generally provided the highest prediction accuracies in all prediction tasks. DL did not improve on prediction accuracies from simpler linear models. Further, high correlations between gradient attribution coefficients from DL and model coefficients from linear models suggested the models ranked the importance of features in similar ways, which indirectly suggested the similarity in models' strategies for making predictive decision to some extent. This highlights that model complexity is unlikely to improve detection of associations between structural connectomes and complex phenotypes with the current sample size.",,doi:https://doi.org/10.1002/hbm.26182; doi:https://doi.org/10.1002/hbm.26182; html:https://europepmc.org/articles/PMC9980898; pdf:https://europepmc.org/articles/PMC9980898?pdf=render
+37221222,https://doi.org/10.1038/s41397-023-00307-w,SLCO1B1*5 is protective against non-senile cataracts in cohort prescribed statins: analysis in a British-South Asian cohort.,"Magavern EF, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",,The pharmacogenomics journal,2023,2023-05-23,Y,,,,"<h4>Background</h4>Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity.<h4>Methods</h4>The Genes & Health cohort consists of British-Bangladeshi and British-Pakistani participants from East London, Manchester and Bradford, UK. SLCO1B1*5 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B1*5 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not.<h4>Results</h4>Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5-0.9, p 0.007)).<h4>Conclusions</h4>Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.",,pdf:https://www.nature.com/articles/s41397-023-00307-w.pdf; doi:https://doi.org/10.1038/s41397-023-00307-w; html:https://europepmc.org/articles/PMC10506906; pdf:https://europepmc.org/articles/PMC10506906?pdf=render
 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,,,,"<h4>Background</h4>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.<h4>Methods and design</h4>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.<h4>Discussion</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0257361&type=printable; doi:https://doi.org/10.1371/journal.pone.0257361; html:https://europepmc.org/articles/PMC8460020; pdf:https://europepmc.org/articles/PMC8460020?pdf=render
 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,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-019-6888-9; doi:https://doi.org/10.1186/s12889-019-6888-9; html:https://europepmc.org/articles/PMC6525436; pdf:https://europepmc.org/articles/PMC6525436?pdf=render
 36562446,https://doi.org/10.1136/bmj-2021-069048,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, Lumbers RT, 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.",,BMJ (Clinical research ed.),2022,2022-08-29,Y,,,,,,pdf:https://www.bmj.com/content/bmj/378/bmj-2021-069048.full.pdf; doi:https://doi.org/10.1136/bmj-2021-069048; html:https://europepmc.org/articles/PMC9403753
@@ -1794,8 +1794,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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,,,"<h4>Background and purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://link.springer.com/content/pdf/10.1007/s12471-022-01670-2.pdf; 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,,,"<h4>Background</h4>BMI underestimates and overestimates body fat in children from South Asian and Black ethnic groups, respectively.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/jpubhealth/article-pdf/42/4/e541/34469388/fdz188.pdf; doi:https://doi.org/10.1093/pubmed/fdz188; html:https://europepmc.org/articles/PMC7685848; pdf:https://europepmc.org/articles/PMC7685848?pdf=render
 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. ,pdf:https://www.nature.com/articles/s41433-018-0229-6.pdf; 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
-35477539,https://doi.org/10.1136/gutjnl-2021-326183,Activation of innate-adaptive immune machinery by poly(I:C) exposes a therapeutic vulnerability to prevent relapse in stroma-rich colon cancer.,"Corry SM, McCorry AM, Lannagan TR, Leonard NA, Fisher NC, Byrne RM, Tsantoulis P, Cortes-Lavaud X, Amirkhah R, Redmond KL, McCooey AJ, Malla SB, Rogan E, Sakhnevych S, Gillespie MA, White M, Richman SD, Jackstadt RF, Campbell AD, Maguire S, S:CORT and ACRCelerate consortia, McDade SS, Longley DB, Loughrey MB, Coleman HG, Kerr EM, Tejpar S, Maughan T, Leedham SJ, Small DM, Ryan AE, Sansom OJ, Lawler M, Dunne PD.",,Gut,2022,2022-04-27,Y,Cancer; Colorectal Cancer; Adjuvant Treatment; Colon Carcinogenesis,,,"<h4>Objective</h4>Stroma-rich tumours represent a poor prognostic subtype in stage II/III colon cancer (CC), with high relapse rates and limited response to standard adjuvant chemotherapy.<h4>Design</h4>To address the lack of efficacious therapeutic options for patients with stroma-rich CC, we stratified our human tumour cohorts according to stromal content, enabling identification of the biology underpinning relapse and potential therapeutic vulnerabilities specifically within stroma-rich tumours that could be exploited clinically. Following human tumour-based discovery and independent clinical validation, we use a series of <i>in vitro</i> and stroma-rich <i>in vivo</i> models to test and validate the therapeutic potential of elevating the biology associated with reduced relapse in human tumours.<h4>Results</h4>By performing our analyses specifically within the stroma-rich/high-fibroblast (HiFi) subtype of CC, we identify and validate the clinical value of a HiFi-specific prognostic signature (HPS), which stratifies tumours based on STAT1-related signalling (High-HPS v Low-HPS=HR 0.093, CI 0.019 to 0.466). Using <i>in silico, in vitro</i> and <i>in vivo</i> models, we demonstrate that the HPS is associated with antigen processing and presentation within discrete immune lineages in stroma-rich CC, downstream of double-stranded RNA and viral response signalling. Treatment with the TLR3 agonist poly(I:C) elevated the HPS signalling and antigen processing phenotype across <i>in vitro</i> and <i>in vivo</i> models. In an <i>in vivo</i> model of stroma-rich CC, poly(I:C) treatment significantly increased systemic cytotoxic T cell activity (p<0.05) and reduced liver metastases (p<0.0002).<h4>Conclusion</h4>This study reveals new biological insight that offers a novel therapeutic option to reduce relapse rates in patients with the worst prognosis CC.",,pdf:https://gut.bmj.com/content/gutjnl/early/2022/04/10/gutjnl-2021-326183.full.pdf; doi:https://doi.org/10.1136/gutjnl-2021-326183; html:https://europepmc.org/articles/PMC9664095; pdf:https://europepmc.org/articles/PMC9664095?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Main text</h4>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.<h4>Conclusion</h4>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.",,pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04951-6; doi:https://doi.org/10.1186/s13063-020-04951-6; html:https://europepmc.org/articles/PMC7788716; pdf:https://europepmc.org/articles/PMC7788716?pdf=render
+35477539,https://doi.org/10.1136/gutjnl-2021-326183,Activation of innate-adaptive immune machinery by poly(I:C) exposes a therapeutic vulnerability to prevent relapse in stroma-rich colon cancer.,"Corry SM, McCorry AM, Lannagan TR, Leonard NA, Fisher NC, Byrne RM, Tsantoulis P, Cortes-Lavaud X, Amirkhah R, Redmond KL, McCooey AJ, Malla SB, Rogan E, Sakhnevych S, Gillespie MA, White M, Richman SD, Jackstadt RF, Campbell AD, Maguire S, S:CORT and ACRCelerate consortia, McDade SS, Longley DB, Loughrey MB, Coleman HG, Kerr EM, Tejpar S, Maughan T, Leedham SJ, Small DM, Ryan AE, Sansom OJ, Lawler M, Dunne PD.",,Gut,2022,2022-04-27,Y,Cancer; Colorectal Cancer; Adjuvant Treatment; Colon Carcinogenesis,,,"<h4>Objective</h4>Stroma-rich tumours represent a poor prognostic subtype in stage II/III colon cancer (CC), with high relapse rates and limited response to standard adjuvant chemotherapy.<h4>Design</h4>To address the lack of efficacious therapeutic options for patients with stroma-rich CC, we stratified our human tumour cohorts according to stromal content, enabling identification of the biology underpinning relapse and potential therapeutic vulnerabilities specifically within stroma-rich tumours that could be exploited clinically. Following human tumour-based discovery and independent clinical validation, we use a series of <i>in vitro</i> and stroma-rich <i>in vivo</i> models to test and validate the therapeutic potential of elevating the biology associated with reduced relapse in human tumours.<h4>Results</h4>By performing our analyses specifically within the stroma-rich/high-fibroblast (HiFi) subtype of CC, we identify and validate the clinical value of a HiFi-specific prognostic signature (HPS), which stratifies tumours based on STAT1-related signalling (High-HPS v Low-HPS=HR 0.093, CI 0.019 to 0.466). Using <i>in silico, in vitro</i> and <i>in vivo</i> models, we demonstrate that the HPS is associated with antigen processing and presentation within discrete immune lineages in stroma-rich CC, downstream of double-stranded RNA and viral response signalling. Treatment with the TLR3 agonist poly(I:C) elevated the HPS signalling and antigen processing phenotype across <i>in vitro</i> and <i>in vivo</i> models. In an <i>in vivo</i> model of stroma-rich CC, poly(I:C) treatment significantly increased systemic cytotoxic T cell activity (p<0.05) and reduced liver metastases (p<0.0002).<h4>Conclusion</h4>This study reveals new biological insight that offers a novel therapeutic option to reduce relapse rates in patients with the worst prognosis CC.",,pdf:https://gut.bmj.com/content/gutjnl/early/2022/04/10/gutjnl-2021-326183.full.pdf; doi:https://doi.org/10.1136/gutjnl-2021-326183; html:https://europepmc.org/articles/PMC9664095; pdf:https://europepmc.org/articles/PMC9664095?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.",,pdf:https://www.nature.com/articles/s41598-021-85354-8.pdf; doi:https://doi.org/10.1038/s41598-021-85354-8; html:https://europepmc.org/articles/PMC7979876; pdf:https://europepmc.org/articles/PMC7979876?pdf=render
 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,,,"<h4>Background</h4>Childhood depression is relatively common, under-researched and can impact social and cognitive function and self-esteem.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/ije/article-pdf/49/4/1380/34275416/dyaa002.pdf; doi:https://doi.org/10.1093/ije/dyaa002; html:https://europepmc.org/articles/PMC7660154; pdf:https://europepmc.org/articles/PMC7660154?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,,"<h4>Motivation</h4>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.<h4>Results</h4>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.<h4>Availability and implementation</h4>The algorithm is implemented using the MWASTools R/Bioconductor package.<h4>Supplementary information</h4>Supplementary data are available at Bioinformatics online.",,pdf:https://academic.oup.com/bioinformatics/article-pdf/35/11/1916/28759353/bty837.pdf; doi:https://doi.org/10.1093/bioinformatics/bty837; html:https://europepmc.org/articles/PMC6546129; pdf:https://europepmc.org/articles/PMC6546129?pdf=render
@@ -1813,23 +1813,23 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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/m<sup>2</sup> 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.<h4>Conclusions</h4>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.",,pdf:https://www.nature.com/articles/s41366-020-0642-3.pdf; doi:https://doi.org/10.1038/s41366-020-0642-3; html:https://europepmc.org/articles/PMC7577847; pdf:https://europepmc.org/articles/PMC7577847?pdf=render
 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; Inappropriate Deferral; Haemoglobin Screening; Inappropriate Bleeding,,,"<h4>Objective</h4>To compare four haemoglobin measurement methods in whole blood donors.<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/315673/1/tme.12750.pdf; doi:https://doi.org/10.1111/tme.12750; html:https://europepmc.org/articles/PMC8048787; pdf:https://europepmc.org/articles/PMC8048787?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,,,"<h4>Background</h4>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).<h4>Methods</h4>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).<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Chronic Disease Research Foundation, Medical Research Council, Wellcome Trust, Qatar Foundation.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463529; doi:https://doi.org/10.1016/j.ebiom.2022.104243; html:https://europepmc.org/articles/PMC9463529; pdf:https://europepmc.org/articles/PMC9463529?pdf=render
-37920851,https://doi.org/10.1038/s44161-022-00171-0,Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation.,"Mokry M, Boltjes A, Slenders L, Bel-Bordes G, Cui K, Brouwer E, Mekke JM, Depuydt MAC, Timmerman N, Waissi F, Verwer MC, Turner AW, Khan MD, Hodonsky CJ, Benavente ED, Hartman RJG, van den Dungen NAM, Lansu N, Nagyova E, Prange KHM, Kovacic JC, Björkegren JLM, Pavlos E, Andreakos E, Schunkert H, Owens GK, Monaco C, Finn AV, Virmani R, Leeper NJ, de Winther MPJ, Kuiper J, de Borst GJ, Stroes ESG, Civelek M, de Kleijn DPV, den Ruijter HM, Asselbergs FW, van der Laan SW, Miller CL, Pasterkamp G.",,Nature cardiovascular research,2022,2022-12-12,N,,,,"Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved sub-phenotyping. Here we analyze the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These plaque phenotypes were associated with clinical presentation and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia. One of the plaque types with the most severe clinical symptoms pointed to both inflammatory and fibrotic cell lineages. Further, we did a preliminary analysis of potential circulating biomarkers that mark the different plaques phenotypes. In conclusion, the definition of the plaque at risk for a thrombotic event can be fine-tuned by in-depth transcriptomic-based phenotyping. These differential plaque phenotypes prove clinically relevant for both carotid and coronary artery plaques and point to distinct underlying biology of symptomatic lesions.",,doi:https://doi.org/10.1038/s44161-022-00171-0; html:https://europepmc.org/articles/PMC10621615; pdf:https://europepmc.org/articles/PMC10621615?pdf=render; doi:https://doi.org/10.1038/s44161-022-00171-0
 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,"<h4>Background & aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>We identified 6 independent genetic variants associated with liver cT1 that reached the GWAS significance threshold (p <5×10<sup>-8</sup>). 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.<h4>Conclusion</h4>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.<h4>Lay summary</h4>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.",,pdf:http://www.journal-of-hepatology.eu/article/S016882782030194X/pdf; 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
+37920851,https://doi.org/10.1038/s44161-022-00171-0,Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation.,"Mokry M, Boltjes A, Slenders L, Bel-Bordes G, Cui K, Brouwer E, Mekke JM, Depuydt MAC, Timmerman N, Waissi F, Verwer MC, Turner AW, Khan MD, Hodonsky CJ, Benavente ED, Hartman RJG, van den Dungen NAM, Lansu N, Nagyova E, Prange KHM, Kovacic JC, Björkegren JLM, Pavlos E, Andreakos E, Schunkert H, Owens GK, Monaco C, Finn AV, Virmani R, Leeper NJ, de Winther MPJ, Kuiper J, de Borst GJ, Stroes ESG, Civelek M, de Kleijn DPV, den Ruijter HM, Asselbergs FW, van der Laan SW, Miller CL, Pasterkamp G.",,Nature cardiovascular research,2022,2022-12-12,N,,,,"Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved sub-phenotyping. Here we analyze the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These plaque phenotypes were associated with clinical presentation and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia. One of the plaque types with the most severe clinical symptoms pointed to both inflammatory and fibrotic cell lineages. Further, we did a preliminary analysis of potential circulating biomarkers that mark the different plaques phenotypes. In conclusion, the definition of the plaque at risk for a thrombotic event can be fine-tuned by in-depth transcriptomic-based phenotyping. These differential plaque phenotypes prove clinically relevant for both carotid and coronary artery plaques and point to distinct underlying biology of symptomatic lesions.",,doi:https://doi.org/10.1038/s44161-022-00171-0; html:https://europepmc.org/articles/PMC10621615; pdf:https://europepmc.org/articles/PMC10621615?pdf=render; doi:https://doi.org/10.1038/s44161-022-00171-0
 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.",,pdf:https://www.nature.com/articles/s41431-021-00835-8.pdf; doi:https://doi.org/10.1038/s41431-021-00835-8; html:https://europepmc.org/articles/PMC8440598; pdf:https://europepmc.org/articles/PMC8440598?pdf=render
 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,,,"<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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]).<h4>Conclusions</h4>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.",,pdf:http://www.injuryjournal.com/article/S0020138321003429/pdf; doi:https://doi.org/10.1016/j.injury.2021.04.033
-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,,,"<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 <i>a priori</i> 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 <i>p</i>-values 0.04 and 6 × 10<sup>-5</sup>, respectively), with an effect reversal in younger women.<h4>Conclusion</h4>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.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.768972/pdf; doi:https://doi.org/10.3389/fcvm.2022.768972; html:https://europepmc.org/articles/PMC9043514; pdf:https://europepmc.org/articles/PMC9043514?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.",,pdf:https://www.frontiersin.org/articles/10.3389/fnut.2020.00080/pdf; doi:https://doi.org/10.3389/fnut.2020.00080; html:https://europepmc.org/articles/PMC7343846; pdf:https://europepmc.org/articles/PMC7343846?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,,,"<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 <i>a priori</i> 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 <i>p</i>-values 0.04 and 6 × 10<sup>-5</sup>, respectively), with an effect reversal in younger women.<h4>Conclusion</h4>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.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.768972/pdf; doi:https://doi.org/10.3389/fcvm.2022.768972; html:https://europepmc.org/articles/PMC9043514; pdf:https://europepmc.org/articles/PMC9043514?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; Hospitals, Ehealth; Digital Excellence",,,"<h4>Background</h4>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.<h4>Objective</h4>Our aim was to develop an international agreement on a defined set of technological capabilities to assess digital excellence in hospitals.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.jmir.org/2020/8/e17022/PDF; doi:https://doi.org/10.2196/17022; html:https://europepmc.org/articles/PMC7463397
 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; doi:https://doi.org/10.1128/JCM.00670-20; html:https://europepmc.org/articles/PMC7512152; pdf:https://europepmc.org/articles/PMC7512152?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.",,pdf:https://www.mdpi.com/2075-4426/11/8/814/pdf?version=1629458822; doi:https://doi.org/10.3390/jpm11080814; html:https://europepmc.org/articles/PMC8399452; pdf:https://europepmc.org/articles/PMC8399452?pdf=render
 32479194,https://doi.org/10.1161/circulationaha.120.045826,"Lipoprotein(a) in Alzheimer, Atherosclerotic, Cerebrovascular, Thrombotic, and Valvular Disease: Mendelian Randomization Investigation.","Larsson SC, Gill D, Mason AM, Jiang T, Bäck M, Butterworth AS, Burgess S.",,Circulation,2020,2020-06-01,N,Atherosclerosis; Lipoprotein(a); Alzheimer disease; Stroke; Heart valve diseases; Mendelian Randomization Analysis,,,,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.045826; doi:https://doi.org/10.1161/CIRCULATIONAHA.120.045826; html:https://europepmc.org/articles/PMC7614586; pdf:https://europepmc.org/articles/PMC7614586?pdf=render; doi:https://doi.org/10.1161/circulationaha.120.045826
 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).",,pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/46/5/1114/33777256/sbaa040.pdf; 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
 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<sup>+</sup> 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.",,pdf:https://www.nature.com/articles/s41467-020-17477-x.pdf; doi:https://doi.org/10.1038/s41467-020-17477-x; html:https://europepmc.org/articles/PMC7387553; pdf:https://europepmc.org/articles/PMC7387553?pdf=render
-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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02722-5; doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render
 34167318,https://doi.org/10.1161/circulationaha.121.054302,Cardiac Troponin Thresholds and Kinetics to Differentiate Myocardial Injury and Myocardial Infarction.,"Wereski R, Kimenai DM, Taggart C, Doudesis D, Lee KK, Lowry MTH, Bularga A, Lowe DJ, Fujisawa T, Apple FS, Collinson PO, Anand A, Chapman AR, Mills NL.",,Circulation,2021,2021-06-25,Y,Kinetics; Troponin; Myocardial infarction; Predictive Value Of Tests,,,"<h4>Background</h4>Although the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice.<h4>Methods</h4>In a secondary analysis of a multicenter randomized controlled trial, we identified 46 092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment-elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value and specificity were determined at the sex-specific 99th percentile upper reference limit and rule-in thresholds of 64 ng/L and 5-fold of the upper reference limit for a diagnosis of type 1 myocardial infarction.<h4>Results</h4>Troponin was above the 99th percentile in 8188 patients (18%). The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14% and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th-75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold upper reference limit gave a positive predictive value of 57% (95% CI, 56%-58%), 59% (58%-61%), and 62% (60%-64%) and a specificity of 96% (96%-96%), 96% (96%-96%), and 98% (97%-98%), respectively. The absolute, relative, and rate of change in troponin concentration were highest in patients with type 1 myocardial infarction (<i>P</i><0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared with troponin concentration at presentation alone (area under the curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]).<h4>Conclusions</h4>Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01852123.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.054302; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.054302; html:https://europepmc.org/articles/PMC8360674; pdf:https://europepmc.org/articles/PMC8360674?pdf=render
+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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02722-5; doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render
+32548911,https://doi.org/10.1002/ehf2.12779,A registry-based algorithm to predict ejection fraction in patients with heart failure.,"Uijl A, Lund LH, Vaartjes I, Brugts JJ, Linssen GC, Asselbergs FW, Hoes AW, Dahlström U, Koudstaal S, Savarese G.",,ESC heart failure,2020,2020-06-17,Y,Prediction; Ejection fraction; Heart Failure; Electronic Health Records; Hfpef; Hfref; Hfmref,,,"<h4>Aims</h4>Left ventricular ejection fraction (EF) is required to categorize heart failure (HF) [i.e. HF with preserved (HFpEF), mid-range (HFmrEF), and reduced (HFrEF) EF] but is often not captured in population-based cohorts or non-HF registries. The aim was to create an algorithm that identifies EF subphenotypes for research purposes.<h4>Methods and results</h4>We included 42 061 HF patients from the Swedish Heart Failure Registry. As primary analysis, we performed two logistic regression models including 22 variables to predict (i) EF≥ vs. <50% and (ii) EF≥ vs. <40%. In the secondary analysis, we performed a multivariable multinomial analysis with 22 variables to create a model for all three separate EF subphenotypes: HFrEF vs. HFmrEF vs. HFpEF. The models were validated in the database from the CHECK-HF study, a cross-sectional survey of 10 627 patients from the Netherlands. The C-statistic (discrimination) was 0.78 [95% confidence interval (CI) 0.77-0.78] for EF ≥50% and 0.76 (95% CI 0.75-0.76) for EF ≥40%. Similar results were achieved for HFrEF and HFpEF in the multinomial model, but the C-statistic for HFmrEF was lower: 0.63 (95% CI 0.63-0.64). The external validation showed similar discriminative ability to the development cohort.<h4>Conclusions</h4>Routine clinical characteristics could potentially be used to identify different EF subphenotypes in databases where EF is not readily available. Accuracy was good for the prediction of HFpEF and HFrEF but lower for HFmrEF. The proposed algorithm enables more effective research on HF in the big data setting.",,doi:https://doi.org/10.1002/ehf2.12779; doi:https://doi.org/10.1002/ehf2.12779; html:https://europepmc.org/articles/PMC7524089; pdf:https://europepmc.org/articles/PMC7524089?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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvh.13863; doi:https://doi.org/10.1111/jvh.13863
 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-19<sup>1-13</sup>. 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.",,pdf:https://www.nature.com/articles/s41586-022-04569-5.pdf; doi:https://doi.org/10.1038/s41586-022-04569-5; html:https://europepmc.org/articles/PMC9046077; pdf:https://europepmc.org/articles/PMC9046077?pdf=render
-32548911,https://doi.org/10.1002/ehf2.12779,A registry-based algorithm to predict ejection fraction in patients with heart failure.,"Uijl A, Lund LH, Vaartjes I, Brugts JJ, Linssen GC, Asselbergs FW, Hoes AW, Dahlström U, Koudstaal S, Savarese G.",,ESC heart failure,2020,2020-06-17,Y,Prediction; Ejection fraction; Heart Failure; Electronic Health Records; Hfpef; Hfref; Hfmref,,,"<h4>Aims</h4>Left ventricular ejection fraction (EF) is required to categorize heart failure (HF) [i.e. HF with preserved (HFpEF), mid-range (HFmrEF), and reduced (HFrEF) EF] but is often not captured in population-based cohorts or non-HF registries. The aim was to create an algorithm that identifies EF subphenotypes for research purposes.<h4>Methods and results</h4>We included 42 061 HF patients from the Swedish Heart Failure Registry. As primary analysis, we performed two logistic regression models including 22 variables to predict (i) EF≥ vs. <50% and (ii) EF≥ vs. <40%. In the secondary analysis, we performed a multivariable multinomial analysis with 22 variables to create a model for all three separate EF subphenotypes: HFrEF vs. HFmrEF vs. HFpEF. The models were validated in the database from the CHECK-HF study, a cross-sectional survey of 10 627 patients from the Netherlands. The C-statistic (discrimination) was 0.78 [95% confidence interval (CI) 0.77-0.78] for EF ≥50% and 0.76 (95% CI 0.75-0.76) for EF ≥40%. Similar results were achieved for HFrEF and HFpEF in the multinomial model, but the C-statistic for HFmrEF was lower: 0.63 (95% CI 0.63-0.64). The external validation showed similar discriminative ability to the development cohort.<h4>Conclusions</h4>Routine clinical characteristics could potentially be used to identify different EF subphenotypes in databases where EF is not readily available. Accuracy was good for the prediction of HFpEF and HFrEF but lower for HFmrEF. The proposed algorithm enables more effective research on HF in the big data setting.",,doi:https://doi.org/10.1002/ehf2.12779; doi:https://doi.org/10.1002/ehf2.12779; html:https://europepmc.org/articles/PMC7524089; pdf:https://europepmc.org/articles/PMC7524089?pdf=render
 37128097,https://doi.org/10.1038/s43016-020-0092-z,RETRACTED ARTICLE: Dietary metabotype modelling predicts individual responses to dietary interventions.,"Garcia-Perez I, Posma JM, Chambers ES, Mathers JC, Draper J, Beckmann M, Nicholson JK, Holmes E, Frost G.",,Nature food,2020,2020-06-17,N,,,,"Habitual consumption of poor quality diets is linked directly to risk factors for many non-communicable diseases. This has resulted in the vast majority of countries and the World Health Organization developing policies for healthy eating to reduce the prevalence of non-communicable diseases in the population. However, there is mounting evidence of variability in individual metabolic responses to any dietary intervention. We have developed a method for applying a pipeline for understanding interindividual differences in response to diet, based on coupling data from highly controlled dietary studies with deep metabolic phenotyping. In this feasibility study, we create an individual Dietary Metabotype Score (DMS) that embodies interindividual variability in dietary response and captures consequent dynamic changes in concentrations of urinary metabolites. We find an inverse relationship between the DMS and blood glucose concentration. There is also a relationship between the DMS and urinary metabolic energy loss. Furthermore, we use a metabolic entropy approach to visualize individual and collective responses to dietary interventions. Potentially, the DMS offers a method to target and to enhance dietary response at the individual level, thereby reducing the burden of non-communicable diseases at the population level.",,html:http://hdl.handle.net/10044/1/80100; doi:https://doi.org/10.1038/s43016-020-0092-z
 33201485,https://doi.org/10.1007/s12471-020-01517-8,ONCOR: design of the Dutch cardio-oncology registry.,"Kamphuis JAM, Linschoten M, Cramer MJ, Alsemgeest F, van Kessel DJW, Urgel K, Post MC, Manintveld OC, Hassing HC, Liesting C, Wardeh AJ, Olde Bijvank EGM, Schaap J, Stevense-den Boer AM, Doevendans PA, Asselbergs FW, Teske AJ.",,Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation,2021,2020-11-17,Y,Research Design; Registries; Cardio-oncology,,,"<h4>Background</h4>The relative new subspecialty 'cardio-oncology' was established to meet the growing demand for an interdisciplinary approach to the management of cancer therapy-related cardiovascular adverse events. In recent years, specialised cardio-oncology services have been implemented worldwide, which all strive to improve the cardiovascular health of cancer patients. However, limited data are currently available on the outcomes and experiences of these specialised services, and optimal strategies for cardio-oncological care have not been established.<h4>Aim</h4>The ONCOR registry has been created for prospective data collection and evaluation of cardio-oncological care in daily practice.<h4>Methods</h4>Dutch hospitals using a standardised cardio-oncology care pathway are included in this national, multicentre, observational cohort study. All patients visiting these cardio-oncology services are eligible for study inclusion. Data collection at baseline consists of the (planned) cancer treatment and the cardiovascular risk profile, which are used to estimate the cardiotoxic risk. Information regarding invasive and noninvasive tests is collected during the time patients receive cardio-oncological care. Outcome data consist of the incidence of cardiovascular complications and major adverse cardiac events, and the impact of these events on the oncological treatment.<h4>Discussion</h4>Outcomes of the ONCOR registry may aid in gaining more insight into the incidence of cancer therapy-related cardiovascular complications. The registry facilitates research on mechanisms of cardiovascular complications and on diagnostic, prognostic and therapeutic strategies. In addition, it provides a platform for future (interventional) studies. Centres with cardio-oncology services that are interested in contributing to the ONCOR registry are hereby invited to participate.",,pdf:https://link.springer.com/content/pdf/10.1007/s12471-020-01517-8.pdf; doi:https://doi.org/10.1007/s12471-020-01517-8; html:https://europepmc.org/articles/PMC8062648; pdf:https://europepmc.org/articles/PMC8062648?pdf=render
 36245269,https://doi.org/10.15252/embj.2022111857,Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation.,"Yu X, Ni T, Munson G, Zhang P, Gilbert RJC.",,The EMBO journal,2022,2022-10-17,Y,Cryo-electron Tomography; Cryo-em; Subtomogram Averaging; Pore-forming Protein; Perforin-2,,,"Perforin-2 (PFN2, MPEG1) is a key pore-forming protein in mammalian innate immunity restricting intracellular bacteria proliferation. It forms a membrane-bound pre-pore complex that converts to a pore-forming structure upon acidification; but its mechanism of conformational transition has been debated. Here we used cryo-electron microscopy, tomography and subtomogram averaging to determine structures of PFN2 in pre-pore and pore conformations in isolation and bound to liposomes. In isolation and upon acidification, the pre-assembled complete pre-pore rings convert to pores in both flat ring and twisted conformations. On membranes, in situ assembled PFN2 pre-pores display various degrees of completeness; whereas PFN2 pores are mainly incomplete arc structures that follow the same subunit packing arrangements as found in isolation. Both assemblies on membranes use their P2 β-hairpin for binding to the lipid membrane surface. Overall, these structural snapshots suggest a molecular mechanism for PFN2 pre-pore to pore transition on a targeted membrane, potentially using the twisted pore as an intermediate or alternative state to the flat conformation, with the capacity to cause bilayer distortion during membrane insertion.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.15252/embj.2022111857; doi:https://doi.org/10.15252/embj.2022111857; html:https://europepmc.org/articles/PMC9713709; pdf:https://europepmc.org/articles/PMC9713709?pdf=render
@@ -1878,8 +1878,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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),,,"<b>Background:</b> 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. <b>Methods:</b> 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 <sup>hi</sup>), and an age- and sex- matched IFN <sup>low</sup> SLE patient and healthy donor. <b>Results:</b> We confirmed the presence of a rare cytotoxic CD4 <sup>+</sup> T cell (CTL) subset, which was exclusively present in the IFN <sup>hi</sup> patient. Furthermore, we identified additional alterations consistent with increased immune activation in this patient, most notably a shift towards terminally differentiated CD57 <sup>+</sup> CD8 <sup>+</sup> T cell and CD16 <sup>+</sup> NK <sup>dim</sup> phenotypes, and the presence of a subset of recently-activated naïve CD4 <sup>+</sup> T cells. <b>Conclusions:</b> 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 <sup>hi</sup> 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 <sup>+</sup> CD4 <sup>+</sup> CTLs.",,pdf:https://wellcomeopenresearch.org/articles/6-149/v2/pdf; doi:https://doi.org/10.12688/wellcomeopenres.16883.2; html:https://europepmc.org/articles/PMC9046903; pdf:https://europepmc.org/articles/PMC9046903?pdf=render
 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,,,"<h4>Background</h4>We aimed to examine the multimorbidity patterns within a representative sample of UK older adults and their association with concurrent and subsequent memory.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://academic.oup.com/biomedgerontology/article-pdf/76/5/867/37955188/glab009.pdf; doi:https://doi.org/10.1093/gerona/glab009; html:https://europepmc.org/articles/PMC8087269; pdf:https://europepmc.org/articles/PMC8087269?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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1878-0261.13038; doi:https://doi.org/10.1002/1878-0261.13038; html:https://europepmc.org/articles/PMC8486593; pdf:https://europepmc.org/articles/PMC8486593?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,,,"<h4>Background and purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%; <i>P</i>=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.<h4>Conclusions</h4>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.",,pdf:https://europepmc.org/articles/pmc8607920?pdf=render; doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?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,,,"<h4>Purpose</h4>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.<h4>Methods</h4>We defined a project plan including the scope and requirements, infrastructure and interface, data quality and study population, validation and evaluation of the CDSS.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://link.springer.com/content/pdf/10.1007/s12471-019-01308-w.pdf; doi:https://doi.org/10.1007/s12471-019-01308-w; html:https://europepmc.org/articles/PMC6712110; pdf:https://europepmc.org/articles/PMC6712110?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,,,"<h4>Background and purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%; <i>P</i>=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.<h4>Conclusions</h4>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.",,pdf:https://europepmc.org/articles/pmc8607920?pdf=render; doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?pdf=render
 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.",,pdf:https://www.nature.com/articles/s41598-022-08351-5.pdf; doi:https://doi.org/10.1038/s41598-022-08351-5; html:https://europepmc.org/articles/PMC8943120; pdf:https://europepmc.org/articles/PMC8943120?pdf=render
 33444378,https://doi.org/10.1371/journal.pcbi.1008417,Probabilistic transmission models incorporating sequencing data for healthcare-associated Clostridioides difficile outperform heuristic rules and identify strain-specific differences in transmission.,"Eyre DW, Laager M, Walker AS, Cooper BS, Wilson DJ, CDC Modeling Infectious Diseases in Healthcare Program (MInD-Healthcare).",,PLoS computational biology,2021,2021-01-14,Y,,,,"Fitting stochastic transmission models to electronic patient data can offer detailed insights into the transmission of healthcare-associated infections and improve infection control. Pathogen whole-genome sequencing may improve the precision of model inferences, but computational constraints have limited modelling applications predominantly to small datasets and specific outbreaks, whereas large-scale sequencing studies have mostly relied on simple rules for identifying/excluding plausible transmission. We present a novel approach for integrating detailed epidemiological data on patient contact networks in hospitals with large-scale pathogen sequencing data. We apply our approach to study Clostridioides difficile transmission using a dataset of 1223 infections in Oxfordshire, UK, 2007-2011. 262 (21% [95% credibility interval 20-22%]) infections were estimated to have been acquired from another known case. There was heterogeneity by sequence type (ST) in the proportion of cases acquired from another case with the highest rates in ST1 (ribotype-027), ST42 (ribotype-106) and ST3 (ribotype-001). These same STs also had higher rates of transmission mediated via environmental contamination/spores persisting after patient discharge/recovery; for ST1 these persisted longer than for most other STs except ST3 and ST42. We also identified variation in transmission between hospitals, medical specialties and over time; by 2011 nearly all transmission from known cases had ceased in our hospitals. Our findings support previous work suggesting only a minority of C. difficile infections are acquired from known cases but highlight a greater role for environmental contamination than previously thought. Our approach is applicable to other healthcare-associated infections. Our findings have important implications for effective control of C. difficile.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008417&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1008417; html:https://europepmc.org/articles/PMC7840057; pdf:https://europepmc.org/articles/PMC7840057?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,,"<h4>Background</h4>Results from observational studies regarding associations between fish (including shellfish) intake and cardiovascular disease risk factors, including blood pressure (BP) and BMI, are inconsistent.<h4>Objective</h4>To investigate associations of fish consumption and associated urinary metabolites with BP and BMI in free-living populations.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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; doi:https://doi.org/10.1093/ajcn/nqz293; html:https://europepmc.org/articles/PMC6997096; pdf:https://europepmc.org/articles/PMC6997096?pdf=render
@@ -1897,11 +1897,11 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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,,,"<h4>Background</h4>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.<h4>Aim</h4>To describe the volume and variation of coded clinical activity in general practice, taking respiratory disease and laboratory procedures as examples.<h4>Design and setting</h4>Working on behalf of NHS England, a cohort study was conducted of 23.8 million patient records in general practice, <i>in situ</i> using OpenSAFELY.<h4>Method</h4>Activity using Clinical Terms Version 3 codes and keyword searches from January 2019 to September 2020 are described.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://bjgp.org/content/bjgp/72/714/e63.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0380; html:https://europepmc.org/articles/PMC8589464; pdf:https://europepmc.org/articles/PMC8589464?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjpaedsopen.bmj.com/content/bmjpo/5/1/e001112.full.pdf; doi:https://doi.org/10.1136/bmjpo-2021-001112; html:https://europepmc.org/articles/PMC8208018; pdf:https://europepmc.org/articles/PMC8208018?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.",,pdf:https://www.nature.com/articles/s41467-020-18783-0.pdf; doi:https://doi.org/10.1038/s41467-020-18783-0; html:https://europepmc.org/articles/PMC7538915; pdf:https://europepmc.org/articles/PMC7538915?pdf=render
-35879886,https://doi.org/10.1017/s0033291722002501,"Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.","Young KS, Purves KL, Hübel C, Davies MR, Thompson KN, Bristow S, Krebs G, Danese A, Hirsch C, Parsons CE, Vassos E, Adey BN, Bright S, Hegemann L, Lee YT, Kalsi G, Monssen D, Mundy J, Peel AJ, Rayner C, Rogers HC, Ter Kuile A, Ward C, York K, Lin Y, Palmos AB, Schmidt U, Veale D, Nicholson TR, Pollak TA, Stevelink SAM, Moukhtarian T, Martineau AR, Holt H, Maughan B, Al-Chalabi A, Chaudhuri KR, Richardson MP, Bradley JR, Chinnery PF, Kingston N, Papadia S, Stirrups KE, Linger R, Hotopf M, Eley TC, Breen G.",,Psychological medicine,2023,2022-07-26,Y,Depression; Anxiety; Ptsd; Covid-19,,,"<h4>Background</h4>The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.<h4>Method</h4>Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (<i>n</i> = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.<h4>Results</h4>Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.<h4>Conclusions</h4>We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/8C3760ED596F1ED8B80F729AC5E47B9B/S0033291722002501a.pdf/div-class-title-depression-anxiety-and-ptsd-symptoms-before-and-during-the-covid-19-pandemic-in-the-uk-div.pdf; doi:https://doi.org/10.1017/S0033291722002501; html:https://europepmc.org/articles/PMC10482709; pdf:https://europepmc.org/articles/PMC10482709?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.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa49960/Download/0049960-14052019134527.pdf; doi:https://doi.org/10.1016/j.evalprogplan.2019.03.002
+35879886,https://doi.org/10.1017/s0033291722002501,"Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.","Young KS, Purves KL, Hübel C, Davies MR, Thompson KN, Bristow S, Krebs G, Danese A, Hirsch C, Parsons CE, Vassos E, Adey BN, Bright S, Hegemann L, Lee YT, Kalsi G, Monssen D, Mundy J, Peel AJ, Rayner C, Rogers HC, Ter Kuile A, Ward C, York K, Lin Y, Palmos AB, Schmidt U, Veale D, Nicholson TR, Pollak TA, Stevelink SAM, Moukhtarian T, Martineau AR, Holt H, Maughan B, Al-Chalabi A, Chaudhuri KR, Richardson MP, Bradley JR, Chinnery PF, Kingston N, Papadia S, Stirrups KE, Linger R, Hotopf M, Eley TC, Breen G.",,Psychological medicine,2023,2022-07-26,Y,Depression; Anxiety; Ptsd; Covid-19,,,"<h4>Background</h4>The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.<h4>Method</h4>Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (<i>n</i> = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.<h4>Results</h4>Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.<h4>Conclusions</h4>We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/8C3760ED596F1ED8B80F729AC5E47B9B/S0033291722002501a.pdf/div-class-title-depression-anxiety-and-ptsd-symptoms-before-and-during-the-covid-19-pandemic-in-the-uk-div.pdf; doi:https://doi.org/10.1017/S0033291722002501; html:https://europepmc.org/articles/PMC10482709; pdf:https://europepmc.org/articles/PMC10482709?pdf=render
 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,,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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; doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?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; Cancer Therapy–related Cardiac Dysfunction; Anthracycline‐related Cardiomyopathy,,,"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; <i>P</i>=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; <i>P</i>=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; pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025935
 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,,,"<h4>Background and purpose</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.029042; doi:https://doi.org/10.1161/STROKEAHA.120.029042; html:https://europepmc.org/articles/PMC7382539; pdf:https://europepmc.org/articles/PMC7382539?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; Cancer Therapy–related Cardiac Dysfunction; Anthracycline‐related Cardiomyopathy,,,"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; <i>P</i>=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; <i>P</i>=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; pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025935
 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 genome<sup>1,2</sup>. 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.",,pdf:https://www.nature.com/articles/s41586-022-04712-2.pdf; doi:https://doi.org/10.1038/s41586-022-04712-2; html:https://europepmc.org/articles/PMC9117138; pdf:https://europepmc.org/articles/PMC9117138?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,,,"<h4>Background</h4>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.<h4>Objectives</h4>This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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
 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 <i>whole society</i> processes <i>,</i> 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, <i>GroundsWell</i>, 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; doi:https://doi.org/10.12688/wellcomeopenres.18175.1; html:https://europepmc.org/articles/PMC9971655; pdf:https://europepmc.org/articles/PMC9971655?pdf=render
@@ -1916,8 +1916,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 31748235,https://doi.org/10.1136/bmj.l6055,Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres.,"Kaura A, 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, Kharbanda R, Lord GM, Melikian N, Patel RS, Perera D, Shah AM, Francis DP, Mayet J.",,BMJ (Clinical research ed.),2019,2019-11-20,Y,,,,"<h4>Objective</h4>To determine the relation between age and troponin level and its prognostic implication.<h4>Design</h4>Retrospective cohort study.<h4>Setting</h4>Five cardiovascular centres in the UK National Institute for Health Research Health Informatics Collaborative (UK-NIHR HIC).<h4>Participants</h4>257 948 consecutive patients undergoing troponin testing for any clinical reason between 2010 and 2017.<h4>Main outcome measure</h4>All cause mortality.<h4>Results</h4>257 948 patients had troponin measured during the study period. Analyses on troponin were performed using the peak troponin level, which was the highest troponin level measured during the patient's hospital stay. Troponin levels were standardised as a multiple of each laboratory's 99th centile of the upper limit of normal (ULN). During a median follow-up of 1198 days (interquartile range 514-1866 days), 55 850 (21.7%) deaths occurred. A positive troponin result (that is, higher than the upper limit of normal) signified a 3.2 higher mortality hazard (95% confidence interval 3.1 to 3.2) over three years. Mortality varied noticeably with age, with a hazard ratio of 10.6 (8.5 to 13.3) in 18-29 year olds and 1.5 (1.4 to 1.6) in those older than 90. A positive troponin result was associated with an approximately 15 percentage points higher absolute three year mortality across all age groups. The excess mortality with a positive troponin result was heavily concentrated in the first few weeks. Results were analysed using multivariable adjusted restricted cubic spline Cox regression. A direct relation was seen between troponin level and mortality in patients without acute coronary syndrome (ACS, n=120 049), whereas an inverted U shaped relation was found in patients with ACS (n=14 468), with a paradoxical decline in mortality at peak troponin levels >70×ULN. In the group with ACS, the inverted U shaped relation persisted after multivariable adjustment in those who were managed invasively; however, a direct positive relation was found between troponin level and mortality in patients managed non-invasively.<h4>Conclusions</h4>A positive troponin result was associated with a clinically important increased mortality, regardless of age, even if the level was only slightly above normal. The excess mortality with a raised troponin was heavily concentrated in the first few weeks.<h4>Study registration</h4>ClinicalTrials.gov NCT03507309.",Kaura et al. used a large database of about a quarter of a million patients who had toponin measurements and concluded that there was an association between positive troponin results and mortality regardless of age ,pdf:https://www.bmj.com/content/bmj/367/bmj.l6055.full.pdf; doi:https://doi.org/10.1136/bmj.l6055; html:https://europepmc.org/articles/PMC6865859
 30765456,https://doi.org/10.1136/injuryprev-2018-043014,Crash characteristics of on-road single-bicycle crashes: an under-recognised problem.,"Beck B, Stevenson MR, Cameron P, Oxley J, Newstead S, Olivier J, Boufous S, Gabbe BJ.",,Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention,2019,2019-02-14,N,epidemiology; Functional Outcome; Bicycle,,,"Compared with crashes with motor vehicles, single-bicycle crashes are an under-recognised contributor to cycling injury and the aetiology is poorly understood. Using an in-depth crash investigation technique, this study describes the crash characteristics and patient outcomes of a sample of cyclists admitted to hospital following on-road bicycle crashes. Enrolled cyclists completed a structured interview, and injury details and patient outcomes were extracted from trauma registries. Single-bicycle crashes (n=62) accounted for 48% of on-road crashes and commonly involved experienced cyclists. Common single-bicycle crash types included loss-of-control events, interactions with tram tracks, striking potholes or objects or resulting from mechanical issues with the bicycle. To address single-bicycle crashes, targeted countermeasures are required for each of these specific crash types.",,pdf:https://figshare.com/articles/journal_contribution/Crash_characteristics_of_on-road_single-bicycle_crashes_an_under-recognised_problem/19807744/1/files/35209867.pdf; doi:https://doi.org/10.1136/injuryprev-2018-043014
 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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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).<h4>Ethics and dissemination</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/5/e038530.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038530; html:https://europepmc.org/articles/PMC7239518; pdf:https://europepmc.org/articles/PMC7239518?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,,,,,,pdf:http://www.journalofhospitalinfection.com/article/S0195670121000712/pdf; 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
 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,,,"<h4>Introduction</h4>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.<h4>Objective</h4>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).<h4>Methods</h4>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).<h4>Conclusion</h4>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.<h4>Highlights</h4>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.",,pdf:https://ijpds.org/article/download/412/533; doi:https://doi.org/10.23889/ijpds.v3i1.412; html:https://europepmc.org/articles/PMC7299475; pdf:https://europepmc.org/articles/PMC7299475?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,,,,,,pdf:http://www.journalofhospitalinfection.com/article/S0195670121000712/pdf; 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
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://www.thelancet.com/article/S0140673622011096/pdf; 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
 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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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; doi:https://doi.org/10.1016/j.diabet.2022.101418
 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,,,"<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%).<h4>Conclusions</h4>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.",,pdf:https://www.pure.ed.ac.uk/ws/files/124987758/AAM_Association_of_physical_health_multimorbidity....pdf; doi:https://doi.org/10.1016/j.schres.2019.10.061
@@ -1925,8 +1925,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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,,,,,,pdf:https://bjgp.org/content/bjgp/70/699/477.full.pdf; 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
 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,,,"<h4>Background</h4>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<sup>+</sup> 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<sup>+</sup> and CD8<sup>+</sup> subpopulations, and changes in markers of cellular ageing in CD8<sup>+</sup> T lymphocytes.<h4>Methods</h4>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<sup>+</sup> and CD4<sup>+</sup> lymphocyte subsets, and analysis of recent thymic emigrant cells. Telomere length within CD8<sup>+</sup> T lymphocytes was assessed, as well as the expression of the telomerase reverse transcriptase enzyme (hTERT), and the cell-ageing markers p16<sup>INK4a</sup> and p21<sup>CIP1/Waf1</sup>.<h4>Results</h4>The number of CD8<sup>+</sup> TEMRA T cells was found to be significantly reduced in PD patients compared to controls. The expression of p16<sup>INK4a</sup> in CD8<sup>+</sup> lymphocytes was also lower in patients versus controls. Chronic latent CMV infection was associated with increased senescent CD8<sup>+</sup> lymphocytes in healthy controls, but this shift was less apparent in PD patients.<h4>Conclusions</h4>Taken together, our data demonstrate a reduction in CD8<sup>+</sup> T cell replicative senescence which is present at the earliest stages of Parkinson's disease.",,pdf:https://jneuroinflammation.biomedcentral.com/track/pdf/10.1186/s12974-021-02287-9; doi:https://doi.org/10.1186/s12974-021-02287-9; html:https://europepmc.org/articles/PMC8513368; pdf:https://europepmc.org/articles/PMC8513368?pdf=render
 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,,,"<h4>Objective</h4>To develop a tool predicting individualised treatment for gonorrhoea, enabling treatment with previously recommended antibiotics, to reduce use of last-line treatment ceftriaxone.<h4>Design</h4>A modelling study.<h4>Setting</h4>England and Wales.<h4>Participants</h4>Individuals accessing sentinel health services.<h4>Intervention</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e042893.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042893; html:https://europepmc.org/articles/PMC8237724; pdf:https://europepmc.org/articles/PMC8237724?pdf=render
-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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:http://www.internationaljournalofcardiology.com/article/S0167527320338341/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.09.053
 31073125,https://doi.org/10.1038/s41533-019-0132-z,Systematic review of clinical prediction models to support the diagnosis of asthma in primary care.,"Daines L, McLean S, Buelo A, Lewis S, Sheikh A, Pinnock H.",,NPJ primary care respiratory medicine,2019,2019-05-09,Y,,The Human Phenome,,"Diagnosing asthma is challenging. Misdiagnosis can lead to untreated symptoms, incorrect treatment and avoidable deaths. The best combination of clinical features and tests to achieve a diagnosis of asthma is unclear. As asthma is usually diagnosed in non-specialist settings, a clinical prediction model to aid the assessment of the probability of asthma in primary care may improve diagnostic accuracy. We aimed to identify and describe existing prediction models to support the diagnosis of asthma in children and adults in primary care. We searched Medline, Embase, CINAHL, TRIP and US National Guidelines Clearinghouse databases from 1 January 1990 to 23 November 17. We included prediction models designed for use in primary care or equivalent settings to aid the diagnostic decision-making of clinicians assessing patients with symptoms suggesting asthma. Two reviewers independently screened titles, abstracts and full texts for eligibility, extracted data and assessed risk of bias. From 13,798 records, 53 full-text articles were reviewed. We included seven modelling studies; all were at high risk of bias. Model performance varied, and the area under the receiving operating characteristic curve ranged from 0.61 to 0.82. Patient-reported wheeze, symptom variability and history of allergy or allergic rhinitis were associated with asthma. In conclusion, clinical prediction models may support the diagnosis of asthma in primary care, but existing models are at high risk of bias and thus unreliable for informing practice. Future studies should adhere to recognised standards, conduct model validation and include a broader range of clinical data to derive a prediction model of value for clinicians.",,pdf:https://www.nature.com/articles/s41533-019-0132-z.pdf; doi:https://doi.org/10.1038/s41533-019-0132-z; html:https://europepmc.org/articles/PMC6509212; pdf:https://europepmc.org/articles/PMC6509212?pdf=render
+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,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:http://www.internationaljournalofcardiology.com/article/S0167527320338341/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.09.053
 32032817,https://doi.org/10.1016/j.nicl.2020.102172,Distinguishing between paediatric brain tumour types using multi-parametric magnetic resonance imaging and machine learning: A multi-site study.,"Grist JT, Withey S, MacPherson L, Oates A, Powell S, Novak J, Abernethy L, Pizer B, Grundy R, Bailey S, Mitra D, Arvanitis TN, Auer DP, Avula S, Peet AC.",,NeuroImage. Clinical,2020,2020-01-23,Y,Diffusion; Perfusion; Machine Learning,Understanding the Causes of Disease,cancer and neoplasms,"The imaging and subsequent accurate diagnosis of paediatric brain tumours presents a radiological challenge, with magnetic resonance imaging playing a key role in providing tumour specific imaging information. Diffusion weighted and perfusion imaging are commonly used to aid the non-invasive diagnosis of children's brain tumours, but are usually evaluated by expert qualitative review. Quantitative studies are mainly single centre and single modality. The aim of this work was to combine multi-centre diffusion and perfusion imaging, with machine learning, to develop machine learning based classifiers to discriminate between three common paediatric tumour types. The results show that diffusion and perfusion weighted imaging of both the tumour and whole brain provide significant features which differ between tumour types, and that combining these features gives the optimal machine learning classifier with >80% predictive precision. This work represents a step forward to aid in the non-invasive diagnosis of paediatric brain tumours, using advanced clinical imaging.",Grist et al. team trained computers to analyse brain images from children for identification of tumours. They’ve shown that applying analytical methods to enable machine distinguishes between the entire brain area and the tumour area in the images more than 80% improves how machine analyses the image to identify exact tumour area. ,doi:https://doi.org/10.1016/j.nicl.2020.102172; doi:https://doi.org/10.1016/j.nicl.2020.102172; html:https://europepmc.org/articles/PMC7005468; pdf:https://europepmc.org/articles/PMC7005468?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.",,pdf:https://www.nature.com/articles/s41467-021-27950-w.pdf; doi:https://doi.org/10.1038/s41467-021-27950-w; html:https://europepmc.org/articles/PMC8752864; pdf:https://europepmc.org/articles/PMC8752864?pdf=render
 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,,,"<h4>Background</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.",,pdf:http://www.internationaljournalofcardiology.com/article/S016752732031679X/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.04.068
@@ -1936,8 +1936,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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,,,"<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>ClinicalTrials.gov NCT04435041; https://clinicaltrials.gov/ct2/show/NCT04435041.<h4>International registered report identifier (irrid)</h4>DERR1-10.2196/30083.",,pdf:https://www.researchprotocols.org/2021/10/e30083/PDF; doi:https://doi.org/10.2196/30083; html:https://europepmc.org/articles/PMC8494068
 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,,,,,,pdf:https://academic.oup.com/ije/article-pdf/48/3/678/29005217/dyz073.pdf; doi:https://doi.org/10.1093/ije/dyz073; html:https://europepmc.org/articles/PMC6659362; pdf:https://europepmc.org/articles/PMC6659362?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Bill & Melinda Gates Foundation, National Institute on Minority Health and Health Disparities, and National Heart, Lung, and Blood Institute.",,pdf:http://www.thelancet.com/article/S0140673621016093/pdf; 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
-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,,,,"<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003907&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003907; html:https://europepmc.org/articles/PMC8887739; pdf:https://europepmc.org/articles/PMC8887739?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 development<sup>1,2</sup>. 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 arborization<sup>3,4</sup>. 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.",,pdf:https://discovery.ucl.ac.uk/10110799/1/Meyer_accepted_version.pdf; 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
+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,,,,"<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003907&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003907; html:https://europepmc.org/articles/PMC8887739; pdf:https://europepmc.org/articles/PMC8887739?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,,,"<h4>Background</h4>Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCM<sub>SMP</sub>), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCM<sub>SMN</sub>). Genotype-specific differences have been reported in cardiac function. Moreover, HCM<sub>SMN</sub> patients have later disease onset and a better prognosis than HCM<sub>SMP</sub> 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.<h4>Methods</h4>A proteomics screen was performed in cardiac tissue from 39 HCM<sub>SMP</sub> patients, 11HCM<sub>SMN</sub> patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novel <i>MYBPC3</i><sub>2373insG</sub> mouse model was used to confirm functional relevance of our proteomic findings.<h4>Results</h4>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 HCM<sub>SMP</sub> than in HCM<sub>SMN</sub> and controls. Higher tubulin detyrosination was also found in 2 unrelated <i>MYBPC3</i> mouse models and its inhibition with parthenolide normalized contraction and relaxation time of isolated cardiomyocytes.<h4>Conclusions</h4>Our findings indicate that microtubules and especially its detyrosination contribute to the pathomechanism of patients with HCM<sub>SMP</sub>. This is of clinical importance since it represents a potential treatment target to improve cardiac function in patients with HCM<sub>SMP</sub>, whereas a beneficial effect may be limited in patients with HCM<sub>SMN</sub>.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.120.007022; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.120.007022; html:https://europepmc.org/articles/PMC7819533; pdf:https://europepmc.org/articles/PMC7819533?pdf=render
 30981377,https://doi.org/10.1016/j.aap.2019.03.007,How much space do drivers provide when passing cyclists? Understanding the impact of motor vehicle and infrastructure characteristics on passing distance.,"Beck B, Chong D, Olivier J, Perkins M, Tsay A, Rushford A, Li L, Cameron P, Fry R, Johnson M.",,Accident; analysis and prevention,2019,2019-04-10,N,Road Infrastructure; Overtaking; Cyclist Safety; Passing Distance,,,"<h4>Background</h4>Understanding factors that influence the distance that drivers provide when passing cyclists is critical to reducing subjective risk and improving cycling participation. This study aimed to quantify passing distance and assess the impact of motor vehicle and road infrastructure characteristics on passing distance.<h4>Methods</h4>An on-road observational study was conducted in Victoria, Australia. Participants had a custom device installed on their bicycle and rode as per their usual cycling for one to two weeks. A hierarchical linear model was used to investigate the relationship between motor vehicle and infrastructure characteristics (location, presence of on-road marked bicycle lane and the presence of parked cars on the kerbside) and passing distance (defined as the lateral distance between the end of the bicycle handlebars and the passing motor vehicle).<h4>Results</h4>Sixty cyclists recorded 18,527 passing events over 422 trips. The median passing distance was 173 cm (Q1: 137 cm, Q3: 224 cm) and 1085 (5.9%) passing events were less than 100 cm. Relative to sedans, 4WDs had a reduced mean passing distance of 15 cm (Q1: 12 cm, Q3: 17 cm) and buses had a reduced mean passing distance of 28 cm (Q1: 16 cm, Q3: 40 cm). Relative to passing events that occurred on roads without a marked bicycle lane and without parked cars, passing events on roads with a bike lane with no parked cars had a reduced mean passing distance of 27 cm (Q1: 25 cm, Q3: 29 cm), and passing events on roads with a bike lane and parked cars had a mean lower passing distance of 40 cm (Q1: 37 cm, Q3: 43 cm).<h4>Conclusions</h4>One in every 17 passing events was a close (<100 cm) passing event. We identified that on-road bicycle lanes and parked cars reduced passing distance. These data can be used to inform the selection and design of cycling-related infrastructure and road use with the aim of improving safety for cyclists.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa50030/Download/0050030-20052019102229.pdf; doi:https://doi.org/10.1016/j.aap.2019.03.007
 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,,"<h4>Objectives</h4>To investigate recorded poor insight in relation to mental health and service use outcomes in a cohort with first-episode psychosis.<h4>Design</h4>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.<h4>Setting</h4>The clinical record text at the South London and Maudsley National Health Service Trust in the UK was used.<h4>Participants</h4>We applied the algorithm to characterise a cohort of 2026 patients with first-episode psychosis attending an early intervention service.<h4>Primary and secondary outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/6/e028929.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-028929; html:https://europepmc.org/articles/PMC6577359; pdf:https://europepmc.org/articles/PMC6577359?pdf=render
@@ -1956,8 +1956,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 35142634,https://doi.org/10.2196/31885,Investigating Genetic and Other Determinants of First-Onset Myocardial Infarction in Malaysia: Protocol for the Malaysian Acute Vascular Events Risk Study.,"Chowdhury R, Noh MFM, Ismail SR, van Daalen KR, Kamaruddin PSNM, Zulkiply SH, Azizul NH, Khalid NM, Ali A, Idris IM, Mei YS, Abdullah SR, Faridus N, Yusof NAM, Yusoff NNFM, Jamal R, Rahim AAA, Ghapar AKA, Radhakrishnan AK, Fong AYY, Ismail O, Krishinan S, Lee CY, Bang LH, Mageswaren E, Mahendran K, Amin NHM, Muthusamy G, Jin AOH, Ramli AW, Ross NT, Ruhani AI, Yahya M, Yusoff Y, Abidin SKZ, Amado L, Bolton T, Weston S, Crawte J, Ovenden N, Michielsen A, Monower MM, Mahiyuddin WRW, Wood A, Di Angelantonio E, Sulaiman NS, Danesh J, Butterworth AS.",,JMIR research protocols,2022,2022-02-10,Y,Myocardial infarction; Malaysia; Cardiovascular disease; Case-control study,,,"<h4>Background</h4>Although the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse.<h4>Objective</h4>The Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results.<h4>Methods</h4>By June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire.<h4>Results</h4>Tobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P<.001), previous smoking (OR 1.34, 95% CI 1.12-1.60; P=.001), a history of high blood pressure (OR 2.13, 95% CI 1.86-2.44; P<.001), a history of diabetes mellitus (OR 2.72, 95% CI 2.34-3.17; P<.001), a family history of coronary heart disease (OR 1.28, 95% CI 1.07-1.55; P=.009), and obesity (BMI >30 kg/m<sup>2</sup>; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models.<h4>Conclusions</h4>The MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action.<h4>International registered report identifier (irrid)</h4>RR1-10.2196/31885.",,pdf:https://www.researchprotocols.org/2022/2/e31885/PDF; doi:https://doi.org/10.2196/31885; html:https://europepmc.org/articles/PMC8874931
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S2213260021001648/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00164-8; html:https://europepmc.org/articles/PMC8410610
 34458849,https://doi.org/10.1093/oxfimm/iqab014,Protease inhibitor plasma concentrations associate with COVID-19 infection.,"Medjeral-Thomas NR, Troldborg A, Hansen AG, Pihl R, Clarke CL, Peters JE, Thomas DC, Willicombe M, Palarasah Y, Botto M, Pickering MC, Thiel S.",,Oxford open immunology,2021,2021-07-07,Y,Coronavirus; Protease inhibitors; innate immunity; Covid-19,,,"Protease inhibitors influence a range of innate immunity and inflammatory pathways. We quantified plasma concentrations of key anti-inflammatory protease inhibitors in chronic haemodialysis patients with coronavirus disease 2019 (COVID-19). The samples were collected early in the disease course to determine whether plasma protease inhibitor levels associated with the presence and severity of COVID-19. We used antibody-based immunoassays to measure plasma concentrations of C1 esterase inhibitor, alpha2-macroglobulin, antithrombin and inter-alpha-inhibitor heavy chain 4 (ITIH4) in 100 serial samples from 27 haemodialysis patients with COVID-19. ITIH4 was tested in two assays, one measuring intact ITIH4 and another also detecting any fragmented ITIH4 (total ITIH4). Control cohorts were 32 haemodialysis patients without COVID-19 and 32 healthy controls. We compared protease inhibitor concentration based on current and future COVID-19 severity and with C-reactive protein. Results were adjusted for repeated measures and multiple comparisons. Analysis of all available samples demonstrated lower plasma C1 esterase inhibitor and α2M and higher total ITIH4 in COVID-19 compared with dialysis controls. These differences were also seen in the first sample collected after COVID-19 diagnosis, a median of 4 days from diagnostic swab. Plasma ITIH4 levels were higher in severe than the non-severe COVID-19. Serum C-reactive protein correlated positively with plasma levels of antithrombin, intact ITIH4 and total ITIH4. In conclusion, plasma protease inhibitor concentrations are altered in COVID-19.",,pdf:https://academic.oup.com/ooim/article-pdf/2/1/iqab014/48744499/iqab014.pdf; doi:https://doi.org/10.1093/oxfimm/iqab014; html:https://europepmc.org/articles/PMC8371939; pdf:https://europepmc.org/articles/PMC8371939?pdf=render
-33332257,https://doi.org/10.1099/mgen.0.000434,Read trimming has minimal effect on bacterial SNP-calling accuracy. ,Bush SJ.,,Microbial genomics,2020,2020-12-11,Y,,,,"Read alignment is the central step of many analytic pipelines that perform variant calling. To reduce error, it is common practice to pre-process raw sequencing reads to remove low-quality bases and residual adapter contamination, a procedure collectively known as 'trimming'. Trimming is widely assumed to increase the accuracy of variant calling, although there are relatively few systematic evaluations of its effects and no clear consensus on its efficacy. As sequencing datasets increase both in number and size, it is worthwhile reappraising computational operations of ambiguous benefit, particularly when the scope of many analyses now routinely incorporates thousands of samples, increasing the time and cost required. Using a curated set of 17 Gram-negative bacterial genomes, this study initially evaluated the impact of four read-trimming utilities (Atropos, fastp, Trim Galore and Trimmomatic), each used with a range of stringencies, on the accuracy and completeness of three bacterial SNP-calling pipelines. It was found that read trimming made only small, and statistically insignificant, increases in SNP-calling accuracy even when using the highest-performing pre-processor in this study, fastp. To extend these findings, >6500 publicly archived sequencing datasets from Escherichia coli, Mycobacterium tuberculosis and Staphylococcus aureus were re-analysed using a common analytic pipeline. Of the approximately 125 million SNPs and 1.25 million indels called across all samples, the same bases were called in 98.8 and 91.9 % of cases, respectively, irrespective of whether raw reads or trimmed reads were used. Nevertheless, the proportion of mixed calls (i.e. calls where <100 % of the reads support the variant allele; considered a proxy of false positives) was significantly reduced after trimming, which suggests that while trimming rarely alters the set of variant bases, it can affect the proportion of reads supporting each call. It was concluded that read quality- and adapter-trimming add relatively little value to a SNP-calling pipeline and may only be necessary if small differences in the absolute number of SNP calls, or the false call rate, are critical. Broadly similar conclusions can be drawn about the utility of trimming to an indel-calling pipeline. Read trimming remains routinely performed prior to variant calling likely out of concern that doing otherwise would typically have negative consequences. While historically this may have been the case, the data in this study suggests that read trimming is not always a practical necessity.",,doi:https://doi.org/10.1099/mgen.0.000434; doi:https://doi.org/10.1099/mgen.0.000434; html:https://europepmc.org/articles/PMC8116680; pdf:https://europepmc.org/articles/PMC8116680?pdf=render
 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.",,pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.190297; doi:https://doi.org/10.1098/rsob.190297; html:https://europepmc.org/articles/PMC7241076; pdf:https://europepmc.org/articles/PMC7241076?pdf=render
+33332257,https://doi.org/10.1099/mgen.0.000434,Read trimming has minimal effect on bacterial SNP-calling accuracy. ,Bush SJ.,,Microbial genomics,2020,2020-12-11,Y,,,,"Read alignment is the central step of many analytic pipelines that perform variant calling. To reduce error, it is common practice to pre-process raw sequencing reads to remove low-quality bases and residual adapter contamination, a procedure collectively known as 'trimming'. Trimming is widely assumed to increase the accuracy of variant calling, although there are relatively few systematic evaluations of its effects and no clear consensus on its efficacy. As sequencing datasets increase both in number and size, it is worthwhile reappraising computational operations of ambiguous benefit, particularly when the scope of many analyses now routinely incorporates thousands of samples, increasing the time and cost required. Using a curated set of 17 Gram-negative bacterial genomes, this study initially evaluated the impact of four read-trimming utilities (Atropos, fastp, Trim Galore and Trimmomatic), each used with a range of stringencies, on the accuracy and completeness of three bacterial SNP-calling pipelines. It was found that read trimming made only small, and statistically insignificant, increases in SNP-calling accuracy even when using the highest-performing pre-processor in this study, fastp. To extend these findings, >6500 publicly archived sequencing datasets from Escherichia coli, Mycobacterium tuberculosis and Staphylococcus aureus were re-analysed using a common analytic pipeline. Of the approximately 125 million SNPs and 1.25 million indels called across all samples, the same bases were called in 98.8 and 91.9 % of cases, respectively, irrespective of whether raw reads or trimmed reads were used. Nevertheless, the proportion of mixed calls (i.e. calls where <100 % of the reads support the variant allele; considered a proxy of false positives) was significantly reduced after trimming, which suggests that while trimming rarely alters the set of variant bases, it can affect the proportion of reads supporting each call. It was concluded that read quality- and adapter-trimming add relatively little value to a SNP-calling pipeline and may only be necessary if small differences in the absolute number of SNP calls, or the false call rate, are critical. Broadly similar conclusions can be drawn about the utility of trimming to an indel-calling pipeline. Read trimming remains routinely performed prior to variant calling likely out of concern that doing otherwise would typically have negative consequences. While historically this may have been the case, the data in this study suggests that read trimming is not always a practical necessity.",,doi:https://doi.org/10.1099/mgen.0.000434; doi:https://doi.org/10.1099/mgen.0.000434; html:https://europepmc.org/articles/PMC8116680; pdf:https://europepmc.org/articles/PMC8116680?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,,,"<h4>Purpose</h4>To prospectively validate two risk scores to predict mortality (4C Mortality) and in-hospital deterioration (4C Deterioration) among adults hospitalised with COVID-19.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.<h4>Trial registration number</h4>ISRCTN66726260.",,pdf:https://thorax.bmj.com/content/thoraxjnl/77/6/606.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-217629; html:https://europepmc.org/articles/PMC8610617; pdf:https://europepmc.org/articles/PMC8610617?pdf=render
 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,,,"<h4>Objective</h4>To investigate the associations of symptoms of mania and depression with clinical outcomes in people with unipolar depression.<h4>Design</h4>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.<h4>Setting</h4>The South London and Maudsley Clinical Record Interactive Search database.<h4>Participants</h4>All patients presenting with unipolar depression between 1 April 2006 and 31 March 2018.<h4>Exposure</h4>(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.<h4>Main outcomes</h4>(1) Bipolar or psychotic disorder diagnosis. (2) Psychiatric hospital admission.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056541.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056541; html:https://europepmc.org/articles/PMC9058769; pdf:https://europepmc.org/articles/PMC9058769?pdf=render
 37923486,https://doi.org/10.1016/s2352-3018(23)00233-3,Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration.,"Rein SM, Lodi S, Logan RW, Touloumi G, Antoniadou A, Wittkop L, Bonnet F, van Sighem A, van der Valk M, Reiss P, Klein MB, Young J, Jarrin I, d'Arminio Monforte A, Tavelli A, Meyer L, Tran L, Gill MJ, Lang R, Surial B, Haas AD, Justice AC, Rentsch CT, Phillips A, Sabin CA, Miro JM, Trickey A, Ingle SM, Sterne JAC, Hernán MA, Antiretroviral Therapy Cohort Collaboration and the HIV-CAUSAL Collaboration.",,The lancet. HIV,2023,2023-11-01,N,,,,"<h4>Background</h4>A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events.<h4>Methods</h4>We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (≤50 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates.<h4>Findings</h4>The analysis in ART-naive individuals included 10 767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (-0·43 to 0·36). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373 965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference -0·068% (-0·60 to 0·52).<h4>Interpretation</h4>We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV.<h4>Funding</h4>National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism.",,doi:https://doi.org/10.1016/S2352-3018(23)00233-3
@@ -1986,8 +1986,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 31792462,https://doi.org/10.1038/s41591-019-0665-2,Plasma protein patterns as comprehensive indicators of health.,"Williams SA, Kivimaki M, Langenberg C, Hingorani AD, Casas JP, Bouchard C, Jonasson C, Sarzynski MA, Shipley MJ, Alexander L, Ash J, Bauer T, Chadwick J, Datta G, DeLisle RK, Hagar Y, Hinterberg M, Ostroff R, Weiss S, Ganz P, Wareham NJ.",,Nature medicine,2019,2019-12-02,N,,,,"Proteins are effector molecules that mediate the functions of genes<sup>1,2</sup> and modulate comorbidities<sup>3-10</sup>, behaviors and drug treatments<sup>11</sup>. They represent an enormous potential resource for personalized, systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized health assessment across many health conditions simultaneously has not been tested. Here, we show that plasma protein expression patterns strongly encode for multiple different health states, future disease risks and lifestyle behaviors. We developed and validated protein-phenotype models for 11 different health indicators: liver fat, kidney filtration, percentage body fat, visceral fat mass, lean body mass, cardiopulmonary fitness, physical activity, alcohol consumption, cigarette smoking, diabetes risk and primary cardiovascular event risk. The analyses were prospectively planned, documented and executed at scale on archived samples and clinical data, with a total of ~85 million protein measurements in 16,894 participants. Our proof-of-concept study demonstrates that protein expression patterns reliably encode for many different health issues, and that large-scale protein scanning<sup>12-16</sup> coupled with machine learning is viable for the development and future simultaneous delivery of multiple measures of health. We anticipate that, with further validation and the addition of more protein-phenotype models, this approach could enable a single-source, individualized so-called liquid health check.",,pdf:https://europepmc.org/articles/pmc6922049?pdf=render; doi:https://doi.org/10.1038/s41591-019-0665-2; html:https://europepmc.org/articles/PMC6922049; pdf:https://europepmc.org/articles/PMC6922049?pdf=render; doi:https://doi.org/10.1038/s41591-019-0665-2
 34609275,https://doi.org/10.1099/mgen.0.000630,"A genomic epidemiological study shows that prevalence of antimicrobial resistance in <i>Enterobacterales</i> is associated with the livestock host, as well as antimicrobial usage.","AbuOun M, Jones H, Stubberfield E, Gilson D, Shaw LP, Hubbard ATM, Chau KK, Sebra R, Peto TEA, Crook DW, Read DS, Gweon HS, Walker AS, Stoesser N, Smith RP, Anjum MF, On Behalf Of The Rehab Consortium.",,Microbial genomics,2021,2021-10-01,Y,Plasmid; Livestock; Antimicrobial resistance; Antimicrobial Usage,,,,,doi:https://doi.org/10.1099/mgen.0.000630; doi:https://doi.org/10.1099/mgen.0.000630; html:https://europepmc.org/articles/PMC8627209; pdf:https://europepmc.org/articles/PMC8627209?pdf=render
 36568709,https://doi.org/10.1136/bmjmed-2022-000215,Burden and treatment of chronic obstructive pulmonary disease among people using illicit opioids: matched cohort study in England.,"Lewer D, Cox S, Hurst JR, Padmanathan P, Petersen I, Quint JK.",,BMJ medicine,2022,2022-09-28,Y,"Substance-related disorders; Pulmonary disease, chronic obstructive; epidemiology; Health Services; Primary Health Care; Healthcare Disparities",,,"<h4>Objective</h4>To understand the burden of chronic obstructive pulmonary disease among people who use illicit opioids such as heroin, and evaluate inequalities in treatment.<h4>Design</h4>Cohort study.<h4>Setting</h4>Patients registered at primary care practices in England.<h4>Participants</h4>106 789 patients in the Clinical Practice Research Datalink with illicit opioid use recorded between 2001 and 2018, and a subcohort of 3903 patients with a diagnosis of chronic obstructive pulmonary disease. For both cohorts, the study sampled a comparison group with no history of illicit opioids that was matched by age, sex, and general practice.<h4>Main outcome measures</h4>In the base cohort: diagnosis of chronic obstructive pulmonary disease and death due to the disease. In the subcohort: five treatments (influenza vaccine, pneumococcal vaccine, pulmonary rehabilitation, bronchodilators or corticosteroids, and smoking cessation support) and exacerbations requiring hospital admission.<h4>Results</h4>680 of 106 789 participants died due to chronic obstructive pulmonary disease, representing 5.1% of all cause deaths. Illicit opioid use was associated with 14.59 times (95% confidence interval 12.28 to 17.33) the risk of death related to chronic obstructive pulmonary disease, and 5.89 times (5.62 to 6.18) the risk of a diagnosis of the disease. Among patients with a new diagnosis, comorbid illicit opioid use was associated with current smoking, underweight, worse lung function, and more severe breathlessness. After adjusting for these differences, illicit opioids were associated with 1.96 times (1.82 to 2.12) times the risk of exacerbations requiring hospital admission, but not associated with a substantially different probability of the five treatments.<h4>Conclusions</h4>Death due to chronic obstructive pulmonary disease is about 15 times more common among people who use illicit opioids than the general population. This inequality does not appear to be explained by differences in treatment, but late diagnosis of the disease among people who use illicit opioids might contribute.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000215.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000215; html:https://europepmc.org/articles/PMC9770021; pdf:https://europepmc.org/articles/PMC9770021?pdf=render
-37173061,https://doi.org/10.1016/j.ajcnut.2022.12.021,"Evidence for human milk as a biological system and recommendations for study design-a report from ""Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)"" Working Group 4.","Donovan SM, Aghaeepour N, Andres A, Azad MB, Becker M, Carlson SE, Järvinen KM, Lin W, Lönnerdal B, Slupsky CM, Steiber AL, Raiten DJ.",,The American journal of clinical nutrition,2023,2023-04-01,Y,Immune; systems biology; Human Milk; Microbiome; Infant Development,,,"Human milk contains all of the essential nutrients required by the infant within a complex matrix that enhances the bioavailability of many of those nutrients. In addition, human milk is a source of bioactive components, living cells and microbes that facilitate the transition to life outside the womb. Our ability to fully appreciate the importance of this matrix relies on the recognition of short- and long-term health benefits and, as highlighted in previous sections of this supplement, its ecology (i.e., interactions among the lactating parent and breastfed infant as well as within the context of the human milk matrix itself). Designing and interpreting studies to address this complexity depends on the availability of new tools and technologies that account for such complexity. Past efforts have often compared human milk to infant formula, which has provided some insight into the bioactivity of human milk, as a whole, or of individual milk components supplemented with formula. However, this experimental approach cannot capture the contributions of the individual components to the human milk ecology, the interaction between these components within the human milk matrix, or the significance of the matrix itself to enhance human milk bioactivity on outcomes of interest. This paper presents approaches to explore human milk as a biological system and the functional implications of that system and its components. Specifically, we discuss study design and data collection considerations and how emerging analytical technologies, bioinformatics, and systems biology approaches could be applied to advance our understanding of this critical aspect of human biology.",,doi:https://doi.org/10.1016/j.ajcnut.2022.12.021; html:https://europepmc.org/articles/PMC10356565; pdf:https://europepmc.org/articles/PMC10356565?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,,,"<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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
+37173061,https://doi.org/10.1016/j.ajcnut.2022.12.021,"Evidence for human milk as a biological system and recommendations for study design-a report from ""Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)"" Working Group 4.","Donovan SM, Aghaeepour N, Andres A, Azad MB, Becker M, Carlson SE, Järvinen KM, Lin W, Lönnerdal B, Slupsky CM, Steiber AL, Raiten DJ.",,The American journal of clinical nutrition,2023,2023-04-01,Y,Immune; systems biology; Human Milk; Microbiome; Infant Development,,,"Human milk contains all of the essential nutrients required by the infant within a complex matrix that enhances the bioavailability of many of those nutrients. In addition, human milk is a source of bioactive components, living cells and microbes that facilitate the transition to life outside the womb. Our ability to fully appreciate the importance of this matrix relies on the recognition of short- and long-term health benefits and, as highlighted in previous sections of this supplement, its ecology (i.e., interactions among the lactating parent and breastfed infant as well as within the context of the human milk matrix itself). Designing and interpreting studies to address this complexity depends on the availability of new tools and technologies that account for such complexity. Past efforts have often compared human milk to infant formula, which has provided some insight into the bioactivity of human milk, as a whole, or of individual milk components supplemented with formula. However, this experimental approach cannot capture the contributions of the individual components to the human milk ecology, the interaction between these components within the human milk matrix, or the significance of the matrix itself to enhance human milk bioactivity on outcomes of interest. This paper presents approaches to explore human milk as a biological system and the functional implications of that system and its components. Specifically, we discuss study design and data collection considerations and how emerging analytical technologies, bioinformatics, and systems biology approaches could be applied to advance our understanding of this critical aspect of human biology.",,doi:https://doi.org/10.1016/j.ajcnut.2022.12.021; html:https://europepmc.org/articles/PMC10356565; pdf:https://europepmc.org/articles/PMC10356565?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,,,,,,pdf:https://academic.oup.com/ije/article-pdf/52/1/e38/49127215/dyac171.pdf; doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render
 36697134,https://doi.org/10.1016/j.jacc.2022.10.034,Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis.,"Ćorović A, Wall C, Nus M, Gopalan D, Huang Y, Imaz M, Zulcinski M, Peverelli M, Uryga A, Lambert J, Bressan D, Maughan RT, Pericleous C, Dubash S, Jordan N, Jayne DR, Hoole SP, Calvert PA, Dean AF, Rassl D, Barwick T, Iles M, Frontini M, Hannon G, Manavaki R, Fryer TD, Aloj L, Graves MJ, Gilbert FJ, Dweck MR, Newby DE, Fayad ZA, Reynolds G, Morgan AW, Aboagye EO, Davenport AP, Jørgensen HF, Mallat Z, Bennett MR, Peters JE, Rudd JHF, Mason JC, Tarkin JM.",,Journal of the American College of Cardiology,2023,2023-01-01,Y,Atherosclerosis; Inflammation; Molecular Imaging; Giant Cell Arteritis; Takayasu Arteritis; Somatostatin Receptor,,,"<h4>Background</h4>Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures.<h4>Objectives</h4>We aimed to investigate somatostatin receptor 2 (SST<sub>2</sub>) as a novel inflammation-specific molecular imaging target in LVV.<h4>Methods</h4>In a prospective, observational cohort study, in vivo arterial SST<sub>2</sub> expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using <sup>68</sup>Ga-DOTATATE and <sup>18</sup>F-FET-βAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing.<h4>Results</h4>Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST<sub>2</sub> maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST<sub>2</sub> signal was not elevated in any of the control subjects. SST<sub>2</sub> PET/MRI was generally consistent with <sup>18</sup>F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST<sub>2</sub> maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST<sub>2</sub> expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers.<h4>Conclusions</h4>SST<sub>2</sub> PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810).",,doi:https://doi.org/10.1016/j.jacc.2022.10.034; doi:https://doi.org/10.1016/j.jacc.2022.10.034; html:https://europepmc.org/articles/PMC9883634; pdf:https://europepmc.org/articles/PMC9883634?pdf=render
 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",,pdf:https://openres.ersjournals.com/content/erjor/early/2023/01/26/23120541.00274-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00274-2022; html:https://europepmc.org/articles/PMC9790090; pdf:https://europepmc.org/articles/PMC9790090?pdf=render
@@ -1999,11 +1999,11 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 31478583,https://doi.org/10.1002/ejhf.1615,Association between beta-blocker use and mortality/morbidity in older patients with heart failure with reduced ejection fraction. A propensity score-matched analysis from the Swedish Heart Failure Registry.,"Stolfo D, Uijl A, Benson L, Schrage B, Fudim M, Asselbergs FW, Koudstaal S, Sinagra G, Dahlström U, Rosano G, Savarese G.",,European journal of heart failure,2020,2019-10-23,N,Elderly; Heart Failure; Beta-blocker; Registry; Swedehf,Improving Public Health,cardiovascular,"<h4>Background</h4>Beta-blockers reduce mortality and morbidity in heart failure (HF) with reduced ejection fraction (HFrEF). However, patients older than 80 years are poorly represented in randomized controlled trials. We assessed the association between beta-blocker use and outcomes in HFrEF patients aged ≥80 years.<h4>Methods and results</h4>We included patients with an ejection fraction <40% and aged ≥80 years from the Swedish HF Registry. The association between beta-blocker use, all-cause mortality and cardiovascular (CV) mortality/HF hospitalization was assessed by Cox proportional hazard models in a 1:1 propensity score-matched cohort. To assess consistency, the same analyses were performed in a positive control cohort with age <80 years. A negative control outcome analysis was run using hospitalization for cancer as endpoint. Of 6562 patients aged ≥80 years, 5640 (86%) received beta-blockers. In the matched cohort including 1732 patients, beta-blocker use was associated with a significant reduction in the risk of all-cause mortality [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.79-0.99]. Reduction in CV mortality/HF hospitalization was not significant (HR 0.94, 95% CI 0.85-1.05) due to the lack of association with HF hospitalization, whereas CV death was significantly reduced. After adjustment rather than matching for the propensity score in the overall cohort, beta-blocker use was associated with reduced risk of all outcomes. In patients aged <80 years, use of beta-blockers was associated with reduced risk of all-cause death (HR 0.79, 95% CI 0.68-0.92) and of the composite outcome (HR 0.88, 95% CI 0.77-0.99).<h4>Conclusions</h4>In HFrEF patients ≥80 years of age, use of beta-blockers was high and was associated with improved all-cause and CV survival.",This study looked at 6562 people with severe heart failure and whether there was an association between taking beta-blockers (a drug to control heart rate) and heart disease. They used a national Swedish registry of patients with heart failure and compared those who were taking beta blockers (866 patients) to those not taking beta blockers (866 patients). The study found that patients who were taking beta blockers tended also to have lower risk of heart complications and were more likely to survive.,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.1615; doi:https://doi.org/10.1002/ejhf.1615
 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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>https://doi.org/10.17605/OSF.IO/PMYTA.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e059258.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059258; html:https://europepmc.org/articles/PMC9083394; pdf:https://europepmc.org/articles/PMC9083394?pdf=render
 36914875,https://doi.org/10.1038/s41588-023-01314-0,Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.,"Shrine N, Izquierdo AG, Chen J, Packer R, Hall RJ, Guyatt AL, Batini C, Thompson RJ, Pavuluri C, Malik V, Hobbs BD, Moll M, Kim W, Tal-Singer R, Bakke P, Fawcett KA, John C, Coley K, Piga NN, Pozarickij A, Lin K, Millwood IY, Chen Z, Li L, China Kadoorie Biobank Collaborative Group, Wijnant SRA, Lahousse L, Brusselle G, Uitterlinden AG, Manichaikul A, Oelsner EC, Rich SS, Barr RG, Kerr SM, Vitart V, Brown MR, Wielscher M, Imboden M, Jeong A, Bartz TM, Gharib SA, Flexeder C, Karrasch S, Gieger C, Peters A, Stubbe B, Hu X, Ortega VE, Meyers DA, Bleecker ER, Gabriel SB, Gupta N, Smith AV, Luan J, Zhao JH, Hansen AF, Langhammer A, Willer C, Bhatta L, Porteous D, Smith BH, Campbell A, Sofer T, Lee J, Daviglus ML, Yu B, Lim E, Xu H, O'Connor GT, Thareja G, Albagha OME, Qatar Genome Program Research (QGPR) Consortium, Suhre K, Granell R, Faquih TO, Hiemstra PS, Slats AM, Mullin BH, Hui J, James A, Beilby J, Patasova K, Hysi P, Koskela JT, Wyss AB, Jin J, Sikdar S, Lee M, May-Wilson S, Pirastu N, Kentistou KA, Joshi PK, Timmers PRHJ, Williams AT, Free RC, Wang X, Morrison JL, Gilliland FD, Chen Z, Wang CA, Foong RE, Harris SE, Taylor A, Redmond P, Cook JP, Mahajan A, Lind L, Palviainen T, Lehtimäki T, Raitakari OT, Kaprio J, Rantanen T, Pietiläinen KH, Cox SR, Pennell CE, Hall GL, Gauderman WJ, Brightling C, Wilson JF, Vasankari T, Laitinen T, Salomaa V, Mook-Kanamori DO, Timpson NJ, Zeggini E, Dupuis J, Hayward C, Brumpton B, Langenberg C, Weiss S, Homuth G, Schmidt CO, Probst-Hensch N, Jarvelin MR, Morrison AC, Polasek O, Rudan I, Lee JH, Sayers I, Rawlins EL, Dudbridge F, Silverman EK, Strachan DP, Walters RG, Morris AP, London SJ, Cho MH, Wain LV, Hall IP, Tobin MD.",,Nature genetics,2023,2023-03-13,Y,,,,"Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.",,pdf:https://www.nature.com/articles/s41588-023-01314-0.pdf; doi:https://doi.org/10.1038/s41588-023-01314-0; html:https://europepmc.org/articles/PMC10011137; pdf:https://europepmc.org/articles/PMC10011137?pdf=render
+32935027,https://doi.org/10.23889/ijpds.v4i1.1093,Health Data Linkage for UK Public Interest Research: Key Obstacles and Solutions.,"Mourby MJ, Doidge J, Jones KH, Aidinlis S, Smith H, Bell J, Gilbert R, Dutey-Magni P, Kaye J.",,International journal of population data science,2019,2019-04-02,Y,,,,"<h4>Introduction</h4>Analysis of linked health data can generate important, even life-saving, insights into population health. Yet obstacles both legal and organisational in nature can impede this work.<h4>Approach</h4>We focus on three UK infrastructures set up to link and share data for research: the Administrative Data Research Network, NHS Digital, and the Secure Anonymised Information Linkage Databank. Bringing an interdisciplinary perspective, we identify key issues underpinning their challenges and successes in linking health data for research.<h4>Results</h4>We identify examples of uncertainty surrounding legal powers to share and link data, and around data protection obligations, as well as systemic delays and historic public backlash. These issues require updated official guidance on the relevant law, approaches to linkage which are planned for impact and ongoing utility, greater transparency between data providers and researchers, and engagement with the patient population which is both high-profile and carefully considered.<h4>Conclusions</h4>Health data linkage for research presents varied challenges, to which there can be no single solution. Our recommendations would require action from a number of data providers and regulators to be meaningfully advanced. This illustrates the scale and complexity of the challenge of health data linkage, in the UK and beyond: a challenge which our case studies suggest no single organisation can combat alone. Planned programmes of linkage are critical because they allow time for organisations to address these challenges without adversely affecting the feasibility of individual research projects.",,pdf:https://ijpds.org/article/download/1093/1035; doi:https://doi.org/10.23889/ijpds.v4i1.1093; html:https://europepmc.org/articles/PMC7482514; pdf:https://europepmc.org/articles/PMC7482514?pdf=render
 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.",,pdf:https://bmcmedethics.biomedcentral.com/counter/pdf/10.1186/s12910-022-00875-9; doi:https://doi.org/10.1186/s12910-022-00875-9; html:https://europepmc.org/articles/PMC9756740; pdf:https://europepmc.org/articles/PMC9756740?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.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009162&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009162; html:https://europepmc.org/articles/PMC8297940; pdf:https://europepmc.org/articles/PMC8297940?pdf=render
-32935027,https://doi.org/10.23889/ijpds.v4i1.1093,Health Data Linkage for UK Public Interest Research: Key Obstacles and Solutions.,"Mourby MJ, Doidge J, Jones KH, Aidinlis S, Smith H, Bell J, Gilbert R, Dutey-Magni P, Kaye J.",,International journal of population data science,2019,2019-04-02,Y,,,,"<h4>Introduction</h4>Analysis of linked health data can generate important, even life-saving, insights into population health. Yet obstacles both legal and organisational in nature can impede this work.<h4>Approach</h4>We focus on three UK infrastructures set up to link and share data for research: the Administrative Data Research Network, NHS Digital, and the Secure Anonymised Information Linkage Databank. Bringing an interdisciplinary perspective, we identify key issues underpinning their challenges and successes in linking health data for research.<h4>Results</h4>We identify examples of uncertainty surrounding legal powers to share and link data, and around data protection obligations, as well as systemic delays and historic public backlash. These issues require updated official guidance on the relevant law, approaches to linkage which are planned for impact and ongoing utility, greater transparency between data providers and researchers, and engagement with the patient population which is both high-profile and carefully considered.<h4>Conclusions</h4>Health data linkage for research presents varied challenges, to which there can be no single solution. Our recommendations would require action from a number of data providers and regulators to be meaningfully advanced. This illustrates the scale and complexity of the challenge of health data linkage, in the UK and beyond: a challenge which our case studies suggest no single organisation can combat alone. Planned programmes of linkage are critical because they allow time for organisations to address these challenges without adversely affecting the feasibility of individual research projects.",,pdf:https://ijpds.org/article/download/1093/1035; doi:https://doi.org/10.23889/ijpds.v4i1.1093; html:https://europepmc.org/articles/PMC7482514; pdf:https://europepmc.org/articles/PMC7482514?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.",,pdf:https://www.nature.com/articles/s41467-022-35454-4.pdf; doi:https://doi.org/10.1038/s41467-022-35454-4; html:https://europepmc.org/articles/PMC9753891; pdf:https://europepmc.org/articles/PMC9753891?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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR, Wellcome Trust.",,pdf:http://www.thelancet.com/article/S2352396422000627/pdf; doi:https://doi.org/10.1016/j.ebiom.2022.103878; html:https://europepmc.org/articles/PMC8856886; pdf:https://europepmc.org/articles/PMC8856886?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.",,pdf:https://www.nature.com/articles/s41467-022-35454-4.pdf; doi:https://doi.org/10.1038/s41467-022-35454-4; html:https://europepmc.org/articles/PMC9753891; pdf:https://europepmc.org/articles/PMC9753891?pdf=render
 32184442,https://doi.org/10.1038/s42003-020-0857-9,Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank.,"Olafsdottir T, Thorleifsson G, Sulem P, Stefansson OA, Medek H, Olafsson K, Ingthorsson O, Gudmundsson V, Jonsdottir I, Halldorsson GH, Kristjansson RP, Frigge ML, Stefansdottir L, Sigurdsson JK, Oddsson A, Sigurdsson A, Eggertsson HP, Melsted P, Halldorsson BV, Lund SH, Styrkarsdottir U, Steinthorsdottir V, Gudmundsson J, Holm H, Tragante V, Asselbergs FW, Thorsteinsdottir U, Gudbjartsson DF, Jonsdottir K, Rafnar T, Stefansson K.",,Communications biology,2020,2020-03-17,Y,,,,"Pelvic organ prolapse (POP) is a downward descent of one or more of the pelvic organs, resulting in a protrusion of the vaginal wall and/or uterus. We performed a genome-wide association study of POP using data from Iceland and the UK Biobank, a total of 15,010 cases with hospital-based diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P < 5 × 10<sup>-8</sup>); seven common (minor allele frequency >5%) and one with minor allele frequency of 4.87%. Some of the variants associating with POP also associated with traits of similar pathophysiology. Of these, rs3820282, which may alter the estrogen-based regulation of WNT4, also associates with leiomyoma of uterus, gestational duration and endometriosis. Rs3791675 at EFEMP1, a gene involved in connective tissue homeostasis, also associates with hernias and carpal tunnel syndrome. Our results highlight the role of connective tissue metabolism and estrogen exposure in the etiology of POP.",,pdf:https://www.nature.com/articles/s42003-020-0857-9.pdf; doi:https://doi.org/10.1038/s42003-020-0857-9; html:https://europepmc.org/articles/PMC7078216; pdf:https://europepmc.org/articles/PMC7078216?pdf=render
 32862087,https://doi.org/10.1016/j.atherosclerosis.2020.07.014,Sex-specific predictors of PCSK9 levels in a European population: The IMPROVE study.,"Ferri N, Ruscica M, Coggi D, Bonomi A, Amato M, Frigerio B, Sansaro D, Ravani A, Veglia F, Capra N, Lupo MG, Macchi C, Castelnuovo S, Savonen K, Silveira A, Kurl S, Giral P, Pirro M, Strawbridge RJ, Gigante B, Smit AJ, Tremoli E, Colombo GI, Baldassarre D, IMPROVE study group.",,Atherosclerosis,2020,2020-07-30,N,Atherosclerosis; Cardiovascular risk factors; Sex differences; Pcsk9 Predictors,,,"<h4>Background and aims</h4>Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of low-density lipoprotein cholesterol plasma levels. Circulating PCSK9, which differs between genders, represents a valid pharmacological target for preventing cardiovascular (CV) events. We aimed to investigate sex-related associations between PCSK9 plasma levels and biochemical and anthropomorphic factors, and familial and personal morbidities, in a large European cohort (n = 3673) of men (47.9%) and women (52.1%).<h4>Methods</h4>Individuals (aged 54-79 years) free of CV diseases were enrolled in seven centers of five European countries: Finland, France, Italy, the Netherlands, and Sweden. PCSK9 plasma levels were measured by ELISA.<h4>Results</h4>PCSK9 was higher in women than in men. Multiple linear regression analysis showed that latitude, sex, and treatments with statins and fibrates were the strongest predictors of PCSK9 in the whole group. These variables, together with triglycerides and high-density lipoprotein cholesterol, were also associated with PCSK9 in men or women. Mean corpuscular hemoglobin concentration and pack-years were PCSK9 independent predictors in women, whereas hypercholesterolemia and physical activity were independent predictors in men. The associations between PCSK9 and latitude, uric acid, diabetes, hypercholesterolemia and physical activity were significantly different in men and women (p<sub>interaction</sub> <0.05 for all).<h4>Conclusions</h4>Besides confirming the association with lipids in the whole group, our study revealed previously unknown differences in PCSK9 predictors in men and women. These might be taken into account when defining individual risk for CV events and/or for refining PCSK9 lowering treatments.",,pdf:http://www.atherosclerosis-journal.com/article/S0021915020303816/pdf; doi:https://doi.org/10.1016/j.atherosclerosis.2020.07.014
 36269859,https://doi.org/10.1073/pnas.2206083119,Metabolome-wide association study on <i>ABCA7</i> 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 <i>ABCA7</i> (<i>P</i> = 5.0 × 10<sup>-5</sup> to 1.3 × 10<sup>-44</sup>). 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 <i>Abca7</i> knockout mice, compared with wild type (WT) (<i>P</i> = 0.049-1.4 × 10<sup>-5</sup>), 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 <i>ABCA7</i> 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; doi:https://doi.org/10.1073/pnas.2206083119; html:https://europepmc.org/articles/PMC9618092; pdf:https://europepmc.org/articles/PMC9618092?pdf=render
@@ -2046,8 +2046,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 32724858,https://doi.org/10.1136/bmjophth-2020-000481,Outcomes important to patients with non-infectious posterior segment-involving uveitis: a qualitative study.,"Tallouzi MO, Moore DJ, Bucknall N, Murray PI, Calvert MJ, Denniston AK, Mathers JM.",,BMJ open ophthalmology,2020,2020-07-21,Y,Inflammation; Public Health; Treatment Other,,,"<h4>Objective</h4>Uveitis, a group of disorders characterised by intraocular inflammation, causes 10%-15% of total blindness in the developed world. The most sight-threatening forms of non-infectious uveitis are those affecting the posterior segment of the eye, collectively known as posterior segment-involving uveitis (PSIU). Numerous different clinical outcomes have been used in trials evaluating treatments for PSIU, but these may not represent patients' and carers' concerns. Therefore, the aims of this study were to understand the impact of PSIU on adult patients' and carers' lives and to explore what outcomes of treatment are important to them.<h4>Methods and analysis</h4>Four focus group discussions were undertaken to understand the perspectives of adult patients (=18) and carers (10) with PSIU. Participants were grouped according to whether or not their uveitis was complicated by the sight-threatening condition uveitic macular oedema. Discussions were audio-recorded, transcribed and analysed using the framework analytical approach. Outcomes were identified and grouped into outcome domains.<h4>Results</h4>Eleven core domains were identified as important to patients and carers undergoing treatment for PSIU, comprising (1) visual function, (2) symptoms, (3) functional ability, (4) impact on relationships, (5) financial impact, (6) psychological morbidity and emotional well-being, (7) psychosocial adjustment to uveitis, (8) doctor/patient/interprofessional relationships and access to healthcare, (9) treatment burden, (10) treatment side effects, and (11) disease control.<h4>Conclusion</h4>The domains identified represent patients' and carers' experience and perspectives and can be used to reflect on outcomes assessed in PSIU. They will directly inform the development of a core outcome set for PSIU clinical trials.",,pdf:https://bmjophth.bmj.com/content/bmjophth/5/1/e000481.full.pdf; doi:https://doi.org/10.1136/bmjophth-2020-000481; html:https://europepmc.org/articles/PMC7375431; pdf:https://europepmc.org/articles/PMC7375431?pdf=render
 31806382,https://doi.org/10.1016/j.injury.2019.11.023,Variation in documented inhalation injury rates following burn injury in Australia and New Zealand.,"Tracy LM, Dyson K, Mercier LL, Cleland H, McInnes JA, Cameron PA, Singer Y, Edgar DW, Darton A, Gabbe BJ.",,Injury,2020,2019-11-17,N,Variation; Australia; New Zealand; Inhalation Injury; Burn Registry,,,"<h4>Introduction</h4>The negative impact of inhalation injuries on in-hospital outcomes for burn patients is well known, but the burns community is yet to form a consensus on diagnostic criteria and clinical definitions. The diagnosis of inhalation injuries is consequently highly subjective. This study aimed to assess the variation in the rate of documented inhalation injury for adult patients in Australian and New Zealand burn units.<h4>Methods</h4>Data for sequential admissions collected from eight adult burn centres across Australia and New Zealand between July 2009 and June 2016 were extracted from the Burns Registry of Australia and New Zealand (BRANZ). Inhalation injury was classified in two ways: (i) a field in the BRANZ data dictionary, and (ii) through a series of International Classification of Disease 10th Revision Australian Modification (ICD-10-AM) codes. Variation in inhalation injury prevalence was assessed using descriptive statistics, funnel plots, logistic regression, and predicted probabilities.<h4>Results</h4>There were 11,206 admissions to BRANZ sites over the study period. Inhalation injury prevalence was the highest at Site D (13.1% for the BRANZ field and 11.8% for the ICD-10-AM codes), but there was significant variation between the contributing sites and the inhalation injury classification methods.<h4>Conclusion</h4>There is significant variation in the prevalence of documented inhalation injury among Australian and New Zealand burns units. The variation in the prevalence of documented inhalation injury across Australian and New Zealand sites reinforces the need for a consensus definition in the diagnosis of these injuries. Further work is required to improve data quality and reconcile the differences between clinical and ICD-10-AM coding prevalence before changes in clinical practice can be recommended from these data.",,doi:https://doi.org/10.1016/j.injury.2019.11.023
 30778056,https://doi.org/10.1038/s41467-019-08797-8,Towards a data-integrated cell.,"Malod-Dognin N, Petschnigg J, Windels SFL, Povh J, Hemingway H, Ketteler R, Pržulj N.",,Nature communications,2019,2019-02-18,Y,,Applied Analytics,,"We are increasingly accumulating molecular data about a cell. The challenge is how to integrate them within a unified conceptual and computational framework enabling new discoveries. Hence, we propose a novel, data-driven concept of an integrated cell, iCell. Also, we introduce a computational prototype of an iCell, which integrates three omics, tissue-specific molecular interaction network types. We construct iCells of four cancers and the corresponding tissue controls and identify the most rewired genes in cancer. Many of them are of unknown function and cannot be identified as different in cancer in any specific molecular network. We biologically validate that they have a role in cancer by knockdown experiments followed by cell viability assays. We find additional support through Kaplan-Meier survival curves of thousands of patients. Finally, we extend this analysis to uncover pan-cancer genes. Our methodology is universal and enables integrative comparisons of diverse omics data over cells and tissues.",,pdf:https://www.nature.com/articles/s41467-019-08797-8.pdf; doi:https://doi.org/10.1038/s41467-019-08797-8; html:https://europepmc.org/articles/PMC6379402; pdf:https://europepmc.org/articles/PMC6379402?pdf=render
-31666709,https://doi.org/10.1038/s41433-019-0657-y,Comment on: 'Quantification of anterior chamber reaction after intravitreal injections of conbercept and ranibizumab: a pilot study'.,"Minocha A, Liu X, Denniston AK, Petrushkin H, Solebo AL.",,"Eye (London, England)",2020,2019-10-30,N,,,,,,pdf:https://www.nature.com/articles/s41433-019-0657-y.pdf; doi:https://doi.org/10.1038/s41433-019-0657-y; html:https://europepmc.org/articles/PMC7376231; pdf:https://europepmc.org/articles/PMC7376231?pdf=render; doi:https://doi.org/10.1038/s41433-019-0657-y
 31013802,https://doi.org/10.3390/ijerph16081325,Using Patient-Reported Outcomes to Predict Revision Arthroplasty Following Femoral Neck Fracture: Enhancing the Value of Clinical Registries through Data Linkage. ,"Ekegren CL, de Steiger R, Edwards ER, Page RS, Hau R, Liew S, Oppy A, Gabbe BJ.",,International journal of environmental research and public health,2019,2019-04-12,Y,,Improving Public Health,,"The aim of this study was to determine the association between patient-reported outcome measures (PROMs) six months following femoral neck fracture after a low fall and future arthroplasty, and the factors associated with this. Six-month post-fracture PROMs were collected from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) for patients aged >55 years who were admitted for a femoral neck fracture after a low fall between March 2007 and June 2015. These cases were linked with those registered by Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) up to October 2016. Multivariable analysis was performed using a Cox proportional hazards model to determine factors associated with future arthroplasty, including six-month PROMs. Of the 7077 hip fracture patients registered by VOTOR during the study period, 2325 met the inclusion criteria. Internal fixation being used for the initial hip fracture surgery, being younger and having no pre-injury disability were all independently associated with future revision or conversion to arthroplasty. Out of all PROMs, reporting pain and discomfort six months post-fracture was associated with a 9.5-fold increase in the risk of future arthroplasty (95% CI: 3.81, 23.67). The value of clinical registries can be enhanced via data linkage, in this case by using PROMs to predict arthroplasty following femoral neck fracture.",,pdf:https://www.mdpi.com/1660-4601/16/8/1325/pdf?version=1555077276; doi:https://doi.org/10.3390/ijerph16081325; html:https://europepmc.org/articles/PMC6517898; pdf:https://europepmc.org/articles/PMC6517898?pdf=render
+31666709,https://doi.org/10.1038/s41433-019-0657-y,Comment on: 'Quantification of anterior chamber reaction after intravitreal injections of conbercept and ranibizumab: a pilot study'.,"Minocha A, Liu X, Denniston AK, Petrushkin H, Solebo AL.",,"Eye (London, England)",2020,2019-10-30,N,,,,,,pdf:https://www.nature.com/articles/s41433-019-0657-y.pdf; doi:https://doi.org/10.1038/s41433-019-0657-y; html:https://europepmc.org/articles/PMC7376231; pdf:https://europepmc.org/articles/PMC7376231?pdf=render; doi:https://doi.org/10.1038/s41433-019-0657-y
 36180121,https://doi.org/10.1136/bmjopen-2021-057712,Development of a core outcome set and identification of patient-reportable outcomes for primary brain tumour trials: protocol for the COBra study.,"Retzer A, Sivell S, Scott H, Nelson A, Bulbeck H, Seddon K, Grant R, Adams R, Watts C, Aiyegbusi OL, Kearns P, Cruz Rivera S, Dirven L, Baddeley E, Calvert M, Byrne A.",,BMJ open,2022,2022-09-30,Y,Clinical Trials; Qualitative Research; Adult Palliative Care; Neurological Oncology,,,"<h4>Introduction</h4>Primary brain tumours, specifically gliomas, are a rare disease group. The disease and treatment negatively impacts on patients and those close to them. The high rates of physical and cognitive morbidity differ from other cancers causing reduced health-related quality of life. Glioma trials using outcomes that allow holistic analysis of treatment benefits and risks enable informed care decisions. Currently, outcome assessment in glioma trials is inconsistent, hindering evidence synthesis. A core outcome set (COS) - an agreed minimum set of outcomes to be measured and reported - may address this. International initiatives focus on defining core outcomes assessments across brain tumour types. This protocol describes the development of a COS involving UK stakeholders for use in glioma trials, applicable across glioma types, with provision to identify subsets as required. Due to stakeholder interest in data reported from the patient perspective, outcomes from the COS that can be patient-reported will be identified.<h4>Methods and analysis</h4>Stage I: (1) trial registry review to identify outcomes collected in glioma trials and (2) systematic review of qualitative literature exploring glioma patient and key stakeholder research priorities. Stage II: semi-structured interviews with glioma patients and caregivers. Outcome lists will be generated from stages I and II. Stage III: study team will remove duplicate items from the outcome lists and ensure accessible terminology for inclusion in the Delphi survey. Stage IV: a two-round Delphi process whereby the outcomes will be rated by key stakeholders. Stage V: a consensus meeting where participants will finalise the COS. The study team will identify the COS outcomes that can be patient-reported. Further research is needed to match patient-reported outcomes to available measures.<h4>Ethics and dissemination</h4>Ethical approval was obtained (REF SMREC 21/59, Cardiff University School of Medicine Research Ethics Committee). Study findings will be disseminated widely through conferences and journal publication. The final COS will be adopted and promoted by patient and carer groups and its use by funders encouraged.<h4>Prospero registration number</h4>CRD42021236979.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e057712.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057712; html:https://europepmc.org/articles/PMC9528585; pdf:https://europepmc.org/articles/PMC9528585?pdf=render
 35131700,https://doi.org/10.1016/j.media.2022.102366,Multi-dynamic modelling reveals strongly time-varying resting fMRI correlations.,"Pervaiz U, Vidaurre D, Gohil C, Smith SM, Woolrich MW.",,Medical image analysis,2022,2022-01-29,Y,Hidden Markov model; Functional Connectivity; Deep Learning; Dynamic Functional Connectivity; Lstm; Rnns; Time-varying Functional Connectivity; Transient Brain Networks; Adversarial Learning,,,"The activity of functional brain networks is responsible for the emergence of time-varying cognition and behaviour. Accordingly, time-varying correlations (Functional Connectivity) in resting fMRI have been shown to be predictive of behavioural traits, and psychiatric and neurological conditions. Typically, methods that measure time varying Functional Connectivity (FC), such as sliding windows approaches, do not separately model when changes occur in the mean activity levels from when changes occur in the FC, therefore conflating these two distinct types of modulation. We show that this can bias the estimation of time-varying FC to appear more stable over time than it actually is. Here, we propose an alternative approach that models changes in the mean brain activity and in the FC as being able to occur at different times to each other. We refer to this method as the Multi-dynamic Adversarial Generator Encoder (MAGE) model, which includes a model of the network dynamics that captures long-range time dependencies, and is estimated on fMRI data using principles of Generative Adversarial Networks. We evaluated the approach across several simulation studies and resting fMRI data from the Human Connectome Project (1003 subjects), as well as from UK Biobank (13301 subjects). Importantly, we find that separating fluctuations in the mean activity levels from those in the FC reveals much stronger changes in FC over time, and is a better predictor of individual behavioural variability.",,doi:https://doi.org/10.1016/j.media.2022.102366; doi:https://doi.org/10.1016/j.media.2022.102366; html:https://europepmc.org/articles/PMC8907871; pdf:https://europepmc.org/articles/PMC8907871?pdf=render
 32558637,https://doi.org/10.1099/mgen.0.000393,Evaluation of methods for detecting human reads in microbial sequencing datasets. ,"Bush SJ, Connor TR, Peto TEA, Crook DW, Walker AS.",,Microbial genomics,2020,2020-07-01,Y,,,,"Sequencing data from host-associated microbes can often be contaminated by the body of the investigator or research subject. Human DNA is typically removed from microbial reads either by subtractive alignment (dropping all reads that map to the human genome) or by using a read classification tool to predict those of human origin, and then discarding them. To inform best practice guidelines, we benchmarked eight alignment-based and two classification-based methods of human read detection using simulated data from 10 clinically prevalent bacteria and three viruses, into which contaminating human reads had been added. While the majority of methods successfully detected >99 % of the human reads, they were distinguishable by variance. The most precise methods, with negligible variance, were Bowtie2 and SNAP, both of which misidentified few, if any, bacterial reads (and no viral reads) as human. While correctly detecting a similar number of human reads, methods based on taxonomic classification, such as Kraken2 and Centrifuge, could misclassify bacterial reads as human, although the extent of this was species-specific. Among the most sensitive methods of human read detection was BWA, although this also made the greatest number of false positive classifications. Across all methods, the set of human reads not identified as such, although often representing <0.1 % of the total reads, were non-randomly distributed along the human genome with many originating from the repeat-rich sex chromosomes. For viral reads and longer (>300 bp) bacterial reads, the highest performing approaches were classification-based, using Kraken2 or Centrifuge. For shorter (c. 150 bp) bacterial reads, combining multiple methods of human read detection maximized the recovery of human reads from contaminated short read datasets without being compromised by false positives. A particularly high-performance approach with shorter bacterial reads was a two-stage classification using Bowtie2 followed by SNAP. Using this approach, we re-examined 11 577 publicly archived bacterial read sets for hitherto undetected human contamination. We were able to extract a sufficient number of reads to call known human SNPs, including those with clinical significance, in 6 % of the samples. These results show that phenotypically distinct human sequence is detectable in publicly archived microbial read datasets.",,doi:https://doi.org/10.1099/mgen.0.000393; doi:https://doi.org/10.1099/mgen.0.000393; html:https://europepmc.org/articles/PMC7478626; pdf:https://europepmc.org/articles/PMC7478626?pdf=render
@@ -2070,18 +2070,18 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 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,,,"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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].",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/5/e038974.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038974; html:https://europepmc.org/articles/PMC7239532; pdf:https://europepmc.org/articles/PMC7239532?pdf=render
 35537820,https://doi.org/10.1136/thoraxjnl-2021-217993,Mendelian randomisation of eosinophils and other cell types in relation to lung function and disease.,"Guyatt A, John C, Williams AT, Shrine N, Reeve NF, SpiroMeta consortium, Sayers I, Hall I, Wain LV, Sheehan N, Dudbridge F, Tobin MD.",,Thorax,2023,2022-05-10,Y,respiratory infection; Copd Epidemiology; Eosinophil Biology; Asthma Mechanisms; Asthma Epidemiology; Asthma Genetics; Copd Exacerbations Mechanisms,,,"<h4>Rationale</h4>Eosinophils are associated with airway inflammation in respiratory disease. Eosinophil production and survival is controlled partly by interleukin-5: anti-interleukin-5 agents reduce asthma and response correlates with baseline eosinophil counts. However, whether raised eosinophils are causally related to chronic obstructive pulmonary disease (COPD) and other respiratory phenotypes is not well understood.<h4>Objectives</h4>We investigated causality between eosinophils and: lung function, acute exacerbations of COPD, asthma-COPD overlap (ACO), moderate-to-severe asthma and respiratory infections.<h4>Methods</h4>We performed Mendelian randomisation (MR) using 151 variants from genome-wide association studies of blood eosinophils in UK Biobank/INTERVAL, and respiratory traits in UK Biobank/SpiroMeta, using methods relying on different assumptions for validity. We performed multivariable analyses using eight cell types where there was possible evidence of causation by eosinophils.<h4>Measurements and main results</h4>Causal estimates derived from individual variants were highly heterogeneous, which may arise from pleiotropy. The average effect of raising eosinophils was to increase risk of ACO (weighted median OR per SD eosinophils, 1.44 (95%CI 1.19 to 1.74)), and moderate-severe asthma (weighted median OR 1.50 (95%CI 1.23 to 1.83)), and to reduce forced expiratory volume in 1 s (FEV<sub>1</sub>)/forced vital capacity (FVC) and FEV<sub>1</sub> (weighted median estimator, SD FEV<sub>1</sub>/FVC: -0.054 (95% CI -0.078 to -0.029), effect only prominent in individuals with asthma).<h4>Conclusions</h4>Broad consistency across MR methods may suggest causation by eosinophils (although of uncertain magnitude), yet heterogeneity necessitates caution: other important mechanisms may be responsible for the impairment of respiratory health by these eosinophil-raising variants. These results could suggest that anti-IL5 agents (designed to lower eosinophils) may be valuable in treating other respiratory conditions, including people with overlapping features of asthma and COPD.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/05/10/thoraxjnl-2021-217993.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-217993; html:https://europepmc.org/articles/PMC10176352; pdf:https://europepmc.org/articles/PMC10176352?pdf=render
 36810190,https://doi.org/10.1136/bmjebm-2023-112253,Digitally enabled decentralised research: opportunities to improve the efficiency of clinical trials and observational studies.,"Aiyegbusi OL, Davies EH, Myles P, Williams T, Frost C, Haroon S, Hughes SE, Wilson R, McMullan C, Subramanian A, Nirantharakumar K, Calvert MJ.",,BMJ evidence-based medicine,2023,2023-02-21,Y,information technology; drug discovery; Drug Development; Covid-19,,,,,pdf:https://ebm.bmj.com/content/ebmed/early/2023/02/20/bmjebm-2023-112253.full.pdf; doi:https://doi.org/10.1136/bmjebm-2023-112253; html:https://europepmc.org/articles/PMC10579468; pdf:https://europepmc.org/articles/PMC10579468?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,,,"<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.mdpi.com/2077-0383/11/23/7163/pdf?version=1670311452; doi:https://doi.org/10.3390/jcm11237163; html:https://europepmc.org/articles/PMC9738639; pdf:https://europepmc.org/articles/PMC9738639?pdf=render
 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; doi:https://doi.org/10.1016/j.jchf.2019.01.009
+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,,,"<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://www.mdpi.com/2077-0383/11/23/7163/pdf?version=1670311452; doi:https://doi.org/10.3390/jcm11237163; html:https://europepmc.org/articles/PMC9738639; pdf:https://europepmc.org/articles/PMC9738639?pdf=render
 34320164,https://doi.org/10.1093/cvr/cvab239,"The RECOVERY trial: cardiovascular implications of a large, simple randomized trial in COVID-19.","Pessoa-Amorim G, Mafham MM.",,Cardiovascular research,2021,2021-07-01,Y,Immunomodulation; Antiviral; Randomized Trial; Antithrombotic; Covid-19,,,,,pdf:https://academic.oup.com/cardiovascres/article-pdf/117/9/e110/39354428/cvab239.pdf; doi:https://doi.org/10.1093/cvr/cvab239; html:https://europepmc.org/articles/PMC8318096; pdf:https://europepmc.org/articles/PMC8318096?pdf=render
 36442657,https://doi.org/10.1016/j.jad.2022.11.051,Factors associated with anxiety disorder comorbidity.,"Davies MR, Glen K, Mundy J, Ter Kuile AR, Adey BN, Armour C, Assary E, Coleman JRI, Goldsmith KA, Hirsch CR, Hotopf M, Hübel C, Jones IR, Kalsi G, Krebs G, McIntosh AM, Morneau-Vaillancourt G, Peel AJ, Purves KL, Lee SH, Skelton M, Smith DJ, Veale D, Walters JTR, Young KS, Zvrskovec J, Breen G, Eley TC.",,Journal of affective disorders,2023,2022-11-26,Y,Affective Disorders; Comorbidity; Anxiety Disorders; Depressive Disorders; Polygenic Risk Score,,,"<h4>Background</h4>Anxiety and depressive disorders often co-occur and the order of their emergence may be associated with different clinical outcomes. However, minimal research has been conducted on anxiety-anxiety comorbidity. This study examined factors associated with anxiety comorbidity and anxiety-MDD temporal sequence.<h4>Methods</h4>Online, self-report data were collected from the UK-based GLAD and COPING NBR cohorts (N = 38,775). Logistic regression analyses compared differences in sociodemographic, trauma, and clinical factors between single anxiety, anxiety-anxiety comorbidity, anxiety-MDD (major depressive disorder) comorbidity, and MDD-only. Additionally, anxiety-first and MDD-first anxiety-MDD were compared. Differences in familial risk were assessed in those participants with self-reported family history or genotype data.<h4>Results</h4>Anxiety-anxiety and anxiety-MDD had higher rates of self-reported anxiety or depressive disorder diagnoses, younger age of onset, and higher recurrence than single anxiety. Anxiety-MDD displayed greater clinical severity/complexity than MDD only. Anxiety-anxiety had more severe current anxiety symptoms, less severe current depressive symptoms, and reduced likelihood of self-reporting an anxiety/depressive disorder diagnosis than anxiety-MDD. Anxiety-first anxiety-MDD had a younger age of onset, more severe anxiety symptoms, and less likelihood of self-reporting a diagnosis than MDD-first. Minimal differences in familial risk were found.<h4>Limitations</h4>Self-report, retrospective measures may introduce recall bias. The familial risk analyses were likely underpowered.<h4>Conclusions</h4>Anxiety-anxiety comorbidity displayed a similarly severe and complex profile of symptoms as anxiety-MDD but distinct features. For anxiety-MDD, first-onset anxiety had an earlier age of onset and greater severity than MDD-first. Anxiety disorders and comorbidity warrant further investigation and attention in research and practice.",,doi:https://doi.org/10.1016/j.jad.2022.11.051; doi:https://doi.org/10.1016/j.jad.2022.11.051; html:https://europepmc.org/articles/PMC10202820
 31844048,https://doi.org/10.1038/s41467-019-13585-5,Genome-wide analysis identifies molecular systems and 149 genetic loci associated with income.,"Hill WD, Davies NM, Ritchie SJ, Skene NG, Bryois J, Bell S, Di Angelantonio E, Roberts DJ, Xueyi S, Davies G, Liewald DCM, Porteous DJ, Hayward C, Butterworth AS, McIntosh AM, Gale CR, Deary IJ.",,Nature communications,2019,2019-12-16,Y,,Understanding the Causes of Disease,,"Socioeconomic position (SEP) is a multi-dimensional construct reflecting (and influencing) multiple socio-cultural, physical, and environmental factors. In a sample of 286,301 participants from UK Biobank, we identify 30 (29 previously unreported) independent-loci associated with income. Using a method to meta-analyze data from genetically-correlated traits, we identify an additional 120 income-associated loci. These loci show clear evidence of functionality, with transcriptional differences identified across multiple cortical tissues, and links to GABAergic and serotonergic neurotransmission. By combining our genome wide association study on income with data from eQTL studies and chromatin interactions, 24 genes are prioritized for follow up, 18 of which were previously associated with intelligence. We identify intelligence as one of the likely causal, partly-heritable phenotypes that might bridge the gap between molecular genetic inheritance and phenotypic consequence in terms of income differences. These results indicate that, in modern era Great Britain, genetic effects contribute towards some of the observed socioeconomic inequalities.","This study linked genetic sequencing data and information on household income to identify parts of the genome that are more common in people who live in more affluent households. The authors identified 150 parts of the genome that were associated with income, and found that these genetic regions were more commonly expressed in the brain and testes. The results indicate that intelligence and income are causally linked, and suggest that genetics partly explain a small amount of variation (~2%) in household income in the UK.",pdf:https://www.nature.com/articles/s41467-019-13585-5.pdf; doi:https://doi.org/10.1038/s41467-019-13585-5; html:https://europepmc.org/articles/PMC6915786; pdf:https://europepmc.org/articles/PMC6915786?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,,,"<h4>Background</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0211-7; doi:https://doi.org/10.1186/s13326-019-0211-7; html:https://europepmc.org/articles/PMC6849161; pdf:https://europepmc.org/articles/PMC6849161?pdf=render
 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,,,"<h4>Aims</h4>The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure.<h4>Methods and results</h4>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<sup>-8</sup> under an additive genetic model.<h4>Conclusions</h4>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.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.13517; doi:https://doi.org/10.1002/ehf2.13517; html:https://europepmc.org/articles/PMC8712846; pdf:https://europepmc.org/articles/PMC8712846?pdf=render
-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,,,,"<h4>Objectives</h4>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.<h4>Design</h4>Cohort study.<h4>Setting</h4>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.<h4>Participants</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://www.bmj.com/content/bmj/381/bmj-2022-072976.full.pdf; doi:https://doi.org/10.1136/bmj-2022-072976; html:https://europepmc.org/articles/PMC10282241; pdf:https://europepmc.org/articles/PMC10282241?pdf=render
 35977952,https://doi.org/10.1038/s41467-022-29931-z,GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements.,"Dixon PH, Levine AP, Cebola I, Chan MMY, Amin AS, Aich A, Mozere M, Maude H, Mitchell AL, Zhang J, NIHR BioResource, Genomics England Research Consortium Collaborators, Chambers J, Syngelaki A, Donnelly J, Cooley S, Geary M, Nicolaides K, Thorsell M, Hague WM, Estiu MC, Marschall HU, Gale DP, Williamson C.",,Nature communications,2022,2022-08-17,Y,,,,"Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility.",,pdf:https://www.nature.com/articles/s41467-022-29931-z.pdf; doi:https://doi.org/10.1038/s41467-022-29931-z; html:https://europepmc.org/articles/PMC9385867; pdf:https://europepmc.org/articles/PMC9385867?pdf=render
-37757828,https://doi.org/10.1016/j.cell.2023.08.028,Influence of autozygosity on common disease risk across the phenotypic spectrum.,"Malawsky DS, van Walree E, Jacobs BM, Heng TH, Huang QQ, Sabir AH, Rahman S, Sharif SM, Khan A, Mirkov MU, 23andMe Research Team, Genes & Health Research Team, Kuwahara H, Gao X, Alkuraya FS, Posthuma D, Newman WG, Griffiths CJ, Mathur R, van Heel DA, Finer S, O'Connell J, Martin HC.",,Cell,2023,2023-09-26,Y,Consanguinity; Medical genetics; Recessive; Autozygosity; Common Diseases; Diverse Cohorts,,,"Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F<sub>ROH</sub>) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of F<sub>ROH</sub>. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between F<sub>ROH</sub> and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n = 480,282). We estimated that autozygosity due to consanguinity accounts for 5%-18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity.",,doi:https://doi.org/10.1016/j.cell.2023.08.028; html:https://europepmc.org/articles/PMC10580289; pdf:https://europepmc.org/articles/PMC10580289?pdf=render
-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.",,pdf:https://academic.oup.com/jcem/article-pdf/105/12/e4230/41829325/dgaa627.pdf; doi:https://doi.org/10.1210/clinem/dgaa627; html:https://europepmc.org/articles/PMC7499588; pdf:https://europepmc.org/articles/PMC7499588?pdf=render
+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,,,,"<h4>Objectives</h4>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.<h4>Design</h4>Cohort study.<h4>Setting</h4>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.<h4>Participants</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",,pdf:https://www.bmj.com/content/bmj/381/bmj-2022-072976.full.pdf; doi:https://doi.org/10.1136/bmj-2022-072976; html:https://europepmc.org/articles/PMC10282241; pdf:https://europepmc.org/articles/PMC10282241?pdf=render
 31331193,https://doi.org/10.1161/circulationaha.119.041546,Impact of <i>ADCY9</i> 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",,"<h4>Background</h4>Exploratory analyses of previous randomized trials generated a hypothesis that the clinical response to cholesteryl ester transfer protein (CETP) inhibitor therapy differs by <i>ADCY9</i> 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 <i>ADCY9</i> genotype on response to anacetrapib in the REVEAL trial.<h4>Methods</h4>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 <i>ADCY9</i> rs1967309 genotype.<h4>Results</h4>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 <i>ADCY9</i> 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 <i>P</i> for interaction = 0.96. Furthermore, there were no associations between <i>ADCY9</i> genotype and the proportional reductions in the separate components of major vascular events or meaningful differences in lipid response to anacetrapib.<h4>Conclusions</h4>The REVEAL trial is the single largest study to date evaluating the <i>ADCY9</i> pharmacogenetic interaction. It provides no support for the hypothesis that <i>ADCY9</i> 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.<h4>Clinical trial registration</h4>URL: https://www.<h4>Clinicaltrials</h4>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; doi:https://doi.org/10.1161/CIRCULATIONAHA.119.041546; html:https://europepmc.org/articles/PMC6749971; pdf:https://europepmc.org/articles/PMC6749971?pdf=render
+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.",,pdf:https://academic.oup.com/jcem/article-pdf/105/12/e4230/41829325/dgaa627.pdf; doi:https://doi.org/10.1210/clinem/dgaa627; html:https://europepmc.org/articles/PMC7499588; pdf:https://europepmc.org/articles/PMC7499588?pdf=render
+37757828,https://doi.org/10.1016/j.cell.2023.08.028,Influence of autozygosity on common disease risk across the phenotypic spectrum.,"Malawsky DS, van Walree E, Jacobs BM, Heng TH, Huang QQ, Sabir AH, Rahman S, Sharif SM, Khan A, Mirkov MU, 23andMe Research Team, Genes & Health Research Team, Kuwahara H, Gao X, Alkuraya FS, Posthuma D, Newman WG, Griffiths CJ, Mathur R, van Heel DA, Finer S, O'Connell J, Martin HC.",,Cell,2023,2023-09-26,Y,Consanguinity; Medical genetics; Recessive; Autozygosity; Common Diseases; Diverse Cohorts,,,"Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F<sub>ROH</sub>) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of F<sub>ROH</sub>. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between F<sub>ROH</sub> and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n = 480,282). We estimated that autozygosity due to consanguinity accounts for 5%-18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity.",,doi:https://doi.org/10.1016/j.cell.2023.08.028; html:https://europepmc.org/articles/PMC10580289; pdf:https://europepmc.org/articles/PMC10580289?pdf=render
 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 <i>Enterobacteriaceae</i> 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 <i>Enterobacteriaceae</i> 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; doi:https://doi.org/10.1099/mgen.0.000453; html:https://europepmc.org/articles/PMC7725331; pdf:https://europepmc.org/articles/PMC7725331?pdf=render
 37316763,https://doi.org/10.1007/s10875-023-01530-7,Autosomal Dominant STAT6 Gain of Function Causes Severe Atopy Associated with Lymphoma.,"Minskaia E, Maimaris J, Jenkins P, Albuquerque AS, Hong Y, Eleftheriou D, Gilmour KC, Grace R, Moreira F, Grimbacher B, NIHR Bioresource-Rare Diseases Consortium, Morris EC, Burns SO.",,Journal of clinical immunology,2023,2023-06-14,Y,Lymphoma; STAT6; Atopy; Gain-of-function,,,"The transcription factor STAT6 (Signal Transducer and Activator of Transcription 6) is a key regulator of Th2 (T-helper 2) mediated allergic inflammation via the IL-4 (interleukin-4) JAK (Janus kinase)/STAT signalling pathway. We identified a novel heterozygous germline mutation STAT6 c.1255G > C, p.D419H leading to overactivity of IL-4 JAK/STAT signalling pathway, in a kindred affected by early-onset atopic dermatitis, food allergy, eosinophilic asthma, anaphylaxis and follicular lymphoma. STAT6 D419H expression and functional activity were compared with wild type STAT6 in transduced HEK293T cells and to healthy control primary skin fibroblasts and peripheral blood mononuclear cells (PBMC). We observed consistently higher STAT6 levels at baseline and higher STAT6 and phosphorylated STAT6 following IL-4 stimulation in D419H cell lines and primary cells compared to wild type controls. The pSTAT6/STAT6 ratios were unchanged between D419H and control cells suggesting that elevated pSTAT6 levels resulted from higher total basal STAT6 expression. The selective JAK1/JAK2 inhibitor ruxolitinib reduced pSTAT6 levels in D419H HEK293T cells and patient PBMC. Nuclear staining demonstrated increased STAT6 in patient fibroblasts at baseline and both STAT6 and pSTAT6 after IL-4 stimulation. We also observed higher transcriptional upregulation of downstream genes (XBP1 and EPAS1) in patient PBMC. Our study confirms STAT6 gain of function (GOF) as a novel monogenetic cause of early onset atopic disease. The clinical association of lymphoma in our kindred, along with previous data linking somatic STAT6 D419H mutations to follicular lymphoma suggest that patients with STAT6 GOF disease may be at higher risk of lymphomagenesis.245 words.",,pdf:https://link.springer.com/content/pdf/10.1007/s10875-023-01530-7.pdf; doi:https://doi.org/10.1007/s10875-023-01530-7; html:https://europepmc.org/articles/PMC10499697; pdf:https://europepmc.org/articles/PMC10499697?pdf=render
 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,,,"<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",,pdf:https://neurologyopen.bmj.com/content/bmjno/3/1/e000133.full.pdf; doi:https://doi.org/10.1136/bmjno-2021-000133; html:https://europepmc.org/articles/PMC8183200; pdf:https://europepmc.org/articles/PMC8183200?pdf=render
@@ -2113,8 +2113,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 32792438,https://doi.org/10.1136/bmjopen-2019-036564,Association between health indicators of maternal adversity and the rate of infant entry to local authority care in England: a longitudinal ecological study.,"Pearson RJ, Jay MA, Wijlaars LPMM, De Stavola B, Syed S, Bedston SJ, Gilbert R.",,BMJ open,2020,2020-08-13,Y,epidemiology; Public Health; Child Protection,,,"<h4>Objective</h4>Infants enter care at varying rates across local authorities (LAs) in England, but evidence is lacking on what is driving these differences. With this ecological study, we aimed to explore the extent to which adversity indicated within women's hospitalisation histories, predelivery, explained the rate of infant entry into care.<h4>Methods</h4>We used two longitudinal person-level data sets on hospitalisations and entries to care to create annual measures for 131 English LAs, between 2006/2007 and 2013/2014 (April-March). We combined these measures by LA and financial year, along with other publicly available data on LA characteristics. We used linear mixed-effects models to analyse the relationship between the outcome-LA-specific rate of infant entry into care (per 10 000 infants in the LA population) - and LA-specific percentage of live births with maternal history of adversity-related hospital admissions (ie, substance misuse, mental health problems or violence-related admissions in the 3 years before delivery), adjusted for other predictors of entry into care.<h4>Results</h4>Rate of infant entry into care (mean: 85.16 per 10 000, SD: 41.07) and percentage of live births with maternal history of adversity-related hospital admissions (4.62%, 2.44%) varied greatly by LA. The prevalence of maternal adversity accounted for 24% of the variation in rate of entry (95% CI 14% to 35%). After adjustment, a percentage point increase in prevalence of maternal adversity-both within and between LAs-was associated with an estimated 2.56 (per 10 000) more infants entering care (1.31-3.82).<h4>Conclusions</h4>The prevalence of maternal adversity before birth helped to explain the variation in LA rates of infant entry into care. Preventive interventions are needed to improve maternal well-being before and during pregnancy, and potentially reduce risk of child maltreatment and therefore entries to care. Evidence on who to target and data to evaluate change require linkage between parent-child healthcare data and administrative data from children's social care.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/8/e036564.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-036564; html:https://europepmc.org/articles/PMC7430489; pdf:https://europepmc.org/articles/PMC7430489?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Lundbeck Foundation.",,pdf:http://www.thelancet.com/article/S2589750019301219/pdf; doi:https://doi.org/10.1016/S2589-7500(19)30121-9
 31308017,https://doi.org/10.2337/dc18-2423,"Educational and Health Outcomes of Children Treated for Type 1 Diabetes: Scotland-Wide Record Linkage Study of 766,047 Children.","Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A, Lindsay RS, Mackay DF, Pell JP.",,Diabetes care,2019,2019-07-15,N,,,,"<h4>Objective</h4>This study was conducted to determine the association between childhood type 1 diabetes and educational and health outcomes.<h4>Research design and methods</h4>Record linkage of nine Scotland-wide databases (diabetes register, dispensed prescriptions, maternity records, hospital admissions, death certificates, annual pupil census, school absences/exclusions, school examinations, and unemployment) produced a cohort of 766,047 singleton children born in Scotland who attended Scottish schools between 2009 and 2013. We compared the health and education outcomes of schoolchildren receiving insulin with their peers, adjusting for potential confounders.<h4>Results</h4>The 3,330 children (0.47%) treated for type 1 diabetes were more likely to be admitted to the hospital (adjusted hazard ratio [HR] 3.97, 95% CI 3.79-4.16), die (adjusted HR 3.84, 95% CI 1.98-7.43), be absent from school (adjusted incidence rate ratio [IRR] 1.34, 95% CI 1.30-1.39), and have learning difficulties (adjusted odds ratio [OR] 1.19, 95% CI 1.03-1.38). Among children with type 1 diabetes, higher mean HbA<sub>1c</sub> (particularly HbA<sub>1c</sub> in the highest quintile) was associated with greater absenteeism (adjusted IRR 1.75, 95% CI 1.56-1.96), increased school exclusion (adjusted IRR 2.82, 95% CI 1.14-6.98), poorer attainment (adjusted OR 3.52, 95% CI 1.72-7.18), and higher risk of unemployment (adjusted OR 2.01, 95% CI 1.05-3.85).<h4>Conclusions</h4>Children with type 1 diabetes fare worse than their peers in respect of education and health outcomes, especially if they have higher mean HbA<sub>1c</sub>. Interventions are required to minimize school absence and ensure that it does not affect educational attainment.",,pdf:https://care.diabetesjournals.org/content/diacare/42/9/1700.full.pdf; doi:https://doi.org/10.2337/dc18-2423; html:https://europepmc.org/articles/PMC6706279; pdf:https://europepmc.org/articles/PMC6706279?pdf=render; doi:https://doi.org/10.2337/dc18-2423
-34563995,https://doi.org/10.1016/j.schres.2021.09.006,"The impact of cigarette smoking on life expectancy in schizophrenia, schizoaffective disorder and bipolar affective disorder: An electronic case register cohort study.","Chesney E, Robson D, Patel R, Shetty H, Richardson S, Chang CK, McGuire P, McNeill A.",,Schizophrenia research,2021,2021-09-23,Y,Mortality; Schizophrenia; Tobacco; Smoking; Life expectancy; Bipolar Affective Disorder,,,"Severe mental disorders are associated with a life expectancy that is 10-20 years shorter than the general population's. The prevalence of cigarette smoking in these populations is very high. We examined the effect of smoking on life expectancy and survival in patients with a diagnosis of schizophrenia, schizoaffective disorder or bipolar affective disorder from 2007 to 2018 in South East London, UK. Smoking status was determined using unstructured text data extracted from electronic health records. A total of 21,588 patients were identified of which 16,717, (77.4%) were classified as current smokers and 3438 (15.9%) as non-smokers. In female participants, life expectancy at birth was 67.6 years in current smokers (95% CI: 66.4-68.8) and 74.9 years in non-smokers (95% CI: 72.8-77.0), a difference of 7.3 years. In male participants, life expectancy at birth was 63.5 years in current smokers (95% CI: 62.5-64.5) and 68.5 years in non-smokers (95% CI, 64.4-72.6), a difference of 5.0 years. Adjusted survival models found that current smoking status was associated with an increased mortality risk for both females (aHR: 1.42, 95% CI: 1.21-1.66, p < 0.001) and males (aHR: 1.49; 95% CI: 1.25-1.79, p < 0.001). In terms of the effect sizes, these risks were similar to those associated with a diagnosis of co-morbid alcohol or opioid use disorder. Smoking may account for a substantial proportion of the reduced life expectancy in patients with psychotic disorders. Increased emphasis on reducing cigarette smoking in these populations may be the most effective way to reduce the mortality gap with the general population.",,doi:https://doi.org/10.1016/j.schres.2021.09.006; doi:https://doi.org/10.1016/j.schres.2021.09.006; html:https://europepmc.org/articles/PMC8653908
 31995663,https://doi.org/10.1111/cts.12725,Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.,"Pan S, Tsakok T, Dand N, Lonsdale DO, Loeff FC, Bloem K, de Vries A, Baudry D, Duckworth M, Mahil S, Pushpa-Rajah A, Russell A, Alsharqi A, Becher G, Murphy R, Wahie S, Wright A, Griffiths CEM, Reynolds NJ, Barker J, Warren RB, David Burden A, Rispens T, Standing JF, Smith CH, BADBIR Study Group, the BSTOP Study Group, the PSORT Consortium.",,Clinical and translational science,2020,2020-01-29,Y,,,skin,"Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (E<sub>max</sub> ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring ""dashboard"" to individualize dosing and improve treatment outcomes.",,pdf:https://ascpt.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cts.12725; doi:https://doi.org/10.1111/cts.12725; html:https://europepmc.org/articles/PMC7070790; pdf:https://europepmc.org/articles/PMC7070790?pdf=render
+34563995,https://doi.org/10.1016/j.schres.2021.09.006,"The impact of cigarette smoking on life expectancy in schizophrenia, schizoaffective disorder and bipolar affective disorder: An electronic case register cohort study.","Chesney E, Robson D, Patel R, Shetty H, Richardson S, Chang CK, McGuire P, McNeill A.",,Schizophrenia research,2021,2021-09-23,Y,Mortality; Schizophrenia; Tobacco; Smoking; Life expectancy; Bipolar Affective Disorder,,,"Severe mental disorders are associated with a life expectancy that is 10-20 years shorter than the general population's. The prevalence of cigarette smoking in these populations is very high. We examined the effect of smoking on life expectancy and survival in patients with a diagnosis of schizophrenia, schizoaffective disorder or bipolar affective disorder from 2007 to 2018 in South East London, UK. Smoking status was determined using unstructured text data extracted from electronic health records. A total of 21,588 patients were identified of which 16,717, (77.4%) were classified as current smokers and 3438 (15.9%) as non-smokers. In female participants, life expectancy at birth was 67.6 years in current smokers (95% CI: 66.4-68.8) and 74.9 years in non-smokers (95% CI: 72.8-77.0), a difference of 7.3 years. In male participants, life expectancy at birth was 63.5 years in current smokers (95% CI: 62.5-64.5) and 68.5 years in non-smokers (95% CI, 64.4-72.6), a difference of 5.0 years. Adjusted survival models found that current smoking status was associated with an increased mortality risk for both females (aHR: 1.42, 95% CI: 1.21-1.66, p < 0.001) and males (aHR: 1.49; 95% CI: 1.25-1.79, p < 0.001). In terms of the effect sizes, these risks were similar to those associated with a diagnosis of co-morbid alcohol or opioid use disorder. Smoking may account for a substantial proportion of the reduced life expectancy in patients with psychotic disorders. Increased emphasis on reducing cigarette smoking in these populations may be the most effective way to reduce the mortality gap with the general population.",,doi:https://doi.org/10.1016/j.schres.2021.09.006; doi:https://doi.org/10.1016/j.schres.2021.09.006; html:https://europepmc.org/articles/PMC8653908
 31647808,https://doi.org/10.1371/journal.pgen.1008405,Causal relationships between obesity and the leading causes of death in women and men.,"Censin JC, Peters SAE, Bovijn J, Ferreira T, Pulit SL, Mägi R, Mahajan A, Holmes MV, Lindgren CM.",,PLoS genetics,2019,2019-10-24,Y,,Understanding the Causes of Disease,,"Obesity traits are causally implicated with risk of cardiometabolic diseases. It remains unclear whether there are similar causal effects of obesity traits on other non-communicable diseases. Also, it is largely unexplored whether there are any sex-specific differences in the causal effects of obesity traits on cardiometabolic diseases and other leading causes of death. We constructed sex-specific genetic risk scores (GRS) for three obesity traits; body mass index (BMI), waist-hip ratio (WHR), and WHR adjusted for BMI, including 565, 324, and 337 genetic variants, respectively. These GRSs were then used as instrumental variables to assess associations between the obesity traits and leading causes of mortality in the UK Biobank using Mendelian randomization. We also investigated associations with potential mediators, including smoking, glycemic and blood pressure traits. Sex-differences were subsequently assessed by Cochran's Q-test (Phet). A Mendelian randomization analysis of 228,466 women and 195,041 men showed that obesity causes coronary artery disease, stroke (particularly ischemic), chronic obstructive pulmonary disease, lung cancer, type 2 and 1 diabetes mellitus, non-alcoholic fatty liver disease, chronic liver disease, and acute and chronic renal failure. Higher BMI led to higher risk of type 2 diabetes in women than in men (Phet = 1.4×10-5). Waist-hip-ratio led to a higher risk of chronic obstructive pulmonary disease (Phet = 3.7×10-6) and higher risk of chronic renal failure (Phet = 1.0×10-4) in men than women. Obesity traits have an etiological role in the majority of the leading global causes of death. Sex differences exist in the effects of obesity traits on risk of type 2 diabetes, chronic obstructive pulmonary disease, and renal failure, which may have downstream implications for public health.","This study aimed to quantify (as genetic risk scores) the causal effects of obesity on leading causes of death, separately, in men and women. Analysis of genetic data for 228,466 women and 195,041 men showed that obesity causes coronary artery disease, stroke, chronic obstructive pulmonary disease, lung cancer, type 2 and 1 diabetes mellitus, non-alcoholic fatty liver disease, chronic liver disease, and acute and chronic renal failure. The authors identified some important differences in these causal effects for men and women.",pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008405&type=printable; doi:https://doi.org/10.1371/journal.pgen.1008405; html:https://europepmc.org/articles/PMC6812754; pdf:https://europepmc.org/articles/PMC6812754?pdf=render
 32709645,https://doi.org/10.1136/bmjopen-2019-035968,Infant formula composition and educational performance: a protocol to extend follow-up for a set of randomised controlled trials using linked administrative education records.,"Verfürden M, Harron K, Jerrim J, Fewtrell M, Gilbert R.",,BMJ open,2020,2020-07-23,Y,Public Health; Clinical Trials; Paediatric Neurology; Nutrition & Dietetics,,,"<h4>Introduction</h4>The effect of infant nutrition on long-term cognition is important for parents and policy makers. However, most clinical trials typically have short follow-up periods, when measures of cognition are poorly predictive of later function. The few trials with longer-term follow-up have high levels of attrition, which can lead to selection bias, and in turn to erroneous interpretation of long-term harms and benefits of infant nutrition. We address the need for unbiased, long-term follow-up, by linking measures of educational performance from administrative education records. Educational performance is a meaningful marker of cognitive function in children and it is strongly correlated with IQ. We aim to evaluate educational performance for children who, as infants, were part of a series of trials that randomised participants to either nutritionally modified infant formula or standard formula. Most trialists anticipated positive effects of these interventions on later cognitive function.<h4>Methods and analysis</h4>Using data from 1923 participants of seven randomised infant formula trials linked to the English National Pupil Database (NPD), this study will provide new insights into the effect of nutrient intake in infancy on school achievement. Our primary outcome will be the mean differences in z-scores between intervention and control groups for a compulsory Mathematics exam sat at age 16. Secondary outcomes will be z-scores for a compulsory English exam at age 16 and z-scores for compulsory Mathematics and English exams at age 11. We will also evaluate intervention effects on the likelihood of receiving special educational needs (SEN) support. All analyses will be performed separately by trial.<h4>Ethics and dissemination</h4>Research ethics approval, and approval from the Health Research Authority Confidentiality Advisory Group, has been obtained for this study. The results of this study will be disseminated to scientific, practitioner, and lay audiences, submitted for publication in peer-reviewed journals, and will contribute towards a PhD dissertation.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/7/e035968.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-035968; html:https://europepmc.org/articles/PMC7380883; pdf:https://europepmc.org/articles/PMC7380883?pdf=render
 33208942,https://doi.org/10.1038/s41586-020-2927-z,Host ANP32A mediates the assembly of the influenza virus replicase.,"Carrique L, Fan H, Walker AP, Keown JR, Sharps J, Staller E, Barclay WS, Fodor E, Grimes JM.",,Nature,2020,2020-11-18,Y,,,,"Aquatic birds represent a vast reservoir from which new pandemic influenza A viruses can emerge<sup>1</sup>. Influenza viruses contain a negative-sense segmented RNA genome that is transcribed and replicated by the viral heterotrimeric RNA polymerase (FluPol) in the context of viral ribonucleoprotein complexes<sup>2,3</sup>. RNA polymerases of avian influenza A viruses (FluPolA) replicate viral RNA inefficiently in human cells because of species-specific differences in acidic nuclear phosphoprotein 32 (ANP32), a family of essential host proteins for FluPol activity<sup>4</sup>. Host-adaptive mutations, particularly a glutamic-acid-to-lysine mutation at amino acid residue 627 (E627K) in the 627 domain of the PB2 subunit, enable avian FluPolA to overcome this restriction and efficiently replicate viral RNA in the presence of human ANP32 proteins. However, the molecular mechanisms of genome replication and the interplay with ANP32 proteins remain largely unknown. Here we report cryo-electron microscopy structures of influenza C virus polymerase (FluPolC) in complex with human and chicken ANP32A. In both structures, two FluPolC molecules form an asymmetric dimer bridged by the N-terminal leucine-rich repeat domain of ANP32A. The C-terminal low-complexity acidic region of ANP32A inserts between the two juxtaposed PB2 627 domains of the asymmetric FluPolA dimer, suggesting a mechanism for how the adaptive PB2(E627K) mutation enables the replication of viral RNA in mammalian hosts. We propose that this complex represents a replication platform for the viral RNA genome, in which one of the FluPol molecules acts as a replicase while the other initiates the assembly of the nascent replication product into a viral ribonucleoprotein complex.",,pdf:https://www.nature.com/articles/s41586-020-2927-z.pdf; doi:https://doi.org/10.1038/s41586-020-2927-z; html:https://europepmc.org/articles/PMC7116770; pdf:https://europepmc.org/articles/PMC7116770?pdf=render
@@ -2126,11 +2126,11 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 31350032,https://doi.org/10.1016/j.burns.2019.07.003,"Epidemiology of burn-related fatalities in Australia and New Zealand, 2009-2015.","McInnes JA, Cleland HJ, Cameron PA, Darton A, Tracy LM, Wood FM, Singer Y, Gabbe BJ.",,Burns : journal of the International Society for Burn Injuries,2019,2019-07-24,N,Burns; Mortality; Australia; New Zealand; epidemiology; Fatality,,,"<h4>Background</h4>Knowledge of the epidemiology of burn-related fatalities is limited, with most previous studies based on hospital and burn centre data only.<h4>Aims</h4>To describe the epidemiological characteristics of all burn-related fatalities in Australia and New Zealand, and to identify any trends in burn-related fatality incidence over the study period.<h4>Methods</h4>Data from the National Coronial Information System, including data for pre-hospital and in-hospital burn-related fatality cases, was used to examine the characteristics of burn-related fatalities occurring in Australia and New Zealand from 2009 to 2015. Burn-related fatality rates per 100,000 population were estimated, and incidence trends assessed using Poisson regression analysis.<h4>Results</h4>Of the 310 burn-related fatalities that occurred in Australia and New Zealand, 2009-2015, 41% occurred in a pre-hospital setting. Overall, most burn-related fatality cases were fire related, occurred at home, and were of people aged 41-80 years. One quarter of all burn-related fatalities were a result of intentional self-harm. The population incidence of all burn-related fatalities combined, and for NSW, decreased over the study period.<h4>Conclusions</h4>This study has identified the importance of examining all burn-related fatalities. If this is not done, vulnerable population subgroups will be missed and prevention efforts poorly targeted.",,doi:https://doi.org/10.1016/j.burns.2019.07.003
 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,,,,"<h4>Background</h4>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).<h4>Objectives</h4>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.<h4>Search methods</h4>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%.<h4>Data collection and analysis</h4>We used standard methodological procedures expected by Cochrane.<h4>Main results</h4>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).<h4>Authors' conclusions</h4>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.",,pdf:https://discovery.ucl.ac.uk/10044558/1/Lumbers_et_al-2017-.pdf; 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
 33185739,https://doi.org/10.1007/s00395-020-00828-6,Functional investigation of the coronary artery disease gene SVEP1.,"Winkler MJ, Müller P, Sharifi AM, Wobst J, Winter H, Mokry M, Ma L, van der Laan SW, Pang S, Miritsch B, Hinterdobler J, Werner J, Stiller B, Güldener U, Webb TR, Asselbergs FW, Björkegren JLM, Maegdefessel L, Schunkert H, Sager HB, Kessler T.",,Basic research in cardiology,2020,2020-11-13,Y,Genetics; Atherosclerosis; coronary artery disease; Svep1,,,"A missense variant of the sushi, von Willebrand factor type A, EGF and pentraxin domain containing protein 1 (SVEP1) is genome-wide significantly associated with coronary artery disease. The mechanisms how SVEP1 impacts atherosclerosis are not known. We found endothelial cells (EC) and vascular smooth muscle cells to represent the major cellular source of SVEP1 in plaques. Plaques were larger in atherosclerosis-prone Svep1 haploinsufficient (ApoE<sup>-/-</sup>Svep1<sup>+/-</sup>) compared to Svep1 wild-type mice (ApoE<sup>-/-</sup>Svep1<sup>+/+</sup>) and ApoE<sup>-/-</sup>Svep1<sup>+/-</sup> mice displayed elevated plaque neutrophil, Ly6C<sup>high</sup> monocyte, and macrophage numbers. We assessed how leukocytes accumulated more inside plaques in ApoE<sup>-/-</sup>Svep1<sup>+/-</sup> mice and found enhanced leukocyte recruitment from blood into plaques. In vitro, we examined how SVEP1 deficiency promotes leukocyte recruitment and found elevated expression of the leukocyte attractant chemokine (C-X-C motif) ligand 1 (CXCL1) in EC after incubation with missense compared to wild-type SVEP1. Increasing wild-type SVEP1 levels silenced endothelial CXCL1 release. In line, plasma Cxcl1 levels were elevated in ApoE<sup>-/-</sup>Svep1<sup>+/-</sup> mice. Our studies reveal an atheroprotective role of SVEP1. Deficiency of wild-type Svep1 increased endothelial CXCL1 expression leading to enhanced recruitment of proinflammatory leukocytes from blood to plaque. Consequently, elevated vascular inflammation resulted in enhanced plaque progression in Svep1 deficiency.",,pdf:https://link.springer.com/content/pdf/10.1007/s00395-020-00828-6.pdf; doi:https://doi.org/10.1007/s00395-020-00828-6; html:https://europepmc.org/articles/PMC7666586; pdf:https://europepmc.org/articles/PMC7666586?pdf=render
-37794492,https://doi.org/10.1186/s13073-023-01233-z,Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.,"Neumann A, Ohlei O, Küçükali F, Bos IJ, Timsina J, Vos S, Prokopenko D, Tijms BM, Andreasson U, Blennow K, Vandenberghe R, Scheltens P, Teunissen CE, Engelborghs S, Frisoni GB, Blin O, Richardson JC, Bordet R, Lleó A, Alcolea D, Popp J, Marsh TW, Gorijala P, Clark C, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Van Broeckhoven C, Tanzi RE, Ten Kate M, Lill CM, Barkhof F, Cruchaga C, Lovestone S, Streffer J, Zetterberg H, Visser PJ, Sleegers K, Bertram L, EMIF-AD & ADNI study group.",,Genome medicine,2023,2023-10-04,Y,Principal component analysis; Biomarkers; Alzheimer’s disease; Dementia; Cerebrospinal fluid (CSF); multivariate analysis; Structural Equation Modeling; Mediation; Genome-wide Association Study (Gwas),,,"<h4>Background</h4>Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.<h4>Methods</h4>We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n = 205 controls, n = 546 mild cognitive impairment, n = 222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects.<h4>Results</h4>Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers.<h4>Conclusions</h4>These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.",,pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-023-01233-z; doi:https://doi.org/10.1186/s13073-023-01233-z; html:https://europepmc.org/articles/PMC10548686; pdf:https://europepmc.org/articles/PMC10548686?pdf=render
-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; doi:https://doi.org/10.1099/mgen.0.000700; html:https://europepmc.org/articles/PMC8743558; pdf:https://europepmc.org/articles/PMC8743558?pdf=render
 32283057,https://doi.org/10.1016/j.jid.2020.03.957,"Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study.","Loeff FC, Tsakok T, Dijk L, Hart MH, Duckworth M, Baudry D, Russell A, Dand N, van Leeuwen A, Griffiths CEM, Reynolds NJ, Barker J, Burden AD, Warren RB, de Vries A, Bloem K, Wolbink GJ, Smith CH, Rispens T, BADBIR, BSTOP Study Groups, PSORT consortium.",,The Journal of investigative dermatology,2020,2020-04-10,N,,,,"Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI] = 3.2-4.2) and in 10.6% (95% CI = 7.9-13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (-0.62 μg/ml [95% CI = -1.190 to -0.30] and -0.74 μg/ml [95% CI = -1.09 to -0.47], respectively) and higher absolute PASI (6.6 [95% CI = 3.0-9.9] and 1.9 [95% CI = 0.4-4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI = 3.9-8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.",,pdf:http://www.jidonline.org/article/S0022202X20313701/pdf; doi:https://doi.org/10.1016/j.jid.2020.03.957
-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; Multi-stakeholder; Start-ups; Small Medium-sized Enterprises,,,"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.",,pdf:https://link.springer.com/content/pdf/10.1007/s12325-023-02511-3.pdf; doi:https://doi.org/10.1007/s12325-023-02511-3; html:https://europepmc.org/articles/PMC10092909; pdf:https://europepmc.org/articles/PMC10092909?pdf=render
+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; doi:https://doi.org/10.1099/mgen.0.000700; html:https://europepmc.org/articles/PMC8743558; pdf:https://europepmc.org/articles/PMC8743558?pdf=render
 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.",,pdf:https://www.nature.com/articles/s41467-021-25703-3.pdf; doi:https://doi.org/10.1038/s41467-021-25703-3; html:https://europepmc.org/articles/PMC8463530; pdf:https://europepmc.org/articles/PMC8463530?pdf=render
+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; Multi-stakeholder; Start-ups; Small Medium-sized Enterprises,,,"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.",,pdf:https://link.springer.com/content/pdf/10.1007/s12325-023-02511-3.pdf; doi:https://doi.org/10.1007/s12325-023-02511-3; html:https://europepmc.org/articles/PMC10092909; pdf:https://europepmc.org/articles/PMC10092909?pdf=render
+37794492,https://doi.org/10.1186/s13073-023-01233-z,Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.,"Neumann A, Ohlei O, Küçükali F, Bos IJ, Timsina J, Vos S, Prokopenko D, Tijms BM, Andreasson U, Blennow K, Vandenberghe R, Scheltens P, Teunissen CE, Engelborghs S, Frisoni GB, Blin O, Richardson JC, Bordet R, Lleó A, Alcolea D, Popp J, Marsh TW, Gorijala P, Clark C, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Van Broeckhoven C, Tanzi RE, Ten Kate M, Lill CM, Barkhof F, Cruchaga C, Lovestone S, Streffer J, Zetterberg H, Visser PJ, Sleegers K, Bertram L, EMIF-AD & ADNI study group.",,Genome medicine,2023,2023-10-04,Y,Principal component analysis; Biomarkers; Alzheimer’s disease; Dementia; Cerebrospinal fluid (CSF); multivariate analysis; Structural Equation Modeling; Mediation; Genome-wide Association Study (Gwas),,,"<h4>Background</h4>Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.<h4>Methods</h4>We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n = 205 controls, n = 546 mild cognitive impairment, n = 222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects.<h4>Results</h4>Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers.<h4>Conclusions</h4>These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.",,pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-023-01233-z; doi:https://doi.org/10.1186/s13073-023-01233-z; html:https://europepmc.org/articles/PMC10548686; pdf:https://europepmc.org/articles/PMC10548686?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,,"<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.",pdf:https://academic.oup.com/europace/article-pdf/21/12/1776/31175830/euz220.pdf; doi:https://doi.org/10.1093/europace/euz220; html:https://europepmc.org/articles/PMC6888023; pdf:https://europepmc.org/articles/PMC6888023?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.", ,pdf:http://www.cell.com/article/S0002929720300033/pdf; 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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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).<h4>Interpretation</h4>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.<h4>Funding</h4>Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S1473309919304013/pdf; doi:https://doi.org/10.1016/S1473-3099(19)30401-3; html:https://europepmc.org/articles/PMC7340495
@@ -2182,12 +2182,12 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 31479209,https://doi.org/10.1056/nejmoa1907096,A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI.,"Claassens DMF, Vos GJA, Bergmeijer TO, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Janssen PWA, Kelder JC, Postma MJ, de Boer A, Boersma C, Deneer VHM, Ten Berg JM.",,The New England journal of medicine,2019,2019-09-03,N,,Better Care,cardiovascular,"BACKGROUND:It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors. METHODS:We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS:For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS:In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.).",,pdf:https://pure.rug.nl/ws/files/99703867/A_Genotype_Guided_Strategy_for_Oral_P2Y12_Inhibitors_in_Primary_PCI.pdf; doi:https://doi.org/10.1056/NEJMoa1907096
 34426706,https://doi.org/10.1038/s41591-021-01441-3,"Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases.","Cai N, Gomez-Duran A, Yonova-Doing E, Kundu K, Burgess AI, Golder ZJ, Calabrese C, Bonder MJ, Camacho M, Lawson RA, Li L, Williams-Gray CH, ICICLE-PD Study Group, Di Angelantonio E, Roberts DJ, Watkins NA, Ouwehand WH, Butterworth AS, Stewart ID, Pietzner M, Wareham NJ, Langenberg C, Danesh J, Walter K, Rothwell PM, Howson JMM, Stegle O, Chinnery PF, Soranzo N.",,Nature medicine,2021,2021-08-23,N,,,,"Mitochondrial DNA (mtDNA) variants influence the risk of late-onset human diseases, but the reasons for this are poorly understood. Undertaking a hypothesis-free analysis of 5,689 blood-derived biomarkers with mtDNA variants in 16,220 healthy donors, here we show that variants defining mtDNA haplogroups Uk and H4 modulate the level of circulating N-formylmethionine (fMet), which initiates mitochondrial protein translation. In human cytoplasmic hybrid (cybrid) lines, fMet modulated both mitochondrial and cytosolic proteins on multiple levels, through transcription, post-translational modification and proteolysis by an N-degron pathway, abolishing known differences between mtDNA haplogroups. In a further 11,966 individuals, fMet levels contributed to all-cause mortality and the disease risk of several common cardiovascular disorders. Together, these findings indicate that fMet plays a key role in common age-related disease through pleiotropic effects on cell proteostasis.",,pdf:https://push-zb.helmholtz-muenchen.de/deliver.php?id=34427; doi:https://doi.org/10.1038/s41591-021-01441-3
 31678026,https://doi.org/10.1016/s1473-3099(19)30410-4,Quantifying risks and interventions that have affected the burden of lower respiratory infections among children younger than 5 years: an analysis for the Global Burden of Disease Study 2017.,GBD 2017 Lower Respiratory Infections Collaborators.,,The Lancet. Infectious diseases,2020,2019-10-31,Y,,,,"<h4>Background</h4>Despite large reductions in under-5 lower respiratory infection (LRI) mortality in many locations, the pace of progress for LRIs has generally lagged behind that of other childhood infectious diseases. To better inform programmes and policies focused on preventing and treating LRIs, we assessed the contributions and patterns of risk factor attribution, intervention coverage, and sociodemographic development in 195 countries and territories by drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) LRI estimates.<h4>Methods</h4>We used four strategies to model LRI burden: the mortality due to LRIs was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive ensemble modelling tool; the incidence of LRIs was modelled using population representative surveys, health-care utilisation data, and scientific literature in a compartmental meta-regression tool; the attribution of risk factors for LRI mortality was modelled in a counterfactual framework; and trends in LRI mortality were analysed applying changes in exposure to risk factors over time. In GBD, infectious disease mortality, including that due to LRI, is among HIV-negative individuals. We categorised locations based on their burden in 1990 to make comparisons in the changing burden between 1990 and 2017 and evaluate the relative percent change in mortality rate, incidence, and risk factor exposure to explain differences in the health loss associated with LRIs among children younger than 5 years.<h4>Findings</h4>In 2017, LRIs caused 808 920 deaths (95% uncertainty interval 747 286-873 591) in children younger than 5 years. Since 1990, there has been a substantial decrease in the number of deaths (from 2 337 538 to 808 920 deaths; 65·4% decrease, 61·5-68·5) and in mortality rate (from 362·7 deaths [330·1-392·0] per 100 000 children to 118·9 deaths [109·8-128·3] per 100 000 children; 67·2% decrease, 63·5-70·1). LRI incidence declined globally (32·4% decrease, 27·2-37·5). The percent change in under-5 mortality rate and incidence has varied across locations. Among the risk factors assessed in this study, those responsible for the greatest decrease in under-5 LRI mortality between 1990 and 2017 were increased coverage of vaccination against Haemophilus influenza type b (11·4% decrease, 0·0-24·5), increased pneumococcal vaccine coverage (6·3% decrease, 6·1-6·3), and reductions in household air pollution (8·4%, 6·8-9·2).<h4>Interpretation</h4>Our findings show that there have been substantial but uneven declines in LRI mortality among countries between 1990 and 2017. Although improvements in indicators of sociodemographic development could explain some of these trends, changes in exposure to modifiable risk factors are related to the rates of decline in LRI mortality. No single intervention would universally accelerate reductions in health loss associated with LRIs in all settings, but emphasising the most dominant risk factors, particularly in countries with high case fatality, can contribute to the reduction of preventable deaths.<h4>Funding</h4>Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/s1473-3099(19)30410-4; doi:https://doi.org/10.1016/S1473-3099(19)30410-4; html:https://europepmc.org/articles/PMC7185492
-34316022,https://doi.org/10.1038/s41416-021-01505-8,Assessing the role of cortisol in cancer: a wide-ranged Mendelian randomisation study.,"Larsson SC, Lee WH, Kar S, Burgess S, Allara E.",,British journal of cancer,2021,2021-07-27,N,,,,"<h4>Background</h4>Cortisol's immunosuppressive, obesogenic, and hyperglycaemic effects suggest that it may play a role in cancer development. However, whether cortisol increases cancer risk is not known. We investigated the potential causal association between plasma cortisol and risk of overall and common site-specific cancers using Mendelian randomisation.<h4>Methods</h4>Three genetic variants associated with morning plasma cortisol levels at the genome-wide significance level (P < 5 × 10<sup>-8</sup>) in the Cortisol Network consortium were used as genetic instruments. Summary-level genome-wide association study data for the cancer outcomes were obtained from large-scale cancer consortia, the UK Biobank, and the FinnGen consortium. Two-sample Mendelian randomisation analyses were performed using the fixed-effects inverse-variance weighted method. Estimates across data sources were combined using meta-analysis.<h4>Results</h4>A standard deviation increase in genetically predicted plasma cortisol was associated with increased risk of endometrial cancer (odds ratio 1.50, 95% confidence interval 1.13-1.99; P = 0.005). There was no significant association between genetically predicted plasma cortisol and risk of other common site-specific cancers, including breast, ovarian, prostate, colorectal, lung, or malignant skin cancer, or overall cancer.<h4>Conclusions</h4>These results indicate that elevated plasma cortisol levels may increase the risk of endometrial cancer but not other cancers. The mechanism by which this occurs remains to be investigated.",,pdf:http://uu.diva-portal.org/smash/get/diva2:1617122/FULLTEXT01; doi:https://doi.org/10.1038/s41416-021-01505-8; html:https://europepmc.org/articles/PMC8476513; pdf:https://europepmc.org/articles/PMC8476513?pdf=render; doi:https://doi.org/10.1038/s41416-021-01505-8
 31115347,https://doi.org/10.2196/12412,Health Data Processes: A Framework for Analyzing and Discussing Efficient Use and Reuse of Health Data With a Focus on Patient-Reported Outcome Measures.,"Hjollund NHI, Valderas JM, Kyte D, Calvert MJ.",,Journal of medical Internet research,2019,2019-05-21,Y,Data collection; Medical Informatics; Patient-physician Relationship; Patient-reported Outcome,,,"The collection and use of patient health data are central to any kind of activity in the health care system. These data may be produced during routine clinical processes or obtained directly from the patient using patient-reported outcome (PRO) measures. Although efficiency and other reasons justify data availability for a range of potentially relevant uses, these data are nearly always collected for a single specific purpose. The health care literature reflects this narrow scope, and there is limited literature on the joint use of health data for daily clinical use, clinical research, surveillance, and administrative purposes. The aim of this paper is to provide a framework for discussing the efficient use of health data with a specific focus on the role of PRO measures. PRO data may be used at an individual patient level to inform patient care or shared decision making and to tailor care to individual needs or group-level needs as a complement to health record data, such as that on mortality and readmission, in order to inform service delivery and measure the real-world effectiveness of treatment. PRO measures may be used either for their own sake, to provide valuable information from the patient perspective, or as a proxy for clinical data that would otherwise not be feasible to collect. We introduce a framework to analyze any health care activity that involves health data. The framework consists of four data processes (patient identification, data collection, data aggregation and data use), further structured into two dichotomous dimensions in each data process (level: group vs patient; timeframe: ad hoc vs systematic). This framework is used to analyze various health activities with respect to joint use of data, considering the technical, legal, organizational, and logistical challenges that characterize each data process. Finally, we propose a model for joint use of health data with data collected during follow-up as a base. Demands for health data will continue to increase, which will further add to the need for the concerted use and reuse of PRO data for parallel purposes. Repeated and uncoordinated PRO data collection for the same patient for different purposes results in misuse of resources for the patient and the health care system as well as reduced response rates owing to questionnaire fatigue. PRO data can be routinely collected both at the hospital (from inpatients as well as outpatients) and outside of hospital settings; in primary or social care settings; or in the patient's home, provided the health informatics infrastructure is in place. In the future, clinical settings are likely to be a prominent source of PRO data; however, we are also likely to see increased remote collection of PRO data by patients in their own home (telePRO). Data collection for research and quality surveillance will have to adapt to this circumstance and adopt complementary data capture methods that take advantage of the utility of PRO data collected during daily clinical practice. The European Union's regulation with respect to the protection of personal data-General Data Protection Regulation-imposes severe restrictions on the use of health data for parallel purposes, and steps should be taken to alleviate the consequences while still protecting personal data against misuse.",,pdf:https://www.jmir.org/2019/5/e12412/PDF; doi:https://doi.org/10.2196/12412; html:https://europepmc.org/articles/PMC6547770
-37681566,https://doi.org/10.1161/jaha.123.030280,Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women.,"Tschiderer L, Peters SAE, van der Schouw YT, van Westing AC, Tong TYN, Willeit P, Seekircher L, Moreno-Iribas C, Huerta JM, Crous-Bou M, Söderholm M, Schulze MB, Johansson C, Själander S, Heath AK, Macciotta A, Dahm CC, Ibsen DB, Pala V, Mellemkjær L, Burgess S, Wood A, Kaaks R, Katzke V, Amiano P, Rodriguez-Barranco M, Engström G, Weiderpass E, Tjønneland A, Halkjær J, Panico S, Danesh J, Butterworth A, Onland-Moret NC.",,Journal of the American Heart Association,2023,2023-09-08,Y,Stroke; Age At Menopause; Mendelian Randomization Analysis; Observational Analysis,,,"Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8-13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07-1.12) for stroke, 1.09 (95% CI, 1.06-1.13) for ischemic stroke, 1.10 (95% CI, 1.04-1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08-1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84-1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. Conclusions In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030280; doi:https://doi.org/10.1161/JAHA.123.030280; html:https://europepmc.org/articles/PMC10547274; pdf:https://europepmc.org/articles/PMC10547274?pdf=render
+34316022,https://doi.org/10.1038/s41416-021-01505-8,Assessing the role of cortisol in cancer: a wide-ranged Mendelian randomisation study.,"Larsson SC, Lee WH, Kar S, Burgess S, Allara E.",,British journal of cancer,2021,2021-07-27,N,,,,"<h4>Background</h4>Cortisol's immunosuppressive, obesogenic, and hyperglycaemic effects suggest that it may play a role in cancer development. However, whether cortisol increases cancer risk is not known. We investigated the potential causal association between plasma cortisol and risk of overall and common site-specific cancers using Mendelian randomisation.<h4>Methods</h4>Three genetic variants associated with morning plasma cortisol levels at the genome-wide significance level (P < 5 × 10<sup>-8</sup>) in the Cortisol Network consortium were used as genetic instruments. Summary-level genome-wide association study data for the cancer outcomes were obtained from large-scale cancer consortia, the UK Biobank, and the FinnGen consortium. Two-sample Mendelian randomisation analyses were performed using the fixed-effects inverse-variance weighted method. Estimates across data sources were combined using meta-analysis.<h4>Results</h4>A standard deviation increase in genetically predicted plasma cortisol was associated with increased risk of endometrial cancer (odds ratio 1.50, 95% confidence interval 1.13-1.99; P = 0.005). There was no significant association between genetically predicted plasma cortisol and risk of other common site-specific cancers, including breast, ovarian, prostate, colorectal, lung, or malignant skin cancer, or overall cancer.<h4>Conclusions</h4>These results indicate that elevated plasma cortisol levels may increase the risk of endometrial cancer but not other cancers. The mechanism by which this occurs remains to be investigated.",,pdf:http://uu.diva-portal.org/smash/get/diva2:1617122/FULLTEXT01; doi:https://doi.org/10.1038/s41416-021-01505-8; html:https://europepmc.org/articles/PMC8476513; pdf:https://europepmc.org/articles/PMC8476513?pdf=render; doi:https://doi.org/10.1038/s41416-021-01505-8
 35360896,https://doi.org/10.1021/acs.analchem.1c03592,Finding Correspondence between Metabolomic Features in Untargeted Liquid Chromatography-Mass Spectrometry Metabolomics Datasets.,"Climaco Pinto R, Karaman I, Lewis MR, Hällqvist J, Kaluarachchi M, Graça G, Chekmeneva E, Durainayagam B, Ghanbari M, Ikram MA, Zetterberg H, Griffin J, Elliott P, Tzoulaki I, Dehghan A, Herrington D, Ebbels T.",,Analytical chemistry,2022,2022-03-31,Y,,,,"Integration of multiple datasets can greatly enhance bioanalytical studies, for example, by increasing power to discover and validate biomarkers. In liquid chromatography-mass spectrometry (LC-MS) metabolomics, it is especially hard to combine untargeted datasets since the majority of metabolomic features are not annotated and thus cannot be matched by chemical identity. Typically, the information available for each feature is retention time (RT), mass-to-charge ratio (<i>m</i>/<i>z</i>), and feature intensity (FI). Pairs of features from the same metabolite in separate datasets can exhibit small but significant differences, making matching very challenging. Current methods to address this issue are too simple or rely on assumptions that cannot be met in all cases. We present a method to find feature correspondence between two similar LC-MS metabolomics experiments or batches using only the features' RT, <i>m</i>/<i>z</i>, and FI. We demonstrate the method on both real and synthetic datasets, using six orthogonal validation strategies to gauge the matching quality. In our main example, 4953 features were uniquely matched, of which 585 (96.8%) of 604 manually annotated features were correct. In a second example, 2324 features could be uniquely matched, with 79 (90.8%) out of 87 annotated features correctly matched. Most of the missed annotated matches are between features that behave very differently from modeled inter-dataset shifts of RT, MZ, and FI. In a third example with simulated data with 4755 features per dataset, 99.6% of the matches were correct. Finally, the results of matching three other dataset pairs using our method are compared with a published alternative method, metabCombiner, showing the advantages of our approach. The method can be applied using M2S (Match 2 Sets), a free, open-source MATLAB toolbox, available at https://github.com/rjdossan/M2S.",,pdf:https://pubs.acs.org/doi/pdf/10.1021/acs.analchem.1c03592; doi:https://doi.org/10.1021/acs.analchem.1c03592; html:https://europepmc.org/articles/PMC9008693; pdf:https://europepmc.org/articles/PMC9008693?pdf=render
-36792666,https://doi.org/10.1038/s41467-023-36486-0,SVEP1 is an endogenous ligand for the orphan receptor PEAR1.,"Elenbaas JS, Pudupakkam U, Ashworth KJ, Kang CJ, Patel V, Santana K, Jung IH, Lee PC, Burks KH, Amrute JM, Mecham RP, Halabi CM, Alisio A, Di Paola J, Stitziel NO.",,Nature communications,2023,2023-02-15,Y,,,,"Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes vascular disease and associates with platelet reactivity in humans. Here, using a human genomic and proteomic approach, we identify a high affinity, disease-relevant, and potentially targetable interaction between SVEP1 and the orphan receptor Platelet and Endothelial Aggregation Receptor 1 (PEAR1). This interaction promotes PEAR1 phosphorylation and disease associated AKT/mTOR signaling in vascular cells and platelets. Mice lacking SVEP1 have reduced platelet activation, and exogenous SVEP1 induces PEAR1-dependent activation of platelets. SVEP1 and PEAR1 causally and concordantly relate to platelet phenotypes and cardiovascular disease in humans, as determined by Mendelian Randomization. Targeting this receptor-ligand interaction may be a viable therapeutic strategy to treat or prevent cardiovascular and thrombotic disease.",,pdf:https://www.nature.com/articles/s41467-023-36486-0.pdf; doi:https://doi.org/10.1038/s41467-023-36486-0; html:https://europepmc.org/articles/PMC9932102; pdf:https://europepmc.org/articles/PMC9932102?pdf=render
+37681566,https://doi.org/10.1161/jaha.123.030280,Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women.,"Tschiderer L, Peters SAE, van der Schouw YT, van Westing AC, Tong TYN, Willeit P, Seekircher L, Moreno-Iribas C, Huerta JM, Crous-Bou M, Söderholm M, Schulze MB, Johansson C, Själander S, Heath AK, Macciotta A, Dahm CC, Ibsen DB, Pala V, Mellemkjær L, Burgess S, Wood A, Kaaks R, Katzke V, Amiano P, Rodriguez-Barranco M, Engström G, Weiderpass E, Tjønneland A, Halkjær J, Panico S, Danesh J, Butterworth A, Onland-Moret NC.",,Journal of the American Heart Association,2023,2023-09-08,Y,Stroke; Age At Menopause; Mendelian Randomization Analysis; Observational Analysis,,,"Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8-13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07-1.12) for stroke, 1.09 (95% CI, 1.06-1.13) for ischemic stroke, 1.10 (95% CI, 1.04-1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08-1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84-1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. Conclusions In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030280; doi:https://doi.org/10.1161/JAHA.123.030280; html:https://europepmc.org/articles/PMC10547274; pdf:https://europepmc.org/articles/PMC10547274?pdf=render
 30842207,https://doi.org/10.1136/heartjnl-2019-314763,Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes: a systematic review and meta-analysis.,"Du H, Li X, Su N, Li L, Hao X, Gao H, Kwong JS, Vandvik PO, Yang X, Nemeth I, Mordi IR, Li Q, Zhang L, Rao L, Lang CC, Li J, Tian H, Li S.",,Heart (British Cardiac Society),2019,2019-03-06,N,Cardiovascular disease; Systematic review; Lipid-lowering Drugs; Low-density Lipoprotein Cholesterol; Proprotein Convertase Subtilisin/kexin Type 9 Inhibitors,,,"<h4>Background</h4>To evaluate the effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on major adverse cardiovascular events (MACE).<h4>Methods</h4>Our systematic review included randomised controlled trials if they studied PCSK9 inhibitors in patients for primary and/or secondary prevention of cardiovascular diseases or with hypercholesterolaemia/hyperlipidaemia. Dichotomous variables from individual studies were pooled by relative risks (RR) and their 95% CIs using the random-effect model. Risk difference (RD) in the 10-year frame was also estimated using the pooled RR and the estimated baseline risk using the control group. Grading of Recommendation Assessment, Development and Evaluation was used to assess the quality of evidence.<h4>Results</h4>We included 54 trials with 97 910 patients in the analysis. Compared with controls, PCSK9 inhibitors significantly reduced the risk of MACE by 16% (RR, 0.84; 95% CI 0.79 to 0.89; RD: 47 fewer per 1000 vs 286 as the baseline risk; 95% CI 32 to 59 fewer), non-fatal myocardial infarction (MI) by 17% (RR, 0.83; 95% CI 0.74 to 0.93; RD, 35 fewer per 1000 vs 207 as the baseline; 95% CI 13 to 53 fewer) and any stroke by 25% (RR, 0.75; 95% CI 0.65 to 0.85; RD, 16 fewer per 1000 vs 61 as the baseline; 95% CI 9 to 21 fewer) with moderate quality evidence. No significant differences were found between PCSK9 inhibitors and control groups in all-cause mortality, cardiovascular death, heart failure or unstable angina with low-quality evidence.<h4>Conclusions</h4>This study demonstrated that PCSK9 inhibitors could significantly reduce the risk of MACE, non-fatal MI and stroke.<h4>Trial registration</h4>PROSPERO; CRD42017073904.",,pdf:https://discovery.dundee.ac.uk/ws/files/30348534/Author_Accepted_Manuscript.pdf; doi:https://doi.org/10.1136/heartjnl-2019-314763
+36792666,https://doi.org/10.1038/s41467-023-36486-0,SVEP1 is an endogenous ligand for the orphan receptor PEAR1.,"Elenbaas JS, Pudupakkam U, Ashworth KJ, Kang CJ, Patel V, Santana K, Jung IH, Lee PC, Burks KH, Amrute JM, Mecham RP, Halabi CM, Alisio A, Di Paola J, Stitziel NO.",,Nature communications,2023,2023-02-15,Y,,,,"Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes vascular disease and associates with platelet reactivity in humans. Here, using a human genomic and proteomic approach, we identify a high affinity, disease-relevant, and potentially targetable interaction between SVEP1 and the orphan receptor Platelet and Endothelial Aggregation Receptor 1 (PEAR1). This interaction promotes PEAR1 phosphorylation and disease associated AKT/mTOR signaling in vascular cells and platelets. Mice lacking SVEP1 have reduced platelet activation, and exogenous SVEP1 induces PEAR1-dependent activation of platelets. SVEP1 and PEAR1 causally and concordantly relate to platelet phenotypes and cardiovascular disease in humans, as determined by Mendelian Randomization. Targeting this receptor-ligand interaction may be a viable therapeutic strategy to treat or prevent cardiovascular and thrombotic disease.",,pdf:https://www.nature.com/articles/s41467-023-36486-0.pdf; doi:https://doi.org/10.1038/s41467-023-36486-0; html:https://europepmc.org/articles/PMC9932102; pdf:https://europepmc.org/articles/PMC9932102?pdf=render
 34307493,https://doi.org/10.3389/fcvm.2021.677574,Automated Quality-Controlled Cardiovascular Magnetic Resonance Pericardial Fat Quantification Using a Convolutional Neural Network in the UK Biobank.,"Bard A, Raisi-Estabragh Z, Ardissino M, Lee AM, Pugliese F, Dey D, Sarkar S, Munroe PB, Neubauer S, Harvey NC, Petersen SE.",,Frontiers in cardiovascular medicine,2021,2021-07-07,Y,Obesity; Neural network; Machine Learning; Cardiovascular Magnetic Resonance; Pericardial Fat; Automated Image Analysis; Epicardial Fat,,,"<b>Background:</b> Pericardial adipose tissue (PAT) may represent a novel risk marker for cardiovascular disease. However, absence of rapid radiation-free PAT quantification methods has precluded its examination in large cohorts. <b>Objectives:</b> We developed a fully automated quality-controlled tool for cardiovascular magnetic resonance (CMR) PAT quantification in the UK Biobank (UKB). <b>Methods:</b> Image analysis comprised contouring an en-bloc PAT area on four-chamber cine images. We created a ground truth manual analysis dataset randomly split into training and test sets. We built a neural network for automated segmentation using a Multi-residual U-net architecture with incorporation of permanently active dropout layers to facilitate quality control of the model's output using Monte Carlo sampling. We developed an in-built quality control feature, which presents predicted Dice scores. We evaluated model performance against the test set (<i>n</i> = 87), the whole UKB Imaging cohort (<i>n</i> = 45,519), and an external dataset (<i>n</i> = 103). In an independent dataset, we compared automated CMR and cardiac computed tomography (CCT) PAT quantification. Finally, we tested association of CMR PAT with diabetes in the UKB (<i>n</i> = 42,928). <b>Results:</b> Agreement between automated and manual segmentations in the test set was almost identical to inter-observer variability (mean Dice score = 0.8). The quality control method predicted individual Dice scores with Pearson <i>r</i> = 0.75. Model performance remained high in the whole UKB Imaging cohort and in the external dataset, with medium-good quality segmentation in 94.3% (mean Dice score = 0.77) and 94.4% (mean Dice score = 0.78), respectively. There was high correlation between CMR and CCT PAT measures (Pearson <i>r</i> = 0.72, <i>p</i>-value 5.3 ×10<sup>-18</sup>). Larger CMR PAT area was associated with significantly greater odds of diabetes independent of age, sex, and body mass index. <b>Conclusions:</b> We present a novel fully automated method for CMR PAT quantification with good model performance on independent and external datasets, high correlation with reference standard CCT PAT measurement, and expected clinical associations with diabetes.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.677574/pdf; doi:https://doi.org/10.3389/fcvm.2021.677574; html:https://europepmc.org/articles/PMC8294033; pdf:https://europepmc.org/articles/PMC8294033?pdf=render
 33849854,https://doi.org/10.1136/bmjopen-2020-045206,Protocol for a scoping review exploring the use of patient-reported outcomes in adult social care.,"Hughes SE, Aiyegbusi OL, Lasserson DS, Collis P, Cruz Rivera S, McMullan C, Turner GM, Glasby J, Calvert M.",,BMJ open,2021,2021-04-13,Y,Protocols & Guidelines; Quality In Health Care; Organisation Of Health Services,,,"<h4>Introduction</h4>Patient-reported outcomes (PROs) are measures of a person's own views of their health, functioning and quality of life. They are typically assessed using validated, self-completed questionnaires known as patient-reported outcome measures (PROMs). PROMs are used in healthcare settings to support care planning, clinical decision-making, patient-practitioner communication and quality improvement. PROMs have a potential role in the delivery of social care where people often have multiple and complex long-term health conditions. However, the use of PROMs in this context is currently unclear. The objective of this scoping review is to explore the evidence relating to the use of PROMs in adult social care.<h4>Methods and analyses</h4>The electronic databases Medline (Ovid), PsychInfo (Ovid), ASSIA (ProQuest), Social Care Online (SCIE), Web of Science and EMBASE (Ovid) were searched on 29 September 2020 to identify eligible studies and other publically available documents published since 2010. A grey literature search and hand searching of citations and reference lists of the included studies will also be undertaken. No restrictions on study design or language of publication will be applied. Screening and data extraction will be completed independently by two reviewers. Quality appraisal of the included documents will use the Critical Appraisal Skills Programme and AACODS (Authority, Accuracy, Coverage, Objectivity, Date, Significance) checklists. A customised data charting table will be used for data extraction, with analysis of qualitative data using the framework method. The review findings will be presented as tables and in a narrative summary.<h4>Ethics and dissemination</h4>Ethical review is not required as scoping reviews are a form of secondary data analysis that synthesise data from publically available sources. Review findings will be shared with service users and other relevant stakeholders and disseminated through a peer-reviewed publication and conference presentations. This protocol is registered on the Open Science Framework (www.osf.io).",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/4/e045206.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-045206; html:https://europepmc.org/articles/PMC8051391; pdf:https://europepmc.org/articles/PMC8051391?pdf=render
 31730918,https://doi.org/10.1016/j.jclinepi.2019.11.006,Data mining information from electronic health records produced high yield and accuracy for current smoking status.,"Groenhof TKJ, Koers LR, Blasse E, de Groot M, Grobbee DE, Bots ML, Asselbergs FW, Lely AT, Haitjema S, UPOD, UCC-CVRM Study Groups.",,Journal of clinical epidemiology,2020,2019-11-12,N,data mining; Data Quality; Electronic Health Records; Text Mining; Learning Healthcare System; Routine Clinical Data,The Human Phenome,,"<h4>Objectives</h4>Researchers are increasingly using routine clinical data for care evaluations and feedback to patients and clinicians. The quality of these evaluations depends on the quality and completeness of the input data.<h4>Study design and setting</h4>We assessed the performance of an electronic health record (EHR)-based data mining algorithm, using the example of the smoking status in a cardiovascular population. As a reference standard, we used the questionnaire from the Utrecht Cardiovascular Cohort (UCC). To assess diagnostic accuracy, we calculated sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV).<h4>Results</h4>We analyzed 1,661 patients included in the UCC to January 18, 2019. Of those, 14% (n = 238) had missing information on smoking status in the UCC questionnaire. Data mining provided information on smoking status in 99% of the 1,661 participants. Diagnostic accuracy for current smoking was sensitivity 88%, specificity 92%, NPV 98%, and PPV 63%. From false positives, 85% reported they had quit smoking at the time of the UCC.<h4>Conclusion</h4>Data mining showed great potential in retrieving information on smoking (a near complete yield). Its diagnostic performance is good for negative smoking statuses. The implications of misclassification with data mining are dependent on the application of the data.",Utilises data mining and routine data to identify a patients smoking status. Does not account for long term smoking behaviour and is limited by the smaller size the dataset.,pdf:http://www.jclinepi.com/article/S0895435619304846/pdf; doi:https://doi.org/10.1016/j.jclinepi.2019.11.006
@@ -2309,8 +2309,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 34135082,https://doi.org/10.1681/asn.2020071070,Plasma Proteomics of Renal Function: A Transethnic Meta-Analysis and Mendelian Randomization Study.,"Matías-García PR, Wilson R, Guo Q, Zaghlool SB, Eales JM, Xu X, Charchar FJ, Dormer J, Maalmi H, Schlosser P, Elhadad MA, Nano J, Sharma S, Peters A, Fornoni A, Mook-Kanamori DO, Winkelmann J, Danesh J, Di Angelantonio E, Ouwehand WH, Watkins NA, Roberts DJ, Petrera A, Graumann J, Koenig W, Hveem K, Jonasson C, Köttgen A, Butterworth A, Prunotto M, Hauck SM, Herder C, Suhre K, Gieger C, Tomaszewski M, Teumer A, Teumer A, Waldenberger M, Human Kidney Tissue Resource.",,Journal of the American Society of Nephrology : JASN,2021,2021-06-16,N,Genetic epidemiology; glomerular filtration rate; Gene Expression; Plasma Proteomics; Chronic Kidney Disease; Biomarker Discovery; Mendelian Randomization; Epidemiology And Outcomes; Testican-2,,,"<h4>Background</h4>Studies on the relationship between renal function and the human plasma proteome have identified several potential biomarkers. However, investigations have been conducted largely in European populations, and causality of the associations between plasma proteins and kidney function has never been addressed.<h4>Methods</h4>A cross-sectional study of 993 plasma proteins among 2882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified transethnic associations between eGFR/CKD and proteomic biomarkers. For the replicated associations, two-sample bidirectional Mendelian randomization (MR) was used to investigate potential causal relationships. Publicly available datasets and transcriptomic data from independent studies were used to examine the association between gene expression in kidney tissue and eGFR.<h4>Results</h4>In total, 57 plasma proteins were associated with eGFR, including one novel protein. Of these, 23 were additionally associated with CKD. The strongest inferred causal effect was the positive effect of eGFR on testican-2, in line with the known biological role of this protein and the expression of its protein-coding gene (<i>SPOCK2</i>) in renal tissue. We also observed suggestive evidence of an effect of melanoma inhibitory activity (MIA), carbonic anhydrase III, and cystatin-M on eGFR.<h4>Conclusions</h4>In a discovery-replication setting, we identified 57 proteins transethnically associated with eGFR. The revealed causal relationships are an important stepping stone in establishing testican-2 as a clinically relevant physiological marker of kidney disease progression, and point to additional proteins warranting further investigation.",,pdf:https://jasn.asnjournals.org/content/jnephrol/32/7/1747.full.pdf; doi:https://doi.org/10.1681/ASN.2020071070; html:https://europepmc.org/articles/PMC8425654; doi:https://doi.org/10.1681/asn.2020071070
 34225492,https://doi.org/10.1128/mbio.02531-20,Structural Basis for a Neutralizing Antibody Response Elicited by a Recombinant Hantaan Virus Gn Immunogen.,"Rissanen I, Krumm SA, Stass R, Whitaker A, Voss JE, Bruce EA, Rothenberger S, Kunz S, Burton DR, Huiskonen JT, Botten JW, Bowden TA, Doores KJ.",,mBio,2021,2021-07-06,Y,Structure; Glycoprotein; Hantavirus; Neutralizing antibody; Zoonosis,,,"Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two glycoproteins, Gn and Gc, which are responsible for negotiating host cell entry and constitute key therapeutic targets. Here, we demonstrate that recombinantly derived Gn from Hantaan virus (HTNV) elicits a neutralizing antibody response (serum dilution that inhibits 50% infection [ID<sub>50</sub>], 1:200 to 1:850) in an animal model. Using antigen-specific B cell sorting, we isolated monoclonal antibodies (mAbs) exhibiting neutralizing and non-neutralizing activity, termed mAb HTN-Gn1 and mAb nnHTN-Gn2, respectively. Crystallographic analysis reveals that these mAbs target spatially distinct epitopes at disparate sites of the N-terminal region of the HTNV Gn ectodomain. Epitope mapping onto a model of the higher order (Gn-Gc)<sub>4</sub> spike supports the immune accessibility of the mAb HTN-Gn1 epitope, a hypothesis confirmed by electron cryo-tomography of the antibody with virus-like particles. These data define natively exposed regions of the hantaviral Gn that can be targeted in immunogen design. <b>IMPORTANCE</b> The spillover of pathogenic hantaviruses from rodent reservoirs into the human population poses a continued threat to human health. Here, we show that a recombinant form of the Hantaan virus (HTNV) surface-displayed glycoprotein, Gn, elicits a neutralizing antibody response in rabbits. We isolated a neutralizing (HTN-Gn1) and a non-neutralizing (nnHTN-Gn2) monoclonal antibody and provide the first molecular-level insights into how the Gn glycoprotein may be targeted by the antibody-mediated immune response. These findings may guide rational vaccine design approaches focused on targeting the hantavirus glycoprotein envelope.",,pdf:https://helda.helsinki.fi/bitstream/10138/341549/1/mBio.02531_20.pdf; doi:https://doi.org/10.1128/mBio.02531-20; html:https://europepmc.org/articles/PMC8406324; pdf:https://europepmc.org/articles/PMC8406324?pdf=render
 31844323,https://doi.org/10.1038/s41588-019-0549-x,N<sup>6</sup>-methyladenosine regulates the stability of RNA:DNA hybrids in human cells.,"Abakir A, Giles TC, Cristini A, Foster JM, Dai N, Starczak M, Rubio-Roldan A, Li M, Eleftheriou M, Crutchley J, Flatt L, Young L, Gaffney DJ, Denning C, Dalhus B, Emes RD, Gackowski D, Corrêa IR, Garcia-Perez JL, Klungland A, Gromak N, Ruzov A.",,Nature genetics,2020,2019-12-16,Y,,,,"R-loops are nucleic acid structures formed by an RNA:DNA hybrid and unpaired single-stranded DNA that represent a source of genomic instability in mammalian cells<sup>1-4</sup>. Here we show that N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification, contributing to different aspects of messenger RNA metabolism<sup>5,6</sup>, is detectable on the majority of RNA:DNA hybrids in human pluripotent stem cells. We demonstrate that m<sup>6</sup>A-containing R-loops accumulate during G<sub>2</sub>/M and are depleted at G<sub>0</sub>/G<sub>1</sub> phases of the cell cycle, and that the m<sup>6</sup>A reader promoting mRNA degradation, YTHDF2 (ref. <sup>7</sup>), interacts with R-loop-enriched loci in dividing cells. Consequently, YTHDF2 knockout leads to increased R-loop levels, cell growth retardation and accumulation of γH2AX, a marker for DNA double-strand breaks, in mammalian cells. Our results suggest that m<sup>6</sup>A regulates accumulation of R-loops, implying a role for this modification in safeguarding genomic stability.",,pdf:https://europepmc.org/articles/pmc6974403?pdf=render; doi:https://doi.org/10.1038/s41588-019-0549-x; html:https://europepmc.org/articles/PMC6974403; pdf:https://europepmc.org/articles/PMC6974403?pdf=render
-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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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]; <i>P</i>=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; <i>P</i>=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; <i>P</i>=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.<h4>Conclusions</h4>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.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.057888; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.057888; html:https://europepmc.org/articles/PMC9047645; pdf:https://europepmc.org/articles/PMC9047645?pdf=render
 31770382,https://doi.org/10.1371/journal.pmed.1002974,"Long-term mortality in mothers of infants with neonatal abstinence syndrome: A population-based parallel-cohort study in England and Ontario, Canada.","Guttmann A, Blackburn R, Amartey A, Zhou L, Wijlaars L, Saunders N, Harron K, Chiu M, Gilbert R.",,PLoS medicine,2019,2019-11-26,Y,,Improving Public Health,,"<h4>Background</h4>Opioid addiction is a major public health threat to healthy life expectancy; however, little is known of long-term mortality for mothers with opioid use in pregnancy. Pregnancy and delivery care are opportunities to improve access to addiction and supportive services. Treating neonatal abstinence syndrome (NAS) as a marker of opioid use during pregnancy, this study reports long-term maternal mortality among mothers with a birth affected by NAS in relation to that of mothers without a NAS-affected birth in 2 high-prevalence jurisdictions, England and Ontario, Canada.<h4>Methods and findings</h4>We conducted a population-based study using linked administrative health data to develop parallel cohorts of mother-infant dyads in England and Ontario between 2002 and 2012. The study population comprised 13,577 and 4,966 mothers of infants with NAS and 4,205,675 and 929,985 control mothers in England and Ontario, respectively. Death records captured all-cause maternal mortality after delivery through March 31, 2016, and cause-specific maternal mortality to December 31, 2014. The primary exposure was a live birth of an infant with NAS, and the main outcome was all deaths among mothers following their date of delivery. We modelled the association between NAS and all-cause maternal mortality using Cox regression, and the cumulative incidence of cause-specific mortality within a competing risks framework. All-cause mortality rates, 10-year cumulative incidence risk of death, and crude and age-adjusted hazard ratios were calculated. Estimated crude 10-year mortality based on Kaplan-Meier curves in mothers of infants with NAS was 5.1% (95% CI 4.7%-5.6%) in England and 4.6% (95% CI 3.8%-5.5%) in Ontario versus 0.4% (95% CI 0.41%-0.42%) in England and 0.4% (95% CI 0.38%-0.41%) in Ontario for controls (p < 0.001 for all comparisons). Survival curves showed no clear inflection point or period of heightened risk. The crude hazard ratio for all-cause mortality was 12.1 (95% 11.1-13.2; p < 0.001) in England and 11.4 (9.7-13.4; p < 0.001) in Ontario; age adjustment did not reduce the hazard ratios. The cumulative incidence of death was higher among NAS mothers than controls for almost all causes of death. The majority of deaths were by avoidable causes, defined as those that are preventable, amenable to care, or both. Limitations included lack of direct measures of maternal opioid use, other substance misuse, and treatments or supports received.<h4>Conclusions</h4>In this study, we found that approximately 1 in 20 mothers of infants with NAS died within 10 years of delivery in both England and Canada-a mortality risk 11-12 times higher than for control mothers. Risk of death was not limited to the early postpartum period targeted by most public health programs. Policy responses to the current opioid epidemic require effective strategies for long-term support to improve the health and welfare of opioid-using mothers and their children.",This paper investigates the mortality of mothers of infants with Neonatal abstinence syndrome. This population has a greatly increased mortality compared to mothers who don't have NAS. The paper highlights the lack of long term support for this group.,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1002974&type=printable; doi:https://doi.org/10.1371/journal.pmed.1002974; html:https://europepmc.org/articles/PMC6879118; pdf:https://europepmc.org/articles/PMC6879118?pdf=render
+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,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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]; <i>P</i>=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; <i>P</i>=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; <i>P</i>=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.<h4>Conclusions</h4>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.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.057888; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.057888; html:https://europepmc.org/articles/PMC9047645; pdf:https://europepmc.org/articles/PMC9047645?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,,,,"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0273687&type=printable; doi:https://doi.org/10.1371/journal.pone.0273687; html:https://europepmc.org/articles/PMC9462779; pdf:https://europepmc.org/articles/PMC9462779?pdf=render
 34857774,https://doi.org/10.1038/s41598-021-00854-x,Application of information theoretic feature selection and machine learning methods for the development of genetic risk prediction models.,"Jalali-Najafabadi F, Stadler M, Dand N, Jadon D, Soomro M, Ho P, Marzo-Ortega H, Helliwell P, Korendowych E, Simpson MA, Packham J, Smith CH, Barker JN, McHugh N, Warren RB, Barton A, Bowes J, BADBIR Study Group, BSTOP Study Group.",,Scientific reports,2021,2021-12-02,Y,,,,"In view of the growth of clinical risk prediction models using genetic data, there is an increasing need for studies that use appropriate methods to select the optimum number of features from a large number of genetic variants with a high degree of redundancy between features due to linkage disequilibrium (LD). Filter feature selection methods based on information theoretic criteria, are well suited to this challenge and will identify a subset of the original variables that should result in more accurate prediction. However, data collected from cohort studies are often high-dimensional genetic data with potential confounders presenting challenges to feature selection and risk prediction machine learning models. Patients with psoriasis are at high risk of developing a chronic arthritis known as psoriatic arthritis (PsA). The prevalence of PsA in this patient group can be up to 30% and the identification of high risk patients represents an important clinical research which would allow early intervention and a reduction of disability. This also provides us with an ideal scenario for the development of clinical risk prediction models and an opportunity to explore the application of information theoretic criteria methods. In this study, we developed the feature selection and psoriatic arthritis (PsA) risk prediction models that were applied to a cross-sectional genetic dataset of 1462 PsA cases and 1132 cutaneous-only psoriasis (PsC) cases using 2-digit HLA alleles imputed using the SNP2HLA algorithm. We also developed stratification method to mitigate the impact of potential confounder features and illustrate that confounding features impact the feature selection. The mitigated dataset was used in training of seven supervised algorithms. 80% of data was randomly used for training of seven supervised machine learning methods using stratified nested cross validation and 20% was selected randomly as a holdout set for internal validation. The risk prediction models were then further validated in UK Biobank dataset containing data on 1187 participants and a set of features overlapping with the training dataset.Performance of these methods has been evaluated using the area under the curve (AUC), accuracy, precision, recall, F1 score and decision curve analysis(net benefit). The best model is selected based on three criteria: the 'lowest number of feature subset' with the 'maximal average AUC over the nested cross validation' and good generalisability to the UK Biobank dataset. In the original dataset, with over 100 different bootstraps and seven feature selection (FS) methods, HLA_C_*06 was selected as the most informative genetic variant. When the dataset is mitigated the single most important genetic features based on rank was identified as HLA_B_*27 by the seven different feature selection methods, consistent with previous analyses of this data using regression based methods. However, the predictive accuracy of these single features in post mitigation was found to be moderate (AUC= 0.54 (internal cross validation), AUC=0.53 (internal hold out set), AUC=0.55(external data set)). Sequentially adding additional HLA features based on rank improved the performance of the Random Forest classification model where 20 2-digit features selected by Interaction Capping (ICAP) demonstrated (AUC= 0.61 (internal cross validation), AUC=0.57 (internal hold out set), AUC=0.58 (external dataset)). The stratification method for mitigation of confounding features and filter information theoretic feature selection can be applied to a high dimensional dataset with the potential confounders.",,pdf:https://www.nature.com/articles/s41598-021-00854-x.pdf; doi:https://doi.org/10.1038/s41598-021-00854-x; html:https://europepmc.org/articles/PMC8640070; pdf:https://europepmc.org/articles/PMC8640070?pdf=render
 32334655,https://doi.org/10.1016/s0140-6736(20)30608-5,"Health sector spending and spending on HIV/AIDS, tuberculosis, and malaria, and development assistance for health: progress towards Sustainable Development Goal 3.",Global Burden of Disease Health Financing Collaborator Network.,,"Lancet (London, England)",2020,2020-04-23,Y,,Better Care,infection,"<h4>Background</h4>Sustainable Development Goal (SDG) 3 aims to ""ensure healthy lives and promote well-being for all at all ages"". While a substantial effort has been made to quantify progress towards SDG3, less research has focused on tracking spending towards this goal. We used spending estimates to measure progress in financing the priority areas of SDG3, examine the association between outcomes and financing, and identify where resource gains are most needed to achieve the SDG3 indicators for which data are available.<h4>Methods</h4>We estimated domestic health spending, disaggregated by source (government, out-of-pocket, and prepaid private) from 1995 to 2017 for 195 countries and territories. For disease-specific health spending, we estimated spending for HIV/AIDS and tuberculosis for 135 low-income and middle-income countries, and malaria in 106 malaria-endemic countries, from 2000 to 2017. We also estimated development assistance for health (DAH) from 1990 to 2019, by source, disbursing development agency, recipient, and health focus area, including DAH for pandemic preparedness. Finally, we estimated future health spending for 195 countries and territories from 2018 until 2030. We report all spending estimates in inflation-adjusted 2019 US$, unless otherwise stated.<h4>Findings</h4>Since the development and implementation of the SDGs in 2015, global health spending has increased, reaching $7·9 trillion (95% uncertainty interval 7·8-8·0) in 2017 and is expected to increase to $11·0 trillion (10·7-11·2) by 2030. In 2017, in low-income and middle-income countries spending on HIV/AIDS was $20·2 billion (17·0-25·0) and on tuberculosis it was $10·9 billion (10·3-11·8), and in malaria-endemic countries spending on malaria was $5·1 billion (4·9-5·4). Development assistance for health was $40·6 billion in 2019 and HIV/AIDS has been the health focus area to receive the highest contribution since 2004. In 2019, $374 million of DAH was provided for pandemic preparedness, less than 1% of DAH. Although spending has increased across HIV/AIDS, tuberculosis, and malaria since 2015, spending has not increased in all countries, and outcomes in terms of prevalence, incidence, and per-capita spending have been mixed. The proportion of health spending from pooled sources is expected to increase from 81·6% (81·6-81·7) in 2015 to 83·1% (82·8-83·3) in 2030.<h4>Interpretation</h4>Health spending on SDG3 priority areas has increased, but not in all countries, and progress towards meeting the SDG3 targets has been mixed and has varied by country and by target. The evidence on the scale-up of spending and improvements in health outcomes suggest a nuanced relationship, such that increases in spending do not always results in improvements in outcomes. Although countries will probably need more resources to achieve SDG3, other constraints in the broader health system such as inefficient allocation of resources across interventions and populations, weak governance systems, human resource shortages, and drug shortages, will also need to be addressed.<h4>Funding</h4>The Bill & Melinda Gates Foundation.",,pdf:https://dro.deakin.edu.au/articles/journal_contribution/Health_sector_spending_and_spending_on_HIV_AIDS_tuberculosis_and_malaria_and_development_assistance_for_health_progress_towards_Sustainable_Development_Goal_3/20707408/1/files/36922243.pdf; doi:https://doi.org/10.1016/S0140-6736(20)30608-5; html:https://europepmc.org/articles/PMC7180045
@@ -2412,8 +2412,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 36703164,https://doi.org/10.1186/s13073-022-01152-5,Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry.,"Mueller SH, Lai AG, Valkovskaya M, Michailidou K, Bolla MK, Wang Q, Dennis J, Lush M, Abu-Ful Z, Ahearn TU, Andrulis IL, Anton-Culver H, Antonenkova NN, Arndt V, Aronson KJ, Augustinsson A, Baert T, Freeman LEB, Beckmann MW, Behrens S, Benitez J, Bermisheva M, Blomqvist C, Bogdanova NV, Bojesen SE, Bonanni B, Brenner H, Brucker SY, Buys SS, Castelao JE, Chan TL, Chang-Claude J, Chanock SJ, Choi JY, Chung WK, NBCS Collaborators, Colonna SV, CTS Consortium, Cornelissen S, Couch FJ, Czene K, Daly MB, Devilee P, Dörk T, Dossus L, Dwek M, Eccles DM, Ekici AB, Eliassen AH, Engel C, Evans DG, Fasching PA, Fletcher O, Flyger H, Gago-Dominguez M, Gao YT, García-Closas M, García-Sáenz JA, Genkinger J, Gentry-Maharaj A, Grassmann F, Guénel P, Gündert M, Haeberle L, Hahnen E, Haiman CA, Håkansson N, Hall P, Harkness EF, Harrington PA, Hartikainen JM, Hartman M, Hein A, Ho WK, Hooning MJ, Hoppe R, Hopper JL, Houlston RS, Howell A, Hunter DJ, Huo D, ABCTB Investigators, Ito H, Iwasaki M, Jakubowska A, Janni W, John EM, Jones ME, Jung A, Kaaks R, Kang D, Khusnutdinova EK, Kim SW, Kitahara CM, Koutros S, Kraft P, Kristensen VN, Kubelka-Sabit K, Kurian AW, Kwong A, Lacey JV, Lambrechts D, Le Marchand L, Li J, Linet M, Lo WY, Long J, Lophatananon A, Mannermaa A, Manoochehri M, Margolin S, Matsuo K, Mavroudis D, Menon U, Muir K, Murphy RA, Nevanlinna H, Newman WG, Niederacher D, O'Brien KM, Obi N, Offit K, Olopade OI, Olshan AF, Olsson H, Park SK, Patel AV, Patel A, Perou CM, Peto J, Pharoah PDP, Plaseska-Karanfilska D, Presneau N, Rack B, Radice P, Ramachandran D, Rashid MU, Rennert G, Romero A, Ruddy KJ, Ruebner M, Saloustros E, Sandler DP, Sawyer EJ, Schmidt MK, Schmutzler RK, Schneider MO, Scott C, Shah M, Sharma P, Shen CY, Shu XO, Simard J, Surowy H, Tamimi RM, Tapper WJ, Taylor JA, Teo SH, Teras LR, Toland AE, Tollenaar RAEM, Torres D, Torres-Mejía G, Troester MA, Truong T, Vachon CM, Vijai J, Weinberg CR, Wendt C, Winqvist R, Wolk A, Wu AH, Yamaji T, Yang XR, Yu JC, Zheng W, Ziogas A, Ziv E, Dunning AM, Easton DF, Hemingway H, Hamann U, Kuchenbaecker KB.",,Genome medicine,2023,2023-01-26,Y,Gene regulation; Genome-wide Association Study; Breast Cancer Susceptibility; Rare Variants; Diverse Ancestry,,,"<h4>Background</h4>Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.<h4>Methods</h4>We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.<h4>Results</h4>In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10<sup>-6</sup>) and AC058822.1 (P = 1.47 × 10<sup>-4</sup>), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.<h4>Conclusions</h4>Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10<sup>-5</sup>), demonstrating the importance of diversifying study cohorts.",,pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-022-01152-5; doi:https://doi.org/10.1186/s13073-022-01152-5; html:https://europepmc.org/articles/PMC9878779; pdf:https://europepmc.org/articles/PMC9878779?pdf=render
 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 <i>MUC5B</i>.",,pdf:https://helda.helsinki.fi/bitstream/10138/355828/1/Leveraging_global_multi_ancestry_meta_a...pdf; doi:https://doi.org/10.1016/j.xgen.2022.100181; html:https://europepmc.org/articles/PMC9903787; pdf:https://europepmc.org/articles/PMC9903787?pdf=render
 36068517,https://doi.org/10.1186/s12916-022-02486-y,"The prevalence of onchocerciasis in Africa and Yemen, 2000-2018: a geospatial analysis.","Schmidt CA, Cromwell EA, Hill E, Donkers KM, Schipp MF, Johnson KB, Pigott DM, LBD 2019 Neglected Tropical Diseases Collaborators, Hay SI.",,BMC medicine,2022,2022-09-07,Y,Onchocerciasis; Neglected Tropical Diseases; Geospatial Model,,,"<h4>Background</h4>Onchocerciasis is a disease caused by infection with Onchocerca volvulus, which is transmitted to humans via the bite of several species of black fly, and is responsible for permanent blindness or vision loss, as well as severe skin disease. Predominantly endemic in parts of Africa and Yemen, preventive chemotherapy with mass drug administration of ivermectin is the primary intervention recommended for the elimination of its transmission.<h4>Methods</h4>A dataset of 18,116 geo-referenced prevalence survey datapoints was used to model annual 2000-2018 infection prevalence in Africa and Yemen. Using Bayesian model-based geostatistics, we generated spatially continuous estimates of all-age 2000-2018 onchocerciasis infection prevalence at the 5 × 5-km resolution as well as aggregations to the national level, along with corresponding estimates of the uncertainty in these predictions.<h4>Results</h4>As of 2018, the prevalence of onchocerciasis infection continues to be concentrated across central and western Africa, with the highest mean estimates at the national level in Ghana (12.2%, 95% uncertainty interval [UI] 5.0-22.7). Mean estimates exceed 5% infection prevalence at the national level for Cameroon, Central African Republic, Democratic Republic of the Congo (DRC), Guinea-Bissau, Sierra Leone, and South Sudan.<h4>Conclusions</h4>Our analysis suggests that onchocerciasis infection has declined over the last two decades throughout western and central Africa. Focal areas of Angola, Cameroon, the Democratic Republic of the Congo, Ethiopia, Ghana, Guinea, Mali, Nigeria, South Sudan, and Uganda continue to have mean microfiladermia prevalence estimates exceeding 25%. At and above this level, the continuation or initiation of mass drug administration with ivermectin is supported. If national programs aim to eliminate onchocerciasis infection, additional surveillance or supervision of areas of predicted high prevalence would be warranted to ensure sufficiently high coverage of program interventions.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02486-y; doi:https://doi.org/10.1186/s12916-022-02486-y; html:https://europepmc.org/articles/PMC9449300; pdf:https://europepmc.org/articles/PMC9449300?pdf=render
-37595128,https://doi.org/10.1097/hep.0000000000000361,The global fatty liver disease Sustainable Development Goal country score for 195 countries and territories.,"Lazarus JV, Han H, Mark HE, Alqahtani SA, Schattenberg JM, Soriano JB, White TM, Zelber-Sagi S, Dirac MA, GBD Fatty Liver Disease Sustainable Development Goal Collaborators.",,"Hepatology (Baltimore, Md.)",2023,2023-04-18,Y,,,,"<h4>Background and aims</h4>Fatty liver disease is highly prevalent, resulting in overarching wellbeing and economic costs. Addressing it requires comprehensive and coordinated multisectoral action. We developed a fatty liver disease Sustainable Development Goal (SDG) country score to provide insights into country-level preparedness to address fatty liver disease through a whole-of-society lens.<h4>Approach and results</h4>We developed 2 fatty liver disease-SDG score sets. The first included 6 indicators (child wasting, child overweight, noncommunicable disease mortality, a universal health coverage service coverage index, health worker density, and education attainment), covering 195 countries and territories between 1990 and 2017. The second included the aforementioned indicators plus an urban green space indicator, covering 60 countries and territories for which 2017 data were available. To develop the fatty liver disease-SDG score, indicators were categorized as ""positive"" or ""negative"" and scaled from 0 to 100. Higher scores indicate better preparedness levels. Fatty liver disease-SDG scores varied between countries and territories (n = 195), from 14.6 (95% uncertainty interval: 8.9 to 19.4) in Niger to 93.5 (91.6 to 95.3) in Japan; 18 countries and territories scored > 85. Regionally, the high-income super-region had the highest score at 88.8 (87.3 to 90.1) in 2017, whereas south Asia had the lowest score at 44.1 (42.4 to 45.8). Between 1990 and 2017, the fatty liver disease-SDG score increased in all super-regions, with the greatest increase in south Asia, but decreased in 8 countries and territories.<h4>Conclusions</h4>The fatty liver disease-SDG score provides a strategic advocacy tool at the national and global levels for the liver health field and noncommunicable disease advocates, highlighting the multisectoral collaborations needed to address fatty liver disease, and noncommunicable diseases overall.",,html:https://journals.lww.com/hep/Abstract/9900/The_global_Fatty_Liver_Disease_Sustainable.395.aspx; doi:https://doi.org/10.1097/HEP.0000000000000361; html:https://europepmc.org/articles/PMC10442089; pdf:https://europepmc.org/articles/PMC10442089?pdf=render
 32654539,https://doi.org/10.1161/circulationaha.119.045526,Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.,"Mahmoodi BK, Tragante V, Kleber ME, Holmes MV, Schmidt AF, McCubrey RO, Howe LJ, Direk K, Allayee H, Baranova EV, Braund PS, Delgado GE, Eriksson N, Gijsberts CM, Gong Y, Hartiala J, Heydarpour M, Pasterkamp G, Kotti S, Kuukasjärvi P, Lenzini PA, Levin D, Lyytikäinen LP, Muehlschlegel JD, Nelson CP, Nikus K, Pilbrow AP, Wilson Tang WH, van der Laan SW, van Setten J, Vilmundarson RO, Deanfield J, Deloukas P, Dudbridge F, James S, Mordi IR, Teren A, Bergmeijer TO, Body SC, Bots M, Burkhardt R, Cooper-DeHoff RM, Cresci S, Danchin N, Doughty RN, Grobbee DE, Hagström E, Hazen SL, Held C, Hoefer IE, Hovingh GK, Johnson JA, Kaczor MP, Kähönen M, Klungel OH, Laurikka JO, Lehtimäki T, Maitland-van der Zee AH, McPherson R, Palmer CN, Kraaijeveld AO, Pepine CJ, Sanak M, Sattar N, Scholz M, Simon T, Spertus JA, Stewart AFR, Szczeklik W, Thiery J, Visseren FLJ, Waltenberger J, Richards AM, Lang CC, Cameron VA, Åkerblom A, Pare G, März W, Samani NJ, Hingorani AD, Ten Berg JM, Wallentin L, Asselbergs FW, Patel RS.",,Circulation,2020,2020-07-13,N,Thrombosis; Myocardial infarction; Single nucleotide polymorphism; Prognosis; coronary artery disease; Secondary Prevention; Genetic Association Studies,,,"<h4>Background</h4>Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD.<h4>Methods</h4>We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality.<h4>Results</h4>The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; <i>I</i><sup><i>2</i></sup>=28%; <i>P</i>-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity.<h4>Conclusions</h4>Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.119.045526; doi:https://doi.org/10.1161/CIRCULATIONAHA.119.045526; html:https://europepmc.org/articles/PMC7493828; pdf:https://europepmc.org/articles/PMC7493828?pdf=render; doi:https://doi.org/10.1161/circulationaha.119.045526
+37595128,https://doi.org/10.1097/hep.0000000000000361,The global fatty liver disease Sustainable Development Goal country score for 195 countries and territories.,"Lazarus JV, Han H, Mark HE, Alqahtani SA, Schattenberg JM, Soriano JB, White TM, Zelber-Sagi S, Dirac MA, GBD Fatty Liver Disease Sustainable Development Goal Collaborators.",,"Hepatology (Baltimore, Md.)",2023,2023-04-18,Y,,,,"<h4>Background and aims</h4>Fatty liver disease is highly prevalent, resulting in overarching wellbeing and economic costs. Addressing it requires comprehensive and coordinated multisectoral action. We developed a fatty liver disease Sustainable Development Goal (SDG) country score to provide insights into country-level preparedness to address fatty liver disease through a whole-of-society lens.<h4>Approach and results</h4>We developed 2 fatty liver disease-SDG score sets. The first included 6 indicators (child wasting, child overweight, noncommunicable disease mortality, a universal health coverage service coverage index, health worker density, and education attainment), covering 195 countries and territories between 1990 and 2017. The second included the aforementioned indicators plus an urban green space indicator, covering 60 countries and territories for which 2017 data were available. To develop the fatty liver disease-SDG score, indicators were categorized as ""positive"" or ""negative"" and scaled from 0 to 100. Higher scores indicate better preparedness levels. Fatty liver disease-SDG scores varied between countries and territories (n = 195), from 14.6 (95% uncertainty interval: 8.9 to 19.4) in Niger to 93.5 (91.6 to 95.3) in Japan; 18 countries and territories scored > 85. Regionally, the high-income super-region had the highest score at 88.8 (87.3 to 90.1) in 2017, whereas south Asia had the lowest score at 44.1 (42.4 to 45.8). Between 1990 and 2017, the fatty liver disease-SDG score increased in all super-regions, with the greatest increase in south Asia, but decreased in 8 countries and territories.<h4>Conclusions</h4>The fatty liver disease-SDG score provides a strategic advocacy tool at the national and global levels for the liver health field and noncommunicable disease advocates, highlighting the multisectoral collaborations needed to address fatty liver disease, and noncommunicable diseases overall.",,html:https://journals.lww.com/hep/Abstract/9900/The_global_Fatty_Liver_Disease_Sustainable.395.aspx; doi:https://doi.org/10.1097/HEP.0000000000000361; html:https://europepmc.org/articles/PMC10442089; pdf:https://europepmc.org/articles/PMC10442089?pdf=render
 33069326,https://doi.org/10.1016/s0140-6736(20)30925-9,"Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.",GBD 2019 Diseases and Injuries Collaborators.,,"Lancet (London, England)",2020,2020-10-01,Y,,,,"<h4>Background</h4>In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries.<h4>Methods</h4>GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution.<h4>Findings</h4>Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990-2010 time period, with the greatest annualised rate of decline occurring in the 0-9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10-24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10-24 years were also in the top ten in the 25-49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50-74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI.<h4>Interpretation</h4>As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve.<h4>Funding</h4>Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S0140673620309259/pdf; doi:https://doi.org/10.1016/S0140-6736(20)30925-9; html:https://europepmc.org/articles/PMC7567026
 35697829,https://doi.org/10.1038/s42003-022-03448-z,Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals.,"Winkler TW, Rasheed H, Teumer A, Gorski M, Rowan BX, Stanzick KJ, Thomas LF, Tin A, Hoppmann A, Chu AY, Tayo B, Thio CHL, Cusi D, Chai JF, Sieber KB, Horn K, Li M, Scholz M, Cocca M, Wuttke M, van der Most PJ, Yang Q, Ghasemi S, Nutile T, Li Y, Pontali G, Günther F, Dehghan A, Correa A, Parsa A, Feresin A, de Vries APJ, Zonderman AB, Smith AV, Oldehinkel AJ, De Grandi A, Rosenkranz AR, Franke A, Teren A, Metspalu A, Hicks AA, Morris AP, Tönjes A, Morgan A, Podgornaia AI, Peters A, Körner A, Mahajan A, Campbell A, Freedman BI, Spedicati B, Ponte B, Schöttker B, Brumpton B, Banas B, Krämer BK, Jung B, Åsvold BO, Smith BH, Ning B, Penninx BWJH, Vanderwerff BR, Psaty BM, Kammerer CM, Langefeld CD, Hayward C, Spracklen CN, Robinson-Cohen C, Hartman CA, Lindgren CM, Wang C, Sabanayagam C, Heng CK, Lanzani C, Khor CC, Cheng CY, Fuchsberger C, Gieger C, Shaffer CM, Schulz CA, Willer CJ, Chasman DI, Gudbjartsson DF, Ruggiero D, Toniolo D, Czamara D, Porteous DJ, Waterworth DM, Mascalzoni D, Mook-Kanamori DO, Reilly DF, Daw EW, Hofer E, Boerwinkle E, Salvi E, Bottinger EP, Tai ES, Catamo E, Rizzi F, Guo F, Rivadeneira F, Guilianini F, Sveinbjornsson G, Ehret G, Waeber G, Biino G, Girotto G, Pistis G, Nadkarni GN, Delgado GE, Montgomery GW, Snieder H, Campbell H, White HD, Gao H, Stringham HM, Schmidt H, Li H, Brenner H, Holm H, Kirsten H, Kramer H, Rudan I, Nolte IM, Tzoulaki I, Olafsson I, Martins J, Cook JP, Wilson JF, Halbritter J, Felix JF, Divers J, Kooner JS, Lee JJ, O'Connell J, Rotter JI, Liu J, Xu J, Thiery J, Ärnlöv J, Kuusisto J, Jakobsdottir J, Tremblay J, Chambers JC, Whitfield JB, Gaziano JM, Marten J, Coresh J, Jonas JB, Mychaleckyj JC, Christensen K, Eckardt KU, Mohlke KL, Endlich K, Dittrich K, Ryan KA, Rice KM, Taylor KD, Ho K, Nikus K, Matsuda K, Strauch K, Miliku K, Hveem K, Lind L, Wallentin L, Yerges-Armstrong LM, Raffield LM, Phillips LS, Launer LJ, Lyytikäinen LP, Lange LA, Citterio L, Klaric L, Ikram MA, Ising M, Kleber ME, Francescatto M, Concas MP, Ciullo M, Piratsu M, Orho-Melander M, Laakso M, Loeffler M, Perola M, de Borst MH, Gögele M, Bianca M, Lukas MA, Feitosa MF, Biggs ML, Wojczynski MK, Kavousi M, Kanai M, Akiyama M, Yasuda M, Nauck M, Waldenberger M, Chee ML, Chee ML, Boehnke M, Preuss MH, Stumvoll M, Province MA, Evans MK, O'Donoghue ML, Kubo M, Kähönen M, Kastarinen M, Nalls MA, Kuokkanen M, Ghanbari M, Bochud M, Josyula NS, Martin NG, Tan NYQ, Palmer ND, Pirastu N, Schupf N, Verweij N, Hutri-Kähönen N, Mononen N, Bansal N, Devuyst O, Melander O, Raitakari OT, Polasek O, Manunta P, Gasparini P, Mishra PP, Sulem P, Magnusson PKE, Elliott P, Ridker PM, Hamet P, Svensson PO, Joshi PK, Kovacs P, Pramstaller PP, Rossing P, Vollenweider P, van der Harst P, Dorajoo R, Sim RZH, Burkhardt R, Tao R, Noordam R, Mägi R, Schmidt R, de Mutsert R, Rueedi R, van Dam RM, Carroll RJ, Gansevoort RT, Loos RJF, Felicita SC, Sedaghat S, Padmanabhan S, Freitag-Wolf S, Pendergrass SA, Graham SE, Gordon SD, Hwang SJ, Kerr SM, Vaccargiu S, Patil SB, Hallan S, Bakker SJL, Lim SC, Lucae S, Vogelezang S, Bergmann S, Corre T, Ahluwalia TS, Lehtimäki T, Boutin TS, Meitinger T, Wong TY, Bergler T, Rabelink TJ, Esko T, Haller T, Thorsteinsdottir U, Völker U, Foo VHX, Salomaa V, Vitart V, Giedraitis V, Gudnason V, Jaddoe VWV, Huang W, Zhang W, Wei WB, Kiess W, März W, Koenig W, Lieb W, Gao X, Sim X, Wang YX, Friedlander Y, Tham YC, Kamatani Y, Okada Y, Milaneschi Y, Yu Z, Lifelines cohort study, DiscovEHR/MyCode study, VA Million Veteran Program, Stark KJ, Stefansson K, Böger CA, Hung AM, Kronenberg F, Köttgen A, Pattaro C, Heid IM.",,Communications biology,2022,2022-06-13,Y,,,,"Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n<sub>DM</sub> = 178,691, n<sub>noDM</sub> = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.",,pdf:https://www.nature.com/articles/s42003-022-03448-z.pdf; doi:https://doi.org/10.1038/s42003-022-03448-z; html:https://europepmc.org/articles/PMC9192715; pdf:https://europepmc.org/articles/PMC9192715?pdf=render
 30698716,https://doi.org/10.1093/aje/kwz005,Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.,"de Vries PS, Brown MR, Bentley AR, Sung YJ, Winkler TW, Ntalla I, Schwander K, Kraja AT, Guo X, Franceschini N, Cheng CY, Sim X, Vojinovic D, Huffman JE, Musani SK, Li C, Feitosa MF, Richard MA, Noordam R, Aschard H, Bartz TM, Bielak LF, Deng X, Dorajoo R, Lohman KK, Manning AK, Rankinen T, Smith AV, Tajuddin SM, Evangelou E, Graff M, Alver M, Boissel M, Chai JF, Chen X, Divers J, Gandin I, Gao C, Goel A, Hagemeijer Y, Harris SE, Hartwig FP, He M, Horimoto ARVR, Hsu FC, Jackson AU, Kasturiratne A, Komulainen P, Kühnel B, Laguzzi F, Lee JH, Luan J, Lyytikäinen LP, Matoba N, Nolte IM, Pietzner M, Riaz M, Said MA, Scott RA, Sofer T, Stančáková A, Takeuchi F, Tayo BO, van der Most PJ, Varga TV, Wang Y, Ware EB, Wen W, Yanek LR, Zhang W, Zhao JH, Afaq S, Amin N, Amini M, Arking DE, Aung T, Ballantyne C, Boerwinkle E, Broeckel U, Campbell A, Canouil M, Charumathi S, Chen YI, Connell JM, de Faire U, de Las Fuentes L, de Mutsert R, de Silva HJ, Ding J, Dominiczak AF, Duan Q, Eaton CB, Eppinga RN, Faul JD, Fisher V, Forrester T, Franco OH, Friedlander Y, Ghanbari M, Giulianini F, Grabe HJ, Grove ML, Gu CC, Harris TB, Heikkinen S, Heng CK, Hirata M, Hixson JE, Howard BV, Ikram MA, InterAct Consortium, Jacobs DR, Johnson C, Jonas JB, Kammerer CM, Katsuya T, Khor CC, Kilpeläinen TO, Koh WP, Koistinen HA, Kolcic I, Kooperberg C, Krieger JE, Kritchevsky SB, Kubo M, Kuusisto J, Lakka TA, Langefeld CD, Langenberg C, Launer LJ, Lehne B, Lemaitre RN, Li Y, Liang J, Liu J, Liu K, Loh M, Louie T, Mägi R, Manichaikul AW, McKenzie CA, Meitinger T, Metspalu A, Milaneschi Y, Milani L, Mohlke KL, Mosley TH, Mukamal KJ, Nalls MA, Nauck M, Nelson CP, Sotoodehnia N, O'Connell JR, Palmer ND, Pazoki R, Pedersen NL, Peters A, Peyser PA, Polasek O, Poulter N, Raffel LJ, Raitakari OT, Reiner AP, Rice TK, Rich SS, Robino A, Robinson JG, Rose LM, Rudan I, Schmidt CO, Schreiner PJ, Scott WR, Sever P, Shi Y, Sidney S, Sims M, Smith BH, Smith JA, Snieder H, Starr JM, Strauch K, Tan N, Taylor KD, Teo YY, Tham YC, Uitterlinden AG, van Heemst D, Vuckovic D, Waldenberger M, Wang L, Wang Y, Wang Z, Wei WB, Williams C, Wilson G, Wojczynski MK, Yao J, Yu B, Yu C, Yuan JM, Zhao W, Zonderman AB, Becker DM, Boehnke M, Bowden DW, Chambers JC, Deary IJ, Esko T, Farrall M, Franks PW, Freedman BI, Froguel P, Gasparini P, Gieger C, Horta BL, Kamatani Y, Kato N, Kooner JS, Laakso M, Leander K, Lehtimäki T, Lifelines Cohort, Groningen, The Netherlands (Lifelines Cohort Study), Magnusson PKE, Penninx B, Pereira AC, Rauramaa R, Samani NJ, Scott J, Shu XO, van der Harst P, Wagenknecht LE, Wang YX, Wareham NJ, Watkins H, Weir DR, Wickremasinghe AR, Zheng W, Elliott P, North KE, Bouchard C, Evans MK, Gudnason V, Liu CT, Liu Y, Psaty BM, Ridker PM, van Dam RM, Kardia SLR, Zhu X, Rotimi CN, Mook-Kanamori DO, Fornage M, Kelly TN, Fox ER, Hayward C, van Duijn CM, Tai ES, Wong TY, Liu J, Rotter JI, Gauderman WJ, Province MA, Munroe PB, Rice K, Chasman DI, Cupples LA, Rao DC, Morrison AC.",,American journal of epidemiology,2019,2019-06-01,N,Lipids; Cholesterol; Triglycerides; alcohol consumption; Genome-wide Association Studies; Gene-environment Interactions; Gene-lifestyle Interactions,,,"A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.",,pdf:https://academic.oup.com/aje/article-pdf/188/6/1033/32921017/kwz005.pdf; doi:https://doi.org/10.1093/aje/kwz005; html:https://europepmc.org/articles/PMC6545280; pdf:https://europepmc.org/articles/PMC6545280?pdf=render; doi:https://doi.org/10.1093/aje/kwz005
diff --git a/data/papers.json b/data/papers.json
index 45326899..936bf6ea 100644
--- a/data/papers.json
+++ b/data/papers.json
@@ -68,38 +68,38 @@
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e064320.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064320; html:https://europepmc.org/articles/PMC9723413; pdf:https://europepmc.org/articles/PMC9723413?pdf=render"
   },
   {
-    "id": "37875536",
-    "doi": "https://doi.org/10.1038/s41467-023-41879-2",
-    "title": "Long-term health impacts of COVID-19 among 242,712 adults in England.",
-    "authorString": "Atchison CJ, Davies B, Cooper E, Lound A, Whitaker M, Hampshire A, Azor A, Donnelly CA, Chadeau-Hyam M, Cooke GS, Ward H, Elliott P.",
+    "id": "36350644",
+    "doi": "https://doi.org/10.1093/nar/gkac1017",
+    "title": "GWAS Central: an expanding resource for finding and visualising genotype and phenotype data from genome-wide association studies.",
+    "authorString": "Beck T, Rowlands T, Shorter T, Brookes AJ.",
     "authorAffiliations": "",
-    "journalTitle": "Nature communications",
+    "journalTitle": "Nucleic acids research",
     "pubYear": "2023",
-    "date": "2023-10-24",
+    "date": "2023-01-01",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "The COVID-19 pandemic is having a lasting impact on health and well-being. We compare current self-reported health, quality of life and symptom profiles for people with ongoing symptoms following COVID-19 to those who have never tested positive for SARS-CoV-2 infection and those who have recovered from COVID-19. Overall, 276,840/800,000 (34\u00b76%) of invited participants took part. Mental health and health-related quality of life were worse among participants with ongoing persistent symptoms post-COVID compared with those who had never had COVID-19 or had recovered. In this study, median duration of COVID-related symptoms (N\u2009=\u2009130,251) was 1\u00b73 weeks (inter-quartile range 6 days to 2 weeks), with 7\u00b75% and 5\u00b72% reporting ongoing symptoms \u226512 weeks and \u226552 weeks respectively. Female sex, \u22651 comorbidity and being infected when Wild-type variant was dominant were associated with higher probability of symptoms lasting \u226512 weeks and longer recovery time in those with persistent symptoms. Although COVID-19 is usually of short duration, some adults experience persistent and burdensome illness.",
+    "abstract": "The GWAS Central resource gathers and curates extensive summary-level genome-wide association study (GWAS) data and puts a range of user-friendly but powerful website tools for the comparison and visualisation of GWAS data at the fingertips of researchers. Through our continued efforts to harmonise and import data received from GWAS authors and consortia, and data sets actively collected from public sources, the database now contains over 72.5 million P-values for over 5000 studies testing over 7.4 million unique genetic markers investigating over 1700 unique phenotypes. Here, we describe an update to integrate this extensive data collection with mouse disease model data to support insights into the functional impact of human genetic variation. GWAS Central has expanded to include mouse gene-phenotype associations observed during mouse gene knockout screens. To allow similar cross-species phenotypes to be compared, terms from mammalian and human phenotype ontologies have been mapped. New interactive interfaces to find, correlate and view human and mouse genotype-phenotype associations are included in the website toolkit. Additionally, the integrated browser for interrogating multiple association data sets has been updated and a GA4GH Beacon API endpoint has been added for discovering variants tested in GWAS. The GWAS Central resource is accessible at https://www.gwascentral.org/.",
     "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41467-023-41879-2.pdf; doi:https://doi.org/10.1038/s41467-023-41879-2; html:https://europepmc.org/articles/PMC10598213; pdf:https://europepmc.org/articles/PMC10598213?pdf=render"
+    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825503; doi:https://doi.org/10.1093/nar/gkac1017; html:https://europepmc.org/articles/PMC9825503; pdf:https://europepmc.org/articles/PMC9825503?pdf=render"
   },
   {
-    "id": "36350644",
-    "doi": "https://doi.org/10.1093/nar/gkac1017",
-    "title": "GWAS Central: an expanding resource for finding and visualising genotype and phenotype data from genome-wide association studies.",
-    "authorString": "Beck T, Rowlands T, Shorter T, Brookes AJ.",
+    "id": "37875536",
+    "doi": "https://doi.org/10.1038/s41467-023-41879-2",
+    "title": "Long-term health impacts of COVID-19 among 242,712 adults in England.",
+    "authorString": "Atchison CJ, Davies B, Cooper E, Lound A, Whitaker M, Hampshire A, Azor A, Donnelly CA, Chadeau-Hyam M, Cooke GS, Ward H, Elliott P.",
     "authorAffiliations": "",
-    "journalTitle": "Nucleic acids research",
+    "journalTitle": "Nature communications",
     "pubYear": "2023",
-    "date": "2023-01-01",
+    "date": "2023-10-24",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "The GWAS Central resource gathers and curates extensive summary-level genome-wide association study (GWAS) data and puts a range of user-friendly but powerful website tools for the comparison and visualisation of GWAS data at the fingertips of researchers. Through our continued efforts to harmonise and import data received from GWAS authors and consortia, and data sets actively collected from public sources, the database now contains over 72.5 million P-values for over 5000 studies testing over 7.4 million unique genetic markers investigating over 1700 unique phenotypes. Here, we describe an update to integrate this extensive data collection with mouse disease model data to support insights into the functional impact of human genetic variation. GWAS Central has expanded to include mouse gene-phenotype associations observed during mouse gene knockout screens. To allow similar cross-species phenotypes to be compared, terms from mammalian and human phenotype ontologies have been mapped. New interactive interfaces to find, correlate and view human and mouse genotype-phenotype associations are included in the website toolkit. Additionally, the integrated browser for interrogating multiple association data sets has been updated and a GA4GH Beacon API endpoint has been added for discovering variants tested in GWAS. The GWAS Central resource is accessible at https://www.gwascentral.org/.",
+    "abstract": "The COVID-19 pandemic is having a lasting impact on health and well-being. We compare current self-reported health, quality of life and symptom profiles for people with ongoing symptoms following COVID-19 to those who have never tested positive for SARS-CoV-2 infection and those who have recovered from COVID-19. Overall, 276,840/800,000 (34\u00b76%) of invited participants took part. Mental health and health-related quality of life were worse among participants with ongoing persistent symptoms post-COVID compared with those who had never had COVID-19 or had recovered. In this study, median duration of COVID-related symptoms (N\u2009=\u2009130,251) was 1\u00b73 weeks (inter-quartile range 6 days to 2 weeks), with 7\u00b75% and 5\u00b72% reporting ongoing symptoms \u226512 weeks and \u226552 weeks respectively. Female sex, \u22651 comorbidity and being infected when Wild-type variant was dominant were associated with higher probability of symptoms lasting \u226512 weeks and longer recovery time in those with persistent symptoms. Although COVID-19 is usually of short duration, some adults experience persistent and burdensome illness.",
     "laySummary": "",
-    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825503; doi:https://doi.org/10.1093/nar/gkac1017; html:https://europepmc.org/articles/PMC9825503; pdf:https://europepmc.org/articles/PMC9825503?pdf=render"
+    "urls": "pdf:https://www.nature.com/articles/s41467-023-41879-2.pdf; doi:https://doi.org/10.1038/s41467-023-41879-2; html:https://europepmc.org/articles/PMC10598213; pdf:https://europepmc.org/articles/PMC10598213?pdf=render"
   },
   {
     "id": "36572492",
@@ -1614,23 +1614,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-022-03031-y; doi:https://doi.org/10.1186/s12882-022-03031-y; html:https://europepmc.org/articles/PMC9843843; pdf:https://europepmc.org/articles/PMC9843843?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 <i>via</i> 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": "pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1146702/pdf; doi:https://doi.org/10.3389/fimmu.2023.1146702; html:https://europepmc.org/articles/PMC10087108; pdf:https://europepmc.org/articles/PMC10087108?pdf=render"
-  },
   {
     "id": "33252680",
     "doi": "https://doi.org/10.1093/ageing/afaa252",
@@ -1648,6 +1631,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ageing/article-pdf/50/4/1208/38839537/afaa252.pdf; 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"
   },
+  {
+    "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 <i>via</i> 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": "pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1146702/pdf; 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",
@@ -1921,21 +1921,21 @@
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10125882; doi:https://doi.org/10.1177/02692163231167212; html:https://europepmc.org/articles/PMC10125882; pdf:https://europepmc.org/articles/PMC10125882?pdf=render"
   },
   {
-    "id": "36600681",
-    "doi": "https://doi.org/10.1177/17562848221145612",
-    "title": "Artificial intelligence-based personalized nutrition and prediction of irritable bowel syndrome patients.",
-    "authorString": "Acharjee A, Choudhury SP.",
+    "id": "34216888",
+    "doi": "https://doi.org/10.1016/j.compbiomed.2021.104556",
+    "title": "NFnetFu: A novel workflow for microbiome data fusion.",
+    "authorString": "Bisht V, Acharjee A, Gkoutos GV.",
     "authorAffiliations": "",
-    "journalTitle": "Therapeutic advances in gastroenterology",
-    "pubYear": "2022",
-    "date": "2022-12-26",
+    "journalTitle": "Computers in biology and medicine",
+    "pubYear": "2021",
+    "date": "2021-06-08",
     "isOpenAccess": "Y",
-    "keywords": "",
+    "keywords": "Clustering; Microbiome; Fuzzy Inference; Network Fusion",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "",
+    "abstract": "Microbiome data analysis and its interpretation into meaningful biological insights remain very challenging for numerous reasons, perhaps most prominently, due to the need to account for multiple factors, including collinearity, sparsity (excessive zeros) and effect size, that the complex experimental workflow and subsequent downstream data analysis require. Moreover, a meaningful microbiome data analysis necessitates the development of interpretable models that incorporate inferences across available data as well as background biomedical knowledge. We developed a multimodal framework that considers sparsity (excessive zeros), lower effect size, intrinsically microbial correlations, i.e., collinearity, as well as background biomedical knowledge in the form of a cluster-infused enriched network architecture. Finally, our framework also provides a candidate taxa/Operational Taxonomic Unit (OTU) that can be targeted for future validation experiments. We have developed a tool, the term NFnetFU (Neuro Fuzzy network Fusion), that encompasses our framework and have made it freely available at https://github.com/VartikaBisht6197/NFnetFu.",
     "laySummary": "",
-    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806427; doi:https://doi.org/10.1177/17562848221145612; html:https://europepmc.org/articles/PMC9806427; pdf:https://europepmc.org/articles/PMC9806427?pdf=render"
+    "urls": "doi:https://doi.org/10.1016/j.compbiomed.2021.104556; doi:https://doi.org/10.1016/j.compbiomed.2021.104556; html:https://europepmc.org/articles/PMC8404037"
   },
   {
     "id": "35501368",
@@ -1955,21 +1955,21 @@
     "urls": "pdf:https://www.nature.com/articles/s41431-022-01107-9.pdf; doi:https://doi.org/10.1038/s41431-022-01107-9; html:https://europepmc.org/articles/PMC9712543; pdf:https://europepmc.org/articles/PMC9712543?pdf=render"
   },
   {
-    "id": "34216888",
-    "doi": "https://doi.org/10.1016/j.compbiomed.2021.104556",
-    "title": "NFnetFu: A novel workflow for microbiome data fusion.",
-    "authorString": "Bisht V, Acharjee A, Gkoutos GV.",
+    "id": "36600681",
+    "doi": "https://doi.org/10.1177/17562848221145612",
+    "title": "Artificial intelligence-based personalized nutrition and prediction of irritable bowel syndrome patients.",
+    "authorString": "Acharjee A, Choudhury SP.",
     "authorAffiliations": "",
-    "journalTitle": "Computers in biology and medicine",
-    "pubYear": "2021",
-    "date": "2021-06-08",
+    "journalTitle": "Therapeutic advances in gastroenterology",
+    "pubYear": "2022",
+    "date": "2022-12-26",
     "isOpenAccess": "Y",
-    "keywords": "Clustering; Microbiome; Fuzzy Inference; Network Fusion",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "Microbiome data analysis and its interpretation into meaningful biological insights remain very challenging for numerous reasons, perhaps most prominently, due to the need to account for multiple factors, including collinearity, sparsity (excessive zeros) and effect size, that the complex experimental workflow and subsequent downstream data analysis require. Moreover, a meaningful microbiome data analysis necessitates the development of interpretable models that incorporate inferences across available data as well as background biomedical knowledge. We developed a multimodal framework that considers sparsity (excessive zeros), lower effect size, intrinsically microbial correlations, i.e., collinearity, as well as background biomedical knowledge in the form of a cluster-infused enriched network architecture. Finally, our framework also provides a candidate taxa/Operational Taxonomic Unit (OTU) that can be targeted for future validation experiments. We have developed a tool, the term NFnetFU (Neuro Fuzzy network Fusion), that encompasses our framework and have made it freely available at https://github.com/VartikaBisht6197/NFnetFu.",
+    "abstract": "",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.compbiomed.2021.104556; doi:https://doi.org/10.1016/j.compbiomed.2021.104556; html:https://europepmc.org/articles/PMC8404037"
+    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806427; doi:https://doi.org/10.1177/17562848221145612; html:https://europepmc.org/articles/PMC9806427; pdf:https://europepmc.org/articles/PMC9806427?pdf=render"
   },
   {
     "id": "34850818",
@@ -2379,23 +2379,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/11/e054861.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054861; html:https://europepmc.org/articles/PMC8609490; pdf:https://europepmc.org/articles/PMC8609490?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": "pdf:https://www.degruyter.com/document/doi/10.1515/dx-2022-0052/pdf; doi:https://doi.org/10.1515/dx-2022-0052"
-  },
   {
     "id": "32741245",
     "doi": "https://doi.org/10.1177/0954411920946526",
@@ -2413,6 +2396,23 @@
     "laySummary": "",
     "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/0954411920946526; doi:https://doi.org/10.1177/0954411920946526; html:https://europepmc.org/articles/PMC7675765; pdf:https://europepmc.org/articles/PMC7675765?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": "pdf:https://www.degruyter.com/document/doi/10.1515/dx-2022-0052/pdf; doi:https://doi.org/10.1515/dx-2022-0052"
+  },
   {
     "id": "34911741",
     "doi": "https://doi.org/10.1136/heartjnl-2021-320047",
@@ -2515,23 +2515,6 @@
     "laySummary": "",
     "urls": "pdf:https://emj.bmj.com/content/emermed/early/2023/09/25/emermed-2022-212440.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212440"
   },
-  {
-    "id": "37124948",
-    "doi": "https://doi.org/10.1016/j.lanepe.2023.100638",
-    "title": "Severity of Omicron BA.5 variant and protective effect of vaccination: national cohort and matched analyses in Scotland.",
-    "authorString": "Robertson C, Kerr S, Sheikh A.",
-    "authorAffiliations": "",
-    "journalTitle": "The Lancet regional health. Europe",
-    "pubYear": "2023",
-    "date": "2023-04-14",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.lanepe.2023.100638; doi:https://doi.org/10.1016/j.lanepe.2023.100638; html:https://europepmc.org/articles/PMC10139952; pdf:https://europepmc.org/articles/PMC10139952?pdf=render"
-  },
   {
     "id": "34376975",
     "doi": "https://doi.org/10.1177/11779322211035921",
@@ -2549,6 +2532,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1177/11779322211035921; doi:https://doi.org/10.1177/11779322211035921; html:https://europepmc.org/articles/PMC8323418; pdf:https://europepmc.org/articles/PMC8323418?pdf=render"
   },
+  {
+    "id": "37124948",
+    "doi": "https://doi.org/10.1016/j.lanepe.2023.100638",
+    "title": "Severity of Omicron BA.5 variant and protective effect of vaccination: national cohort and matched analyses in Scotland.",
+    "authorString": "Robertson C, Kerr S, Sheikh A.",
+    "authorAffiliations": "",
+    "journalTitle": "The Lancet regional health. Europe",
+    "pubYear": "2023",
+    "date": "2023-04-14",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.lanepe.2023.100638; doi:https://doi.org/10.1016/j.lanepe.2023.100638; html:https://europepmc.org/articles/PMC10139952; pdf:https://europepmc.org/articles/PMC10139952?pdf=render"
+  },
   {
     "id": "37765085",
     "doi": "https://doi.org/10.3390/ph16091277",
@@ -2906,23 +2906,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.bmj.com/content/bmj/378/bmj-2022-071230.full.pdf; doi:https://doi.org/10.1136/bmj-2022-071230; html:https://europepmc.org/articles/PMC9449358; pdf:https://europepmc.org/articles/PMC9449358?pdf=render"
   },
-  {
-    "id": "36810667",
-    "doi": "https://doi.org/10.1210/clinem/dgad103",
-    "title": "Morbidity Associated With Primary Hyperparathyroidism-A Population-based Study With a Subanalysis on Vitamin D.",
-    "authorString": "Soto-Pedre E, Lin YY, Soto-Hernaez J, Newey PJ, Leese GP.",
-    "authorAffiliations": "",
-    "journalTitle": "The Journal of clinical endocrinology and metabolism",
-    "pubYear": "2023",
-    "date": "2023-08-01",
-    "isOpenAccess": "Y",
-    "keywords": "Calcium; Vitamin D; Mortality; Primary Hyperparathyroidism",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Context</h4>Primary hyperparathyroidism (PHPT) is associated with increased risk of morbidity and death, and vitamin D levels are a potentially confounding variable.<h4>Objective</h4>The aim of this study was to assess morbidity and mortality associated with primary hyperparathyroidism (PHPT).<h4>Methods</h4>In this population-based retrospective matched cohort study, data linkage of biochemistry, hospital admissions, prescribing, imaging, pathology, and deaths was used to identify patients across the region of Tayside, Scotland, who had PHPT from 1997 to 2019. Cox proportional hazards models and hazards ratios (HR) were used to explore the relationship between exposure to PHPT and several clinical outcomes. Comparisons were made with an age- and gender-matched cohort.<h4>Results</h4>In 11 616 people with PHPT (66.8% female), with a mean follow-up period of 8.8 years, there was an adjusted HR of death of 2.05 (95% CI, 1.97-2.13) for those exposed to PHPT. There was also an increased risk of cardiovascular disease (HR = 1.34; 95% CI, 1.24-1.45), cerebrovascular disease (HR = 1.29; 95% CI, 1.15-1.45), diabetes (HR = 1.39; 95% CI, 1.26-1.54), renal stones (HR = 3.02; 95% CI, 2.19-4.17) and osteoporosis (HR = 1.31; 95% CI, 1.16-1.49). Following adjustment for serum vitamin D concentrations (n = 2748), increased risks for death, diabetes, renal stones, and osteoporosis persisted, but not for cardiovascular or cerebrovascular disease.<h4>Conclusion</h4>In a large population-based study, PHPT was associated with death, diabetes, renal stones, and osteoporosis, independent of serum vitamin D concentration.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/jcem/advance-article-pdf/doi/10.1210/clinem/dgad103/49516503/dgad103.pdf; doi:https://doi.org/10.1210/clinem/dgad103; html:https://europepmc.org/articles/PMC10438903"
-  },
   {
     "id": "33969335",
     "doi": "https://doi.org/10.1016/j.lanepe.2021.100098",
@@ -2940,6 +2923,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.lanepe.2021.100098; doi:https://doi.org/10.1016/j.lanepe.2021.100098; html:https://europepmc.org/articles/PMC8088780; pdf:https://europepmc.org/articles/PMC8088780?pdf=render"
   },
+  {
+    "id": "36810667",
+    "doi": "https://doi.org/10.1210/clinem/dgad103",
+    "title": "Morbidity Associated With Primary Hyperparathyroidism-A Population-based Study With a Subanalysis on Vitamin D.",
+    "authorString": "Soto-Pedre E, Lin YY, Soto-Hernaez J, Newey PJ, Leese GP.",
+    "authorAffiliations": "",
+    "journalTitle": "The Journal of clinical endocrinology and metabolism",
+    "pubYear": "2023",
+    "date": "2023-08-01",
+    "isOpenAccess": "Y",
+    "keywords": "Calcium; Vitamin D; Mortality; Primary Hyperparathyroidism",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Context</h4>Primary hyperparathyroidism (PHPT) is associated with increased risk of morbidity and death, and vitamin D levels are a potentially confounding variable.<h4>Objective</h4>The aim of this study was to assess morbidity and mortality associated with primary hyperparathyroidism (PHPT).<h4>Methods</h4>In this population-based retrospective matched cohort study, data linkage of biochemistry, hospital admissions, prescribing, imaging, pathology, and deaths was used to identify patients across the region of Tayside, Scotland, who had PHPT from 1997 to 2019. Cox proportional hazards models and hazards ratios (HR) were used to explore the relationship between exposure to PHPT and several clinical outcomes. Comparisons were made with an age- and gender-matched cohort.<h4>Results</h4>In 11 616 people with PHPT (66.8% female), with a mean follow-up period of 8.8 years, there was an adjusted HR of death of 2.05 (95% CI, 1.97-2.13) for those exposed to PHPT. There was also an increased risk of cardiovascular disease (HR = 1.34; 95% CI, 1.24-1.45), cerebrovascular disease (HR = 1.29; 95% CI, 1.15-1.45), diabetes (HR = 1.39; 95% CI, 1.26-1.54), renal stones (HR = 3.02; 95% CI, 2.19-4.17) and osteoporosis (HR = 1.31; 95% CI, 1.16-1.49). Following adjustment for serum vitamin D concentrations (n = 2748), increased risks for death, diabetes, renal stones, and osteoporosis persisted, but not for cardiovascular or cerebrovascular disease.<h4>Conclusion</h4>In a large population-based study, PHPT was associated with death, diabetes, renal stones, and osteoporosis, independent of serum vitamin D concentration.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/jcem/advance-article-pdf/doi/10.1210/clinem/dgad103/49516503/dgad103.pdf; doi:https://doi.org/10.1210/clinem/dgad103; html:https://europepmc.org/articles/PMC10438903"
+  },
   {
     "id": "34183745",
     "doi": "https://doi.org/10.1038/s41598-021-92874-w",
@@ -2991,6 +2991,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1002/pds.5412; doi:https://doi.org/10.1002/pds.5412; html:https://europepmc.org/articles/PMC9305520; pdf:https://europepmc.org/articles/PMC9305520?pdf=render"
   },
+  {
+    "id": "32276644",
+    "doi": "https://doi.org/10.1186/s12942-020-00208-2",
+    "title": "GIS-modelled built-environment exposures reflecting daily mobility for applications in child health research.",
+    "authorString": "Mizen A, Fry R, Rodgers S.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of health geographics",
+    "pubYear": "2020",
+    "date": "2020-04-10",
+    "isOpenAccess": "Y",
+    "keywords": "Environmental exposure; Child Health; Walking; Weighted Network; Daily Mobility; School Commute",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Inaccurately modelled environmental exposures may have important implications for evidence-based policy targeting health promoting or hazardous facilities. Travel routes modelled using GIS generally use shortest network distances or Euclidean buffers to represent journeys with corresponding built-environment exposures calculated along these routes. These methods, however, are an unreliable proxy for calculating child built-environment exposures as child route choice is more complex than shortest network routes.<h4>Methods</h4>We hypothesised that a GIS model informed by characteristics of the built-environment known to influence child route choice could be developed to more accurately model exposures. Using GPS-derived walking commutes to and from school we used logistic regression models to highlight built-environment features important in child route choice (e.g. road type, traffic light count). We then recalculated walking commute routes using a weighted network to incorporate built-environment features. Multilevel regression analyses were used to validate exposure predictions to the retail food environment along the different routing methods.<h4>Results</h4>Children chose routes with more traffic lights and residential roads compared to the modelled shortest network routes. Compared to standard shortest network routes, the GPS-informed weighted network enabled GIS-based walking commutes to be derived with more than three times greater accuracy (38%) for the route to school and more than 12 times greater accuracy (92%) for the route home.<h4>Conclusions</h4>This research advocates using weighted GIS networks to accurately reflect child walking journeys to school. The improved accuracy in route modelling has in turn improved estimates of children's exposures to potentially hazardous features in the environment. Further research is needed to explore if the built-environment features are important internationally. Route and corresponding exposure estimates can be scaled to the population level which will contribute to a better understanding of built-environment exposures on child health and contribute to mobility-based child health policy.",
+    "laySummary": "",
+    "urls": "pdf:https://ij-healthgeographics.biomedcentral.com/track/pdf/10.1186/s12942-020-00208-2; doi:https://doi.org/10.1186/s12942-020-00208-2; html:https://europepmc.org/articles/PMC7147039; pdf:https://europepmc.org/articles/PMC7147039?pdf=render"
+  },
   {
     "id": "36350946",
     "doi": "https://doi.org/10.1093/bjsopen/zrac130",
@@ -3025,23 +3042,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.jmir.org/2022/12/e40035/PDF; doi:https://doi.org/10.2196/40035; html:https://europepmc.org/articles/PMC9822177"
   },
-  {
-    "id": "32276644",
-    "doi": "https://doi.org/10.1186/s12942-020-00208-2",
-    "title": "GIS-modelled built-environment exposures reflecting daily mobility for applications in child health research.",
-    "authorString": "Mizen A, Fry R, Rodgers S.",
-    "authorAffiliations": "",
-    "journalTitle": "International journal of health geographics",
-    "pubYear": "2020",
-    "date": "2020-04-10",
-    "isOpenAccess": "Y",
-    "keywords": "Environmental exposure; Child Health; Walking; Weighted Network; Daily Mobility; School Commute",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Inaccurately modelled environmental exposures may have important implications for evidence-based policy targeting health promoting or hazardous facilities. Travel routes modelled using GIS generally use shortest network distances or Euclidean buffers to represent journeys with corresponding built-environment exposures calculated along these routes. These methods, however, are an unreliable proxy for calculating child built-environment exposures as child route choice is more complex than shortest network routes.<h4>Methods</h4>We hypothesised that a GIS model informed by characteristics of the built-environment known to influence child route choice could be developed to more accurately model exposures. Using GPS-derived walking commutes to and from school we used logistic regression models to highlight built-environment features important in child route choice (e.g. road type, traffic light count). We then recalculated walking commute routes using a weighted network to incorporate built-environment features. Multilevel regression analyses were used to validate exposure predictions to the retail food environment along the different routing methods.<h4>Results</h4>Children chose routes with more traffic lights and residential roads compared to the modelled shortest network routes. Compared to standard shortest network routes, the GPS-informed weighted network enabled GIS-based walking commutes to be derived with more than three times greater accuracy (38%) for the route to school and more than 12 times greater accuracy (92%) for the route home.<h4>Conclusions</h4>This research advocates using weighted GIS networks to accurately reflect child walking journeys to school. The improved accuracy in route modelling has in turn improved estimates of children's exposures to potentially hazardous features in the environment. Further research is needed to explore if the built-environment features are important internationally. Route and corresponding exposure estimates can be scaled to the population level which will contribute to a better understanding of built-environment exposures on child health and contribute to mobility-based child health policy.",
-    "laySummary": "",
-    "urls": "pdf:https://ij-healthgeographics.biomedcentral.com/track/pdf/10.1186/s12942-020-00208-2; doi:https://doi.org/10.1186/s12942-020-00208-2; html:https://europepmc.org/articles/PMC7147039; pdf:https://europepmc.org/articles/PMC7147039?pdf=render"
-  },
   {
     "id": "37429634",
     "doi": "https://doi.org/10.3399/bjgpo.2023.0057",
@@ -3229,23 +3229,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.lanepe.2022.100428; doi:https://doi.org/10.1016/j.lanepe.2022.100428; html:https://europepmc.org/articles/PMC9213032; pdf:https://europepmc.org/articles/PMC9213032?pdf=render"
   },
-  {
-    "id": "36691218",
-    "doi": "https://doi.org/10.1136/bmjopen-2021-059813",
-    "title": "Evaluation of the shielding initiative in Wales (EVITE Immunity): protocol for a quasiexperimental study.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2022",
-    "date": "2022-09-08",
-    "isOpenAccess": "Y",
-    "keywords": "immunology; Public Health; Health Policy; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e059813.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059813; html:https://europepmc.org/articles/PMC9461087; pdf:https://europepmc.org/articles/PMC9461087?pdf=render"
-  },
   {
     "id": "32300742",
     "doi": "https://doi.org/10.1016/j.eclinm.2020.100296",
@@ -3263,6 +3246,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2589537020300407/pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100296; html:https://europepmc.org/articles/PMC7152819; pdf:https://europepmc.org/articles/PMC7152819?pdf=render"
   },
+  {
+    "id": "36691218",
+    "doi": "https://doi.org/10.1136/bmjopen-2021-059813",
+    "title": "Evaluation of the shielding initiative in Wales (EVITE Immunity): protocol for a quasiexperimental study.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2022",
+    "date": "2022-09-08",
+    "isOpenAccess": "Y",
+    "keywords": "immunology; Public Health; Health Policy; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e059813.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059813; html:https://europepmc.org/articles/PMC9461087; pdf:https://europepmc.org/articles/PMC9461087?pdf=render"
+  },
   {
     "id": "36629285",
     "doi": "https://doi.org/10.1093/eurheartj/ehac758",
@@ -3994,23 +3994,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ageing/article-pdf/52/8/afad141/51124726/afad141.pdf; doi:https://doi.org/10.1093/ageing/afad141; html:https://europepmc.org/articles/PMC10438206; pdf:https://europepmc.org/articles/PMC10438206?pdf=render"
   },
-  {
-    "id": "37607793",
-    "doi": "https://doi.org/10.1136/bmjopen-2023-076296",
-    "title": "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.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2023",
-    "date": "2023-08-22",
-    "isOpenAccess": "Y",
-    "keywords": "Infectious diseases; Randomized controlled trial; Primary Care; Electronic Health Records",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>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?<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>ISRCTN16230629.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1136/bmjopen-2023-076296; doi:https://doi.org/10.1136/bmjopen-2023-076296; html:https://europepmc.org/articles/PMC10445367; pdf:https://europepmc.org/articles/PMC10445367?pdf=render"
-  },
   {
     "id": "32043136",
     "doi": "https://doi.org/10.1093/ageing/afaa018",
@@ -4028,6 +4011,23 @@
     "laySummary": "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).",
     "urls": "pdf:https://academic.oup.com/ageing/article-pdf/49/5/716/33676968/afaa018.pdf; doi:https://doi.org/10.1093/ageing/afaa018; html:https://europepmc.org/articles/PMC7444666; pdf:https://europepmc.org/articles/PMC7444666?pdf=render"
   },
+  {
+    "id": "37607793",
+    "doi": "https://doi.org/10.1136/bmjopen-2023-076296",
+    "title": "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.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2023",
+    "date": "2023-08-22",
+    "isOpenAccess": "Y",
+    "keywords": "Infectious diseases; Randomized controlled trial; Primary Care; Electronic Health Records",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>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?<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>ISRCTN16230629.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1136/bmjopen-2023-076296; doi:https://doi.org/10.1136/bmjopen-2023-076296; html:https://europepmc.org/articles/PMC10445367; pdf:https://europepmc.org/articles/PMC10445367?pdf=render"
+  },
   {
     "id": "36526319",
     "doi": "https://doi.org/10.1136/bmjopen-2022-064910",
@@ -4045,6 +4045,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e064910.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064910; html:https://europepmc.org/articles/PMC9764605; pdf:https://europepmc.org/articles/PMC9764605?pdf=render"
   },
+  {
+    "id": "35473737",
+    "doi": "https://doi.org/10.1136/bmjopen-2021-060413",
+    "title": "Therapies for Long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study).",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2022",
+    "date": "2022-04-26",
+    "isOpenAccess": "Y",
+    "keywords": "Therapeutics; immunology; Public Health; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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\u2009year.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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>1567490.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e060413.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060413; html:https://europepmc.org/articles/PMC9044550; pdf:https://europepmc.org/articles/PMC9044550?pdf=render"
+  },
   {
     "id": "34977922",
     "doi": "https://doi.org/10.1093/ije/dyab243",
@@ -4080,21 +4097,21 @@
     "urls": "doi:https://doi.org/10.1093/ageing/afad157; html:https://europepmc.org/articles/PMC10484725; pdf:https://europepmc.org/articles/PMC10484725?pdf=render"
   },
   {
-    "id": "35473737",
-    "doi": "https://doi.org/10.1136/bmjopen-2021-060413",
-    "title": "Therapies for Long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study).",
-    "authorString": "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.",
+    "id": "33228632",
+    "doi": "https://doi.org/10.1186/s12920-020-00826-6",
+    "title": "A random forest based biomarker discovery and power analysis framework for diagnostics research.",
+    "authorString": "Acharjee A, Larkman J, Xu Y, Cardoso VR, Gkoutos GV.",
     "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2022",
-    "date": "2022-04-26",
+    "journalTitle": "BMC medical genomics",
+    "pubYear": "2020",
+    "date": "2020-11-23",
     "isOpenAccess": "Y",
-    "keywords": "Therapeutics; immunology; Public Health; Covid-19",
+    "keywords": "Biomarker; Feature Selection; Random Forest; Power Study",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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\u2009year.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.<h4>Ethics and dissemination</h4>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.<h4>Trial registration number</h4>1567490.",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",
     "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e060413.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060413; html:https://europepmc.org/articles/PMC9044550; pdf:https://europepmc.org/articles/PMC9044550?pdf=render"
+    "urls": "pdf:https://bmcmedgenomics.biomedcentral.com/track/pdf/10.1186/s12920-020-00826-6; doi:https://doi.org/10.1186/s12920-020-00826-6; html:https://europepmc.org/articles/PMC7685541; pdf:https://europepmc.org/articles/PMC7685541?pdf=render"
   },
   {
     "id": "37480048",
@@ -4113,23 +4130,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-023-03394-6; doi:https://doi.org/10.1186/s12872-023-03394-6; html:https://europepmc.org/articles/PMC10362581; pdf:https://europepmc.org/articles/PMC10362581?pdf=render"
   },
-  {
-    "id": "33228632",
-    "doi": "https://doi.org/10.1186/s12920-020-00826-6",
-    "title": "A random forest based biomarker discovery and power analysis framework for diagnostics research.",
-    "authorString": "Acharjee A, Larkman J, Xu Y, Cardoso VR, Gkoutos GV.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC medical genomics",
-    "pubYear": "2020",
-    "date": "2020-11-23",
-    "isOpenAccess": "Y",
-    "keywords": "Biomarker; Feature Selection; Random Forest; Power Study",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcmedgenomics.biomedcentral.com/track/pdf/10.1186/s12920-020-00826-6; doi:https://doi.org/10.1186/s12920-020-00826-6; html:https://europepmc.org/articles/PMC7685541; pdf:https://europepmc.org/articles/PMC7685541?pdf=render"
-  },
   {
     "id": "37674175",
     "doi": "https://doi.org/10.1186/s12884-023-05958-y",
@@ -4504,23 +4504,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/gigascience/article-pdf/doi/10.1093/gigascience/giad030/50383140/giad030.pdf; doi:https://doi.org/10.1093/gigascience/giad030; html:https://europepmc.org/articles/PMC10176503; pdf:https://europepmc.org/articles/PMC10176503?pdf=render"
   },
-  {
-    "id": "37400731",
-    "doi": "https://doi.org/10.1007/s10802-023-01086-5",
-    "title": "Maternal Mental Health and Children's Problem Behaviours: A Bi-directional Relationship?",
-    "authorString": "Lowthian E, Bedston S, Kristensen SM, Akbari A, Fry R, Huxley K, Johnson R, Kim HS, Owen RK, Taylor C, Griffiths L.",
-    "authorAffiliations": "",
-    "journalTitle": "Research on child and adolescent psychopathology",
-    "pubYear": "2023",
-    "date": "2023-07-04",
-    "isOpenAccess": "Y",
-    "keywords": "Child Development; Bayesian analysis; Structural Equation Modelling; Maternal Mental Health; Millennium Cohort Study",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Transactional theory and the coercive family process model have illustrated how the parent-child relationship is reciprocal. Emerging research using advanced statistical methods has examined these theories, but further investigations are necessary. In this study, we utilised linked health data on maternal mental health disorders and explored their relationship with child problem behaviours via the Strengths and Difficulties Questionnaire for over 13 years. We accessed data from the Millennium Cohort Study, linked to anonymised individual-level population-scale health and administrative data within the Secure Anonymised Information Linkage (SAIL) Databank. We used Bayesian Structural Equation Modelling, specifically Random-Intercept Cross-Lagged Panel Models, to analyse the relationships between mothers and their children. We then explored these models with the addition of time-invariant covariates. We found that a mother's mental health was strongly associated over time, as were children's problem behaviours. We found mixed evidence for bi-directional relationships, with only emotional problems showing bi-directional associations in mid to late childhood. Only child-to-mother pathways were identified for the overall problem behaviour score and peer problems; no associations were found for conduct problems or hyperactivity. All models had strong between-effects and clear socioeconomic and sex differences. We encourage the use of whole family-based support for mental health and problem behaviours, and recommend that socioeconomic, sex and wider differences should be considered as factors in tailoring family-based interventions and support.",
-    "laySummary": "",
-    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s10802-023-01086-5.pdf; doi:https://doi.org/10.1007/s10802-023-01086-5; html:https://europepmc.org/articles/PMC10628040; pdf:https://europepmc.org/articles/PMC10628040?pdf=render"
-  },
   {
     "id": "34440368",
     "doi": "https://doi.org/10.3390/genes12081194",
@@ -4538,6 +4521,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/2073-4425/12/8/1194/pdf?version=1627984735; doi:https://doi.org/10.3390/genes12081194; html:https://europepmc.org/articles/PMC8391428; pdf:https://europepmc.org/articles/PMC8391428?pdf=render"
   },
+  {
+    "id": "37400731",
+    "doi": "https://doi.org/10.1007/s10802-023-01086-5",
+    "title": "Maternal Mental Health and Children's Problem Behaviours: A Bi-directional Relationship?",
+    "authorString": "Lowthian E, Bedston S, Kristensen SM, Akbari A, Fry R, Huxley K, Johnson R, Kim HS, Owen RK, Taylor C, Griffiths L.",
+    "authorAffiliations": "",
+    "journalTitle": "Research on child and adolescent psychopathology",
+    "pubYear": "2023",
+    "date": "2023-07-04",
+    "isOpenAccess": "Y",
+    "keywords": "Child Development; Bayesian analysis; Structural Equation Modelling; Maternal Mental Health; Millennium Cohort Study",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Transactional theory and the coercive family process model have illustrated how the parent-child relationship is reciprocal. Emerging research using advanced statistical methods has examined these theories, but further investigations are necessary. In this study, we utilised linked health data on maternal mental health disorders and explored their relationship with child problem behaviours via the Strengths and Difficulties Questionnaire for over 13 years. We accessed data from the Millennium Cohort Study, linked to anonymised individual-level population-scale health and administrative data within the Secure Anonymised Information Linkage (SAIL) Databank. We used Bayesian Structural Equation Modelling, specifically Random-Intercept Cross-Lagged Panel Models, to analyse the relationships between mothers and their children. We then explored these models with the addition of time-invariant covariates. We found that a mother's mental health was strongly associated over time, as were children's problem behaviours. We found mixed evidence for bi-directional relationships, with only emotional problems showing bi-directional associations in mid to late childhood. Only child-to-mother pathways were identified for the overall problem behaviour score and peer problems; no associations were found for conduct problems or hyperactivity. All models had strong between-effects and clear socioeconomic and sex differences. We encourage the use of whole family-based support for mental health and problem behaviours, and recommend that socioeconomic, sex and wider differences should be considered as factors in tailoring family-based interventions and support.",
+    "laySummary": "",
+    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s10802-023-01086-5.pdf; doi:https://doi.org/10.1007/s10802-023-01086-5; html:https://europepmc.org/articles/PMC10628040; pdf:https://europepmc.org/articles/PMC10628040?pdf=render"
+  },
   {
     "id": "37046692",
     "doi": "https://doi.org/10.3390/cancers15072031",
@@ -4691,23 +4691,6 @@
     "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": "37795045",
-    "doi": "https://doi.org/10.1177/26320843221147855",
-    "title": "Monitoring metrics over time: Why clinical trialists need to systematically collect site performance metrics.",
-    "authorString": "Yorke-Edwards V, Diaz-Montana C, Murray ML, Sydes MR, Love SB.",
-    "authorAffiliations": "",
-    "journalTitle": "Research methods in medicine & health sciences",
-    "pubYear": "2023",
-    "date": "2022-12-21",
-    "isOpenAccess": "N",
-    "keywords": "Clinical Trials; Risk-based Monitoring; Central Monitoring; Centralised Monitoring; Study-Within-A-Trial (Swat)",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Over the last decade, there has been an increasing interest in risk-based monitoring (RBM) in clinical trials, resulting in a number of guidelines from regulators and its inclusion in ICH GCP. However, there is a lack of detail on how to approach RBM from a practical perspective, and insufficient understanding of best practice.<h4>Purpose</h4>We present a method for clinical trials units to track their metrics within clinical trials using descriptive statistics and visualisations.<h4>Research design</h4>We suggest descriptive statistics and visualisations within a SWAT methodology.<h4>Study sample</h4>We illustrate this method using the metrics from TEMPER, a monitoring study carried out in three trials at the MRC Clinical Trials Unit at UCL.<h4>Data collection</h4>The data collection for TEMPER is described in <i>DOI: 10.1177/1740774518793379</i>.<h4>Results</h4>We show the results and discuss a protocol for a Study-Within-A-Trial (SWAT 167) for those wishing to use the method.<h4>Conclusions</h4>The potential benefits metric tracking brings to clinical trials include enhanced assessment of sites for potential corrective action, improved evaluation and contextualisation of the influence of metrics and their thresholds, and the establishment of best practice in RBM. The standardisation of the collection of such monitoring data would benefit both individual trials and the clinical trials community.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1177/26320843221147855; html:https://europepmc.org/articles/PMC7615148; pdf:https://europepmc.org/articles/PMC7615148?pdf=render; doi:https://doi.org/10.1177/26320843221147855"
-  },
   {
     "id": "36217535",
     "doi": "https://doi.org/10.1038/s43856-022-00185-6",
@@ -4725,6 +4708,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s43856-022-00185-6.pdf; 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": "37795045",
+    "doi": "https://doi.org/10.1177/26320843221147855",
+    "title": "Monitoring metrics over time: Why clinical trialists need to systematically collect site performance metrics.",
+    "authorString": "Yorke-Edwards V, Diaz-Montana C, Murray ML, Sydes MR, Love SB.",
+    "authorAffiliations": "",
+    "journalTitle": "Research methods in medicine & health sciences",
+    "pubYear": "2023",
+    "date": "2022-12-21",
+    "isOpenAccess": "N",
+    "keywords": "Clinical Trials; Risk-based Monitoring; Central Monitoring; Centralised Monitoring; Study-Within-A-Trial (Swat)",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Over the last decade, there has been an increasing interest in risk-based monitoring (RBM) in clinical trials, resulting in a number of guidelines from regulators and its inclusion in ICH GCP. However, there is a lack of detail on how to approach RBM from a practical perspective, and insufficient understanding of best practice.<h4>Purpose</h4>We present a method for clinical trials units to track their metrics within clinical trials using descriptive statistics and visualisations.<h4>Research design</h4>We suggest descriptive statistics and visualisations within a SWAT methodology.<h4>Study sample</h4>We illustrate this method using the metrics from TEMPER, a monitoring study carried out in three trials at the MRC Clinical Trials Unit at UCL.<h4>Data collection</h4>The data collection for TEMPER is described in <i>DOI: 10.1177/1740774518793379</i>.<h4>Results</h4>We show the results and discuss a protocol for a Study-Within-A-Trial (SWAT 167) for those wishing to use the method.<h4>Conclusions</h4>The potential benefits metric tracking brings to clinical trials include enhanced assessment of sites for potential corrective action, improved evaluation and contextualisation of the influence of metrics and their thresholds, and the establishment of best practice in RBM. The standardisation of the collection of such monitoring data would benefit both individual trials and the clinical trials community.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1177/26320843221147855; html:https://europepmc.org/articles/PMC7615148; pdf:https://europepmc.org/articles/PMC7615148?pdf=render; doi:https://doi.org/10.1177/26320843221147855"
+  },
   {
     "id": "36701357",
     "doi": "https://doi.org/10.1371/journal.pone.0280943",
@@ -4742,23 +4742,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0280943&type=printable; doi:https://doi.org/10.1371/journal.pone.0280943; html:https://europepmc.org/articles/PMC9879384; pdf:https://europepmc.org/articles/PMC9879384?pdf=render"
   },
-  {
-    "id": "37798357",
-    "doi": "https://doi.org/10.1038/s41598-023-42331-7",
-    "title": "An angiopoietin 2, FGF23, and BMP10 biomarker signature differentiates atrial fibrillation from other concomitant cardiovascular conditions.",
-    "authorString": "Chua W, Cardoso VR, Guasch E, Sinner MF, Al-Taie C, Brady P, Casadei B, Crijns HJGM, Dudink EAMP, Hatem SN, K\u00e4\u00e4b S, Kastner P, Mont L, Nehaj F, Purmah Y, Reyat JS, Schotten U, Sommerfeld LC, Zeemering S, Ziegler A, Gkoutos GV, Kirchhof P, Fabritz L.",
-    "authorAffiliations": "",
-    "journalTitle": "Scientific reports",
-    "pubYear": "2023",
-    "date": "2023-10-05",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Early detection of atrial fibrillation (AF) enables initiation of anticoagulation and early rhythm control therapy to reduce stroke, cardiovascular death, and heart failure. In a cross-sectional, observational study, we aimed to identify a combination of circulating biomolecules reflecting different biological processes to detect prevalent AF in patients with cardiovascular conditions presenting to hospital. Twelve biomarkers identified by reviewing literature and patents were quantified on a high-precision, high-throughput platform in 1485 consecutive patients with cardiovascular conditions (median age 69\u00a0years [Q1, Q3 60, 78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. Logistic regression with backward elimination and a neural network approach considering 7 key clinical characteristics and 12 biomarker concentrations were applied to a randomly sampled discovery cohort (n\u2009=\u2009933) and validated in the remaining patients (n\u2009=\u2009552). In addition to age, sex, and body mass index (BMI), BMP10, ANGPT2, and FGF23 identified patients with prevalent AF (AUC 0.743 [95% CI 0.712, 0.775]). These circulating biomolecules represent distinct pathways associated with atrial cardiomyopathy and AF. Neural networks identified the same variables as the regression-based approach. The validation using regression yielded an AUC of 0.719 (95% CI 0.677, 0.762), corroborated using deep neural networks (AUC 0.784 [95% CI 0.745, 0.822]). Age, sex, BMI and three circulating biomolecules (BMP10, ANGPT2, FGF23) are associated with prevalent AF in unselected patients presenting to hospital. Findings should be externally validated. Results suggest that age and different disease processes approximated by these three biomolecules contribute to AF in patients. Our findings have the potential to improve screening programs for AF after external validation.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41598-023-42331-7.pdf; doi:https://doi.org/10.1038/s41598-023-42331-7; html:https://europepmc.org/articles/PMC10556075; pdf:https://europepmc.org/articles/PMC10556075?pdf=render"
-  },
   {
     "id": "33114263",
     "doi": "https://doi.org/10.3390/ijms21217886",
@@ -4777,21 +4760,21 @@
     "urls": "pdf:https://www.mdpi.com/1422-0067/21/21/7886/pdf?version=1604329387; doi:https://doi.org/10.3390/ijms21217886; html:https://europepmc.org/articles/PMC7660606; pdf:https://europepmc.org/articles/PMC7660606?pdf=render"
   },
   {
-    "id": "34007894",
-    "doi": "https://doi.org/10.23889/ijpds.v6i1.1373",
-    "title": "Visualisation and optimisation of alcohol-related hospital admissions ICD-10 codes in Welsh e-cohort data.",
-    "authorString": "Trefan L, Akbari A, Morgan JS, Farewell DM, Fone D, Lyons RA, Jones Hywel M, Moore SC.",
+    "id": "37798357",
+    "doi": "https://doi.org/10.1038/s41598-023-42331-7",
+    "title": "An angiopoietin 2, FGF23, and BMP10 biomarker signature differentiates atrial fibrillation from other concomitant cardiovascular conditions.",
+    "authorString": "Chua W, Cardoso VR, Guasch E, Sinner MF, Al-Taie C, Brady P, Casadei B, Crijns HJGM, Dudink EAMP, Hatem SN, K\u00e4\u00e4b S, Kastner P, Mont L, Nehaj F, Purmah Y, Reyat JS, Schotten U, Sommerfeld LC, Zeemering S, Ziegler A, Gkoutos GV, Kirchhof P, Fabritz L.",
     "authorAffiliations": "",
-    "journalTitle": "International journal of population data science",
-    "pubYear": "2021",
-    "date": "2021-03-24",
+    "journalTitle": "Scientific reports",
+    "pubYear": "2023",
+    "date": "2023-10-05",
     "isOpenAccess": "Y",
-    "keywords": "Alcohol; Hospital Admission; Optimisation; Icd-10 Codes; E-Cohort Data",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>There was agreement between admission and discharge codes. When more than ten coding fields were used the misclassification rate was less than 1%.<h4>Conclusion</h4>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.",
+    "abstract": "Early detection of atrial fibrillation (AF) enables initiation of anticoagulation and early rhythm control therapy to reduce stroke, cardiovascular death, and heart failure. In a cross-sectional, observational study, we aimed to identify a combination of circulating biomolecules reflecting different biological processes to detect prevalent AF in patients with cardiovascular conditions presenting to hospital. Twelve biomarkers identified by reviewing literature and patents were quantified on a high-precision, high-throughput platform in 1485 consecutive patients with cardiovascular conditions (median age 69\u00a0years [Q1, Q3 60, 78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. Logistic regression with backward elimination and a neural network approach considering 7 key clinical characteristics and 12 biomarker concentrations were applied to a randomly sampled discovery cohort (n\u2009=\u2009933) and validated in the remaining patients (n\u2009=\u2009552). In addition to age, sex, and body mass index (BMI), BMP10, ANGPT2, and FGF23 identified patients with prevalent AF (AUC 0.743 [95% CI 0.712, 0.775]). These circulating biomolecules represent distinct pathways associated with atrial cardiomyopathy and AF. Neural networks identified the same variables as the regression-based approach. The validation using regression yielded an AUC of 0.719 (95% CI 0.677, 0.762), corroborated using deep neural networks (AUC 0.784 [95% CI 0.745, 0.822]). Age, sex, BMI and three circulating biomolecules (BMP10, ANGPT2, FGF23) are associated with prevalent AF in unselected patients presenting to hospital. Findings should be externally validated. Results suggest that age and different disease processes approximated by these three biomolecules contribute to AF in patients. Our findings have the potential to improve screening programs for AF after external validation.",
     "laySummary": "",
-    "urls": "pdf:https://ijpds.org/article/download/1373/3264; doi:https://doi.org/10.23889/ijpds.v6i1.1373; html:https://europepmc.org/articles/PMC8103565; pdf:https://europepmc.org/articles/PMC8103565?pdf=render"
+    "urls": "pdf:https://www.nature.com/articles/s41598-023-42331-7.pdf; doi:https://doi.org/10.1038/s41598-023-42331-7; html:https://europepmc.org/articles/PMC10556075; pdf:https://europepmc.org/articles/PMC10556075?pdf=render"
   },
   {
     "id": "31799783",
@@ -4810,6 +4793,23 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3267; doi:https://doi.org/10.1002/cnm.3267; html:https://europepmc.org/articles/PMC9286682; pdf:https://europepmc.org/articles/PMC9286682?pdf=render"
   },
+  {
+    "id": "34007894",
+    "doi": "https://doi.org/10.23889/ijpds.v6i1.1373",
+    "title": "Visualisation and optimisation of alcohol-related hospital admissions ICD-10 codes in Welsh e-cohort data.",
+    "authorString": "Trefan L, Akbari A, Morgan JS, Farewell DM, Fone D, Lyons RA, Jones Hywel M, Moore SC.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of population data science",
+    "pubYear": "2021",
+    "date": "2021-03-24",
+    "isOpenAccess": "Y",
+    "keywords": "Alcohol; Hospital Admission; Optimisation; Icd-10 Codes; E-Cohort Data",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>There was agreement between admission and discharge codes. When more than ten coding fields were used the misclassification rate was less than 1%.<h4>Conclusion</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://ijpds.org/article/download/1373/3264; doi:https://doi.org/10.23889/ijpds.v6i1.1373; html:https://europepmc.org/articles/PMC8103565; pdf:https://europepmc.org/articles/PMC8103565?pdf=render"
+  },
   {
     "id": "35909058",
     "doi": "https://doi.org/10.1016/s2589-7500(22)00123-6",
@@ -5133,23 +5133,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02877-9; doi:https://doi.org/10.1186/s12916-023-02877-9; html:https://europepmc.org/articles/PMC10283271; pdf:https://europepmc.org/articles/PMC10283271?pdf=render"
   },
-  {
-    "id": "35567479",
-    "doi": "https://doi.org/10.1093/rheumatology/keac283",
-    "title": "Shielding reduced incidence of COVID-19 in patients with inflammatory arthritis but vulnerability is associated with increased mortality.",
-    "authorString": "Cooksey R, Underwood J, Brophy S, Atkinson M, Kennedy J, Choy E.",
-    "authorAffiliations": "",
-    "journalTitle": "Rheumatology (Oxford, England)",
-    "pubYear": "2022",
-    "date": "2022-06-01",
-    "isOpenAccess": "Y",
-    "keywords": "RA; As; PSA; Electronic Health Records; Covid-19; Inflammatory Arthritis",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>Investigate whether individuals with inflammatory arthritis (IA), their treatments and shielding status affect the risk of adverse outcomes from COVID-19 for the entire population of Wales, UK.<h4>Methods</h4>Retrospective, population-based cohort study using linked, anonymized electronic health data from SAIL Databank, including primary/secondary care, rheumatology, Office for National Statistics Mortality and COVID-19 laboratory data. Individuals aged 18\u2009years and over testing positive for COVID-19 between March 2020 and May 2021 with READ Codes present for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis formed the study cases.<h4>Results</h4>A total of 1966 people with IA and 166\u2009602 without tested positive for COVID-19. The incidence rate was 3.5% (1966/56\u2009914) in IA, vs 6% in the general population (166\u2009602/2\u2009760\u2009442), (difference: 2.5%, 95% CI: 2.4%, 2.7%, P\u00a0\u22640.001). In an adjusted Cox proportional hazard model, IA was not associated with higher mortality (HR: 0.56, 95% CI: 0.18, 1.64, P=0.286). Significant risk factors included shielding (HR: 1.52, 95% CI: 1.40, 1.64, P\u00a0\u22640.001), hospitalization for previous infections (HR: 1.20, 95% CI: 1.12, 1.28, P\u00a0\u22640.001), hospitalizations one year pre-pandemic (HR: 1.34, 95% CI: 1.25, 1.44, P\u00a0\u22640.001) and glucocorticoid use (HR: 1.17, 95% CI: 1.09, 1.25, P\u00a0\u22640.001).<h4>Conclusions</h4>Individuals with IA had a lower incidence of COVID-19, probably due to shielding. IA was not associated with increased mortality following COVID-19 infection; being vulnerable (shielded), comorbidities and other factors were associated with increased risk. These key risk factors can identify individuals with IA at greater risk from COVID-19 and advised to shield during high community prevalence.",
-    "laySummary": "",
-    "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa62372/Download/62372__26337__5539f4f995224d80a2156218d11a03cb.pdf; doi:https://doi.org/10.1093/rheumatology/keac283; html:https://europepmc.org/articles/PMC9248059; pdf:https://europepmc.org/articles/PMC9248059?pdf=render"
-  },
   {
     "id": "32565483",
     "doi": "https://doi.org/10.1136/bmjopen-2020-039097",
@@ -5167,6 +5150,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/6/e039097.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-039097; html:https://europepmc.org/articles/PMC7311023; pdf:https://europepmc.org/articles/PMC7311023?pdf=render"
   },
+  {
+    "id": "35567479",
+    "doi": "https://doi.org/10.1093/rheumatology/keac283",
+    "title": "Shielding reduced incidence of COVID-19 in patients with inflammatory arthritis but vulnerability is associated with increased mortality.",
+    "authorString": "Cooksey R, Underwood J, Brophy S, Atkinson M, Kennedy J, Choy E.",
+    "authorAffiliations": "",
+    "journalTitle": "Rheumatology (Oxford, England)",
+    "pubYear": "2022",
+    "date": "2022-06-01",
+    "isOpenAccess": "Y",
+    "keywords": "RA; As; PSA; Electronic Health Records; Covid-19; Inflammatory Arthritis",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>Investigate whether individuals with inflammatory arthritis (IA), their treatments and shielding status affect the risk of adverse outcomes from COVID-19 for the entire population of Wales, UK.<h4>Methods</h4>Retrospective, population-based cohort study using linked, anonymized electronic health data from SAIL Databank, including primary/secondary care, rheumatology, Office for National Statistics Mortality and COVID-19 laboratory data. Individuals aged 18\u2009years and over testing positive for COVID-19 between March 2020 and May 2021 with READ Codes present for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis formed the study cases.<h4>Results</h4>A total of 1966 people with IA and 166\u2009602 without tested positive for COVID-19. The incidence rate was 3.5% (1966/56\u2009914) in IA, vs 6% in the general population (166\u2009602/2\u2009760\u2009442), (difference: 2.5%, 95% CI: 2.4%, 2.7%, P\u00a0\u22640.001). In an adjusted Cox proportional hazard model, IA was not associated with higher mortality (HR: 0.56, 95% CI: 0.18, 1.64, P=0.286). Significant risk factors included shielding (HR: 1.52, 95% CI: 1.40, 1.64, P\u00a0\u22640.001), hospitalization for previous infections (HR: 1.20, 95% CI: 1.12, 1.28, P\u00a0\u22640.001), hospitalizations one year pre-pandemic (HR: 1.34, 95% CI: 1.25, 1.44, P\u00a0\u22640.001) and glucocorticoid use (HR: 1.17, 95% CI: 1.09, 1.25, P\u00a0\u22640.001).<h4>Conclusions</h4>Individuals with IA had a lower incidence of COVID-19, probably due to shielding. IA was not associated with increased mortality following COVID-19 infection; being vulnerable (shielded), comorbidities and other factors were associated with increased risk. These key risk factors can identify individuals with IA at greater risk from COVID-19 and advised to shield during high community prevalence.",
+    "laySummary": "",
+    "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa62372/Download/62372__26337__5539f4f995224d80a2156218d11a03cb.pdf; doi:https://doi.org/10.1093/rheumatology/keac283; html:https://europepmc.org/articles/PMC9248059; pdf:https://europepmc.org/articles/PMC9248059?pdf=render"
+  },
   {
     "id": "36529825",
     "doi": "https://doi.org/10.1007/s40258-022-00777-2",
@@ -5541,23 +5541,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.cell.com/article/S2666389922000514/pdf; 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": "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": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 (P<sub>interaction</sub>\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).<h4>Conclusions</h4>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": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02921-8; 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": "33948220",
     "doi": "https://doi.org/10.1177/20552076211007661",
@@ -5575,6 +5558,23 @@
     "laySummary": "",
     "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/20552076211007661; doi:https://doi.org/10.1177/20552076211007661; html:https://europepmc.org/articles/PMC8054217; pdf:https://europepmc.org/articles/PMC8054217?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": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 (P<sub>interaction</sub>\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).<h4>Conclusions</h4>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": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02921-8; 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": "36332942",
     "doi": "https://doi.org/10.1136/openhrt-2022-002142",
@@ -5660,23 +5660,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ckj/article-pdf/16/2/342/49100412/sfac241.pdf; doi:https://doi.org/10.1093/ckj/sfac241; html:https://europepmc.org/articles/PMC9900564; pdf:https://europepmc.org/articles/PMC9900564?pdf=render"
   },
-  {
-    "id": "34582457",
-    "doi": "https://doi.org/10.1371/journal.pmed.1003777",
-    "title": "Predictive symptoms for COVID-19 in the community: REACT-1 study of over 1 million people.",
-    "authorString": "Elliott J, Whitaker M, Bodinier B, Eales O, Riley S, Ward H, Cooke G, Darzi A, Chadeau-Hyam M, Elliott P.",
-    "authorAffiliations": "",
-    "journalTitle": "PLoS medicine",
-    "pubYear": "2021",
-    "date": "2021-09-28",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003777&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003777; html:https://europepmc.org/articles/PMC8478234; pdf:https://europepmc.org/articles/PMC8478234?pdf=render"
-  },
   {
     "id": "32341912",
     "doi": "https://doi.org/10.1177/2235042x19893470",
@@ -5694,6 +5677,23 @@
     "laySummary": "",
     "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/2235042X19893470; doi:https://doi.org/10.1177/2235042X19893470; html:https://europepmc.org/articles/PMC7171988; pdf:https://europepmc.org/articles/PMC7171988?pdf=render"
   },
+  {
+    "id": "34582457",
+    "doi": "https://doi.org/10.1371/journal.pmed.1003777",
+    "title": "Predictive symptoms for COVID-19 in the community: REACT-1 study of over 1 million people.",
+    "authorString": "Elliott J, Whitaker M, Bodinier B, Eales O, Riley S, Ward H, Cooke G, Darzi A, Chadeau-Hyam M, Elliott P.",
+    "authorAffiliations": "",
+    "journalTitle": "PLoS medicine",
+    "pubYear": "2021",
+    "date": "2021-09-28",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003777&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003777; html:https://europepmc.org/articles/PMC8478234; pdf:https://europepmc.org/articles/PMC8478234?pdf=render"
+  },
   {
     "id": "36193673",
     "doi": "https://doi.org/10.1192/j.eurpsy.2022.2324",
@@ -5796,23 +5796,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2589537021003801/pdf; doi:https://doi.org/10.1016/j.eclinm.2021.101100; html:https://europepmc.org/articles/PMC8548919; pdf:https://europepmc.org/articles/PMC8548919?pdf=render"
   },
-  {
-    "id": "37311808",
-    "doi": "https://doi.org/10.1038/s41467-023-39193-y",
-    "title": "Natural history of long-COVID in a nationwide, population cohort study.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature communications",
-    "pubYear": "2023",
-    "date": "2023-06-13",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41467-023-39193-y.pdf; doi:https://doi.org/10.1038/s41467-023-39193-y; html:https://europepmc.org/articles/PMC10263377; pdf:https://europepmc.org/articles/PMC10263377?pdf=render"
-  },
   {
     "id": "34089614",
     "doi": "https://doi.org/10.1093/ije/dyab028",
@@ -5830,6 +5813,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ije/article-pdf/50/4/1064/40146583/dyab028.pdf; doi:https://doi.org/10.1093/ije/dyab028; html:https://europepmc.org/articles/PMC8195245; pdf:https://europepmc.org/articles/PMC8195245?pdf=render"
   },
+  {
+    "id": "37311808",
+    "doi": "https://doi.org/10.1038/s41467-023-39193-y",
+    "title": "Natural history of long-COVID in a nationwide, population cohort study.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature communications",
+    "pubYear": "2023",
+    "date": "2023-06-13",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41467-023-39193-y.pdf; doi:https://doi.org/10.1038/s41467-023-39193-y; html:https://europepmc.org/articles/PMC10263377; pdf:https://europepmc.org/articles/PMC10263377?pdf=render"
+  },
   {
     "id": "34599903",
     "doi": "https://doi.org/10.1016/s2213-2600(21)00380-5",
@@ -6017,23 +6017,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.bjanaesthesia.org/article/S0007091221003123/pdf; 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"
   },
-  {
-    "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": "<h4>Objective</h4>To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England.<h4>Design</h4>Serial cross-sectional study.<h4>Setting</h4>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).<h4>Study population</h4>Children aged 5-17 years in the community.<h4>Predictors</h4>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.<h4>Main outcome measures</h4>Prevalence of persistent symptoms, reported as those lasting \u22653 months post-COVID-19.<h4>Results</h4>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.<h4>Conclusions</h4>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": "pdf:https://adc.bmj.com/content/archdischild/early/2023/03/01/archdischild-2022-325152.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-325152; html:https://europepmc.org/articles/PMC10313975; pdf:https://europepmc.org/articles/PMC10313975?pdf=render"
-  },
   {
     "id": "35909578",
     "doi": "https://doi.org/10.23889/ijpds.v7i1.1717",
@@ -6051,6 +6034,23 @@
     "laySummary": "",
     "urls": "pdf:https://ijpds.org/article/download/1717/3510; doi:https://doi.org/10.23889/ijpds.v7i1.1717; html:https://europepmc.org/articles/PMC9284510; pdf:https://europepmc.org/articles/PMC9284510?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": "<h4>Objective</h4>To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England.<h4>Design</h4>Serial cross-sectional study.<h4>Setting</h4>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).<h4>Study population</h4>Children aged 5-17 years in the community.<h4>Predictors</h4>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.<h4>Main outcome measures</h4>Prevalence of persistent symptoms, reported as those lasting \u22653 months post-COVID-19.<h4>Results</h4>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.<h4>Conclusions</h4>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": "pdf:https://adc.bmj.com/content/archdischild/early/2023/03/01/archdischild-2022-325152.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-325152; html:https://europepmc.org/articles/PMC10313975; pdf:https://europepmc.org/articles/PMC10313975?pdf=render"
+  },
   {
     "id": "35361119",
     "doi": "https://doi.org/10.1186/s12859-022-04641-x",
@@ -6340,23 +6340,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.schres.2023.08.014"
   },
-  {
-    "id": "37159441",
-    "doi": "https://doi.org/10.1371/journal.pdig.0000218",
-    "title": "Hospital-wide natural language processing summarising the health data of 1 million patients.",
-    "authorString": "Bean DM, Kraljevic Z, Shek A, Teo J, Dobson RJB.",
-    "authorAffiliations": "",
-    "journalTitle": "PLOS digital health",
-    "pubYear": "2023",
-    "date": "2023-05-09",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1371/journal.pdig.0000218; doi:https://doi.org/10.1371/journal.pdig.0000218; html:https://europepmc.org/articles/PMC10168555; pdf:https://europepmc.org/articles/PMC10168555?pdf=render"
-  },
   {
     "id": "31757986",
     "doi": "https://doi.org/10.1038/s41598-019-53454-1",
@@ -6375,21 +6358,21 @@
     "urls": "pdf:https://www.nature.com/articles/s41598-019-53454-1.pdf; doi:https://doi.org/10.1038/s41598-019-53454-1; html:https://europepmc.org/articles/PMC6874647; pdf:https://europepmc.org/articles/PMC6874647?pdf=render"
   },
   {
-    "id": "37185201",
-    "doi": "https://doi.org/10.1136/bmjopen-2022-067337",
-    "title": "Prevalence of HIV in mental health service users: a retrospective cohort study.",
-    "authorString": "Heslin M, Jewell A, Croxford S, Chau C, Smith S, Pittrof R, Covshoff E, Sullivan A, Delpech V, Brown A, King HP, Kakaiya M, Campbell L, Hughes E, Stewart R.",
+    "id": "37159441",
+    "doi": "https://doi.org/10.1371/journal.pdig.0000218",
+    "title": "Hospital-wide natural language processing summarising the health data of 1 million patients.",
+    "authorString": "Bean DM, Kraljevic Z, Shek A, Teo J, Dobson RJB.",
     "authorAffiliations": "",
-    "journalTitle": "BMJ open",
+    "journalTitle": "PLOS digital health",
     "pubYear": "2023",
-    "date": "2023-04-25",
+    "date": "2023-05-09",
     "isOpenAccess": "Y",
-    "keywords": "Mental health; Hiv & Aids; Sexual Medicine",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To examine the prevalence of HIV in a cohort of people who have used secondary mental health services in the UK.<h4>Design</h4>Retrospective cohort study.<h4>Setting</h4>Routinely collected clinical data from secondary mental health services in South London, UK available for research through the Clinical Record Interactive Search tool at the National Institute for Health and Care Research Maudsley Biomedical Research Centre were matched with pseudonymised national HIV surveillance data held by the UK Health Security Agency using a deterministic matching algorithm.<h4>Participants</h4>All adults aged 16+ who presented for the first time to mental health services in the South London and Maudsley (SLaM) National Health Service Trust between 1 January 2007 and 31 December 2018 were included.<h4>Primary outcome</h4>Point prevalence of HIV.<h4>Results</h4>There were 181\u2009177 people who had contact with mental health services for the first time between 2007 and 2018 in SLaM. Overall, 2.47% (n=4481) of those had a recorded HIV diagnosis in national HIV surveillance data at any time (before, during or after contact with mental health services), 24.73 people per 1000. HIV point prevalence was highest in people with a diagnosed substance use disorder at 3.77% (n=784). A substantial percentage of the sample did not have a formal mental health diagnosis (27%), but even with those excluded, the point prevalence remained high at 2.31%. Around two-thirds of people had their diagnosis of HIV before contact with mental health services (67%; n=1495).<h4>Conclusions</h4>The prevalence of HIV in people who have had contact with mental health services was approximately 2.5 times higher than the general population in the same geographical area. Future work should investigate risk factors and disparities in HIV outcomes between those with and without mental health service contact.",
+    "abstract": "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.",
     "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e067337.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-067337; html:https://europepmc.org/articles/PMC10186409; pdf:https://europepmc.org/articles/PMC10186409?pdf=render"
+    "urls": "doi:https://doi.org/10.1371/journal.pdig.0000218; doi:https://doi.org/10.1371/journal.pdig.0000218; html:https://europepmc.org/articles/PMC10168555; pdf:https://europepmc.org/articles/PMC10168555?pdf=render"
   },
   {
     "id": "32723851",
@@ -6408,6 +6391,23 @@
     "laySummary": "",
     "urls": "pdf:https://informatics.bmj.com/content/bmjhci/27/2/e100122.full.pdf; doi:https://doi.org/10.1136/bmjhci-2019-100122; html:https://europepmc.org/articles/PMC7388881; pdf:https://europepmc.org/articles/PMC7388881?pdf=render"
   },
+  {
+    "id": "37185201",
+    "doi": "https://doi.org/10.1136/bmjopen-2022-067337",
+    "title": "Prevalence of HIV in mental health service users: a retrospective cohort study.",
+    "authorString": "Heslin M, Jewell A, Croxford S, Chau C, Smith S, Pittrof R, Covshoff E, Sullivan A, Delpech V, Brown A, King HP, Kakaiya M, Campbell L, Hughes E, Stewart R.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2023",
+    "date": "2023-04-25",
+    "isOpenAccess": "Y",
+    "keywords": "Mental health; Hiv & Aids; Sexual Medicine",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To examine the prevalence of HIV in a cohort of people who have used secondary mental health services in the UK.<h4>Design</h4>Retrospective cohort study.<h4>Setting</h4>Routinely collected clinical data from secondary mental health services in South London, UK available for research through the Clinical Record Interactive Search tool at the National Institute for Health and Care Research Maudsley Biomedical Research Centre were matched with pseudonymised national HIV surveillance data held by the UK Health Security Agency using a deterministic matching algorithm.<h4>Participants</h4>All adults aged 16+ who presented for the first time to mental health services in the South London and Maudsley (SLaM) National Health Service Trust between 1 January 2007 and 31 December 2018 were included.<h4>Primary outcome</h4>Point prevalence of HIV.<h4>Results</h4>There were 181\u2009177 people who had contact with mental health services for the first time between 2007 and 2018 in SLaM. Overall, 2.47% (n=4481) of those had a recorded HIV diagnosis in national HIV surveillance data at any time (before, during or after contact with mental health services), 24.73 people per 1000. HIV point prevalence was highest in people with a diagnosed substance use disorder at 3.77% (n=784). A substantial percentage of the sample did not have a formal mental health diagnosis (27%), but even with those excluded, the point prevalence remained high at 2.31%. Around two-thirds of people had their diagnosis of HIV before contact with mental health services (67%; n=1495).<h4>Conclusions</h4>The prevalence of HIV in people who have had contact with mental health services was approximately 2.5 times higher than the general population in the same geographical area. Future work should investigate risk factors and disparities in HIV outcomes between those with and without mental health service contact.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e067337.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-067337; html:https://europepmc.org/articles/PMC10186409; pdf:https://europepmc.org/articles/PMC10186409?pdf=render"
+  },
   {
     "id": "35902613",
     "doi": "https://doi.org/10.1038/s41467-022-32096-4",
@@ -7156,23 +7156,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264529&type=printable; doi:https://doi.org/10.1371/journal.pone.0264529; html:https://europepmc.org/articles/PMC8880762; pdf:https://europepmc.org/articles/PMC8880762?pdf=render"
   },
-  {
-    "id": "34183342",
-    "doi": "https://doi.org/10.1136/bmjopen-2020-046392",
-    "title": "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.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2021",
-    "date": "2021-06-28",
-    "isOpenAccess": "Y",
-    "keywords": "epidemiology; Public Health; Adult Intensive & Critical Care; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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/).<h4>Trial registration number</h4>ISRCTN11811602.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e046392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046392; html:https://europepmc.org/articles/PMC8245289; pdf:https://europepmc.org/articles/PMC8245289?pdf=render"
-  },
   {
     "id": "34693751",
     "doi": "https://doi.org/10.1177/14799731211053332",
@@ -7190,6 +7173,23 @@
     "laySummary": "",
     "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/14799731211053332; doi:https://doi.org/10.1177/14799731211053332; html:https://europepmc.org/articles/PMC8543738; pdf:https://europepmc.org/articles/PMC8543738?pdf=render"
   },
+  {
+    "id": "34183342",
+    "doi": "https://doi.org/10.1136/bmjopen-2020-046392",
+    "title": "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.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2021",
+    "date": "2021-06-28",
+    "isOpenAccess": "Y",
+    "keywords": "epidemiology; Public Health; Adult Intensive & Critical Care; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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.<h4>Ethics and dissemination</h4>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/).<h4>Trial registration number</h4>ISRCTN11811602.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e046392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046392; html:https://europepmc.org/articles/PMC8245289; pdf:https://europepmc.org/articles/PMC8245289?pdf=render"
+  },
   {
     "id": "34957254",
     "doi": "https://doi.org/10.3389/fcvm.2021.766287",
@@ -7224,23 +7224,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.epidem.2021.100460; doi:https://doi.org/10.1016/j.epidem.2021.100460; html:https://europepmc.org/articles/PMC8193815"
   },
-  {
-    "id": "37203546",
-    "doi": "https://doi.org/10.3233/shti230319",
-    "title": "On the Difficulty of Predicting Engagement with Digital Health for Substance Use.",
-    "authorString": "G\u00fcnther F, Yau C, Elison-Davies S, Wong D.",
-    "authorAffiliations": "",
-    "journalTitle": "Studies in health technology and informatics",
-    "pubYear": "2023",
-    "date": "2023-05-01",
-    "isOpenAccess": "N",
-    "keywords": "Prediction; Engagement; Substance Use; Digital Health",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Digital interventions can be an important instrument in treating substance use disorder. However, most digital mental health interventions suffer from early, frequent user dropout. Early prediction of engagement would allow identification of individuals whose engagement with digital interventions may be too limited to support behaviour change, and subsequently offering them support. To investigate this, we used machine learning models to predict different metrics of real-world engagement with a digital cognitive behavioural therapy intervention widely available in UK addiction services. Our predictor set consisted of baseline data from routinely-collected standardised psychometric measures. Areas under the ROC curve, and correlations between predicted and observed values indicated that baseline data do not contain sufficient information about individual patterns of engagement.",
-    "laySummary": "",
-    "urls": "pdf:https://ebooks.iospress.nl/pdf/doi/10.3233/SHTI230319; doi:https://doi.org/10.3233/SHTI230319"
-  },
   {
     "id": "35310465",
     "doi": "https://doi.org/10.23889/ijpds.v5i4.1697",
@@ -7258,6 +7241,23 @@
     "laySummary": "",
     "urls": "pdf:https://ijpds.org/article/download/1697/3337; doi:https://doi.org/10.23889/ijpds.v5i4.1697; html:https://europepmc.org/articles/PMC8900650; pdf:https://europepmc.org/articles/PMC8900650?pdf=render"
   },
+  {
+    "id": "37203546",
+    "doi": "https://doi.org/10.3233/shti230319",
+    "title": "On the Difficulty of Predicting Engagement with Digital Health for Substance Use.",
+    "authorString": "G\u00fcnther F, Yau C, Elison-Davies S, Wong D.",
+    "authorAffiliations": "",
+    "journalTitle": "Studies in health technology and informatics",
+    "pubYear": "2023",
+    "date": "2023-05-01",
+    "isOpenAccess": "N",
+    "keywords": "Prediction; Engagement; Substance Use; Digital Health",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Digital interventions can be an important instrument in treating substance use disorder. However, most digital mental health interventions suffer from early, frequent user dropout. Early prediction of engagement would allow identification of individuals whose engagement with digital interventions may be too limited to support behaviour change, and subsequently offering them support. To investigate this, we used machine learning models to predict different metrics of real-world engagement with a digital cognitive behavioural therapy intervention widely available in UK addiction services. Our predictor set consisted of baseline data from routinely-collected standardised psychometric measures. Areas under the ROC curve, and correlations between predicted and observed values indicated that baseline data do not contain sufficient information about individual patterns of engagement.",
+    "laySummary": "",
+    "urls": "pdf:https://ebooks.iospress.nl/pdf/doi/10.3233/SHTI230319; doi:https://doi.org/10.3233/SHTI230319"
+  },
   {
     "id": "33879450",
     "doi": "https://doi.org/10.1136/heartjnl-2021-319118",
@@ -7581,23 +7581,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/s2666-7568(22)00147-7; 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"
   },
-  {
-    "id": "PMC9644982",
-    "doi": "https://doi.org/",
-    "title": "Assessing the impacts of COVID-19 on Care Homes in Wales.",
-    "authorString": "Fry R, Hollinghurst J, North L, Emmerson C, Long S, Akbari A, Gravenor M, Lyons R.",
-    "authorAffiliations": "",
-    "journalTitle": "International journal of population data science",
-    "pubYear": null,
-    "date": "2022-11-21",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "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": "34145260",
     "doi": "https://doi.org/10.1038/s41467-021-23935-x",
@@ -7615,6 +7598,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-021-23935-x.pdf; doi:https://doi.org/10.1038/s41467-021-23935-x; html:https://europepmc.org/articles/PMC8213785; pdf:https://europepmc.org/articles/PMC8213785?pdf=render"
   },
+  {
+    "id": "PMC9644982",
+    "doi": "https://doi.org/",
+    "title": "Assessing the impacts of COVID-19 on Care Homes in Wales.",
+    "authorString": "Fry R, Hollinghurst J, North L, Emmerson C, Long S, Akbari A, Gravenor M, Lyons R.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of population data science",
+    "pubYear": null,
+    "date": "2022-11-21",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "",
+    "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": "36992264",
     "doi": "https://doi.org/10.3390/vaccines11030680",
@@ -7853,23 +7853,6 @@
     "laySummary": "",
     "urls": "pdf:https://bjsm.bmj.com/content/bjsports/early/2022/02/15/bjsports-2021-104050.full.pdf; doi:https://doi.org/10.1136/bjsports-2021-104050; html:https://europepmc.org/articles/PMC9484395; pdf:https://europepmc.org/articles/PMC9484395?pdf=render"
   },
-  {
-    "id": "37934728",
-    "doi": "https://doi.org/10.1093/jamia/ocad212",
-    "title": "Multi-faceted analysis and prediction for the outbreak of pediatric respiratory syncytial virus.",
-    "authorString": "Yang C, Gao J, Glass L, Cross A, Sun J.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of the American Medical Informatics Association : JAMIA",
-    "pubYear": "2023",
-    "date": "2023-11-02",
-    "isOpenAccess": "N",
-    "keywords": "Respiratory syncytial virus (RSV); Pediatric Diseases; Deep Learning; Tensor Factorization",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>Respiratory syncytial virus (RSV) is a significant cause of pediatric hospitalizations. This article aims to utilize multisource data and leverage the tensor methods to uncover distinct RSV geographic clusters and develop an accurate RSV prediction model for future seasons.<h4>Materials and methods</h4>This study utilizes 5-year RSV data from sources, including medical claims, CDC surveillance data, and Google search trends. We conduct spatiotemporal tensor analysis and prediction for pediatric RSV in the United States by designing (i) a nonnegative tensor factorization model for pediatric RSV diseases and location clustering; (ii) and a recurrent neural network tensor regression model for county-level trend prediction using the disease and location features.<h4>Results</h4>We identify a clustering hierarchy of pediatric diseases: Three common geographic clusters of RSV outbreaks were identified from independent sources, showing an annual RSV trend shifting across different US regions, from the South and Southeast regions to the Central and Northeast regions and then to the West and Northwest regions, while precipitation and temperature were found as correlative factors with the coefficient of determination R2\u22480.5, respectively. Our regression model accurately predicted the 2022-2023 RSV season at the county level, achieving R2\u22480.3 mean absolute error MAE\u2009<\u20090.4 and a Pearson correlation greater than 0.75, which significantly outperforms the baselines with P-values <.05.<h4>Conclusion</h4>Our proposed framework provides a thorough analysis of RSV disease in the United States, which enables healthcare providers to better prepare for potential outbreaks, anticipate increased demand for services and supplies, and save more lives with timely interventions.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1093/jamia/ocad212"
-  },
   {
     "id": "32613083",
     "doi": "https://doi.org/10.12688/wellcomeopenres.15922.2",
@@ -7887,6 +7870,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.12688/wellcomeopenres.15922.2; html:https://europepmc.org/articles/PMC7317462; pdf:https://europepmc.org/articles/PMC7317462?pdf=render"
   },
+  {
+    "id": "37934728",
+    "doi": "https://doi.org/10.1093/jamia/ocad212",
+    "title": "Multi-faceted analysis and prediction for the outbreak of pediatric respiratory syncytial virus.",
+    "authorString": "Yang C, Gao J, Glass L, Cross A, Sun J.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of the American Medical Informatics Association : JAMIA",
+    "pubYear": "2023",
+    "date": "2023-11-02",
+    "isOpenAccess": "N",
+    "keywords": "Respiratory syncytial virus (RSV); Pediatric Diseases; Deep Learning; Tensor Factorization",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>Respiratory syncytial virus (RSV) is a significant cause of pediatric hospitalizations. This article aims to utilize multisource data and leverage the tensor methods to uncover distinct RSV geographic clusters and develop an accurate RSV prediction model for future seasons.<h4>Materials and methods</h4>This study utilizes 5-year RSV data from sources, including medical claims, CDC surveillance data, and Google search trends. We conduct spatiotemporal tensor analysis and prediction for pediatric RSV in the United States by designing (i) a nonnegative tensor factorization model for pediatric RSV diseases and location clustering; (ii) and a recurrent neural network tensor regression model for county-level trend prediction using the disease and location features.<h4>Results</h4>We identify a clustering hierarchy of pediatric diseases: Three common geographic clusters of RSV outbreaks were identified from independent sources, showing an annual RSV trend shifting across different US regions, from the South and Southeast regions to the Central and Northeast regions and then to the West and Northwest regions, while precipitation and temperature were found as correlative factors with the coefficient of determination R2\u22480.5, respectively. Our regression model accurately predicted the 2022-2023 RSV season at the county level, achieving R2\u22480.3 mean absolute error MAE\u2009<\u20090.4 and a Pearson correlation greater than 0.75, which significantly outperforms the baselines with P-values <.05.<h4>Conclusion</h4>Our proposed framework provides a thorough analysis of RSV disease in the United States, which enables healthcare providers to better prepare for potential outbreaks, anticipate increased demand for services and supplies, and save more lives with timely interventions.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1093/jamia/ocad212"
+  },
   {
     "id": "37868035",
     "doi": "https://doi.org/10.1016/j.xgen.2023.100385",
@@ -8278,23 +8278,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1136/bmjment-2023-300762; html:https://europepmc.org/articles/PMC10577765; pdf:https://europepmc.org/articles/PMC10577765?pdf=render"
   },
-  {
-    "id": "36949447",
-    "doi": "https://doi.org/10.1186/s12889-023-15345-z",
-    "title": "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.",
-    "authorString": "Bright D, Hillier S, Song J, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC public health",
-    "pubYear": "2023",
-    "date": "2023-03-22",
-    "isOpenAccess": "Y",
-    "keywords": "Colorectal Cancer; Inequalities; Bowel; Ethnicity; Cancer Screening; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-15345-z; doi:https://doi.org/10.1186/s12889-023-15345-z; html:https://europepmc.org/articles/PMC10031708; pdf:https://europepmc.org/articles/PMC10031708?pdf=render"
-  },
   {
     "id": "34164795",
     "doi": "https://doi.org/10.1007/s40801-021-00256-5",
@@ -8312,6 +8295,23 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s40801-021-00256-5.pdf; doi:https://doi.org/10.1007/s40801-021-00256-5; html:https://europepmc.org/articles/PMC8605959; pdf:https://europepmc.org/articles/PMC8605959?pdf=render"
   },
+  {
+    "id": "36949447",
+    "doi": "https://doi.org/10.1186/s12889-023-15345-z",
+    "title": "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.",
+    "authorString": "Bright D, Hillier S, Song J, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC public health",
+    "pubYear": "2023",
+    "date": "2023-03-22",
+    "isOpenAccess": "Y",
+    "keywords": "Colorectal Cancer; Inequalities; Bowel; Ethnicity; Cancer Screening; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-15345-z; doi:https://doi.org/10.1186/s12889-023-15345-z; html:https://europepmc.org/articles/PMC10031708; pdf:https://europepmc.org/articles/PMC10031708?pdf=render"
+  },
   {
     "id": "35958702",
     "doi": "https://doi.org/10.1007/s40653-021-00433-2",
@@ -8703,23 +8703,6 @@
     "laySummary": "",
     "urls": "pdf:https://n.neurology.org/content/neurology/96/8/e1251.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000011463; html:https://europepmc.org/articles/PMC8055349; pdf:https://europepmc.org/articles/PMC8055349?pdf=render"
   },
-  {
-    "id": "36997954",
-    "doi": "https://doi.org/10.1186/s13063-023-07251-x",
-    "title": "A DELPHI study priority setting the remaining challenges for the use of routinely collected data in trials: COMORANT-UK.",
-    "authorString": "Williams ADN, Davies G, Farrin AJ, Mafham M, Robling M, Sydes MR, Lugg-Widger FV.",
-    "authorAffiliations": "",
-    "journalTitle": "Trials",
-    "pubYear": "2023",
-    "date": "2023-03-30",
-    "isOpenAccess": "Y",
-    "keywords": "Priority Setting; Consensus; Routinely Collected Data; Trials Methodology",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Researchers are increasingly seeking to use routinely collected data to support clinical trials. This approach has the potential to transform the way clinical trials are conducted in the future. The availability of routinely collected data for research, whether healthcare or administrative, has increased, and infrastructure funding has enabled much of this. However, challenges remain at all stages of a trial life cycle. This study, COMORANT-UK, aimed to systematically identify, with key stakeholders across the UK, the ongoing challenges related to trials that seek to use routinely collected data.<h4>Methods</h4>This three-step Delphi method consisted of two rounds of anonymous web-based surveys and a virtual consensus meeting. Stakeholders included trialists, data infrastructures, funders of trials, regulators, data providers and the public. Stakeholders identified research questions or challenges that they considered were of particular importance and then selected their top 10 in the second survey. The ranked questions were taken forward to the consensus meeting for discussion with representatives invited from the stakeholder groups.<h4>Results</h4>In the first survey, 66 respondents yielded over 260 questions or challenges. These were thematically grouped and merged into a list of 40 unique questions. Eighty-eight stakeholders then ranked their top ten from the 40 questions in the second survey. The most common 14 questions were brought to the virtual consensus meeting in which stakeholders agreed a top list of seven questions. We report these seven questions which are within the following domains: trial design, Patient and Public Involvement, trial set-up, trial open and trial data. These questions address both evidence gaps (requiring further methodological research) and implementation gaps (requiring training and/or service re-organisation).<h4>Conclusion</h4>This prioritised list of seven questions should inform the direction of future research in this area and should direct efforts to ensure that the benefits in major infrastructure for routinely collected data are achieved and translated. Without this and future work to address these questions, the potential societal benefits of using routinely collected data to help answer important clinical questions will not be realised.",
-    "laySummary": "",
-    "urls": "pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07251-x; doi:https://doi.org/10.1186/s13063-023-07251-x; html:https://europepmc.org/articles/PMC10064573; pdf:https://europepmc.org/articles/PMC10064573?pdf=render"
-  },
   {
     "id": "35836669",
     "doi": "https://doi.org/10.1097/txd.0000000000001188",
@@ -8737,6 +8720,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1097/txd.0000000000001188; doi:https://doi.org/10.1097/TXD.0000000000001188; html:https://europepmc.org/articles/PMC9276282; pdf:https://europepmc.org/articles/PMC9276282?pdf=render"
   },
+  {
+    "id": "36997954",
+    "doi": "https://doi.org/10.1186/s13063-023-07251-x",
+    "title": "A DELPHI study priority setting the remaining challenges for the use of routinely collected data in trials: COMORANT-UK.",
+    "authorString": "Williams ADN, Davies G, Farrin AJ, Mafham M, Robling M, Sydes MR, Lugg-Widger FV.",
+    "authorAffiliations": "",
+    "journalTitle": "Trials",
+    "pubYear": "2023",
+    "date": "2023-03-30",
+    "isOpenAccess": "Y",
+    "keywords": "Priority Setting; Consensus; Routinely Collected Data; Trials Methodology",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Researchers are increasingly seeking to use routinely collected data to support clinical trials. This approach has the potential to transform the way clinical trials are conducted in the future. The availability of routinely collected data for research, whether healthcare or administrative, has increased, and infrastructure funding has enabled much of this. However, challenges remain at all stages of a trial life cycle. This study, COMORANT-UK, aimed to systematically identify, with key stakeholders across the UK, the ongoing challenges related to trials that seek to use routinely collected data.<h4>Methods</h4>This three-step Delphi method consisted of two rounds of anonymous web-based surveys and a virtual consensus meeting. Stakeholders included trialists, data infrastructures, funders of trials, regulators, data providers and the public. Stakeholders identified research questions or challenges that they considered were of particular importance and then selected their top 10 in the second survey. The ranked questions were taken forward to the consensus meeting for discussion with representatives invited from the stakeholder groups.<h4>Results</h4>In the first survey, 66 respondents yielded over 260 questions or challenges. These were thematically grouped and merged into a list of 40 unique questions. Eighty-eight stakeholders then ranked their top ten from the 40 questions in the second survey. The most common 14 questions were brought to the virtual consensus meeting in which stakeholders agreed a top list of seven questions. We report these seven questions which are within the following domains: trial design, Patient and Public Involvement, trial set-up, trial open and trial data. These questions address both evidence gaps (requiring further methodological research) and implementation gaps (requiring training and/or service re-organisation).<h4>Conclusion</h4>This prioritised list of seven questions should inform the direction of future research in this area and should direct efforts to ensure that the benefits in major infrastructure for routinely collected data are achieved and translated. Without this and future work to address these questions, the potential societal benefits of using routinely collected data to help answer important clinical questions will not be realised.",
+    "laySummary": "",
+    "urls": "pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07251-x; doi:https://doi.org/10.1186/s13063-023-07251-x; html:https://europepmc.org/articles/PMC10064573; pdf:https://europepmc.org/articles/PMC10064573?pdf=render"
+  },
   {
     "id": "37649988",
     "doi": "https://doi.org/10.1093/jamiaopen/ooad078",
@@ -8873,23 +8873,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2666756822000939/pdf; 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"
   },
-  {
-    "id": "36329425",
-    "doi": "https://doi.org/10.1186/s12890-022-02189-3",
-    "title": "Derivation of asthma severity from electronic prescription records using British thoracic society treatment steps.",
-    "authorString": "Tibble H, Sheikh A, Tsanas A.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC pulmonary medicine",
-    "pubYear": "2022",
-    "date": "2022-11-03",
-    "isOpenAccess": "Y",
-    "keywords": "Asthma; Pharmacotherapy; Severity; Pharmacoepidemiology; Electronic Health Records; Treatment Guidelines",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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\u2009+\u2009LABA (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.<h4>Methods</h4>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.<h4>Results</h4>Almost 4.5\u00a0million 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.<h4>Conclusion</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcpulmmed.biomedcentral.com/counter/pdf/10.1186/s12890-022-02189-3; 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": "31612961",
     "doi": "https://doi.org/10.1093/nar/gkz895",
@@ -8907,6 +8890,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/nar/article-pdf/48/D1/D933/31697824/gkz895.pdf; doi:https://doi.org/10.1093/nar/gkz895; html:https://europepmc.org/articles/PMC7145571; pdf:https://europepmc.org/articles/PMC7145571?pdf=render"
   },
+  {
+    "id": "36329425",
+    "doi": "https://doi.org/10.1186/s12890-022-02189-3",
+    "title": "Derivation of asthma severity from electronic prescription records using British thoracic society treatment steps.",
+    "authorString": "Tibble H, Sheikh A, Tsanas A.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC pulmonary medicine",
+    "pubYear": "2022",
+    "date": "2022-11-03",
+    "isOpenAccess": "Y",
+    "keywords": "Asthma; Pharmacotherapy; Severity; Pharmacoepidemiology; Electronic Health Records; Treatment Guidelines",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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\u2009+\u2009LABA (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.<h4>Methods</h4>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.<h4>Results</h4>Almost 4.5\u00a0million 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.<h4>Conclusion</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcpulmmed.biomedcentral.com/counter/pdf/10.1186/s12890-022-02189-3; 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",
@@ -9213,23 +9213,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.3389/fcvm.2023.1141026; html:https://europepmc.org/articles/PMC10541220; pdf:https://europepmc.org/articles/PMC10541220?pdf=render"
   },
-  {
-    "id": "35443953",
-    "doi": "https://doi.org/10.1136/bmjopen-2021-056523",
-    "title": "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.",
-    "authorString": "Eyles E, Redaniel MT, Jones T, Prat M, Keen T.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2022",
-    "date": "2022-04-20",
-    "isOpenAccess": "Y",
-    "keywords": "epidemiology; Statistics & Research Methods; Health Services Administration & Management; Accident & Emergency Medicine",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>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.<h4>Setting</h4>A secondary care hospital in an NHS Trust in South West England.<h4>Participants</h4>Hospital admissions between September 2016 and March 2020, comprising 1291 days.<h4>Primary and secondary outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056523.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056523; html:https://europepmc.org/articles/PMC9021768; pdf:https://europepmc.org/articles/PMC9021768?pdf=render"
-  },
   {
     "id": "33371011",
     "doi": "https://doi.org/10.1136/bmjresp-2020-000770",
@@ -9247,6 +9230,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopenrespres.bmj.com/content/bmjresp/7/1/e000770.full.pdf; doi:https://doi.org/10.1136/bmjresp-2020-000770; html:https://europepmc.org/articles/PMC7754643; pdf:https://europepmc.org/articles/PMC7754643?pdf=render"
   },
+  {
+    "id": "35443953",
+    "doi": "https://doi.org/10.1136/bmjopen-2021-056523",
+    "title": "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.",
+    "authorString": "Eyles E, Redaniel MT, Jones T, Prat M, Keen T.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2022",
+    "date": "2022-04-20",
+    "isOpenAccess": "Y",
+    "keywords": "epidemiology; Statistics & Research Methods; Health Services Administration & Management; Accident & Emergency Medicine",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>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.<h4>Setting</h4>A secondary care hospital in an NHS Trust in South West England.<h4>Participants</h4>Hospital admissions between September 2016 and March 2020, comprising 1291 days.<h4>Primary and secondary outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056523.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056523; html:https://europepmc.org/articles/PMC9021768; pdf:https://europepmc.org/articles/PMC9021768?pdf=render"
+  },
   {
     "id": "33632765",
     "doi": "https://doi.org/10.1136/thoraxjnl-2020-215986",
@@ -9383,23 +9383,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S0140673621001495/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00149-5; html:https://europepmc.org/articles/PMC7884931; pdf:https://europepmc.org/articles/PMC7884931?pdf=render"
   },
-  {
-    "id": "36374585",
-    "doi": "https://doi.org/10.1177/01410768221131897",
-    "title": "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.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of the Royal Society of Medicine",
-    "pubYear": "2023",
-    "date": "2022-11-14",
-    "isOpenAccess": "N",
-    "keywords": "Infectious diseases; Clinical; epidemiology; Public Health; Health Informatics",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>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.<h4>Design</h4>An EHR-based, retrospective cohort study.<h4>Setting</h4>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).<h4>Participants</h4>In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged \u226530 years, respectively.<h4>Main outcome measures</h4>One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021.<h4>Results</h4>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.<h4>Conclusions</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221131897; 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"
-  },
   {
     "id": "31774502",
     "doi": "https://doi.org/10.1093/ehjcvp/pvz071",
@@ -9417,6 +9400,23 @@
     "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": "pdf:https://academic.oup.com/ehjcvp/advance-article-pdf/doi/10.1093/ehjcvp/pvz071/31700014/pvz071.pdf; doi:https://doi.org/10.1093/ehjcvp/pvz071; html:https://europepmc.org/articles/PMC7811400; pdf:https://europepmc.org/articles/PMC7811400?pdf=render"
   },
+  {
+    "id": "36374585",
+    "doi": "https://doi.org/10.1177/01410768221131897",
+    "title": "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.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of the Royal Society of Medicine",
+    "pubYear": "2023",
+    "date": "2022-11-14",
+    "isOpenAccess": "N",
+    "keywords": "Infectious diseases; Clinical; epidemiology; Public Health; Health Informatics",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>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.<h4>Design</h4>An EHR-based, retrospective cohort study.<h4>Setting</h4>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).<h4>Participants</h4>In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged \u226530 years, respectively.<h4>Main outcome measures</h4>One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021.<h4>Results</h4>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.<h4>Conclusions</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221131897; 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"
+  },
   {
     "id": "37745706",
     "doi": "https://doi.org/10.3389/fendo.2023.1266557",
@@ -9842,23 +9842,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41598-020-76860-2.pdf; doi:https://doi.org/10.1038/s41598-020-76860-2; html:https://europepmc.org/articles/PMC7670409; pdf:https://europepmc.org/articles/PMC7670409?pdf=render"
   },
-  {
-    "id": "36933612",
-    "doi": "https://doi.org/10.1016/j.cct.2023.107162",
-    "title": "Healthcare systems data in the context of clinical trials - A comparison of cardiovascular data from a clinical trial dataset with routinely collected data.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "Contemporary clinical trials",
-    "pubYear": "2023",
-    "date": "2023-03-16",
-    "isOpenAccess": "N",
-    "keywords": "Cardiovascular disease; prostate cancer; Clinical Trials; Healthcare Systems Data",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.cct.2023.107162; doi:https://doi.org/10.1016/j.cct.2023.107162"
-  },
   {
     "id": "36874571",
     "doi": "https://doi.org/10.12688/wellcomeopenres.17981.1",
@@ -9876,6 +9859,23 @@
     "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": "36933612",
+    "doi": "https://doi.org/10.1016/j.cct.2023.107162",
+    "title": "Healthcare systems data in the context of clinical trials - A comparison of cardiovascular data from a clinical trial dataset with routinely collected data.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "Contemporary clinical trials",
+    "pubYear": "2023",
+    "date": "2023-03-16",
+    "isOpenAccess": "N",
+    "keywords": "Cardiovascular disease; prostate cancer; Clinical Trials; Healthcare Systems Data",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.cct.2023.107162; doi:https://doi.org/10.1016/j.cct.2023.107162"
+  },
   {
     "id": "33577558",
     "doi": "https://doi.org/10.1371/journal.pmed.1003497",
@@ -9893,23 +9893,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003497&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003497; html:https://europepmc.org/articles/PMC7880491; pdf:https://europepmc.org/articles/PMC7880491?pdf=render"
   },
-  {
-    "id": "36895179",
-    "doi": "https://doi.org/10.1093/eurjpc/zwad055",
-    "title": "Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "European journal of preventive cardiology",
-    "pubYear": "2023",
-    "date": "2023-08-01",
-    "isOpenAccess": "Y",
-    "keywords": "Cardiovascular disease; Chest pain; epidemiology; Primary Health Care; risk; Electronic Health Records",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad055/49604587/zwad055.pdf; doi:https://doi.org/10.1093/eurjpc/zwad055; html:https://europepmc.org/articles/PMC10442054; pdf:https://europepmc.org/articles/PMC10442054?pdf=render"
-  },
   {
     "id": "33971933",
     "doi": "https://doi.org/10.1186/s13063-021-05295-5",
@@ -9927,6 +9910,23 @@
     "laySummary": "",
     "urls": "pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-021-05295-5; doi:https://doi.org/10.1186/s13063-021-05295-5; html:https://europepmc.org/articles/PMC8108438; pdf:https://europepmc.org/articles/PMC8108438?pdf=render"
   },
+  {
+    "id": "36895179",
+    "doi": "https://doi.org/10.1093/eurjpc/zwad055",
+    "title": "Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "European journal of preventive cardiology",
+    "pubYear": "2023",
+    "date": "2023-08-01",
+    "isOpenAccess": "Y",
+    "keywords": "Cardiovascular disease; Chest pain; epidemiology; Primary Health Care; risk; Electronic Health Records",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad055/49604587/zwad055.pdf; doi:https://doi.org/10.1093/eurjpc/zwad055; html:https://europepmc.org/articles/PMC10442054; pdf:https://europepmc.org/articles/PMC10442054?pdf=render"
+  },
   {
     "id": "34527726",
     "doi": "https://doi.org/10.1183/23120541.00167-2021",
@@ -10080,23 +10080,6 @@
     "laySummary": "",
     "urls": "pdf:https://ijpds.org/article/download/1387/3155; doi:https://doi.org/10.23889/ijpds.v6i1.1387; html:https://europepmc.org/articles/PMC8103995; pdf:https://europepmc.org/articles/PMC8103995?pdf=render"
   },
-  {
-    "id": "37000839",
-    "doi": "https://doi.org/10.1371/journal.pone.0279076",
-    "title": "Predicting a diagnosis of ankylosing spondylitis using primary care health records-A machine learning approach.",
-    "authorString": "Kennedy J, Kennedy N, Cooksey R, Choy E, Siebert S, Rahman M, Brophy S.",
-    "authorAffiliations": "",
-    "journalTitle": "PloS one",
-    "pubYear": "2023",
-    "date": "2023-03-31",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279076&type=printable; doi:https://doi.org/10.1371/journal.pone.0279076; html:https://europepmc.org/articles/PMC10065228; pdf:https://europepmc.org/articles/PMC10065228?pdf=render"
-  },
   {
     "id": "35485805",
     "doi": "https://doi.org/10.1017/s003329172200109x",
@@ -10114,6 +10097,23 @@
     "laySummary": "",
     "urls": "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; doi:https://doi.org/10.1017/S003329172200109X; html:https://europepmc.org/articles/PMC10388332; pdf:https://europepmc.org/articles/PMC10388332?pdf=render"
   },
+  {
+    "id": "37000839",
+    "doi": "https://doi.org/10.1371/journal.pone.0279076",
+    "title": "Predicting a diagnosis of ankylosing spondylitis using primary care health records-A machine learning approach.",
+    "authorString": "Kennedy J, Kennedy N, Cooksey R, Choy E, Siebert S, Rahman M, Brophy S.",
+    "authorAffiliations": "",
+    "journalTitle": "PloS one",
+    "pubYear": "2023",
+    "date": "2023-03-31",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279076&type=printable; doi:https://doi.org/10.1371/journal.pone.0279076; html:https://europepmc.org/articles/PMC10065228; pdf:https://europepmc.org/articles/PMC10065228?pdf=render"
+  },
   {
     "id": "36994768",
     "doi": "https://doi.org/10.1002/cphy.c210037",
@@ -10284,23 +10284,6 @@
     "laySummary": "",
     "urls": "pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-022-02745-4; 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": "37699069",
-    "doi": "https://doi.org/10.1093/ehjci/jead218",
-    "title": "Phenotyping left ventricular systolic dysfunction in asymptomatic individuals for improved risk stratification.",
-    "authorString": "Rauseo E, Abdulkareem M, Khan A, Cooper J, Lee AM, Aung N, Slabaugh GG, Petersen SE.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal. Cardiovascular Imaging",
-    "pubYear": "2023",
-    "date": "2023-09-01",
-    "isOpenAccess": "Y",
-    "keywords": "Prognosis; Cardiovascular events; Risk stratification; Heart Failure; Cardiovascular Magnetic Resonance; Left Ventricular Systolic Dysfunction",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>Left ventricular systolic dysfunction (LSVD) is a heterogeneous condition with several factors influencing prognosis. Better phenotyping of asymptomatic individuals can inform preventative strategies. This study aims to explore the clinical phenotypes of LVSD in initially asymptomatic subjects and their association with clinical outcomes and cardiovascular abnormalities through multi-dimensional data clustering.<h4>Methods and results</h4>Clustering analysis was performed on 60 clinically available variables from 1563 UK Biobank participants without pre-existing heart failure (HF) and with left ventricular ejection fraction (LVEF) < 50% on cardiovascular magnetic resonance (CMR) assessment. Risks of developing HF, other cardiovascular events, death, and a composite of major adverse cardiovascular events (MACE) associated with clusters were investigated. Cardiovascular imaging characteristics, not included in the clustering analysis, were also evaluated. Three distinct clusters were identified, differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles. A stepwise increase in risk profile was observed from Cluster 1 to Cluster 3, independent of traditional risk factors and LVEF. Compared with Cluster 1, the lowest risk subset, the risk of MACE ranged from 1.42 [95% confidence interval (CI): 1.03-1.96; P < 0.05] for Cluster 2 to 1.72 (95% CI: 1.36-2.35; P < 0.001) for Cluster 3. Cluster 3, the highest risk profile, had features of adverse cardiovascular imaging with the greatest LV re-modelling, myocardial dysfunction, and decrease in arterial compliance.<h4>Conclusions</h4>Clustering of clinical variables identified three distinct risk profiles and clinical trajectories of LVSD amongst initially asymptomatic subjects. Improved characterization may facilitate tailored interventions based on the LVSD sub-type and improve clinical outcomes.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1093/ehjci/jead218; html:https://europepmc.org/articles/PMC10531121; pdf:https://europepmc.org/articles/PMC10531121?pdf=render"
-  },
   {
     "id": "33716109",
     "doi": "https://doi.org/10.1016/j.jinf.2021.03.002",
@@ -10318,6 +10301,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.journalofinfection.com/article/S0163445321001158/pdf; 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"
   },
+  {
+    "id": "37699069",
+    "doi": "https://doi.org/10.1093/ehjci/jead218",
+    "title": "Phenotyping left ventricular systolic dysfunction in asymptomatic individuals for improved risk stratification.",
+    "authorString": "Rauseo E, Abdulkareem M, Khan A, Cooper J, Lee AM, Aung N, Slabaugh GG, Petersen SE.",
+    "authorAffiliations": "",
+    "journalTitle": "European heart journal. Cardiovascular Imaging",
+    "pubYear": "2023",
+    "date": "2023-09-01",
+    "isOpenAccess": "Y",
+    "keywords": "Prognosis; Cardiovascular events; Risk stratification; Heart Failure; Cardiovascular Magnetic Resonance; Left Ventricular Systolic Dysfunction",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>Left ventricular systolic dysfunction (LSVD) is a heterogeneous condition with several factors influencing prognosis. Better phenotyping of asymptomatic individuals can inform preventative strategies. This study aims to explore the clinical phenotypes of LVSD in initially asymptomatic subjects and their association with clinical outcomes and cardiovascular abnormalities through multi-dimensional data clustering.<h4>Methods and results</h4>Clustering analysis was performed on 60 clinically available variables from 1563 UK Biobank participants without pre-existing heart failure (HF) and with left ventricular ejection fraction (LVEF) < 50% on cardiovascular magnetic resonance (CMR) assessment. Risks of developing HF, other cardiovascular events, death, and a composite of major adverse cardiovascular events (MACE) associated with clusters were investigated. Cardiovascular imaging characteristics, not included in the clustering analysis, were also evaluated. Three distinct clusters were identified, differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles. A stepwise increase in risk profile was observed from Cluster 1 to Cluster 3, independent of traditional risk factors and LVEF. Compared with Cluster 1, the lowest risk subset, the risk of MACE ranged from 1.42 [95% confidence interval (CI): 1.03-1.96; P < 0.05] for Cluster 2 to 1.72 (95% CI: 1.36-2.35; P < 0.001) for Cluster 3. Cluster 3, the highest risk profile, had features of adverse cardiovascular imaging with the greatest LV re-modelling, myocardial dysfunction, and decrease in arterial compliance.<h4>Conclusions</h4>Clustering of clinical variables identified three distinct risk profiles and clinical trajectories of LVSD amongst initially asymptomatic subjects. Improved characterization may facilitate tailored interventions based on the LVSD sub-type and improve clinical outcomes.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1093/ehjci/jead218; html:https://europepmc.org/articles/PMC10531121; pdf:https://europepmc.org/articles/PMC10531121?pdf=render"
+  },
   {
     "id": "36377225",
     "doi": "https://doi.org/10.1177/18333583221135710",
@@ -10353,21 +10353,21 @@
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/trf.17277; doi:https://doi.org/10.1111/trf.17277"
   },
   {
-    "id": "37468148",
-    "doi": "https://doi.org/10.1136/bmj-2023-075133",
-    "title": "Associations between self-reported healthcare disruption due to covid-19 and avoidable hospital admission: evidence from seven linked longitudinal studies for England.",
-    "authorString": "Green MA, McKee M, Hamilton OK, Shaw RJ, Macleod J, Boyd A, Katikireddi SV, LH&W NCS Collaborative.",
+    "id": "32424068",
+    "doi": "https://doi.org/10.1101/gr.250704.119",
+    "title": "Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle.",
+    "authorString": "Fang L, Cai W, Liu S, Canela-Xandri O, Gao Y, Jiang J, Rawlik K, Li B, Schroeder SG, Rosen BD, Li CJ, Sonstegard TS, Alexander LJ, Van Tassell CP, VanRaden PM, Cole JB, Yu Y, Zhang S, Tenesa A, Ma L, Liu GE.",
     "authorAffiliations": "",
-    "journalTitle": "BMJ (Clinical research ed.)",
-    "pubYear": "2023",
-    "date": "2023-07-19",
+    "journalTitle": "Genome research",
+    "pubYear": "2020",
+    "date": "2020-05-18",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>To examine whether there is an association between people who experienced disrupted access to healthcare during the covid-19 pandemic and risk of an avoidable hospital admission.<h4>Design</h4>Observational analysis using evidence from seven linked longitudinal cohort studies for England.<h4>Setting</h4>Studies linked to electronic health records from NHS Digital from 1 March 2020 to 25 August 2022. Data were accessed using the UK Longitudinal Linkage Collaboration trusted research environment.<h4>Participants</h4>Individual level records for 29\u2009276 people.<h4>Main outcome measures</h4>Avoidable hospital admissions defined as emergency hospital admissions for ambulatory care sensitive and emergency urgent care sensitive conditions.<h4>Results</h4>9742 participants (weighted percentage 35%, adjusted for sample structure of longitudinal cohorts) self-reported some form of disrupted access to healthcare during the covid-19 pandemic. People with disrupted access were at increased risk of any (odds ratio 1.80, 95% confidence interval 1.39 to 2.34), acute (2.01, 1.39 to 2.92), and chronic (1.80, 1.31 to 2.48) ambulatory care sensitive hospital admissions. For people who experienced disrupted access to appointments (eg, visiting their doctor or an outpatient department) and procedures (eg, surgery, cancer treatment), positive associations were found with measures of avoidable hospital admissions.<h4>Conclusions</h4>Evidence from linked individual level data shows that people whose access to healthcare was disrupted were more likely to have a potentially preventable hospital admission. The findings highlight the need to increase healthcare investment to tackle the short and long term implications of the pandemic, and to protect treatments and procedures during future pandemics.",
+    "abstract": "By uniformly analyzing 723 RNA-seq data from 91 tissues and cell types, we built a comprehensive gene atlas and studied tissue specificity of genes in cattle. We demonstrated that tissue-specific genes significantly reflected the tissue-relevant biology, showing distinct promoter methylation and evolution patterns (e.g., brain-specific genes evolve slowest, whereas testis-specific genes evolve fastest). Through integrative analyses of those tissue-specific genes with large-scale genome-wide association studies, we detected relevant tissues/cell types and candidate genes for 45 economically important traits in cattle, including blood/immune system (e.g., <i>CCDC88C</i>) for male fertility, brain (e.g., <i>TRIM46</i> and <i>RAB6A</i>) for milk production, and multiple growth-related tissues (e.g., <i>FGF6</i> and <i>CCND2</i>) for body conformation. We validated these findings by using epigenomic data across major somatic tissues and sperm. Collectively, our findings provided novel insights into the genetic and biological mechanisms underlying complex traits in cattle, and our transcriptome atlas can serve as a primary source for biological interpretation, functional validation, studies of adaptive evolution, and genomic improvement in livestock.",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1136/bmj-2023-075133; html:https://europepmc.org/articles/PMC10354595; pdf:https://europepmc.org/articles/PMC10354595?pdf=render"
+    "urls": "pdf:https://genome.cshlp.org/content/30/5/790.full.pdf; doi:https://doi.org/10.1101/gr.250704.119; html:https://europepmc.org/articles/PMC7263193; pdf:https://europepmc.org/articles/PMC7263193?pdf=render"
   },
   {
     "id": "33212507",
@@ -10387,21 +10387,21 @@
     "urls": "pdf:https://academic.oup.com/mbe/article-pdf/38/3/1122/36533820/msaa279.pdf; doi:https://doi.org/10.1093/molbev/msaa279; html:https://europepmc.org/articles/PMC7947781; pdf:https://europepmc.org/articles/PMC7947781?pdf=render"
   },
   {
-    "id": "32424068",
-    "doi": "https://doi.org/10.1101/gr.250704.119",
-    "title": "Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle.",
-    "authorString": "Fang L, Cai W, Liu S, Canela-Xandri O, Gao Y, Jiang J, Rawlik K, Li B, Schroeder SG, Rosen BD, Li CJ, Sonstegard TS, Alexander LJ, Van Tassell CP, VanRaden PM, Cole JB, Yu Y, Zhang S, Tenesa A, Ma L, Liu GE.",
+    "id": "37468148",
+    "doi": "https://doi.org/10.1136/bmj-2023-075133",
+    "title": "Associations between self-reported healthcare disruption due to covid-19 and avoidable hospital admission: evidence from seven linked longitudinal studies for England.",
+    "authorString": "Green MA, McKee M, Hamilton OK, Shaw RJ, Macleod J, Boyd A, Katikireddi SV, LH&W NCS Collaborative.",
     "authorAffiliations": "",
-    "journalTitle": "Genome research",
-    "pubYear": "2020",
-    "date": "2020-05-18",
+    "journalTitle": "BMJ (Clinical research ed.)",
+    "pubYear": "2023",
+    "date": "2023-07-19",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "By uniformly analyzing 723 RNA-seq data from 91 tissues and cell types, we built a comprehensive gene atlas and studied tissue specificity of genes in cattle. We demonstrated that tissue-specific genes significantly reflected the tissue-relevant biology, showing distinct promoter methylation and evolution patterns (e.g., brain-specific genes evolve slowest, whereas testis-specific genes evolve fastest). Through integrative analyses of those tissue-specific genes with large-scale genome-wide association studies, we detected relevant tissues/cell types and candidate genes for 45 economically important traits in cattle, including blood/immune system (e.g., <i>CCDC88C</i>) for male fertility, brain (e.g., <i>TRIM46</i> and <i>RAB6A</i>) for milk production, and multiple growth-related tissues (e.g., <i>FGF6</i> and <i>CCND2</i>) for body conformation. We validated these findings by using epigenomic data across major somatic tissues and sperm. Collectively, our findings provided novel insights into the genetic and biological mechanisms underlying complex traits in cattle, and our transcriptome atlas can serve as a primary source for biological interpretation, functional validation, studies of adaptive evolution, and genomic improvement in livestock.",
+    "abstract": "<h4>Objectives</h4>To examine whether there is an association between people who experienced disrupted access to healthcare during the covid-19 pandemic and risk of an avoidable hospital admission.<h4>Design</h4>Observational analysis using evidence from seven linked longitudinal cohort studies for England.<h4>Setting</h4>Studies linked to electronic health records from NHS Digital from 1 March 2020 to 25 August 2022. Data were accessed using the UK Longitudinal Linkage Collaboration trusted research environment.<h4>Participants</h4>Individual level records for 29\u2009276 people.<h4>Main outcome measures</h4>Avoidable hospital admissions defined as emergency hospital admissions for ambulatory care sensitive and emergency urgent care sensitive conditions.<h4>Results</h4>9742 participants (weighted percentage 35%, adjusted for sample structure of longitudinal cohorts) self-reported some form of disrupted access to healthcare during the covid-19 pandemic. People with disrupted access were at increased risk of any (odds ratio 1.80, 95% confidence interval 1.39 to 2.34), acute (2.01, 1.39 to 2.92), and chronic (1.80, 1.31 to 2.48) ambulatory care sensitive hospital admissions. For people who experienced disrupted access to appointments (eg, visiting their doctor or an outpatient department) and procedures (eg, surgery, cancer treatment), positive associations were found with measures of avoidable hospital admissions.<h4>Conclusions</h4>Evidence from linked individual level data shows that people whose access to healthcare was disrupted were more likely to have a potentially preventable hospital admission. The findings highlight the need to increase healthcare investment to tackle the short and long term implications of the pandemic, and to protect treatments and procedures during future pandemics.",
     "laySummary": "",
-    "urls": "pdf:https://genome.cshlp.org/content/30/5/790.full.pdf; doi:https://doi.org/10.1101/gr.250704.119; html:https://europepmc.org/articles/PMC7263193; pdf:https://europepmc.org/articles/PMC7263193?pdf=render"
+    "urls": "doi:https://doi.org/10.1136/bmj-2023-075133; html:https://europepmc.org/articles/PMC10354595; pdf:https://europepmc.org/articles/PMC10354595?pdf=render"
   },
   {
     "id": "36808078",
@@ -10607,23 +10607,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e054376.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054376; html:https://europepmc.org/articles/PMC8808438; pdf:https://europepmc.org/articles/PMC8808438?pdf=render"
   },
-  {
-    "id": "36805366",
-    "doi": "https://doi.org/10.2196/43419",
-    "title": "Prediction of Suicidal Behaviors in the Middle-aged Population: Machine Learning Analyses of UK Biobank.",
-    "authorString": "Wang J, Qiu J, Zhu T, Zeng Y, Yang H, Shang Y, Yin J, Sun Y, Qu Y, Valdimarsd\u00f3ttir UA, Song H.",
-    "authorAffiliations": "",
-    "journalTitle": "JMIR public health and surveillance",
-    "pubYear": "2023",
-    "date": "2023-02-20",
-    "isOpenAccess": "Y",
-    "keywords": "Sex; Model; Behavior; Genetic susceptibility; Data; Suicide; risk; Machine Learning; Risk Prediction; Cost-effective; Machine Learning Approach; Suicidal Behaviors",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Suicidal behaviors, including suicide deaths and attempts, are major public health concerns. However, previous suicide models required a huge amount of input features, resulting in limited applicability in clinical practice.<h4>Objective</h4>We aimed to construct applicable models (ie, with limited features) for short- and long-term suicidal behavior prediction. We further validated these models among individuals with different genetic risks of suicide.<h4>Methods</h4>Based on the prospective cohort of UK Biobank, we included 223 (0.06%) eligible cases of suicide attempts or deaths, according to hospital inpatient or death register data within 1 year from baseline and randomly selected 4460 (1.18%) controls (1:20) without such records. We similarly identified 833 (0.22%) cases of suicidal behaviors 1 to 6 years from baseline and 16,660 (4.42%) corresponding controls. Based on 143 input features, mainly including sociodemographic, environmental, and psychosocial factors; medical history; and polygenic risk scores (PRS) for suicidality, we applied a bagged balanced light gradient-boosting machine (LightGBM) with stratified 10-fold cross-validation and grid-search to construct the full prediction models for suicide attempts or deaths within 1 year or between 1 and 6 years. The Shapley Additive Explanations (SHAP) approach was used to quantify the importance of input features, and the top 20 features with the highest SHAP values were selected to train the applicable models. The external validity of the established models was assessed among 50,310 individuals who participated in UK Biobank repeated assessments both overall and by the level of PRS for suicidality.<h4>Results</h4>Individuals with suicidal behaviors were on average 56 years old, with equal sex distribution. The application of these full models in the external validation data set demonstrated good model performance, with the area under the receiver operating characteristic (AUROC) curves of 0.919 and 0.892 within 1 year and between 1 and 6 years, respectively. Importantly, the applicable models with the top 20 most important features showed comparable external-validated performance (AUROC curves of 0.901 and 0.885) as the full models, based on which we found that individuals in the top quintile of predicted risk accounted for 91.7% (n=11) and 80.7% (n=25) of all suicidality cases within 1 year and during 1 to 6 years, respectively. We further obtained comparable prediction accuracy when applying these models to subpopulations with different genetic susceptibilities to suicidality. For example, for the 1-year risk prediction, the AUROC curves were 0.907 and 0.885 for the high (>2nd tertile of PRS) and low (<1st) genetic susceptibilities groups, respectively.<h4>Conclusions</h4>We established applicable machine learning-based models for predicting both the short- and long-term risk of suicidality with high accuracy across populations of varying genetic risk for suicide, highlighting a cost-effective method of identifying individuals with a high risk of suicidality.",
-    "laySummary": "",
-    "urls": "pdf:https://publichealth.jmir.org/2023/1/e43419/PDF; doi:https://doi.org/10.2196/43419; html:https://europepmc.org/articles/PMC9989910"
-  },
   {
     "id": "31315158",
     "doi": "https://doi.org/10.1002/cnm.3235",
@@ -10642,21 +10625,21 @@
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3235; doi:https://doi.org/10.1002/cnm.3235; html:https://europepmc.org/articles/PMC6851543; pdf:https://europepmc.org/articles/PMC6851543?pdf=render"
   },
   {
-    "id": "36001371",
-    "doi": "https://doi.org/10.2196/38122",
-    "title": "Deployment of a Free-Text Analytics Platform at a UK National Health Service Research Hospital: CogStack at University College London Hospitals.",
-    "authorString": "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.",
+    "id": "36805366",
+    "doi": "https://doi.org/10.2196/43419",
+    "title": "Prediction of Suicidal Behaviors in the Middle-aged Population: Machine Learning Analyses of UK Biobank.",
+    "authorString": "Wang J, Qiu J, Zhu T, Zeng Y, Yang H, Shang Y, Yin J, Sun Y, Qu Y, Valdimarsd\u00f3ttir UA, Song H.",
     "authorAffiliations": "",
-    "journalTitle": "JMIR medical informatics",
-    "pubYear": "2022",
-    "date": "2022-08-24",
+    "journalTitle": "JMIR public health and surveillance",
+    "pubYear": "2023",
+    "date": "2023-02-20",
     "isOpenAccess": "Y",
-    "keywords": "Information Retrieval; Natural Language Processing; Text Mining; Electronic Health Record System; Clinical Support",
+    "keywords": "Sex; Model; Behavior; Genetic susceptibility; Data; Suicide; risk; Machine Learning; Risk Prediction; Cost-effective; Machine Learning Approach; Suicidal Behaviors",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>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).<h4>Objective</h4>We describe the deployment of the EHR interfacing information extraction and retrieval platform CogStack at University College London Hospitals (UCLH).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",
+    "abstract": "<h4>Background</h4>Suicidal behaviors, including suicide deaths and attempts, are major public health concerns. However, previous suicide models required a huge amount of input features, resulting in limited applicability in clinical practice.<h4>Objective</h4>We aimed to construct applicable models (ie, with limited features) for short- and long-term suicidal behavior prediction. We further validated these models among individuals with different genetic risks of suicide.<h4>Methods</h4>Based on the prospective cohort of UK Biobank, we included 223 (0.06%) eligible cases of suicide attempts or deaths, according to hospital inpatient or death register data within 1 year from baseline and randomly selected 4460 (1.18%) controls (1:20) without such records. We similarly identified 833 (0.22%) cases of suicidal behaviors 1 to 6 years from baseline and 16,660 (4.42%) corresponding controls. Based on 143 input features, mainly including sociodemographic, environmental, and psychosocial factors; medical history; and polygenic risk scores (PRS) for suicidality, we applied a bagged balanced light gradient-boosting machine (LightGBM) with stratified 10-fold cross-validation and grid-search to construct the full prediction models for suicide attempts or deaths within 1 year or between 1 and 6 years. The Shapley Additive Explanations (SHAP) approach was used to quantify the importance of input features, and the top 20 features with the highest SHAP values were selected to train the applicable models. The external validity of the established models was assessed among 50,310 individuals who participated in UK Biobank repeated assessments both overall and by the level of PRS for suicidality.<h4>Results</h4>Individuals with suicidal behaviors were on average 56 years old, with equal sex distribution. The application of these full models in the external validation data set demonstrated good model performance, with the area under the receiver operating characteristic (AUROC) curves of 0.919 and 0.892 within 1 year and between 1 and 6 years, respectively. Importantly, the applicable models with the top 20 most important features showed comparable external-validated performance (AUROC curves of 0.901 and 0.885) as the full models, based on which we found that individuals in the top quintile of predicted risk accounted for 91.7% (n=11) and 80.7% (n=25) of all suicidality cases within 1 year and during 1 to 6 years, respectively. We further obtained comparable prediction accuracy when applying these models to subpopulations with different genetic susceptibilities to suicidality. For example, for the 1-year risk prediction, the AUROC curves were 0.907 and 0.885 for the high (>2nd tertile of PRS) and low (<1st) genetic susceptibilities groups, respectively.<h4>Conclusions</h4>We established applicable machine learning-based models for predicting both the short- and long-term risk of suicidality with high accuracy across populations of varying genetic risk for suicide, highlighting a cost-effective method of identifying individuals with a high risk of suicidality.",
     "laySummary": "",
-    "urls": "pdf:https://medinform.jmir.org/2022/8/e38122/PDF; doi:https://doi.org/10.2196/38122; html:https://europepmc.org/articles/PMC9453582"
+    "urls": "pdf:https://publichealth.jmir.org/2023/1/e43419/PDF; doi:https://doi.org/10.2196/43419; html:https://europepmc.org/articles/PMC9989910"
   },
   {
     "id": "30950797",
@@ -10675,6 +10658,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.jmir.org/2019/4/e12286/PDF; doi:https://doi.org/10.2196/12286; html:https://europepmc.org/articles/PMC6473205"
   },
+  {
+    "id": "36001371",
+    "doi": "https://doi.org/10.2196/38122",
+    "title": "Deployment of a Free-Text Analytics Platform at a UK National Health Service Research Hospital: CogStack at University College London Hospitals.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "JMIR medical informatics",
+    "pubYear": "2022",
+    "date": "2022-08-24",
+    "isOpenAccess": "Y",
+    "keywords": "Information Retrieval; Natural Language Processing; Text Mining; Electronic Health Record System; Clinical Support",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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).<h4>Objective</h4>We describe the deployment of the EHR interfacing information extraction and retrieval platform CogStack at University College London Hospitals (UCLH).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://medinform.jmir.org/2022/8/e38122/PDF; doi:https://doi.org/10.2196/38122; html:https://europepmc.org/articles/PMC9453582"
+  },
   {
     "id": "34249083",
     "doi": "https://doi.org/10.3389/fgene.2021.652878",
@@ -10743,23 +10743,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.vaccine.2022.02.056; doi:https://doi.org/10.1016/j.vaccine.2022.02.056; html:https://europepmc.org/articles/PMC8849863"
   },
-  {
-    "id": "37717234",
-    "doi": "https://doi.org/10.1111/1742-6723.14312",
-    "title": "Prevalence of alcohol and other drug detections in non-transport injury events.",
-    "authorString": "Lau G, Mitra B, Gabbe BJ, Dietze PM, Reeder S, Cameron PA, Smit V, Schneider HG, Symons E, Koolstra C, Stewart C, Beck B.",
-    "authorAffiliations": "",
-    "journalTitle": "Emergency medicine Australasia : EMA",
-    "pubYear": "2023",
-    "date": "2023-09-17",
-    "isOpenAccess": "N",
-    "keywords": "Alcoholic Intoxication; Illicit Drug; Blood Alcohol Content; Wounds And Injury; Substance-related Disorder; Substance Use Detection",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To measure the prevalence of alcohol and/or other drug (AOD) detections in suspected major trauma patients with non-transport injuries who presented to an adult major trauma centre.<h4>Methods</h4>This registry-based cohort study examined the prevalence of AOD detections in patients aged \u226518\u2009years who: (i) sustained non-transport injuries; and (ii) met predefined trauma call-out criteria and were therefore managed by an interdisciplinary trauma team between 1 July 2021 and 31 December 2022. Prevalence was measured using routine in-hospital blood alcohol and urine drug screens.<h4>Results</h4>A total of 1469 cases met the inclusion criteria. Of cases with a valid blood test (n\u2009=\u20091248, 85.0%), alcohol was detected in 313 (25.1%) patients. Of the 733 (49.9%) cases with urine drug screen results, cannabinoids were most commonly detected (n\u2009=\u2009103, 14.1%), followed by benzodiazepines (n\u2009=\u200998, 13.4%), amphetamine-type substances (n\u2009= 80, 10.9%), opioids (n\u2009=\u200928, 3.8%) and cocaine (n\u2009=\u200917, 2.3%). Alcohol and/or at least one other drug was detected in 37.4% (n\u2009=\u2009472) of cases with either a blood alcohol or urine drug test completed (n\u2009=\u20091263, 86.0%). Multiple substances were detected in 16.6% (n\u2009=\u2009119) of cases with both blood alcohol and urine drug screens (n\u2009=\u2009718, 48.9%). Detections were prevalent in cases of interpersonal violence (n\u2009=\u2009123/179, 68.7%) and intentional self-harm (n\u2009=\u200950/106, 47.2%), and in those occurring on Friday and Saturday nights (n\u2009=\u2009118/191, 61.8%).<h4>Conclusion</h4>AOD detections were common in trauma patients with non-transport injury causes. Population-level surveillance is needed to inform prevention strategies that address AOD use as a significant risk factor for serious injury.",
-    "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.14312; doi:https://doi.org/10.1111/1742-6723.14312"
-  },
   {
     "id": "35079022",
     "doi": "https://doi.org/10.1038/s41467-022-28157-3",
@@ -10777,6 +10760,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-022-28157-3.pdf; doi:https://doi.org/10.1038/s41467-022-28157-3; html:https://europepmc.org/articles/PMC8789777; pdf:https://europepmc.org/articles/PMC8789777?pdf=render"
   },
+  {
+    "id": "37717234",
+    "doi": "https://doi.org/10.1111/1742-6723.14312",
+    "title": "Prevalence of alcohol and other drug detections in non-transport injury events.",
+    "authorString": "Lau G, Mitra B, Gabbe BJ, Dietze PM, Reeder S, Cameron PA, Smit V, Schneider HG, Symons E, Koolstra C, Stewart C, Beck B.",
+    "authorAffiliations": "",
+    "journalTitle": "Emergency medicine Australasia : EMA",
+    "pubYear": "2023",
+    "date": "2023-09-17",
+    "isOpenAccess": "N",
+    "keywords": "Alcoholic Intoxication; Illicit Drug; Blood Alcohol Content; Wounds And Injury; Substance-related Disorder; Substance Use Detection",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To measure the prevalence of alcohol and/or other drug (AOD) detections in suspected major trauma patients with non-transport injuries who presented to an adult major trauma centre.<h4>Methods</h4>This registry-based cohort study examined the prevalence of AOD detections in patients aged \u226518\u2009years who: (i) sustained non-transport injuries; and (ii) met predefined trauma call-out criteria and were therefore managed by an interdisciplinary trauma team between 1 July 2021 and 31 December 2022. Prevalence was measured using routine in-hospital blood alcohol and urine drug screens.<h4>Results</h4>A total of 1469 cases met the inclusion criteria. Of cases with a valid blood test (n\u2009=\u20091248, 85.0%), alcohol was detected in 313 (25.1%) patients. Of the 733 (49.9%) cases with urine drug screen results, cannabinoids were most commonly detected (n\u2009=\u2009103, 14.1%), followed by benzodiazepines (n\u2009=\u200998, 13.4%), amphetamine-type substances (n\u2009= 80, 10.9%), opioids (n\u2009=\u200928, 3.8%) and cocaine (n\u2009=\u200917, 2.3%). Alcohol and/or at least one other drug was detected in 37.4% (n\u2009=\u2009472) of cases with either a blood alcohol or urine drug test completed (n\u2009=\u20091263, 86.0%). Multiple substances were detected in 16.6% (n\u2009=\u2009119) of cases with both blood alcohol and urine drug screens (n\u2009=\u2009718, 48.9%). Detections were prevalent in cases of interpersonal violence (n\u2009=\u2009123/179, 68.7%) and intentional self-harm (n\u2009=\u200950/106, 47.2%), and in those occurring on Friday and Saturday nights (n\u2009=\u2009118/191, 61.8%).<h4>Conclusion</h4>AOD detections were common in trauma patients with non-transport injury causes. Population-level surveillance is needed to inform prevention strategies that address AOD use as a significant risk factor for serious injury.",
+    "laySummary": "",
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.14312; doi:https://doi.org/10.1111/1742-6723.14312"
+  },
   {
     "id": "37657941",
     "doi": "https://doi.org/10.1212/wnl.0000000000207777",
@@ -11049,23 +11049,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41746-023-00749-3.pdf; doi:https://doi.org/10.1038/s41746-023-00749-3; html:https://europepmc.org/articles/PMC9938183; pdf:https://europepmc.org/articles/PMC9938183?pdf=render"
   },
-  {
-    "id": "37777816",
-    "doi": "https://doi.org/10.1186/s13643-023-02337-8",
-    "title": "Patient-reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.",
-    "authorString": "Taylor S, Law K, Coomber-Moore J, Davies M, Thistlewaite F, Calvert M, Aiyegbusi O, Yorke J.",
-    "authorAffiliations": "",
-    "journalTitle": "Systematic reviews",
-    "pubYear": "2023",
-    "date": "2023-09-30",
-    "isOpenAccess": "Y",
-    "keywords": "Cancer; Systematic; Review; Quality of life; Patient-reported Outcomes (Pros); Adoptive Cell Therapy (Act)",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life during and after treatment. The systematic review aims to characterise the breadth of PROs utilised in ACT cancer care and provide guidance for the use of PROs in this patient population in the future.<h4>Methods</h4>A systematic search was conducted (MEDLINE, PsycINFO, Embase and CINAHL) in August 2021 by two reviewers. Search terms covered the following: \"adoptive cell therapy\", \"patient-reported outcomes\" and \"cancer\". Studies were included if they used a PRO measure to report the impact of ACT. The methodological quality of PROs was assessed. Forward and backward reference searching was conducted of any relevant papers. A quality grading scale was applied based on Cochrane and Revenson criteria for classification of high-quality studies. Key data from the studies and the included PROs was extracted by two researchers and tabulated.<h4>Results</h4>One-hundred nine papers were identified; 11 papers were included. The majority of studies were single-arm trials or observational studies. Twenty-two different PROs were identified; none was ACT specific. The PROMIS-29 and EQ-5D were most commonly used. Few studies collected PRO data in the first 1-2\u00a0weeks. Four studies followed patients up for over a year, and a further four studies followed patients for approximately 3\u00a0months.<h4>Discussion</h4>None of the PROs identified have been designed specifically for ACT. Appropriateness of existing instruments should be considered. It should be considered whether it is appropriate to collect data more frequently in the acute stage and then less frequently during follow-up. It should be considered if one tool is suitable at all time points or if the tool should be adapted depending on time since treatment. More research is needed to identify the exact timings of PRO assessments, and qualitative work with patients is needed to determine the most important issues for them throughout the treatment and follow-up.",
-    "laySummary": "",
-    "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02337-8; doi:https://doi.org/10.1186/s13643-023-02337-8; html:https://europepmc.org/articles/PMC10541698; pdf:https://europepmc.org/articles/PMC10541698?pdf=render"
-  },
   {
     "id": "32206896",
     "doi": "https://doi.org/10.1007/s00394-020-02220-5",
@@ -11083,6 +11066,23 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00394-020-02220-5.pdf; doi:https://doi.org/10.1007/s00394-020-02220-5; html:https://europepmc.org/articles/PMC7867553; pdf:https://europepmc.org/articles/PMC7867553?pdf=render"
   },
+  {
+    "id": "37777816",
+    "doi": "https://doi.org/10.1186/s13643-023-02337-8",
+    "title": "Patient-reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.",
+    "authorString": "Taylor S, Law K, Coomber-Moore J, Davies M, Thistlewaite F, Calvert M, Aiyegbusi O, Yorke J.",
+    "authorAffiliations": "",
+    "journalTitle": "Systematic reviews",
+    "pubYear": "2023",
+    "date": "2023-09-30",
+    "isOpenAccess": "Y",
+    "keywords": "Cancer; Systematic; Review; Quality of life; Patient-reported Outcomes (Pros); Adoptive Cell Therapy (Act)",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life during and after treatment. The systematic review aims to characterise the breadth of PROs utilised in ACT cancer care and provide guidance for the use of PROs in this patient population in the future.<h4>Methods</h4>A systematic search was conducted (MEDLINE, PsycINFO, Embase and CINAHL) in August 2021 by two reviewers. Search terms covered the following: \"adoptive cell therapy\", \"patient-reported outcomes\" and \"cancer\". Studies were included if they used a PRO measure to report the impact of ACT. The methodological quality of PROs was assessed. Forward and backward reference searching was conducted of any relevant papers. A quality grading scale was applied based on Cochrane and Revenson criteria for classification of high-quality studies. Key data from the studies and the included PROs was extracted by two researchers and tabulated.<h4>Results</h4>One-hundred nine papers were identified; 11 papers were included. The majority of studies were single-arm trials or observational studies. Twenty-two different PROs were identified; none was ACT specific. The PROMIS-29 and EQ-5D were most commonly used. Few studies collected PRO data in the first 1-2\u00a0weeks. Four studies followed patients up for over a year, and a further four studies followed patients for approximately 3\u00a0months.<h4>Discussion</h4>None of the PROs identified have been designed specifically for ACT. Appropriateness of existing instruments should be considered. It should be considered whether it is appropriate to collect data more frequently in the acute stage and then less frequently during follow-up. It should be considered if one tool is suitable at all time points or if the tool should be adapted depending on time since treatment. More research is needed to identify the exact timings of PRO assessments, and qualitative work with patients is needed to determine the most important issues for them throughout the treatment and follow-up.",
+    "laySummary": "",
+    "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02337-8; doi:https://doi.org/10.1186/s13643-023-02337-8; html:https://europepmc.org/articles/PMC10541698; pdf:https://europepmc.org/articles/PMC10541698?pdf=render"
+  },
   {
     "id": "37840686",
     "doi": "https://doi.org/10.3389/fdgth.2023.1184919",
@@ -11117,23 +11117,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aor.14628; doi:https://doi.org/10.1111/aor.14628"
   },
-  {
-    "id": "37105743",
-    "doi": "https://doi.org/10.3399/bjgp.2022.0353",
-    "title": "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.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners",
-    "pubYear": "2023",
-    "date": "2023-04-27",
-    "isOpenAccess": "Y",
-    "keywords": "Diagnosis; Chronic disease; Anxiety; Primary Health Care; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Aim</h4>To explore the effects of COVID-19 on the recorded incidence of 17 long-term conditions.<h4>Design and setting</h4>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.<h4>Method</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://bjgp.org/content/bjgp/early/2023/03/06/BJGP.2022.0353.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0353; html:https://europepmc.org/articles/PMC9997656; pdf:https://europepmc.org/articles/PMC9997656?pdf=render"
-  },
   {
     "id": "33446033",
     "doi": "https://doi.org/10.1177/1460458220977579",
@@ -11168,6 +11151,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s42003-020-01613-w.pdf; 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": "37105743",
+    "doi": "https://doi.org/10.3399/bjgp.2022.0353",
+    "title": "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.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners",
+    "pubYear": "2023",
+    "date": "2023-04-27",
+    "isOpenAccess": "Y",
+    "keywords": "Diagnosis; Chronic disease; Anxiety; Primary Health Care; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Aim</h4>To explore the effects of COVID-19 on the recorded incidence of 17 long-term conditions.<h4>Design and setting</h4>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.<h4>Method</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://bjgp.org/content/bjgp/early/2023/03/06/BJGP.2022.0353.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0353; html:https://europepmc.org/articles/PMC9997656; pdf:https://europepmc.org/articles/PMC9997656?pdf=render"
+  },
   {
     "id": "35365351",
     "doi": "https://doi.org/10.1016/j.injury.2022.03.039",
@@ -11236,23 +11236,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e063836.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063836; html:https://europepmc.org/articles/PMC9923297; pdf:https://europepmc.org/articles/PMC9923297?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": "33711543",
     "doi": "https://doi.org/10.1016/j.jbi.2021.103728",
@@ -11270,6 +11253,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jbi.2021.103728; doi:https://doi.org/10.1016/j.jbi.2021.103728"
   },
+  {
+    "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": "36748660",
     "doi": "https://doi.org/10.1111/head.14465",
@@ -11627,23 +11627,6 @@
     "laySummary": "",
     "urls": "pdf:https://boneandjoint.org.uk/article/10.1302/2633-1462.312.BJO-2022-0130.R1/pdf; 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"
   },
-  {
-    "id": "37679419",
-    "doi": "https://doi.org/10.1038/s41588-023-01462-3",
-    "title": "GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.",
-    "authorString": "Lagou V, Jiang L, Ulrich A, Zudina L, Gonz\u00e1lez KSG, Balkhiyarova Z, Faggian A, Maina JG, Chen S, Todorov PV, Sharapov S, David A, Marullo L, M\u00e4gi R, Rujan RM, Ahlqvist E, Thorleifsson G, Gao \u0397, \u0395vangelou \u0395, Benyamin B, Scott RA, Isaacs A, Zhao JH, Willems SM, Johnson T, Gieger C, Grallert H, Meisinger C, M\u00fcller-Nurasyid M, Strawbridge RJ, Goel A, Rybin D, Albrecht E, Jackson AU, Stringham HM, Corr\u00eaa IR, Farber-Eger E, Steinthorsdottir V, Uitterlinden AG, Munroe PB, Brown MJ, Schmidberger J, Holmen O, Thorand B, Hveem K, Wilsgaard T, Mohlke KL, Wang Z, GWA-PA Consortium, Shmeliov A, den Hoed M, Loos RJF, Kratzer W, Haenle M, Koenig W, Boehm BO, Tan TM, Tomas A, Salem V, Barroso I, Tuomilehto J, Boehnke M, Florez JC, Hamsten A, Watkins H, Nj\u00f8lstad I, Wichmann HE, Caulfield MJ, Khaw KT, van Duijn CM, Hofman A, Wareham NJ, Langenberg C, Whitfield JB, Martin NG, Montgomery G, Scapoli C, Tzoulaki I, Elliott P, Thorsteinsdottir U, Stefansson K, Brittain EL, McCarthy MI, Froguel P, Sexton PM, Wootten D, Groop L, Dupuis J, Meigs JB, Deganutti G, Demirkan A, Pers TH, Reynolds CA, Aulchenko YS, Kaakinen MA, Jones B, Prokopenko I, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC).",
-    "authorAffiliations": "",
-    "journalTitle": "Nature genetics",
-    "pubYear": "2023",
-    "date": "2023-09-07",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1038/s41588-023-01462-3; html:https://europepmc.org/articles/PMC10484788; pdf:https://europepmc.org/articles/PMC10484788?pdf=render"
-  },
   {
     "id": "34784292",
     "doi": "https://doi.org/10.2196/32587",
@@ -11661,6 +11644,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.researchprotocols.org/2021/12/e32587/PDF; doi:https://doi.org/10.2196/32587; html:https://europepmc.org/articles/PMC8658240"
   },
+  {
+    "id": "37679419",
+    "doi": "https://doi.org/10.1038/s41588-023-01462-3",
+    "title": "GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.",
+    "authorString": "Lagou V, Jiang L, Ulrich A, Zudina L, Gonz\u00e1lez KSG, Balkhiyarova Z, Faggian A, Maina JG, Chen S, Todorov PV, Sharapov S, David A, Marullo L, M\u00e4gi R, Rujan RM, Ahlqvist E, Thorleifsson G, Gao \u0397, \u0395vangelou \u0395, Benyamin B, Scott RA, Isaacs A, Zhao JH, Willems SM, Johnson T, Gieger C, Grallert H, Meisinger C, M\u00fcller-Nurasyid M, Strawbridge RJ, Goel A, Rybin D, Albrecht E, Jackson AU, Stringham HM, Corr\u00eaa IR, Farber-Eger E, Steinthorsdottir V, Uitterlinden AG, Munroe PB, Brown MJ, Schmidberger J, Holmen O, Thorand B, Hveem K, Wilsgaard T, Mohlke KL, Wang Z, GWA-PA Consortium, Shmeliov A, den Hoed M, Loos RJF, Kratzer W, Haenle M, Koenig W, Boehm BO, Tan TM, Tomas A, Salem V, Barroso I, Tuomilehto J, Boehnke M, Florez JC, Hamsten A, Watkins H, Nj\u00f8lstad I, Wichmann HE, Caulfield MJ, Khaw KT, van Duijn CM, Hofman A, Wareham NJ, Langenberg C, Whitfield JB, Martin NG, Montgomery G, Scapoli C, Tzoulaki I, Elliott P, Thorsteinsdottir U, Stefansson K, Brittain EL, McCarthy MI, Froguel P, Sexton PM, Wootten D, Groop L, Dupuis J, Meigs JB, Deganutti G, Demirkan A, Pers TH, Reynolds CA, Aulchenko YS, Kaakinen MA, Jones B, Prokopenko I, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC).",
+    "authorAffiliations": "",
+    "journalTitle": "Nature genetics",
+    "pubYear": "2023",
+    "date": "2023-09-07",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1038/s41588-023-01462-3; html:https://europepmc.org/articles/PMC10484788; pdf:https://europepmc.org/articles/PMC10484788?pdf=render"
+  },
   {
     "id": "30727941",
     "doi": "https://doi.org/10.1186/s12859-019-2633-8",
@@ -12120,23 +12120,6 @@
     "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": "pdf:https://www.nature.com/articles/s41398-019-0635-y.pdf; 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": "37562944",
-    "doi": "https://doi.org/10.1136/emermed-2023-213186",
-    "title": "Biases in the collection of blood alcohol data for adult major trauma patients in Victoria, Australia.",
-    "authorString": "Lau G, Gabbe B, Mitra B, Dietze P, Reeder S, Cameron P, Read DJ, Symons E, Beck B.",
-    "authorAffiliations": "",
-    "journalTitle": "Emergency medicine journal : EMJ",
-    "pubYear": "2023",
-    "date": "2023-08-10",
-    "isOpenAccess": "N",
-    "keywords": "epidemiology; wounds and injuries; toxicology; Alcohol Abuse",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>In-hospital alcohol testing provides an opportunity to implement prevention strategies for patients with high risk of experiencing repeated alcohol-related injuries. However, barriers to alcohol testing in emergency settings can prevent patients from being tested. In this study, we aimed to understand potential biases in current data on the completion of blood alcohol tests for major trauma patients at hospitals in Victoria, Australia.<h4>Methods</h4>Victorian State Trauma Registry data on all adult major trauma patients from 1 January 2018 to 31 December 2021 were used. Characteristics associated with having a blood alcohol test recorded in the registry were assessed using logistic regression models.<h4>Results</h4>This study included 14\u2009221 major trauma patients, of which 4563 (32.1%) had a blood alcohol test recorded. Having a blood alcohol test completed was significantly associated with age, socioeconomic disadvantage level, preferred language, having pre-existing mental health or substance use conditions, smoking status, presenting during times associated with heavy community alcohol consumption, injury cause and intent, and Glasgow Coma Scale scores (p<0.05). Restricting analyses to patients from a trauma centre where blood alcohol testing was part of routine clinical care mitigated most biases. However, relative to patients injured while driving a motor vehicle/motorcycle, lower odds of testing were still observed for patients with injuries from flames/scalds/contact burns (adjusted OR (aOR)=0.33, 95%\u2009CI 0.18 to 0.61) and low falls (aOR=0.17, 95% CI 0.12 to 0.25). Higher odds of testing were associated with pre-existing mental health (aOR=1.39, 95% CI 1.02 to 1.89) or substance use conditions (aOR=2.33, 95% CI to 1.47-3.70), and living in a more disadvantaged area (most disadvantaged quintile relative to least disadvantaged quintile: aOR=2.30, 95% CI 1.52 to 3.48).<h4>Conclusion</h4>Biases in the collection of blood alcohol data likely impact the surveillance of alcohol-related injuries. Routine alcohol testing after major trauma is needed to accurately inform epidemiology and the subsequent implementation of strategies for reducing alcohol-related injuries.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1136/emermed-2023-213186"
-  },
   {
     "id": "35032176",
     "doi": "https://doi.org/10.1007/s00125-021-05640-y",
@@ -12154,6 +12137,23 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00125-021-05640-y.pdf; doi:https://doi.org/10.1007/s00125-021-05640-y; html:https://europepmc.org/articles/PMC8894164; pdf:https://europepmc.org/articles/PMC8894164?pdf=render"
   },
+  {
+    "id": "37562944",
+    "doi": "https://doi.org/10.1136/emermed-2023-213186",
+    "title": "Biases in the collection of blood alcohol data for adult major trauma patients in Victoria, Australia.",
+    "authorString": "Lau G, Gabbe B, Mitra B, Dietze P, Reeder S, Cameron P, Read DJ, Symons E, Beck B.",
+    "authorAffiliations": "",
+    "journalTitle": "Emergency medicine journal : EMJ",
+    "pubYear": "2023",
+    "date": "2023-08-10",
+    "isOpenAccess": "N",
+    "keywords": "epidemiology; wounds and injuries; toxicology; Alcohol Abuse",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>In-hospital alcohol testing provides an opportunity to implement prevention strategies for patients with high risk of experiencing repeated alcohol-related injuries. However, barriers to alcohol testing in emergency settings can prevent patients from being tested. In this study, we aimed to understand potential biases in current data on the completion of blood alcohol tests for major trauma patients at hospitals in Victoria, Australia.<h4>Methods</h4>Victorian State Trauma Registry data on all adult major trauma patients from 1 January 2018 to 31 December 2021 were used. Characteristics associated with having a blood alcohol test recorded in the registry were assessed using logistic regression models.<h4>Results</h4>This study included 14\u2009221 major trauma patients, of which 4563 (32.1%) had a blood alcohol test recorded. Having a blood alcohol test completed was significantly associated with age, socioeconomic disadvantage level, preferred language, having pre-existing mental health or substance use conditions, smoking status, presenting during times associated with heavy community alcohol consumption, injury cause and intent, and Glasgow Coma Scale scores (p<0.05). Restricting analyses to patients from a trauma centre where blood alcohol testing was part of routine clinical care mitigated most biases. However, relative to patients injured while driving a motor vehicle/motorcycle, lower odds of testing were still observed for patients with injuries from flames/scalds/contact burns (adjusted OR (aOR)=0.33, 95%\u2009CI 0.18 to 0.61) and low falls (aOR=0.17, 95% CI 0.12 to 0.25). Higher odds of testing were associated with pre-existing mental health (aOR=1.39, 95% CI 1.02 to 1.89) or substance use conditions (aOR=2.33, 95% CI to 1.47-3.70), and living in a more disadvantaged area (most disadvantaged quintile relative to least disadvantaged quintile: aOR=2.30, 95% CI 1.52 to 3.48).<h4>Conclusion</h4>Biases in the collection of blood alcohol data likely impact the surveillance of alcohol-related injuries. Routine alcohol testing after major trauma is needed to accurately inform epidemiology and the subsequent implementation of strategies for reducing alcohol-related injuries.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1136/emermed-2023-213186"
+  },
   {
     "id": "35637502",
     "doi": "https://doi.org/10.1186/s12889-022-13453-w",
@@ -12409,23 +12409,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-020-17696-2.pdf; doi:https://doi.org/10.1038/s41467-020-17696-2; html:https://europepmc.org/articles/PMC7395761; pdf:https://europepmc.org/articles/PMC7395761?pdf=render"
   },
-  {
-    "id": "33780550",
-    "doi": "https://doi.org/10.1111/anae.15457",
-    "title": "Impact of a physician - critical care practitioner pre-hospital service in Wales on trauma survival: a retrospective analysis of linked registry data.",
-    "authorString": "Lyons J, Gabbe BJ, Rawlinson D, Lockey D, Fry RJ, Akbari A, Lyons RA.",
-    "authorAffiliations": "",
-    "journalTitle": "Anaesthesia",
-    "pubYear": "2021",
-    "date": "2021-03-29",
-    "isOpenAccess": "N",
-    "keywords": "Trauma; Survival; Critical Care; Pre-hospital Care",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The Emergency Medical Retrieval and Transfer Service for Wales launched in 2015. This service delivers senior pre-hospital doctors and advanced critical care practitioners to the scene of time-critical life- and limb-threatening incidents to provide advanced decision-making and pre-hospital clinical care. The impact of the service on 30-day mortality was evaluated retrospectively using a data linkage system. The study included patients who sustained moderate-to-severe blunt traumatic injuries (injury severity score\u00a0\u2265\u00a09) between 27 April 2015 and 30 November 2018. The association between pre-hospital management by the Emergency Medical Retrieval and Transfer Service and 30-day mortality was assessed using multivariable logistic regression. In total, data from 4035 patients were analysed, of which 412 (10%) were treated by the Emergency Medical Retrieval and Transfer Service. A greater proportion of patients treated by the Emergency Medical Retrieval and Transfer Service had an injury severity score\u00a0\u2265\u00a016 and Glasgow coma scale\u00a0\u2264\u00a012 (288 (70%) vs. 1435 (40%) and 126 (31%) vs. 325 (9%), respectively). The unadjusted 30-day mortality rate was 11.7% for patients managed by the Emergency Medical Retrieval and Transfer Service compared with 9.6% for patients managed by standard pre-hospital care services. However, after adjustment for differences in case-mix, the 30-day mortality rate for patients treated by the Emergency Medical Retrieval and Transfer Service was 37% lower (adjusted odds ratio 0.63 (95%CI 0.41-0.97); p\u00a0=\u00a00.037). The introduction of an emergency medical retrieval service was associated with a reduction in 30-day mortality for patients with blunt traumatic injury.",
-    "laySummary": "",
-    "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa56616/Download/56616__19761__8c6edaf906b846a69c8b19bdb94d015d.pdf; doi:https://doi.org/10.1111/anae.15457"
-  },
   {
     "id": "29716529",
     "doi": "https://doi.org/10.1186/s12883-018-1058-8",
@@ -12443,6 +12426,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmcneurol.biomedcentral.com/track/pdf/10.1186/s12883-018-1058-8; doi:https://doi.org/10.1186/s12883-018-1058-8; html:https://europepmc.org/articles/PMC5930853; pdf:https://europepmc.org/articles/PMC5930853?pdf=render"
   },
+  {
+    "id": "33780550",
+    "doi": "https://doi.org/10.1111/anae.15457",
+    "title": "Impact of a physician - critical care practitioner pre-hospital service in Wales on trauma survival: a retrospective analysis of linked registry data.",
+    "authorString": "Lyons J, Gabbe BJ, Rawlinson D, Lockey D, Fry RJ, Akbari A, Lyons RA.",
+    "authorAffiliations": "",
+    "journalTitle": "Anaesthesia",
+    "pubYear": "2021",
+    "date": "2021-03-29",
+    "isOpenAccess": "N",
+    "keywords": "Trauma; Survival; Critical Care; Pre-hospital Care",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "The Emergency Medical Retrieval and Transfer Service for Wales launched in 2015. This service delivers senior pre-hospital doctors and advanced critical care practitioners to the scene of time-critical life- and limb-threatening incidents to provide advanced decision-making and pre-hospital clinical care. The impact of the service on 30-day mortality was evaluated retrospectively using a data linkage system. The study included patients who sustained moderate-to-severe blunt traumatic injuries (injury severity score\u00a0\u2265\u00a09) between 27 April 2015 and 30 November 2018. The association between pre-hospital management by the Emergency Medical Retrieval and Transfer Service and 30-day mortality was assessed using multivariable logistic regression. In total, data from 4035 patients were analysed, of which 412 (10%) were treated by the Emergency Medical Retrieval and Transfer Service. A greater proportion of patients treated by the Emergency Medical Retrieval and Transfer Service had an injury severity score\u00a0\u2265\u00a016 and Glasgow coma scale\u00a0\u2264\u00a012 (288 (70%) vs. 1435 (40%) and 126 (31%) vs. 325 (9%), respectively). The unadjusted 30-day mortality rate was 11.7% for patients managed by the Emergency Medical Retrieval and Transfer Service compared with 9.6% for patients managed by standard pre-hospital care services. However, after adjustment for differences in case-mix, the 30-day mortality rate for patients treated by the Emergency Medical Retrieval and Transfer Service was 37% lower (adjusted odds ratio 0.63 (95%CI 0.41-0.97); p\u00a0=\u00a00.037). The introduction of an emergency medical retrieval service was associated with a reduction in 30-day mortality for patients with blunt traumatic injury.",
+    "laySummary": "",
+    "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa56616/Download/56616__19761__8c6edaf906b846a69c8b19bdb94d015d.pdf; doi:https://doi.org/10.1111/anae.15457"
+  },
   {
     "id": "33619467",
     "doi": "https://doi.org/10.1093/jamiaopen/ooaa047",
@@ -12630,23 +12630,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0243843&type=printable; doi:https://doi.org/10.1371/journal.pone.0243843; html:https://europepmc.org/articles/PMC7737962; pdf:https://europepmc.org/articles/PMC7737962?pdf=render"
   },
-  {
-    "id": "37609702",
-    "doi": "https://doi.org/10.1002/pds.5681",
-    "title": "Adverse drug reactions and hospital admissions: Large case-control study of patients aged 65-100\u2009years using linked English primary care and hospital data.",
-    "authorString": "van Staa TP, Pirmohamed M, Sharma A, Ashcroft DM, Buchan I.",
-    "authorAffiliations": "",
-    "journalTitle": "Pharmacoepidemiology and drug safety",
-    "pubYear": "2023",
-    "date": "2023-08-23",
-    "isOpenAccess": "N",
-    "keywords": "Adverse drug reactions; Primary Care; Medicines; Pharmacovigilance; Polypharmacy",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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\u2009days 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).<h4>Results</h4>The overall population included 121\u2009546 cases with an ADR-related and 849\u2009769 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).<h4>Conclusions and relevance</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pds.5681; doi:https://doi.org/10.1002/pds.5681"
-  },
   {
     "id": "35896970",
     "doi": "https://doi.org/10.1186/s12879-022-07628-4",
@@ -12664,6 +12647,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-022-07628-4; doi:https://doi.org/10.1186/s12879-022-07628-4; html:https://europepmc.org/articles/PMC9326417; pdf:https://europepmc.org/articles/PMC9326417?pdf=render"
   },
+  {
+    "id": "37609702",
+    "doi": "https://doi.org/10.1002/pds.5681",
+    "title": "Adverse drug reactions and hospital admissions: Large case-control study of patients aged 65-100\u2009years using linked English primary care and hospital data.",
+    "authorString": "van Staa TP, Pirmohamed M, Sharma A, Ashcroft DM, Buchan I.",
+    "authorAffiliations": "",
+    "journalTitle": "Pharmacoepidemiology and drug safety",
+    "pubYear": "2023",
+    "date": "2023-08-23",
+    "isOpenAccess": "N",
+    "keywords": "Adverse drug reactions; Primary Care; Medicines; Pharmacovigilance; Polypharmacy",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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\u2009days 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).<h4>Results</h4>The overall population included 121\u2009546 cases with an ADR-related and 849\u2009769 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).<h4>Conclusions and relevance</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pds.5681; doi:https://doi.org/10.1002/pds.5681"
+  },
   {
     "id": "36525457",
     "doi": "https://doi.org/10.1371/journal.pone.0279250",
@@ -12715,23 +12715,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41698-022-00269-5.pdf; doi:https://doi.org/10.1038/s41698-022-00269-5; html:https://europepmc.org/articles/PMC9021198; pdf:https://europepmc.org/articles/PMC9021198?pdf=render"
   },
-  {
-    "id": "36745557",
-    "doi": "https://doi.org/10.1093/bjd/ljac132",
-    "title": "Factors associated with depression, anxiety and severe mental illness among adults with atopic eczema or psoriasis: a systematic review and meta-analysis.",
-    "authorString": "Adesanya EI, Matthewman J, Schonmann Y, Hayes JF, Henderson A, Mathur R, Mulick AR, Smith CH, Langan SM, Mansfield KE.",
-    "authorAffiliations": "",
-    "journalTitle": "The British journal of dermatology",
-    "pubYear": "2023",
-    "date": "2023-03-01",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear.<h4>Objectives</h4>To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis.<h4>Methods</h4>We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis.<h4>Results</h4>We included 21 studies (11 observational, 10 RCTs). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety - one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest that female sex and psoriatic arthritis were associated with depression [female sex: odds ratio (OR) 1.62, 95% confidence interval (CI) 1.09-2.40, 95% prediction intervals (PIs) 0.62-4.23, I2 = 24.90%, \u03c42 = 0.05; psoriatic arthritis: OR 2.26, 95% CI 1.56-3.25, 95% PI 0.21-24.23, I2 = 0.00%, \u03c42 = 0.00] and anxiety (female sex: OR 2.59, 95% CI 1.32-5.07, 95% PI 0.00-3956.27, I2 = 61.90%, \u03c42 = 0.22; psoriatic arthritis: OR 1.98, 95% CI 1.33-2.94, I2 = 0.00%, \u03c42 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR 1.14, 95% CI 1.05-1.25, I2 0.00%, \u03c42 = 0.00), but not depression. Evidence from RCTs suggested that adults with AE or psoriasis given placebo had higher depression and anxiety scores compared with comparators given targeted treatment (e.g. biologic agents).<h4>Conclusions</h4>Our review highlights limited existing research on factors associated with depression, anxiety and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested that AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared with skin disease treated with targeted therapy; however, follow-up was limited. Therefore, long-term effects on mental health are unclear.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/bjd/article-pdf/188/4/460/51790111/ljac132.pdf; doi:https://doi.org/10.1093/bjd/ljac132"
-  },
   {
     "id": "32310142",
     "doi": "https://doi.org/10.2196/14306",
@@ -12749,6 +12732,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.2196/14306; doi:https://doi.org/10.2196/14306; html:https://europepmc.org/articles/PMC7199134"
   },
+  {
+    "id": "36745557",
+    "doi": "https://doi.org/10.1093/bjd/ljac132",
+    "title": "Factors associated with depression, anxiety and severe mental illness among adults with atopic eczema or psoriasis: a systematic review and meta-analysis.",
+    "authorString": "Adesanya EI, Matthewman J, Schonmann Y, Hayes JF, Henderson A, Mathur R, Mulick AR, Smith CH, Langan SM, Mansfield KE.",
+    "authorAffiliations": "",
+    "journalTitle": "The British journal of dermatology",
+    "pubYear": "2023",
+    "date": "2023-03-01",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear.<h4>Objectives</h4>To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis.<h4>Methods</h4>We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis.<h4>Results</h4>We included 21 studies (11 observational, 10 RCTs). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety - one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest that female sex and psoriatic arthritis were associated with depression [female sex: odds ratio (OR) 1.62, 95% confidence interval (CI) 1.09-2.40, 95% prediction intervals (PIs) 0.62-4.23, I2 = 24.90%, \u03c42 = 0.05; psoriatic arthritis: OR 2.26, 95% CI 1.56-3.25, 95% PI 0.21-24.23, I2 = 0.00%, \u03c42 = 0.00] and anxiety (female sex: OR 2.59, 95% CI 1.32-5.07, 95% PI 0.00-3956.27, I2 = 61.90%, \u03c42 = 0.22; psoriatic arthritis: OR 1.98, 95% CI 1.33-2.94, I2 = 0.00%, \u03c42 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR 1.14, 95% CI 1.05-1.25, I2 0.00%, \u03c42 = 0.00), but not depression. Evidence from RCTs suggested that adults with AE or psoriasis given placebo had higher depression and anxiety scores compared with comparators given targeted treatment (e.g. biologic agents).<h4>Conclusions</h4>Our review highlights limited existing research on factors associated with depression, anxiety and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested that AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared with skin disease treated with targeted therapy; however, follow-up was limited. Therefore, long-term effects on mental health are unclear.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/bjd/article-pdf/188/4/460/51790111/ljac132.pdf; doi:https://doi.org/10.1093/bjd/ljac132"
+  },
   {
     "id": "34626176",
     "doi": "https://doi.org/10.1093/brain/awab253",
@@ -12834,23 +12834,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41598-022-26141-x.pdf; doi:https://doi.org/10.1038/s41598-022-26141-x; html:https://europepmc.org/articles/PMC9789116; pdf:https://europepmc.org/articles/PMC9789116?pdf=render"
   },
-  {
-    "id": "37190903",
-    "doi": "https://doi.org/10.1002/ijc.34548",
-    "title": "Cancer incidence and mortality in 23\u2009000 patients with type 1 diabetes in the UK: Long-term follow-up.",
-    "authorString": "Swerdlow AJ, Jones ME, Slater SD, Burden ACF, Botha JL, Waugh NR, Morris AD, Gatling W, Gillespie KM, Patterson CC, Schoemaker MJ.",
-    "authorAffiliations": "",
-    "journalTitle": "International journal of cancer",
-    "pubYear": "2023",
-    "date": "2023-05-15",
-    "isOpenAccess": "N",
-    "keywords": "Cancer; type 1 diabetes; Cohort",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Type 2 diabetes is associated with raised risk of several cancers, but for type 1 diabetes risk data are fewer and inconsistent We assembled a cohort of 23\u2009473 UK patients with insulin-treated diabetes diagnosed at ages <30, almost all of whom will have had type 1 diabetes, and for comparison 5058 diagnosed at ages 30 to 49, of whom we estimate two-thirds will have had type 2, and followed them for an average of 30\u2009years for cancer incidence and mortality compared with general population rates. Patients aged <30 at diabetes diagnosis had significantly raised risks only for ovarian (standardised incidence ratio\u2009=\u20091.58; 95% confidence interval 1.16-2.11; P\u2009<\u2009.01) and vulval (3.55; 1.94-5.96; P\u2009<\u2009.001) cancers, with greatest risk when diabetes was diagnosed at ages 10-14. Risks of cancer overall (0.89; 0.84-0.95; P\u2009<\u2009.001) and sites including lung and larynx were significantly diminished. Patients diagnosed with diabetes at ages 30 to 49 had significantly raised risks of liver (1.76;1.08-2.72) and kidney (1.46;1.03-2.00) cancers, and reduced risk of cancer overall (0.89; 0.84-0.95). The raised ovarian and vulval cancer risks in patients with type 1 diabetes, especially with diabetes diagnosed around pubertal ages, suggest possible susceptibility of these organs at puberty to metabolic disruption at diabetes onset. Reduced risk of cancer overall, particularly smoking and alcohol-related sites, might reflect adoption of a healthy lifestyle.",
-    "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.34548; doi:https://doi.org/10.1002/ijc.34548"
-  },
   {
     "id": "35012379",
     "doi": "https://doi.org/10.1177/17407745211069985",
@@ -12868,6 +12851,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1177/17407745211069985; doi:https://doi.org/10.1177/17407745211069985; html:https://europepmc.org/articles/PMC9036147; pdf:https://europepmc.org/articles/PMC9036147?pdf=render"
   },
+  {
+    "id": "37190903",
+    "doi": "https://doi.org/10.1002/ijc.34548",
+    "title": "Cancer incidence and mortality in 23\u2009000 patients with type 1 diabetes in the UK: Long-term follow-up.",
+    "authorString": "Swerdlow AJ, Jones ME, Slater SD, Burden ACF, Botha JL, Waugh NR, Morris AD, Gatling W, Gillespie KM, Patterson CC, Schoemaker MJ.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of cancer",
+    "pubYear": "2023",
+    "date": "2023-05-15",
+    "isOpenAccess": "N",
+    "keywords": "Cancer; type 1 diabetes; Cohort",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Type 2 diabetes is associated with raised risk of several cancers, but for type 1 diabetes risk data are fewer and inconsistent We assembled a cohort of 23\u2009473 UK patients with insulin-treated diabetes diagnosed at ages <30, almost all of whom will have had type 1 diabetes, and for comparison 5058 diagnosed at ages 30 to 49, of whom we estimate two-thirds will have had type 2, and followed them for an average of 30\u2009years for cancer incidence and mortality compared with general population rates. Patients aged <30 at diabetes diagnosis had significantly raised risks only for ovarian (standardised incidence ratio\u2009=\u20091.58; 95% confidence interval 1.16-2.11; P\u2009<\u2009.01) and vulval (3.55; 1.94-5.96; P\u2009<\u2009.001) cancers, with greatest risk when diabetes was diagnosed at ages 10-14. Risks of cancer overall (0.89; 0.84-0.95; P\u2009<\u2009.001) and sites including lung and larynx were significantly diminished. Patients diagnosed with diabetes at ages 30 to 49 had significantly raised risks of liver (1.76;1.08-2.72) and kidney (1.46;1.03-2.00) cancers, and reduced risk of cancer overall (0.89; 0.84-0.95). The raised ovarian and vulval cancer risks in patients with type 1 diabetes, especially with diabetes diagnosed around pubertal ages, suggest possible susceptibility of these organs at puberty to metabolic disruption at diabetes onset. Reduced risk of cancer overall, particularly smoking and alcohol-related sites, might reflect adoption of a healthy lifestyle.",
+    "laySummary": "",
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.34548; doi:https://doi.org/10.1002/ijc.34548"
+  },
   {
     "id": "30423068",
     "doi": "https://doi.org/10.1093/bioinformatics/bty605",
@@ -13038,6 +13038,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41366-021-00846-x.pdf; 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": "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": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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]).<h4>Conclusions</h4>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": "pdf:https://academic.oup.com/ageing/article-pdf/50/4/1019/40971734/afab060.pdf; doi:https://doi.org/10.1093/ageing/afab060; html:https://europepmc.org/articles/PMC7989651; pdf:https://europepmc.org/articles/PMC7989651?pdf=render"
+  },
   {
     "id": "37717030",
     "doi": "https://doi.org/10.1186/s13756-023-01280-6",
@@ -13055,6 +13072,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1186/s13756-023-01280-6; doi:https://doi.org/10.1186/s13756-023-01280-6; html:https://europepmc.org/articles/PMC10504725; pdf:https://europepmc.org/articles/PMC10504725?pdf=render"
   },
+  {
+    "id": "35964473",
+    "doi": "https://doi.org/10.1016/j.socscimed.2022.115237",
+    "title": "\"We've all got the virus inside us now\": Disaggregating public health relations and responsibilities for health protection in pandemic London.",
+    "authorString": "Kasstan B, Mounier-Jack S, Gaskell KM, Eggo RM, Marks M, Chantler T.",
+    "authorAffiliations": "",
+    "journalTitle": "Social science & medicine (1982)",
+    "pubYear": "2022",
+    "date": "2022-08-07",
+    "isOpenAccess": "Y",
+    "keywords": "Pandemic; Public Health; Judaism; Responsibility; London; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.socscimed.2022.115237; doi:https://doi.org/10.1016/j.socscimed.2022.115237; html:https://europepmc.org/articles/PMC9357441; pdf:https://europepmc.org/articles/PMC9357441?pdf=render"
+  },
   {
     "id": "37306981",
     "doi": "https://doi.org/10.1001/jamaneurol.2023.1580",
@@ -13073,38 +13107,21 @@
     "urls": "doi:https://doi.org/10.1001/jamaneurol.2023.1580"
   },
   {
-    "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.",
+    "id": "34266851",
+    "doi": "https://doi.org/10.1136/bmjhci-2021-100356",
+    "title": "Development of a core competency framework for clinical informatics. ",
+    "authorString": "Davies A, Mueller J, Hassey A, Moulton G.",
     "authorAffiliations": "",
-    "journalTitle": "Age and ageing",
+    "journalTitle": "BMJ health & care informatics",
     "pubYear": "2021",
-    "date": "2021-06-01",
-    "isOpenAccess": "Y",
-    "keywords": "Mortality; Morbidity; Older People; Long-term Care; Covid-19; Sars-cov-2",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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]).<h4>Conclusions</h4>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": "pdf:https://academic.oup.com/ageing/article-pdf/50/4/1019/40971734/afab060.pdf; doi:https://doi.org/10.1093/ageing/afab060; html:https://europepmc.org/articles/PMC7989651; pdf:https://europepmc.org/articles/PMC7989651?pdf=render"
-  },
-  {
-    "id": "35964473",
-    "doi": "https://doi.org/10.1016/j.socscimed.2022.115237",
-    "title": "\"We've all got the virus inside us now\": Disaggregating public health relations and responsibilities for health protection in pandemic London.",
-    "authorString": "Kasstan B, Mounier-Jack S, Gaskell KM, Eggo RM, Marks M, Chantler T.",
-    "authorAffiliations": "",
-    "journalTitle": "Social science & medicine (1982)",
-    "pubYear": "2022",
-    "date": "2022-08-07",
+    "date": "2021-07-01",
     "isOpenAccess": "Y",
-    "keywords": "Pandemic; Public Health; Judaism; Responsibility; London; Covid-19",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "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.",
+    "abstract": "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.",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.socscimed.2022.115237; doi:https://doi.org/10.1016/j.socscimed.2022.115237; html:https://europepmc.org/articles/PMC9357441; pdf:https://europepmc.org/articles/PMC9357441?pdf=render"
+    "urls": "pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100356.full.pdf; doi:https://doi.org/10.1136/bmjhci-2021-100356; html:https://europepmc.org/articles/PMC8286765; pdf:https://europepmc.org/articles/PMC8286765?pdf=render"
   },
   {
     "id": "36446449",
@@ -13123,23 +13140,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061849.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061849; html:https://europepmc.org/articles/PMC9709811; pdf:https://europepmc.org/articles/PMC9709811?pdf=render"
   },
-  {
-    "id": "34266851",
-    "doi": "https://doi.org/10.1136/bmjhci-2021-100356",
-    "title": "Development of a core competency framework for clinical informatics. ",
-    "authorString": "Davies A, Mueller J, Hassey A, Moulton G.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ health & care informatics",
-    "pubYear": "2021",
-    "date": "2021-07-01",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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.",
-    "laySummary": "",
-    "urls": "pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100356.full.pdf; doi:https://doi.org/10.1136/bmjhci-2021-100356; html:https://europepmc.org/articles/PMC8286765; pdf:https://europepmc.org/articles/PMC8286765?pdf=render"
-  },
   {
     "id": "33402395",
     "doi": "https://doi.org/10.1136/jech-2020-215204",
@@ -13361,23 +13361,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2213260021005427/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00542-7; html:https://europepmc.org/articles/PMC8786320"
   },
-  {
-    "id": "37191413",
-    "doi": "https://doi.org/10.14336/ad.2022.1107",
-    "title": "Conceptual Overview of Biological Age Estimation.",
-    "authorString": "Salih A, Nichols T, Szabo L, Petersen SE, Raisi-Estabragh Z.",
-    "authorAffiliations": "",
-    "journalTitle": "Aging and disease",
-    "pubYear": "2023",
-    "date": "2023-06-01",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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.",
-    "laySummary": "",
-    "urls": "pdf:http://www.aginganddisease.org/EN/PDF/10.14336/AD.2022.1107; doi:https://doi.org/10.14336/AD.2022.1107; html:https://europepmc.org/articles/PMC10187689; pdf:https://europepmc.org/articles/PMC10187689?pdf=render"
-  },
   {
     "id": "35296643",
     "doi": "https://doi.org/10.1038/s41467-022-28517-z",
@@ -13395,6 +13378,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-022-28517-z.pdf; doi:https://doi.org/10.1038/s41467-022-28517-z; html:https://europepmc.org/articles/PMC8927425; pdf:https://europepmc.org/articles/PMC8927425?pdf=render"
   },
+  {
+    "id": "37191413",
+    "doi": "https://doi.org/10.14336/ad.2022.1107",
+    "title": "Conceptual Overview of Biological Age Estimation.",
+    "authorString": "Salih A, Nichols T, Szabo L, Petersen SE, Raisi-Estabragh Z.",
+    "authorAffiliations": "",
+    "journalTitle": "Aging and disease",
+    "pubYear": "2023",
+    "date": "2023-06-01",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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.",
+    "laySummary": "",
+    "urls": "pdf:http://www.aginganddisease.org/EN/PDF/10.14336/AD.2022.1107; doi:https://doi.org/10.14336/AD.2022.1107; html:https://europepmc.org/articles/PMC10187689; pdf:https://europepmc.org/articles/PMC10187689?pdf=render"
+  },
   {
     "id": "35781133",
     "doi": "https://doi.org/10.3310/zyzc8514",
@@ -13735,23 +13735,6 @@
     "laySummary": "",
     "urls": "pdf:https://ieeexplore.ieee.org/ielx7/6221020/9281055/09210178.pdf; doi:https://doi.org/10.1109/JBHI.2020.3027987; html:https://europepmc.org/articles/PMC8545177; pdf:https://europepmc.org/articles/PMC8545177?pdf=render"
   },
-  {
-    "id": "37008054",
-    "doi": "https://doi.org/10.14336/ad.2022.0829",
-    "title": "Identifying Dynamic Patterns of Polypharmacy for Patients with Dementia from Primary Care Electronic Health Records: A Machine Learning Driven Longitudinal Study.",
-    "authorString": "Longo E, Burnett B, Bauermeister S, Zhou SM.",
-    "authorAffiliations": "",
-    "journalTitle": "Aging and disease",
-    "pubYear": "2023",
-    "date": "2023-04-01",
-    "isOpenAccess": "Y",
-    "keywords": "Diagnosis; Dementia; Patient Safety; Machine Learning; Polypharmacy; Electronic Health Records; Exploratory Factor Analysis",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "It is unclear how medication use evolved before diagnosis of dementia (DoD). This study aims to identify varied patterns of polypharmacy before DoD, their prevalence and possible complications. We collected primary care e-health records for 33,451 dementia patients in Wales from 1990 to 2015. The medication uses in every 5-year period along with 20-years prior to dementia diagnosis were considered. Exploratory factor analysis was used to identify clusters of medicines for every 5-year period. The prevalence of patients taking three or more medications was 82.16%, 69.7%, 41.1% and 5.5% in the Period 1 (0-5 years before DoD) ~ Period 4 (16-20 years before DoD) respectively. The Period 1 showed 3 clusters of polypharmacy - medicines for respiratory/urinary infections, arthropathies and rheumatism, and cardio-vascular disease (CVD) (66.55%); medicines for infections, arthropathies and rheumatism (AR), cardio-metabolic disease (CMD) and depression (22.02%); and medicines for arthropathies, rheumatism and osteoarthritis (2.6%). The Period 2 showed 4 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (69.7%); medicines for CVD and depression (3%); medicines for CMD and arthropathies (0.3%); and medicines for AR, and CVD (2,5%). The Period 3 showed 6 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (41.1%); medicines for CVD, acute-respiratory-infection (ARI), and arthropathies (1.25%); medicines for AR (1.16%); medicines for depression, anxiety (0.06%); medicines for CMD (1.4%); and medicines for dermatologic disorders (0.9%). The Period 4 showed 3 main clusters of polypharmacy - medicines for infections, arthropathy, and CVD (5.5%); medicines for anxiety, ARI (2.4%); and medicines for ARI and CVD (2.1%). As the development towards dementia progressed, the associative diseases tended to cluster with a larger prevalence in each cluster. Farther away before DoD, the clusters of polypharmacy tended to be clearly distinct between each other, resulting in an increasing number of patterns, but in a smaller prevalence.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.14336/ad.2022.0829; doi:https://doi.org/10.14336/AD.2022.0829; html:https://europepmc.org/articles/PMC10017143; pdf:https://europepmc.org/articles/PMC10017143?pdf=render"
-  },
   {
     "id": "37705832",
     "doi": "https://doi.org/10.5837/bjc.2023.003",
@@ -13769,6 +13752,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.5837/bjc.2023.003; html:https://europepmc.org/articles/PMC10495762; pdf:https://europepmc.org/articles/PMC10495762?pdf=render; doi:https://doi.org/10.5837/bjc.2023.003"
   },
+  {
+    "id": "37008054",
+    "doi": "https://doi.org/10.14336/ad.2022.0829",
+    "title": "Identifying Dynamic Patterns of Polypharmacy for Patients with Dementia from Primary Care Electronic Health Records: A Machine Learning Driven Longitudinal Study.",
+    "authorString": "Longo E, Burnett B, Bauermeister S, Zhou SM.",
+    "authorAffiliations": "",
+    "journalTitle": "Aging and disease",
+    "pubYear": "2023",
+    "date": "2023-04-01",
+    "isOpenAccess": "Y",
+    "keywords": "Diagnosis; Dementia; Patient Safety; Machine Learning; Polypharmacy; Electronic Health Records; Exploratory Factor Analysis",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "It is unclear how medication use evolved before diagnosis of dementia (DoD). This study aims to identify varied patterns of polypharmacy before DoD, their prevalence and possible complications. We collected primary care e-health records for 33,451 dementia patients in Wales from 1990 to 2015. The medication uses in every 5-year period along with 20-years prior to dementia diagnosis were considered. Exploratory factor analysis was used to identify clusters of medicines for every 5-year period. The prevalence of patients taking three or more medications was 82.16%, 69.7%, 41.1% and 5.5% in the Period 1 (0-5 years before DoD) ~ Period 4 (16-20 years before DoD) respectively. The Period 1 showed 3 clusters of polypharmacy - medicines for respiratory/urinary infections, arthropathies and rheumatism, and cardio-vascular disease (CVD) (66.55%); medicines for infections, arthropathies and rheumatism (AR), cardio-metabolic disease (CMD) and depression (22.02%); and medicines for arthropathies, rheumatism and osteoarthritis (2.6%). The Period 2 showed 4 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (69.7%); medicines for CVD and depression (3%); medicines for CMD and arthropathies (0.3%); and medicines for AR, and CVD (2,5%). The Period 3 showed 6 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (41.1%); medicines for CVD, acute-respiratory-infection (ARI), and arthropathies (1.25%); medicines for AR (1.16%); medicines for depression, anxiety (0.06%); medicines for CMD (1.4%); and medicines for dermatologic disorders (0.9%). The Period 4 showed 3 main clusters of polypharmacy - medicines for infections, arthropathy, and CVD (5.5%); medicines for anxiety, ARI (2.4%); and medicines for ARI and CVD (2.1%). As the development towards dementia progressed, the associative diseases tended to cluster with a larger prevalence in each cluster. Farther away before DoD, the clusters of polypharmacy tended to be clearly distinct between each other, resulting in an increasing number of patterns, but in a smaller prevalence.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.14336/ad.2022.0829; doi:https://doi.org/10.14336/AD.2022.0829; html:https://europepmc.org/articles/PMC10017143; pdf:https://europepmc.org/articles/PMC10017143?pdf=render"
+  },
   {
     "id": "37140153",
     "doi": "https://doi.org/10.1093/ehjci/jead093",
@@ -13820,23 +13820,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/mbe/article-pdf/39/3/msac034/42692776/msac034.pdf; doi:https://doi.org/10.1093/molbev/msac034; html:https://europepmc.org/articles/PMC8892942; pdf:https://europepmc.org/articles/PMC8892942?pdf=render"
   },
-  {
-    "id": "36834176",
-    "doi": "https://doi.org/10.3390/ijerph20043477",
-    "title": "Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "International journal of environmental research and public health",
-    "pubYear": "2023",
-    "date": "2023-02-16",
-    "isOpenAccess": "Y",
-    "keywords": "Rehabilitation; Systematic review; Pvs; Non-pharmacological Intervention; Covid-19; Long Covid; Post-covid-19 Condition; Post-acute Sequelae Of Sars-cov-2 Infection (Pasc); Post-Viral Syndromes",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Registration</h4>The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.",
-    "laySummary": "",
-    "urls": "pdf:https://www.mdpi.com/1660-4601/20/4/3477/pdf?version=1677135187; doi:https://doi.org/10.3390/ijerph20043477; html:https://europepmc.org/articles/PMC9967466; pdf:https://europepmc.org/articles/PMC9967466?pdf=render"
-  },
   {
     "id": "31000744",
     "doi": "https://doi.org/10.1038/s41598-019-42036-w",
@@ -13854,6 +13837,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41598-019-42036-w.pdf; doi:https://doi.org/10.1038/s41598-019-42036-w; html:https://europepmc.org/articles/PMC6473002; pdf:https://europepmc.org/articles/PMC6473002?pdf=render"
   },
+  {
+    "id": "36834176",
+    "doi": "https://doi.org/10.3390/ijerph20043477",
+    "title": "Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of environmental research and public health",
+    "pubYear": "2023",
+    "date": "2023-02-16",
+    "isOpenAccess": "Y",
+    "keywords": "Rehabilitation; Systematic review; Pvs; Non-pharmacological Intervention; Covid-19; Long Covid; Post-covid-19 Condition; Post-acute Sequelae Of Sars-cov-2 Infection (Pasc); Post-Viral Syndromes",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Registration</h4>The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.",
+    "laySummary": "",
+    "urls": "pdf:https://www.mdpi.com/1660-4601/20/4/3477/pdf?version=1677135187; doi:https://doi.org/10.3390/ijerph20043477; html:https://europepmc.org/articles/PMC9967466; pdf:https://europepmc.org/articles/PMC9967466?pdf=render"
+  },
   {
     "id": "35765786",
     "doi": "https://doi.org/10.7189/jogh.12.04052",
@@ -13973,6 +13973,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jtha.2023.07.008"
   },
+  {
+    "id": "34571200",
+    "doi": "https://doi.org/10.1016/j.jaip.2021.09.026",
+    "title": "Atopic Eczema-Associated Fracture Risk and Oral Corticosteroids: A Population-Based Cohort Study.",
+    "authorString": "Matthewman J, Mansfield KE, Prieto-Alhambra D, Mulick AR, Smeeth L, Lowe KE, Silverwood RJ, Langan SM.",
+    "authorAffiliations": "",
+    "journalTitle": "The journal of allergy and clinical immunology. In practice",
+    "pubYear": "2022",
+    "date": "2021-09-24",
+    "isOpenAccess": "Y",
+    "keywords": "Fracture; Atopic Eczema; Atopic Dermatitis; osteoporotic fracture; Oral Corticosteroids",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Evidence suggests adults with atopic eczema have increased fracture risk. However, it is unclear whether oral corticosteroids explain the association.<h4>Objective</h4>To assess to what extent oral corticosteroids mediate the relationship between atopic eczema and fractures.<h4>Methods</h4>We conducted a cohort study using English primary care (Clinical Practice Research Datalink) and hospital admissions (Hospital Episode Statistics) records (1998-2016) including adults (18 years old and older) with atopic eczema matched (age, sex, and general practice) with up to 5 adults without atopic eczema. We used Cox regression to estimate hazard ratios (HRs) for specific major osteoporotic fractures (hip, spine, pelvis, or wrist) and for any-site fracture comparing individuals with atopic eczema with those without, adjusting for 6 different definitions of time-updated oral corticosteroid use (ever any prescription, ever high-dose, and recent, cumulative, current, or peak dose).<h4>Results</h4>We identified 526,808 individuals with atopic eczema and 2,569,030 without. We saw evidence of an association between atopic eczema and major osteoporotic fractures (eg, spine HR 1.15, 99% CI 1.08-1.22; hip HR 1.11, 99% CI 1.08-1.15) that remained after additionally adjusting for oral corticosteroids (eg, cumulative corticosteroid dose: spine HR 1.09, 99% CI 1.03-1.16; hip HR 1.09, 99% CI 1.06-1.12). Fracture rates were higher in people with severe atopic eczema than in people without even after adjusting for oral corticosteroids (eg, spine HR [99% CI]: confounder-adjusted 2.31 [1.91-2.81]; additionally adjusted for cumulative dose 1.71 [1.40-2.09]).<h4>Conclusions</h4>Our findings suggest that little of the association between atopic eczema and major osteoporotic fractures is explained by oral corticosteroid use.",
+    "laySummary": "",
+    "urls": "pdf:http://www.jaci-inpractice.org/article/S2213219821010187/pdf; doi:https://doi.org/10.1016/j.jaip.2021.09.026; html:https://europepmc.org/articles/PMC7612204; pdf:https://europepmc.org/articles/PMC7612204?pdf=render"
+  },
   {
     "id": "36593100",
     "doi": "https://doi.org/10.1136/heartjnl-2022-322124",
@@ -14007,23 +14024,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead166/50880139/jead166.pdf; doi:https://doi.org/10.1093/ehjci/jead166; html:https://europepmc.org/articles/PMC10610755; pdf:https://europepmc.org/articles/PMC10610755?pdf=render"
   },
-  {
-    "id": "34571200",
-    "doi": "https://doi.org/10.1016/j.jaip.2021.09.026",
-    "title": "Atopic Eczema-Associated Fracture Risk and Oral Corticosteroids: A Population-Based Cohort Study.",
-    "authorString": "Matthewman J, Mansfield KE, Prieto-Alhambra D, Mulick AR, Smeeth L, Lowe KE, Silverwood RJ, Langan SM.",
-    "authorAffiliations": "",
-    "journalTitle": "The journal of allergy and clinical immunology. In practice",
-    "pubYear": "2022",
-    "date": "2021-09-24",
-    "isOpenAccess": "Y",
-    "keywords": "Fracture; Atopic Eczema; Atopic Dermatitis; osteoporotic fracture; Oral Corticosteroids",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Evidence suggests adults with atopic eczema have increased fracture risk. However, it is unclear whether oral corticosteroids explain the association.<h4>Objective</h4>To assess to what extent oral corticosteroids mediate the relationship between atopic eczema and fractures.<h4>Methods</h4>We conducted a cohort study using English primary care (Clinical Practice Research Datalink) and hospital admissions (Hospital Episode Statistics) records (1998-2016) including adults (18 years old and older) with atopic eczema matched (age, sex, and general practice) with up to 5 adults without atopic eczema. We used Cox regression to estimate hazard ratios (HRs) for specific major osteoporotic fractures (hip, spine, pelvis, or wrist) and for any-site fracture comparing individuals with atopic eczema with those without, adjusting for 6 different definitions of time-updated oral corticosteroid use (ever any prescription, ever high-dose, and recent, cumulative, current, or peak dose).<h4>Results</h4>We identified 526,808 individuals with atopic eczema and 2,569,030 without. We saw evidence of an association between atopic eczema and major osteoporotic fractures (eg, spine HR 1.15, 99% CI 1.08-1.22; hip HR 1.11, 99% CI 1.08-1.15) that remained after additionally adjusting for oral corticosteroids (eg, cumulative corticosteroid dose: spine HR 1.09, 99% CI 1.03-1.16; hip HR 1.09, 99% CI 1.06-1.12). Fracture rates were higher in people with severe atopic eczema than in people without even after adjusting for oral corticosteroids (eg, spine HR [99% CI]: confounder-adjusted 2.31 [1.91-2.81]; additionally adjusted for cumulative dose 1.71 [1.40-2.09]).<h4>Conclusions</h4>Our findings suggest that little of the association between atopic eczema and major osteoporotic fractures is explained by oral corticosteroid use.",
-    "laySummary": "",
-    "urls": "pdf:http://www.jaci-inpractice.org/article/S2213219821010187/pdf; doi:https://doi.org/10.1016/j.jaip.2021.09.026; html:https://europepmc.org/articles/PMC7612204; pdf:https://europepmc.org/articles/PMC7612204?pdf=render"
-  },
   {
     "id": "37032516",
     "doi": "https://doi.org/10.1111/aor.14537",
@@ -14058,23 +14058,6 @@
     "laySummary": "",
     "urls": "pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/85021/8/mSystems-2020-Penney-e00677-20.full.pdf; doi:https://doi.org/10.1128/mSystems.00677-20; html:https://europepmc.org/articles/PMC7716389; pdf:https://europepmc.org/articles/PMC7716389?pdf=render"
   },
-  {
-    "id": "35640889",
-    "doi": "https://doi.org/10.1093/ehjci/jeac101",
-    "title": "Pericardial adiposity is independently linked to adverse cardiovascular phenotypes: a CMR study of 42 598 UK Biobank participants.",
-    "authorString": "Ardissino M, McCracken C, Bard A, Antoniades C, Neubauer S, Harvey NC, Petersen SE, Raisi-Estabragh Z.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal. Cardiovascular Imaging",
-    "pubYear": "2022",
-    "date": "2022-10-01",
-    "isOpenAccess": "Y",
-    "keywords": "Arterial stiffness; Cardiovascular Magnetic Resonance; Left ventricle; Pericardial Fat; Left Atrium; Cardiometabolic Disease",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/ehjcimaging/article-pdf/23/11/1471/46583486/jeac101.pdf; doi:https://doi.org/10.1093/ehjci/jeac101; html:https://europepmc.org/articles/PMC9584621; pdf:https://europepmc.org/articles/PMC9584621?pdf=render"
-  },
   {
     "id": "31607513",
     "doi": "https://doi.org/10.1016/j.cell.2019.08.051",
@@ -14092,6 +14075,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.cell.com/article/S0092867419310025/pdf; doi:https://doi.org/10.1016/j.cell.2019.08.051; html:https://europepmc.org/articles/PMC6939869; pdf:https://europepmc.org/articles/PMC6939869?pdf=render; doi:https://doi.org/10.1016/j.cell.2019.08.051"
   },
+  {
+    "id": "35640889",
+    "doi": "https://doi.org/10.1093/ehjci/jeac101",
+    "title": "Pericardial adiposity is independently linked to adverse cardiovascular phenotypes: a CMR study of 42 598 UK Biobank participants.",
+    "authorString": "Ardissino M, McCracken C, Bard A, Antoniades C, Neubauer S, Harvey NC, Petersen SE, Raisi-Estabragh Z.",
+    "authorAffiliations": "",
+    "journalTitle": "European heart journal. Cardiovascular Imaging",
+    "pubYear": "2022",
+    "date": "2022-10-01",
+    "isOpenAccess": "Y",
+    "keywords": "Arterial stiffness; Cardiovascular Magnetic Resonance; Left ventricle; Pericardial Fat; Left Atrium; Cardiometabolic Disease",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/ehjcimaging/article-pdf/23/11/1471/46583486/jeac101.pdf; doi:https://doi.org/10.1093/ehjci/jeac101; html:https://europepmc.org/articles/PMC9584621; pdf:https://europepmc.org/articles/PMC9584621?pdf=render"
+  },
   {
     "id": "34543272",
     "doi": "https://doi.org/10.1371/journal.pcbi.1009324",
@@ -14602,23 +14602,6 @@
     "laySummary": "",
     "urls": "pdf:https://kclpure.kcl.ac.uk/ws/files/173598342/ESC_Heart_Failure_2022_Godec_Cardiovascular_outcomes_associated_with_treatment_of_type_2_diabetes_in_patients_with.pdf; doi:https://doi.org/10.1002/ehf2.13910; html:https://europepmc.org/articles/PMC9065866; pdf:https://europepmc.org/articles/PMC9065866?pdf=render"
   },
-  {
-    "id": "37703231",
-    "doi": "https://doi.org/10.1371/journal.pdig.0000334",
-    "title": "A population-based study exploring phenotypic clusters and clinical outcomes in stroke using unsupervised machine learning approach.",
-    "authorString": "Akyea RK, Ntaios G, Kontopantelis E, Georgiopoulos G, Soria D, Asselbergs FW, Kai J, Weng SF, Qureshi N.",
-    "authorAffiliations": "",
-    "journalTitle": "PLOS digital health",
-    "pubYear": "2023",
-    "date": "2023-09-13",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Individuals developing stroke have varying clinical characteristics, demographic, and biochemical profiles. This heterogeneity in phenotypic characteristics can impact on cardiovascular disease (CVD) morbidity and mortality outcomes. This study uses a novel clustering approach to stratify individuals with incident stroke into phenotypic clusters and evaluates the differential burden of recurrent stroke and other cardiovascular outcomes. We used linked clinical data from primary care, hospitalisations, and death records in the UK. A data-driven clustering analysis (kamila algorithm) was used in 48,114 patients aged \u2265 18 years with incident stroke, from 1-Jan-1998 to 31-Dec-2017 and no prior history of serious vascular events. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for subsequent adverse outcomes, for each of the generated clusters. Adverse outcomes included coronary heart disease (CHD), recurrent stroke, peripheral vascular disease (PVD), heart failure, CVD-related and all-cause mortality. Four distinct phenotypes with varying underlying clinical characteristics were identified in patients with incident stroke. Compared with cluster 1 (n = 5,201, 10.8%), the risk of composite recurrent stroke and CVD-related mortality was higher in the other 3 clusters (cluster 2 [n = 18,655, 38.8%]: hazard ratio [HR], 1.07; 95% CI, 1.02-1.12; cluster 3 [n = 10,244, 21.3%]: HR, 1.20; 95% CI, 1.14-1.26; and cluster 4 [n = 14,014, 29.1%]: HR, 1.44; 95% CI: 1.37-1.50). Similar trends in risk were observed for composite recurrent stroke and all-cause mortality outcome, and subsequent recurrent stroke outcome. However, results were not consistent for subsequent risk in CHD, PVD, heart failure, CVD-related mortality, and all-cause mortality. In this proof of principle study, we demonstrated how a heterogenous population of patients with incident stroke can be stratified into four relatively homogenous phenotypes with differential risk of recurrent and major cardiovascular outcomes. This offers an opportunity to revisit the stratification of care for patients with incident stroke to improve patient outcomes.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1371/journal.pdig.0000334; html:https://europepmc.org/articles/PMC10499205; pdf:https://europepmc.org/articles/PMC10499205?pdf=render"
-  },
   {
     "id": "36197964",
     "doi": "https://doi.org/10.1126/scitranslmed.abq4810",
@@ -14636,6 +14619,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.science.org/doi/pdf/10.1126/scitranslmed.abq4810?download=true; doi:https://doi.org/10.1126/scitranslmed.abq4810"
   },
+  {
+    "id": "37703231",
+    "doi": "https://doi.org/10.1371/journal.pdig.0000334",
+    "title": "A population-based study exploring phenotypic clusters and clinical outcomes in stroke using unsupervised machine learning approach.",
+    "authorString": "Akyea RK, Ntaios G, Kontopantelis E, Georgiopoulos G, Soria D, Asselbergs FW, Kai J, Weng SF, Qureshi N.",
+    "authorAffiliations": "",
+    "journalTitle": "PLOS digital health",
+    "pubYear": "2023",
+    "date": "2023-09-13",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Individuals developing stroke have varying clinical characteristics, demographic, and biochemical profiles. This heterogeneity in phenotypic characteristics can impact on cardiovascular disease (CVD) morbidity and mortality outcomes. This study uses a novel clustering approach to stratify individuals with incident stroke into phenotypic clusters and evaluates the differential burden of recurrent stroke and other cardiovascular outcomes. We used linked clinical data from primary care, hospitalisations, and death records in the UK. A data-driven clustering analysis (kamila algorithm) was used in 48,114 patients aged \u2265 18 years with incident stroke, from 1-Jan-1998 to 31-Dec-2017 and no prior history of serious vascular events. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for subsequent adverse outcomes, for each of the generated clusters. Adverse outcomes included coronary heart disease (CHD), recurrent stroke, peripheral vascular disease (PVD), heart failure, CVD-related and all-cause mortality. Four distinct phenotypes with varying underlying clinical characteristics were identified in patients with incident stroke. Compared with cluster 1 (n = 5,201, 10.8%), the risk of composite recurrent stroke and CVD-related mortality was higher in the other 3 clusters (cluster 2 [n = 18,655, 38.8%]: hazard ratio [HR], 1.07; 95% CI, 1.02-1.12; cluster 3 [n = 10,244, 21.3%]: HR, 1.20; 95% CI, 1.14-1.26; and cluster 4 [n = 14,014, 29.1%]: HR, 1.44; 95% CI: 1.37-1.50). Similar trends in risk were observed for composite recurrent stroke and all-cause mortality outcome, and subsequent recurrent stroke outcome. However, results were not consistent for subsequent risk in CHD, PVD, heart failure, CVD-related mortality, and all-cause mortality. In this proof of principle study, we demonstrated how a heterogenous population of patients with incident stroke can be stratified into four relatively homogenous phenotypes with differential risk of recurrent and major cardiovascular outcomes. This offers an opportunity to revisit the stratification of care for patients with incident stroke to improve patient outcomes.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1371/journal.pdig.0000334; html:https://europepmc.org/articles/PMC10499205; pdf:https://europepmc.org/articles/PMC10499205?pdf=render"
+  },
   {
     "id": "36864090",
     "doi": "https://doi.org/10.1038/s41598-023-30369-6",
@@ -14755,23 +14755,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000276.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000276; html:https://europepmc.org/articles/PMC9951378; pdf:https://europepmc.org/articles/PMC9951378?pdf=render"
   },
-  {
-    "id": "36276403",
-    "doi": "https://doi.org/10.3389/fpubh.2022.875198",
-    "title": "The mental health experiences of ethnic minorities in the UK during the Coronavirus pandemic: A qualitative exploration.",
-    "authorString": "Van Bortel T, Lombardo C, Guo L, Solomon S, Martin S, Hughes K, Weeks L, Crepaz-Keay D, McDaid S, Chantler O, Thorpe L, Morton A, Davidson G, John A, Kousoulis AA.",
-    "authorAffiliations": "",
-    "journalTitle": "Frontiers in public health",
-    "pubYear": "2022",
-    "date": "2022-10-06",
-    "isOpenAccess": "Y",
-    "keywords": "Mental health; United Kingdom; Inequalities; Ethnic Minorities; Covid-19; Coronavirus Pandemic; Bame Ethnicity",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Worldwide, the Coronavirus pandemic has had a major impact on people's health, lives, and livelihoods. However, this impact has not been felt equally across various population groups. People from ethnic minority backgrounds in the UK have been more adversely affected by the pandemic, especially in terms of their physical health. Their mental health, on the other hand, has received less attention. This study aimed to explore the mental health experiences of UK adults from ethnic minorities during the Coronavirus pandemic. This work forms part of our wider long-term UK population study \"Mental Health in the Pandemic.\"<h4>Methods</h4>We conducted an exploratory qualitative study with people from ethnic minority communities across the UK. A series of in-depth interviews were conducted with 15 women, 14 men and 1 non-binary person from ethnic minority backgrounds, aged between 18 and 65 years old (mean age = 40). We utilized purposefully selected maximum variation sampling in order to capture as wide a variety of views, perceptions and experiences as possible. Inclusion criteria: adults (18+) from ethnic minorities across the UK; able to provide full consent to participate; able to participate in a video- or phone-call interview. All interviews took place <i>via</i> MS Teams or Zoom. The gathered data were transcribed verbatim and underwent thematic analysis following Braun and Clarke carried out using NVivo 12 software.<h4>Results</h4>The qualitative data analysis yielded seven overarching themes: (1) pandemic-specific mental health and wellbeing experiences; (2) issues relating to the media; (3) coping mechanisms; (4) worries around and attitudes toward vaccination; (5) suggestions for support in moving forward; (6) best and worst experiences during pandemic and lockdowns; (7) biggest areas of change in personal life. Generally, participants' mental health experiences varied with some not being affected by the pandemic in a way related to their ethnicity, some sharing positive experiences and coping strategies (exercising more, spending more time with family, community cohesion), and some expressing negative experiences (eating or drinking more, feeling more isolated, or even racism and abuse, especially toward Asian communities). Concerns were raised around trust issues in relation to the media, the inadequate representation of ethnic minorities, and the spread of fake news especially on social media. Attitudes toward vaccinations varied too, with some people more willing to have the vaccine than others.<h4>Conclusion</h4>This study's findings highlight the diversity in the pandemic mental health experiences of ethnic minorities in the UK and has implications for policy, practice and further research. To enable moving forward beyond the pandemic, our study surfaced the need for culturally appropriate mental health support, financial support (as a key mental health determinant), accurate media representation, and clear communication messaging from the Governments of the UK.",
-    "laySummary": "",
-    "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.875198/pdf; doi:https://doi.org/10.3389/fpubh.2022.875198; html:https://europepmc.org/articles/PMC9582845; pdf:https://europepmc.org/articles/PMC9582845?pdf=render"
-  },
   {
     "id": "31104603",
     "doi": "https://doi.org/10.1098/rstb.2018.0276",
@@ -14806,6 +14789,23 @@
     "laySummary": "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.",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/9/11/e031365.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-031365; html:https://europepmc.org/articles/PMC6858200; pdf:https://europepmc.org/articles/PMC6858200?pdf=render"
   },
+  {
+    "id": "36276403",
+    "doi": "https://doi.org/10.3389/fpubh.2022.875198",
+    "title": "The mental health experiences of ethnic minorities in the UK during the Coronavirus pandemic: A qualitative exploration.",
+    "authorString": "Van Bortel T, Lombardo C, Guo L, Solomon S, Martin S, Hughes K, Weeks L, Crepaz-Keay D, McDaid S, Chantler O, Thorpe L, Morton A, Davidson G, John A, Kousoulis AA.",
+    "authorAffiliations": "",
+    "journalTitle": "Frontiers in public health",
+    "pubYear": "2022",
+    "date": "2022-10-06",
+    "isOpenAccess": "Y",
+    "keywords": "Mental health; United Kingdom; Inequalities; Ethnic Minorities; Covid-19; Coronavirus Pandemic; Bame Ethnicity",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Worldwide, the Coronavirus pandemic has had a major impact on people's health, lives, and livelihoods. However, this impact has not been felt equally across various population groups. People from ethnic minority backgrounds in the UK have been more adversely affected by the pandemic, especially in terms of their physical health. Their mental health, on the other hand, has received less attention. This study aimed to explore the mental health experiences of UK adults from ethnic minorities during the Coronavirus pandemic. This work forms part of our wider long-term UK population study \"Mental Health in the Pandemic.\"<h4>Methods</h4>We conducted an exploratory qualitative study with people from ethnic minority communities across the UK. A series of in-depth interviews were conducted with 15 women, 14 men and 1 non-binary person from ethnic minority backgrounds, aged between 18 and 65 years old (mean age = 40). We utilized purposefully selected maximum variation sampling in order to capture as wide a variety of views, perceptions and experiences as possible. Inclusion criteria: adults (18+) from ethnic minorities across the UK; able to provide full consent to participate; able to participate in a video- or phone-call interview. All interviews took place <i>via</i> MS Teams or Zoom. The gathered data were transcribed verbatim and underwent thematic analysis following Braun and Clarke carried out using NVivo 12 software.<h4>Results</h4>The qualitative data analysis yielded seven overarching themes: (1) pandemic-specific mental health and wellbeing experiences; (2) issues relating to the media; (3) coping mechanisms; (4) worries around and attitudes toward vaccination; (5) suggestions for support in moving forward; (6) best and worst experiences during pandemic and lockdowns; (7) biggest areas of change in personal life. Generally, participants' mental health experiences varied with some not being affected by the pandemic in a way related to their ethnicity, some sharing positive experiences and coping strategies (exercising more, spending more time with family, community cohesion), and some expressing negative experiences (eating or drinking more, feeling more isolated, or even racism and abuse, especially toward Asian communities). Concerns were raised around trust issues in relation to the media, the inadequate representation of ethnic minorities, and the spread of fake news especially on social media. Attitudes toward vaccinations varied too, with some people more willing to have the vaccine than others.<h4>Conclusion</h4>This study's findings highlight the diversity in the pandemic mental health experiences of ethnic minorities in the UK and has implications for policy, practice and further research. To enable moving forward beyond the pandemic, our study surfaced the need for culturally appropriate mental health support, financial support (as a key mental health determinant), accurate media representation, and clear communication messaging from the Governments of the UK.",
+    "laySummary": "",
+    "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.875198/pdf; doi:https://doi.org/10.3389/fpubh.2022.875198; html:https://europepmc.org/articles/PMC9582845; pdf:https://europepmc.org/articles/PMC9582845?pdf=render"
+  },
   {
     "id": "37740900",
     "doi": "https://doi.org/10.1093/ageing/afad176",
@@ -14908,23 +14908,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0237298&type=printable; doi:https://doi.org/10.1371/journal.pone.0237298; html:https://europepmc.org/articles/PMC7425844; pdf:https://europepmc.org/articles/PMC7425844?pdf=render"
   },
-  {
-    "id": "36719715",
-    "doi": "https://doi.org/10.2196/41248",
-    "title": "Patterns in the Use of Heart Failure Telemonitoring: Post Hoc Analysis of the e-Vita Heart Failure Trial.",
-    "authorString": "Brons M, Ten Klooster I, van Gemert-Pijnen L, Jaarsma T, Asselbergs FW, Oerlemans MIFJ, Koudstaal S, Rutten FH.",
-    "authorAffiliations": "",
-    "journalTitle": "JMIR cardio",
-    "pubYear": "2023",
-    "date": "2023-01-31",
-    "isOpenAccess": "Y",
-    "keywords": "Adherence; Heart Failure; Patient Monitoring; Remote Monitoring; Telemonitoring; Ehealth; Electronic Personal Health Record",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Research on the use of home telemonitoring data and adherence to it can provide new insights into telemonitoring for the daily management of patients with heart failure (HF).<h4>Objective</h4>We described the use of a telemonitoring platform-including remote patient monitoring of blood pressure, pulse, and weight-and the use of the electronic personal health record. Patient characteristics were assessed in both adherent and nonadherent patients to weight transmissions.<h4>Methods</h4>We used the data of the e-Vita HF study, a 3-arm parallel randomized trial performed in stable patients with HF managed in outpatient clinics in the Netherlands. In this study, data were analyzed from the participants in the intervention arm (ie, e-Vita HF platform). Adherence to weight transmissions was defined as transmitting weight \u22653 times per week for at least 42 weeks during a year.<h4>Results</h4>Data from 150 patients (mean age 67, SD 11 years; n=37, 25% female; n=123, 82% self-assessed New York Heart Association class I-II) were analyzed. One-year adherence to weight transmissions was 74% (n=111). Patients adherent to weight transmissions were less often hospitalized for HF in the 6 months before enrollment in the study compared to those who were nonadherent (n=9, 8% vs n=9, 23%; P=.02). The percentage of patients visiting the personal health record dropped steadily over time (n=140, 93% vs n=59, 39% at one year). With univariable analyses, there was no significant correlation between patient characteristics and adherence to weight transmissions.<h4>Conclusions</h4>Adherence to remote patient monitoring was high among stable patients with HF and best for weighing; however, adherence decreased over time. Clinical and demographic variables seem not related to adherence to transmitting weight.<h4>Trial registration</h4>ClinicalTrials.gov NCT01755988; https://clinicaltrials.gov/ct2/show/NCT01755988.",
-    "laySummary": "",
-    "urls": "pdf:https://cardio.jmir.org/2023/1/e41248/PDF; doi:https://doi.org/10.2196/41248; html:https://europepmc.org/articles/PMC9929726; pdf:https://europepmc.org/articles/PMC9929726?pdf=render"
-  },
   {
     "id": "31611193",
     "doi": "https://doi.org/10.1136/archdischild-2019-317248",
@@ -14942,6 +14925,23 @@
     "laySummary": "",
     "urls": "pdf:https://adc.bmj.com/content/archdischild/105/4/347.full.pdf; doi:https://doi.org/10.1136/archdischild-2019-317248; html:https://europepmc.org/articles/PMC7146921; pdf:https://europepmc.org/articles/PMC7146921?pdf=render"
   },
+  {
+    "id": "36719715",
+    "doi": "https://doi.org/10.2196/41248",
+    "title": "Patterns in the Use of Heart Failure Telemonitoring: Post Hoc Analysis of the e-Vita Heart Failure Trial.",
+    "authorString": "Brons M, Ten Klooster I, van Gemert-Pijnen L, Jaarsma T, Asselbergs FW, Oerlemans MIFJ, Koudstaal S, Rutten FH.",
+    "authorAffiliations": "",
+    "journalTitle": "JMIR cardio",
+    "pubYear": "2023",
+    "date": "2023-01-31",
+    "isOpenAccess": "Y",
+    "keywords": "Adherence; Heart Failure; Patient Monitoring; Remote Monitoring; Telemonitoring; Ehealth; Electronic Personal Health Record",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Research on the use of home telemonitoring data and adherence to it can provide new insights into telemonitoring for the daily management of patients with heart failure (HF).<h4>Objective</h4>We described the use of a telemonitoring platform-including remote patient monitoring of blood pressure, pulse, and weight-and the use of the electronic personal health record. Patient characteristics were assessed in both adherent and nonadherent patients to weight transmissions.<h4>Methods</h4>We used the data of the e-Vita HF study, a 3-arm parallel randomized trial performed in stable patients with HF managed in outpatient clinics in the Netherlands. In this study, data were analyzed from the participants in the intervention arm (ie, e-Vita HF platform). Adherence to weight transmissions was defined as transmitting weight \u22653 times per week for at least 42 weeks during a year.<h4>Results</h4>Data from 150 patients (mean age 67, SD 11 years; n=37, 25% female; n=123, 82% self-assessed New York Heart Association class I-II) were analyzed. One-year adherence to weight transmissions was 74% (n=111). Patients adherent to weight transmissions were less often hospitalized for HF in the 6 months before enrollment in the study compared to those who were nonadherent (n=9, 8% vs n=9, 23%; P=.02). The percentage of patients visiting the personal health record dropped steadily over time (n=140, 93% vs n=59, 39% at one year). With univariable analyses, there was no significant correlation between patient characteristics and adherence to weight transmissions.<h4>Conclusions</h4>Adherence to remote patient monitoring was high among stable patients with HF and best for weighing; however, adherence decreased over time. Clinical and demographic variables seem not related to adherence to transmitting weight.<h4>Trial registration</h4>ClinicalTrials.gov NCT01755988; https://clinicaltrials.gov/ct2/show/NCT01755988.",
+    "laySummary": "",
+    "urls": "pdf:https://cardio.jmir.org/2023/1/e41248/PDF; doi:https://doi.org/10.2196/41248; html:https://europepmc.org/articles/PMC9929726; pdf:https://europepmc.org/articles/PMC9929726?pdf=render"
+  },
   {
     "id": "37143831",
     "doi": "https://doi.org/10.1183/23120541.00591-2022",
@@ -14976,23 +14976,6 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s10654-022-00934-w.pdf; doi:https://doi.org/10.1007/s10654-022-00934-w; html:https://europepmc.org/articles/PMC9792414; pdf:https://europepmc.org/articles/PMC9792414?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": "35634533",
     "doi": "https://doi.org/10.12688/wellcomeopenres.17360.1",
@@ -15011,21 +14994,21 @@
     "urls": "doi:https://doi.org/10.12688/wellcomeopenres.17360.1; html:https://europepmc.org/articles/PMC9120928; pdf:https://europepmc.org/articles/PMC9120928?pdf=render"
   },
   {
-    "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": "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": "Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer",
-    "pubYear": "2023",
-    "date": "2023-08-22",
-    "isOpenAccess": "Y",
-    "keywords": "Analgesia; Cancer; Pain; Primary Care; Prescription; Covid-19 Pandemic",
+    "journalTitle": "The Lancet. Digital health",
+    "pubYear": "2022",
+    "date": "2022-08-29",
+    "isOpenAccess": "N",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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": "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": "pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07944-8.pdf; doi:https://doi.org/10.1007/s00520-023-07944-8; html:https://europepmc.org/articles/PMC10444652; pdf:https://europepmc.org/articles/PMC10444652?pdf=render"
+    "urls": "doi:https://doi.org/10.1016/s2589-7500(22)00151-0; doi:https://doi.org/10.1016/S2589-7500(22)00151-0"
   },
   {
     "id": "31153319",
@@ -15044,6 +15027,23 @@
     "laySummary": "",
     "urls": "pdf:https://asa.scitation.org/doi/pdf/10.1121/1.5100272; 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": "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": "Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer",
+    "pubYear": "2023",
+    "date": "2023-08-22",
+    "isOpenAccess": "Y",
+    "keywords": "Analgesia; Cancer; Pain; Primary Care; Prescription; Covid-19 Pandemic",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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": "pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07944-8.pdf; doi:https://doi.org/10.1007/s00520-023-07944-8; html:https://europepmc.org/articles/PMC10444652; pdf:https://europepmc.org/articles/PMC10444652?pdf=render"
+  },
   {
     "id": "32864476",
     "doi": "https://doi.org/10.23889/ijpds.v5i1.1157",
@@ -15061,23 +15061,6 @@
     "laySummary": "",
     "urls": "pdf:https://ijpds.org/article/download/1157/2531; doi:https://doi.org/10.23889/ijpds.v5i1.1157; html:https://europepmc.org/articles/PMC7115985; pdf:https://europepmc.org/articles/PMC7115985?pdf=render"
   },
-  {
-    "id": "35698725",
-    "doi": "https://doi.org/10.1016/s2665-9913(22)00098-4",
-    "title": "Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "The Lancet. Rheumatology",
-    "pubYear": "2022",
-    "date": "2022-06-09",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>We identified 17\u2009672\u2009065 adults; 1\u2009163\u2009438 adults (640\u2009164 [55\u00b70%] women and 523\u2009274 [45\u00b70%] men, and 827\u2009457 [71\u00b71%] of White ethnicity) had immune-mediated inflammatory diseases, and 16\u2009508\u2009627 people (8\u2009215\u2009020 [49\u00b78%] women and 8\u2009293\u2009607 [50\u00b72%] men, and 10\u2009614\u2009096 [64\u00b73%] of White ethnicity) were included as the general population. Of 1\u2009163\u2009438 adults with immune-mediated inflammatory diseases, 19\u2009119 (1\u00b76%) received targeted immune-modifying therapy and 181\u2009694 (15\u00b76%) 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\u00b723, 95% CI 1\u00b720-1\u00b727) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1\u00b715, 1\u00b711-1\u00b718). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1\u00b724, 95% CI 1\u00b721-1\u00b728; mediator-adjusted 1\u00b716, 1\u00b712-1\u00b719) and hospital admission (confounder-adjusted 1\u00b732, 1\u00b729-1\u00b735; mediator-adjusted 1\u00b720, 1\u00b717-1\u00b723). 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\u00b703, 95% CI 0\u00b780-1\u00b733), and after additionally adjusting for current glucocorticoid use (1\u00b701, 0\u00b778-1\u00b730). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL\u201123 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\u00b768, 95% CI 1\u00b711-2\u00b756), with some attenuation after excluding people with haematological malignancies or organ transplants (1\u00b7<b>54, 0</b>\u00b7<b>95</b>-<b>2</b>\u00b7<b>49</b>).<h4>Interpretation</h4>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.<h4>Funding</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:http://www.thelancet.com/article/S2665991322000984/pdf; 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"
-  },
   {
     "id": "31628383",
     "doi": "https://doi.org/10.1038/s41598-019-51562-6",
@@ -15095,6 +15078,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41598-019-51562-6.pdf; doi:https://doi.org/10.1038/s41598-019-51562-6; html:https://europepmc.org/articles/PMC6802378; pdf:https://europepmc.org/articles/PMC6802378?pdf=render"
   },
+  {
+    "id": "35698725",
+    "doi": "https://doi.org/10.1016/s2665-9913(22)00098-4",
+    "title": "Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "The Lancet. Rheumatology",
+    "pubYear": "2022",
+    "date": "2022-06-09",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>We identified 17\u2009672\u2009065 adults; 1\u2009163\u2009438 adults (640\u2009164 [55\u00b70%] women and 523\u2009274 [45\u00b70%] men, and 827\u2009457 [71\u00b71%] of White ethnicity) had immune-mediated inflammatory diseases, and 16\u2009508\u2009627 people (8\u2009215\u2009020 [49\u00b78%] women and 8\u2009293\u2009607 [50\u00b72%] men, and 10\u2009614\u2009096 [64\u00b73%] of White ethnicity) were included as the general population. Of 1\u2009163\u2009438 adults with immune-mediated inflammatory diseases, 19\u2009119 (1\u00b76%) received targeted immune-modifying therapy and 181\u2009694 (15\u00b76%) 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\u00b723, 95% CI 1\u00b720-1\u00b727) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1\u00b715, 1\u00b711-1\u00b718). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1\u00b724, 95% CI 1\u00b721-1\u00b728; mediator-adjusted 1\u00b716, 1\u00b712-1\u00b719) and hospital admission (confounder-adjusted 1\u00b732, 1\u00b729-1\u00b735; mediator-adjusted 1\u00b720, 1\u00b717-1\u00b723). 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\u00b703, 95% CI 0\u00b780-1\u00b733), and after additionally adjusting for current glucocorticoid use (1\u00b701, 0\u00b778-1\u00b730). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL\u201123 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\u00b768, 95% CI 1\u00b711-2\u00b756), with some attenuation after excluding people with haematological malignancies or organ transplants (1\u00b7<b>54, 0</b>\u00b7<b>95</b>-<b>2</b>\u00b7<b>49</b>).<h4>Interpretation</h4>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.<h4>Funding</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:http://www.thelancet.com/article/S2665991322000984/pdf; 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"
+  },
   {
     "id": "34286192",
     "doi": "https://doi.org/10.7861/fhj.2021-0083",
@@ -15333,23 +15333,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e041536.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-041536; html:https://europepmc.org/articles/PMC7797241; pdf:https://europepmc.org/articles/PMC7797241?pdf=render"
   },
-  {
-    "id": "35921096",
-    "doi": "https://doi.org/10.1001/jamacardio.2022.2333",
-    "title": "Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease: A Factorial Mendelian Randomization Study.",
-    "authorString": "Cupido AJ, Reeskamp LF, Hingorani AD, Finan C, Asselbergs FW, Hovingh GK, Schmidt AF.",
-    "authorAffiliations": "",
-    "journalTitle": "JAMA cardiology",
-    "pubYear": "2022",
-    "date": "2022-09-01",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Importance</h4>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.<h4>Objective</h4>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.<h4>Design, setting, and participants</h4>Two-sample 2\u2009\u00d7\u20092 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.<h4>Exposures</h4>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.<h4>Main outcomes and measures</h4>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.<h4>Results</h4>Data for 425\u202f354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229\u202f399 (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\u2009=\u2009.34 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\u2009=\u2009.83 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).<h4>Conclusions and relevance</h4>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.",
-    "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": "33249608",
     "doi": "https://doi.org/10.1111/opo.12765",
@@ -15367,6 +15350,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1111/opo.12765"
   },
+  {
+    "id": "35921096",
+    "doi": "https://doi.org/10.1001/jamacardio.2022.2333",
+    "title": "Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease: A Factorial Mendelian Randomization Study.",
+    "authorString": "Cupido AJ, Reeskamp LF, Hingorani AD, Finan C, Asselbergs FW, Hovingh GK, Schmidt AF.",
+    "authorAffiliations": "",
+    "journalTitle": "JAMA cardiology",
+    "pubYear": "2022",
+    "date": "2022-09-01",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Importance</h4>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.<h4>Objective</h4>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.<h4>Design, setting, and participants</h4>Two-sample 2\u2009\u00d7\u20092 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.<h4>Exposures</h4>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.<h4>Main outcomes and measures</h4>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.<h4>Results</h4>Data for 425\u202f354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229\u202f399 (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\u2009=\u2009.34 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\u2009=\u2009.83 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).<h4>Conclusions and relevance</h4>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.",
+    "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": "31416346",
     "doi": "https://doi.org/10.1161/circulationaha.119.041980",
@@ -15384,23 +15384,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1161/circulationaha.119.041980; doi:https://doi.org/10.1161/CIRCULATIONAHA.119.041980; html:https://europepmc.org/articles/PMC6749969; pdf:https://europepmc.org/articles/PMC6749969?pdf=render"
   },
-  {
-    "id": "36644660",
-    "doi": "https://doi.org/10.1177/20552076221128677",
-    "title": "Evaluation of prototype risk prediction tools for clinicians and people living with type 2 diabetes in North West London using the think aloud method.",
-    "authorString": "Gardner C, Wake D, Brodie D, Silverstein A, Young S, Cunningham S, Sainsbury C, Ilia M, Lucas A, Willis T, Halligan J.",
-    "authorAffiliations": "",
-    "journalTitle": "Digital health",
-    "pubYear": "2023",
-    "date": "2023-01-08",
-    "isOpenAccess": "Y",
-    "keywords": "Artificial intelligence; Internet; Diabetes; Qualitative; risk factors; Machine Learning; Health Informatics; Behaviour Change; Personalised Medicine; Digital Health",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1177/20552076221128677; doi:https://doi.org/10.1177/20552076221128677; html:https://europepmc.org/articles/PMC9834412; pdf:https://europepmc.org/articles/PMC9834412?pdf=render"
-  },
   {
     "id": "33704068",
     "doi": "https://doi.org/10.7554/elife.64827",
@@ -15418,6 +15401,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.7554/elife.64827; doi:https://doi.org/10.7554/eLife.64827; html:https://europepmc.org/articles/PMC8064756; pdf:https://europepmc.org/articles/PMC8064756?pdf=render"
   },
+  {
+    "id": "36644660",
+    "doi": "https://doi.org/10.1177/20552076221128677",
+    "title": "Evaluation of prototype risk prediction tools for clinicians and people living with type 2 diabetes in North West London using the think aloud method.",
+    "authorString": "Gardner C, Wake D, Brodie D, Silverstein A, Young S, Cunningham S, Sainsbury C, Ilia M, Lucas A, Willis T, Halligan J.",
+    "authorAffiliations": "",
+    "journalTitle": "Digital health",
+    "pubYear": "2023",
+    "date": "2023-01-08",
+    "isOpenAccess": "Y",
+    "keywords": "Artificial intelligence; Internet; Diabetes; Qualitative; risk factors; Machine Learning; Health Informatics; Behaviour Change; Personalised Medicine; Digital Health",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1177/20552076221128677; doi:https://doi.org/10.1177/20552076221128677; html:https://europepmc.org/articles/PMC9834412; pdf:https://europepmc.org/articles/PMC9834412?pdf=render"
+  },
   {
     "id": "32954362",
     "doi": "https://doi.org/10.1038/s43016-020-0093-y",
@@ -15452,23 +15452,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/2075-4426/12/8/1230/pdf?version=1659687887; doi:https://doi.org/10.3390/jpm12081230; html:https://europepmc.org/articles/PMC9410389; pdf:https://europepmc.org/articles/PMC9410389?pdf=render"
   },
-  {
-    "id": "37395705",
-    "doi": "https://doi.org/10.1167/tvst.12.7.3",
-    "title": "Reliability of Optical Coherence Tomography Angiography Retinal Blood Flow Analyses.",
-    "authorString": "Courtie EF, Gilani A, Capewell N, Kale AU, Hui BTK, Liu X, Montesano G, Teussink M, Denniston AK, Veenith T, Blanch RJ.",
-    "authorAffiliations": "",
-    "journalTitle": "Translational vision science & technology",
-    "pubYear": "2023",
-    "date": "2023-07-01",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.<h4>Translational relevance</h4>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.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1167/tvst.12.7.3; doi:https://doi.org/10.1167/tvst.12.7.3; html:https://europepmc.org/articles/PMC10324418; pdf:https://europepmc.org/articles/PMC10324418?pdf=render"
-  },
   {
     "id": "36581539",
     "doi": "https://doi.org/10.1016/j.jpsychires.2022.12.015",
@@ -15486,6 +15469,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jpsychires.2022.12.015; doi:https://doi.org/10.1016/j.jpsychires.2022.12.015"
   },
+  {
+    "id": "37395705",
+    "doi": "https://doi.org/10.1167/tvst.12.7.3",
+    "title": "Reliability of Optical Coherence Tomography Angiography Retinal Blood Flow Analyses.",
+    "authorString": "Courtie EF, Gilani A, Capewell N, Kale AU, Hui BTK, Liu X, Montesano G, Teussink M, Denniston AK, Veenith T, Blanch RJ.",
+    "authorAffiliations": "",
+    "journalTitle": "Translational vision science & technology",
+    "pubYear": "2023",
+    "date": "2023-07-01",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.<h4>Translational relevance</h4>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.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1167/tvst.12.7.3; doi:https://doi.org/10.1167/tvst.12.7.3; html:https://europepmc.org/articles/PMC10324418; pdf:https://europepmc.org/articles/PMC10324418?pdf=render"
+  },
   {
     "id": "33653161",
     "doi": "https://doi.org/10.1177/1740774520976617",
@@ -15503,23 +15503,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/1740774520976617; doi:https://doi.org/10.1177/1740774520976617; html:https://europepmc.org/articles/PMC8174009; pdf:https://europepmc.org/articles/PMC8174009?pdf=render"
   },
-  {
-    "id": "35132056",
-    "doi": "https://doi.org/10.1038/s41467-022-28252-5",
-    "title": "Genome-wide association meta-analysis identifies 29 new acne susceptibility loci.",
-    "authorString": "Mitchell BL, Saklatvala JR, Dand N, Hagenbeek FA, Li X, Min JL, Thomas L, Bartels M, Jan Hottenga J, Lupton MK, Boomsma DI, Dong X, Hveem K, L\u00f8set M, Martin NG, Barker JN, Han J, Smith CH, Renter\u00eda ME, Simpson MA.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature communications",
-    "pubYear": "2022",
-    "date": "2022-02-07",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial consequences. Here, we perform a GWAS meta-analysis comprising 20,165 individuals with acne from nine independent European ancestry cohorts. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches, we identify putative causal genes at several acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6% of the variance in acne liability in an independent cohort.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41467-022-28252-5.pdf; doi:https://doi.org/10.1038/s41467-022-28252-5; html:https://europepmc.org/articles/PMC8821634; pdf:https://europepmc.org/articles/PMC8821634?pdf=render"
-  },
   {
     "id": "34026049",
     "doi": "https://doi.org/10.12688/f1000research.25484.2",
@@ -15538,38 +15521,21 @@
     "urls": "pdf:https://f1000research.com/articles/9-1095/v2/pdf; doi:https://doi.org/10.12688/f1000research.25484.2; html:https://europepmc.org/articles/PMC8108552; pdf:https://europepmc.org/articles/PMC8108552?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": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1291; doi:https://doi.org/10.1002/ctm2.1291; html:https://europepmc.org/articles/PMC10280047; pdf:https://europepmc.org/articles/PMC10280047?pdf=render"
-  },
-  {
-    "id": "34435642",
-    "doi": "https://doi.org/10.1093/eurheartj/ehab350",
-    "title": "Evidence to support magnetic resonance conditional labelling of all pacemaker and defibrillator leads in patients with cardiac implantable electronic devices.",
-    "authorString": "Bhuva AN, Moralee R, Brunker T, Lascelles K, Cash L, Patel KP, Lowe M, Sekhri N, Alpendurada F, Pennell DJ, Schilling R, Lambiase PD, Chow A, Moon JC, Litt H, Baksi AJ, Manisty CH.",
+    "id": "35132056",
+    "doi": "https://doi.org/10.1038/s41467-022-28252-5",
+    "title": "Genome-wide association meta-analysis identifies 29 new acne susceptibility loci.",
+    "authorString": "Mitchell BL, Saklatvala JR, Dand N, Hagenbeek FA, Li X, Min JL, Thomas L, Bartels M, Jan Hottenga J, Lupton MK, Boomsma DI, Dong X, Hveem K, L\u00f8set M, Martin NG, Barker JN, Han J, Smith CH, Renter\u00eda ME, Simpson MA.",
     "authorAffiliations": "",
-    "journalTitle": "European heart journal",
+    "journalTitle": "Nature communications",
     "pubYear": "2022",
-    "date": "2022-07-01",
+    "date": "2022-02-07",
     "isOpenAccess": "Y",
-    "keywords": "Pacemaker; Magnetic Resonance Imaging; Defibrillator",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Aims</h4>Many cardiac pacemakers and defibrillators are not approved by regulators for magnetic resonance imaging (MRI). Even following generator exchange to an approved magnetic resonance (MR)-conditional model, many systems remain classified 'non-MR conditional' due to the leads. This classification makes patient access to MRI challenging, but there is no evidence of increased clinical risk. We compared the effect of MRI on non-MR conditional and MR-conditional pacemaker and defibrillator leads.<h4>Methods and results</h4>Patients undergoing clinical 1.5T MRI with pacemakers and defibrillators in three centres over 5 years were included. Magnetic resonance imaging protocols were similar for MR-conditional and non-MR conditional systems. Devices were interrogated pre- and immediately post-scan, and at follow-up, and adverse clinical events recorded. Lead parameter changes peri-scan were stratified by MR-conditional labelling. A total of 1148 MRI examinations were performed in 970 patients (54% non-MR conditional systems, 39% defibrillators, 15% pacing-dependent) with 2268 leads. There were no lead-related adverse clinical events, and no clinically significant immediate or late lead parameter changes following MRI in either MR-conditional or non-MR conditional leads. Small reductions in atrial and right ventricular sensed amplitudes and impedances were similar between groups, with no difference in the proportion of leads with parameter changes greater than pre-defined thresholds (7.1%, 95% confidence interval: 6.1-8.3).<h4>Conclusions</h4>There was no increased risk of MRI in patients with non-MR conditional pacemaker or defibrillator leads when following recommended protocols. Standardizing MR conditions for all leads would significantly improve access to MRI by enabling patients to be scanned in non-specialist centres, with no discernible incremental risk.",
+    "abstract": "Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial consequences. Here, we perform a GWAS meta-analysis comprising 20,165 individuals with acne from nine independent European ancestry cohorts. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches, we identify putative causal genes at several acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6% of the variance in acne liability in an independent cohort.",
     "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehab350/39932149/ehab350.pdf; doi:https://doi.org/10.1093/eurheartj/ehab350; html:https://europepmc.org/articles/PMC9259370; pdf:https://europepmc.org/articles/PMC9259370?pdf=render"
+    "urls": "pdf:https://www.nature.com/articles/s41467-022-28252-5.pdf; doi:https://doi.org/10.1038/s41467-022-28252-5; html:https://europepmc.org/articles/PMC8821634; pdf:https://europepmc.org/articles/PMC8821634?pdf=render"
   },
   {
     "id": "32665523",
@@ -15589,21 +15555,38 @@
     "urls": "html:https://journals.lww.com/jhypertension/Fulltext/2020/12000/Association_of_SBP_and_BMI_with_cognitive_and.22.aspx; doi:https://doi.org/10.1097/HJH.0000000000002579"
   },
   {
-    "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 .",
+    "id": "34435642",
+    "doi": "https://doi.org/10.1093/eurheartj/ehab350",
+    "title": "Evidence to support magnetic resonance conditional labelling of all pacemaker and defibrillator leads in patients with cardiac implantable electronic devices.",
+    "authorString": "Bhuva AN, Moralee R, Brunker T, Lascelles K, Cash L, Patel KP, Lowe M, Sekhri N, Alpendurada F, Pennell DJ, Schilling R, Lambiase PD, Chow A, Moon JC, Litt H, Baksi AJ, Manisty CH.",
     "authorAffiliations": "",
-    "journalTitle": "BMJ medicine",
+    "journalTitle": "European heart journal",
+    "pubYear": "2022",
+    "date": "2022-07-01",
+    "isOpenAccess": "Y",
+    "keywords": "Pacemaker; Magnetic Resonance Imaging; Defibrillator",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>Many cardiac pacemakers and defibrillators are not approved by regulators for magnetic resonance imaging (MRI). Even following generator exchange to an approved magnetic resonance (MR)-conditional model, many systems remain classified 'non-MR conditional' due to the leads. This classification makes patient access to MRI challenging, but there is no evidence of increased clinical risk. We compared the effect of MRI on non-MR conditional and MR-conditional pacemaker and defibrillator leads.<h4>Methods and results</h4>Patients undergoing clinical 1.5T MRI with pacemakers and defibrillators in three centres over 5 years were included. Magnetic resonance imaging protocols were similar for MR-conditional and non-MR conditional systems. Devices were interrogated pre- and immediately post-scan, and at follow-up, and adverse clinical events recorded. Lead parameter changes peri-scan were stratified by MR-conditional labelling. A total of 1148 MRI examinations were performed in 970 patients (54% non-MR conditional systems, 39% defibrillators, 15% pacing-dependent) with 2268 leads. There were no lead-related adverse clinical events, and no clinically significant immediate or late lead parameter changes following MRI in either MR-conditional or non-MR conditional leads. Small reductions in atrial and right ventricular sensed amplitudes and impedances were similar between groups, with no difference in the proportion of leads with parameter changes greater than pre-defined thresholds (7.1%, 95% confidence interval: 6.1-8.3).<h4>Conclusions</h4>There was no increased risk of MRI in patients with non-MR conditional pacemaker or defibrillator leads when following recommended protocols. Standardizing MR conditions for all leads would significantly improve access to MRI by enabling patients to be scanned in non-specialist centres, with no discernible incremental risk.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehab350/39932149/ehab350.pdf; doi:https://doi.org/10.1093/eurheartj/ehab350; html:https://europepmc.org/articles/PMC9259370; pdf:https://europepmc.org/articles/PMC9259370?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": "2023-02-14",
+    "date": "2023-06-01",
     "isOpenAccess": "Y",
-    "keywords": "epidemiology; Heart Failure; Cardiology; Covid-19",
+    "keywords": "Obesity; Population admixture; body mass index; Polygenic Risk Score; Trans-ethnic",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Objective</h4>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.<h4>Design</h4>Registry based observational study.<h4>Setting</h4>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.<h4>Participants</h4>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).<h4>Main outcome measures</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000245.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render"
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1291; doi:https://doi.org/10.1002/ctm2.1291; html:https://europepmc.org/articles/PMC10280047; pdf:https://europepmc.org/articles/PMC10280047?pdf=render"
   },
   {
     "id": "32908801",
@@ -15622,6 +15605,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1167/tvst.9.9.38; doi:https://doi.org/10.1167/tvst.9.9.38; html:https://europepmc.org/articles/PMC7453042; pdf:https://europepmc.org/articles/PMC7453042?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": "<h4>Objective</h4>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.<h4>Design</h4>Registry based observational study.<h4>Setting</h4>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.<h4>Participants</h4>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).<h4>Main outcome measures</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000245.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render"
+  },
   {
     "id": "33692093",
     "doi": "https://doi.org/10.1136/heartjnl-2020-318557",
@@ -15673,23 +15673,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41598-022-16639-9.pdf; doi:https://doi.org/10.1038/s41598-022-16639-9; html:https://europepmc.org/articles/PMC9329281; pdf:https://europepmc.org/articles/PMC9329281?pdf=render"
   },
-  {
-    "id": "34985035",
-    "doi": "https://doi.org/10.1097/htr.0000000000000741",
-    "title": "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.",
-    "authorString": "Gabbe BJ, Braaf S, Cameron PA, Berecki-Gisolf J.",
-    "authorAffiliations": "",
-    "journalTitle": "The Journal of head trauma rehabilitation",
-    "pubYear": "2022",
-    "date": "2022-01-01",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>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.<h4>Setting</h4>Victoria, Australia.<h4>Participants</h4>Adult (\u226518 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.<h4>Design</h4>Registry-based cohort study.<h4>Main measures</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>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.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1097/HTR.0000000000000741"
-  },
   {
     "id": "32060159",
     "doi": "https://doi.org/10.1136/bmjopen-2019-034396",
@@ -15707,6 +15690,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/2/e034396.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-034396; html:https://europepmc.org/articles/PMC7045100; pdf:https://europepmc.org/articles/PMC7045100?pdf=render"
   },
+  {
+    "id": "34985035",
+    "doi": "https://doi.org/10.1097/htr.0000000000000741",
+    "title": "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.",
+    "authorString": "Gabbe BJ, Braaf S, Cameron PA, Berecki-Gisolf J.",
+    "authorAffiliations": "",
+    "journalTitle": "The Journal of head trauma rehabilitation",
+    "pubYear": "2022",
+    "date": "2022-01-01",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>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.<h4>Setting</h4>Victoria, Australia.<h4>Participants</h4>Adult (\u226518 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.<h4>Design</h4>Registry-based cohort study.<h4>Main measures</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>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.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1097/HTR.0000000000000741"
+  },
   {
     "id": "37827807",
     "doi": "https://doi.org/10.1136/bmjresp-2023-001806",
@@ -15741,23 +15741,6 @@
     "laySummary": "",
     "urls": "html:https://journals.lww.com/epidem/Fulltext/2022/01000/The_Authors_Respond.22.aspx; doi:https://doi.org/10.1097/EDE.0000000000001429"
   },
-  {
-    "id": "37645022",
-    "doi": "https://doi.org/10.1183/20734735.0058-2023",
-    "title": "The impact of poor housing and indoor air quality on respiratory health in children.",
-    "authorString": "Holden KA, Lee AR, Hawcutt DB, Sinha IP.",
-    "authorAffiliations": "",
-    "journalTitle": "Breathe (Sheffield, England)",
-    "pubYear": "2023",
-    "date": "2023-06-01",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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.<h4>Educational aims</h4>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.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1183/20734735.0058-2023; html:https://europepmc.org/articles/PMC10461733; pdf:https://europepmc.org/articles/PMC10461733?pdf=render"
-  },
   {
     "id": "34671274",
     "doi": "https://doi.org/10.3389/fphys.2021.730736",
@@ -15775,6 +15758,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fphys.2021.730736/pdf; doi:https://doi.org/10.3389/fphys.2021.730736; html:https://europepmc.org/articles/PMC8521153; pdf:https://europepmc.org/articles/PMC8521153?pdf=render"
   },
+  {
+    "id": "37645022",
+    "doi": "https://doi.org/10.1183/20734735.0058-2023",
+    "title": "The impact of poor housing and indoor air quality on respiratory health in children.",
+    "authorString": "Holden KA, Lee AR, Hawcutt DB, Sinha IP.",
+    "authorAffiliations": "",
+    "journalTitle": "Breathe (Sheffield, England)",
+    "pubYear": "2023",
+    "date": "2023-06-01",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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.<h4>Educational aims</h4>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.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1183/20734735.0058-2023; html:https://europepmc.org/articles/PMC10461733; pdf:https://europepmc.org/articles/PMC10461733?pdf=render"
+  },
   {
     "id": "37532769",
     "doi": "https://doi.org/10.1038/s42003-023-05171-9",
@@ -15843,6 +15843,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1093/eurheartj/ehac650"
   },
+  {
+    "id": "32946551",
+    "doi": "https://doi.org/10.1093/ageing/afaa158",
+    "title": "Do home modifications reduce care home admissions for older people? A matched control evaluation of the Care & Repair Cymru service in Wales.",
+    "authorString": "Hollinghurst J, Fry R, Akbari A, Watkins A, Williams N, Hillcoat-Nall\u00e9tamby S, Lyons RA, Clegg A, Rodgers SE.",
+    "authorAffiliations": "",
+    "journalTitle": "Age and ageing",
+    "pubYear": "2020",
+    "date": "2020-10-01",
+    "isOpenAccess": "Y",
+    "keywords": "Frailty; Interventions; Older People; Care Homes; Administrative Data",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>home advice and modification interventions aim to promote independent living for those living in the community, but quantitative evidence of their effectiveness is limited.<h4>Aim</h4>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.<h4>Study design and setting</h4>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.<h4>Methods</h4>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\u00a0=\u200993,863) compared to a matched control group (N\u00a0=\u200993,863). Kaplan-Meier curves were used to investigate time to a care home admission.<h4>Results</h4>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)].<h4>Conclusions</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/ageing/article-pdf/49/6/1056/33993322/afaa158.pdf; doi:https://doi.org/10.1093/ageing/afaa158; html:https://europepmc.org/articles/PMC7583515; pdf:https://europepmc.org/articles/PMC7583515?pdf=render"
+  },
   {
     "id": "34516619",
     "doi": "https://doi.org/10.1093/ehjci/jeab178",
@@ -15861,21 +15878,21 @@
     "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeab178/40357499/jeab178.pdf; doi:https://doi.org/10.1093/ehjci/jeab178; html:https://europepmc.org/articles/PMC9584619; pdf:https://europepmc.org/articles/PMC9584619?pdf=render"
   },
   {
-    "id": "32946551",
-    "doi": "https://doi.org/10.1093/ageing/afaa158",
-    "title": "Do home modifications reduce care home admissions for older people? A matched control evaluation of the Care & Repair Cymru service in Wales.",
-    "authorString": "Hollinghurst J, Fry R, Akbari A, Watkins A, Williams N, Hillcoat-Nall\u00e9tamby S, Lyons RA, Clegg A, Rodgers SE.",
+    "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": "Age and ageing",
+    "journalTitle": "JMIR research protocols",
     "pubYear": "2020",
-    "date": "2020-10-01",
+    "date": "2020-08-07",
     "isOpenAccess": "Y",
-    "keywords": "Frailty; Interventions; Older People; Care Homes; Administrative Data",
+    "keywords": "Alcohol; Engagement; Mhealth; Mobile Health; Excessive Alcohol Consumption; Smartphone App; Push Notifications; Digital Behavior Change; Micro-randomized Trial",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>home advice and modification interventions aim to promote independent living for those living in the community, but quantitative evidence of their effectiveness is limited.<h4>Aim</h4>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.<h4>Study design and setting</h4>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.<h4>Methods</h4>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\u00a0=\u200993,863) compared to a matched control group (N\u00a0=\u200993,863). Kaplan-Meier curves were used to investigate time to a care home admission.<h4>Results</h4>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)].<h4>Conclusions</h4>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.",
+    "abstract": "<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>International registered report identifier (irrid)</h4>DERR1-10.2196/18690.",
     "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/ageing/article-pdf/49/6/1056/33993322/afaa158.pdf; doi:https://doi.org/10.1093/ageing/afaa158; html:https://europepmc.org/articles/PMC7583515; pdf:https://europepmc.org/articles/PMC7583515?pdf=render"
+    "urls": "pdf:https://www.researchprotocols.org/2020/8/e18690/PDF; doi:https://doi.org/10.2196/18690; html:https://europepmc.org/articles/PMC7442945"
   },
   {
     "id": "37751239",
@@ -15894,23 +15911,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.2196/49438; html:https://europepmc.org/articles/PMC10565627"
   },
-  {
-    "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": "<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>International registered report identifier (irrid)</h4>DERR1-10.2196/18690.",
-    "laySummary": "",
-    "urls": "pdf:https://www.researchprotocols.org/2020/8/e18690/PDF; doi:https://doi.org/10.2196/18690; html:https://europepmc.org/articles/PMC7442945"
-  },
   {
     "id": "34328624",
     "doi": "https://doi.org/10.1007/s11695-021-05493-9",
@@ -15928,23 +15928,6 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11695-021-05493-9.pdf; doi:https://doi.org/10.1007/s11695-021-05493-9; html:https://europepmc.org/articles/PMC8323543; pdf:https://europepmc.org/articles/PMC8323543?pdf=render"
   },
-  {
-    "id": "37516479",
-    "doi": "https://doi.org/10.1016/s2468-2667(23)00126-3",
-    "title": "Insights from linking police domestic abuse data and health data in South Wales, UK: a linked routine data analysis using decision tree classification.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "The Lancet. Public health",
-    "pubYear": "2023",
-    "date": "2023-08-01",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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\u00b78%) were female. Within a year of a domestic abuse incident, 3650 (41\u00b79%) individuals had an outcome. Factors associated with experiencing an outcome within 12 months of the PPN included younger victim age (hazard ratio 1\u00b7183 [95% CI 1\u00b7053-1\u00b7329], p=0\u00b70048), further PPN submissions after the initial referral (1\u00b7383 [1\u00b7295-1\u00b7476]; p<0\u00b70001), injury at the scene (1\u00b7484 [1\u00b7368-1\u00b7609]; p<0\u00b70001), assessed high risk (1\u00b7600 [1\u00b7444-1\u00b7773]; p<0\u00b70001), referral to other agencies (1\u00b7518 [1\u00b7358-1\u00b7697]; p<0\u00b70001), history of violence (1\u00b7229 [1\u00b7134-1\u00b7333]; p<0\u00b70001), attempted strangulation (1\u00b7311 [1\u00b7148-1\u00b7497]; p<0\u00b70001), and pregnancy (1\u00b7372 [1\u00b7142-1\u00b7648]; p=0\u00b70007). 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.<h4>Interpretation</h4>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.<h4>Funding</h4>National Institute for Health Research.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/S2468-2667(23)00126-3"
-  },
   {
     "id": "34798287",
     "doi": "https://doi.org/10.1016/j.jclinepi.2021.11.023",
@@ -15962,6 +15945,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.jclinepi.com/article/S0895435621003759/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.11.023"
   },
+  {
+    "id": "37516479",
+    "doi": "https://doi.org/10.1016/s2468-2667(23)00126-3",
+    "title": "Insights from linking police domestic abuse data and health data in South Wales, UK: a linked routine data analysis using decision tree classification.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "The Lancet. Public health",
+    "pubYear": "2023",
+    "date": "2023-08-01",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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\u00b78%) were female. Within a year of a domestic abuse incident, 3650 (41\u00b79%) individuals had an outcome. Factors associated with experiencing an outcome within 12 months of the PPN included younger victim age (hazard ratio 1\u00b7183 [95% CI 1\u00b7053-1\u00b7329], p=0\u00b70048), further PPN submissions after the initial referral (1\u00b7383 [1\u00b7295-1\u00b7476]; p<0\u00b70001), injury at the scene (1\u00b7484 [1\u00b7368-1\u00b7609]; p<0\u00b70001), assessed high risk (1\u00b7600 [1\u00b7444-1\u00b7773]; p<0\u00b70001), referral to other agencies (1\u00b7518 [1\u00b7358-1\u00b7697]; p<0\u00b70001), history of violence (1\u00b7229 [1\u00b7134-1\u00b7333]; p<0\u00b70001), attempted strangulation (1\u00b7311 [1\u00b7148-1\u00b7497]; p<0\u00b70001), and pregnancy (1\u00b7372 [1\u00b7142-1\u00b7648]; p=0\u00b70007). 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.<h4>Interpretation</h4>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.<h4>Funding</h4>National Institute for Health Research.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/S2468-2667(23)00126-3"
+  },
   {
     "id": "34088700",
     "doi": "https://doi.org/10.2337/dc20-2518",
@@ -15996,23 +15996,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e047101.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-047101; html:https://europepmc.org/articles/PMC7817800; pdf:https://europepmc.org/articles/PMC7817800?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-omics<sup>1</sup>. Here we examine a large cohort (the INTERVAL study<sup>2</sup>; 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 Biobank<sup>3</sup> 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": "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; doi:https://doi.org/10.1038/s41586-023-05844-9; html:https://europepmc.org/articles/PMC10323211; pdf:https://europepmc.org/articles/PMC10323211?pdf=render; doi:https://doi.org/10.1038/s41586-023-05844-9"
-  },
   {
     "id": "37649471",
     "doi": "https://doi.org/10.23889/ijpds.v6i3.1705",
@@ -16030,6 +16013,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.23889/ijpds.v6i3.1705; html:https://europepmc.org/articles/PMC10464864; pdf:https://europepmc.org/articles/PMC10464864?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-omics<sup>1</sup>. Here we examine a large cohort (the INTERVAL study<sup>2</sup>; 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 Biobank<sup>3</sup> 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": "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; doi:https://doi.org/10.1038/s41586-023-05844-9; html:https://europepmc.org/articles/PMC10323211; pdf:https://europepmc.org/articles/PMC10323211?pdf=render; doi:https://doi.org/10.1038/s41586-023-05844-9"
+  },
   {
     "id": "36707908",
     "doi": "https://doi.org/10.1186/s13643-023-02173-w",
@@ -16183,23 +16183,6 @@
     "laySummary": "",
     "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa56833/Download/56833__19829__9b0bb77f67e84342b525fbccaba98e67.pdf; doi:https://doi.org/10.1080/02640414.2021.1928409"
   },
-  {
-    "id": "36942567",
-    "doi": "https://doi.org/10.1161/circep.122.011585",
-    "title": "Outcomes of Early Rhythm Control Therapy in Patients With Atrial Fibrillation and a High Comorbidity Burden in Large Real-World Cohorts.",
-    "authorString": "Dickow J, Kany S, Roth Cardoso V, Ellinor PT, Gkoutos GV, Van Houten HK, Kirchhof P, Metzner A, Noseworthy PA, Yao X, Rillig A.",
-    "authorAffiliations": "",
-    "journalTitle": "Circulation. Arrhythmia and electrophysiology",
-    "pubYear": "2023",
-    "date": "2023-03-21",
-    "isOpenAccess": "N",
-    "keywords": "Atrial fibrillation; Stroke; Catheter ablation; Heart Failure; Comorbidity",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>We identified 109\u2009739 patients with newly diagnosed atrial fibrillation in a large United States deidentified administrative claims database (OptumLabs) and 11\u2009625 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 (CHA<sub>2</sub>DS<sub>2</sub>-VASc score \u22654); (2) ERC and lower comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-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 (CHA<sub>2</sub>DS<sub>2</sub>-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.<h4>Results</h4>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]; <i>P</i>=0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63-0.94]; <i>P</i>=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]; <i>P</i>=0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83-1.06]; <i>P</i>=0.310). The comorbidity burden interacted with ERC in the UKB (interaction- <i>P</i>=0.027) but not in OptumLabs (interaction-<i>P</i>=0.720). ERC was not associated with an increased risk for the primary safety outcome.<h4>Conclusions</h4>ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score \u22654).",
-    "laySummary": "",
-    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCEP.122.011585; doi:https://doi.org/10.1161/CIRCEP.122.011585"
-  },
   {
     "id": "34610958",
     "doi": "https://doi.org/10.1136/emermed-2019-209368",
@@ -16234,6 +16217,23 @@
     "laySummary": "",
     "urls": "pdf:https://discovery.ucl.ac.uk/10110375/1/Syed%20and%20Gilbert%20%282020%29.%20Are%20children%20who%20are%20home%20from%20school%20at%20an%20increased%20risk%20of%20child%20maltreatment.pdf; doi:https://doi.org/10.1093/pubmed/fdaa115"
   },
+  {
+    "id": "36942567",
+    "doi": "https://doi.org/10.1161/circep.122.011585",
+    "title": "Outcomes of Early Rhythm Control Therapy in Patients With Atrial Fibrillation and a High Comorbidity Burden in Large Real-World Cohorts.",
+    "authorString": "Dickow J, Kany S, Roth Cardoso V, Ellinor PT, Gkoutos GV, Van Houten HK, Kirchhof P, Metzner A, Noseworthy PA, Yao X, Rillig A.",
+    "authorAffiliations": "",
+    "journalTitle": "Circulation. Arrhythmia and electrophysiology",
+    "pubYear": "2023",
+    "date": "2023-03-21",
+    "isOpenAccess": "N",
+    "keywords": "Atrial fibrillation; Stroke; Catheter ablation; Heart Failure; Comorbidity",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>We identified 109\u2009739 patients with newly diagnosed atrial fibrillation in a large United States deidentified administrative claims database (OptumLabs) and 11\u2009625 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 (CHA<sub>2</sub>DS<sub>2</sub>-VASc score \u22654); (2) ERC and lower comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-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 (CHA<sub>2</sub>DS<sub>2</sub>-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.<h4>Results</h4>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]; <i>P</i>=0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63-0.94]; <i>P</i>=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]; <i>P</i>=0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83-1.06]; <i>P</i>=0.310). The comorbidity burden interacted with ERC in the UKB (interaction- <i>P</i>=0.027) but not in OptumLabs (interaction-<i>P</i>=0.720). ERC was not associated with an increased risk for the primary safety outcome.<h4>Conclusions</h4>ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score \u22654).",
+    "laySummary": "",
+    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCEP.122.011585; doi:https://doi.org/10.1161/CIRCEP.122.011585"
+  },
   {
     "id": "31329239",
     "doi": "https://doi.org/10.1093/jamia/ocz105",
@@ -16421,23 +16421,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.1016032/pdf; doi:https://doi.org/10.3389/fcvm.2022.1016032; html:https://europepmc.org/articles/PMC9681217; pdf:https://europepmc.org/articles/PMC9681217?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": "<h4>Introduction</h4>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).<h4>Methods</h4>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).<h4>Results</h4>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).<h4>Conclusion</h4>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": "34506014",
     "doi": "https://doi.org/10.1007/s11605-020-04612-8",
@@ -16455,6 +16438,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1007/s11605-020-04612-8"
   },
+  {
+    "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": "<h4>Introduction</h4>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).<h4>Methods</h4>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).<h4>Results</h4>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).<h4>Conclusion</h4>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": "35440465",
     "doi": "https://doi.org/10.3399/bjgp.2021.0689",
@@ -16540,23 +16540,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14444; doi:https://doi.org/10.1002/ehf2.14444; html:https://europepmc.org/articles/PMC10375103; pdf:https://europepmc.org/articles/PMC10375103?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": "<h4>Aims</h4>To determine differences in the management of diabetic kidney disease (DKD) relevant to patient sex, ethnicity and socio-economic group in UK primary care.<h4>Methods</h4>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.<h4>Results</h4>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), HbA<sub>1c</sub> : 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 HbA<sub>1c</sub> : 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).<h4>Conclusions</h4>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; doi:https://doi.org/10.1111/dme.15153"
-  },
   {
     "id": "35642867",
     "doi": "https://doi.org/10.1111/bjhp.12606",
@@ -16574,6 +16557,23 @@
     "laySummary": "",
     "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa60128/Download/60128__24479__4d74009536e649b0b17180e2bfd80435.pdf; doi:https://doi.org/10.1111/bjhp.12606; html:https://europepmc.org/articles/PMC9347957; pdf:https://europepmc.org/articles/PMC9347957?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": "<h4>Aims</h4>To determine differences in the management of diabetic kidney disease (DKD) relevant to patient sex, ethnicity and socio-economic group in UK primary care.<h4>Methods</h4>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.<h4>Results</h4>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), HbA<sub>1c</sub> : 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 HbA<sub>1c</sub> : 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).<h4>Conclusions</h4>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; doi:https://doi.org/10.1111/dme.15153"
+  },
   {
     "id": "37669576",
     "doi": "https://doi.org/10.1016/j.schres.2023.08.024",
@@ -16608,6 +16608,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1080/09638288.2021.2008526"
   },
+  {
+    "id": "33707775",
+    "doi": "https://doi.org/10.1038/s41591-021-01266-0",
+    "title": "Plasma metabolites to profile pathways in noncommunicable disease multimorbidity.",
+    "authorString": "Pietzner M, Stewart ID, Raffler J, Khaw KT, Michelotti GA, Kastenm\u00fcller G, Wareham NJ, Langenberg C.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature medicine",
+    "pubYear": "2021",
+    "date": "2021-03-11",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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.",
+    "laySummary": "",
+    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127079; 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"
+  },
   {
     "id": "37658971",
     "doi": "https://doi.org/10.1007/s11897-023-00626-w",
@@ -16642,23 +16659,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1038/s41591-023-02608-w"
   },
-  {
-    "id": "33707775",
-    "doi": "https://doi.org/10.1038/s41591-021-01266-0",
-    "title": "Plasma metabolites to profile pathways in noncommunicable disease multimorbidity.",
-    "authorString": "Pietzner M, Stewart ID, Raffler J, Khaw KT, Michelotti GA, Kastenm\u00fcller G, Wareham NJ, Langenberg C.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature medicine",
-    "pubYear": "2021",
-    "date": "2021-03-11",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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.",
-    "laySummary": "",
-    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127079; 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"
-  },
   {
     "id": "34270458",
     "doi": "https://doi.org/10.4269/ajtmh.21-0482",
@@ -16727,6 +16727,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-019-4286-8; doi:https://doi.org/10.1186/s12913-019-4286-8; html:https://europepmc.org/articles/PMC6720086; pdf:https://europepmc.org/articles/PMC6720086?pdf=render"
   },
+  {
+    "id": "32908284",
+    "doi": "https://doi.org/10.1038/s41591-020-1037-7",
+    "title": "Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension.",
+    "authorString": "Cruz Rivera S, Liu X, Chan AW, Denniston AK, Calvert MJ, SPIRIT-AI and CONSORT-AI Working Group, SPIRIT-AI and CONSORT-AI Steering Group, SPIRIT-AI and CONSORT-AI Consensus Group.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature medicine",
+    "pubYear": "2020",
+    "date": "2020-09-09",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41591-020-1037-7.pdf; doi:https://doi.org/10.1038/s41591-020-1037-7; html:https://europepmc.org/articles/PMC7598944; pdf:https://europepmc.org/articles/PMC7598944?pdf=render"
+  },
   {
     "id": "34912046",
     "doi": "https://doi.org/10.1038/s41366-021-01048-1",
@@ -16745,10 +16762,10 @@
     "urls": "pdf:https://www.nature.com/articles/s41366-021-01048-1.pdf; doi:https://doi.org/10.1038/s41366-021-01048-1; html:https://europepmc.org/articles/PMC8671878; pdf:https://europepmc.org/articles/PMC8671878?pdf=render"
   },
   {
-    "id": "32908284",
-    "doi": "https://doi.org/10.1038/s41591-020-1037-7",
-    "title": "Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension.",
-    "authorString": "Cruz Rivera S, Liu X, Chan AW, Denniston AK, Calvert MJ, SPIRIT-AI and CONSORT-AI Working Group, SPIRIT-AI and CONSORT-AI Steering Group, SPIRIT-AI and CONSORT-AI Consensus Group.",
+    "id": "32908283",
+    "doi": "https://doi.org/10.1038/s41591-020-1034-x",
+    "title": "Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI extension.",
+    "authorString": "Liu X, Cruz Rivera S, Moher D, Calvert MJ, Denniston AK, SPIRIT-AI and CONSORT-AI Working Group.",
     "authorAffiliations": "",
     "journalTitle": "Nature medicine",
     "pubYear": "2020",
@@ -16757,26 +16774,26 @@
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "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.",
+    "abstract": "The CONSORT 2010 statement provides minimum guidelines for reporting randomized 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.",
     "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41591-020-1037-7.pdf; doi:https://doi.org/10.1038/s41591-020-1037-7; html:https://europepmc.org/articles/PMC7598944; pdf:https://europepmc.org/articles/PMC7598944?pdf=render"
+    "urls": "pdf:https://www.nature.com/articles/s41591-020-1034-x.pdf; doi:https://doi.org/10.1038/s41591-020-1034-x; html:https://europepmc.org/articles/PMC7598943; pdf:https://europepmc.org/articles/PMC7598943?pdf=render"
   },
   {
-    "id": "32908283",
-    "doi": "https://doi.org/10.1038/s41591-020-1034-x",
-    "title": "Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI extension.",
-    "authorString": "Liu X, Cruz Rivera S, Moher D, Calvert MJ, Denniston AK, SPIRIT-AI and CONSORT-AI Working Group.",
+    "id": "33678589",
+    "doi": "https://doi.org/10.1016/s2589-7500(20)30317-4",
+    "title": "Health data poverty: an assailable barrier to equitable digital health care.",
+    "authorString": "Ibrahim H, Liu X, Zariffa N, Morris AD, Denniston AK.",
     "authorAffiliations": "",
-    "journalTitle": "Nature medicine",
-    "pubYear": "2020",
-    "date": "2020-09-09",
-    "isOpenAccess": "Y",
+    "journalTitle": "The Lancet. Digital health",
+    "pubYear": "2021",
+    "date": "2021-03-04",
+    "isOpenAccess": "N",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "The CONSORT 2010 statement provides minimum guidelines for reporting randomized 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.",
+    "abstract": "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.",
     "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41591-020-1034-x.pdf; doi:https://doi.org/10.1038/s41591-020-1034-x; html:https://europepmc.org/articles/PMC7598943; pdf:https://europepmc.org/articles/PMC7598943?pdf=render"
+    "urls": "pdf:http://www.thelancet.com/article/S2589750020303174/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30317-4"
   },
   {
     "id": "36932161",
@@ -16795,23 +16812,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41433-023-02478-z.pdf; doi:https://doi.org/10.1038/s41433-023-02478-z; html:https://europepmc.org/articles/PMC10022552; pdf:https://europepmc.org/articles/PMC10022552?pdf=render"
   },
-  {
-    "id": "33678589",
-    "doi": "https://doi.org/10.1016/s2589-7500(20)30317-4",
-    "title": "Health data poverty: an assailable barrier to equitable digital health care.",
-    "authorString": "Ibrahim H, Liu X, Zariffa N, Morris AD, Denniston AK.",
-    "authorAffiliations": "",
-    "journalTitle": "The Lancet. Digital health",
-    "pubYear": "2021",
-    "date": "2021-03-04",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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.",
-    "laySummary": "",
-    "urls": "pdf:http://www.thelancet.com/article/S2589750020303174/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30317-4"
-  },
   {
     "id": "34053271",
     "doi": "https://doi.org/10.1098/rstb.2020.0266",
@@ -16846,23 +16846,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1167/tvst.9.13.5; doi:https://doi.org/10.1167/tvst.9.13.5; html:https://europepmc.org/articles/PMC7718823; pdf:https://europepmc.org/articles/PMC7718823?pdf=render"
   },
-  {
-    "id": "34859617",
-    "doi": "https://doi.org/10.1002/edm2.309",
-    "title": "The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "Endocrinology, diabetes & metabolism",
-    "pubYear": "2022",
-    "date": "2021-12-03",
-    "isOpenAccess": "Y",
-    "keywords": "Diabetes; Complications; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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\u00a0=\u00a00.093) and 1.18 (95% CI 0.90-1.54, p\u00a0=\u00a00.226) in DM+C and DM-C, respectively.<h4>Conclusions</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/edm2.309; doi:https://doi.org/10.1002/edm2.309; html:https://europepmc.org/articles/PMC8754243; pdf:https://europepmc.org/articles/PMC8754243?pdf=render"
-  },
   {
     "id": "31748543",
     "doi": "https://doi.org/10.1038/s41398-019-0613-4",
@@ -16880,6 +16863,23 @@
     "laySummary": "This study aimed to identify parts of the genome that cause chronic pain (self-reported as lasting 3+ months), or major depressive disorder (MDD) and to investigate if these two conditions share common genetic causes. They identified 11 different parts of the genome where a specific change (SNP) was linked to chronic pain (6 parts of the genome), MDD (9 parts), or symptoms shared by both conditions (4 parts). The results also suggest that one of parts of the genome that causes chronic pain may influence the development of MDD (but not vice versa), including through lifestyle factors.",
     "urls": "pdf:https://www.nature.com/articles/s41398-019-0613-4.pdf; doi:https://doi.org/10.1038/s41398-019-0613-4; html:https://europepmc.org/articles/PMC6868167; pdf:https://europepmc.org/articles/PMC6868167?pdf=render"
   },
+  {
+    "id": "34859617",
+    "doi": "https://doi.org/10.1002/edm2.309",
+    "title": "The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "Endocrinology, diabetes & metabolism",
+    "pubYear": "2022",
+    "date": "2021-12-03",
+    "isOpenAccess": "Y",
+    "keywords": "Diabetes; Complications; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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\u00a0=\u00a00.093) and 1.18 (95% CI 0.90-1.54, p\u00a0=\u00a00.226) in DM+C and DM-C, respectively.<h4>Conclusions</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/edm2.309; doi:https://doi.org/10.1002/edm2.309; html:https://europepmc.org/articles/PMC8754243; pdf:https://europepmc.org/articles/PMC8754243?pdf=render"
+  },
   {
     "id": "33085509",
     "doi": "https://doi.org/10.7326/m20-4986",
@@ -17084,23 +17084,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2589750020302193/pdf; 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": "37311637",
-    "doi": "https://doi.org/10.1136/bmjopen-2023-071973",
-    "title": "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.",
-    "authorString": "Etoori D, Park MH, Blackburn RM, Fitzsimons KJ, Butterworth S, Medina J, Mc Grath-Lone L, Russell C, van der Meulen J.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2023",
-    "date": "2023-06-13",
-    "isOpenAccess": "Y",
-    "keywords": "epidemiology; Paediatric Surgery; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>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).<h4>Design</h4>National observational study of administrative hospital data.<h4>Setting</h4>National Health Service hospitals in England.<h4>Study population</h4>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).<h4>Main exposure</h4>Procedure date (2020/2021 vs 2019/2020).<h4>Main outcomes</h4>Numbers and timing (age in months) of first primary CLP procedures.<h4>Results</h4>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\u2009months (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.<h4>Conclusion</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/6/e071973.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-071973; html:https://europepmc.org/articles/PMC10276964; pdf:https://europepmc.org/articles/PMC10276964?pdf=render"
-  },
   {
     "id": "35271547",
     "doi": "https://doi.org/10.1097/ta.0000000000003592",
@@ -17118,6 +17101,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1097/TA.0000000000003592"
   },
+  {
+    "id": "37311637",
+    "doi": "https://doi.org/10.1136/bmjopen-2023-071973",
+    "title": "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.",
+    "authorString": "Etoori D, Park MH, Blackburn RM, Fitzsimons KJ, Butterworth S, Medina J, Mc Grath-Lone L, Russell C, van der Meulen J.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2023",
+    "date": "2023-06-13",
+    "isOpenAccess": "Y",
+    "keywords": "epidemiology; Paediatric Surgery; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>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).<h4>Design</h4>National observational study of administrative hospital data.<h4>Setting</h4>National Health Service hospitals in England.<h4>Study population</h4>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).<h4>Main exposure</h4>Procedure date (2020/2021 vs 2019/2020).<h4>Main outcomes</h4>Numbers and timing (age in months) of first primary CLP procedures.<h4>Results</h4>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\u2009months (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.<h4>Conclusion</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/6/e071973.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-071973; html:https://europepmc.org/articles/PMC10276964; pdf:https://europepmc.org/articles/PMC10276964?pdf=render"
+  },
   {
     "id": "37118525",
     "doi": "https://doi.org/10.1038/s43587-022-00328-3",
@@ -17254,23 +17254,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.science.org/history/7d0b03b2-b465-410e-a40d-7300157d8b54/science.abl9551.v1.pdf; doi:https://doi.org/10.1126/science.abl9551"
   },
-  {
-    "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": "<h4>Aim</h4>This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.<h4>Methods</h4>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.<h4>Results</h4>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)].<h4>Conclusion</h4>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": "pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf; doi:https://doi.org/10.1093/ehjqcco/qcad029"
-  },
   {
     "id": "33990383",
     "doi": "https://doi.org/10.1136/gutjnl-2020-323546",
@@ -17288,6 +17271,23 @@
     "laySummary": "",
     "urls": "pdf:https://gut.bmj.com/content/gutjnl/71/4/705.full.pdf; doi:https://doi.org/10.1136/gutjnl-2020-323546; html:https://europepmc.org/articles/PMC8921573; pdf:https://europepmc.org/articles/PMC8921573?pdf=render"
   },
+  {
+    "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": "<h4>Aim</h4>This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.<h4>Methods</h4>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.<h4>Results</h4>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)].<h4>Conclusion</h4>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": "pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf; doi:https://doi.org/10.1093/ehjqcco/qcad029"
+  },
   {
     "id": "35650647",
     "doi": "https://doi.org/10.1186/s41512-022-00124-y",
@@ -17373,23 +17373,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopenrespres.bmj.com/content/bmjresp/8/1/e000967.full.pdf; doi:https://doi.org/10.1136/bmjresp-2021-000967; html:https://europepmc.org/articles/PMC8261886; pdf:https://europepmc.org/articles/PMC8261886?pdf=render"
   },
-  {
-    "id": "35471746",
-    "doi": "https://doi.org/10.1186/s13613-022-01011-x",
-    "title": "The resilient intensive care unit.",
-    "authorString": "Salluh JIF, Kurtz P, Bastos LSL, Quintairos A, Zampieri FG, Bozza FA.",
-    "authorAffiliations": "",
-    "journalTitle": "Annals of intensive care",
-    "pubYear": "2022",
-    "date": "2022-04-26",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>The COVID-19 pandemic tested the capacity of intensive care units (ICU) to respond to a crisis and demonstrated their fragility. Unsurprisingly, higher than usual mortality rates, lengths of stay (LOS), and ICU-acquired complications occurred during the pandemic. However, worse outcomes were not universal nor constant across ICUs and significant variation in outcomes was reported, demonstrating that some ICUs could adequately manage the surge of COVID-19.<h4>Methods</h4>In the present editorial, we discuss the concept of a resilient Intensive Care Unit, including which metrics can be used to address the capacity to respond, sustain results and incorporate new practices that lead to improvement.<h4>Results</h4>We believe that a resiliency analysis adds a component of preparedness to the usual ICU performance evaluation and outcomes metrics to be used during the crisis and in regular times.<h4>Conclusions</h4>The COVID-19 pandemic demonstrated the need for a resilient health system. Although this concept has been discussed for health systems, it was not tested in intensive care. Future studies should evaluate this concept to improve ICU organization for standard and pandemic times.",
-    "laySummary": "",
-    "urls": "pdf:https://annalsofintensivecare.springeropen.com/track/pdf/10.1186/s13613-022-01011-x; doi:https://doi.org/10.1186/s13613-022-01011-x; html:https://europepmc.org/articles/PMC9038989; pdf:https://europepmc.org/articles/PMC9038989?pdf=render"
-  },
   {
     "id": "32046816",
     "doi": "https://doi.org/10.2807/1560-7917.es.2020.25.5.2000080",
@@ -17408,21 +17391,21 @@
     "urls": "pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/5/eurosurv-25-5-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.5.2000080&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.5.2000080; html:https://europepmc.org/articles/PMC7014668; pdf:https://europepmc.org/articles/PMC7014668?pdf=render"
   },
   {
-    "id": "36357675",
-    "doi": "https://doi.org/10.1038/s41591-022-02046-0",
-    "title": "Rare and common genetic determinants of metabolic individuality and their effects on human health.",
-    "authorString": "Surendran P, Stewart ID, Au Yeung VPW, Pietzner M, Raffler J, W\u00f6rheide 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, Kastenm\u00fcller G, Fauman EB, Suhre K, Butterworth AS, Langenberg C.",
+    "id": "35471746",
+    "doi": "https://doi.org/10.1186/s13613-022-01011-x",
+    "title": "The resilient intensive care unit.",
+    "authorString": "Salluh JIF, Kurtz P, Bastos LSL, Quintairos A, Zampieri FG, Bozza FA.",
     "authorAffiliations": "",
-    "journalTitle": "Nature medicine",
+    "journalTitle": "Annals of intensive care",
     "pubYear": "2022",
-    "date": "2022-11-10",
+    "date": "2022-04-26",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "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\u2009<\u20091.25\u2009\u00d7\u200910<sup>-11</sup>) within 330 genomic regions, with rare variants (minor allele frequency\u2009\u2264\u20091%) 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.",
+    "abstract": "<h4>Background</h4>The COVID-19 pandemic tested the capacity of intensive care units (ICU) to respond to a crisis and demonstrated their fragility. Unsurprisingly, higher than usual mortality rates, lengths of stay (LOS), and ICU-acquired complications occurred during the pandemic. However, worse outcomes were not universal nor constant across ICUs and significant variation in outcomes was reported, demonstrating that some ICUs could adequately manage the surge of COVID-19.<h4>Methods</h4>In the present editorial, we discuss the concept of a resilient Intensive Care Unit, including which metrics can be used to address the capacity to respond, sustain results and incorporate new practices that lead to improvement.<h4>Results</h4>We believe that a resiliency analysis adds a component of preparedness to the usual ICU performance evaluation and outcomes metrics to be used during the crisis and in regular times.<h4>Conclusions</h4>The COVID-19 pandemic demonstrated the need for a resilient health system. Although this concept has been discussed for health systems, it was not tested in intensive care. Future studies should evaluate this concept to improve ICU organization for standard and pandemic times.",
     "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41591-022-02046-0.pdf; doi:https://doi.org/10.1038/s41591-022-02046-0; html:https://europepmc.org/articles/PMC9671801; pdf:https://europepmc.org/articles/PMC9671801?pdf=render"
+    "urls": "pdf:https://annalsofintensivecare.springeropen.com/track/pdf/10.1186/s13613-022-01011-x; doi:https://doi.org/10.1186/s13613-022-01011-x; html:https://europepmc.org/articles/PMC9038989; pdf:https://europepmc.org/articles/PMC9038989?pdf=render"
   },
   {
     "id": "30532623",
@@ -17442,21 +17425,21 @@
     "urls": "pdf:https://bdj.pensoft.net/article/29232/download/pdf/; doi:https://doi.org/10.3897/BDJ.6.e29232; html:https://europepmc.org/articles/PMC6281706; pdf:https://europepmc.org/articles/PMC6281706?pdf=render"
   },
   {
-    "id": "37124165",
-    "doi": "https://doi.org/10.1016/j.ufug.2023.127934",
-    "title": "Effects of the onset of the COVID-19 pandemic restrictions on park crime in London, England: An interrupted time series analysis.",
-    "authorString": "Hajna S, Cummins S.",
+    "id": "36357675",
+    "doi": "https://doi.org/10.1038/s41591-022-02046-0",
+    "title": "Rare and common genetic determinants of metabolic individuality and their effects on human health.",
+    "authorString": "Surendran P, Stewart ID, Au Yeung VPW, Pietzner M, Raffler J, W\u00f6rheide 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, Kastenm\u00fcller G, Fauman EB, Suhre K, Butterworth AS, Langenberg C.",
     "authorAffiliations": "",
-    "journalTitle": "Urban forestry & urban greening",
-    "pubYear": "2023",
-    "date": "2023-04-11",
+    "journalTitle": "Nature medicine",
+    "pubYear": "2022",
+    "date": "2022-11-10",
     "isOpenAccess": "Y",
-    "keywords": "Parks; Crimes; Covid-19",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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).",
+    "abstract": "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\u2009<\u20091.25\u2009\u00d7\u200910<sup>-11</sup>) within 330 genomic regions, with rare variants (minor allele frequency\u2009\u2264\u20091%) 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.",
     "laySummary": "",
-    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088280; doi:https://doi.org/10.1016/j.ufug.2023.127934; html:https://europepmc.org/articles/PMC10088280; pdf:https://europepmc.org/articles/PMC10088280?pdf=render"
+    "urls": "pdf:https://www.nature.com/articles/s41591-022-02046-0.pdf; doi:https://doi.org/10.1038/s41591-022-02046-0; html:https://europepmc.org/articles/PMC9671801; pdf:https://europepmc.org/articles/PMC9671801?pdf=render"
   },
   {
     "id": "32301135",
@@ -17475,6 +17458,23 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/opo.12685; doi:https://doi.org/10.1111/opo.12685"
   },
+  {
+    "id": "37124165",
+    "doi": "https://doi.org/10.1016/j.ufug.2023.127934",
+    "title": "Effects of the onset of the COVID-19 pandemic restrictions on park crime in London, England: An interrupted time series analysis.",
+    "authorString": "Hajna S, Cummins S.",
+    "authorAffiliations": "",
+    "journalTitle": "Urban forestry & urban greening",
+    "pubYear": "2023",
+    "date": "2023-04-11",
+    "isOpenAccess": "Y",
+    "keywords": "Parks; Crimes; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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).",
+    "laySummary": "",
+    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088280; doi:https://doi.org/10.1016/j.ufug.2023.127934; html:https://europepmc.org/articles/PMC10088280; pdf:https://europepmc.org/articles/PMC10088280?pdf=render"
+  },
   {
     "id": "37133927",
     "doi": "https://doi.org/10.2196/45534",
@@ -17645,23 +17645,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e064586.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064586; html:https://europepmc.org/articles/PMC9511592; pdf:https://europepmc.org/articles/PMC9511592?pdf=render"
   },
-  {
-    "id": "37284234",
-    "doi": "https://doi.org/10.1140/epjds/s13688-023-00391-9",
-    "title": "The shock, the coping, the resilience: smartphone application use reveals Covid-19 lockdown effects on human behaviors.",
-    "authorString": "Liu XF, Wang ZZ, Xu XK, Wu Y, Zhao Z, Deng H, Wang P, Chao N, Huang YC.",
-    "authorAffiliations": "",
-    "journalTitle": "EPJ data science",
-    "pubYear": "2023",
-    "date": "2023-06-05",
-    "isOpenAccess": "Y",
-    "keywords": "Human behaviors; Natural Experiment; Lockdown; Smartphone Apps; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming \"digital residents.\" This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?pdf=render"
-  },
   {
     "id": "31666244",
     "doi": "https://doi.org/10.1136/archdischild-2019-317271",
@@ -17696,6 +17679,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1111/bjd.18889; doi:https://doi.org/10.1111/bjd.18889; html:https://europepmc.org/articles/PMC7587014; pdf:https://europepmc.org/articles/PMC7587014?pdf=render"
   },
+  {
+    "id": "37284234",
+    "doi": "https://doi.org/10.1140/epjds/s13688-023-00391-9",
+    "title": "The shock, the coping, the resilience: smartphone application use reveals Covid-19 lockdown effects on human behaviors.",
+    "authorString": "Liu XF, Wang ZZ, Xu XK, Wu Y, Zhao Z, Deng H, Wang P, Chao N, Huang YC.",
+    "authorAffiliations": "",
+    "journalTitle": "EPJ data science",
+    "pubYear": "2023",
+    "date": "2023-06-05",
+    "isOpenAccess": "Y",
+    "keywords": "Human behaviors; Natural Experiment; Lockdown; Smartphone Apps; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming \"digital residents.\" This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?pdf=render"
+  },
   {
     "id": "35403174",
     "doi": "https://doi.org/10.14218/jctp.2022.00003",
@@ -17798,23 +17798,6 @@
     "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": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.18526; doi:https://doi.org/10.1111/bjd.18526; html:https://europepmc.org/articles/PMC7383980; pdf:https://europepmc.org/articles/PMC7383980?pdf=render"
   },
-  {
-    "id": "37805492",
-    "doi": "https://doi.org/10.1186/s12864-023-09663-0",
-    "title": "Mapping the epigenomic landscape of human monocytes following innate immune activation reveals context-specific mechanisms driving endotoxin tolerance.",
-    "authorString": "Amarasinghe HE, Zhang P, Whalley JP, Allcock A, Migliorini G, Brown AC, Scozzafava G, Knight JC.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC genomics",
-    "pubYear": "2023",
-    "date": "2023-10-07",
-    "isOpenAccess": "Y",
-    "keywords": "Chromatin Accessibility; Expression Quantitative Trait Loci; Endotoxin Tolerance; Human Monocytes; Enhancer Rna; Context-specificity",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Monocytes are key mediators of innate immunity to infection, undergoing profound and dynamic changes in epigenetic state and immune function which are broadly protective but may be dysregulated in disease. Here, we aimed to advance understanding of epigenetic regulation following innate immune activation, acutely and in endotoxin tolerant states.<h4>Methods</h4>We exposed human primary monocytes from healthy donors (n\u2009=\u20096) to interferon-\u03b3 or differing combinations of endotoxin (lipopolysaccharide), including acute response (2\u00a0h) and two models of endotoxin tolerance: repeated stimulations (6\u2009+\u20096\u00a0h) and prolonged exposure to endotoxin (24\u00a0h). Another subset of monocytes was left untreated (na\u00efve). We identified context-specific regulatory elements based on epigenetic signatures for chromatin accessibility (ATAC-seq) and regulatory non-coding RNAs from total RNA sequencing.<h4>Results</h4>We present an atlas of differential gene expression for endotoxin and interferon response, identifying widespread context specific changes. Across assayed states, only 24-29% of genes showing differential exon usage are also differential at the gene level. Overall, 19.9% (6,884 of 34,616) of repeatedly observed ATAC peaks were differential in at least one condition, the majority upregulated on stimulation and located in distal regions (64.1% vs 45.9% of non-differential peaks) within which sequences were less conserved than non-differential peaks. We identified enhancer-derived RNA signatures specific to different monocyte states that correlated with chromatin accessibility changes. The endotoxin tolerance models showed distinct chromatin accessibility and transcriptomic signatures, with integrated analysis identifying genes and pathways involved in the inflammatory response, detoxification, metabolism and wound healing. We leveraged eQTL mapping for the same monocyte activation states to link potential enhancers with specific genes, identifying 1,946 unique differential ATAC peaks with 1,340 expression associated genes. We further use this to inform understanding of reported GWAS, for example involving FCHO1 and coronary artery disease.<h4>Conclusion</h4>This study reports context-specific regulatory elements based on transcriptomic profiling and epigenetic signatures for enhancer-derived RNAs and chromatin accessibility in immune tolerant monocyte states, and demonstrates the informativeness of linking such elements and eQTL to inform future mechanistic studies aimed at defining therapeutic targets of immunosuppression and diseases.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1186/s12864-023-09663-0; html:https://europepmc.org/articles/PMC10559536; pdf:https://europepmc.org/articles/PMC10559536?pdf=render"
-  },
   {
     "id": "34194954",
     "doi": "https://doi.org/10.1002/advs.202100707",
@@ -17832,6 +17815,23 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202100707; doi:https://doi.org/10.1002/advs.202100707; html:https://europepmc.org/articles/PMC8224424; pdf:https://europepmc.org/articles/PMC8224424?pdf=render"
   },
+  {
+    "id": "37805492",
+    "doi": "https://doi.org/10.1186/s12864-023-09663-0",
+    "title": "Mapping the epigenomic landscape of human monocytes following innate immune activation reveals context-specific mechanisms driving endotoxin tolerance.",
+    "authorString": "Amarasinghe HE, Zhang P, Whalley JP, Allcock A, Migliorini G, Brown AC, Scozzafava G, Knight JC.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC genomics",
+    "pubYear": "2023",
+    "date": "2023-10-07",
+    "isOpenAccess": "Y",
+    "keywords": "Chromatin Accessibility; Expression Quantitative Trait Loci; Endotoxin Tolerance; Human Monocytes; Enhancer Rna; Context-specificity",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Monocytes are key mediators of innate immunity to infection, undergoing profound and dynamic changes in epigenetic state and immune function which are broadly protective but may be dysregulated in disease. Here, we aimed to advance understanding of epigenetic regulation following innate immune activation, acutely and in endotoxin tolerant states.<h4>Methods</h4>We exposed human primary monocytes from healthy donors (n\u2009=\u20096) to interferon-\u03b3 or differing combinations of endotoxin (lipopolysaccharide), including acute response (2\u00a0h) and two models of endotoxin tolerance: repeated stimulations (6\u2009+\u20096\u00a0h) and prolonged exposure to endotoxin (24\u00a0h). Another subset of monocytes was left untreated (na\u00efve). We identified context-specific regulatory elements based on epigenetic signatures for chromatin accessibility (ATAC-seq) and regulatory non-coding RNAs from total RNA sequencing.<h4>Results</h4>We present an atlas of differential gene expression for endotoxin and interferon response, identifying widespread context specific changes. Across assayed states, only 24-29% of genes showing differential exon usage are also differential at the gene level. Overall, 19.9% (6,884 of 34,616) of repeatedly observed ATAC peaks were differential in at least one condition, the majority upregulated on stimulation and located in distal regions (64.1% vs 45.9% of non-differential peaks) within which sequences were less conserved than non-differential peaks. We identified enhancer-derived RNA signatures specific to different monocyte states that correlated with chromatin accessibility changes. The endotoxin tolerance models showed distinct chromatin accessibility and transcriptomic signatures, with integrated analysis identifying genes and pathways involved in the inflammatory response, detoxification, metabolism and wound healing. We leveraged eQTL mapping for the same monocyte activation states to link potential enhancers with specific genes, identifying 1,946 unique differential ATAC peaks with 1,340 expression associated genes. We further use this to inform understanding of reported GWAS, for example involving FCHO1 and coronary artery disease.<h4>Conclusion</h4>This study reports context-specific regulatory elements based on transcriptomic profiling and epigenetic signatures for enhancer-derived RNAs and chromatin accessibility in immune tolerant monocyte states, and demonstrates the informativeness of linking such elements and eQTL to inform future mechanistic studies aimed at defining therapeutic targets of immunosuppression and diseases.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1186/s12864-023-09663-0; html:https://europepmc.org/articles/PMC10559536; pdf:https://europepmc.org/articles/PMC10559536?pdf=render"
+  },
   {
     "id": "37198478",
     "doi": "https://doi.org/10.1038/s41586-023-06034-3",
@@ -18308,23 +18308,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1186/s13643-023-02261-x; doi:https://doi.org/10.1186/s13643-023-02261-x; html:https://europepmc.org/articles/PMC10237080; pdf:https://europepmc.org/articles/PMC10237080?pdf=render"
   },
-  {
-    "id": "37538142",
-    "doi": "https://doi.org/10.1093/ehjdh/ztad037",
-    "title": "Predicting left ventricular hypertrophy from the 12-lead electrocardiogram in the UK Biobank imaging study using machine learning.",
-    "authorString": "Naderi H, Ram\u00edrez J, van Duijvenboden S, Pujadas ER, Aung N, Wang L, Anwar Ahmed Chahal C, Lekadir K, Petersen SE, Munroe PB.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal. Digital health",
-    "pubYear": "2023",
-    "date": "2023-06-01",
-    "isOpenAccess": "Y",
-    "keywords": "Electrocardiogram; Left ventricular hypertrophy; Cardiovascular Screening; Machine Learning; Cardiovascular Magnetic Resonance Imaging",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>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.<h4>Methods and results</h4>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 (<i>P</i> < 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.<h4>Conclusion</h4>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.",
-    "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": "32979970",
     "doi": "https://doi.org/10.1016/s0140-6736(20)31966-8",
@@ -18342,6 +18325,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S0140673620319668/pdf; 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"
   },
+  {
+    "id": "30969971",
+    "doi": "https://doi.org/10.1371/journal.pone.0213435",
+    "title": "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.",
+    "authorString": "Griffiths LJ, Cortina-Borja M, Tingay K, Bandyopadhyay A, Akbari A, DeStavola BL, Bedford H, Lyons RA, Dezateux C.",
+    "authorAffiliations": "",
+    "journalTitle": "PloS one",
+    "pubYear": "2019",
+    "date": "2019-04-10",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "Improving Public Health",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0213435&type=printable; doi:https://doi.org/10.1371/journal.pone.0213435; html:https://europepmc.org/articles/PMC6457613; pdf:https://europepmc.org/articles/PMC6457613?pdf=render"
+  },
   {
     "id": "34125897",
     "doi": "https://doi.org/10.1093/nar/gkab449",
@@ -18360,21 +18360,21 @@
     "urls": "doi:https://doi.org/10.1093/nar/gkab449; doi:https://doi.org/10.1093/nar/gkab449; html:https://europepmc.org/articles/PMC8262728; pdf:https://europepmc.org/articles/PMC8262728?pdf=render"
   },
   {
-    "id": "30969971",
-    "doi": "https://doi.org/10.1371/journal.pone.0213435",
-    "title": "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.",
-    "authorString": "Griffiths LJ, Cortina-Borja M, Tingay K, Bandyopadhyay A, Akbari A, DeStavola BL, Bedford H, Lyons RA, Dezateux C.",
+    "id": "37538142",
+    "doi": "https://doi.org/10.1093/ehjdh/ztad037",
+    "title": "Predicting left ventricular hypertrophy from the 12-lead electrocardiogram in the UK Biobank imaging study using machine learning.",
+    "authorString": "Naderi H, Ram\u00edrez J, van Duijvenboden S, Pujadas ER, Aung N, Wang L, Anwar Ahmed Chahal C, Lekadir K, Petersen SE, Munroe PB.",
     "authorAffiliations": "",
-    "journalTitle": "PloS one",
-    "pubYear": "2019",
-    "date": "2019-04-10",
+    "journalTitle": "European heart journal. Digital health",
+    "pubYear": "2023",
+    "date": "2023-06-01",
     "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "Improving Public Health",
+    "keywords": "Electrocardiogram; Left ventricular hypertrophy; Cardiovascular Screening; Machine Learning; Cardiovascular Magnetic Resonance Imaging",
+    "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.",
+    "abstract": "<h4>Aims</h4>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.<h4>Methods and results</h4>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 (<i>P</i> < 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.<h4>Conclusion</h4>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.",
     "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0213435&type=printable; doi:https://doi.org/10.1371/journal.pone.0213435; html:https://europepmc.org/articles/PMC6457613; pdf:https://europepmc.org/articles/PMC6457613?pdf=render"
+    "urls": "doi:https://doi.org/10.1093/ehjdh/ztad037; html:https://europepmc.org/articles/PMC10393938; pdf:https://europepmc.org/articles/PMC10393938?pdf=render"
   },
   {
     "id": "34137744",
@@ -18427,23 +18427,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1093/ehjqcco/qcac039; html:https://europepmc.org/articles/PMC9442847; pdf:https://europepmc.org/articles/PMC9442847?pdf=render; doi:https://doi.org/10.1093/ehjqcco/qcac039"
   },
-  {
-    "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": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Discussion</h4>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.<h4>Trial registration</h4>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": "32894757",
     "doi": "https://doi.org/10.1093/ageing/afaa138",
@@ -18461,6 +18444,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ageing/article-pdf/50/3/795/37807880/afaa138.pdf; doi:https://doi.org/10.1093/ageing/afaa138; html:https://europepmc.org/articles/PMC8098797; pdf:https://europepmc.org/articles/PMC8098797?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": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Discussion</h4>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.<h4>Trial registration</h4>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": "36810251",
     "doi": "https://doi.org/10.1172/jci.insight.156643",
@@ -18495,23 +18495,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0805-0; doi:https://doi.org/10.1186/s12911-019-0805-0; html:https://europepmc.org/articles/PMC6472089; pdf:https://europepmc.org/articles/PMC6472089?pdf=render"
   },
-  {
-    "id": "37730605",
-    "doi": "https://doi.org/10.1186/s12889-023-16523-9",
-    "title": "Inequalities and mental health during the Coronavirus pandemic in the UK: a mixed-methods exploration.",
-    "authorString": "Lombardo C, Guo L, Solomon S, Crepaz-Keay D, McDaid S, Thorpe L, Martin S, John A, Morton A, Davidson G, Kousoulis AA, Van Bortel T.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC public health",
-    "pubYear": "2023",
-    "date": "2023-09-20",
-    "isOpenAccess": "Y",
-    "keywords": "Coronavirus; Mental health; Pandemic; United Kingdom; Inequalities; Social Determinants; Inequity; Adult Population; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>The World Health Organisation declared the novel Coronavirus disease (COVID-19) a global pandemic on 11th March 2020. Since then, the world has been firmly in its grip. At the time of writing, there were more than 767,972,961 million confirmed cases and over 6,950,655 million deaths. While the main policy focus has been on controlling the virus and ensuring vaccine roll-out and uptake, the population mental health impacts of the pandemic are expected to be long-term, with certain population groups affected more than others.<h4>Methods</h4>The overall objectives of our 'Coronavirus: Mental Health and the Pandemic' study were to explore UK adults' experiences of the Coronavirus pandemic and to gain insights into the mental health impacts, population-level changes over time, current and future mental health needs, and how these can best be addressed. The wider mixed-methods study consisted of repeated cross-sectional surveys and embedded qualitative sub-studies including in-depth interviews and focus group discussions with the wider UK adult population. For this particular inequalities and mental health sub-study, we used mixed methods data from our cross-sectional surveys and we carried out three Focus Group Discussions with a maximum variation sample from across the UK adult population. The discussions covered the broader topic of 'Inequalities and mental health during the Coronavirus pandemic in the UK' and took place online between April and August 2020. Focus Groups transcripts were analysed using thematic analysis in NVIVO. Cross-sectional survey data were analysed using STATA for descriptive statistics.<h4>Results</h4>Three broad main themes emerged, each supporting a number of sub-themes: (1) Impacts of the pandemic; (2) Moving forward: needs and recommendations; (3) Coping mechanisms and resilience. Findings showed that participants described their experiences of the pandemic in relation to its impact on themselves and on different groups of people. Their experiences illustrated how the pandemic and subsequent measures had exacerbated existing inequalities and created new ones, and triggered various emotional responses. Participants also described their coping strategies and what worked and did not work for them, as well as support needs and recommendations for moving forward through, and out of, the pandemic; all of which are valuable learnings to be considered in policy making for improving mental health and for ensuring future preparedness.<h4>Conclusions</h4>The pandemic is taking a long-term toll on the nations' mental health which will continue to have impacts for years to come. It is therefore crucial to learn the vital lessons learned from this pandemic. Specific as well as whole-government policies need to respond to this, address inequalities and the different needs across the life-course and across society, and take a holistic approach to mental health improvement across the UK.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-16523-9; doi:https://doi.org/10.1186/s12889-023-16523-9; html:https://europepmc.org/articles/PMC10510114; pdf:https://europepmc.org/articles/PMC10510114?pdf=render"
-  },
   {
     "id": "33655501",
     "doi": "https://doi.org/10.1111/bjd.19885",
@@ -18529,6 +18512,23 @@
     "laySummary": "",
     "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660846/7/Mulick_etal_2021_Four-childhood-atopic-dermatitis-subtypes.pdf; 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"
   },
+  {
+    "id": "37730605",
+    "doi": "https://doi.org/10.1186/s12889-023-16523-9",
+    "title": "Inequalities and mental health during the Coronavirus pandemic in the UK: a mixed-methods exploration.",
+    "authorString": "Lombardo C, Guo L, Solomon S, Crepaz-Keay D, McDaid S, Thorpe L, Martin S, John A, Morton A, Davidson G, Kousoulis AA, Van Bortel T.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC public health",
+    "pubYear": "2023",
+    "date": "2023-09-20",
+    "isOpenAccess": "Y",
+    "keywords": "Coronavirus; Mental health; Pandemic; United Kingdom; Inequalities; Social Determinants; Inequity; Adult Population; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>The World Health Organisation declared the novel Coronavirus disease (COVID-19) a global pandemic on 11th March 2020. Since then, the world has been firmly in its grip. At the time of writing, there were more than 767,972,961 million confirmed cases and over 6,950,655 million deaths. While the main policy focus has been on controlling the virus and ensuring vaccine roll-out and uptake, the population mental health impacts of the pandemic are expected to be long-term, with certain population groups affected more than others.<h4>Methods</h4>The overall objectives of our 'Coronavirus: Mental Health and the Pandemic' study were to explore UK adults' experiences of the Coronavirus pandemic and to gain insights into the mental health impacts, population-level changes over time, current and future mental health needs, and how these can best be addressed. The wider mixed-methods study consisted of repeated cross-sectional surveys and embedded qualitative sub-studies including in-depth interviews and focus group discussions with the wider UK adult population. For this particular inequalities and mental health sub-study, we used mixed methods data from our cross-sectional surveys and we carried out three Focus Group Discussions with a maximum variation sample from across the UK adult population. The discussions covered the broader topic of 'Inequalities and mental health during the Coronavirus pandemic in the UK' and took place online between April and August 2020. Focus Groups transcripts were analysed using thematic analysis in NVIVO. Cross-sectional survey data were analysed using STATA for descriptive statistics.<h4>Results</h4>Three broad main themes emerged, each supporting a number of sub-themes: (1) Impacts of the pandemic; (2) Moving forward: needs and recommendations; (3) Coping mechanisms and resilience. Findings showed that participants described their experiences of the pandemic in relation to its impact on themselves and on different groups of people. Their experiences illustrated how the pandemic and subsequent measures had exacerbated existing inequalities and created new ones, and triggered various emotional responses. Participants also described their coping strategies and what worked and did not work for them, as well as support needs and recommendations for moving forward through, and out of, the pandemic; all of which are valuable learnings to be considered in policy making for improving mental health and for ensuring future preparedness.<h4>Conclusions</h4>The pandemic is taking a long-term toll on the nations' mental health which will continue to have impacts for years to come. It is therefore crucial to learn the vital lessons learned from this pandemic. Specific as well as whole-government policies need to respond to this, address inequalities and the different needs across the life-course and across society, and take a holistic approach to mental health improvement across the UK.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-16523-9; doi:https://doi.org/10.1186/s12889-023-16523-9; html:https://europepmc.org/articles/PMC10510114; pdf:https://europepmc.org/articles/PMC10510114?pdf=render"
+  },
   {
     "id": "36691123",
     "doi": "https://doi.org/10.1136/bmjopen-2022-063199",
@@ -18614,23 +18614,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ehjdh/article-pdf/2/4/635/41972750/ztab082.pdf; doi:https://doi.org/10.1093/ehjdh/ztab082; html:https://europepmc.org/articles/PMC9707970; pdf:https://europepmc.org/articles/PMC9707970?pdf=render"
   },
-  {
-    "id": "36721180",
-    "doi": "https://doi.org/10.1186/s12961-022-00956-6",
-    "title": "Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "Health research policy and systems",
-    "pubYear": "2023",
-    "date": "2023-01-31",
-    "isOpenAccess": "Y",
-    "keywords": "Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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\u00a0employ mixed methods to better understand the underlying causes of service disruptions.",
-    "laySummary": "",
-    "urls": "pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render"
-  },
   {
     "id": "29457906",
     "doi": "https://doi.org/10.1021/acs.jproteome.7b00879",
@@ -18648,6 +18631,23 @@
     "laySummary": "",
     "urls": "pdf:https://pubs.acs.org/doi/pdf/10.1021/acs.jproteome.7b00879; doi:https://doi.org/10.1021/acs.jproteome.7b00879; html:https://europepmc.org/articles/PMC5891819; pdf:https://europepmc.org/articles/PMC5891819?pdf=render"
   },
+  {
+    "id": "36721180",
+    "doi": "https://doi.org/10.1186/s12961-022-00956-6",
+    "title": "Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "Health research policy and systems",
+    "pubYear": "2023",
+    "date": "2023-01-31",
+    "isOpenAccess": "Y",
+    "keywords": "Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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\u00a0employ mixed methods to better understand the underlying causes of service disruptions.",
+    "laySummary": "",
+    "urls": "pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render"
+  },
   {
     "id": "32975552",
     "doi": "https://doi.org/10.1001/jamapediatrics.2020.4573",
@@ -18869,23 +18869,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.researchprotocols.org/2023/1/e42965/PDF; doi:https://doi.org/10.2196/42965; html:https://europepmc.org/articles/PMC9936366"
   },
-  {
-    "id": "37813531",
-    "doi": "https://doi.org/10.1136/bmjopen-2023-073162",
-    "title": "Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.",
-    "authorString": "Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2023",
-    "date": "2023-10-09",
-    "isOpenAccess": "Y",
-    "keywords": "Obstetrics; epidemiology; Maternal Medicine",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.<h4>Methods and analysis</h4>Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3\u2009months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.<h4>Ethics and dissemination</h4>Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render"
-  },
   {
     "id": "PMC8855010",
     "doi": "https://doi.org/",
@@ -18903,6 +18886,23 @@
     "laySummary": "",
     "urls": "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"
   },
+  {
+    "id": "37813531",
+    "doi": "https://doi.org/10.1136/bmjopen-2023-073162",
+    "title": "Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.",
+    "authorString": "Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2023",
+    "date": "2023-10-09",
+    "isOpenAccess": "Y",
+    "keywords": "Obstetrics; epidemiology; Maternal Medicine",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.<h4>Methods and analysis</h4>Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3\u2009months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.<h4>Ethics and dissemination</h4>Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render"
+  },
   {
     "id": "33766511",
     "doi": "https://doi.org/10.1016/j.jid.2021.02.744",
@@ -19005,23 +19005,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cea.13741; doi:https://doi.org/10.1111/cea.13741"
   },
-  {
-    "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": "<h4>Objectives</h4>To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.",
-    "laySummary": "",
-    "urls": "pdf:https://heart.bmj.com/content/heartjnl/early/2023/03/21/heartjnl-2022-321888.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321888; html:https://europepmc.org/articles/PMC10314020; pdf:https://europepmc.org/articles/PMC10314020?pdf=render"
-  },
   {
     "id": "31194737",
     "doi": "https://doi.org/10.1371/journal.pgen.1008164",
@@ -19039,6 +19022,23 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008164&type=printable; doi:https://doi.org/10.1371/journal.pgen.1008164; html:https://europepmc.org/articles/PMC6592570; pdf:https://europepmc.org/articles/PMC6592570?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": "<h4>Objectives</h4>To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.",
+    "laySummary": "",
+    "urls": "pdf:https://heart.bmj.com/content/heartjnl/early/2023/03/21/heartjnl-2022-321888.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321888; html:https://europepmc.org/articles/PMC10314020; pdf:https://europepmc.org/articles/PMC10314020?pdf=render"
+  },
   {
     "id": "37190768",
     "doi": "https://doi.org/10.1017/s2045796023000276",
@@ -19260,23 +19260,6 @@
     "laySummary": "",
     "urls": "html:http://hdl.handle.net/20.500.11820/885f92d9-96bd-467c-893a-d5eb23d109e9; doi:https://doi.org/10.1136/thoraxjnl-2020-215566"
   },
-  {
-    "id": "37519214",
-    "doi": "https://doi.org/10.1177/09622802231188518",
-    "title": "Multiple imputation approaches for epoch-level accelerometer data in trials.",
-    "authorString": "Tackney MS, Williamson E, Cook DG, Limb E, Harris T, Carpenter J.",
-    "authorAffiliations": "",
-    "journalTitle": "Statistical methods in medical research",
-    "pubYear": "2023",
-    "date": "2023-07-31",
-    "isOpenAccess": "Y",
-    "keywords": "Missing Data; Accelerometer; Multiple Imputation; Wearables; Physical Activity Trial",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Clinical trials that investigate physical activity interventions often use accelerometers to measure step count at a very granular level, for example in 5-second epochs. Participants typically wear the accelerometer for a week-long period at baseline, and for one or more week-long follow-up periods after the intervention. The data is aggregated to provide daily or weekly step counts for the primary analysis. Missing data are common as participants may not wear the device as per protocol. Approaches to handling missing data in the literature have defined missingness on the day level using a threshold on daily weartime, which leads to loss of information on the time of day when data are missing. We propose an approach to identifying and classifying missingness at the finer epoch-level and present two approaches to handling missingness using multiple imputation. Firstly, we present a parametric approach which accounts for the number of missing epochs per day. Secondly, we describe a non-parametric approach where missing periods during the day are replaced by donor data from the same person where possible, or data from a different person who is matched on demographic and physical activity-related variables. Our simulation studies show that the non-parametric approach leads to estimates of the effect of treatment that are least biased while maintaining small standard errors. We illustrate the application of these different multiple imputation strategies to the analysis of the 2017 PACE-UP trial. The proposed framework is likely to be applicable to other digital health outcomes and to other wearable devices.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/09622802231188518; doi:https://doi.org/10.1177/09622802231188518; html:https://europepmc.org/articles/PMC10563375; pdf:https://europepmc.org/articles/PMC10563375?pdf=render"
-  },
   {
     "id": "35022215",
     "doi": "https://doi.org/10.1136/bmj-2021-067519",
@@ -19294,6 +19277,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.bmj.com/content/bmj/376/bmj-2021-067519.full.pdf; doi:https://doi.org/10.1136/bmj-2021-067519; html:https://europepmc.org/articles/PMC8753487; pdf:https://europepmc.org/articles/PMC8753487?pdf=render"
   },
+  {
+    "id": "37519214",
+    "doi": "https://doi.org/10.1177/09622802231188518",
+    "title": "Multiple imputation approaches for epoch-level accelerometer data in trials.",
+    "authorString": "Tackney MS, Williamson E, Cook DG, Limb E, Harris T, Carpenter J.",
+    "authorAffiliations": "",
+    "journalTitle": "Statistical methods in medical research",
+    "pubYear": "2023",
+    "date": "2023-07-31",
+    "isOpenAccess": "Y",
+    "keywords": "Missing Data; Accelerometer; Multiple Imputation; Wearables; Physical Activity Trial",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Clinical trials that investigate physical activity interventions often use accelerometers to measure step count at a very granular level, for example in 5-second epochs. Participants typically wear the accelerometer for a week-long period at baseline, and for one or more week-long follow-up periods after the intervention. The data is aggregated to provide daily or weekly step counts for the primary analysis. Missing data are common as participants may not wear the device as per protocol. Approaches to handling missing data in the literature have defined missingness on the day level using a threshold on daily weartime, which leads to loss of information on the time of day when data are missing. We propose an approach to identifying and classifying missingness at the finer epoch-level and present two approaches to handling missingness using multiple imputation. Firstly, we present a parametric approach which accounts for the number of missing epochs per day. Secondly, we describe a non-parametric approach where missing periods during the day are replaced by donor data from the same person where possible, or data from a different person who is matched on demographic and physical activity-related variables. Our simulation studies show that the non-parametric approach leads to estimates of the effect of treatment that are least biased while maintaining small standard errors. We illustrate the application of these different multiple imputation strategies to the analysis of the 2017 PACE-UP trial. The proposed framework is likely to be applicable to other digital health outcomes and to other wearable devices.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/09622802231188518; doi:https://doi.org/10.1177/09622802231188518; html:https://europepmc.org/articles/PMC10563375; pdf:https://europepmc.org/articles/PMC10563375?pdf=render"
+  },
   {
     "id": "33130851",
     "doi": "https://doi.org/10.1093/ije/dyaa216",
@@ -19583,23 +19583,6 @@
     "laySummary": "",
     "urls": "pdf:https://discovery.ucl.ac.uk/10149151/1/Dobson_The%20COPILOT%20Raw%20Illumina%20Genotyping%20QC%20Protocol_VoR.pdf; doi:https://doi.org/10.1002/cpz1.373"
   },
-  {
-    "id": "37477360",
-    "doi": "https://doi.org/10.1097/ypg.0000000000000349",
-    "title": "Schizophrenia polygenic risk score and type 2 diabetes onset in older adults with no schizophrenia diagnosis.",
-    "authorString": "Shamsutdinova D, Ajnakina O, Roberts A, Stahl D.",
-    "authorAffiliations": "",
-    "journalTitle": "Psychiatric genetics",
-    "pubYear": "2023",
-    "date": "2023-07-04",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>An association between type 2 diabetes (T2DM) and schizophrenia has long been observed, and recent research revealed presence of shared genetic factors. However, epidemiological evidence was inconsistent, some reported insignificant contribution of genetic factors to T2DM-schizophrenia comorbidity. Prior works studied people with schizophrenia, particularly, antipsychotic-naive patients, or those during the first psychotic experience to limit schizophrenia-related environmental factors. In contrast, we controlled such factors by utilizing a general population sample of individuals undiagnosed with schizophrenia. We hypothesized that if schizophrenia genetics impact T2DM development and such impact is not fully mediated by schizophrenia-related environment, people with high polygenic schizophrenia risk would exhibit elevated T2DM incidence.<h4>Methods</h4>Using a population-representative sample of adults aged \u226550 from English Longitudinal Study of Ageing ( n \u2005=\u20055968, 493 T2DM cases, average follow-up 8.7 years), we investigated if schizophrenia polygenic risk score (PGS-SZ) is associated with T2DM onset. A proportional hazards model with interval censoring was adjusted for age and sex (Model 1), and age, sex, BMI, hypertension, cardiovascular diseases, exercise, smoking, depressive symptoms and T2DM polygenic risk score (Model 2). According to the power calculations, hazard rates > 1.14 per standard deviation in PGS-SZ could be detected.<h4>Results</h4>We did not observe a significant association between PGS-SZ and T2DM incidence (hazard ratio 1.04; 95% CI 0.93-1.15; and\u20051.01, 95% CI\u20050.94-1.09).<h4>Conclusion</h4>Our results suggest low contribution of the intrinsic biological mechanisms driven by the polygenic risk of schizophrenia on future T2DM onset. Further research is needed.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1097/YPG.0000000000000349; html:https://europepmc.org/articles/PMC10501355; pdf:https://europepmc.org/articles/PMC10501355?pdf=render"
-  },
   {
     "id": "32717063",
     "doi": "https://doi.org/10.1093/cvr/cvaa233",
@@ -19617,6 +19600,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1093/cvr/cvaa233; doi:https://doi.org/10.1093/cvr/cvaa233; html:https://europepmc.org/articles/PMC8152696; pdf:https://europepmc.org/articles/PMC8152696?pdf=render"
   },
+  {
+    "id": "37477360",
+    "doi": "https://doi.org/10.1097/ypg.0000000000000349",
+    "title": "Schizophrenia polygenic risk score and type 2 diabetes onset in older adults with no schizophrenia diagnosis.",
+    "authorString": "Shamsutdinova D, Ajnakina O, Roberts A, Stahl D.",
+    "authorAffiliations": "",
+    "journalTitle": "Psychiatric genetics",
+    "pubYear": "2023",
+    "date": "2023-07-04",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>An association between type 2 diabetes (T2DM) and schizophrenia has long been observed, and recent research revealed presence of shared genetic factors. However, epidemiological evidence was inconsistent, some reported insignificant contribution of genetic factors to T2DM-schizophrenia comorbidity. Prior works studied people with schizophrenia, particularly, antipsychotic-naive patients, or those during the first psychotic experience to limit schizophrenia-related environmental factors. In contrast, we controlled such factors by utilizing a general population sample of individuals undiagnosed with schizophrenia. We hypothesized that if schizophrenia genetics impact T2DM development and such impact is not fully mediated by schizophrenia-related environment, people with high polygenic schizophrenia risk would exhibit elevated T2DM incidence.<h4>Methods</h4>Using a population-representative sample of adults aged \u226550 from English Longitudinal Study of Ageing ( n \u2005=\u20055968, 493 T2DM cases, average follow-up 8.7 years), we investigated if schizophrenia polygenic risk score (PGS-SZ) is associated with T2DM onset. A proportional hazards model with interval censoring was adjusted for age and sex (Model 1), and age, sex, BMI, hypertension, cardiovascular diseases, exercise, smoking, depressive symptoms and T2DM polygenic risk score (Model 2). According to the power calculations, hazard rates > 1.14 per standard deviation in PGS-SZ could be detected.<h4>Results</h4>We did not observe a significant association between PGS-SZ and T2DM incidence (hazard ratio 1.04; 95% CI 0.93-1.15; and\u20051.01, 95% CI\u20050.94-1.09).<h4>Conclusion</h4>Our results suggest low contribution of the intrinsic biological mechanisms driven by the polygenic risk of schizophrenia on future T2DM onset. Further research is needed.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1097/YPG.0000000000000349; html:https://europepmc.org/articles/PMC10501355; pdf:https://europepmc.org/articles/PMC10501355?pdf=render"
+  },
   {
     "id": "34907415",
     "doi": "https://doi.org/10.1093/ehjci/jeab266",
@@ -19651,6 +19651,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.compbiomed.2021.104542; doi:https://doi.org/10.1016/j.compbiomed.2021.104542; html:https://europepmc.org/articles/PMC8404035"
   },
+  {
+    "id": "33652931",
+    "doi": "https://doi.org/10.3390/jcm10050921",
+    "title": "Diagnosis and Risk Prediction of Dilated Cardiomyopathy in the Era of Big Data and Genomics. ",
+    "authorString": "Sammani A, Baas AF, Asselbergs FW, Te Riele ASJM.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of clinical medicine",
+    "pubYear": "2021",
+    "date": "2021-02-26",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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.",
+    "laySummary": "",
+    "urls": "pdf:https://www.mdpi.com/2077-0383/10/5/921/pdf?version=1615467325; doi:https://doi.org/10.3390/jcm10050921; html:https://europepmc.org/articles/PMC7956169; pdf:https://europepmc.org/articles/PMC7956169?pdf=render"
+  },
   {
     "id": "37538742",
     "doi": "https://doi.org/10.1098/rsos.221469",
@@ -19685,23 +19702,6 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00615-z.pdf; doi:https://doi.org/10.1007/s11897-023-00615-z; html:https://europepmc.org/articles/PMC10589200; pdf:https://europepmc.org/articles/PMC10589200?pdf=render"
   },
-  {
-    "id": "33652931",
-    "doi": "https://doi.org/10.3390/jcm10050921",
-    "title": "Diagnosis and Risk Prediction of Dilated Cardiomyopathy in the Era of Big Data and Genomics. ",
-    "authorString": "Sammani A, Baas AF, Asselbergs FW, Te Riele ASJM.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of clinical medicine",
-    "pubYear": "2021",
-    "date": "2021-02-26",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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.",
-    "laySummary": "",
-    "urls": "pdf:https://www.mdpi.com/2077-0383/10/5/921/pdf?version=1615467325; doi:https://doi.org/10.3390/jcm10050921; html:https://europepmc.org/articles/PMC7956169; pdf:https://europepmc.org/articles/PMC7956169?pdf=render"
-  },
   {
     "id": "36854461",
     "doi": "https://doi.org/10.1136/bmj-2022-073149",
@@ -19991,23 +19991,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199026&type=printable; doi:https://doi.org/10.1371/journal.pone.0199026; html:https://europepmc.org/articles/PMC6019102; pdf:https://europepmc.org/articles/PMC6019102?pdf=render"
   },
-  {
-    "id": "35435219",
-    "doi": "https://doi.org/10.1093/ehjqcco/qcac016",
-    "title": "Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.",
-    "authorString": "Raisi-Estabragh Z, Kobo O, Freeman P, Petersen SE, Kolman L, Miller RJH, Roguin A, Van Spall HGC, Vuong J, Yang EH, Mamas MA.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal. Quality of care & clinical outcomes",
-    "pubYear": "2022",
-    "date": "2022-12-01",
-    "isOpenAccess": "Y",
-    "keywords": "Cancer; Cardiovascular disease; epidemiology; Cardiovascular Mortality; Mortality Trends; Cardio-oncology",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.<h4>Methods and results</h4>We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629\u00a0308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).<h4>Conclusion</h4>We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcac016/43887262/qcac016.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac016; html:https://europepmc.org/articles/PMC9745666; pdf:https://europepmc.org/articles/PMC9745666?pdf=render"
-  },
   {
     "id": "32282926",
     "doi": "https://doi.org/10.1111/bjd.19122",
@@ -20025,6 +20008,23 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.19122; doi:https://doi.org/10.1111/bjd.19122"
   },
+  {
+    "id": "35435219",
+    "doi": "https://doi.org/10.1093/ehjqcco/qcac016",
+    "title": "Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.",
+    "authorString": "Raisi-Estabragh Z, Kobo O, Freeman P, Petersen SE, Kolman L, Miller RJH, Roguin A, Van Spall HGC, Vuong J, Yang EH, Mamas MA.",
+    "authorAffiliations": "",
+    "journalTitle": "European heart journal. Quality of care & clinical outcomes",
+    "pubYear": "2022",
+    "date": "2022-12-01",
+    "isOpenAccess": "Y",
+    "keywords": "Cancer; Cardiovascular disease; epidemiology; Cardiovascular Mortality; Mortality Trends; Cardio-oncology",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.<h4>Methods and results</h4>We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629\u00a0308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).<h4>Conclusion</h4>We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcac016/43887262/qcac016.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac016; html:https://europepmc.org/articles/PMC9745666; pdf:https://europepmc.org/articles/PMC9745666?pdf=render"
+  },
   {
     "id": "31827124",
     "doi": "https://doi.org/10.1038/s41598-019-54849-w",
@@ -20195,23 +20195,6 @@
     "laySummary": "",
     "urls": "pdf:https://medinform.jmir.org/2022/11/e38168/PDF; doi:https://doi.org/10.2196/38168; html:https://europepmc.org/articles/PMC9682451"
   },
-  {
-    "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": "The American journal of cardiology",
-    "pubYear": "2023",
-    "date": "2023-06-20",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "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.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.amjcard.2023.05.039"
-  },
   {
     "id": "34304930",
     "doi": "https://doi.org/10.1016/j.burns.2021.06.007",
@@ -20230,21 +20213,21 @@
     "urls": "doi:https://doi.org/10.1016/j.burns.2021.06.007"
   },
   {
-    "id": "36692937",
-    "doi": "https://doi.org/10.2196/42866",
-    "title": "The Feasibility of Implementing Remote Measurement Technologies in Psychological Treatment for Depression: Mixed Methods Study on Engagement.",
-    "authorString": "de Angel V, Adeleye F, Zhang Y, Cummins N, Munir S, Lewis S, Laporta Puyal E, Matcham F, Sun S, Folarin AA, Ranjan Y, Conde P, Rashid Z, Dobson R, Hotopf M.",
+    "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": "JMIR mental health",
+    "journalTitle": "The American journal of cardiology",
     "pubYear": "2023",
-    "date": "2023-01-24",
-    "isOpenAccess": "Y",
-    "keywords": "Depression; Mobile phone; Anxiety; Smartphone; Mhealth; Mobile Health; Wearable Devices; Digital Health; Digital Phenotyping; Passive Sensing",
+    "date": "2023-06-20",
+    "isOpenAccess": "N",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>Remote measurement technologies (RMTs) such as smartphones and wearables can help improve treatment for depression by providing objective, continuous, and ecologically valid insights into mood and behavior. Engagement with RMTs is varied and highly context dependent; however, few studies have investigated their feasibility in the context of treatment.<h4>Objective</h4>A mixed methods design was used to evaluate engagement with active and passive data collection via RMT in people with depression undergoing psychotherapy. We evaluated the effects of treatment on 2 different types of engagement: study attrition (engagement with study protocol) and patterns of missing data (engagement with digital devices), which we termed data availability. Qualitative interviews were conducted to help interpret the differences in engagement.<h4>Methods</h4>A total of 66 people undergoing psychological therapy for depression were followed up for 7 months. Active data were gathered from weekly questionnaires and speech and cognitive tasks, and passive data were gathered from smartphone sensors and a Fitbit (Fitbit Inc) wearable device.<h4>Results</h4>The overall retention rate was 60%. Higher-intensity treatment (\u03c7<sup>2</sup><sub>1</sub>=4.6; P=.03) and higher baseline anxiety (t<sub>56.28</sub>=-2.80, 2-tailed; P=.007) were associated with attrition, but depression severity was not (t<sub>50.4</sub>=-0.18; P=.86). A trend toward significance was found for the association between longer treatments and increased attrition (U=339.5; P=.05). Data availability was higher for active data than for passive data initially but declined at a sharper rate (90%-30% drop in 7 months). As for passive data, wearable data availability fell from a maximum of 80% to 45% at 7 months but showed higher overall data availability than smartphone-based data, which remained stable at the range of 20%-40% throughout. Missing data were more prevalent among GPS location data, followed by among Bluetooth data, then among accelerometry data. As for active data, speech and cognitive tasks had lower completion rates than clinical questionnaires. The participants in treatment provided less Fitbit data but more active data than those on the waiting list.<h4>Conclusions</h4>Different data streams showed varied patterns of missing data, despite being gathered from the same device. Longer and more complex treatments and clinical characteristics such as higher baseline anxiety may reduce long-term engagement with RMTs, and different devices may show opposite patterns of missingness during treatment. This has implications for the scalability and uptake of RMTs in health care settings, the generalizability and accuracy of the data collected by these methods, feature construction, and the appropriateness of RMT use in the long term.",
+    "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": "pdf:https://mental.jmir.org/2023/1/e42866/PDF; doi:https://doi.org/10.2196/42866; html:https://europepmc.org/articles/PMC9906314"
+    "urls": "doi:https://doi.org/10.1016/j.amjcard.2023.05.039"
   },
   {
     "id": "31558464",
@@ -20263,6 +20246,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/9/9/e033013.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-033013; html:https://europepmc.org/articles/PMC6773283; pdf:https://europepmc.org/articles/PMC6773283?pdf=render"
   },
+  {
+    "id": "36692937",
+    "doi": "https://doi.org/10.2196/42866",
+    "title": "The Feasibility of Implementing Remote Measurement Technologies in Psychological Treatment for Depression: Mixed Methods Study on Engagement.",
+    "authorString": "de Angel V, Adeleye F, Zhang Y, Cummins N, Munir S, Lewis S, Laporta Puyal E, Matcham F, Sun S, Folarin AA, Ranjan Y, Conde P, Rashid Z, Dobson R, Hotopf M.",
+    "authorAffiliations": "",
+    "journalTitle": "JMIR mental health",
+    "pubYear": "2023",
+    "date": "2023-01-24",
+    "isOpenAccess": "Y",
+    "keywords": "Depression; Mobile phone; Anxiety; Smartphone; Mhealth; Mobile Health; Wearable Devices; Digital Health; Digital Phenotyping; Passive Sensing",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Remote measurement technologies (RMTs) such as smartphones and wearables can help improve treatment for depression by providing objective, continuous, and ecologically valid insights into mood and behavior. Engagement with RMTs is varied and highly context dependent; however, few studies have investigated their feasibility in the context of treatment.<h4>Objective</h4>A mixed methods design was used to evaluate engagement with active and passive data collection via RMT in people with depression undergoing psychotherapy. We evaluated the effects of treatment on 2 different types of engagement: study attrition (engagement with study protocol) and patterns of missing data (engagement with digital devices), which we termed data availability. Qualitative interviews were conducted to help interpret the differences in engagement.<h4>Methods</h4>A total of 66 people undergoing psychological therapy for depression were followed up for 7 months. Active data were gathered from weekly questionnaires and speech and cognitive tasks, and passive data were gathered from smartphone sensors and a Fitbit (Fitbit Inc) wearable device.<h4>Results</h4>The overall retention rate was 60%. Higher-intensity treatment (\u03c7<sup>2</sup><sub>1</sub>=4.6; P=.03) and higher baseline anxiety (t<sub>56.28</sub>=-2.80, 2-tailed; P=.007) were associated with attrition, but depression severity was not (t<sub>50.4</sub>=-0.18; P=.86). A trend toward significance was found for the association between longer treatments and increased attrition (U=339.5; P=.05). Data availability was higher for active data than for passive data initially but declined at a sharper rate (90%-30% drop in 7 months). As for passive data, wearable data availability fell from a maximum of 80% to 45% at 7 months but showed higher overall data availability than smartphone-based data, which remained stable at the range of 20%-40% throughout. Missing data were more prevalent among GPS location data, followed by among Bluetooth data, then among accelerometry data. As for active data, speech and cognitive tasks had lower completion rates than clinical questionnaires. The participants in treatment provided less Fitbit data but more active data than those on the waiting list.<h4>Conclusions</h4>Different data streams showed varied patterns of missing data, despite being gathered from the same device. Longer and more complex treatments and clinical characteristics such as higher baseline anxiety may reduce long-term engagement with RMTs, and different devices may show opposite patterns of missingness during treatment. This has implications for the scalability and uptake of RMTs in health care settings, the generalizability and accuracy of the data collected by these methods, feature construction, and the appropriateness of RMT use in the long term.",
+    "laySummary": "",
+    "urls": "pdf:https://mental.jmir.org/2023/1/e42866/PDF; doi:https://doi.org/10.2196/42866; html:https://europepmc.org/articles/PMC9906314"
+  },
   {
     "id": "34145643",
     "doi": "https://doi.org/10.1111/jdv.17450",
@@ -20518,23 +20518,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0202359&type=printable; doi:https://doi.org/10.1371/journal.pone.0202359; html:https://europepmc.org/articles/PMC6124703; pdf:https://europepmc.org/articles/PMC6124703?pdf=render"
   },
-  {
-    "id": "35796550",
-    "doi": "https://doi.org/10.1093/hmg/ddac153",
-    "title": "The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study.",
-    "authorString": "Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.",
-    "authorAffiliations": "",
-    "journalTitle": "Human molecular genetics",
-    "pubYear": "2022",
-    "date": "2022-11-01",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD endpoints in up to 1\u2009153\u2009768 European (maximum 123\u2009668 cases) and 212\u2009453 East Asian (maximum 29\u2009319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple CVDs, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL) cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac153/45277324/ddac153.pdf; doi:https://doi.org/10.1093/hmg/ddac153"
-  },
   {
     "id": "35536740",
     "doi": "https://doi.org/10.1136/bmjopen-2021-052884",
@@ -20552,6 +20535,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/12/e052884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052884; html:https://europepmc.org/articles/PMC8719215; pdf:https://europepmc.org/articles/PMC8719215?pdf=render"
   },
+  {
+    "id": "35796550",
+    "doi": "https://doi.org/10.1093/hmg/ddac153",
+    "title": "The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study.",
+    "authorString": "Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.",
+    "authorAffiliations": "",
+    "journalTitle": "Human molecular genetics",
+    "pubYear": "2022",
+    "date": "2022-11-01",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD endpoints in up to 1\u2009153\u2009768 European (maximum 123\u2009668 cases) and 212\u2009453 East Asian (maximum 29\u2009319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple CVDs, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL) cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac153/45277324/ddac153.pdf; doi:https://doi.org/10.1093/hmg/ddac153"
+  },
   {
     "id": "35579056",
     "doi": "https://doi.org/10.1111/eci.13814",
@@ -20654,23 +20654,6 @@
     "laySummary": "",
     "urls": "pdf:https://ora.ox.ac.uk/objects/uuid:aefe90da-8a81-4cfa-981a-bb36eca6faa3/files/r6w924c60k; doi:https://doi.org/10.1161/HYPERTENSIONAHA.122.19354; html:https://europepmc.org/articles/PMC9640248; pdf:https://europepmc.org/articles/PMC9640248?pdf=render"
   },
-  {
-    "id": "35804579",
-    "doi": "https://doi.org/10.3390/ani12131679",
-    "title": "Genetic Basis of Dilated Cardiomyopathy in Dogs and Its Potential as a Bidirectional Model.",
-    "authorString": "Gaar-Humphreys KR, Spanjersberg TCF, Santarelli G, Grinwis GCM, Szatm\u00e1ri V, Roelen BAJ, Vink A, van Tintelen JP, Asselbergs FW, Fieten H, Harakalova M, van Steenbeek FG.",
-    "authorAffiliations": "",
-    "journalTitle": "Animals : an open access journal from MDPI",
-    "pubYear": "2022",
-    "date": "2022-06-29",
-    "isOpenAccess": "Y",
-    "keywords": "cardiovascular; Human Induced Pluripotent Stem Cells; Fibrofatty Infiltration; Attenuated Wavy Fibers; Canine Induced Pluripotent Stem Cells",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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.",
-    "laySummary": "",
-    "urls": "pdf:https://www.mdpi.com/2076-2615/12/13/1679/pdf?version=1656561768; doi:https://doi.org/10.3390/ani12131679; html:https://europepmc.org/articles/PMC9265105; pdf:https://europepmc.org/articles/PMC9265105?pdf=render"
-  },
   {
     "id": "35623313",
     "doi": "https://doi.org/10.1016/j.ejrad.2022.110366",
@@ -20688,6 +20671,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.ejrad.2022.110366"
   },
+  {
+    "id": "35804579",
+    "doi": "https://doi.org/10.3390/ani12131679",
+    "title": "Genetic Basis of Dilated Cardiomyopathy in Dogs and Its Potential as a Bidirectional Model.",
+    "authorString": "Gaar-Humphreys KR, Spanjersberg TCF, Santarelli G, Grinwis GCM, Szatm\u00e1ri V, Roelen BAJ, Vink A, van Tintelen JP, Asselbergs FW, Fieten H, Harakalova M, van Steenbeek FG.",
+    "authorAffiliations": "",
+    "journalTitle": "Animals : an open access journal from MDPI",
+    "pubYear": "2022",
+    "date": "2022-06-29",
+    "isOpenAccess": "Y",
+    "keywords": "cardiovascular; Human Induced Pluripotent Stem Cells; Fibrofatty Infiltration; Attenuated Wavy Fibers; Canine Induced Pluripotent Stem Cells",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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.",
+    "laySummary": "",
+    "urls": "pdf:https://www.mdpi.com/2076-2615/12/13/1679/pdf?version=1656561768; doi:https://doi.org/10.3390/ani12131679; html:https://europepmc.org/articles/PMC9265105; pdf:https://europepmc.org/articles/PMC9265105?pdf=render"
+  },
   {
     "id": "37670953",
     "doi": "https://doi.org/10.23889/ijpds.v8i1.2113",
@@ -21181,23 +21181,6 @@
     "laySummary": "",
     "urls": "pdf:https://mhealth.jmir.org/2022/1/e28095/PDF; doi:https://doi.org/10.2196/28095; html:https://europepmc.org/articles/PMC8838593"
   },
-  {
-    "id": "37422075",
-    "doi": "https://doi.org/10.1016/j.jval.2023.06.019",
-    "title": "Perspectives on Patient-Reported Outcome Data After Treatment Discontinuation in Cancer Clinical Trials.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research",
-    "pubYear": "2023",
-    "date": "2023-07-06",
-    "isOpenAccess": "N",
-    "keywords": "Oncology; Clinical Trials; Patient-reported Outcomes; Multistakeholder Perspective",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Stakeholders recognized that any PRO data collection after treatment discontinuation should have clearly defined objectives to ensure that data can be analyzed and reported.<h4>Conclusions</h4>Data collection after discontinuation without a justification for its use wastes patients' time and effort and is unethical.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.jval.2023.06.019"
-  },
   {
     "id": "35743743",
     "doi": "https://doi.org/10.3390/jpm12060958",
@@ -21215,6 +21198,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/2075-4426/12/6/958/pdf?version=1655284846; doi:https://doi.org/10.3390/jpm12060958; html:https://europepmc.org/articles/PMC9225330; pdf:https://europepmc.org/articles/PMC9225330?pdf=render"
   },
+  {
+    "id": "37422075",
+    "doi": "https://doi.org/10.1016/j.jval.2023.06.019",
+    "title": "Perspectives on Patient-Reported Outcome Data After Treatment Discontinuation in Cancer Clinical Trials.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research",
+    "pubYear": "2023",
+    "date": "2023-07-06",
+    "isOpenAccess": "N",
+    "keywords": "Oncology; Clinical Trials; Patient-reported Outcomes; Multistakeholder Perspective",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Stakeholders recognized that any PRO data collection after treatment discontinuation should have clearly defined objectives to ensure that data can be analyzed and reported.<h4>Conclusions</h4>Data collection after discontinuation without a justification for its use wastes patients' time and effort and is unethical.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.jval.2023.06.019"
+  },
   {
     "id": "33500288",
     "doi": "https://doi.org/10.1136/bmjopen-2020-042945",
@@ -21606,23 +21606,6 @@
     "laySummary": "",
     "urls": "pdf:https://bjgpopen.org/content/bjgpoa/4/5/bjgpopen20X101109.full.pdf; doi:https://doi.org/10.3399/bjgpopen20X101109; html:https://europepmc.org/articles/PMC7880177; pdf:https://europepmc.org/articles/PMC7880177?pdf=render"
   },
-  {
-    "id": "36298714",
-    "doi": "https://doi.org/10.3390/v14102159",
-    "title": "Production and Characterisation of Stabilised PV-3 Virus-like Particles Using <i>Pichia pastoris</i>.",
-    "authorString": "Sherry L, Grehan K, Swanson JJ, Bahar MW, Porta C, Fry EE, Stuart DI, Rowlands DJ, Stonehouse NJ.",
-    "authorAffiliations": "",
-    "journalTitle": "Viruses",
-    "pubYear": "2022",
-    "date": "2022-09-30",
-    "isOpenAccess": "Y",
-    "keywords": "Poliovirus; Vaccine; virus-like particle; Pichia\u00a0pastoris",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Following the success of global vaccination programmes using the live-attenuated oral and inactivated poliovirus vaccines (OPV and IPV), wild poliovirus (PV) is now only endemic in Afghanistan and Pakistan. However, the continued use of these vaccines poses potential risks to the eradication of PV. The production of recombinant PV virus-like particles (VLPs), which lack the viral genome offer great potential as next-generation vaccines for the post-polio world. We have previously reported production of PV VLPs using <i>Pichia pastoris</i>, however, these VLPs were in the non-native conformation (C Ag), which would not produce effective protection against PV. Here, we build on this work and show that it is possible to produce wt PV-3 and thermally stabilised PV-3 (referred to as PV-3 SC8) VLPs in the native conformation (D Ag) using <i>Pichia pastoris</i>. We show that the PV-3 SC8 VLPs provide a much-improved D:C antigen ratio as compared to wt PV-3, whilst exhibiting greater thermostability than the current IPV vaccine. Finally, we determine the cryo-EM structure of the yeast-derived PV-3 SC8 VLPs and compare this to previously published PV-3 D Ag structures, highlighting the similarities between these recombinantly expressed VLPs and the infectious virus, further emphasising their potential as a next-generation vaccine candidate for PV.",
-    "laySummary": "",
-    "urls": "pdf:https://www.mdpi.com/1999-4915/14/10/2159/pdf?version=1665465973; doi:https://doi.org/10.3390/v14102159; html:https://europepmc.org/articles/PMC9611624; pdf:https://europepmc.org/articles/PMC9611624?pdf=render"
-  },
   {
     "id": "31361079",
     "doi": "https://doi.org/10.1111/1742-6723.13361",
@@ -21640,6 +21623,23 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.13361; doi:https://doi.org/10.1111/1742-6723.13361"
   },
+  {
+    "id": "36298714",
+    "doi": "https://doi.org/10.3390/v14102159",
+    "title": "Production and Characterisation of Stabilised PV-3 Virus-like Particles Using <i>Pichia pastoris</i>.",
+    "authorString": "Sherry L, Grehan K, Swanson JJ, Bahar MW, Porta C, Fry EE, Stuart DI, Rowlands DJ, Stonehouse NJ.",
+    "authorAffiliations": "",
+    "journalTitle": "Viruses",
+    "pubYear": "2022",
+    "date": "2022-09-30",
+    "isOpenAccess": "Y",
+    "keywords": "Poliovirus; Vaccine; virus-like particle; Pichia\u00a0pastoris",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Following the success of global vaccination programmes using the live-attenuated oral and inactivated poliovirus vaccines (OPV and IPV), wild poliovirus (PV) is now only endemic in Afghanistan and Pakistan. However, the continued use of these vaccines poses potential risks to the eradication of PV. The production of recombinant PV virus-like particles (VLPs), which lack the viral genome offer great potential as next-generation vaccines for the post-polio world. We have previously reported production of PV VLPs using <i>Pichia pastoris</i>, however, these VLPs were in the non-native conformation (C Ag), which would not produce effective protection against PV. Here, we build on this work and show that it is possible to produce wt PV-3 and thermally stabilised PV-3 (referred to as PV-3 SC8) VLPs in the native conformation (D Ag) using <i>Pichia pastoris</i>. We show that the PV-3 SC8 VLPs provide a much-improved D:C antigen ratio as compared to wt PV-3, whilst exhibiting greater thermostability than the current IPV vaccine. Finally, we determine the cryo-EM structure of the yeast-derived PV-3 SC8 VLPs and compare this to previously published PV-3 D Ag structures, highlighting the similarities between these recombinantly expressed VLPs and the infectious virus, further emphasising their potential as a next-generation vaccine candidate for PV.",
+    "laySummary": "",
+    "urls": "pdf:https://www.mdpi.com/1999-4915/14/10/2159/pdf?version=1665465973; doi:https://doi.org/10.3390/v14102159; html:https://europepmc.org/articles/PMC9611624; pdf:https://europepmc.org/articles/PMC9611624?pdf=render"
+  },
   {
     "id": "35259281",
     "doi": "https://doi.org/10.1111/acel.13524",
@@ -21760,21 +21760,21 @@
     "urls": "pdf:https://respiratory-research.biomedcentral.com/counter/pdf/10.1186/s12931-022-02130-6; 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": "36689332",
-    "doi": "https://doi.org/10.1093/neuonc/noad021",
-    "title": "GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data.",
-    "authorString": "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.",
+    "id": "30972781",
+    "doi": "https://doi.org/10.1111/apt.15232",
+    "title": "Early and late mortality following unscheduled admissions for severe liver disease across England and Wales.",
+    "authorString": "Roberts SE, John A, Brown J, Napier DJ, Lyons RA, Williams JG.",
     "authorAffiliations": "",
-    "journalTitle": "Neuro-oncology",
-    "pubYear": "2023",
-    "date": "2023-07-01",
+    "journalTitle": "Alimentary pharmacology & therapeutics",
+    "pubYear": "2019",
+    "date": "2019-04-11",
     "isOpenAccess": "Y",
-    "keywords": "Immune; Deconvolution; Glioblastoma; Neoplastic; Transcriptomics",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https://gbmdeconvoluter.leeds.ac.uk.",
+    "abstract": "<h4>Background</h4>There is a known shortfall in hepatology service resources across England and Wales.<h4>Aim</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>Mortality for alcoholic liver disease and hepatic failure was 23.4% and 35.4% respectively at 60\u00a0days and 61.8% and 57.1% at 5\u00a0years. Standardised mortality ratios (SMRs) were extremely high at 60\u00a0days (184 and 117 respectively) and remained highly increased at 5\u00a0years (16.7 and 6.3). Mortality at 5\u00a0years 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.<h4>Conclusions</h4>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.",
     "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/neuro-oncology/advance-article-pdf/doi/10.1093/neuonc/noad021/49522012/noad021.pdf; doi:https://doi.org/10.1093/neuonc/noad021; html:https://europepmc.org/articles/PMC10326489; pdf:https://europepmc.org/articles/PMC10326489?pdf=render"
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/apt.15232; doi:https://doi.org/10.1111/apt.15232; html:https://europepmc.org/articles/PMC6519290; pdf:https://europepmc.org/articles/PMC6519290?pdf=render"
   },
   {
     "id": "36240828",
@@ -21794,21 +21794,21 @@
     "urls": "pdf:https://www.repository.cam.ac.uk/bitstreams/bb5465bd-c08f-4c3d-ab0e-87fee39fc92b/download; doi:https://doi.org/10.1016/S2214-109X(22)00358-8; html:https://europepmc.org/articles/PMC9573849"
   },
   {
-    "id": "30972781",
-    "doi": "https://doi.org/10.1111/apt.15232",
-    "title": "Early and late mortality following unscheduled admissions for severe liver disease across England and Wales.",
-    "authorString": "Roberts SE, John A, Brown J, Napier DJ, Lyons RA, Williams JG.",
+    "id": "36689332",
+    "doi": "https://doi.org/10.1093/neuonc/noad021",
+    "title": "GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data.",
+    "authorString": "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.",
     "authorAffiliations": "",
-    "journalTitle": "Alimentary pharmacology & therapeutics",
-    "pubYear": "2019",
-    "date": "2019-04-11",
+    "journalTitle": "Neuro-oncology",
+    "pubYear": "2023",
+    "date": "2023-07-01",
     "isOpenAccess": "Y",
-    "keywords": "",
+    "keywords": "Immune; Deconvolution; Glioblastoma; Neoplastic; Transcriptomics",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>There is a known shortfall in hepatology service resources across England and Wales.<h4>Aim</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>Mortality for alcoholic liver disease and hepatic failure was 23.4% and 35.4% respectively at 60\u00a0days and 61.8% and 57.1% at 5\u00a0years. Standardised mortality ratios (SMRs) were extremely high at 60\u00a0days (184 and 117 respectively) and remained highly increased at 5\u00a0years (16.7 and 6.3). Mortality at 5\u00a0years 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.<h4>Conclusions</h4>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.",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https://gbmdeconvoluter.leeds.ac.uk.",
     "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/apt.15232; doi:https://doi.org/10.1111/apt.15232; html:https://europepmc.org/articles/PMC6519290; pdf:https://europepmc.org/articles/PMC6519290?pdf=render"
+    "urls": "pdf:https://academic.oup.com/neuro-oncology/advance-article-pdf/doi/10.1093/neuonc/noad021/49522012/noad021.pdf; doi:https://doi.org/10.1093/neuonc/noad021; html:https://europepmc.org/articles/PMC10326489; pdf:https://europepmc.org/articles/PMC10326489?pdf=render"
   },
   {
     "id": "37278928",
@@ -21827,23 +21827,6 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s12265-023-10398-2.pdf; doi:https://doi.org/10.1007/s12265-023-10398-2"
   },
-  {
-    "id": "35504525",
-    "doi": "https://doi.org/10.1016/j.jclinepi.2022.04.025",
-    "title": "How traditional informed consent impairs inclusivity in a learning healthcare system: lessons learned from the Utrecht Cardiovascular Cohort.",
-    "authorString": "Groenhof TKJ, Mostert M, Lea NC, Haitjema S, de Vries MC, van Dijk WB, Grobbee DE, Asselbergs FW, Bots ML, van der Graaf R.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of clinical epidemiology",
-    "pubYear": "2022",
-    "date": "2022-04-30",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.jclinepi.2022.04.025"
-  },
   {
     "id": "34426417",
     "doi": "https://doi.org/10.1136/bmjhci-2021-100385",
@@ -21861,6 +21844,23 @@
     "laySummary": "",
     "urls": "pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100385.full.pdf; doi:https://doi.org/10.1136/bmjhci-2021-100385; html:https://europepmc.org/articles/PMC8383863; pdf:https://europepmc.org/articles/PMC8383863?pdf=render"
   },
+  {
+    "id": "35504525",
+    "doi": "https://doi.org/10.1016/j.jclinepi.2022.04.025",
+    "title": "How traditional informed consent impairs inclusivity in a learning healthcare system: lessons learned from the Utrecht Cardiovascular Cohort.",
+    "authorString": "Groenhof TKJ, Mostert M, Lea NC, Haitjema S, de Vries MC, van Dijk WB, Grobbee DE, Asselbergs FW, Bots ML, van der Graaf R.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of clinical epidemiology",
+    "pubYear": "2022",
+    "date": "2022-04-30",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.jclinepi.2022.04.025"
+  },
   {
     "id": "36819459",
     "doi": "https://doi.org/10.1210/jendso/bvad020",
@@ -22065,23 +22065,6 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328307; doi:https://doi.org/10.1164/rccm.201902-0286OC; html:https://europepmc.org/articles/PMC7328307; pdf:https://europepmc.org/articles/PMC7328307?pdf=render; doi:https://doi.org/10.1164/rccm.201902-0286oc"
   },
-  {
-    "id": "35802687",
-    "doi": "https://doi.org/10.1371/journal.pone.0270668",
-    "title": "Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "PloS one",
-    "pubYear": "2022",
-    "date": "2022-07-08",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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\u00b782 [0\u00b771-0\u00b795, p = 0\u00b7008]] and sarilumab [0\u00b780 [0\u00b761-1\u00b704, p = 0\u00b709]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1\u00b703 [95%CI 0\u00b781-1\u00b732, p = 0\u00b780]. The p-value for the global test of inconsistency was 0\u00b728.<h4>Conclusions</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0270668&type=printable; doi:https://doi.org/10.1371/journal.pone.0270668; html:https://europepmc.org/articles/PMC9269978; pdf:https://europepmc.org/articles/PMC9269978?pdf=render"
-  },
   {
     "id": "32651323",
     "doi": "https://doi.org/10.3233/jad-200338",
@@ -22099,6 +22082,23 @@
     "laySummary": "",
     "urls": "pdf:https://eprints.gla.ac.uk/217500/1/217500.pdf; doi:https://doi.org/10.3233/JAD-200338"
   },
+  {
+    "id": "35802687",
+    "doi": "https://doi.org/10.1371/journal.pone.0270668",
+    "title": "Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "PloS one",
+    "pubYear": "2022",
+    "date": "2022-07-08",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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\u00b782 [0\u00b771-0\u00b795, p = 0\u00b7008]] and sarilumab [0\u00b780 [0\u00b761-1\u00b704, p = 0\u00b709]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1\u00b703 [95%CI 0\u00b781-1\u00b732, p = 0\u00b780]. The p-value for the global test of inconsistency was 0\u00b728.<h4>Conclusions</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0270668&type=printable; doi:https://doi.org/10.1371/journal.pone.0270668; html:https://europepmc.org/articles/PMC9269978; pdf:https://europepmc.org/articles/PMC9269978?pdf=render"
+  },
   {
     "id": "37814896",
     "doi": "https://doi.org/10.1161/circgen.123.004181",
@@ -22235,23 +22235,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.dovepress.com/getfile.php?fileID=68078; doi:https://doi.org/10.2147/COPD.S298585; html:https://europepmc.org/articles/PMC8018552; pdf:https://europepmc.org/articles/PMC8018552?pdf=render"
   },
-  {
-    "id": "35355205",
-    "doi": "https://doi.org/10.1007/s11897-022-00544-3",
-    "title": "LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review.",
-    "authorString": "Printezi MI, Yousif LIE, Kamphuis JAM, van Laake LW, Cramer MJ, Hobbelink MGG, Asselbergs FW, Teske AJ.",
-    "authorAffiliations": "",
-    "journalTitle": "Current heart failure reports",
-    "pubYear": "2022",
-    "date": "2022-03-30",
-    "isOpenAccess": "Y",
-    "keywords": "Cardiotoxicity; Echocardiography; Left ventricular ejection fraction; Cardiac Magnetic Resonance Imaging; Cardio-oncology; Multigated Acquisition Scan",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Purpose of review</h4>The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably.<h4>Recent findings</h4>In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.",
-    "laySummary": "",
-    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11897-022-00544-3.pdf; doi:https://doi.org/10.1007/s11897-022-00544-3; html:https://europepmc.org/articles/PMC9177497; pdf:https://europepmc.org/articles/PMC9177497?pdf=render"
-  },
   {
     "id": "33735069",
     "doi": "https://doi.org/10.1016/s2589-7500(20)30240-5",
@@ -22269,6 +22252,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2589750020302405/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30240-5"
   },
+  {
+    "id": "35355205",
+    "doi": "https://doi.org/10.1007/s11897-022-00544-3",
+    "title": "LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review.",
+    "authorString": "Printezi MI, Yousif LIE, Kamphuis JAM, van Laake LW, Cramer MJ, Hobbelink MGG, Asselbergs FW, Teske AJ.",
+    "authorAffiliations": "",
+    "journalTitle": "Current heart failure reports",
+    "pubYear": "2022",
+    "date": "2022-03-30",
+    "isOpenAccess": "Y",
+    "keywords": "Cardiotoxicity; Echocardiography; Left ventricular ejection fraction; Cardiac Magnetic Resonance Imaging; Cardio-oncology; Multigated Acquisition Scan",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Purpose of review</h4>The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably.<h4>Recent findings</h4>In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.",
+    "laySummary": "",
+    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11897-022-00544-3.pdf; doi:https://doi.org/10.1007/s11897-022-00544-3; html:https://europepmc.org/articles/PMC9177497; pdf:https://europepmc.org/articles/PMC9177497?pdf=render"
+  },
   {
     "id": "33328453",
     "doi": "https://doi.org/10.1038/s41467-020-19996-z",
@@ -22337,6 +22337,23 @@
     "laySummary": "",
     "urls": "pdf:https://hal.univ-lorraine.fr/hal-03320880/file/1-s2.0-S1071916421002025-main.pdf; doi:https://doi.org/10.1016/j.cardfail.2021.05.012"
   },
+  {
+    "id": "34429368",
+    "doi": "https://doi.org/10.1136/heartjnl-2021-319566",
+    "title": "Sex disparity in subsequent outcomes in survivors of coronary heart disease.",
+    "authorString": "Akyea RK, Kontopantelis E, Kai J, Weng SF, Patel RS, Asselbergs FW, Qureshi N.",
+    "authorAffiliations": "",
+    "journalTitle": "Heart (British Cardiac Society)",
+    "pubYear": "2022",
+    "date": "2021-08-24",
+    "isOpenAccess": "N",
+    "keywords": "Sex difference; Coronary Heart Disease; Secondary Prevention; Competing Risks; Major Adverse Cardiovascular Events",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>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.<h4>Methods</h4>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\u2009702 adults (aged \u226518 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.<h4>Results</h4>There were 143\u2009702 adults with any incident CHD (either angina, myocardial infarction or coronary revascularisation). Women (n=63\u2009078, 43.9%) were older than men (median age, 73 vs 66 years). First subsequent MACE outcome was observed in 91\u2009706 (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\u2009543, 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\u2009503, 20.5%) (HR, 1.05 (1.02 to 1.07); HRsd, 1.11 (1.08 to 1.13)).<h4>Conclusions</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://heart.bmj.com/content/heartjnl/108/1/37.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-319566"
+  },
   {
     "id": "36224602",
     "doi": "https://doi.org/10.1186/s12916-022-02544-5",
@@ -22354,6 +22371,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02544-5; doi:https://doi.org/10.1186/s12916-022-02544-5; html:https://europepmc.org/articles/PMC9558944; pdf:https://europepmc.org/articles/PMC9558944?pdf=render"
   },
+  {
+    "id": "30745170",
+    "doi": "https://doi.org/10.1016/j.ebiom.2019.02.005",
+    "title": "Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "EBioMedicine",
+    "pubYear": "2019",
+    "date": "2019-02-08",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "Understanding the Causes of Disease",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>Ordinal genome-wide association study of suicidality in the UK Biobank cohort comparing: 'no suicidality' controls (N\u202f=\u202f83,557); 'thoughts that life was not worth living' (N\u202f=\u202f21,063); 'ever contemplated self-harm' (N\u202f=\u202f13,038); 'act of deliberate self-harm in the past' (N\u202f=\u202f2498); and 'previous suicide attempt' (N\u202f=\u202f2666).<h4>Outcomes</h4>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 (r<sub>g</sub> 0\u00b781).<h4>Interpretation</h4>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).",
+    "laySummary": "",
+    "urls": "pdf:http://www.thelancet.com/article/S2352396419300775/pdf; 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"
+  },
   {
     "id": "37206266",
     "doi": "https://doi.org/10.1002/jha2.698",
@@ -22371,23 +22405,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1002/jha2.698; doi:https://doi.org/10.1002/jha2.698; html:https://europepmc.org/articles/PMC10188477; pdf:https://europepmc.org/articles/PMC10188477?pdf=render"
   },
-  {
-    "id": "34429368",
-    "doi": "https://doi.org/10.1136/heartjnl-2021-319566",
-    "title": "Sex disparity in subsequent outcomes in survivors of coronary heart disease.",
-    "authorString": "Akyea RK, Kontopantelis E, Kai J, Weng SF, Patel RS, Asselbergs FW, Qureshi N.",
-    "authorAffiliations": "",
-    "journalTitle": "Heart (British Cardiac Society)",
-    "pubYear": "2022",
-    "date": "2021-08-24",
-    "isOpenAccess": "N",
-    "keywords": "Sex difference; Coronary Heart Disease; Secondary Prevention; Competing Risks; Major Adverse Cardiovascular Events",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>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.<h4>Methods</h4>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\u2009702 adults (aged \u226518 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.<h4>Results</h4>There were 143\u2009702 adults with any incident CHD (either angina, myocardial infarction or coronary revascularisation). Women (n=63\u2009078, 43.9%) were older than men (median age, 73 vs 66 years). First subsequent MACE outcome was observed in 91\u2009706 (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\u2009543, 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\u2009503, 20.5%) (HR, 1.05 (1.02 to 1.07); HRsd, 1.11 (1.08 to 1.13)).<h4>Conclusions</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://heart.bmj.com/content/heartjnl/108/1/37.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-319566"
-  },
   {
     "id": "36228971",
     "doi": "https://doi.org/10.1016/j.jclinepi.2022.10.011",
@@ -22405,23 +22422,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; 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": "30745170",
-    "doi": "https://doi.org/10.1016/j.ebiom.2019.02.005",
-    "title": "Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "EBioMedicine",
-    "pubYear": "2019",
-    "date": "2019-02-08",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "Understanding the Causes of Disease",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>Ordinal genome-wide association study of suicidality in the UK Biobank cohort comparing: 'no suicidality' controls (N\u202f=\u202f83,557); 'thoughts that life was not worth living' (N\u202f=\u202f21,063); 'ever contemplated self-harm' (N\u202f=\u202f13,038); 'act of deliberate self-harm in the past' (N\u202f=\u202f2498); and 'previous suicide attempt' (N\u202f=\u202f2666).<h4>Outcomes</h4>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 (r<sub>g</sub> 0\u00b781).<h4>Interpretation</h4>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).",
-    "laySummary": "",
-    "urls": "pdf:http://www.thelancet.com/article/S2352396419300775/pdf; 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"
-  },
   {
     "id": "32579178",
     "doi": "https://doi.org/10.1001/jamadermatol.2020.1948",
@@ -22490,23 +22490,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ana.25642; doi:https://doi.org/10.1002/ana.25642; html:https://europepmc.org/articles/PMC6944510; pdf:https://europepmc.org/articles/PMC6944510?pdf=render"
   },
-  {
-    "id": "36828655",
-    "doi": "https://doi.org/10.1136/bmjopen-2022-068718",
-    "title": "Maternal and child outcomes for pregnant women with pre-existing multiple long-term conditions: protocol for an observational study in the UK.",
-    "authorString": "Lee SI, Hope H, O'Reilly D, Kent L, Santorelli G, Subramanian A, Moss N, Azcoaga-Lorenzo A, Fagbamigbe AF, Nelson-Piercy C, Yau C, McCowan C, Kennedy JI, Phillips K, Singh M, Mhereeg M, Cockburn N, Brocklehurst P, Plachcinski R, Riley RD, Thangaratinam S, Brophy S, Hemali Sudasinghe SPB, Agrawal U, Vowles Z, Abel KM, Nirantharakumar K, Black M, Eastwood KA, MuM-PreDiCT.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2023",
-    "date": "2023-02-24",
-    "isOpenAccess": "Y",
-    "keywords": "Obstetrics; epidemiology; Maternal Medicine",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions).<h4>Methods and analysis</h4>Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses.<h4>Ethics and dissemination</h4>Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e068718.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-068718; html:https://europepmc.org/articles/PMC9972454; pdf:https://europepmc.org/articles/PMC9972454?pdf=render"
-  },
   {
     "id": "34870256",
     "doi": "https://doi.org/10.1016/j.lanepe.2021.100267",
@@ -22524,6 +22507,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.lanepe.2021.100267; doi:https://doi.org/10.1016/j.lanepe.2021.100267; html:https://europepmc.org/articles/PMC8629724; pdf:https://europepmc.org/articles/PMC8629724?pdf=render"
   },
+  {
+    "id": "36828655",
+    "doi": "https://doi.org/10.1136/bmjopen-2022-068718",
+    "title": "Maternal and child outcomes for pregnant women with pre-existing multiple long-term conditions: protocol for an observational study in the UK.",
+    "authorString": "Lee SI, Hope H, O'Reilly D, Kent L, Santorelli G, Subramanian A, Moss N, Azcoaga-Lorenzo A, Fagbamigbe AF, Nelson-Piercy C, Yau C, McCowan C, Kennedy JI, Phillips K, Singh M, Mhereeg M, Cockburn N, Brocklehurst P, Plachcinski R, Riley RD, Thangaratinam S, Brophy S, Hemali Sudasinghe SPB, Agrawal U, Vowles Z, Abel KM, Nirantharakumar K, Black M, Eastwood KA, MuM-PreDiCT.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2023",
+    "date": "2023-02-24",
+    "isOpenAccess": "Y",
+    "keywords": "Obstetrics; epidemiology; Maternal Medicine",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions).<h4>Methods and analysis</h4>Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses.<h4>Ethics and dissemination</h4>Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e068718.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-068718; html:https://europepmc.org/articles/PMC9972454; pdf:https://europepmc.org/articles/PMC9972454?pdf=render"
+  },
   {
     "id": "33053479",
     "doi": "https://doi.org/10.1016/j.chiabu.2020.104760",
@@ -22660,23 +22660,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.ijcard.2021.10.029"
   },
-  {
-    "id": "35087703",
-    "doi": "https://doi.org/10.5334/aogh.3465",
-    "title": "Household Air Pollution and Respiratory Symptoms a Month Before and During the Stringent COVID-19 Lockdown Levels 5 and 4 in South Africa.",
-    "authorString": "Wright CY, Kapwata T, Abdelatif N, Batini C, Wernecke B, Kunene Z, Millar DA, Mathee A, Street R, Panchal R, Hansell A, Cordell R, Hey JV.",
-    "authorAffiliations": "",
-    "journalTitle": "Annals of global health",
-    "pubYear": "2022",
-    "date": "2022-01-10",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Household air pollution (HAP) is associated with adverse human health impacts. During COVID-19 Lockdown Levels 5 and 4 (the most stringent levels), South Africans remained at home, potentially increasing their exposure to HAP.<h4>Objectives</h4>To investigate changes in fuel use behaviours/patterns of use affecting HAP exposure and associated HAP-related respiratory health outcomes during COVID-19 Lockdown Levels 5 and 4.<h4>Methods</h4>This was a cross-sectional online and telephonic survey of participants from an existing database. Logistic regression and McNemar's test were used to analyse household-level data.<h4>Results</h4>Among 2 505 participants, while electricity was the main energy source for cooking and heating the month before and during Lockdown Levels 5 and 4, some households used less electricity during Lockdown Levels 5 and 4 or switched to \"dirty fuels.\" One third of participants reported presence of environmental tobacco smoke in the home, a source of HAP associated with respiratory illnesses. Prevalence of HAP-related respiratory health outcomes were <10% (except dry cough). Majority of households reported cooking more, cleaning more and spending more time indoors during Lockdown Levels 5 and 4 - potentially exposed to HAP.<h4>Conclusion</h4>Should South Africa return to Lockdown Levels 5 or 4, awareness raising about the risks associated with HAP as well as messaging information for prevention of exposure to HAP, including environmental tobacco smoke, and associated adverse health impacts will be necessary.",
-    "laySummary": "",
-    "urls": "pdf:http://www.annalsofglobalhealth.org/articles/10.5334/aogh.3465/galley/3414/download/; doi:https://doi.org/10.5334/aogh.3465; html:https://europepmc.org/articles/PMC8757382; pdf:https://europepmc.org/articles/PMC8757382?pdf=render"
-  },
   {
     "id": "31711543",
     "doi": "https://doi.org/10.1186/s13326-019-0214-4",
@@ -22694,6 +22677,23 @@
     "laySummary": " 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",
     "urls": "pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0214-4; doi:https://doi.org/10.1186/s13326-019-0214-4; html:https://europepmc.org/articles/PMC6849160; pdf:https://europepmc.org/articles/PMC6849160?pdf=render"
   },
+  {
+    "id": "35087703",
+    "doi": "https://doi.org/10.5334/aogh.3465",
+    "title": "Household Air Pollution and Respiratory Symptoms a Month Before and During the Stringent COVID-19 Lockdown Levels 5 and 4 in South Africa.",
+    "authorString": "Wright CY, Kapwata T, Abdelatif N, Batini C, Wernecke B, Kunene Z, Millar DA, Mathee A, Street R, Panchal R, Hansell A, Cordell R, Hey JV.",
+    "authorAffiliations": "",
+    "journalTitle": "Annals of global health",
+    "pubYear": "2022",
+    "date": "2022-01-10",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Household air pollution (HAP) is associated with adverse human health impacts. During COVID-19 Lockdown Levels 5 and 4 (the most stringent levels), South Africans remained at home, potentially increasing their exposure to HAP.<h4>Objectives</h4>To investigate changes in fuel use behaviours/patterns of use affecting HAP exposure and associated HAP-related respiratory health outcomes during COVID-19 Lockdown Levels 5 and 4.<h4>Methods</h4>This was a cross-sectional online and telephonic survey of participants from an existing database. Logistic regression and McNemar's test were used to analyse household-level data.<h4>Results</h4>Among 2 505 participants, while electricity was the main energy source for cooking and heating the month before and during Lockdown Levels 5 and 4, some households used less electricity during Lockdown Levels 5 and 4 or switched to \"dirty fuels.\" One third of participants reported presence of environmental tobacco smoke in the home, a source of HAP associated with respiratory illnesses. Prevalence of HAP-related respiratory health outcomes were <10% (except dry cough). Majority of households reported cooking more, cleaning more and spending more time indoors during Lockdown Levels 5 and 4 - potentially exposed to HAP.<h4>Conclusion</h4>Should South Africa return to Lockdown Levels 5 or 4, awareness raising about the risks associated with HAP as well as messaging information for prevention of exposure to HAP, including environmental tobacco smoke, and associated adverse health impacts will be necessary.",
+    "laySummary": "",
+    "urls": "pdf:http://www.annalsofglobalhealth.org/articles/10.5334/aogh.3465/galley/3414/download/; doi:https://doi.org/10.5334/aogh.3465; html:https://europepmc.org/articles/PMC8757382; pdf:https://europepmc.org/articles/PMC8757382?pdf=render"
+  },
   {
     "id": "35410933",
     "doi": "https://doi.org/10.1136/bmjopen-2021-057885",
@@ -22762,23 +22762,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.dovepress.com/getfile.php?fileID=88236; doi:https://doi.org/10.2147/CLEP.S384605; html:https://europepmc.org/articles/PMC10030004; pdf:https://europepmc.org/articles/PMC10030004?pdf=render"
   },
-  {
-    "id": "37407123",
-    "doi": "https://doi.org/10.1016/j.jcmg.2023.01.016",
-    "title": "Ischemic Heart Disease and Vascular\u00a0Risk\u00a0Factors Are Associated With Accelerated Brain Aging.",
-    "authorString": "Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE.",
-    "authorAffiliations": "",
-    "journalTitle": "JACC. Cardiovascular imaging",
-    "pubYear": "2023",
-    "date": "2023-04-12",
-    "isOpenAccess": "Y",
-    "keywords": "brain aging; ischemic heart disease; Cognitive Decline; Vascular Risk Factors; Brain Health",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.<h4>Objectives</h4>The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.<h4>Methods</h4>Brain age was estimated in subjects with prevalent IHD (n\u00a0=\u00a01,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n\u00a0=\u00a035,237).<h4>Results</h4>Prevalent IHD was linked to significantly accelerated brain aging (P\u00a0< 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13\u00a0[95%\u00a0CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.<h4>Conclusions</h4>Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.jcmg.2023.01.016; html:https://europepmc.org/articles/PMC10317841; pdf:https://europepmc.org/articles/PMC10317841?pdf=render"
-  },
   {
     "id": "35381001",
     "doi": "https://doi.org/10.1371/journal.pgen.1010093",
@@ -22796,6 +22779,23 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010093&type=printable; doi:https://doi.org/10.1371/journal.pgen.1010093; html:https://europepmc.org/articles/PMC9022822; pdf:https://europepmc.org/articles/PMC9022822?pdf=render"
   },
+  {
+    "id": "37407123",
+    "doi": "https://doi.org/10.1016/j.jcmg.2023.01.016",
+    "title": "Ischemic Heart Disease and Vascular\u00a0Risk\u00a0Factors Are Associated With Accelerated Brain Aging.",
+    "authorString": "Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE.",
+    "authorAffiliations": "",
+    "journalTitle": "JACC. Cardiovascular imaging",
+    "pubYear": "2023",
+    "date": "2023-04-12",
+    "isOpenAccess": "Y",
+    "keywords": "brain aging; ischemic heart disease; Cognitive Decline; Vascular Risk Factors; Brain Health",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.<h4>Objectives</h4>The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.<h4>Methods</h4>Brain age was estimated in subjects with prevalent IHD (n\u00a0=\u00a01,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n\u00a0=\u00a035,237).<h4>Results</h4>Prevalent IHD was linked to significantly accelerated brain aging (P\u00a0< 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13\u00a0[95%\u00a0CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.<h4>Conclusions</h4>Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.jcmg.2023.01.016; html:https://europepmc.org/articles/PMC10317841; pdf:https://europepmc.org/articles/PMC10317841?pdf=render"
+  },
   {
     "id": "35866236",
     "doi": "https://doi.org/10.7189/jogh.12.05033",
@@ -22932,23 +22932,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/s2352-3018(23)00028-0; 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": "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": "2023-09-01",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Importance</h4>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.<h4>Objective</h4>To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes.<h4>Design, setting, and participants</h4>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.<h4>Exposure</h4>LTL.<h4>Main outcomes and measures</h4>Cardiovascular imaging traits and HF.<h4>Results</h4>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.<h4>Conclusions and relevance</h4>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": "pdf:https://jamanetwork.com/journals/jamacardiology/articlepdf/2807386/jamacardiology_aung_2023_oi_230032_1689092909.06174.pdf; doi:https://doi.org/10.1001/jamacardio.2023.2167; html:https://europepmc.org/articles/PMC10372756"
-  },
   {
     "id": "35152298",
     "doi": "https://doi.org/10.1093/ehjci/jeac030",
@@ -22966,6 +22949,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeac030/42506545/jeac030.pdf; doi:https://doi.org/10.1093/ehjci/jeac030; html:https://europepmc.org/articles/PMC9762936; pdf:https://europepmc.org/articles/PMC9762936?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": "2023-09-01",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Importance</h4>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.<h4>Objective</h4>To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes.<h4>Design, setting, and participants</h4>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.<h4>Exposure</h4>LTL.<h4>Main outcomes and measures</h4>Cardiovascular imaging traits and HF.<h4>Results</h4>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.<h4>Conclusions and relevance</h4>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": "pdf:https://jamanetwork.com/journals/jamacardiology/articlepdf/2807386/jamacardiology_aung_2023_oi_230032_1689092909.06174.pdf; doi:https://doi.org/10.1001/jamacardio.2023.2167; html:https://europepmc.org/articles/PMC10372756"
+  },
   {
     "id": "PMC8718341",
     "doi": "https://doi.org/",
@@ -23085,23 +23085,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/cid/article-pdf/72/Supplement_3/S172/38618862/ciab192.pdf; doi:https://doi.org/10.1093/cid/ciab192; html:https://europepmc.org/articles/PMC8201574; pdf:https://europepmc.org/articles/PMC8201574?pdf=render"
   },
-  {
-    "id": "36732776",
-    "doi": "https://doi.org/10.1186/s13040-023-00321-5",
-    "title": "LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes.",
-    "authorString": "Alasiri A, Karczewski KJ, Cole B, Loza BL, Moore JH, van der Laan SW, Asselbergs FW, Keating BJ, van Setten J.",
-    "authorAffiliations": "",
-    "journalTitle": "BioData mining",
-    "pubYear": "2023",
-    "date": "2023-02-02",
-    "isOpenAccess": "Y",
-    "keywords": "Human Genetic; Loss-of-function Variants; Compound Heterozygotes; Knockout Genes",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Loss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. The association of LoF variants with complex diseases and traits may lead to the discovery and validation of novel therapeutic targets. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect. Moreover, there is a lack of methods for detecting knockout genes caused by compound heterozygous (CH) LoF variants.<h4>Results</h4>We have developed the Loss-of-Function ToolKit (LoFTK), which allows efficient and automated prediction of LoF variants from genotyped, imputed and sequenced genomes. LoFTK enables the identification of genes that are inactive in one or two copies and provides summary statistics for downstream analyses. LoFTK can identify CH LoF variants, which result in LoF genes with two copies lost. Using data from parents and offspring we show that 96% of CH LoF genes predicted by LoFTK in the offspring have the respective alleles donated by each parent.<h4>Conclusions</h4>LoFTK is a command-line based tool that provides a reliable computational workflow for predicting LoF variants from genotyped and sequenced genomes, identifying genes that are inactive in 1 or 2 copies. LoFTK is an open software and is freely available to non-commercial users at https://github.com/CirculatoryHealth/LoFTK .",
-    "laySummary": "",
-    "urls": "pdf:https://biodatamining.biomedcentral.com/counter/pdf/10.1186/s13040-023-00321-5; doi:https://doi.org/10.1186/s13040-023-00321-5; html:https://europepmc.org/articles/PMC9893534; pdf:https://europepmc.org/articles/PMC9893534?pdf=render"
-  },
   {
     "id": "33206055",
     "doi": "https://doi.org/10.2196/19650",
@@ -23119,6 +23102,23 @@
     "laySummary": "",
     "urls": "pdf:https://diabetes.jmir.org/2020/4/e19650/PDF; doi:https://doi.org/10.2196/19650; html:https://europepmc.org/articles/PMC7710444; pdf:https://europepmc.org/articles/PMC7710444?pdf=render"
   },
+  {
+    "id": "36732776",
+    "doi": "https://doi.org/10.1186/s13040-023-00321-5",
+    "title": "LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes.",
+    "authorString": "Alasiri A, Karczewski KJ, Cole B, Loza BL, Moore JH, van der Laan SW, Asselbergs FW, Keating BJ, van Setten J.",
+    "authorAffiliations": "",
+    "journalTitle": "BioData mining",
+    "pubYear": "2023",
+    "date": "2023-02-02",
+    "isOpenAccess": "Y",
+    "keywords": "Human Genetic; Loss-of-function Variants; Compound Heterozygotes; Knockout Genes",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Loss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. The association of LoF variants with complex diseases and traits may lead to the discovery and validation of novel therapeutic targets. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect. Moreover, there is a lack of methods for detecting knockout genes caused by compound heterozygous (CH) LoF variants.<h4>Results</h4>We have developed the Loss-of-Function ToolKit (LoFTK), which allows efficient and automated prediction of LoF variants from genotyped, imputed and sequenced genomes. LoFTK enables the identification of genes that are inactive in one or two copies and provides summary statistics for downstream analyses. LoFTK can identify CH LoF variants, which result in LoF genes with two copies lost. Using data from parents and offspring we show that 96% of CH LoF genes predicted by LoFTK in the offspring have the respective alleles donated by each parent.<h4>Conclusions</h4>LoFTK is a command-line based tool that provides a reliable computational workflow for predicting LoF variants from genotyped and sequenced genomes, identifying genes that are inactive in 1 or 2 copies. LoFTK is an open software and is freely available to non-commercial users at https://github.com/CirculatoryHealth/LoFTK .",
+    "laySummary": "",
+    "urls": "pdf:https://biodatamining.biomedcentral.com/counter/pdf/10.1186/s13040-023-00321-5; doi:https://doi.org/10.1186/s13040-023-00321-5; html:https://europepmc.org/articles/PMC9893534; pdf:https://europepmc.org/articles/PMC9893534?pdf=render"
+  },
   {
     "id": "32345651",
     "doi": "https://doi.org/10.2337/dc19-2116",
@@ -23289,23 +23289,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e066288.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?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": "<h4>Background</h4>A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.<h4>Objective</h4>We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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": "pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1017337/pdf; doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render"
-  },
   {
     "id": "32017129",
     "doi": "https://doi.org/10.5694/mja2.50485",
@@ -23323,6 +23306,23 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50485; doi:https://doi.org/10.5694/mja2.50485"
   },
+  {
+    "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": "<h4>Background</h4>A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.<h4>Objective</h4>We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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": "pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1017337/pdf; doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render"
+  },
   {
     "id": "33148619",
     "doi": "https://doi.org/10.1136/bmj.m3919",
@@ -23578,23 +23578,6 @@
     "laySummary": "",
     "urls": "html:https://journals.lww.com/epidem/Fulltext/2021/09000/Weight_Change_and_the_Onset_of_Cardiovascular.19.aspx; doi:https://doi.org/10.1097/EDE.0000000000001393; html:https://europepmc.org/articles/PMC8318567; pdf:https://europepmc.org/articles/PMC8318567?pdf=render"
   },
-  {
-    "id": "37750555",
-    "doi": "https://doi.org/10.1161/jaha.123.030766",
-    "title": "Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.",
-    "authorString": "Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B, REVEAL Collaborative Group.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of the American Heart Association",
-    "pubYear": "2023",
-    "date": "2023-09-26",
-    "isOpenAccess": "N",
-    "keywords": "Cardiovascular diseases; Quality of life; United States; United Kingdom; Secondary Prevention; Health Care Costs",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Background Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention. Methods and Results Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21\u2009820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (\u00a35830 [United Kingdom], $14\u2009133 [US Medicare]), of myocardial infarction with urgent CRV procedure (\u00a35614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (\u00a34674/\u00a34651 and $15\u2009251/$17\u2009539). Conclusions Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1161/JAHA.123.030766; html:https://europepmc.org/articles/PMC7615160; pdf:https://europepmc.org/articles/PMC7615160?pdf=render; doi:https://doi.org/10.1161/jaha.123.030766"
-  },
   {
     "id": "31109684",
     "doi": "https://doi.org/10.1016/j.injury.2019.05.004",
@@ -23629,6 +23612,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.jove.com/pdf/60794/implementation-real-time-psychosis-risk-detection-alerting-system; doi:https://doi.org/10.3791/60794; html:https://europepmc.org/articles/PMC7272223; pdf:https://europepmc.org/articles/PMC7272223?pdf=render; doi:https://doi.org/10.3791/60794"
   },
+  {
+    "id": "37750555",
+    "doi": "https://doi.org/10.1161/jaha.123.030766",
+    "title": "Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.",
+    "authorString": "Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B, REVEAL Collaborative Group.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of the American Heart Association",
+    "pubYear": "2023",
+    "date": "2023-09-26",
+    "isOpenAccess": "N",
+    "keywords": "Cardiovascular diseases; Quality of life; United States; United Kingdom; Secondary Prevention; Health Care Costs",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Background Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention. Methods and Results Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21\u2009820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (\u00a35830 [United Kingdom], $14\u2009133 [US Medicare]), of myocardial infarction with urgent CRV procedure (\u00a35614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (\u00a34674/\u00a34651 and $15\u2009251/$17\u2009539). Conclusions Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1161/JAHA.123.030766; html:https://europepmc.org/articles/PMC7615160; pdf:https://europepmc.org/articles/PMC7615160?pdf=render; doi:https://doi.org/10.1161/jaha.123.030766"
+  },
   {
     "id": "33959646",
     "doi": "https://doi.org/10.3389/fcvm.2021.658915",
@@ -23714,23 +23714,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1136/bmjopen-2023-074626; html:https://europepmc.org/articles/PMC10503363; pdf:https://europepmc.org/articles/PMC10503363?pdf=render"
   },
-  {
-    "id": "37339333",
-    "doi": "https://doi.org/10.1002/jia2.26104",
-    "title": "COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of the International AIDS Society",
-    "pubYear": "2023",
-    "date": "2023-06-01",
-    "isOpenAccess": "Y",
-    "keywords": "Mortality; HIV; South Africa; Cd4 Count; Covid-19; Sars-cov-2",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>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.<h4>Methods</h4>We analysed observational cohort data on all PWH aged \u226515 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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.26104; doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render"
-  },
   {
     "id": "31671849",
     "doi": "https://doi.org/10.3390/ijerph16214178",
@@ -23749,21 +23732,21 @@
     "urls": "pdf:https://www.mdpi.com/1660-4601/16/21/4178/pdf?version=1573119054; doi:https://doi.org/10.3390/ijerph16214178; html:https://europepmc.org/articles/PMC6862192; pdf:https://europepmc.org/articles/PMC6862192?pdf=render"
   },
   {
-    "id": "37348789",
-    "doi": "https://doi.org/10.1016/j.jhep.2023.05.046",
-    "title": "Liver disease is a significant risk factor for cardiovascular outcomes - A UK Biobank study.",
-    "authorString": "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.",
+    "id": "37339333",
+    "doi": "https://doi.org/10.1002/jia2.26104",
+    "title": "COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa.",
+    "authorString": "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.",
     "authorAffiliations": "",
-    "journalTitle": "Journal of hepatology",
+    "journalTitle": "Journal of the International AIDS Society",
     "pubYear": "2023",
-    "date": "2023-06-20",
-    "isOpenAccess": "N",
-    "keywords": "Cardiac; MRI; Imaging; Hepatic; Heart Failure; liver disease; Cvd; Nafld; Atrial Fibrilliation",
+    "date": "2023-06-01",
+    "isOpenAccess": "Y",
+    "keywords": "Mortality; HIV; South Africa; Cd4 Count; Covid-19; Sars-cov-2",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background & aims</h4>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.<h4>Methods</h4>Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan\u00ae 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).<h4>Results</h4>A total of 33,616 participants (mean age 65 years, mean BMI 26\u00a0kg/m<sup>2</sup>, mean haemoglobin A1c 35\u00a0mmol/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\u00a0= 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\u00a0= 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p\u00a0= 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).<h4>Conclusion</h4>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.<h4>Impact and implications</h4>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.",
+    "abstract": "<h4>Introduction</h4>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.<h4>Methods</h4>We analysed observational cohort data on all PWH aged \u226515 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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",
     "laySummary": "",
-    "urls": "pdf:https://discovery.ucl.ac.uk/id/eprint/10175737/1/1-s2.0-S0168827823004208-main.pdf; doi:https://doi.org/10.1016/j.jhep.2023.05.046"
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.26104; doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render"
   },
   {
     "id": "33591280",
@@ -23799,6 +23782,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/12/e038324.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038324; html:https://europepmc.org/articles/PMC7772326; pdf:https://europepmc.org/articles/PMC7772326?pdf=render"
   },
+  {
+    "id": "37348789",
+    "doi": "https://doi.org/10.1016/j.jhep.2023.05.046",
+    "title": "Liver disease is a significant risk factor for cardiovascular outcomes - A UK Biobank study.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of hepatology",
+    "pubYear": "2023",
+    "date": "2023-06-20",
+    "isOpenAccess": "N",
+    "keywords": "Cardiac; MRI; Imaging; Hepatic; Heart Failure; liver disease; Cvd; Nafld; Atrial Fibrilliation",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background & aims</h4>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.<h4>Methods</h4>Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan\u00ae 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).<h4>Results</h4>A total of 33,616 participants (mean age 65 years, mean BMI 26\u00a0kg/m<sup>2</sup>, mean haemoglobin A1c 35\u00a0mmol/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\u00a0= 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\u00a0= 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p\u00a0= 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).<h4>Conclusion</h4>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.<h4>Impact and implications</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://discovery.ucl.ac.uk/id/eprint/10175737/1/1-s2.0-S0168827823004208-main.pdf; doi:https://doi.org/10.1016/j.jhep.2023.05.046"
+  },
   {
     "id": "37748493",
     "doi": "https://doi.org/10.1016/s2213-2600(23)00262-x",
@@ -23850,23 +23850,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-019-11451-y.pdf; doi:https://doi.org/10.1038/s41467-019-11451-y; html:https://europepmc.org/articles/PMC6692500; pdf:https://europepmc.org/articles/PMC6692500?pdf=render"
   },
-  {
-    "id": "37755828",
-    "doi": "https://doi.org/10.1001/jamanetworkopen.2023.36023",
-    "title": "Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials: A Systematic Review.",
-    "authorString": "Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Douglas SRG, Rizzo RRN, Devonshire JJ, Williams SA, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne JAC, Sharp MK, Stuart EA, Hern\u00e1n MA, Lee H, McAuley JH.",
-    "authorAffiliations": "",
-    "journalTitle": "JAMA network open",
-    "pubYear": "2023",
-    "date": "2023-09-05",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Importance</h4>Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice.<h4>Objective</h4>To assess the reporting of observational studies that explicitly aimed to emulate a target trial.<h4>Evidence review</h4>We searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation.<h4>Findings</h4>A total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation.<h4>Conclusion and relevance</h4>In this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1001/jamanetworkopen.2023.36023; html:https://europepmc.org/articles/PMC10534275"
-  },
   {
     "id": "33788869",
     "doi": "https://doi.org/10.1371/journal.pone.0249258",
@@ -23901,6 +23884,23 @@
     "laySummary": "",
     "urls": "pdf:https://nutrition.bmj.com/content/bmjnph/3/2/247.full.pdf; doi:https://doi.org/10.1136/bmjnph-2020-000107; html:https://europepmc.org/articles/PMC7841812; pdf:https://europepmc.org/articles/PMC7841812?pdf=render"
   },
+  {
+    "id": "37755828",
+    "doi": "https://doi.org/10.1001/jamanetworkopen.2023.36023",
+    "title": "Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials: A Systematic Review.",
+    "authorString": "Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Douglas SRG, Rizzo RRN, Devonshire JJ, Williams SA, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne JAC, Sharp MK, Stuart EA, Hern\u00e1n MA, Lee H, McAuley JH.",
+    "authorAffiliations": "",
+    "journalTitle": "JAMA network open",
+    "pubYear": "2023",
+    "date": "2023-09-05",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Importance</h4>Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice.<h4>Objective</h4>To assess the reporting of observational studies that explicitly aimed to emulate a target trial.<h4>Evidence review</h4>We searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation.<h4>Findings</h4>A total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation.<h4>Conclusion and relevance</h4>In this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1001/jamanetworkopen.2023.36023; html:https://europepmc.org/articles/PMC10534275"
+  },
   {
     "id": "36764723",
     "doi": "https://doi.org/10.1136/bmjopen-2022-067254",
@@ -23918,23 +23918,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e067254.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-067254; html:https://europepmc.org/articles/PMC9923317; pdf:https://europepmc.org/articles/PMC9923317?pdf=render"
   },
-  {
-    "id": "33836256",
-    "doi": "https://doi.org/10.1016/j.jclinepi.2021.03.025",
-    "title": "Internal-external cross-validation helped to evaluate the generalizability of prediction models in large clustered datasets.",
-    "authorString": "Takada T, Nijman S, Denaxas S, Snell KIE, Uijl A, Nguyen TL, Asselbergs FW, Debray TPA.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of clinical epidemiology",
-    "pubYear": "2021",
-    "date": "2021-04-06",
-    "isOpenAccess": "N",
-    "keywords": "Heterogeneity; Discrimination; Validation; Prediction model; calibration; Model Comparison",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To illustrate how to evaluate the need of complex strategies for developing generalizable prediction models in large clustered datasets.<h4>Study design and setting</h4>We developed eight Cox regression models to estimate the risk of heart failure using a large population-level dataset. These models differed in the number of predictors, the functional form of the predictor effects (non-linear effects and interaction) and the estimation method (maximum likelihood and penalization). Internal-external cross-validation was used to evaluate the models' generalizability across the included general practices.<h4>Results</h4>Among 871,687 individuals from 225 general practices, 43,987 (5.5%) developed heart failure during a median follow-up time of 5.8 years. For discrimination, the simplest prediction model yielded a good concordance statistic, which was not much improved by adopting complex strategies. Between-practice heterogeneity in discrimination was similar in all models. For calibration, the simplest model performed satisfactorily. Although accounting for non-linear effects and interaction slightly improved the calibration slope, it also led to more heterogeneity in the observed/expected ratio. Similar results were found in a second case study involving patients with stroke.<h4>Conclusion</h4>In large clustered datasets, prediction model studies may adopt internal-external cross-validation to evaluate the generalizability of competing models, and to identify promising modelling strategies.",
-    "laySummary": "",
-    "urls": "pdf:http://www.jclinepi.com/article/S0895435621001074/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.03.025"
-  },
   {
     "id": "31446403",
     "doi": "https://doi.org/10.1136/bmjopen-2018-026677",
@@ -23952,6 +23935,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/9/8/e026677.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-026677; html:https://europepmc.org/articles/PMC6720466; pdf:https://europepmc.org/articles/PMC6720466?pdf=render"
   },
+  {
+    "id": "33836256",
+    "doi": "https://doi.org/10.1016/j.jclinepi.2021.03.025",
+    "title": "Internal-external cross-validation helped to evaluate the generalizability of prediction models in large clustered datasets.",
+    "authorString": "Takada T, Nijman S, Denaxas S, Snell KIE, Uijl A, Nguyen TL, Asselbergs FW, Debray TPA.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of clinical epidemiology",
+    "pubYear": "2021",
+    "date": "2021-04-06",
+    "isOpenAccess": "N",
+    "keywords": "Heterogeneity; Discrimination; Validation; Prediction model; calibration; Model Comparison",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To illustrate how to evaluate the need of complex strategies for developing generalizable prediction models in large clustered datasets.<h4>Study design and setting</h4>We developed eight Cox regression models to estimate the risk of heart failure using a large population-level dataset. These models differed in the number of predictors, the functional form of the predictor effects (non-linear effects and interaction) and the estimation method (maximum likelihood and penalization). Internal-external cross-validation was used to evaluate the models' generalizability across the included general practices.<h4>Results</h4>Among 871,687 individuals from 225 general practices, 43,987 (5.5%) developed heart failure during a median follow-up time of 5.8 years. For discrimination, the simplest prediction model yielded a good concordance statistic, which was not much improved by adopting complex strategies. Between-practice heterogeneity in discrimination was similar in all models. For calibration, the simplest model performed satisfactorily. Although accounting for non-linear effects and interaction slightly improved the calibration slope, it also led to more heterogeneity in the observed/expected ratio. Similar results were found in a second case study involving patients with stroke.<h4>Conclusion</h4>In large clustered datasets, prediction model studies may adopt internal-external cross-validation to evaluate the generalizability of competing models, and to identify promising modelling strategies.",
+    "laySummary": "",
+    "urls": "pdf:http://www.jclinepi.com/article/S0895435621001074/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.03.025"
+  },
   {
     "id": "31994239",
     "doi": "https://doi.org/10.1002/bimj.201900041",
@@ -24003,23 +24003,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1056/nejmc2113864; doi:https://doi.org/10.1056/NEJMc2113864; html:https://europepmc.org/articles/PMC8552534; pdf:https://europepmc.org/articles/PMC8552534?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": "pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010726&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010726; html:https://europepmc.org/articles/PMC9744322; pdf:https://europepmc.org/articles/PMC9744322?pdf=render"
-  },
   {
     "id": "32846977",
     "doi": "https://doi.org/10.3390/ijerph17176139",
@@ -24037,6 +24020,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/1660-4601/17/17/6139/pdf?version=1598511551; doi:https://doi.org/10.3390/ijerph17176139; html:https://europepmc.org/articles/PMC7504024; pdf:https://europepmc.org/articles/PMC7504024?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": "pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010726&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010726; html:https://europepmc.org/articles/PMC9744322; pdf:https://europepmc.org/articles/PMC9744322?pdf=render"
+  },
   {
     "id": "36512045",
     "doi": "https://doi.org/10.1007/s00330-022-09323-z",
@@ -24190,23 +24190,6 @@
     "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": "36869930",
-    "doi": "https://doi.org/10.1007/s00520-023-07633-6",
-    "title": "Cost consequences of unscheduled emergency admissions in cancer patients in the last year of life.",
-    "authorString": "McFerran E, Cairnduff V, Elder R, Gavin A, Lawler M.",
-    "authorAffiliations": "",
-    "journalTitle": "Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer",
-    "pubYear": "2023",
-    "date": "2023-03-04",
-    "isOpenAccess": "Y",
-    "keywords": "Neoplasms; Death; Palliative care; Emergency Care; Cost Consequences",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>Cancer is a leading cause of death. This paper examines the utilisation of unscheduled emergency end-of-life healthcare and estimates expenditure in this domain. We explore care patterns and quantify the likely benefits from service reconfigurations which may influence rates of hospital admission and deaths.<h4>Methods</h4>Using prevalence-based retrospective data from the Northern Ireland General Registrar's Office linked by cancer diagnosis to Patient Administration episode data for unscheduled emergency care (1st January 2014 to 31st December 2015), we estimate unscheduled-emergency-care costs in the last year of life. We model potential resources released by reductions in length-of-stay for cancer patients. Linear regression examined patient characteristics affecting length of stay.<h4>Results</h4>A total of 3134 cancer patients used 60,746 days of unscheduled emergency care (average 19.5 days). Of these, 48.9% had \u22651 admission during their last 28 days of life. Total estimated cost was \u00a328,684,261, averaging \u00a39200 per person. Lung cancer patients had the highest proportion of admissions (23.2%, mean length of stay = 17.9 days, mean cost=\u00a37224). The highest service use and total cost was in those diagnosed at stage IV (38.4%), who\u00a0required 22,099 days of care, costing \u00a39,629,014. Palliative care support, identified in 25.5% of patients, contributed \u00a31,322,328. A 3-day reduction in\u00a0the mean length of stay with a 10% reduction in admissions, could reduce costs by \u00a37.37 million. Regression analyses explained 41% of length-of-stay variability.<h4>Conclusions</h4>The cost burden from unscheduled care use in the last year of life of cancer patients is significant. Opportunities to prioritise service reconfiguration for high-costing users emphasized lung and colorectal cancers as offering the greatest potential to influence outcomes.",
-    "laySummary": "",
-    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07633-6.pdf; doi:https://doi.org/10.1007/s00520-023-07633-6; html:https://europepmc.org/articles/PMC9985568; pdf:https://europepmc.org/articles/PMC9985568?pdf=render"
-  },
   {
     "id": "31282950",
     "doi": "https://doi.org/10.1001/jamaneurol.2019.1812",
@@ -24224,6 +24207,23 @@
     "laySummary": "",
     "urls": "pdf:https://jamanetwork.com/journals/jamaneurology/articlepdf/2737044/jamaneurology_adderley_2019_oi_190046.pdf; doi:https://doi.org/10.1001/jamaneurol.2019.1812; html:https://europepmc.org/articles/PMC6618853"
   },
+  {
+    "id": "36869930",
+    "doi": "https://doi.org/10.1007/s00520-023-07633-6",
+    "title": "Cost consequences of unscheduled emergency admissions in cancer patients in the last year of life.",
+    "authorString": "McFerran E, Cairnduff V, Elder R, Gavin A, Lawler M.",
+    "authorAffiliations": "",
+    "journalTitle": "Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer",
+    "pubYear": "2023",
+    "date": "2023-03-04",
+    "isOpenAccess": "Y",
+    "keywords": "Neoplasms; Death; Palliative care; Emergency Care; Cost Consequences",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>Cancer is a leading cause of death. This paper examines the utilisation of unscheduled emergency end-of-life healthcare and estimates expenditure in this domain. We explore care patterns and quantify the likely benefits from service reconfigurations which may influence rates of hospital admission and deaths.<h4>Methods</h4>Using prevalence-based retrospective data from the Northern Ireland General Registrar's Office linked by cancer diagnosis to Patient Administration episode data for unscheduled emergency care (1st January 2014 to 31st December 2015), we estimate unscheduled-emergency-care costs in the last year of life. We model potential resources released by reductions in length-of-stay for cancer patients. Linear regression examined patient characteristics affecting length of stay.<h4>Results</h4>A total of 3134 cancer patients used 60,746 days of unscheduled emergency care (average 19.5 days). Of these, 48.9% had \u22651 admission during their last 28 days of life. Total estimated cost was \u00a328,684,261, averaging \u00a39200 per person. Lung cancer patients had the highest proportion of admissions (23.2%, mean length of stay = 17.9 days, mean cost=\u00a37224). The highest service use and total cost was in those diagnosed at stage IV (38.4%), who\u00a0required 22,099 days of care, costing \u00a39,629,014. Palliative care support, identified in 25.5% of patients, contributed \u00a31,322,328. A 3-day reduction in\u00a0the mean length of stay with a 10% reduction in admissions, could reduce costs by \u00a37.37 million. Regression analyses explained 41% of length-of-stay variability.<h4>Conclusions</h4>The cost burden from unscheduled care use in the last year of life of cancer patients is significant. Opportunities to prioritise service reconfiguration for high-costing users emphasized lung and colorectal cancers as offering the greatest potential to influence outcomes.",
+    "laySummary": "",
+    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07633-6.pdf; doi:https://doi.org/10.1007/s00520-023-07633-6; html:https://europepmc.org/articles/PMC9985568; pdf:https://europepmc.org/articles/PMC9985568?pdf=render"
+  },
   {
     "id": "35861678",
     "doi": "https://doi.org/10.2196/36989",
@@ -24360,23 +24360,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/mbe/advance-article-pdf/doi/10.1093/molbev/msad070/49594873/msad070.pdf; doi:https://doi.org/10.1093/molbev/msad070; html:https://europepmc.org/articles/PMC10118308; pdf:https://europepmc.org/articles/PMC10118308?pdf=render"
   },
-  {
-    "id": "36482104",
-    "doi": "https://doi.org/10.1038/s41591-022-02100-x",
-    "title": "Association of wearable device-measured vigorous intermittent lifestyle physical activity with mortality.",
-    "authorString": "Stamatakis E, Ahmadi MN, Gill JMR, Th\u00f8gersen-Ntoumani C, Gibala MJ, Doherty A, Hamer M.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature medicine",
-    "pubYear": "2022",
-    "date": "2022-12-08",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Wearable devices can capture unexplored movement patterns such as brief bursts of vigorous intermittent lifestyle physical activity (VILPA) that is embedded into everyday life, rather than being done as leisure time exercise. Here, we examined the association of VILPA with all-cause, cardiovascular disease (CVD) and cancer mortality in 25,241 nonexercisers (mean age 61.8\u2009years, 14,178 women/11,063 men) in the UK Biobank. Over an average follow-up of 6.9\u2009years, during which 852 deaths occurred, VILPA was inversely associated with all three of these outcomes in a near-linear fashion. Compared with participants who engaged in no VILPA, participants who engaged in VILPA at the sample median VILPA frequency of 3\u2009length-standardized bouts per day (lasting 1 or 2\u2009min each) showed a 38%-40% reduction in all-cause and cancer mortality risk and a 48%-49% reduction in CVD mortality risk. Moreover, the sample median VILPA duration of 4.4\u2009min per day was associated with a 26%-30% reduction in all-cause and cancer mortality risk and a 32%-34% reduction in CVD mortality risk. We obtained similar results when repeating the above analyses for vigorous physical activity (VPA) in 62,344 UK Biobank participants who exercised (1,552 deaths, 35,290 women/27,054 men). These results indicate that small amounts of vigorous nonexercise physical activity are associated with substantially lower mortality. VILPA in nonexercisers appears to elicit similar effects to VPA in exercisers, suggesting that VILPA may be a suitable physical activity target, especially in people not able or willing to exercise.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41591-022-02100-x.pdf; doi:https://doi.org/10.1038/s41591-022-02100-x; html:https://europepmc.org/articles/PMC9800274; pdf:https://europepmc.org/articles/PMC9800274?pdf=render"
-  },
   {
     "id": "33615277",
     "doi": "https://doi.org/10.1016/j.xpro.2021.100334",
@@ -24394,6 +24377,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.xpro.2021.100334; 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": "36482104",
+    "doi": "https://doi.org/10.1038/s41591-022-02100-x",
+    "title": "Association of wearable device-measured vigorous intermittent lifestyle physical activity with mortality.",
+    "authorString": "Stamatakis E, Ahmadi MN, Gill JMR, Th\u00f8gersen-Ntoumani C, Gibala MJ, Doherty A, Hamer M.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature medicine",
+    "pubYear": "2022",
+    "date": "2022-12-08",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Wearable devices can capture unexplored movement patterns such as brief bursts of vigorous intermittent lifestyle physical activity (VILPA) that is embedded into everyday life, rather than being done as leisure time exercise. Here, we examined the association of VILPA with all-cause, cardiovascular disease (CVD) and cancer mortality in 25,241 nonexercisers (mean age 61.8\u2009years, 14,178 women/11,063 men) in the UK Biobank. Over an average follow-up of 6.9\u2009years, during which 852 deaths occurred, VILPA was inversely associated with all three of these outcomes in a near-linear fashion. Compared with participants who engaged in no VILPA, participants who engaged in VILPA at the sample median VILPA frequency of 3\u2009length-standardized bouts per day (lasting 1 or 2\u2009min each) showed a 38%-40% reduction in all-cause and cancer mortality risk and a 48%-49% reduction in CVD mortality risk. Moreover, the sample median VILPA duration of 4.4\u2009min per day was associated with a 26%-30% reduction in all-cause and cancer mortality risk and a 32%-34% reduction in CVD mortality risk. We obtained similar results when repeating the above analyses for vigorous physical activity (VPA) in 62,344 UK Biobank participants who exercised (1,552 deaths, 35,290 women/27,054 men). These results indicate that small amounts of vigorous nonexercise physical activity are associated with substantially lower mortality. VILPA in nonexercisers appears to elicit similar effects to VPA in exercisers, suggesting that VILPA may be a suitable physical activity target, especially in people not able or willing to exercise.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41591-022-02100-x.pdf; doi:https://doi.org/10.1038/s41591-022-02100-x; html:https://europepmc.org/articles/PMC9800274; pdf:https://europepmc.org/articles/PMC9800274?pdf=render"
+  },
   {
     "id": "36063293",
     "doi": "https://doi.org/10.1186/s12348-022-00304-3",
@@ -24666,23 +24666,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead038/49101708/kead038.pdf; doi:https://doi.org/10.1093/rheumatology/kead038; html:https://europepmc.org/articles/PMC10629784; pdf:https://europepmc.org/articles/PMC10629784?pdf=render"
   },
-  {
-    "id": "37730620",
-    "doi": "https://doi.org/10.1186/s13643-023-02333-y",
-    "title": "What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.",
-    "authorString": "Rahtz E, Bell SL, Nurse A, Wheeler BW, Guell C, Elliott LR, Thompson CW, McDougall CW, Lovell R.",
-    "authorAffiliations": "",
-    "journalTitle": "Systematic reviews",
-    "pubYear": "2023",
-    "date": "2023-09-20",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits.<h4>Methods</h4>An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed.<h4>Discussion</h4>The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.",
-    "laySummary": "",
-    "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02333-y; doi:https://doi.org/10.1186/s13643-023-02333-y; html:https://europepmc.org/articles/PMC10512649; pdf:https://europepmc.org/articles/PMC10512649?pdf=render"
-  },
   {
     "id": "34002035",
     "doi": "https://doi.org/10.1038/s41366-021-00807-4",
@@ -24700,6 +24683,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41366-021-00807-4.pdf; doi:https://doi.org/10.1038/s41366-021-00807-4; html:https://europepmc.org/articles/PMC8236409; pdf:https://europepmc.org/articles/PMC8236409?pdf=render"
   },
+  {
+    "id": "37730620",
+    "doi": "https://doi.org/10.1186/s13643-023-02333-y",
+    "title": "What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.",
+    "authorString": "Rahtz E, Bell SL, Nurse A, Wheeler BW, Guell C, Elliott LR, Thompson CW, McDougall CW, Lovell R.",
+    "authorAffiliations": "",
+    "journalTitle": "Systematic reviews",
+    "pubYear": "2023",
+    "date": "2023-09-20",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits.<h4>Methods</h4>An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed.<h4>Discussion</h4>The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.",
+    "laySummary": "",
+    "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02333-y; doi:https://doi.org/10.1186/s13643-023-02333-y; html:https://europepmc.org/articles/PMC10512649; pdf:https://europepmc.org/articles/PMC10512649?pdf=render"
+  },
   {
     "id": "33654696",
     "doi": "https://doi.org/10.1093/burnst/tkaa044",
@@ -24819,23 +24819,6 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364733; doi:https://doi.org/10.1080/20008066.2022.2105577; html:https://europepmc.org/articles/PMC9364733; pdf:https://europepmc.org/articles/PMC9364733?pdf=render"
   },
-  {
-    "id": "34535985",
-    "doi": "https://doi.org/10.1002/hep4.1805",
-    "title": "Genome-Wide Association Study of NAFLD Using Electronic Health Records.",
-    "authorString": "Fairfield CJ, Drake TM, Pius R, Bretherick AD, Campbell A, Clark DW, Fallowfield JA, Hayward C, Henderson NC, Joshi PK, Mills NL, Porteous DJ, Ramachandran P, Semple RK, Shaw CA, Sudlow CLM, Timmers PRHJ, Wilson JF, Wigmore SJ, Harrison EM, Spiliopoulou A.",
-    "authorAffiliations": "",
-    "journalTitle": "Hepatology communications",
-    "pubYear": "2022",
-    "date": "2021-09-17",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Genome-wide association studies (GWAS) have identified several risk loci for nonalcoholic fatty liver disease (NAFLD). Previous studies have largely relied on small sample sizes and have assessed quantitative traits. We performed a case-control GWAS in the UK Biobank using recorded diagnosis of NAFLD based on diagnostic codes recommended in recent consensus guidelines. We performed a GWAS of 4,761 cases of NAFLD and 373,227 healthy controls without evidence of NAFLD. Sensitivity analyses were performed excluding other co-existing hepatic pathology, adjusting for body mass index (BMI) and adjusting for alcohol intake. A total of 9,723,654 variants were assessed by logistic regression adjusted for age, sex, genetic principal components, and genotyping batch. We performed a GWAS meta-analysis using available summary association statistics. Six risk loci were identified (P\u00a0<\u00a05*10<sup>-8</sup> ) (apolipoprotein E [APOE], patatin-like phospholipase domain containing 3 [PNPLA3, transmembrane 6 superfamily member 2 [TM6SF2], glucokinase regulator [GCKR], mitochondrial amidoxime reducing component 1 [MARC1], and tribbles pseudokinase 1 [TRIB1]). All loci retained significance in sensitivity analyses without co-existent hepatic pathology and after adjustment for BMI. PNPLA3 and TM6SF2 remained significant after adjustment for alcohol (alcohol intake was known in only 158,388 individuals), with others demonstrating consistent direction and magnitude of effect. All six loci were significant on meta-analysis. Rs429358 (P\u00a0=\u00a02.17*10<sup>-11</sup> ) is a missense variant within the APOE gene determining \u03f54 versus \u03f52/\u03f53 alleles. The \u03f54 allele of APOE offered protection against NAFLD (odds ratio for heterozygotes 0.84 [95% confidence interval 0.78-0.90] and homozygotes 0.64 [0.50-0.79]). Conclusion: This GWAS replicates six known NAFLD-susceptibility loci and confirms that the \u03f54 allele of APOE is associated with protection against NAFLD. The results are consistent with published GWAS using histological and radiological measures of NAFLD, confirming that NAFLD identified through diagnostic codes from consensus guidelines is a valid alternative to more invasive and costly approaches.",
-    "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep4.1805; doi:https://doi.org/10.1002/hep4.1805; html:https://europepmc.org/articles/PMC8793997; pdf:https://europepmc.org/articles/PMC8793997?pdf=render"
-  },
   {
     "id": "31756303",
     "doi": "https://doi.org/10.1161/circgen.119.002711",
@@ -24854,21 +24837,21 @@
     "urls": "doi:https://doi.org/10.1161/CIRCGEN.119.002711; html:https://europepmc.org/articles/PMC6922071; pdf:https://europepmc.org/articles/PMC6922071?pdf=render; pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.119.002711"
   },
   {
-    "id": "35244709",
-    "doi": "https://doi.org/10.1093/europace/euac022",
-    "title": "Impact of oral anticoagulation on the association between frailty and clinical outcomes in people with atrial fibrillation: nationwide primary care records on treatment analysis.",
-    "authorString": "Wilkinson C, Wu J, Clegg A, Nadarajah R, Rockwood K, Todd O, Gale CP.",
+    "id": "34535985",
+    "doi": "https://doi.org/10.1002/hep4.1805",
+    "title": "Genome-Wide Association Study of NAFLD Using Electronic Health Records.",
+    "authorString": "Fairfield CJ, Drake TM, Pius R, Bretherick AD, Campbell A, Clark DW, Fallowfield JA, Hayward C, Henderson NC, Joshi PK, Mills NL, Porteous DJ, Ramachandran P, Semple RK, Shaw CA, Sudlow CLM, Timmers PRHJ, Wilson JF, Wigmore SJ, Harrison EM, Spiliopoulou A.",
     "authorAffiliations": "",
-    "journalTitle": "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",
+    "journalTitle": "Hepatology communications",
     "pubYear": "2022",
-    "date": "2022-07-01",
+    "date": "2021-09-17",
     "isOpenAccess": "Y",
-    "keywords": "Bleeding; Atrial fibrillation; Stroke; Frailty; Outcome; Oral Anticoagulation; Oral Anticoagulation Prescription",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Aims</h4>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.<h4>Methods and results</h4>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 \u22652 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.<h4>Conclusion</h4>Frailty among people with AF is common. The OAC was associated with a reduction in the primary endpoint across all degrees of frailty.",
+    "abstract": "Genome-wide association studies (GWAS) have identified several risk loci for nonalcoholic fatty liver disease (NAFLD). Previous studies have largely relied on small sample sizes and have assessed quantitative traits. We performed a case-control GWAS in the UK Biobank using recorded diagnosis of NAFLD based on diagnostic codes recommended in recent consensus guidelines. We performed a GWAS of 4,761 cases of NAFLD and 373,227 healthy controls without evidence of NAFLD. Sensitivity analyses were performed excluding other co-existing hepatic pathology, adjusting for body mass index (BMI) and adjusting for alcohol intake. A total of 9,723,654 variants were assessed by logistic regression adjusted for age, sex, genetic principal components, and genotyping batch. We performed a GWAS meta-analysis using available summary association statistics. Six risk loci were identified (P\u00a0<\u00a05*10<sup>-8</sup> ) (apolipoprotein E [APOE], patatin-like phospholipase domain containing 3 [PNPLA3, transmembrane 6 superfamily member 2 [TM6SF2], glucokinase regulator [GCKR], mitochondrial amidoxime reducing component 1 [MARC1], and tribbles pseudokinase 1 [TRIB1]). All loci retained significance in sensitivity analyses without co-existent hepatic pathology and after adjustment for BMI. PNPLA3 and TM6SF2 remained significant after adjustment for alcohol (alcohol intake was known in only 158,388 individuals), with others demonstrating consistent direction and magnitude of effect. All six loci were significant on meta-analysis. Rs429358 (P\u00a0=\u00a02.17*10<sup>-11</sup> ) is a missense variant within the APOE gene determining \u03f54 versus \u03f52/\u03f53 alleles. The \u03f54 allele of APOE offered protection against NAFLD (odds ratio for heterozygotes 0.84 [95% confidence interval 0.78-0.90] and homozygotes 0.64 [0.50-0.79]). Conclusion: This GWAS replicates six known NAFLD-susceptibility loci and confirms that the \u03f54 allele of APOE is associated with protection against NAFLD. The results are consistent with published GWAS using histological and radiological measures of NAFLD, confirming that NAFLD identified through diagnostic codes from consensus guidelines is a valid alternative to more invasive and costly approaches.",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1093/europace/euac022; doi:https://doi.org/10.1093/europace/euac022; html:https://europepmc.org/articles/PMC9326851; pdf:https://europepmc.org/articles/PMC9326851?pdf=render"
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep4.1805; doi:https://doi.org/10.1002/hep4.1805; html:https://europepmc.org/articles/PMC8793997; pdf:https://europepmc.org/articles/PMC8793997?pdf=render"
   },
   {
     "id": "34237806",
@@ -24887,6 +24870,23 @@
     "laySummary": "",
     "urls": "pdf:https://discovery.ucl.ac.uk/10135735/1/Asselbergs_10.1515_dmdi-2021-0104.pdf; doi:https://doi.org/10.1515/dmdi-2021-0104"
   },
+  {
+    "id": "35244709",
+    "doi": "https://doi.org/10.1093/europace/euac022",
+    "title": "Impact of oral anticoagulation on the association between frailty and clinical outcomes in people with atrial fibrillation: nationwide primary care records on treatment analysis.",
+    "authorString": "Wilkinson C, Wu J, Clegg A, Nadarajah R, Rockwood K, Todd O, Gale CP.",
+    "authorAffiliations": "",
+    "journalTitle": "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",
+    "pubYear": "2022",
+    "date": "2022-07-01",
+    "isOpenAccess": "Y",
+    "keywords": "Bleeding; Atrial fibrillation; Stroke; Frailty; Outcome; Oral Anticoagulation; Oral Anticoagulation Prescription",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>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.<h4>Methods and results</h4>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 \u22652 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.<h4>Conclusion</h4>Frailty among people with AF is common. The OAC was associated with a reduction in the primary endpoint across all degrees of frailty.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1093/europace/euac022; doi:https://doi.org/10.1093/europace/euac022; html:https://europepmc.org/articles/PMC9326851; pdf:https://europepmc.org/articles/PMC9326851?pdf=render"
+  },
   {
     "id": "33072403",
     "doi": "https://doi.org/10.1186/s40959-020-00079-3",
@@ -24989,23 +24989,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/jacamr/article-pdf/5/2/dlad039/49747584/dlad039.pdf; doi:https://doi.org/10.1093/jacamr/dlad039; html:https://europepmc.org/articles/PMC10072237; pdf:https://europepmc.org/articles/PMC10072237?pdf=render"
   },
-  {
-    "id": "35639667",
-    "doi": "https://doi.org/10.1093/eurheartj/ehac238",
-    "title": "Critical appraisal of artificial intelligence-based prediction models for cardiovascular disease.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal",
-    "pubYear": "2022",
-    "date": "2022-08-01",
-    "isOpenAccess": "Y",
-    "keywords": "Prediction; Artificial intelligence; Diagnosis; Prognosis; Machine Learning; Digital Health",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/eurheartj/article-pdf/43/31/2921/45333809/ehac238.pdf; doi:https://doi.org/10.1093/eurheartj/ehac238; html:https://europepmc.org/articles/PMC9443991; pdf:https://europepmc.org/articles/PMC9443991?pdf=render"
-  },
   {
     "id": "32810544",
     "doi": "https://doi.org/10.1016/j.ijcard.2020.08.030",
@@ -25023,6 +25006,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.internationaljournalofcardiology.com/article/S0167527320335579/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.08.030"
   },
+  {
+    "id": "35639667",
+    "doi": "https://doi.org/10.1093/eurheartj/ehac238",
+    "title": "Critical appraisal of artificial intelligence-based prediction models for cardiovascular disease.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "European heart journal",
+    "pubYear": "2022",
+    "date": "2022-08-01",
+    "isOpenAccess": "Y",
+    "keywords": "Prediction; Artificial intelligence; Diagnosis; Prognosis; Machine Learning; Digital Health",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/eurheartj/article-pdf/43/31/2921/45333809/ehac238.pdf; doi:https://doi.org/10.1093/eurheartj/ehac238; html:https://europepmc.org/articles/PMC9443991; pdf:https://europepmc.org/articles/PMC9443991?pdf=render"
+  },
   {
     "id": "34980174",
     "doi": "https://doi.org/10.1186/s12967-021-03210-9",
@@ -25091,23 +25091,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41533-022-00280-0.pdf; 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": "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": "32639589",
     "doi": "https://doi.org/10.1111/bcp.14458",
@@ -25125,6 +25108,23 @@
     "laySummary": "",
     "urls": "pdf:https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bcp.14458; doi:https://doi.org/10.1111/bcp.14458"
   },
+  {
+    "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": "34396190",
     "doi": "https://doi.org/10.1016/j.jaccao.2019.09.007",
@@ -25261,23 +25261,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1080/09602011.2020.1744453"
   },
-  {
-    "id": "34906385",
-    "doi": "https://doi.org/10.1016/j.burns.2021.07.025",
-    "title": "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.",
-    "authorString": "Cleland H, Tracy LM, Singer Y, Wood F, Gong J, Cameron P, Gabbe BJ.",
-    "authorAffiliations": "",
-    "journalTitle": "Burns : journal of the International Society for Burn Injuries",
-    "pubYear": "2022",
-    "date": "2021-08-12",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.burns.2021.07.025"
-  },
   {
     "id": "30554166",
     "doi": "https://doi.org/10.1136/injuryprev-2018-043019",
@@ -25295,6 +25278,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1136/injuryprev-2018-043019"
   },
+  {
+    "id": "34906385",
+    "doi": "https://doi.org/10.1016/j.burns.2021.07.025",
+    "title": "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.",
+    "authorString": "Cleland H, Tracy LM, Singer Y, Wood F, Gong J, Cameron P, Gabbe BJ.",
+    "authorAffiliations": "",
+    "journalTitle": "Burns : journal of the International Society for Burn Injuries",
+    "pubYear": "2022",
+    "date": "2021-08-12",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.burns.2021.07.025"
+  },
   {
     "id": "34930919",
     "doi": "https://doi.org/10.1038/s41467-021-26280-1",
@@ -25329,23 +25329,6 @@
     "laySummary": "",
     "urls": "pdf:https://bjgp.org/content/bjgp/71/707/e441.full.pdf; doi:https://doi.org/10.3399/bjgp20X714161; html:https://europepmc.org/articles/PMC8041293; pdf:https://europepmc.org/articles/PMC8041293?pdf=render"
   },
-  {
-    "id": "36423925",
-    "doi": "https://doi.org/10.1136/thorax-2022-219591",
-    "title": "Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK).",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "Thorax",
-    "pubYear": "2023",
-    "date": "2022-11-23",
-    "isOpenAccess": "Y",
-    "keywords": "Asthma; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.<h4>Study registration number</h4>NCT04330599.",
-    "laySummary": "",
-    "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render"
-  },
   {
     "id": "32238333",
     "doi": "https://doi.org/10.2196/16400",
@@ -25380,6 +25363,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41591-020-0916-2.pdf; 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"
   },
+  {
+    "id": "36423925",
+    "doi": "https://doi.org/10.1136/thorax-2022-219591",
+    "title": "Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK).",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "Thorax",
+    "pubYear": "2023",
+    "date": "2022-11-23",
+    "isOpenAccess": "Y",
+    "keywords": "Asthma; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.<h4>Study registration number</h4>NCT04330599.",
+    "laySummary": "",
+    "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render"
+  },
   {
     "id": "34040552",
     "doi": "https://doi.org/10.3389/fpsyt.2021.627996",
@@ -25448,6 +25448,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.jmir.org/2020/8/e20169/PDF; doi:https://doi.org/10.2196/20169; html:https://europepmc.org/articles/PMC7450371"
   },
+  {
+    "id": "33605084",
+    "doi": "https://doi.org/10.1111/jcmm.16388",
+    "title": "P62-positive aggregates are homogenously distributed in the myocardium and associated with the type of mutation in genetic cardiomyopathy.",
+    "authorString": "van der Klooster ZJ, Sepehrkhouy S, Dooijes D, Te Rijdt WP, Schuiringa FSAM, Lingeman J, van Tintelen JP, Harakalova M, Goldschmeding R, Suurmeijer AJH, Asselbergs FW, Vink A.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of cellular and molecular medicine",
+    "pubYear": "2021",
+    "date": "2021-02-18",
+    "isOpenAccess": "Y",
+    "keywords": "Histology; Pathology; Senescence; Genetic; Cardiomyopathy; Autophagy; P62; Phospholamban; Desminopathy; Sequestosome-1",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Genetic cardiomyopathy is caused by mutations in various genes. The accumulation of potentially proteotoxic mutant protein aggregates due to insufficient autophagy is a possible mechanism of disease development. The objective of this study was to investigate the distribution in the myocardium of such aggregates in relation to specific pathogenic genetic mutations in cardiomyopathy hearts. Hearts from 32 genetic cardiomyopathy patients, 4 non-genetic cardiomyopathy patients and 5 controls were studied. Microscopic slices from an entire midventricular heart slice were stained for p62 (sequestosome-1, marker for aggregated proteins destined for autophagy). The percentage of cardiomyocytes with p62 accumulation was higher in cardiomyopathy hearts (median 3.3%) than in healthy controls (0.3%; P\u00a0<\u00a0.0001). p62 accumulation was highest in the desmin (15.6%) and phospholamban (7.2%) groups. P62 accumulation was homogeneously distributed in the myocardium. Fibrosis was not associated with p62 accumulation in subgroup analysis of phospholamban hearts. In conclusion, accumulation of p62-positive protein aggregates is homogeneously distributed in the myocardium independently of fibrosis distribution and associated with desmin and phospholamban cardiomyopathy. Proteotoxic protein accumulation is a diffuse process in the myocardium while a more localized second hit, such as local strain during exercise, might determine whether this leads to regional myocyte decay.",
+    "laySummary": "",
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.16388; doi:https://doi.org/10.1111/jcmm.16388; html:https://europepmc.org/articles/PMC7957157; pdf:https://europepmc.org/articles/PMC7957157?pdf=render"
+  },
   {
     "id": "37391266",
     "doi": "https://doi.org/10.1016/s2589-7500(23)00087-0",
@@ -25500,21 +25517,21 @@
     "urls": "pdf:https://academic.oup.com/eurjcn/advance-article-pdf/doi/10.1093/eurjcn/zvac098/47022353/zvac098.pdf; doi:https://doi.org/10.1093/eurjcn/zvac098; html:https://europepmc.org/articles/PMC10353909; pdf:https://europepmc.org/articles/PMC10353909?pdf=render"
   },
   {
-    "id": "33605084",
-    "doi": "https://doi.org/10.1111/jcmm.16388",
-    "title": "P62-positive aggregates are homogenously distributed in the myocardium and associated with the type of mutation in genetic cardiomyopathy.",
-    "authorString": "van der Klooster ZJ, Sepehrkhouy S, Dooijes D, Te Rijdt WP, Schuiringa FSAM, Lingeman J, van Tintelen JP, Harakalova M, Goldschmeding R, Suurmeijer AJH, Asselbergs FW, Vink A.",
+    "id": "34785789",
+    "doi": "https://doi.org/10.1038/s41591-021-01546-9",
+    "title": "Patient-reported outcomes in the regulatory approval of medical devices.",
+    "authorString": "Cruz Rivera S, Dickens AP, Aiyegbusi OL, Flint R, Fleetcroft C, McPherson D, Collis P, Calvert MJ.",
     "authorAffiliations": "",
-    "journalTitle": "Journal of cellular and molecular medicine",
+    "journalTitle": "Nature medicine",
     "pubYear": "2021",
-    "date": "2021-02-18",
-    "isOpenAccess": "Y",
-    "keywords": "Histology; Pathology; Senescence; Genetic; Cardiomyopathy; Autophagy; P62; Phospholamban; Desminopathy; Sequestosome-1",
+    "date": "2021-12-01",
+    "isOpenAccess": "N",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "Genetic cardiomyopathy is caused by mutations in various genes. The accumulation of potentially proteotoxic mutant protein aggregates due to insufficient autophagy is a possible mechanism of disease development. The objective of this study was to investigate the distribution in the myocardium of such aggregates in relation to specific pathogenic genetic mutations in cardiomyopathy hearts. Hearts from 32 genetic cardiomyopathy patients, 4 non-genetic cardiomyopathy patients and 5 controls were studied. Microscopic slices from an entire midventricular heart slice were stained for p62 (sequestosome-1, marker for aggregated proteins destined for autophagy). The percentage of cardiomyocytes with p62 accumulation was higher in cardiomyopathy hearts (median 3.3%) than in healthy controls (0.3%; P\u00a0<\u00a0.0001). p62 accumulation was highest in the desmin (15.6%) and phospholamban (7.2%) groups. P62 accumulation was homogeneously distributed in the myocardium. Fibrosis was not associated with p62 accumulation in subgroup analysis of phospholamban hearts. In conclusion, accumulation of p62-positive protein aggregates is homogeneously distributed in the myocardium independently of fibrosis distribution and associated with desmin and phospholamban cardiomyopathy. Proteotoxic protein accumulation is a diffuse process in the myocardium while a more localized second hit, such as local strain during exercise, might determine whether this leads to regional myocyte decay.",
+    "abstract": "",
     "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.16388; doi:https://doi.org/10.1111/jcmm.16388; html:https://europepmc.org/articles/PMC7957157; pdf:https://europepmc.org/articles/PMC7957157?pdf=render"
+    "urls": "pdf:http://pure-oai.bham.ac.uk/ws/files/149366889/The_role_of_PROs_MedicalDevices_NatMed_FINAL_Sep_REVISED_CLEANCOPY2.pdf; doi:https://doi.org/10.1038/s41591-021-01546-9"
   },
   {
     "id": "37210036",
@@ -25533,23 +25550,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jacc.2023.05.005"
   },
-  {
-    "id": "34785789",
-    "doi": "https://doi.org/10.1038/s41591-021-01546-9",
-    "title": "Patient-reported outcomes in the regulatory approval of medical devices.",
-    "authorString": "Cruz Rivera S, Dickens AP, Aiyegbusi OL, Flint R, Fleetcroft C, McPherson D, Collis P, Calvert MJ.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature medicine",
-    "pubYear": "2021",
-    "date": "2021-12-01",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "laySummary": "",
-    "urls": "pdf:http://pure-oai.bham.ac.uk/ws/files/149366889/The_role_of_PROs_MedicalDevices_NatMed_FINAL_Sep_REVISED_CLEANCOPY2.pdf; doi:https://doi.org/10.1038/s41591-021-01546-9"
-  },
   {
     "id": "35047183",
     "doi": "https://doi.org/10.7189/jogh.11.01011",
@@ -25737,23 +25737,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1111/dme.13945"
   },
-  {
-    "id": "36335192",
-    "doi": "https://doi.org/10.1038/s41598-022-22218-9",
-    "title": "Genetic insights into smoking behaviours in 10,558 men of African ancestry from continental Africa and the UK.",
-    "authorString": "Piga NN, Boua PR, Soremekun C, Shrine N, Coley K, Brandenburg JT, Tobin MD, Ramsay M, Fatumo S, Choudhury A, Batini C.",
-    "authorAffiliations": "",
-    "journalTitle": "Scientific reports",
-    "pubYear": "2022",
-    "date": "2022-11-05",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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\u2009<\u20095\u2009\u00d7\u200910<sup>-6</sup>, 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.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41598-022-22218-9.pdf; doi:https://doi.org/10.1038/s41598-022-22218-9; html:https://europepmc.org/articles/PMC9637114; pdf:https://europepmc.org/articles/PMC9637114?pdf=render"
-  },
   {
     "id": "34173614",
     "doi": "https://doi.org/10.1016/s2666-7568(20)30012-x",
@@ -25771,6 +25754,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/s2666-7568(20)30012-x; doi:https://doi.org/10.1016/S2666-7568(20)30012-X; html:https://europepmc.org/articles/PMC7574931; pdf:https://europepmc.org/articles/PMC7574931?pdf=render"
   },
+  {
+    "id": "36335192",
+    "doi": "https://doi.org/10.1038/s41598-022-22218-9",
+    "title": "Genetic insights into smoking behaviours in 10,558 men of African ancestry from continental Africa and the UK.",
+    "authorString": "Piga NN, Boua PR, Soremekun C, Shrine N, Coley K, Brandenburg JT, Tobin MD, Ramsay M, Fatumo S, Choudhury A, Batini C.",
+    "authorAffiliations": "",
+    "journalTitle": "Scientific reports",
+    "pubYear": "2022",
+    "date": "2022-11-05",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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\u2009<\u20095\u2009\u00d7\u200910<sup>-6</sup>, 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.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41598-022-22218-9.pdf; doi:https://doi.org/10.1038/s41598-022-22218-9; html:https://europepmc.org/articles/PMC9637114; pdf:https://europepmc.org/articles/PMC9637114?pdf=render"
+  },
   {
     "id": "32401709",
     "doi": "https://doi.org/10.1016/s2468-2667(20)30112-2",
@@ -26009,23 +26009,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.jmir.org/2020/6/e18185/PDF; doi:https://doi.org/10.2196/18185; html:https://europepmc.org/articles/PMC7381072"
   },
-  {
-    "id": "37808344",
-    "doi": "https://doi.org/10.1016/j.jacadv.2023.100573",
-    "title": "<i>CYP2C19</i> Genotype Prevalence and Association With Recurrent Myocardial Infarction in British-South Asians Treated With\u00a0Clopidogrel.",
-    "authorString": "Magavern EF, Jacobs B, Warren H, Finocchiaro G, Finer S, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",
-    "authorAffiliations": "",
-    "journalTitle": "JACC. Advances",
-    "pubYear": "2023",
-    "date": "2023-09-01",
-    "isOpenAccess": "Y",
-    "keywords": "Pharmacogenomics; ischemic heart disease; Pharmacotherapy; Preventive Cardiology",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in <i>CYP2C19</i> and their relationship with clinical efficacy have not included South Asian populations.<h4>Objectives</h4>The objective of this study was to assess prevalence of common <i>CYP2C19</i> genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.<h4>Methods</h4>The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. <i>CYP2C19</i> diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification.<h4>Results</h4>Genes & Health cohort participants (N\u00a0=\u00a044,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function <i>CYP2C19</i> allele. The prevalence of poor metabolizers carrying 2\u00a0<i>CYP2C19</i> loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; <i>P</i>\u00a0=\u00a00.019).<h4>Conclusions</h4>A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.jacadv.2023.100573; html:https://europepmc.org/articles/PMC10550831; pdf:https://europepmc.org/articles/PMC10550831?pdf=render"
-  },
   {
     "id": "32935062",
     "doi": "https://doi.org/10.23889/ijpds.v5i2.1383",
@@ -26043,6 +26026,23 @@
     "laySummary": "",
     "urls": "pdf:https://ijpds.org/article/download/1383/2566; doi:https://doi.org/10.23889/ijpds.v5i2.1383; html:https://europepmc.org/articles/PMC7473253; pdf:https://europepmc.org/articles/PMC7473253?pdf=render"
   },
+  {
+    "id": "37808344",
+    "doi": "https://doi.org/10.1016/j.jacadv.2023.100573",
+    "title": "<i>CYP2C19</i> Genotype Prevalence and Association With Recurrent Myocardial Infarction in British-South Asians Treated With\u00a0Clopidogrel.",
+    "authorString": "Magavern EF, Jacobs B, Warren H, Finocchiaro G, Finer S, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",
+    "authorAffiliations": "",
+    "journalTitle": "JACC. Advances",
+    "pubYear": "2023",
+    "date": "2023-09-01",
+    "isOpenAccess": "Y",
+    "keywords": "Pharmacogenomics; ischemic heart disease; Pharmacotherapy; Preventive Cardiology",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in <i>CYP2C19</i> and their relationship with clinical efficacy have not included South Asian populations.<h4>Objectives</h4>The objective of this study was to assess prevalence of common <i>CYP2C19</i> genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.<h4>Methods</h4>The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. <i>CYP2C19</i> diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification.<h4>Results</h4>Genes & Health cohort participants (N\u00a0=\u00a044,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function <i>CYP2C19</i> allele. The prevalence of poor metabolizers carrying 2\u00a0<i>CYP2C19</i> loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; <i>P</i>\u00a0=\u00a00.019).<h4>Conclusions</h4>A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.jacadv.2023.100573; html:https://europepmc.org/articles/PMC10550831; pdf:https://europepmc.org/articles/PMC10550831?pdf=render"
+  },
   {
     "id": "32909959",
     "doi": "https://doi.org/10.1136/bmj.m3164",
@@ -26111,23 +26111,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/s0140-6736(20)31356-8; 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"
   },
-  {
-    "id": "36357634",
-    "doi": "https://doi.org/10.1007/s00467-022-05789-7",
-    "title": "Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.",
-    "authorString": "Downie ML, Gupta S, Chan MMY, Sadeghi-Alavijeh O, Cao J, Parekh RS, Diz CB, Bierzynska A, Levine AP, Pepper RJ, Stanescu H, Saleem MA, Kleta R, Bockenhauer D, Koziell AB, Gale DP.",
-    "authorAffiliations": "",
-    "journalTitle": "Pediatric nephrology (Berlin, Germany)",
-    "pubYear": "2023",
-    "date": "2022-11-10",
-    "isOpenAccess": "Y",
-    "keywords": "Paediatrics; Minimal Change Disease; Focal Segmental Glomerulosclerosis; Monogenic; Genetic Risk Score; Steroid-resistant Nephrotic Syndrome; Steroid-sensitive Nephrotic Syndrome",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways.<h4>Methods</h4>We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls.<h4>Results</h4>The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS.<h4>Conclusions</h4>The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. A higher resolution version of the Graphical abstract is available as Supplementary information.",
-    "laySummary": "",
-    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05789-7.pdf; doi:https://doi.org/10.1007/s00467-022-05789-7; html:https://europepmc.org/articles/PMC10154254; pdf:https://europepmc.org/articles/PMC10154254?pdf=render"
-  },
   {
     "id": "35434685",
     "doi": "https://doi.org/10.1016/j.lanepe.2022.100381",
@@ -26145,6 +26128,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.lanepe.2022.100381; 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": "36357634",
+    "doi": "https://doi.org/10.1007/s00467-022-05789-7",
+    "title": "Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.",
+    "authorString": "Downie ML, Gupta S, Chan MMY, Sadeghi-Alavijeh O, Cao J, Parekh RS, Diz CB, Bierzynska A, Levine AP, Pepper RJ, Stanescu H, Saleem MA, Kleta R, Bockenhauer D, Koziell AB, Gale DP.",
+    "authorAffiliations": "",
+    "journalTitle": "Pediatric nephrology (Berlin, Germany)",
+    "pubYear": "2023",
+    "date": "2022-11-10",
+    "isOpenAccess": "Y",
+    "keywords": "Paediatrics; Minimal Change Disease; Focal Segmental Glomerulosclerosis; Monogenic; Genetic Risk Score; Steroid-resistant Nephrotic Syndrome; Steroid-sensitive Nephrotic Syndrome",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways.<h4>Methods</h4>We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls.<h4>Results</h4>The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS.<h4>Conclusions</h4>The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. A higher resolution version of the Graphical abstract is available as Supplementary information.",
+    "laySummary": "",
+    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05789-7.pdf; doi:https://doi.org/10.1007/s00467-022-05789-7; html:https://europepmc.org/articles/PMC10154254; pdf:https://europepmc.org/articles/PMC10154254?pdf=render"
+  },
   {
     "id": "33048945",
     "doi": "https://doi.org/10.1371/journal.pmed.1003290",
@@ -26179,23 +26179,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41366-021-00896-1.pdf; 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": "35365070",
-    "doi": "https://doi.org/10.1186/s12879-022-07268-8",
-    "title": "Impact of non-pharmaceutical interventions on SARS-CoV-2 outbreaks in English care homes: a modelling study.",
-    "authorString": "Rosello A, Barnard RC, Smith DRM, Evans S, Grimm F, Davies NG, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Modelling Working Group, Deeny SR, Knight GM, Edmunds WJ.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC infectious diseases",
-    "pubYear": "2022",
-    "date": "2022-04-01",
-    "isOpenAccess": "Y",
-    "keywords": "PCR; Testing; mathematical model; Long-term Care Facility; Care Home; Non-pharmaceutical Interventions; Covid-19; Sars-cov-2",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>COVID-19 outbreaks still occur in English care homes despite the interventions in place.<h4>Methods</h4>We developed a stochastic compartmental model to simulate the spread of SARS-CoV-2 within an English care home. We quantified the outbreak risk with baseline non-pharmaceutical interventions (NPIs) already in place, the role of community prevalence in driving outbreaks, and the relative contribution of all importation routes into a fully susceptible care home. We also considered the potential impact of additional control measures in care homes with and without immunity, namely: increasing staff and resident testing frequency, using lateral flow antigen testing (LFD) tests instead of polymerase chain reaction (PCR), enhancing infection prevention and control (IPC), increasing the proportion of residents isolated, shortening the delay to isolation, improving the effectiveness of isolation, restricting visitors and limiting staff to working in one care home. We additionally present a Shiny application for users to apply this model to their facility of interest, specifying care home, outbreak and intervention characteristics.<h4>Results</h4>The model suggests that importation of SARS-CoV-2 by staff, from the community, is the main driver of outbreaks, that importation by visitors or from hospitals is rare, and that the past testing strategy (monthly testing of residents and daily testing of staff by PCR) likely provides negligible benefit in preventing outbreaks. Daily staff testing by LFD was 39% (95% 18-55%) effective in preventing outbreaks at 30\u00a0days compared to no testing.<h4>Conclusions</h4>Increasing the frequency of testing in staff and enhancing IPC are important to preventing importations to the care home. Further work is needed to understand the impact of vaccination in this population, which is likely to be very effective in preventing outbreaks.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/s12879-022-07268-8; doi:https://doi.org/10.1186/s12879-022-07268-8; html:https://europepmc.org/articles/PMC8972713; pdf:https://europepmc.org/articles/PMC8972713?pdf=render"
-  },
   {
     "id": "34859219",
     "doi": "https://doi.org/10.1093/braincomms/fcab275",
@@ -26213,6 +26196,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/braincomms/article-pdf/3/4/fcab275/41365065/fcab275.pdf; doi:https://doi.org/10.1093/braincomms/fcab275; html:https://europepmc.org/articles/PMC8633770; pdf:https://europepmc.org/articles/PMC8633770?pdf=render"
   },
+  {
+    "id": "35365070",
+    "doi": "https://doi.org/10.1186/s12879-022-07268-8",
+    "title": "Impact of non-pharmaceutical interventions on SARS-CoV-2 outbreaks in English care homes: a modelling study.",
+    "authorString": "Rosello A, Barnard RC, Smith DRM, Evans S, Grimm F, Davies NG, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Modelling Working Group, Deeny SR, Knight GM, Edmunds WJ.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC infectious diseases",
+    "pubYear": "2022",
+    "date": "2022-04-01",
+    "isOpenAccess": "Y",
+    "keywords": "PCR; Testing; mathematical model; Long-term Care Facility; Care Home; Non-pharmaceutical Interventions; Covid-19; Sars-cov-2",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>COVID-19 outbreaks still occur in English care homes despite the interventions in place.<h4>Methods</h4>We developed a stochastic compartmental model to simulate the spread of SARS-CoV-2 within an English care home. We quantified the outbreak risk with baseline non-pharmaceutical interventions (NPIs) already in place, the role of community prevalence in driving outbreaks, and the relative contribution of all importation routes into a fully susceptible care home. We also considered the potential impact of additional control measures in care homes with and without immunity, namely: increasing staff and resident testing frequency, using lateral flow antigen testing (LFD) tests instead of polymerase chain reaction (PCR), enhancing infection prevention and control (IPC), increasing the proportion of residents isolated, shortening the delay to isolation, improving the effectiveness of isolation, restricting visitors and limiting staff to working in one care home. We additionally present a Shiny application for users to apply this model to their facility of interest, specifying care home, outbreak and intervention characteristics.<h4>Results</h4>The model suggests that importation of SARS-CoV-2 by staff, from the community, is the main driver of outbreaks, that importation by visitors or from hospitals is rare, and that the past testing strategy (monthly testing of residents and daily testing of staff by PCR) likely provides negligible benefit in preventing outbreaks. Daily staff testing by LFD was 39% (95% 18-55%) effective in preventing outbreaks at 30\u00a0days compared to no testing.<h4>Conclusions</h4>Increasing the frequency of testing in staff and enhancing IPC are important to preventing importations to the care home. Further work is needed to understand the impact of vaccination in this population, which is likely to be very effective in preventing outbreaks.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/s12879-022-07268-8; doi:https://doi.org/10.1186/s12879-022-07268-8; html:https://europepmc.org/articles/PMC8972713; pdf:https://europepmc.org/articles/PMC8972713?pdf=render"
+  },
   {
     "id": "33986429",
     "doi": "https://doi.org/10.1038/s41598-021-89743-x",
@@ -26247,23 +26247,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000292&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000292; html:https://europepmc.org/articles/PMC10021216; pdf:https://europepmc.org/articles/PMC10021216?pdf=render"
   },
-  {
-    "id": "36210800",
-    "doi": "https://doi.org/10.1038/s43856-022-00189-2",
-    "title": "Feasibility and ethics of using data from the Scottish newborn blood spot archive for research.",
-    "authorString": "Cunningham-Burley S, McCartney DL, Campbell A, Flaig R, Orange CEL, Porteous C, Aitken M, Mulholland C, Davidson S, McCafferty SM, Murphy L, Wrobel N, McCafferty S, Wallace K, StClair D, Kerr S, Hayward C, McIntosh AM, Sudlow C, Marioni RE, Pell J, Miedzybrodzka Z, Porteous DJ.",
-    "authorAffiliations": "",
-    "journalTitle": "Communications medicine",
-    "pubYear": "2022",
-    "date": "2022-10-06",
-    "isOpenAccess": "Y",
-    "keywords": "epigenomics; epidemiology",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Newborn heel prick blood spots are routinely used to screen for inborn errors of metabolism and life-limiting inherited disorders. The potential value of secondary data from newborn blood spot archives merits ethical consideration and assessment of feasibility for public benefit. Early life exposures and behaviours set health trajectories in childhood and later life. The newborn blood spot is potentially well placed to create an unbiased and cost-effective population-level retrospective birth cohort study. Scotland has retained newborn blood spots for all children born since 1965, around 3 million in total. However, a moratorium on research access is currently in place, pending public consultation.<h4>Methods</h4>We conducted a Citizens' Jury as a first step to explore whether research use of newborn blood spots was in the public interest. We also assessed the feasibility and value of extracting research data from dried blood spots for predictive medicine.<h4>Results</h4>Jurors delivered an agreed verdict that conditional research access to the newborn blood spots was in the public interest. The Chief Medical Officer for Scotland authorised restricted lifting of the current research moratorium to allow a feasibility study. Newborn blood spots from consented Generation Scotland volunteers were retrieved and their potential for both epidemiological and biological research demonstrated.<h4>Conclusions</h4>Through the Citizens' Jury, we have begun to identify under what conditions, if any, should researchers in Scotland be granted access to the archive. Through the feasibility study, we have demonstrated the potential value of research access for health data science and predictive medicine.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s43856-022-00189-2.pdf; doi:https://doi.org/10.1038/s43856-022-00189-2; html:https://europepmc.org/articles/PMC9537278; pdf:https://europepmc.org/articles/PMC9537278?pdf=render"
-  },
   {
     "id": "31220083",
     "doi": "https://doi.org/10.1371/journal.pmed.1002833",
@@ -26281,6 +26264,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1371/journal.pmed.1002833; doi:https://doi.org/10.1371/journal.pmed.1002833; html:https://europepmc.org/articles/PMC6586257; pdf:https://europepmc.org/articles/PMC6586257?pdf=render"
   },
+  {
+    "id": "36210800",
+    "doi": "https://doi.org/10.1038/s43856-022-00189-2",
+    "title": "Feasibility and ethics of using data from the Scottish newborn blood spot archive for research.",
+    "authorString": "Cunningham-Burley S, McCartney DL, Campbell A, Flaig R, Orange CEL, Porteous C, Aitken M, Mulholland C, Davidson S, McCafferty SM, Murphy L, Wrobel N, McCafferty S, Wallace K, StClair D, Kerr S, Hayward C, McIntosh AM, Sudlow C, Marioni RE, Pell J, Miedzybrodzka Z, Porteous DJ.",
+    "authorAffiliations": "",
+    "journalTitle": "Communications medicine",
+    "pubYear": "2022",
+    "date": "2022-10-06",
+    "isOpenAccess": "Y",
+    "keywords": "epigenomics; epidemiology",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Newborn heel prick blood spots are routinely used to screen for inborn errors of metabolism and life-limiting inherited disorders. The potential value of secondary data from newborn blood spot archives merits ethical consideration and assessment of feasibility for public benefit. Early life exposures and behaviours set health trajectories in childhood and later life. The newborn blood spot is potentially well placed to create an unbiased and cost-effective population-level retrospective birth cohort study. Scotland has retained newborn blood spots for all children born since 1965, around 3 million in total. However, a moratorium on research access is currently in place, pending public consultation.<h4>Methods</h4>We conducted a Citizens' Jury as a first step to explore whether research use of newborn blood spots was in the public interest. We also assessed the feasibility and value of extracting research data from dried blood spots for predictive medicine.<h4>Results</h4>Jurors delivered an agreed verdict that conditional research access to the newborn blood spots was in the public interest. The Chief Medical Officer for Scotland authorised restricted lifting of the current research moratorium to allow a feasibility study. Newborn blood spots from consented Generation Scotland volunteers were retrieved and their potential for both epidemiological and biological research demonstrated.<h4>Conclusions</h4>Through the Citizens' Jury, we have begun to identify under what conditions, if any, should researchers in Scotland be granted access to the archive. Through the feasibility study, we have demonstrated the potential value of research access for health data science and predictive medicine.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s43856-022-00189-2.pdf; doi:https://doi.org/10.1038/s43856-022-00189-2; html:https://europepmc.org/articles/PMC9537278; pdf:https://europepmc.org/articles/PMC9537278?pdf=render"
+  },
   {
     "id": "35241573",
     "doi": "https://doi.org/10.1136/bmjqs-2020-012108",
@@ -26417,23 +26417,6 @@
     "laySummary": "",
     "urls": "pdf:https://mhealth.jmir.org/2021/7/e29840/PDF; doi:https://doi.org/10.2196/29840; html:https://europepmc.org/articles/PMC8367113"
   },
-  {
-    "id": "35568032",
-    "doi": "https://doi.org/10.1016/j.ajhg.2022.04.009",
-    "title": "Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites.",
-    "authorString": "Bomba L, Walter K, Guo Q, Surendran P, Kundu K, Nongmaithem S, Karim MA, Stewart ID, Langenberg C, Danesh J, Di Angelantonio E, Roberts DJ, Ouwehand WH, INTERVAL study, Dunham I, Butterworth AS, Soranzo N.",
-    "authorAffiliations": "",
-    "journalTitle": "American journal of human genetics",
-    "pubYear": "2022",
-    "date": "2022-05-13",
-    "isOpenAccess": "Y",
-    "keywords": "Sequencing; Proteomics; drug targets; Metabolomics; Endophenotypes; Loss-of-function; Metabolon; Wgs; Wes; Rare Genetic Variant",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Metabolite levels measured in the human population are endophenotypes for biological processes. We combined sequencing data for 3,924 (whole-exome sequencing, WES, discovery) and 2,805 (whole-genome sequencing, WGS, replication) donors from a prospective cohort of blood donors in England. We used multiple approaches to select and aggregate rare genetic variants (minor allele frequency [MAF]\u00a0<\u00a00.1%) in protein-coding regions and tested their associations with 995 metabolites measured in plasma by using ultra-high-performance liquid chromatography-tandem mass spectrometry. We identified 40 novel associations implicating rare coding variants (27 genes and 38 metabolites), of which 28 (15 genes and 28 metabolites) were replicated. We developed algorithms to prioritize putative driver variants at each locus and used mediation and Mendelian randomization analyses to test directionality at associations of metabolite and protein levels at the ACY1 locus. Overall, 66% of reported associations implicate gene targets of approved drugs or bioactive drug-like compounds, contributing to drug targets' validating efforts.",
-    "laySummary": "",
-    "urls": "pdf:https://www.repository.cam.ac.uk/bitstream/1810/337646/3/1-s2.0-S0002929722001574-main.pdf; doi:https://doi.org/10.1016/j.ajhg.2022.04.009; html:https://europepmc.org/articles/PMC9247822; pdf:https://europepmc.org/articles/PMC9247822?pdf=render"
-  },
   {
     "id": "34796724",
     "doi": "https://doi.org/10.1161/jaha.120.019814",
@@ -26451,6 +26434,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.120.019814; doi:https://doi.org/10.1161/JAHA.120.019814; html:https://europepmc.org/articles/PMC9075396; pdf:https://europepmc.org/articles/PMC9075396?pdf=render"
   },
+  {
+    "id": "35568032",
+    "doi": "https://doi.org/10.1016/j.ajhg.2022.04.009",
+    "title": "Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites.",
+    "authorString": "Bomba L, Walter K, Guo Q, Surendran P, Kundu K, Nongmaithem S, Karim MA, Stewart ID, Langenberg C, Danesh J, Di Angelantonio E, Roberts DJ, Ouwehand WH, INTERVAL study, Dunham I, Butterworth AS, Soranzo N.",
+    "authorAffiliations": "",
+    "journalTitle": "American journal of human genetics",
+    "pubYear": "2022",
+    "date": "2022-05-13",
+    "isOpenAccess": "Y",
+    "keywords": "Sequencing; Proteomics; drug targets; Metabolomics; Endophenotypes; Loss-of-function; Metabolon; Wgs; Wes; Rare Genetic Variant",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Metabolite levels measured in the human population are endophenotypes for biological processes. We combined sequencing data for 3,924 (whole-exome sequencing, WES, discovery) and 2,805 (whole-genome sequencing, WGS, replication) donors from a prospective cohort of blood donors in England. We used multiple approaches to select and aggregate rare genetic variants (minor allele frequency [MAF]\u00a0<\u00a00.1%) in protein-coding regions and tested their associations with 995 metabolites measured in plasma by using ultra-high-performance liquid chromatography-tandem mass spectrometry. We identified 40 novel associations implicating rare coding variants (27 genes and 38 metabolites), of which 28 (15 genes and 28 metabolites) were replicated. We developed algorithms to prioritize putative driver variants at each locus and used mediation and Mendelian randomization analyses to test directionality at associations of metabolite and protein levels at the ACY1 locus. Overall, 66% of reported associations implicate gene targets of approved drugs or bioactive drug-like compounds, contributing to drug targets' validating efforts.",
+    "laySummary": "",
+    "urls": "pdf:https://www.repository.cam.ac.uk/bitstream/1810/337646/3/1-s2.0-S0002929722001574-main.pdf; doi:https://doi.org/10.1016/j.ajhg.2022.04.009; html:https://europepmc.org/articles/PMC9247822; pdf:https://europepmc.org/articles/PMC9247822?pdf=render"
+  },
   {
     "id": "30585256",
     "doi": "https://doi.org/10.1038/s41416-018-0365-6",
@@ -26587,23 +26587,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0253809&type=printable; doi:https://doi.org/10.1371/journal.pone.0253809; html:https://europepmc.org/articles/PMC8336818; pdf:https://europepmc.org/articles/PMC8336818?pdf=render"
   },
-  {
-    "id": "35238940",
-    "doi": "https://doi.org/10.1093/ndt/gfac040",
-    "title": "Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial.",
-    "authorString": "EMPA-KIDNEY Collaborative Group.",
-    "authorAffiliations": "",
-    "journalTitle": "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",
-    "pubYear": "2022",
-    "date": "2022-06-01",
-    "isOpenAccess": "Y",
-    "keywords": "Cardiovascular disease; Empagliflozin; Sodium-glucose Co-transporter 2 Inhibitor; Ckd, Clinical Trial",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>The effects of the sodium-glucose co-transporter 2 inhibitor empagliflozin on renal and cardiovascular disease have not been tested in a dedicated population of people with chronic kidney disease (CKD).<h4>Methods</h4>The EMPA-KIDNEY trial is an international randomized, double-blind, placebo-controlled trial assessing whether empagliflozin 10\u00a0mg daily decreases the risk of kidney disease progression or cardiovascular death in people with CKD. People with or without diabetes mellitus (DM) were eligible provided they had an estimated glomerular filtration rate (eGFR) \u226520 but <45\u00a0mL/min/1.73\u00a0m2 or an eGFR\u00a0\u226545 but <90\u00a0mL/min/1.73\u00a0m2 with a urinary albumin:creatinine ratio (uACR) \u2265200\u00a0mg/g. The trial design is streamlined, as extra work for collaborating sites is kept to a minimum and only essential information is collected.<h4>Results</h4>Between 15 May 2019 and 16 April 2021, 6609 people from eight countries in Europe, North America and East Asia were randomized. The mean age at randomization was 63.8 years [standard deviation (SD) 13.9)], 2192 (33%) were female and 3570 (54%) had no prior history of DM. The mean eGFR was 37.5 mL/min/1.73\u00a0m2 (SD 14.8), including 5185 (78%) with an eGFR\u00a0<45\u00a0mL/min/1.73\u00a0m2. The median uACR was 412 mg/g) (quartile 1-quartile 3 94-1190), with a uACR\u00a0<300\u00a0mg/g\u00a0in 3194 (48%). The causes of kidney disease included diabetic kidney disease [n\u00a0=\u00a02057 (31%)], glomerular disease [n\u00a0=\u00a01669 (25%)], hypertensive/renovascular disease [n\u00a0=\u00a01445 (22%)], other [n\u00a0=\u00a0808 (12%)] and unknown causes [n\u00a0=\u00a0630 (10%)].<h4>Conclusions</h4>EMPA-KIDNEY will evaluate the efficacy and safety of empagliflozin in a widely generalizable population of people with CKD at risk of kidney disease progression. Results are anticipated in 2022.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/ndt/article-pdf/37/7/1317/44138360/gfac040.pdf; doi:https://doi.org/10.1093/ndt/gfac040; html:https://europepmc.org/articles/PMC9217655; pdf:https://europepmc.org/articles/PMC9217655?pdf=render"
-  },
   {
     "id": "30993728",
     "doi": "https://doi.org/10.1111/cen.13990",
@@ -26621,6 +26604,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1111/cen.13990"
   },
+  {
+    "id": "35238940",
+    "doi": "https://doi.org/10.1093/ndt/gfac040",
+    "title": "Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial.",
+    "authorString": "EMPA-KIDNEY Collaborative Group.",
+    "authorAffiliations": "",
+    "journalTitle": "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",
+    "pubYear": "2022",
+    "date": "2022-06-01",
+    "isOpenAccess": "Y",
+    "keywords": "Cardiovascular disease; Empagliflozin; Sodium-glucose Co-transporter 2 Inhibitor; Ckd, Clinical Trial",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>The effects of the sodium-glucose co-transporter 2 inhibitor empagliflozin on renal and cardiovascular disease have not been tested in a dedicated population of people with chronic kidney disease (CKD).<h4>Methods</h4>The EMPA-KIDNEY trial is an international randomized, double-blind, placebo-controlled trial assessing whether empagliflozin 10\u00a0mg daily decreases the risk of kidney disease progression or cardiovascular death in people with CKD. People with or without diabetes mellitus (DM) were eligible provided they had an estimated glomerular filtration rate (eGFR) \u226520 but <45\u00a0mL/min/1.73\u00a0m2 or an eGFR\u00a0\u226545 but <90\u00a0mL/min/1.73\u00a0m2 with a urinary albumin:creatinine ratio (uACR) \u2265200\u00a0mg/g. The trial design is streamlined, as extra work for collaborating sites is kept to a minimum and only essential information is collected.<h4>Results</h4>Between 15 May 2019 and 16 April 2021, 6609 people from eight countries in Europe, North America and East Asia were randomized. The mean age at randomization was 63.8 years [standard deviation (SD) 13.9)], 2192 (33%) were female and 3570 (54%) had no prior history of DM. The mean eGFR was 37.5 mL/min/1.73\u00a0m2 (SD 14.8), including 5185 (78%) with an eGFR\u00a0<45\u00a0mL/min/1.73\u00a0m2. The median uACR was 412 mg/g) (quartile 1-quartile 3 94-1190), with a uACR\u00a0<300\u00a0mg/g\u00a0in 3194 (48%). The causes of kidney disease included diabetic kidney disease [n\u00a0=\u00a02057 (31%)], glomerular disease [n\u00a0=\u00a01669 (25%)], hypertensive/renovascular disease [n\u00a0=\u00a01445 (22%)], other [n\u00a0=\u00a0808 (12%)] and unknown causes [n\u00a0=\u00a0630 (10%)].<h4>Conclusions</h4>EMPA-KIDNEY will evaluate the efficacy and safety of empagliflozin in a widely generalizable population of people with CKD at risk of kidney disease progression. Results are anticipated in 2022.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/ndt/article-pdf/37/7/1317/44138360/gfac040.pdf; doi:https://doi.org/10.1093/ndt/gfac040; html:https://europepmc.org/articles/PMC9217655; pdf:https://europepmc.org/articles/PMC9217655?pdf=render"
+  },
   {
     "id": "33659712",
     "doi": "https://doi.org/10.12688/wellcomeopenres.16431.2",
@@ -26638,23 +26638,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16431.2; html:https://europepmc.org/articles/PMC7901498; pdf:https://europepmc.org/articles/PMC7901498?pdf=render"
   },
-  {
-    "id": "33542327",
-    "doi": "https://doi.org/10.1038/s41598-021-82214-3",
-    "title": "Classification of paediatric brain tumours by diffusion weighted imaging and machine learning.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "Scientific reports",
-    "pubYear": "2021",
-    "date": "2021-02-04",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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\u2009<\u20090.001). A cut off value for mean ADC between Ependymomas and Medulloblastomas was found to be of 0.984\u2009\u00d7\u200910<sup>-3</sup> mm<sup>2</sup>\u00a0s<sup>-1</sup> with sensitivity 80.8% and specificity 80.0%. Overall classification for the ADC histogram metrics were 85% using Na\u00efve 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.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41598-021-82214-3.pdf; 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": "30120083",
     "doi": "https://doi.org/10.1016/j.ebiom.2018.08.004",
@@ -26672,6 +26655,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2352396418302925/pdf; doi:https://doi.org/10.1016/j.ebiom.2018.08.004; html:https://europepmc.org/articles/PMC6154782; pdf:https://europepmc.org/articles/PMC6154782?pdf=render"
   },
+  {
+    "id": "33542327",
+    "doi": "https://doi.org/10.1038/s41598-021-82214-3",
+    "title": "Classification of paediatric brain tumours by diffusion weighted imaging and machine learning.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "Scientific reports",
+    "pubYear": "2021",
+    "date": "2021-02-04",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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\u2009<\u20090.001). A cut off value for mean ADC between Ependymomas and Medulloblastomas was found to be of 0.984\u2009\u00d7\u200910<sup>-3</sup> mm<sup>2</sup>\u00a0s<sup>-1</sup> with sensitivity 80.8% and specificity 80.0%. Overall classification for the ADC histogram metrics were 85% using Na\u00efve 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.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41598-021-82214-3.pdf; 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": "35762393",
     "doi": "https://doi.org/10.1093/oncolo/oyac117",
@@ -26690,21 +26690,21 @@
     "urls": "pdf:https://academic.oup.com/oncolo/article-pdf/27/9/768/45667678/oyac117.pdf; doi:https://doi.org/10.1093/oncolo/oyac117; html:https://europepmc.org/articles/PMC9438918; pdf:https://europepmc.org/articles/PMC9438918?pdf=render"
   },
   {
-    "id": "36408685",
-    "doi": "https://doi.org/10.1161/circheartfailure.122.009526",
-    "title": "Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure.",
-    "authorString": "G\u00fcrg\u00f6ze MT, van Vark LC, Baart SJ, Kardys I, Akkerhuis KM, Manintveld OC, Postmus D, Hillege HL, Lesman-Leegte I, Asselbergs FW, Brunner-la-Rocca HP, van den Bos EJ, Orsel JG, de Ridder SPJ, Pinto YM, Boersma E.",
+    "id": "32346541",
+    "doi": "https://doi.org/10.1093/burnst/tkz004",
+    "title": "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.",
+    "authorString": "Tracy LM, Edgar DW, Schrale R, Cleland H, Gabbe BJ, BRANZ Adult Long-Term Outcomes Pilot Project participating sites and working party.",
     "authorAffiliations": "",
-    "journalTitle": "Circulation. Heart failure",
-    "pubYear": "2023",
-    "date": "2022-11-21",
+    "journalTitle": "Burns & trauma",
+    "pubYear": "2020",
+    "date": "2020-02-27",
     "isOpenAccess": "Y",
-    "keywords": "Prognosis; Biomarkers; Heart Failure; Growth Differentiation Factor 15",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk.<h4>Methods</h4>TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling.<h4>Results</h4>Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785).<h4>Conclusions</h4>Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice.<h4>Registration</h4>URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).",
+    "keywords": "Australia; Pain; New Zealand; Cohort study; Outcomes; Predictor; Itch; Burn Registry",
+    "nationalPriorities": "Better Care",
+    "healthCategories": "injuries and accidents",
+    "abstract": "<h4>Background</h4>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\u00a0months 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.<h4>Methods</h4>Burn patients aged 18\u00a0years 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.<h4>Results</h4>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 \u2265\u200950\u00a0years, 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\u2009\u2265\u200950\u00a0years, respectively.<h4>Conclusions</h4>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.",
     "laySummary": "",
-    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.122.009526; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.122.009526; html:https://europepmc.org/articles/PMC9833118; pdf:https://europepmc.org/articles/PMC9833118?pdf=render"
+    "urls": "pdf:https://academic.oup.com/burnstrauma/article-pdf/doi/10.1093/burnst/tkz004/33423529/tkz004.pdf; doi:https://doi.org/10.1093/burnst/tkz004; html:https://europepmc.org/articles/PMC7175773; pdf:https://europepmc.org/articles/PMC7175773?pdf=render"
   },
   {
     "id": "35193912",
@@ -26724,21 +26724,21 @@
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e053884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053884; html:https://europepmc.org/articles/PMC8867374; pdf:https://europepmc.org/articles/PMC8867374?pdf=render"
   },
   {
-    "id": "32346541",
-    "doi": "https://doi.org/10.1093/burnst/tkz004",
-    "title": "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.",
-    "authorString": "Tracy LM, Edgar DW, Schrale R, Cleland H, Gabbe BJ, BRANZ Adult Long-Term Outcomes Pilot Project participating sites and working party.",
+    "id": "36408685",
+    "doi": "https://doi.org/10.1161/circheartfailure.122.009526",
+    "title": "Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure.",
+    "authorString": "G\u00fcrg\u00f6ze MT, van Vark LC, Baart SJ, Kardys I, Akkerhuis KM, Manintveld OC, Postmus D, Hillege HL, Lesman-Leegte I, Asselbergs FW, Brunner-la-Rocca HP, van den Bos EJ, Orsel JG, de Ridder SPJ, Pinto YM, Boersma E.",
     "authorAffiliations": "",
-    "journalTitle": "Burns & trauma",
-    "pubYear": "2020",
-    "date": "2020-02-27",
+    "journalTitle": "Circulation. Heart failure",
+    "pubYear": "2023",
+    "date": "2022-11-21",
     "isOpenAccess": "Y",
-    "keywords": "Australia; Pain; New Zealand; Cohort study; Outcomes; Predictor; Itch; Burn Registry",
-    "nationalPriorities": "Better Care",
-    "healthCategories": "injuries and accidents",
-    "abstract": "<h4>Background</h4>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\u00a0months 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.<h4>Methods</h4>Burn patients aged 18\u00a0years 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.<h4>Results</h4>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 \u2265\u200950\u00a0years, 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\u2009\u2265\u200950\u00a0years, respectively.<h4>Conclusions</h4>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.",
+    "keywords": "Prognosis; Biomarkers; Heart Failure; Growth Differentiation Factor 15",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk.<h4>Methods</h4>TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling.<h4>Results</h4>Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785).<h4>Conclusions</h4>Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice.<h4>Registration</h4>URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).",
     "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/burnstrauma/article-pdf/doi/10.1093/burnst/tkz004/33423529/tkz004.pdf; doi:https://doi.org/10.1093/burnst/tkz004; html:https://europepmc.org/articles/PMC7175773; pdf:https://europepmc.org/articles/PMC7175773?pdf=render"
+    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.122.009526; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.122.009526; html:https://europepmc.org/articles/PMC9833118; pdf:https://europepmc.org/articles/PMC9833118?pdf=render"
   },
   {
     "id": "33482294",
@@ -26774,23 +26774,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-022-31626-4.pdf; doi:https://doi.org/10.1038/s41467-022-31626-4; html:https://europepmc.org/articles/PMC9283523; pdf:https://europepmc.org/articles/PMC9283523?pdf=render"
   },
-  {
-    "id": "35880304",
-    "doi": "https://doi.org/10.1002/jbmr.4664",
-    "title": "Telomere Length and Risk of Incident Fracture and Arthroplasty: Findings From UK Biobank.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research",
-    "pubYear": "2022",
-    "date": "2022-09-13",
-    "isOpenAccess": "Y",
-    "keywords": "Aging; Osteoporosis; Osteoarthritis; epidemiology; Leucocyte Telomere Length",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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 \u00b1 standard deviation (SD) age 56.4\u2009\u00b1\u20098.0 and 57.0\u2009\u00b1\u20098.3\u2009years, 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. \u00a9 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).",
-    "laySummary": "",
-    "urls": "pdf:https://research-information.bris.ac.uk/files/341783442/J_of_Bone_Mineral_Res_2022_Curtis_Telomere_Length_and_Risk_of_Incident_Fracture_and_Arthroplasty_Findings_From_UK_1_.pdf; doi:https://doi.org/10.1002/jbmr.4664; html:https://europepmc.org/articles/PMC9826022; pdf:https://europepmc.org/articles/PMC9826022?pdf=render"
-  },
   {
     "id": "34345870",
     "doi": "https://doi.org/10.1016/j.bbih.2021.100286",
@@ -26808,6 +26791,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.bbih.2021.100286; doi:https://doi.org/10.1016/j.bbih.2021.100286; html:https://europepmc.org/articles/PMC8261829; pdf:https://europepmc.org/articles/PMC8261829?pdf=render"
   },
+  {
+    "id": "35880304",
+    "doi": "https://doi.org/10.1002/jbmr.4664",
+    "title": "Telomere Length and Risk of Incident Fracture and Arthroplasty: Findings From UK Biobank.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research",
+    "pubYear": "2022",
+    "date": "2022-09-13",
+    "isOpenAccess": "Y",
+    "keywords": "Aging; Osteoporosis; Osteoarthritis; epidemiology; Leucocyte Telomere Length",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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 \u00b1 standard deviation (SD) age 56.4\u2009\u00b1\u20098.0 and 57.0\u2009\u00b1\u20098.3\u2009years, 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. \u00a9 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).",
+    "laySummary": "",
+    "urls": "pdf:https://research-information.bris.ac.uk/files/341783442/J_of_Bone_Mineral_Res_2022_Curtis_Telomere_Length_and_Risk_of_Incident_Fracture_and_Arthroplasty_Findings_From_UK_1_.pdf; doi:https://doi.org/10.1002/jbmr.4664; html:https://europepmc.org/articles/PMC9826022; pdf:https://europepmc.org/articles/PMC9826022?pdf=render"
+  },
   {
     "id": "35099396",
     "doi": "https://doi.org/10.2196/21341",
@@ -27233,23 +27233,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e055773.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055773; html:https://europepmc.org/articles/PMC8867343; pdf:https://europepmc.org/articles/PMC8867343?pdf=render"
   },
-  {
-    "id": "36005401",
-    "doi": "https://doi.org/10.3390/jcdd9080237",
-    "title": "The Relationship of Maternal Gestational Mass Spectrometry-Derived Metabolites with Offspring Congenital Heart Disease: Results from Multivariable and Mendelian Randomization Analyses.",
-    "authorString": "Taylor K, McBride N, Zhao J, Oddie S, Azad R, Wright J, Andreassen OA, Stewart ID, Langenberg C, Magnus MC, Borges MC, Caputo M, Lawlor DA.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of cardiovascular development and disease",
-    "pubYear": "2022",
-    "date": "2022-07-27",
-    "isOpenAccess": "Y",
-    "keywords": "Metabolites; Congenital heart disease; Alspac; Moba; Born In Bradford",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Background: It is plausible that maternal pregnancy metabolism influences the risk of offspring congenital heart disease (CHD). We sought to explore this through a systematic approach using different methods and data. Methods: We undertook multivariable logistic regression of the odds of CHD for 923 mass spectrometry (MS)-derived metabolites in a sub-sample of a UK birth cohort (Born in Bradford (BiB); N = 2605, 46 CHD cases). We considered metabolites reaching a p-value threshold <0.05 to be suggestively associated with CHD. We sought validation of our findings, by repeating the multivariable regression analysis within the BiB cohort for any suggestively associated metabolite that was measured by nuclear magnetic resonance (NMR) or clinical chemistry (N = 7296, 87 CHD cases), and by using genetic risk scores (GRS: weighted genetic risk scores of single nucleotide polymorphisms (SNPs) that were associated with any suggestive metabolite) in Mendelian randomization (MR) analyses. The MR analyses were performed in BiB and two additional European birth cohorts (N = 38,662, 319 CHD cases). Results: In the main multivariable analyses, we identified 44 metabolites suggestively associated with CHD, including those from the following super pathways: amino acids, lipids, co-factors and vitamins, xenobiotics, nucleotides, energy, and several unknown molecules. Of these 44, isoleucine and leucine were available in the larger BiB cohort (NMR), and for these the results were validated. The MR analyses were possible for 27/44 metabolites and for 11 there was consistency with the multivariable regression results. Conclusions: In summary, we have used complimentary data sources and statistical techniques to construct layers of evidence. We found that pregnancy amino acid metabolism, androgenic steroid lipids, and levels of succinylcarnitine could be important contributing factors for CHD.",
-    "laySummary": "",
-    "urls": "pdf:https://www.mdpi.com/2308-3425/9/8/237/pdf?version=1658976309; doi:https://doi.org/10.3390/jcdd9080237; html:https://europepmc.org/articles/PMC9410051; pdf:https://europepmc.org/articles/PMC9410051?pdf=render"
-  },
   {
     "id": "31443926",
     "doi": "https://doi.org/10.1016/s0140-6736(19)31674-5",
@@ -27284,6 +27267,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.jmir.org/2021/4/e26627/PDF; doi:https://doi.org/10.2196/26627; html:https://europepmc.org/articles/PMC8023383"
   },
+  {
+    "id": "36005401",
+    "doi": "https://doi.org/10.3390/jcdd9080237",
+    "title": "The Relationship of Maternal Gestational Mass Spectrometry-Derived Metabolites with Offspring Congenital Heart Disease: Results from Multivariable and Mendelian Randomization Analyses.",
+    "authorString": "Taylor K, McBride N, Zhao J, Oddie S, Azad R, Wright J, Andreassen OA, Stewart ID, Langenberg C, Magnus MC, Borges MC, Caputo M, Lawlor DA.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of cardiovascular development and disease",
+    "pubYear": "2022",
+    "date": "2022-07-27",
+    "isOpenAccess": "Y",
+    "keywords": "Metabolites; Congenital heart disease; Alspac; Moba; Born In Bradford",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Background: It is plausible that maternal pregnancy metabolism influences the risk of offspring congenital heart disease (CHD). We sought to explore this through a systematic approach using different methods and data. Methods: We undertook multivariable logistic regression of the odds of CHD for 923 mass spectrometry (MS)-derived metabolites in a sub-sample of a UK birth cohort (Born in Bradford (BiB); N = 2605, 46 CHD cases). We considered metabolites reaching a p-value threshold <0.05 to be suggestively associated with CHD. We sought validation of our findings, by repeating the multivariable regression analysis within the BiB cohort for any suggestively associated metabolite that was measured by nuclear magnetic resonance (NMR) or clinical chemistry (N = 7296, 87 CHD cases), and by using genetic risk scores (GRS: weighted genetic risk scores of single nucleotide polymorphisms (SNPs) that were associated with any suggestive metabolite) in Mendelian randomization (MR) analyses. The MR analyses were performed in BiB and two additional European birth cohorts (N = 38,662, 319 CHD cases). Results: In the main multivariable analyses, we identified 44 metabolites suggestively associated with CHD, including those from the following super pathways: amino acids, lipids, co-factors and vitamins, xenobiotics, nucleotides, energy, and several unknown molecules. Of these 44, isoleucine and leucine were available in the larger BiB cohort (NMR), and for these the results were validated. The MR analyses were possible for 27/44 metabolites and for 11 there was consistency with the multivariable regression results. Conclusions: In summary, we have used complimentary data sources and statistical techniques to construct layers of evidence. We found that pregnancy amino acid metabolism, androgenic steroid lipids, and levels of succinylcarnitine could be important contributing factors for CHD.",
+    "laySummary": "",
+    "urls": "pdf:https://www.mdpi.com/2308-3425/9/8/237/pdf?version=1658976309; doi:https://doi.org/10.3390/jcdd9080237; html:https://europepmc.org/articles/PMC9410051; pdf:https://europepmc.org/articles/PMC9410051?pdf=render"
+  },
   {
     "id": "37789377",
     "doi": "https://doi.org/10.1186/s12943-023-01863-2",
@@ -27454,23 +27454,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e065142.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-065142; html:https://europepmc.org/articles/PMC9709810; pdf:https://europepmc.org/articles/PMC9709810?pdf=render"
   },
-  {
-    "id": "37208429",
-    "doi": "https://doi.org/10.1038/s41598-023-33391-w",
-    "title": "Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom.",
-    "authorString": "Z\u00f6llner J, Finer S, Linton KJ, Genes and Health Research Team, van Heel DA, Williamson C, Dixon PH.",
-    "authorAffiliations": "",
-    "journalTitle": "Scientific reports",
-    "pubYear": "2023",
-    "date": "2023-05-19",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "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\u2009<\u20095%. 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\u2009=\u200931), intrahepatic cholestasis of pregnancy (ICP, n\u2009=\u200916), cholangiocarcinoma and cirrhosis (n\u2009=\u20092). 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.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1038/s41598-023-33391-w; doi:https://doi.org/10.1038/s41598-023-33391-w; html:https://europepmc.org/articles/PMC10199085; pdf:https://europepmc.org/articles/PMC10199085?pdf=render"
-  },
   {
     "id": "32212911",
     "doi": "https://doi.org/10.1161/jaha.119.013684",
@@ -27488,6 +27471,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.119.013684; doi:https://doi.org/10.1161/JAHA.119.013684; html:https://europepmc.org/articles/PMC7428631; pdf:https://europepmc.org/articles/PMC7428631?pdf=render"
   },
+  {
+    "id": "37208429",
+    "doi": "https://doi.org/10.1038/s41598-023-33391-w",
+    "title": "Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom.",
+    "authorString": "Z\u00f6llner J, Finer S, Linton KJ, Genes and Health Research Team, van Heel DA, Williamson C, Dixon PH.",
+    "authorAffiliations": "",
+    "journalTitle": "Scientific reports",
+    "pubYear": "2023",
+    "date": "2023-05-19",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "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\u2009<\u20095%. 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\u2009=\u200931), intrahepatic cholestasis of pregnancy (ICP, n\u2009=\u200916), cholangiocarcinoma and cirrhosis (n\u2009=\u20092). 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.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1038/s41598-023-33391-w; doi:https://doi.org/10.1038/s41598-023-33391-w; html:https://europepmc.org/articles/PMC10199085; pdf:https://europepmc.org/articles/PMC10199085?pdf=render"
+  },
   {
     "id": "34632432",
     "doi": "https://doi.org/10.1016/s2666-5247(21)00128-2",
@@ -27556,23 +27556,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1164/rccm.201903-0673OC"
   },
-  {
-    "id": "35144751",
-    "doi": "https://doi.org/10.1016/j.jacc.2021.11.045",
-    "title": "Echocardiographic Deformation Imaging\u00a0for Early Detection of Genetic\u00a0Cardiomyopathies: JACC Review Topic of the Week.",
-    "authorString": "Taha K, Kirkels FP, Teske AJ, Asselbergs FW, van Tintelen JP, Doevendans PA, Kutty S, Haugaa KH, Cramer MJ.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of the American College of Cardiology",
-    "pubYear": "2022",
-    "date": "2022-02-01",
-    "isOpenAccess": "N",
-    "keywords": "Early Detection; Speckle Tracking; Family Screening; Deformation Imaging; Genetic Cardiomyopathy",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Clinical screening of the relatives of patients with genetic cardiomyopathies is challenging, as they often lack detectable cardiac abnormalities at presentation. Life-threatening adverse events can already occur in these early stages of disease, so sensitive tools to reveal the earliest signs of disease are needed. The utility of echocardiographic deformation imaging for early detection has been explored for this population in multiple studies but has not been broadly implemented in clinical practice. The authors discuss contemporary evidence on the utility of deformation imaging in relatives of patients with genetic cardiomyopathies. The available body of data shows that deformation imaging reveals early disease-specific abnormalities in dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic cardiomyopathy. Deformation imaging seems promising to enhance the screening and follow-up protocols in relatives, and the authors propose measures to accelerate its implementation in clinical care.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.jacc.2021.11.045; doi:https://doi.org/10.1016/j.jacc.2021.11.045"
-  },
   {
     "id": "34661196",
     "doi": "https://doi.org/10.1093/ehjopen/oeab019",
@@ -27590,6 +27573,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ehjopen/article-pdf/1/2/oeab019/41727950/oeab019.pdf; doi:https://doi.org/10.1093/ehjopen/oeab019; html:https://europepmc.org/articles/PMC8508012; pdf:https://europepmc.org/articles/PMC8508012?pdf=render"
   },
+  {
+    "id": "35144751",
+    "doi": "https://doi.org/10.1016/j.jacc.2021.11.045",
+    "title": "Echocardiographic Deformation Imaging\u00a0for Early Detection of Genetic\u00a0Cardiomyopathies: JACC Review Topic of the Week.",
+    "authorString": "Taha K, Kirkels FP, Teske AJ, Asselbergs FW, van Tintelen JP, Doevendans PA, Kutty S, Haugaa KH, Cramer MJ.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of the American College of Cardiology",
+    "pubYear": "2022",
+    "date": "2022-02-01",
+    "isOpenAccess": "N",
+    "keywords": "Early Detection; Speckle Tracking; Family Screening; Deformation Imaging; Genetic Cardiomyopathy",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Clinical screening of the relatives of patients with genetic cardiomyopathies is challenging, as they often lack detectable cardiac abnormalities at presentation. Life-threatening adverse events can already occur in these early stages of disease, so sensitive tools to reveal the earliest signs of disease are needed. The utility of echocardiographic deformation imaging for early detection has been explored for this population in multiple studies but has not been broadly implemented in clinical practice. The authors discuss contemporary evidence on the utility of deformation imaging in relatives of patients with genetic cardiomyopathies. The available body of data shows that deformation imaging reveals early disease-specific abnormalities in dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic cardiomyopathy. Deformation imaging seems promising to enhance the screening and follow-up protocols in relatives, and the authors propose measures to accelerate its implementation in clinical care.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.jacc.2021.11.045; doi:https://doi.org/10.1016/j.jacc.2021.11.045"
+  },
   {
     "id": "35913736",
     "doi": "https://doi.org/10.1093/ehjqcco/qcac045",
@@ -27607,23 +27607,6 @@
     "laySummary": "",
     "urls": "pdf:https://biblio.ugent.be/publication/01GTEZMFA3PQ4FR2HWVVMJE1PP/file/01GTEZP5YQ68PC7TFPP52TS6QR.pdf; 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"
   },
-  {
-    "id": "37770476",
-    "doi": "https://doi.org/10.1038/s41467-023-41249-y",
-    "title": "Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration.",
-    "authorString": "Austin-Zimmerman I, Levey DF, Giannakopoulou O, Deak JD, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Million Veteran Program, Concato J, Buysse DJ, Gaziano JM, Gottlieb DJ, Polimanti R, Stein MB, Bramon E, Gelernter J.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature communications",
-    "pubYear": "2023",
-    "date": "2023-09-28",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short (\u2009\u2264\u20095\u2009h) and long (\u2009\u2265\u200910\u2009h) sleep duration in adults of European (N\u2009=\u2009445,966), African (N\u2009=\u200927,785), East Asian (N\u2009=\u20093141), and admixed-American (N\u2009=\u200916,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (r<sub>g</sub> = 0.16\u2009\u00b1\u20090.04; p\u2009=\u20090.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1038/s41467-023-41249-y; html:https://europepmc.org/articles/PMC10539313; pdf:https://europepmc.org/articles/PMC10539313?pdf=render"
-  },
   {
     "id": "32685697",
     "doi": "https://doi.org/10.12688/wellcomeopenres.15788.1",
@@ -27641,6 +27624,23 @@
     "laySummary": "",
     "urls": "pdf:https://wellcomeopenresearch.org/articles/5-58/v1/pdf; doi:https://doi.org/10.12688/wellcomeopenres.15788.1; html:https://europepmc.org/articles/PMC7324944; pdf:https://europepmc.org/articles/PMC7324944?pdf=render"
   },
+  {
+    "id": "37770476",
+    "doi": "https://doi.org/10.1038/s41467-023-41249-y",
+    "title": "Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration.",
+    "authorString": "Austin-Zimmerman I, Levey DF, Giannakopoulou O, Deak JD, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Million Veteran Program, Concato J, Buysse DJ, Gaziano JM, Gottlieb DJ, Polimanti R, Stein MB, Bramon E, Gelernter J.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature communications",
+    "pubYear": "2023",
+    "date": "2023-09-28",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short (\u2009\u2264\u20095\u2009h) and long (\u2009\u2265\u200910\u2009h) sleep duration in adults of European (N\u2009=\u2009445,966), African (N\u2009=\u200927,785), East Asian (N\u2009=\u20093141), and admixed-American (N\u2009=\u200916,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (r<sub>g</sub> = 0.16\u2009\u00b1\u20090.04; p\u2009=\u20090.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1038/s41467-023-41249-y; html:https://europepmc.org/articles/PMC10539313; pdf:https://europepmc.org/articles/PMC10539313?pdf=render"
+  },
   {
     "id": "34737870",
     "doi": "https://doi.org/10.7189/jogh.11.15003",
@@ -27658,23 +27658,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.7189/jogh.11.15003; doi:https://doi.org/10.7189/jogh.11.15003; html:https://europepmc.org/articles/PMC8542376; pdf:https://europepmc.org/articles/PMC8542376?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: <i>N</i> <sub>Cases</sub> = 42, <i>N</i> <sub>Control</sub> = 40 490; UK Biobank: <i>N</i> <sub>Cases</sub> = 2091, <i>N</i> <sub>Control</sub> = 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-<i>R</i> <sup>2</sup> 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": "pdf:https://academic.oup.com/braincomms/article-pdf/5/2/fcad041/49521070/fcad041.pdf; doi:https://doi.org/10.1093/braincomms/fcad041; html:https://europepmc.org/articles/PMC10053643; pdf:https://europepmc.org/articles/PMC10053643?pdf=render"
-  },
   {
     "id": "31863937",
     "doi": "https://doi.org/10.1016/j.aap.2019.105333",
@@ -27692,6 +27675,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.aap.2019.105333"
   },
+  {
+    "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: <i>N</i> <sub>Cases</sub> = 42, <i>N</i> <sub>Control</sub> = 40 490; UK Biobank: <i>N</i> <sub>Cases</sub> = 2091, <i>N</i> <sub>Control</sub> = 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-<i>R</i> <sup>2</sup> 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": "pdf:https://academic.oup.com/braincomms/article-pdf/5/2/fcad041/49521070/fcad041.pdf; doi:https://doi.org/10.1093/braincomms/fcad041; html:https://europepmc.org/articles/PMC10053643; pdf:https://europepmc.org/articles/PMC10053643?pdf=render"
+  },
   {
     "id": "36998408",
     "doi": "https://doi.org/10.3389/fmicb.2023.1070340",
@@ -27726,23 +27726,6 @@
     "laySummary": "",
     "urls": "pdf:https://discovery.ucl.ac.uk/10097154/3/Solebo_Liu%20AC%20Flare%20SR%20290919.pdf; doi:https://doi.org/10.1080/09273948.2019.1709650"
   },
-  {
-    "id": "37575973",
-    "doi": "https://doi.org/10.2147/clep.s417176",
-    "title": "Anxiety and Depression in People with Eczema or Psoriasis: A Comparison of Associations in UK Biobank and Linked Primary Care Data.",
-    "authorString": "Matthewman J, Mansfield KE, Hayes JF, Adesanya EI, Smith CH, Roberts A, Langan SM, Henderson AD.",
-    "authorAffiliations": "",
-    "journalTitle": "Clinical epidemiology",
-    "pubYear": "2023",
-    "date": "2023-08-07",
-    "isOpenAccess": "Y",
-    "keywords": "Depression; Psoriasis; Anxiety; Eczema; Cross-sectional study; Data Linkage; Electronic Health Records; Ascertainment; Uk Biobank",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>Previous research has shown associations between eczema and psoriasis and anxiety and depression. We investigated whether associations are consistent across different settings of ascertainment for depression and anxiety, including interview and survey responses from UK Biobank (a large longitudinal cohort recruiting individuals aged 40-69 years between 2006-2010), and linked primary care data, with the aim of drawing more reliable conclusions through triangulation.<h4>Methods</h4>In cross-sectional studies, we estimated associations between eczema or psoriasis and anxiety or depression, defining anxiety or depression as 1) self-reported previous diagnosis at UK Biobank recruitment interview; 2) PHQ-9/GAD-7 score indicating depression or anxiety from a UK Biobank mental health follow-up survey in 2016; and 3) diagnosis in linked primary care electronic health record data.<h4>Results</h4>We analysed 230,047 people with linked Biobank and primary care data. We found poor agreement between the data sources for eczema, psoriasis, anxiety, and depression. Eg, 9474 had a previous eczema diagnosis in primary care data, 4069 self-reported previous eczema diagnosis at the UK biobank interview, and 1536 had eczema in both data sources (for depression 40,455; 13,320; and 9588 respectively). Having eczema or psoriasis (recorded in primary care or baseline interview) was associated with higher odds of anxiety and depression. Eg, the adjusted odds ratio for depression comparing those with eczema to those without was greater than 1 when defining the outcome from 1) the recruitment interview (1.36, 95% confidence interval 1.27-1.45); 2) the follow-up survey (1.24, 1.09-1.39), and 3) primary care records (1.56, 1.50-1.62).<h4>Discussion</h4>Our findings support increased prevalence of mental illness in people with psoriasis and eczema across multiple data sources, which should be considered in planning of mental health services. However, we found poor agreement in disease ascertainment between settings, with implications for data interpretation in electronic health records.",
-    "laySummary": "",
-    "urls": "pdf:https://www.dovepress.com/getfile.php?fileID=91773; doi:https://doi.org/10.2147/CLEP.S417176; html:https://europepmc.org/articles/PMC10421744; pdf:https://europepmc.org/articles/PMC10421744?pdf=render"
-  },
   {
     "id": "31650125",
     "doi": "https://doi.org/10.1016/s2589-7500(19)30012-3",
@@ -27760,6 +27743,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/s2589-7500(19)30012-3; 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": "37575973",
+    "doi": "https://doi.org/10.2147/clep.s417176",
+    "title": "Anxiety and Depression in People with Eczema or Psoriasis: A Comparison of Associations in UK Biobank and Linked Primary Care Data.",
+    "authorString": "Matthewman J, Mansfield KE, Hayes JF, Adesanya EI, Smith CH, Roberts A, Langan SM, Henderson AD.",
+    "authorAffiliations": "",
+    "journalTitle": "Clinical epidemiology",
+    "pubYear": "2023",
+    "date": "2023-08-07",
+    "isOpenAccess": "Y",
+    "keywords": "Depression; Psoriasis; Anxiety; Eczema; Cross-sectional study; Data Linkage; Electronic Health Records; Ascertainment; Uk Biobank",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>Previous research has shown associations between eczema and psoriasis and anxiety and depression. We investigated whether associations are consistent across different settings of ascertainment for depression and anxiety, including interview and survey responses from UK Biobank (a large longitudinal cohort recruiting individuals aged 40-69 years between 2006-2010), and linked primary care data, with the aim of drawing more reliable conclusions through triangulation.<h4>Methods</h4>In cross-sectional studies, we estimated associations between eczema or psoriasis and anxiety or depression, defining anxiety or depression as 1) self-reported previous diagnosis at UK Biobank recruitment interview; 2) PHQ-9/GAD-7 score indicating depression or anxiety from a UK Biobank mental health follow-up survey in 2016; and 3) diagnosis in linked primary care electronic health record data.<h4>Results</h4>We analysed 230,047 people with linked Biobank and primary care data. We found poor agreement between the data sources for eczema, psoriasis, anxiety, and depression. Eg, 9474 had a previous eczema diagnosis in primary care data, 4069 self-reported previous eczema diagnosis at the UK biobank interview, and 1536 had eczema in both data sources (for depression 40,455; 13,320; and 9588 respectively). Having eczema or psoriasis (recorded in primary care or baseline interview) was associated with higher odds of anxiety and depression. Eg, the adjusted odds ratio for depression comparing those with eczema to those without was greater than 1 when defining the outcome from 1) the recruitment interview (1.36, 95% confidence interval 1.27-1.45); 2) the follow-up survey (1.24, 1.09-1.39), and 3) primary care records (1.56, 1.50-1.62).<h4>Discussion</h4>Our findings support increased prevalence of mental illness in people with psoriasis and eczema across multiple data sources, which should be considered in planning of mental health services. However, we found poor agreement in disease ascertainment between settings, with implications for data interpretation in electronic health records.",
+    "laySummary": "",
+    "urls": "pdf:https://www.dovepress.com/getfile.php?fileID=91773; doi:https://doi.org/10.2147/CLEP.S417176; html:https://europepmc.org/articles/PMC10421744; pdf:https://europepmc.org/articles/PMC10421744?pdf=render"
+  },
   {
     "id": "35751107",
     "doi": "https://doi.org/10.1186/s13059-022-02702-1",
@@ -27811,23 +27811,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.tandfonline.com/doi/pdf/10.1080/09273948.2020.1799038?needAccess=true; doi:https://doi.org/10.1080/09273948.2020.1799038; html:https://europepmc.org/articles/PMC8935946; pdf:https://europepmc.org/articles/PMC8935946?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": "<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02948-x; 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": "30102210",
     "doi": "https://doi.org/10.1016/s1470-2045(18)30425-x",
@@ -27862,6 +27845,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.119.14302; doi:https://doi.org/10.1161/HYPERTENSIONAHA.119.14302"
   },
+  {
+    "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": "<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02948-x; 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": "37723491",
     "doi": "https://doi.org/10.1186/s13073-023-01221-3",
@@ -28151,23 +28151,6 @@
     "laySummary": "",
     "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4658151/1/Ascott-etal-2020_Atopic_eczema_and-obesity.pdf; doi:https://doi.org/10.1111/bjd.19597"
   },
-  {
-    "id": "33246414",
-    "doi": "https://doi.org/10.1186/s12874-020-01163-z",
-    "title": "Patient-specific record linkage between emergency department and hospital admission data for a cohort of people who inject drugs: methodological considerations for frequent presenters.",
-    "authorString": "Di Rico R, Nambiar D, Gabbe B, Stoov\u00e9 M, Dietze P.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC medical research methodology",
-    "pubYear": "2020",
-    "date": "2020-11-27",
-    "isOpenAccess": "Y",
-    "keywords": "Methods; Australia; Data Linkage; Record Linkage; Administrative Data; People Who Inject Drugs; Patient Pathways; Frequent Presenters; Vaed; Vemd",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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\u2009=\u20091035, 87%). Allowing 24-h between ED visits and hospital admissions captured more linked records, but increased manual inspection requirements. In linked records (n\u2009=\u20091190), 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.<h4>Conclusions</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcmedresmethodol.biomedcentral.com/track/pdf/10.1186/s12874-020-01163-z; 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": "32294163",
     "doi": "https://doi.org/10.1093/europace/euaa039",
@@ -28185,6 +28168,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/europace/article-pdf/22/5/787/33178222/euaa039.pdf; doi:https://doi.org/10.1093/europace/euaa039; html:https://europepmc.org/articles/PMC7203633; pdf:https://europepmc.org/articles/PMC7203633?pdf=render"
   },
+  {
+    "id": "33246414",
+    "doi": "https://doi.org/10.1186/s12874-020-01163-z",
+    "title": "Patient-specific record linkage between emergency department and hospital admission data for a cohort of people who inject drugs: methodological considerations for frequent presenters.",
+    "authorString": "Di Rico R, Nambiar D, Gabbe B, Stoov\u00e9 M, Dietze P.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC medical research methodology",
+    "pubYear": "2020",
+    "date": "2020-11-27",
+    "isOpenAccess": "Y",
+    "keywords": "Methods; Australia; Data Linkage; Record Linkage; Administrative Data; People Who Inject Drugs; Patient Pathways; Frequent Presenters; Vaed; Vemd",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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\u2009=\u20091035, 87%). Allowing 24-h between ED visits and hospital admissions captured more linked records, but increased manual inspection requirements. In linked records (n\u2009=\u20091190), 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.<h4>Conclusions</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcmedresmethodol.biomedcentral.com/track/pdf/10.1186/s12874-020-01163-z; 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": "34053260",
     "doi": "https://doi.org/10.1098/rstb.2020.0283",
@@ -28424,21 +28424,21 @@
     "urls": "pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.200958; doi:https://doi.org/10.1098/rsos.200958; html:https://europepmc.org/articles/PMC7735342; pdf:https://europepmc.org/articles/PMC7735342?pdf=render"
   },
   {
-    "id": "36717723",
-    "doi": "https://doi.org/10.1038/s41590-022-01380-2",
-    "title": "A patient-centric modeling framework captures recovery from SARS-CoV-2 infection.",
-    "authorString": "Ruffieux H, Hanson AL, Lodge S, Lawler NG, Whiley L, Gray N, Nolan TH, Bergamaschi L, Mescia F, Turner L, de Sa A, Pelly VS, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) BioResource COVID-19 Collaboration, Kotagiri P, Kingston N, Bradley JR, Holmes E, Wist J, Nicholson JK, Lyons PA, Smith KGC, Richardson S, Bantug GR, Hess C.",
+    "id": "34888366",
+    "doi": "https://doi.org/10.3389/fcvm.2021.768245",
+    "title": "MOCOnet: Robust Motion Correction of Cardiovascular Magnetic Resonance T1 Mapping Using Convolutional Neural Networks.",
+    "authorString": "Gonzales RA, Zhang Q, Papie\u017c BW, Werys K, Lukaschuk E, Popescu IA, Burrage MK, Shanmuganathan M, Ferreira VM, Piechnik SK.",
     "authorAffiliations": "",
-    "journalTitle": "Nature immunology",
-    "pubYear": "2023",
-    "date": "2023-01-30",
+    "journalTitle": "Frontiers in cardiovascular medicine",
+    "pubYear": "2021",
+    "date": "2021-11-23",
     "isOpenAccess": "Y",
-    "keywords": "",
+    "keywords": "image registration; Cardiovascular Magnetic Resonance; T1 Mapping; Deep Learning; Shmolli",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct 'systemic recovery' profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app , designed to test our findings prospectively.",
+    "abstract": "<b>Background:</b> 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. <b>Methods:</b> 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). <b>Results:</b> 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\u00b121.5 to 13.3\u00b110.5 (<i>p</i> < 0.001), whereas the baseline method reduced it to 15.8\u00b115.6 (<i>p</i> < 0.001). MOCOnet was significantly better than the baseline method in suppressing motion artefacts and more consistently (<i>p</i> = 0.007). <b>Conclusion:</b> 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.",
     "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41590-022-01380-2.pdf; doi:https://doi.org/10.1038/s41590-022-01380-2; html:https://europepmc.org/articles/PMC9892000; pdf:https://europepmc.org/articles/PMC9892000?pdf=render"
+    "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.768245/pdf; doi:https://doi.org/10.3389/fcvm.2021.768245; html:https://europepmc.org/articles/PMC8649951; pdf:https://europepmc.org/articles/PMC8649951?pdf=render"
   },
   {
     "id": "35354069",
@@ -28458,21 +28458,21 @@
     "urls": "doi:https://doi.org/10.1016/j.cmet.2022.03.002; doi:https://doi.org/10.1016/j.cmet.2022.03.002; html:https://europepmc.org/articles/PMC9097589"
   },
   {
-    "id": "34888366",
-    "doi": "https://doi.org/10.3389/fcvm.2021.768245",
-    "title": "MOCOnet: Robust Motion Correction of Cardiovascular Magnetic Resonance T1 Mapping Using Convolutional Neural Networks.",
-    "authorString": "Gonzales RA, Zhang Q, Papie\u017c BW, Werys K, Lukaschuk E, Popescu IA, Burrage MK, Shanmuganathan M, Ferreira VM, Piechnik SK.",
+    "id": "36717723",
+    "doi": "https://doi.org/10.1038/s41590-022-01380-2",
+    "title": "A patient-centric modeling framework captures recovery from SARS-CoV-2 infection.",
+    "authorString": "Ruffieux H, Hanson AL, Lodge S, Lawler NG, Whiley L, Gray N, Nolan TH, Bergamaschi L, Mescia F, Turner L, de Sa A, Pelly VS, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) BioResource COVID-19 Collaboration, Kotagiri P, Kingston N, Bradley JR, Holmes E, Wist J, Nicholson JK, Lyons PA, Smith KGC, Richardson S, Bantug GR, Hess C.",
     "authorAffiliations": "",
-    "journalTitle": "Frontiers in cardiovascular medicine",
-    "pubYear": "2021",
-    "date": "2021-11-23",
+    "journalTitle": "Nature immunology",
+    "pubYear": "2023",
+    "date": "2023-01-30",
     "isOpenAccess": "Y",
-    "keywords": "image registration; Cardiovascular Magnetic Resonance; T1 Mapping; Deep Learning; Shmolli",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<b>Background:</b> 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. <b>Methods:</b> 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). <b>Results:</b> 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\u00b121.5 to 13.3\u00b110.5 (<i>p</i> < 0.001), whereas the baseline method reduced it to 15.8\u00b115.6 (<i>p</i> < 0.001). MOCOnet was significantly better than the baseline method in suppressing motion artefacts and more consistently (<i>p</i> = 0.007). <b>Conclusion:</b> 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.",
+    "abstract": "The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct 'systemic recovery' profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app , designed to test our findings prospectively.",
     "laySummary": "",
-    "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.768245/pdf; doi:https://doi.org/10.3389/fcvm.2021.768245; html:https://europepmc.org/articles/PMC8649951; pdf:https://europepmc.org/articles/PMC8649951?pdf=render"
+    "urls": "pdf:https://www.nature.com/articles/s41590-022-01380-2.pdf; doi:https://doi.org/10.1038/s41590-022-01380-2; html:https://europepmc.org/articles/PMC9892000; pdf:https://europepmc.org/articles/PMC9892000?pdf=render"
   },
   {
     "id": "36962800",
@@ -28764,38 +28764,38 @@
     "urls": "doi:https://doi.org/10.1038/s41588-023-01379-x; 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": "35482474",
-    "doi": "https://doi.org/10.1111/bjd.21627",
-    "title": "Biomarkers of disease progression in people with psoriasis: a scoping review.",
-    "authorString": "Ramessur R, Corbett M, Marshall D, Acencio ML, Barbosa IA, Dand N, Di Meglio P, Haddad S, Jensen AHM, Koopmann W, Mahil SK, Ostaszewski M, Rahmatulla S, Rastrick J, Saklatvala J, Weidinger S, Wright K, Eyerich K, Ndlovu M, Barker JN, Skov L, Conrad C, Smith CH, BIOMAP consortium.",
+    "id": "35103484",
+    "doi": "https://doi.org/10.1161/circgen.121.003553",
+    "title": "Genetically Predicted Neutrophil-to-Lymphocyte Ratio and Coronary Artery Disease: Evidence From Mendelian Randomization. ",
+    "authorString": "Cupido AJ, Kraaijenhof JM, Burgess S, Asselbergs FW, Hovingh GK, Gill D.",
     "authorAffiliations": "",
-    "journalTitle": "The British journal of dermatology",
+    "journalTitle": "Circulation. Genomic and precision medicine",
     "pubYear": "2022",
-    "date": "2022-07-11",
+    "date": "2022-02-01",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice.<h4>Objectives</h4>To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community.<h4>Methods</h4>A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n\u2009\u2265\u200950) reporting biomarkers associated with disease progression. The main outcomes were any measure of skin severity or any prespecified psoriasis comorbidity. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (longitudinal design and/or use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise, and mapped to relevant cellular and molecular pathways.<h4>Results</h4>Of 181 included studies, most investigated genomic or proteomic biomarkers associated with disease severity (n\u2009=\u2009145) or psoriatic arthritis (n\u2009=\u200930). Methodological and reporting limitations compromised interpretation of findings, most notably a lack of longitudinal studies, and inadequate control for key prognostic factors. The following candidate biomarkers with future potential utility were identified for predicting disease severity: LCE3D, interleukin (IL)23R, IL23A, NFKBIL1 loci, HLA-C*06:02 (genomic), IL-17A, IgG aHDL, GlycA, I-FABP and kallikrein 8 (proteomic), tyramine (metabolomic); psoriatic arthritis: HLA-C*06:02, HLA-B*27, HLA-B*38, HLA-B*08, and variation at the IL23R and IL13 loci (genomic); IL-17A, CXCL10, Mac-2 binding protein, integrin b5, matrix metalloproteinase-3 and macrophage-colony stimulating factor (proteomic) and tyramine and mucic acid (metabolomic); and type 2 diabetes mellitus: variation in IL12B and IL23R loci (genomic). No biomarkers were supported by sufficient evidence for clinical use without further validation.<h4>Conclusions</h4>This review provides a comprehensive catalogue of investigated biomarkers of disease progression in psoriasis. Future studies must address the common methodological limitations identified herein to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic? The current treatment paradigm in psoriasis is reactive. There is a need to develop effective risk-stratified management approaches that can proactively attenuate the substantial burden of disease. Prognostic biomarkers of disease progression have therefore been the focus of intense research. What does this study add? This review is the first to scope, collate and catalogue research investigating biomarkers of disease progression in psoriasis. The review identifies potentially promising candidate biomarkers for further investigation and highlights common important limitations that should be considered when designing and conducting future studies in this area.",
+    "abstract": "",
     "laySummary": "",
-    "urls": "pdf:https://kclpure.kcl.ac.uk/ws/files/177671246/Br_J_Dermatol_2022_Ramessur_Biomarkers_of_disease_progression_in_people_with_psoriasis_a_scoping_review.pdf; doi:https://doi.org/10.1111/bjd.21627; html:https://europepmc.org/articles/PMC9796834; pdf:https://europepmc.org/articles/PMC9796834?pdf=render"
+    "urls": "pdf:https://discovery.ucl.ac.uk/10145750/1/CIRCGEN.121.003553.pdf; doi:https://doi.org/10.1161/CIRCGEN.121.003553; html:https://europepmc.org/articles/PMC7612391; pdf:https://europepmc.org/articles/PMC7612391?pdf=render"
   },
   {
-    "id": "35103484",
-    "doi": "https://doi.org/10.1161/circgen.121.003553",
-    "title": "Genetically Predicted Neutrophil-to-Lymphocyte Ratio and Coronary Artery Disease: Evidence From Mendelian Randomization. ",
-    "authorString": "Cupido AJ, Kraaijenhof JM, Burgess S, Asselbergs FW, Hovingh GK, Gill D.",
+    "id": "35482474",
+    "doi": "https://doi.org/10.1111/bjd.21627",
+    "title": "Biomarkers of disease progression in people with psoriasis: a scoping review.",
+    "authorString": "Ramessur R, Corbett M, Marshall D, Acencio ML, Barbosa IA, Dand N, Di Meglio P, Haddad S, Jensen AHM, Koopmann W, Mahil SK, Ostaszewski M, Rahmatulla S, Rastrick J, Saklatvala J, Weidinger S, Wright K, Eyerich K, Ndlovu M, Barker JN, Skov L, Conrad C, Smith CH, BIOMAP consortium.",
     "authorAffiliations": "",
-    "journalTitle": "Circulation. Genomic and precision medicine",
+    "journalTitle": "The British journal of dermatology",
     "pubYear": "2022",
-    "date": "2022-02-01",
+    "date": "2022-07-11",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "",
+    "abstract": "<h4>Background</h4>Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice.<h4>Objectives</h4>To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community.<h4>Methods</h4>A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n\u2009\u2265\u200950) reporting biomarkers associated with disease progression. The main outcomes were any measure of skin severity or any prespecified psoriasis comorbidity. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (longitudinal design and/or use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise, and mapped to relevant cellular and molecular pathways.<h4>Results</h4>Of 181 included studies, most investigated genomic or proteomic biomarkers associated with disease severity (n\u2009=\u2009145) or psoriatic arthritis (n\u2009=\u200930). Methodological and reporting limitations compromised interpretation of findings, most notably a lack of longitudinal studies, and inadequate control for key prognostic factors. The following candidate biomarkers with future potential utility were identified for predicting disease severity: LCE3D, interleukin (IL)23R, IL23A, NFKBIL1 loci, HLA-C*06:02 (genomic), IL-17A, IgG aHDL, GlycA, I-FABP and kallikrein 8 (proteomic), tyramine (metabolomic); psoriatic arthritis: HLA-C*06:02, HLA-B*27, HLA-B*38, HLA-B*08, and variation at the IL23R and IL13 loci (genomic); IL-17A, CXCL10, Mac-2 binding protein, integrin b5, matrix metalloproteinase-3 and macrophage-colony stimulating factor (proteomic) and tyramine and mucic acid (metabolomic); and type 2 diabetes mellitus: variation in IL12B and IL23R loci (genomic). No biomarkers were supported by sufficient evidence for clinical use without further validation.<h4>Conclusions</h4>This review provides a comprehensive catalogue of investigated biomarkers of disease progression in psoriasis. Future studies must address the common methodological limitations identified herein to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic? The current treatment paradigm in psoriasis is reactive. There is a need to develop effective risk-stratified management approaches that can proactively attenuate the substantial burden of disease. Prognostic biomarkers of disease progression have therefore been the focus of intense research. What does this study add? This review is the first to scope, collate and catalogue research investigating biomarkers of disease progression in psoriasis. The review identifies potentially promising candidate biomarkers for further investigation and highlights common important limitations that should be considered when designing and conducting future studies in this area.",
     "laySummary": "",
-    "urls": "pdf:https://discovery.ucl.ac.uk/10145750/1/CIRCGEN.121.003553.pdf; doi:https://doi.org/10.1161/CIRCGEN.121.003553; html:https://europepmc.org/articles/PMC7612391; pdf:https://europepmc.org/articles/PMC7612391?pdf=render"
+    "urls": "pdf:https://kclpure.kcl.ac.uk/ws/files/177671246/Br_J_Dermatol_2022_Ramessur_Biomarkers_of_disease_progression_in_people_with_psoriasis_a_scoping_review.pdf; doi:https://doi.org/10.1111/bjd.21627; html:https://europepmc.org/articles/PMC9796834; pdf:https://europepmc.org/articles/PMC9796834?pdf=render"
   },
   {
     "id": "30082368",
@@ -28933,23 +28933,6 @@
     "laySummary": "",
     "urls": "pdf:http://eprints.whiterose.ac.uk/134568/7/OArchangelidi_EJPC_accepted.pdf; doi:https://doi.org/10.1177/2047487318785228"
   },
-  {
-    "id": "33821553",
-    "doi": "https://doi.org/10.1002/jia2.25697",
-    "title": "The impact of disruptions due to COVID-19 on HIV transmission and control among men who have sex with men in China.",
-    "authorString": "Booton RD, Fu G, MacGregor L, Li J, Ong JJ, Tucker JD, Turner KM, Tang W, Vickerman P, Mitchell KM.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of the International AIDS Society",
-    "pubYear": "2021",
-    "date": "2021-04-01",
-    "isOpenAccess": "Y",
-    "keywords": "Modelling; Hiv Transmission; Men Who Have Sex With Men; People\u2019s Republic Of China; Key And Vulnerable Populations; Covid-19 Pandemic",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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\u00a0months) 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).<h4>Conclusions</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.25697; doi:https://doi.org/10.1002/jia2.25697; html:https://europepmc.org/articles/PMC8022092; pdf:https://europepmc.org/articles/PMC8022092?pdf=render"
-  },
   {
     "id": "31820220",
     "doi": "https://doi.org/10.1007/s10926-019-09867-w",
@@ -28967,6 +28950,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1007/s10926-019-09867-w"
   },
+  {
+    "id": "33821553",
+    "doi": "https://doi.org/10.1002/jia2.25697",
+    "title": "The impact of disruptions due to COVID-19 on HIV transmission and control among men who have sex with men in China.",
+    "authorString": "Booton RD, Fu G, MacGregor L, Li J, Ong JJ, Tucker JD, Turner KM, Tang W, Vickerman P, Mitchell KM.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of the International AIDS Society",
+    "pubYear": "2021",
+    "date": "2021-04-01",
+    "isOpenAccess": "Y",
+    "keywords": "Modelling; Hiv Transmission; Men Who Have Sex With Men; People\u2019s Republic Of China; Key And Vulnerable Populations; Covid-19 Pandemic",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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\u00a0months) 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).<h4>Conclusions</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.25697; doi:https://doi.org/10.1002/jia2.25697; html:https://europepmc.org/articles/PMC8022092; pdf:https://europepmc.org/articles/PMC8022092?pdf=render"
+  },
   {
     "id": "33367483",
     "doi": "https://doi.org/10.1093/bioinformatics/btaa1079",
@@ -29018,23 +29018,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-022-01842-5; 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": "37269091",
-    "doi": "https://doi.org/10.1177/10870547231172763",
-    "title": "Remote Administration of ADHD-Sensitive Cognitive Tasks: A Pilot Study.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of attention disorders",
-    "pubYear": "2023",
-    "date": "2023-06-02",
-    "isOpenAccess": "Y",
-    "keywords": "ADHD; Remote Monitoring; Response Inhibition; Attention Regulation; Radar-base",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>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.<h4>Method</h4>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 (<i>n</i>\u2009=\u200940).<h4>Results</h4>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.<h4>Conclusion</h4>Remote administration of cognitive tasks successfully captured the difficulties with response inhibition and regulation of attention, supporting the feasibility and validity of remote assessments.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/10870547231172763; doi:https://doi.org/10.1177/10870547231172763; html:https://europepmc.org/articles/PMC10291103; pdf:https://europepmc.org/articles/PMC10291103?pdf=render"
-  },
   {
     "id": "31815634",
     "doi": "https://doi.org/10.1186/s12933-019-0972-4",
@@ -29069,6 +29052,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.031659; doi:https://doi.org/10.1161/STROKEAHA.120.031659; html:https://europepmc.org/articles/PMC7834661; pdf:https://europepmc.org/articles/PMC7834661?pdf=render"
   },
+  {
+    "id": "37269091",
+    "doi": "https://doi.org/10.1177/10870547231172763",
+    "title": "Remote Administration of ADHD-Sensitive Cognitive Tasks: A Pilot Study.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of attention disorders",
+    "pubYear": "2023",
+    "date": "2023-06-02",
+    "isOpenAccess": "Y",
+    "keywords": "ADHD; Remote Monitoring; Response Inhibition; Attention Regulation; Radar-base",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>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.<h4>Method</h4>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 (<i>n</i>\u2009=\u200940).<h4>Results</h4>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.<h4>Conclusion</h4>Remote administration of cognitive tasks successfully captured the difficulties with response inhibition and regulation of attention, supporting the feasibility and validity of remote assessments.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/10870547231172763; doi:https://doi.org/10.1177/10870547231172763; html:https://europepmc.org/articles/PMC10291103; pdf:https://europepmc.org/articles/PMC10291103?pdf=render"
+  },
   {
     "id": "32811694",
     "doi": "https://doi.org/10.1016/j.burns.2020.01.005",
@@ -29477,23 +29477,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.12689; doi:https://doi.org/10.1002/ehf2.12689; html:https://europepmc.org/articles/PMC7373946; pdf:https://europepmc.org/articles/PMC7373946?pdf=render"
   },
-  {
-    "id": "36470992",
-    "doi": "https://doi.org/10.1038/s41375-022-01773-0",
-    "title": "Continuous Indexing of Fibrosis (CIF): improving the assessment and classification of MPN patients.",
-    "authorString": "Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D.",
-    "authorAffiliations": "",
-    "journalTitle": "Leukemia",
-    "pubYear": "2023",
-    "date": "2022-12-05",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to fully capture sample heterogeneity. To improve the quantitation of reticulin fibrosis, we developed a machine learning approach using bone marrow trephine (BMT) samples (n\u2009=\u2009107) from patients diagnosed with MPN or a reactive marrow. The resulting Continuous Indexing of Fibrosis (CIF) enhances the detection and monitoring of fibrosis within BMTs, and aids MPN subtyping. When combined with megakaryocyte feature analysis, CIF discriminates between the frequently challenging differential diagnosis of essential thrombocythemia (ET) and pre-fibrotic myelofibrosis with high predictive accuracy [area under the curve = 0.94]. CIF also shows promise in the identification of MPN patients at risk of disease progression; analysis of samples from 35 patients diagnosed with ET and enrolled in the Primary Thrombocythemia-1 trial identified features predictive of post-ET myelofibrosis (area under the curve = 0.77). In addition to these clinical applications, automated analysis of fibrosis has clear potential to further refine disease classification boundaries and inform future studies of the micro-environmental factors driving disease initiation and progression in MPN and other stem cell disorders.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41375-022-01773-0.pdf; doi:https://doi.org/10.1038/s41375-022-01773-0; html:https://europepmc.org/articles/PMC9898027; pdf:https://europepmc.org/articles/PMC9898027?pdf=render"
-  },
   {
     "id": "32680743",
     "doi": "https://doi.org/10.1016/j.jphys.2020.06.008",
@@ -29511,6 +29494,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jphys.2020.06.008; doi:https://doi.org/10.1016/j.jphys.2020.06.008"
   },
+  {
+    "id": "36470992",
+    "doi": "https://doi.org/10.1038/s41375-022-01773-0",
+    "title": "Continuous Indexing of Fibrosis (CIF): improving the assessment and classification of MPN patients.",
+    "authorString": "Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D.",
+    "authorAffiliations": "",
+    "journalTitle": "Leukemia",
+    "pubYear": "2023",
+    "date": "2022-12-05",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to fully capture sample heterogeneity. To improve the quantitation of reticulin fibrosis, we developed a machine learning approach using bone marrow trephine (BMT) samples (n\u2009=\u2009107) from patients diagnosed with MPN or a reactive marrow. The resulting Continuous Indexing of Fibrosis (CIF) enhances the detection and monitoring of fibrosis within BMTs, and aids MPN subtyping. When combined with megakaryocyte feature analysis, CIF discriminates between the frequently challenging differential diagnosis of essential thrombocythemia (ET) and pre-fibrotic myelofibrosis with high predictive accuracy [area under the curve = 0.94]. CIF also shows promise in the identification of MPN patients at risk of disease progression; analysis of samples from 35 patients diagnosed with ET and enrolled in the Primary Thrombocythemia-1 trial identified features predictive of post-ET myelofibrosis (area under the curve = 0.77). In addition to these clinical applications, automated analysis of fibrosis has clear potential to further refine disease classification boundaries and inform future studies of the micro-environmental factors driving disease initiation and progression in MPN and other stem cell disorders.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41375-022-01773-0.pdf; doi:https://doi.org/10.1038/s41375-022-01773-0; html:https://europepmc.org/articles/PMC9898027; pdf:https://europepmc.org/articles/PMC9898027?pdf=render"
+  },
   {
     "id": "33692554",
     "doi": "https://doi.org/10.1038/s41586-021-03243-6",
@@ -29800,23 +29800,6 @@
     "laySummary": "",
     "urls": "pdf:https://jmir.org/api/download?alt_name=resprot_v10i5e29072_app1.pdf&filename=e079f888f9036dd40808005eb7b49b6f.pdf; doi:https://doi.org/10.2196/29072; html:https://europepmc.org/articles/PMC8153031"
   },
-  {
-    "id": "34173574",
-    "doi": "https://doi.org/10.1016/j.puhip.2020.100039",
-    "title": "Schools and COVID-19: Reopening Pandora's box?",
-    "authorString": "Ziauddeen N, Woods-Townsend K, Saxena S, Gilbert R, Alwan NA.",
-    "authorAffiliations": "",
-    "journalTitle": "Public health in practice (Oxford, England)",
-    "pubYear": "2020",
-    "date": "2020-11-01",
-    "isOpenAccess": "Y",
-    "keywords": "Safety; Covid-19; School Re-Opening",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Schools in countries across the world are reopening as lockdown to slow progression of COVID-19 is eased. The UK government ordered school closures in England from March 20, 2020, later than the rest of Europe. A temporary and limited return for some year groups was trialled from June 2020. Teachers, school governors, the public and doctors have openly challenged the decision. The UK government has struggled to provide enough detailed information to convince the public, teachers and health practitioners, that effective systems for protection, including test, trace and isolate, are in place to prevent and manage outbreaks in schools. Risks of infection on reopening to children, staff and families must be weighed against the harms of closure to children's education and social development. The potential consequences, if the re-opening of schools is managed badly, is subsequent waves of COVID-19 infection leading to more deaths, further school closures and prolonged restrictions, losing any ground gained thus far. This article weighs the evidence for risks and benefits of reopening schools during the pandemic.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.puhip.2020.100039; doi:https://doi.org/10.1016/j.puhip.2020.100039; html:https://europepmc.org/articles/PMC7486860; pdf:https://europepmc.org/articles/PMC7486860?pdf=render"
-  },
   {
     "id": "30887727",
     "doi": "https://doi.org/10.1002/ppul.24314",
@@ -29834,6 +29817,23 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ppul.24314; doi:https://doi.org/10.1002/ppul.24314; html:https://europepmc.org/articles/PMC6617805; pdf:https://europepmc.org/articles/PMC6617805?pdf=render"
   },
+  {
+    "id": "34173574",
+    "doi": "https://doi.org/10.1016/j.puhip.2020.100039",
+    "title": "Schools and COVID-19: Reopening Pandora's box?",
+    "authorString": "Ziauddeen N, Woods-Townsend K, Saxena S, Gilbert R, Alwan NA.",
+    "authorAffiliations": "",
+    "journalTitle": "Public health in practice (Oxford, England)",
+    "pubYear": "2020",
+    "date": "2020-11-01",
+    "isOpenAccess": "Y",
+    "keywords": "Safety; Covid-19; School Re-Opening",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Schools in countries across the world are reopening as lockdown to slow progression of COVID-19 is eased. The UK government ordered school closures in England from March 20, 2020, later than the rest of Europe. A temporary and limited return for some year groups was trialled from June 2020. Teachers, school governors, the public and doctors have openly challenged the decision. The UK government has struggled to provide enough detailed information to convince the public, teachers and health practitioners, that effective systems for protection, including test, trace and isolate, are in place to prevent and manage outbreaks in schools. Risks of infection on reopening to children, staff and families must be weighed against the harms of closure to children's education and social development. The potential consequences, if the re-opening of schools is managed badly, is subsequent waves of COVID-19 infection leading to more deaths, further school closures and prolonged restrictions, losing any ground gained thus far. This article weighs the evidence for risks and benefits of reopening schools during the pandemic.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.puhip.2020.100039; doi:https://doi.org/10.1016/j.puhip.2020.100039; html:https://europepmc.org/articles/PMC7486860; pdf:https://europepmc.org/articles/PMC7486860?pdf=render"
+  },
   {
     "id": "35710247",
     "doi": "https://doi.org/10.1136/bmjopen-2021-060280",
@@ -30208,23 +30208,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41598-021-00748-y.pdf; doi:https://doi.org/10.1038/s41598-021-00748-y; html:https://europepmc.org/articles/PMC8560804; pdf:https://europepmc.org/articles/PMC8560804?pdf=render"
   },
-  {
-    "id": "37221222",
-    "doi": "https://doi.org/10.1038/s41397-023-00307-w",
-    "title": "SLCO1B1*5 is protective against non-senile cataracts in cohort prescribed statins: analysis in a British-South Asian cohort.",
-    "authorString": "Magavern EF, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",
-    "authorAffiliations": "",
-    "journalTitle": "The pharmacogenomics journal",
-    "pubYear": "2023",
-    "date": "2023-05-23",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity.<h4>Methods</h4>The Genes & Health cohort consists of British-Bangladeshi and British-Pakistani participants from East London, Manchester and Bradford, UK. SLCO1B1*5 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B1*5 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not.<h4>Results</h4>Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5-0.9, p 0.007)).<h4>Conclusions</h4>Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41397-023-00307-w.pdf; doi:https://doi.org/10.1038/s41397-023-00307-w; html:https://europepmc.org/articles/PMC10506906; pdf:https://europepmc.org/articles/PMC10506906?pdf=render"
-  },
   {
     "id": "36541441",
     "doi": "https://doi.org/10.1002/hbm.26182",
@@ -30242,6 +30225,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1002/hbm.26182; doi:https://doi.org/10.1002/hbm.26182; html:https://europepmc.org/articles/PMC9980898; pdf:https://europepmc.org/articles/PMC9980898?pdf=render"
   },
+  {
+    "id": "37221222",
+    "doi": "https://doi.org/10.1038/s41397-023-00307-w",
+    "title": "SLCO1B1*5 is protective against non-senile cataracts in cohort prescribed statins: analysis in a British-South Asian cohort.",
+    "authorString": "Magavern EF, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",
+    "authorAffiliations": "",
+    "journalTitle": "The pharmacogenomics journal",
+    "pubYear": "2023",
+    "date": "2023-05-23",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity.<h4>Methods</h4>The Genes & Health cohort consists of British-Bangladeshi and British-Pakistani participants from East London, Manchester and Bradford, UK. SLCO1B1*5 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B1*5 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not.<h4>Results</h4>Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5-0.9, p 0.007)).<h4>Conclusions</h4>Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41397-023-00307-w.pdf; doi:https://doi.org/10.1038/s41397-023-00307-w; html:https://europepmc.org/articles/PMC10506906; pdf:https://europepmc.org/articles/PMC10506906?pdf=render"
+  },
   {
     "id": "34555069",
     "doi": "https://doi.org/10.1371/journal.pone.0257361",
@@ -30463,23 +30463,6 @@
     "laySummary": "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. ",
     "urls": "pdf:https://www.nature.com/articles/s41433-018-0229-6.pdf; 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"
   },
-  {
-    "id": "35477539",
-    "doi": "https://doi.org/10.1136/gutjnl-2021-326183",
-    "title": "Activation of innate-adaptive immune machinery by poly(I:C) exposes a therapeutic vulnerability to prevent relapse in stroma-rich colon cancer.",
-    "authorString": "Corry SM, McCorry AM, Lannagan TR, Leonard NA, Fisher NC, Byrne RM, Tsantoulis P, Cortes-Lavaud X, Amirkhah R, Redmond KL, McCooey AJ, Malla SB, Rogan E, Sakhnevych S, Gillespie MA, White M, Richman SD, Jackstadt RF, Campbell AD, Maguire S, S:CORT and ACRCelerate consortia, McDade SS, Longley DB, Loughrey MB, Coleman HG, Kerr EM, Tejpar S, Maughan T, Leedham SJ, Small DM, Ryan AE, Sansom OJ, Lawler M, Dunne PD.",
-    "authorAffiliations": "",
-    "journalTitle": "Gut",
-    "pubYear": "2022",
-    "date": "2022-04-27",
-    "isOpenAccess": "Y",
-    "keywords": "Cancer; Colorectal Cancer; Adjuvant Treatment; Colon Carcinogenesis",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>Stroma-rich tumours represent a poor prognostic subtype in stage II/III colon cancer (CC), with high relapse rates and limited response to standard adjuvant chemotherapy.<h4>Design</h4>To address the lack of efficacious therapeutic options for patients with stroma-rich CC, we stratified our human tumour cohorts according to stromal content, enabling identification of the biology underpinning relapse and potential therapeutic vulnerabilities specifically within stroma-rich tumours that could be exploited clinically. Following human tumour-based discovery and independent clinical validation, we use a series of <i>in vitro</i> and stroma-rich <i>in vivo</i> models to test and validate the therapeutic potential of elevating the biology associated with reduced relapse in human tumours.<h4>Results</h4>By performing our analyses specifically within the stroma-rich/high-fibroblast (HiFi) subtype of CC, we identify and validate the clinical value of a HiFi-specific prognostic signature (HPS), which stratifies tumours based on STAT1-related signalling (High-HPS v Low-HPS=HR 0.093, CI 0.019 to 0.466). Using <i>in silico, in vitro</i> and <i>in vivo</i> models, we demonstrate that the HPS is associated with antigen processing and presentation within discrete immune lineages in stroma-rich CC, downstream of double-stranded RNA and viral response signalling. Treatment with the TLR3 agonist poly(I:C) elevated the HPS signalling and antigen processing phenotype across <i>in vitro</i> and <i>in vivo</i> models. In an <i>in vivo</i> model of stroma-rich CC, poly(I:C) treatment significantly increased systemic cytotoxic T cell activity (p<0.05) and reduced liver metastases (p<0.0002).<h4>Conclusion</h4>This study reveals new biological insight that offers a novel therapeutic option to reduce relapse rates in patients with the worst prognosis CC.",
-    "laySummary": "",
-    "urls": "pdf:https://gut.bmj.com/content/gutjnl/early/2022/04/10/gutjnl-2021-326183.full.pdf; doi:https://doi.org/10.1136/gutjnl-2021-326183; html:https://europepmc.org/articles/PMC9664095; pdf:https://europepmc.org/articles/PMC9664095?pdf=render"
-  },
   {
     "id": "33407780",
     "doi": "https://doi.org/10.1186/s13063-020-04951-6",
@@ -30497,6 +30480,23 @@
     "laySummary": "",
     "urls": "pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04951-6; doi:https://doi.org/10.1186/s13063-020-04951-6; html:https://europepmc.org/articles/PMC7788716; pdf:https://europepmc.org/articles/PMC7788716?pdf=render"
   },
+  {
+    "id": "35477539",
+    "doi": "https://doi.org/10.1136/gutjnl-2021-326183",
+    "title": "Activation of innate-adaptive immune machinery by poly(I:C) exposes a therapeutic vulnerability to prevent relapse in stroma-rich colon cancer.",
+    "authorString": "Corry SM, McCorry AM, Lannagan TR, Leonard NA, Fisher NC, Byrne RM, Tsantoulis P, Cortes-Lavaud X, Amirkhah R, Redmond KL, McCooey AJ, Malla SB, Rogan E, Sakhnevych S, Gillespie MA, White M, Richman SD, Jackstadt RF, Campbell AD, Maguire S, S:CORT and ACRCelerate consortia, McDade SS, Longley DB, Loughrey MB, Coleman HG, Kerr EM, Tejpar S, Maughan T, Leedham SJ, Small DM, Ryan AE, Sansom OJ, Lawler M, Dunne PD.",
+    "authorAffiliations": "",
+    "journalTitle": "Gut",
+    "pubYear": "2022",
+    "date": "2022-04-27",
+    "isOpenAccess": "Y",
+    "keywords": "Cancer; Colorectal Cancer; Adjuvant Treatment; Colon Carcinogenesis",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>Stroma-rich tumours represent a poor prognostic subtype in stage II/III colon cancer (CC), with high relapse rates and limited response to standard adjuvant chemotherapy.<h4>Design</h4>To address the lack of efficacious therapeutic options for patients with stroma-rich CC, we stratified our human tumour cohorts according to stromal content, enabling identification of the biology underpinning relapse and potential therapeutic vulnerabilities specifically within stroma-rich tumours that could be exploited clinically. Following human tumour-based discovery and independent clinical validation, we use a series of <i>in vitro</i> and stroma-rich <i>in vivo</i> models to test and validate the therapeutic potential of elevating the biology associated with reduced relapse in human tumours.<h4>Results</h4>By performing our analyses specifically within the stroma-rich/high-fibroblast (HiFi) subtype of CC, we identify and validate the clinical value of a HiFi-specific prognostic signature (HPS), which stratifies tumours based on STAT1-related signalling (High-HPS v Low-HPS=HR 0.093, CI 0.019 to 0.466). Using <i>in silico, in vitro</i> and <i>in vivo</i> models, we demonstrate that the HPS is associated with antigen processing and presentation within discrete immune lineages in stroma-rich CC, downstream of double-stranded RNA and viral response signalling. Treatment with the TLR3 agonist poly(I:C) elevated the HPS signalling and antigen processing phenotype across <i>in vitro</i> and <i>in vivo</i> models. In an <i>in vivo</i> model of stroma-rich CC, poly(I:C) treatment significantly increased systemic cytotoxic T cell activity (p<0.05) and reduced liver metastases (p<0.0002).<h4>Conclusion</h4>This study reveals new biological insight that offers a novel therapeutic option to reduce relapse rates in patients with the worst prognosis CC.",
+    "laySummary": "",
+    "urls": "pdf:https://gut.bmj.com/content/gutjnl/early/2022/04/10/gutjnl-2021-326183.full.pdf; doi:https://doi.org/10.1136/gutjnl-2021-326183; html:https://europepmc.org/articles/PMC9664095; pdf:https://europepmc.org/articles/PMC9664095?pdf=render"
+  },
   {
     "id": "33742045",
     "doi": "https://doi.org/10.1038/s41598-021-85354-8",
@@ -30786,23 +30786,6 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463529; doi:https://doi.org/10.1016/j.ebiom.2022.104243; html:https://europepmc.org/articles/PMC9463529; pdf:https://europepmc.org/articles/PMC9463529?pdf=render"
   },
-  {
-    "id": "37920851",
-    "doi": "https://doi.org/10.1038/s44161-022-00171-0",
-    "title": "Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation.",
-    "authorString": "Mokry M, Boltjes A, Slenders L, Bel-Bordes G, Cui K, Brouwer E, Mekke JM, Depuydt MAC, Timmerman N, Waissi F, Verwer MC, Turner AW, Khan MD, Hodonsky CJ, Benavente ED, Hartman RJG, van den Dungen NAM, Lansu N, Nagyova E, Prange KHM, Kovacic JC, Bj\u00f6rkegren JLM, Pavlos E, Andreakos E, Schunkert H, Owens GK, Monaco C, Finn AV, Virmani R, Leeper NJ, de Winther MPJ, Kuiper J, de Borst GJ, Stroes ESG, Civelek M, de Kleijn DPV, den Ruijter HM, Asselbergs FW, van der Laan SW, Miller CL, Pasterkamp G.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature cardiovascular research",
-    "pubYear": "2022",
-    "date": "2022-12-12",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved sub-phenotyping. Here we analyze the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These plaque phenotypes were associated with clinical presentation and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia. One of the plaque types with the most severe clinical symptoms pointed to both inflammatory and fibrotic cell lineages. Further, we did a preliminary analysis of potential circulating biomarkers that mark the different plaques phenotypes. In conclusion, the definition of the plaque at risk for a thrombotic event can be fine-tuned by in-depth transcriptomic-based phenotyping. These differential plaque phenotypes prove clinically relevant for both carotid and coronary artery plaques and point to distinct underlying biology of symptomatic lesions.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1038/s44161-022-00171-0; html:https://europepmc.org/articles/PMC10621615; pdf:https://europepmc.org/articles/PMC10621615?pdf=render; doi:https://doi.org/10.1038/s44161-022-00171-0"
-  },
   {
     "id": "32247823",
     "doi": "https://doi.org/10.1016/j.jhep.2020.03.032",
@@ -30820,6 +30803,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.journal-of-hepatology.eu/article/S016882782030194X/pdf; 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"
   },
+  {
+    "id": "37920851",
+    "doi": "https://doi.org/10.1038/s44161-022-00171-0",
+    "title": "Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation.",
+    "authorString": "Mokry M, Boltjes A, Slenders L, Bel-Bordes G, Cui K, Brouwer E, Mekke JM, Depuydt MAC, Timmerman N, Waissi F, Verwer MC, Turner AW, Khan MD, Hodonsky CJ, Benavente ED, Hartman RJG, van den Dungen NAM, Lansu N, Nagyova E, Prange KHM, Kovacic JC, Bj\u00f6rkegren JLM, Pavlos E, Andreakos E, Schunkert H, Owens GK, Monaco C, Finn AV, Virmani R, Leeper NJ, de Winther MPJ, Kuiper J, de Borst GJ, Stroes ESG, Civelek M, de Kleijn DPV, den Ruijter HM, Asselbergs FW, van der Laan SW, Miller CL, Pasterkamp G.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature cardiovascular research",
+    "pubYear": "2022",
+    "date": "2022-12-12",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved sub-phenotyping. Here we analyze the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These plaque phenotypes were associated with clinical presentation and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia. One of the plaque types with the most severe clinical symptoms pointed to both inflammatory and fibrotic cell lineages. Further, we did a preliminary analysis of potential circulating biomarkers that mark the different plaques phenotypes. In conclusion, the definition of the plaque at risk for a thrombotic event can be fine-tuned by in-depth transcriptomic-based phenotyping. These differential plaque phenotypes prove clinically relevant for both carotid and coronary artery plaques and point to distinct underlying biology of symptomatic lesions.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1038/s44161-022-00171-0; html:https://europepmc.org/articles/PMC10621615; pdf:https://europepmc.org/articles/PMC10621615?pdf=render; doi:https://doi.org/10.1038/s44161-022-00171-0"
+  },
   {
     "id": "33664499",
     "doi": "https://doi.org/10.1038/s41431-021-00835-8",
@@ -30854,23 +30854,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.injuryjournal.com/article/S0020138321003429/pdf; doi:https://doi.org/10.1016/j.injury.2021.04.033"
   },
-  {
-    "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": "<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 <i>a priori</i> 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 <i>p</i>-values 0.04 and 6 \u00d7 10<sup>-5</sup>, respectively), with an effect reversal in younger women.<h4>Conclusion</h4>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": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.768972/pdf; doi:https://doi.org/10.3389/fcvm.2022.768972; html:https://europepmc.org/articles/PMC9043514; pdf:https://europepmc.org/articles/PMC9043514?pdf=render"
-  },
   {
     "id": "32714939",
     "doi": "https://doi.org/10.3389/fnut.2020.00080",
@@ -30888,6 +30871,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fnut.2020.00080/pdf; doi:https://doi.org/10.3389/fnut.2020.00080; html:https://europepmc.org/articles/PMC7343846; pdf:https://europepmc.org/articles/PMC7343846?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": "<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 <i>a priori</i> 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 <i>p</i>-values 0.04 and 6 \u00d7 10<sup>-5</sup>, respectively), with an effect reversal in younger women.<h4>Conclusion</h4>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": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.768972/pdf; doi:https://doi.org/10.3389/fcvm.2022.768972; html:https://europepmc.org/articles/PMC9043514; pdf:https://europepmc.org/articles/PMC9043514?pdf=render"
+  },
   {
     "id": "32808938",
     "doi": "https://doi.org/10.2196/17022",
@@ -30990,6 +30990,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-020-17477-x.pdf; doi:https://doi.org/10.1038/s41467-020-17477-x; html:https://europepmc.org/articles/PMC7387553; pdf:https://europepmc.org/articles/PMC7387553?pdf=render"
   },
+  {
+    "id": "34167318",
+    "doi": "https://doi.org/10.1161/circulationaha.121.054302",
+    "title": "Cardiac Troponin Thresholds and Kinetics to Differentiate Myocardial Injury and Myocardial Infarction.",
+    "authorString": "Wereski R, Kimenai DM, Taggart C, Doudesis D, Lee KK, Lowry MTH, Bularga A, Lowe DJ, Fujisawa T, Apple FS, Collinson PO, Anand A, Chapman AR, Mills NL.",
+    "authorAffiliations": "",
+    "journalTitle": "Circulation",
+    "pubYear": "2021",
+    "date": "2021-06-25",
+    "isOpenAccess": "Y",
+    "keywords": "Kinetics; Troponin; Myocardial infarction; Predictive Value Of Tests",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Although the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice.<h4>Methods</h4>In a secondary analysis of a multicenter randomized controlled trial, we identified 46\u2009092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment-elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value and specificity were determined at the sex-specific 99th percentile upper reference limit and rule-in thresholds of 64 ng/L and 5-fold of the upper reference limit for a diagnosis of type 1 myocardial infarction.<h4>Results</h4>Troponin was above the 99th percentile in 8188 patients (18%). The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14% and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th-75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold upper reference limit gave a positive predictive value of 57% (95% CI, 56%-58%), 59% (58%-61%), and 62% (60%-64%) and a specificity of 96% (96%-96%), 96% (96%-96%), and 98% (97%-98%), respectively. The absolute, relative, and rate of change in troponin concentration were highest in patients with type 1 myocardial infarction (<i>P</i><0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared with troponin concentration at presentation alone (area under the curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]).<h4>Conclusions</h4>Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01852123.",
+    "laySummary": "",
+    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.054302; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.054302; html:https://europepmc.org/articles/PMC8360674; pdf:https://europepmc.org/articles/PMC8360674?pdf=render"
+  },
   {
     "id": "36647047",
     "doi": "https://doi.org/10.1186/s12916-022-02722-5",
@@ -31008,21 +31025,21 @@
     "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02722-5; 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": "34167318",
-    "doi": "https://doi.org/10.1161/circulationaha.121.054302",
-    "title": "Cardiac Troponin Thresholds and Kinetics to Differentiate Myocardial Injury and Myocardial Infarction.",
-    "authorString": "Wereski R, Kimenai DM, Taggart C, Doudesis D, Lee KK, Lowry MTH, Bularga A, Lowe DJ, Fujisawa T, Apple FS, Collinson PO, Anand A, Chapman AR, Mills NL.",
+    "id": "32548911",
+    "doi": "https://doi.org/10.1002/ehf2.12779",
+    "title": "A registry-based algorithm to predict ejection fraction in patients with heart failure.",
+    "authorString": "Uijl A, Lund LH, Vaartjes I, Brugts JJ, Linssen GC, Asselbergs FW, Hoes AW, Dahlstr\u00f6m U, Koudstaal S, Savarese G.",
     "authorAffiliations": "",
-    "journalTitle": "Circulation",
-    "pubYear": "2021",
-    "date": "2021-06-25",
+    "journalTitle": "ESC heart failure",
+    "pubYear": "2020",
+    "date": "2020-06-17",
     "isOpenAccess": "Y",
-    "keywords": "Kinetics; Troponin; Myocardial infarction; Predictive Value Of Tests",
+    "keywords": "Prediction; Ejection fraction; Heart Failure; Electronic Health Records; Hfpef; Hfref; Hfmref",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>Although the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice.<h4>Methods</h4>In a secondary analysis of a multicenter randomized controlled trial, we identified 46\u2009092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment-elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value and specificity were determined at the sex-specific 99th percentile upper reference limit and rule-in thresholds of 64 ng/L and 5-fold of the upper reference limit for a diagnosis of type 1 myocardial infarction.<h4>Results</h4>Troponin was above the 99th percentile in 8188 patients (18%). The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14% and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th-75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold upper reference limit gave a positive predictive value of 57% (95% CI, 56%-58%), 59% (58%-61%), and 62% (60%-64%) and a specificity of 96% (96%-96%), 96% (96%-96%), and 98% (97%-98%), respectively. The absolute, relative, and rate of change in troponin concentration were highest in patients with type 1 myocardial infarction (<i>P</i><0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared with troponin concentration at presentation alone (area under the curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]).<h4>Conclusions</h4>Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01852123.",
+    "abstract": "<h4>Aims</h4>Left ventricular ejection fraction (EF) is required to categorize heart failure (HF) [i.e. HF with preserved (HFpEF), mid-range (HFmrEF), and reduced (HFrEF) EF] but is often not captured in population-based cohorts or non-HF registries. The aim was to create an algorithm that identifies EF subphenotypes for research purposes.<h4>Methods and results</h4>We included 42 061 HF patients from the Swedish Heart Failure Registry. As primary analysis, we performed two logistic regression models including 22 variables to predict (i) EF\u2265 vs. <50% and (ii) EF\u2265 vs. <40%. In the secondary analysis, we performed a multivariable multinomial analysis with 22 variables to create a model for all three separate EF subphenotypes: HFrEF vs. HFmrEF vs. HFpEF. The models were validated in the database from the CHECK-HF study, a cross-sectional survey of 10 627 patients from the Netherlands. The C-statistic (discrimination) was 0.78 [95% confidence interval (CI) 0.77-0.78] for EF \u226550% and 0.76 (95% CI 0.75-0.76) for EF \u226540%. Similar results were achieved for HFrEF and HFpEF in the multinomial model, but the C-statistic for HFmrEF was lower: 0.63 (95% CI 0.63-0.64). The external validation showed similar discriminative ability to the development cohort.<h4>Conclusions</h4>Routine clinical characteristics could potentially be used to identify different EF subphenotypes in databases where EF is not readily available. Accuracy was good for the prediction of HFpEF and HFrEF but lower for HFmrEF. The proposed algorithm enables more effective research on HF in the big data setting.",
     "laySummary": "",
-    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.054302; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.054302; html:https://europepmc.org/articles/PMC8360674; pdf:https://europepmc.org/articles/PMC8360674?pdf=render"
+    "urls": "doi:https://doi.org/10.1002/ehf2.12779; doi:https://doi.org/10.1002/ehf2.12779; html:https://europepmc.org/articles/PMC7524089; pdf:https://europepmc.org/articles/PMC7524089?pdf=render"
   },
   {
     "id": "37338017",
@@ -31058,23 +31075,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41586-022-04569-5.pdf; doi:https://doi.org/10.1038/s41586-022-04569-5; html:https://europepmc.org/articles/PMC9046077; pdf:https://europepmc.org/articles/PMC9046077?pdf=render"
   },
-  {
-    "id": "32548911",
-    "doi": "https://doi.org/10.1002/ehf2.12779",
-    "title": "A registry-based algorithm to predict ejection fraction in patients with heart failure.",
-    "authorString": "Uijl A, Lund LH, Vaartjes I, Brugts JJ, Linssen GC, Asselbergs FW, Hoes AW, Dahlstr\u00f6m U, Koudstaal S, Savarese G.",
-    "authorAffiliations": "",
-    "journalTitle": "ESC heart failure",
-    "pubYear": "2020",
-    "date": "2020-06-17",
-    "isOpenAccess": "Y",
-    "keywords": "Prediction; Ejection fraction; Heart Failure; Electronic Health Records; Hfpef; Hfref; Hfmref",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>Left ventricular ejection fraction (EF) is required to categorize heart failure (HF) [i.e. HF with preserved (HFpEF), mid-range (HFmrEF), and reduced (HFrEF) EF] but is often not captured in population-based cohorts or non-HF registries. The aim was to create an algorithm that identifies EF subphenotypes for research purposes.<h4>Methods and results</h4>We included 42 061 HF patients from the Swedish Heart Failure Registry. As primary analysis, we performed two logistic regression models including 22 variables to predict (i) EF\u2265 vs. <50% and (ii) EF\u2265 vs. <40%. In the secondary analysis, we performed a multivariable multinomial analysis with 22 variables to create a model for all three separate EF subphenotypes: HFrEF vs. HFmrEF vs. HFpEF. The models were validated in the database from the CHECK-HF study, a cross-sectional survey of 10 627 patients from the Netherlands. The C-statistic (discrimination) was 0.78 [95% confidence interval (CI) 0.77-0.78] for EF \u226550% and 0.76 (95% CI 0.75-0.76) for EF \u226540%. Similar results were achieved for HFrEF and HFpEF in the multinomial model, but the C-statistic for HFmrEF was lower: 0.63 (95% CI 0.63-0.64). The external validation showed similar discriminative ability to the development cohort.<h4>Conclusions</h4>Routine clinical characteristics could potentially be used to identify different EF subphenotypes in databases where EF is not readily available. Accuracy was good for the prediction of HFpEF and HFrEF but lower for HFmrEF. The proposed algorithm enables more effective research on HF in the big data setting.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1002/ehf2.12779; doi:https://doi.org/10.1002/ehf2.12779; html:https://europepmc.org/articles/PMC7524089; pdf:https://europepmc.org/articles/PMC7524089?pdf=render"
-  },
   {
     "id": "37128097",
     "doi": "https://doi.org/10.1038/s43016-020-0092-z",
@@ -31891,23 +31891,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1878-0261.13038; doi:https://doi.org/10.1002/1878-0261.13038; html:https://europepmc.org/articles/PMC8486593; pdf:https://europepmc.org/articles/PMC8486593?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*.",
-    "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": "<h4>Background and purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%; <i>P</i>=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.<h4>Conclusions</h4>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": "pdf:https://europepmc.org/articles/pmc8607920?pdf=render; doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?pdf=render"
-  },
   {
     "id": "31372838",
     "doi": "https://doi.org/10.1007/s12471-019-01308-w",
@@ -31925,6 +31908,23 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s12471-019-01308-w.pdf; doi:https://doi.org/10.1007/s12471-019-01308-w; html:https://europepmc.org/articles/PMC6712110; pdf:https://europepmc.org/articles/PMC6712110?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*.",
+    "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": "<h4>Background and purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%; <i>P</i>=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.<h4>Conclusions</h4>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": "pdf:https://europepmc.org/articles/pmc8607920?pdf=render; doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?pdf=render"
+  },
   {
     "id": "35322056",
     "doi": "https://doi.org/10.1038/s41598-022-08351-5",
@@ -32214,23 +32214,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-020-18783-0.pdf; doi:https://doi.org/10.1038/s41467-020-18783-0; html:https://europepmc.org/articles/PMC7538915; pdf:https://europepmc.org/articles/PMC7538915?pdf=render"
   },
-  {
-    "id": "35879886",
-    "doi": "https://doi.org/10.1017/s0033291722002501",
-    "title": "Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.",
-    "authorString": "Young KS, Purves KL, H\u00fcbel C, Davies MR, Thompson KN, Bristow S, Krebs G, Danese A, Hirsch C, Parsons CE, Vassos E, Adey BN, Bright S, Hegemann L, Lee YT, Kalsi G, Monssen D, Mundy J, Peel AJ, Rayner C, Rogers HC, Ter Kuile A, Ward C, York K, Lin Y, Palmos AB, Schmidt U, Veale D, Nicholson TR, Pollak TA, Stevelink SAM, Moukhtarian T, Martineau AR, Holt H, Maughan B, Al-Chalabi A, Chaudhuri KR, Richardson MP, Bradley JR, Chinnery PF, Kingston N, Papadia S, Stirrups KE, Linger R, Hotopf M, Eley TC, Breen G.",
-    "authorAffiliations": "",
-    "journalTitle": "Psychological medicine",
-    "pubYear": "2023",
-    "date": "2022-07-26",
-    "isOpenAccess": "Y",
-    "keywords": "Depression; Anxiety; Ptsd; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.<h4>Method</h4>Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (<i>n</i> = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.<h4>Results</h4>Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.<h4>Conclusions</h4>We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.",
-    "laySummary": "",
-    "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/8C3760ED596F1ED8B80F729AC5E47B9B/S0033291722002501a.pdf/div-class-title-depression-anxiety-and-ptsd-symptoms-before-and-during-the-covid-19-pandemic-in-the-uk-div.pdf; doi:https://doi.org/10.1017/S0033291722002501; html:https://europepmc.org/articles/PMC10482709; pdf:https://europepmc.org/articles/PMC10482709?pdf=render"
-  },
   {
     "id": "30928767",
     "doi": "https://doi.org/10.1016/j.evalprogplan.2019.03.002",
@@ -32248,6 +32231,23 @@
     "laySummary": "",
     "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa49960/Download/0049960-14052019134527.pdf; doi:https://doi.org/10.1016/j.evalprogplan.2019.03.002"
   },
+  {
+    "id": "35879886",
+    "doi": "https://doi.org/10.1017/s0033291722002501",
+    "title": "Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.",
+    "authorString": "Young KS, Purves KL, H\u00fcbel C, Davies MR, Thompson KN, Bristow S, Krebs G, Danese A, Hirsch C, Parsons CE, Vassos E, Adey BN, Bright S, Hegemann L, Lee YT, Kalsi G, Monssen D, Mundy J, Peel AJ, Rayner C, Rogers HC, Ter Kuile A, Ward C, York K, Lin Y, Palmos AB, Schmidt U, Veale D, Nicholson TR, Pollak TA, Stevelink SAM, Moukhtarian T, Martineau AR, Holt H, Maughan B, Al-Chalabi A, Chaudhuri KR, Richardson MP, Bradley JR, Chinnery PF, Kingston N, Papadia S, Stirrups KE, Linger R, Hotopf M, Eley TC, Breen G.",
+    "authorAffiliations": "",
+    "journalTitle": "Psychological medicine",
+    "pubYear": "2023",
+    "date": "2022-07-26",
+    "isOpenAccess": "Y",
+    "keywords": "Depression; Anxiety; Ptsd; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.<h4>Method</h4>Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (<i>n</i> = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.<h4>Results</h4>Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.<h4>Conclusions</h4>We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.",
+    "laySummary": "",
+    "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/8C3760ED596F1ED8B80F729AC5E47B9B/S0033291722002501a.pdf/div-class-title-depression-anxiety-and-ptsd-symptoms-before-and-during-the-covid-19-pandemic-in-the-uk-div.pdf; doi:https://doi.org/10.1017/S0033291722002501; html:https://europepmc.org/articles/PMC10482709; pdf:https://europepmc.org/articles/PMC10482709?pdf=render"
+  },
   {
     "id": "37247330",
     "doi": "https://doi.org/10.1093/eurheartj/ehad260",
@@ -32265,23 +32265,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1093/eurheartj/ehad260; doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?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; Cancer Therapy\u2013related Cardiac Dysfunction; Anthracycline\u2010related Cardiomyopathy",
-    "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; <i>P</i>=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; <i>P</i>=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; pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025935"
-  },
   {
     "id": "32576090",
     "doi": "https://doi.org/10.1161/strokeaha.120.029042",
@@ -32299,6 +32282,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.029042; doi:https://doi.org/10.1161/STROKEAHA.120.029042; html:https://europepmc.org/articles/PMC7382539; pdf:https://europepmc.org/articles/PMC7382539?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; Cancer Therapy\u2013related Cardiac Dysfunction; Anthracycline\u2010related Cardiomyopathy",
+    "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; <i>P</i>=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; <i>P</i>=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; pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025935"
+  },
   {
     "id": "35545669",
     "doi": "https://doi.org/10.1038/s41586-022-04712-2",
@@ -32537,23 +32537,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/5/e038530.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038530; html:https://europepmc.org/articles/PMC7239518; pdf:https://europepmc.org/articles/PMC7239518?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": "pdf:http://www.journalofhospitalinfection.com/article/S0195670121000712/pdf; 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": "32934998",
     "doi": "https://doi.org/10.23889/ijpds.v3i1.412",
@@ -32571,6 +32554,23 @@
     "laySummary": "",
     "urls": "pdf:https://ijpds.org/article/download/412/533; doi:https://doi.org/10.23889/ijpds.v3i1.412; html:https://europepmc.org/articles/PMC7299475; pdf:https://europepmc.org/articles/PMC7299475?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": "pdf:http://www.journalofhospitalinfection.com/article/S0195670121000712/pdf; 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": "35908569",
     "doi": "https://doi.org/10.1016/s0140-6736(22)01109-6",
@@ -32690,23 +32690,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e042893.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042893; html:https://europepmc.org/articles/PMC8237724; pdf:https://europepmc.org/articles/PMC8237724?pdf=render"
   },
-  {
-    "id": "32987048",
-    "doi": "https://doi.org/10.1016/j.ijcard.2020.09.053",
-    "title": "Predicting 10-year risk of recurrent cardiovascular events andcardiovascular interventions in patients with established cardiovascular disease: results from UCC-SMART and REACH.",
-    "authorString": "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.",
-    "authorAffiliations": "",
-    "journalTitle": "International journal of cardiology",
-    "pubYear": "2021",
-    "date": "2020-09-25",
-    "isOpenAccess": "N",
-    "keywords": "Risk Prediction; Cardiovascular Interventions; Major Cardiovascular Events; Patients With Established Cardiovascular Disease",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>Data of patients with established CVD from the UCC-SMART cohort (N\u00a0=\u00a08421) were used for model development, and patient data from REACH Western Europe (N\u00a0=\u00a014,528) and REACH North America (N\u00a0=\u00a019,495) 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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:http://www.internationaljournalofcardiology.com/article/S0167527320338341/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.09.053"
-  },
   {
     "id": "31073125",
     "doi": "https://doi.org/10.1038/s41533-019-0132-z",
@@ -32724,6 +32707,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41533-019-0132-z.pdf; doi:https://doi.org/10.1038/s41533-019-0132-z; html:https://europepmc.org/articles/PMC6509212; pdf:https://europepmc.org/articles/PMC6509212?pdf=render"
   },
+  {
+    "id": "32987048",
+    "doi": "https://doi.org/10.1016/j.ijcard.2020.09.053",
+    "title": "Predicting 10-year risk of recurrent cardiovascular events andcardiovascular interventions in patients with established cardiovascular disease: results from UCC-SMART and REACH.",
+    "authorString": "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.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of cardiology",
+    "pubYear": "2021",
+    "date": "2020-09-25",
+    "isOpenAccess": "N",
+    "keywords": "Risk Prediction; Cardiovascular Interventions; Major Cardiovascular Events; Patients With Established Cardiovascular Disease",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>Data of patients with established CVD from the UCC-SMART cohort (N\u00a0=\u00a08421) were used for model development, and patient data from REACH Western Europe (N\u00a0=\u00a014,528) and REACH North America (N\u00a0=\u00a019,495) 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).<h4>Results</h4>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.<h4>Conclusions</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:http://www.internationaljournalofcardiology.com/article/S0167527320338341/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.09.053"
+  },
   {
     "id": "32032817",
     "doi": "https://doi.org/10.1016/j.nicl.2020.102172",
@@ -32877,23 +32877,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S0140673621016093/pdf; 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"
   },
-  {
-    "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": "<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003907&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003907; html:https://europepmc.org/articles/PMC8887739; pdf:https://europepmc.org/articles/PMC8887739?pdf=render"
-  },
   {
     "id": "32814899",
     "doi": "https://doi.org/10.1038/s41586-020-2635-8",
@@ -32911,6 +32894,23 @@
     "laySummary": "",
     "urls": "pdf:https://discovery.ucl.ac.uk/10110799/1/Meyer_accepted_version.pdf; 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"
   },
+  {
+    "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": "<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003907&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003907; html:https://europepmc.org/articles/PMC8887739; pdf:https://europepmc.org/articles/PMC8887739?pdf=render"
+  },
   {
     "id": "33430602",
     "doi": "https://doi.org/10.1161/circheartfailure.120.007022",
@@ -33217,23 +33217,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ooim/article-pdf/2/1/iqab014/48744499/iqab014.pdf; doi:https://doi.org/10.1093/oxfimm/iqab014; html:https://europepmc.org/articles/PMC8371939; pdf:https://europepmc.org/articles/PMC8371939?pdf=render"
   },
-  {
-    "id": "33332257",
-    "doi": "https://doi.org/10.1099/mgen.0.000434",
-    "title": "Read trimming has minimal effect on bacterial SNP-calling accuracy. ",
-    "authorString": "Bush SJ.",
-    "authorAffiliations": "",
-    "journalTitle": "Microbial genomics",
-    "pubYear": "2020",
-    "date": "2020-12-11",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Read alignment is the central step of many analytic pipelines that perform variant calling. To reduce error, it is common practice to pre-process raw sequencing reads to remove low-quality bases and residual adapter contamination, a procedure collectively known as 'trimming'. Trimming is widely assumed to increase the accuracy of variant calling, although there are relatively few systematic evaluations of its effects and no clear consensus on its efficacy. As sequencing datasets increase both in number and size, it is worthwhile reappraising computational operations of ambiguous benefit, particularly when the scope of many analyses now routinely incorporates thousands of samples, increasing the time and cost required. Using a curated set of 17 Gram-negative bacterial genomes, this study initially evaluated the impact of four read-trimming utilities (Atropos, fastp, Trim Galore and Trimmomatic), each used with a range of stringencies, on the accuracy and completeness of three bacterial SNP-calling pipelines. It was found that read trimming made only small, and statistically insignificant, increases in SNP-calling accuracy even when using the highest-performing pre-processor in this study, fastp. To extend these findings, >6500 publicly archived sequencing datasets from Escherichia coli, Mycobacterium tuberculosis and Staphylococcus aureus were re-analysed using a common analytic pipeline. Of the approximately 125\u2009million SNPs and 1.25\u2009million indels called across all samples, the same bases were called in 98.8 and 91.9\u200a% of cases, respectively, irrespective of whether raw reads or trimmed reads were used. Nevertheless, the proportion of mixed calls (i.e. calls where <100\u200a% of the reads support the variant allele; considered a proxy of false positives) was significantly reduced after trimming, which suggests that while trimming rarely alters the set of variant bases, it can affect the proportion of reads supporting each call. It was concluded that read quality- and adapter-trimming add relatively little value to a SNP-calling pipeline and may only be necessary if small differences in the absolute number of SNP calls, or the false call rate, are critical. Broadly similar conclusions can be drawn about the utility of trimming to an indel-calling pipeline. Read trimming remains routinely performed prior to variant calling likely out of concern that doing otherwise would typically have negative consequences. While historically this may have been the case, the data in this study suggests that read trimming is not always a practical necessity.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1099/mgen.0.000434; doi:https://doi.org/10.1099/mgen.0.000434; html:https://europepmc.org/articles/PMC8116680; pdf:https://europepmc.org/articles/PMC8116680?pdf=render"
-  },
   {
     "id": "32289242",
     "doi": "https://doi.org/10.1098/rsob.190297",
@@ -33251,6 +33234,23 @@
     "laySummary": "",
     "urls": "pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.190297; doi:https://doi.org/10.1098/rsob.190297; html:https://europepmc.org/articles/PMC7241076; pdf:https://europepmc.org/articles/PMC7241076?pdf=render"
   },
+  {
+    "id": "33332257",
+    "doi": "https://doi.org/10.1099/mgen.0.000434",
+    "title": "Read trimming has minimal effect on bacterial SNP-calling accuracy. ",
+    "authorString": "Bush SJ.",
+    "authorAffiliations": "",
+    "journalTitle": "Microbial genomics",
+    "pubYear": "2020",
+    "date": "2020-12-11",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Read alignment is the central step of many analytic pipelines that perform variant calling. To reduce error, it is common practice to pre-process raw sequencing reads to remove low-quality bases and residual adapter contamination, a procedure collectively known as 'trimming'. Trimming is widely assumed to increase the accuracy of variant calling, although there are relatively few systematic evaluations of its effects and no clear consensus on its efficacy. As sequencing datasets increase both in number and size, it is worthwhile reappraising computational operations of ambiguous benefit, particularly when the scope of many analyses now routinely incorporates thousands of samples, increasing the time and cost required. Using a curated set of 17 Gram-negative bacterial genomes, this study initially evaluated the impact of four read-trimming utilities (Atropos, fastp, Trim Galore and Trimmomatic), each used with a range of stringencies, on the accuracy and completeness of three bacterial SNP-calling pipelines. It was found that read trimming made only small, and statistically insignificant, increases in SNP-calling accuracy even when using the highest-performing pre-processor in this study, fastp. To extend these findings, >6500 publicly archived sequencing datasets from Escherichia coli, Mycobacterium tuberculosis and Staphylococcus aureus were re-analysed using a common analytic pipeline. Of the approximately 125\u2009million SNPs and 1.25\u2009million indels called across all samples, the same bases were called in 98.8 and 91.9\u200a% of cases, respectively, irrespective of whether raw reads or trimmed reads were used. Nevertheless, the proportion of mixed calls (i.e. calls where <100\u200a% of the reads support the variant allele; considered a proxy of false positives) was significantly reduced after trimming, which suggests that while trimming rarely alters the set of variant bases, it can affect the proportion of reads supporting each call. It was concluded that read quality- and adapter-trimming add relatively little value to a SNP-calling pipeline and may only be necessary if small differences in the absolute number of SNP calls, or the false call rate, are critical. Broadly similar conclusions can be drawn about the utility of trimming to an indel-calling pipeline. Read trimming remains routinely performed prior to variant calling likely out of concern that doing otherwise would typically have negative consequences. While historically this may have been the case, the data in this study suggests that read trimming is not always a practical necessity.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1099/mgen.0.000434; doi:https://doi.org/10.1099/mgen.0.000434; html:https://europepmc.org/articles/PMC8116680; pdf:https://europepmc.org/articles/PMC8116680?pdf=render"
+  },
   {
     "id": "34810237",
     "doi": "https://doi.org/10.1136/thoraxjnl-2021-217629",
@@ -33727,23 +33727,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000215.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000215; html:https://europepmc.org/articles/PMC9770021; pdf:https://europepmc.org/articles/PMC9770021?pdf=render"
   },
-  {
-    "id": "37173061",
-    "doi": "https://doi.org/10.1016/j.ajcnut.2022.12.021",
-    "title": "Evidence for human milk as a biological system and recommendations for study design-a report from \"Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)\" Working Group 4.",
-    "authorString": "Donovan SM, Aghaeepour N, Andres A, Azad MB, Becker M, Carlson SE, J\u00e4rvinen KM, Lin W, L\u00f6nnerdal B, Slupsky CM, Steiber AL, Raiten DJ.",
-    "authorAffiliations": "",
-    "journalTitle": "The American journal of clinical nutrition",
-    "pubYear": "2023",
-    "date": "2023-04-01",
-    "isOpenAccess": "Y",
-    "keywords": "Immune; systems biology; Human Milk; Microbiome; Infant Development",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Human milk contains all of the essential nutrients required by the infant within a complex matrix that enhances the bioavailability of many of those nutrients. In addition, human milk is a source of bioactive components, living cells and microbes that facilitate the transition to life outside the womb. Our ability to fully appreciate the importance of this matrix relies on the recognition of short- and long-term health benefits and, as highlighted in previous sections of this supplement, its ecology (i.e., interactions among the lactating parent and breastfed infant as well as within the context of the human milk matrix itself). Designing and interpreting studies to address this complexity depends on the availability of new tools and technologies that account for such complexity. Past efforts have often compared human milk to infant formula, which has provided some insight into the bioactivity of human milk, as a whole, or of individual milk components supplemented with formula. However, this experimental approach cannot capture the contributions of the individual components to the human milk ecology, the interaction between these components within the human milk matrix, or the significance of the matrix itself to enhance human milk bioactivity on outcomes of interest. This paper presents approaches to explore human milk as a biological system and the functional implications of that system and its components. Specifically, we discuss study design and data collection considerations and how emerging analytical technologies, bioinformatics, and systems biology approaches could be applied to advance our understanding of this critical aspect of human biology.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.ajcnut.2022.12.021; html:https://europepmc.org/articles/PMC10356565; pdf:https://europepmc.org/articles/PMC10356565?pdf=render"
-  },
   {
     "id": "34321180",
     "doi": "https://doi.org/10.1016/j.aucc.2021.05.013",
@@ -33761,6 +33744,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.aucc.2021.05.013"
   },
+  {
+    "id": "37173061",
+    "doi": "https://doi.org/10.1016/j.ajcnut.2022.12.021",
+    "title": "Evidence for human milk as a biological system and recommendations for study design-a report from \"Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)\" Working Group 4.",
+    "authorString": "Donovan SM, Aghaeepour N, Andres A, Azad MB, Becker M, Carlson SE, J\u00e4rvinen KM, Lin W, L\u00f6nnerdal B, Slupsky CM, Steiber AL, Raiten DJ.",
+    "authorAffiliations": "",
+    "journalTitle": "The American journal of clinical nutrition",
+    "pubYear": "2023",
+    "date": "2023-04-01",
+    "isOpenAccess": "Y",
+    "keywords": "Immune; systems biology; Human Milk; Microbiome; Infant Development",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Human milk contains all of the essential nutrients required by the infant within a complex matrix that enhances the bioavailability of many of those nutrients. In addition, human milk is a source of bioactive components, living cells and microbes that facilitate the transition to life outside the womb. Our ability to fully appreciate the importance of this matrix relies on the recognition of short- and long-term health benefits and, as highlighted in previous sections of this supplement, its ecology (i.e., interactions among the lactating parent and breastfed infant as well as within the context of the human milk matrix itself). Designing and interpreting studies to address this complexity depends on the availability of new tools and technologies that account for such complexity. Past efforts have often compared human milk to infant formula, which has provided some insight into the bioactivity of human milk, as a whole, or of individual milk components supplemented with formula. However, this experimental approach cannot capture the contributions of the individual components to the human milk ecology, the interaction between these components within the human milk matrix, or the significance of the matrix itself to enhance human milk bioactivity on outcomes of interest. This paper presents approaches to explore human milk as a biological system and the functional implications of that system and its components. Specifically, we discuss study design and data collection considerations and how emerging analytical technologies, bioinformatics, and systems biology approaches could be applied to advance our understanding of this critical aspect of human biology.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.ajcnut.2022.12.021; html:https://europepmc.org/articles/PMC10356565; pdf:https://europepmc.org/articles/PMC10356565?pdf=render"
+  },
   {
     "id": "36029521",
     "doi": "https://doi.org/10.1093/ije/dyac171",
@@ -33948,6 +33948,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41588-023-01314-0.pdf; doi:https://doi.org/10.1038/s41588-023-01314-0; html:https://europepmc.org/articles/PMC10011137; pdf:https://europepmc.org/articles/PMC10011137?pdf=render"
   },
+  {
+    "id": "32935027",
+    "doi": "https://doi.org/10.23889/ijpds.v4i1.1093",
+    "title": "Health Data Linkage for UK Public Interest Research: Key Obstacles and Solutions.",
+    "authorString": "Mourby MJ, Doidge J, Jones KH, Aidinlis S, Smith H, Bell J, Gilbert R, Dutey-Magni P, Kaye J.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of population data science",
+    "pubYear": "2019",
+    "date": "2019-04-02",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>Analysis of linked health data can generate important, even life-saving, insights into population health. Yet obstacles both legal and organisational in nature can impede this work.<h4>Approach</h4>We focus on three UK infrastructures set up to link and share data for research: the Administrative Data Research Network, NHS Digital, and the Secure Anonymised Information Linkage Databank. Bringing an interdisciplinary perspective, we identify key issues underpinning their challenges and successes in linking health data for research.<h4>Results</h4>We identify examples of uncertainty surrounding legal powers to share and link data, and around data protection obligations, as well as systemic delays and historic public backlash. These issues require updated official guidance on the relevant law, approaches to linkage which are planned for impact and ongoing utility, greater transparency between data providers and researchers, and engagement with the patient population which is both high-profile and carefully considered.<h4>Conclusions</h4>Health data linkage for research presents varied challenges, to which there can be no single solution. Our recommendations would require action from a number of data providers and regulators to be meaningfully advanced. This illustrates the scale and complexity of the challenge of health data linkage, in the UK and beyond: a challenge which our case studies suggest no single organisation can combat alone. Planned programmes of linkage are critical because they allow time for organisations to address these challenges without adversely affecting the feasibility of individual research projects.",
+    "laySummary": "",
+    "urls": "pdf:https://ijpds.org/article/download/1093/1035; doi:https://doi.org/10.23889/ijpds.v4i1.1093; html:https://europepmc.org/articles/PMC7482514; pdf:https://europepmc.org/articles/PMC7482514?pdf=render"
+  },
   {
     "id": "36527096",
     "doi": "https://doi.org/10.1186/s12910-022-00875-9",
@@ -33983,21 +34000,21 @@
     "urls": "pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009162&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009162; html:https://europepmc.org/articles/PMC8297940; pdf:https://europepmc.org/articles/PMC8297940?pdf=render"
   },
   {
-    "id": "32935027",
-    "doi": "https://doi.org/10.23889/ijpds.v4i1.1093",
-    "title": "Health Data Linkage for UK Public Interest Research: Key Obstacles and Solutions.",
-    "authorString": "Mourby MJ, Doidge J, Jones KH, Aidinlis S, Smith H, Bell J, Gilbert R, Dutey-Magni P, Kaye J.",
+    "id": "35189575",
+    "doi": "https://doi.org/10.1016/j.ebiom.2022.103878",
+    "title": "The impact of hypoxia on B cells in COVID-19.",
+    "authorString": "Kotagiri P, Mescia F, Hanson AL, Turner L, Bergamaschi L, Pe\u00f1alver 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, G\u00f6ttgens B, Toshner M, Hess C, Maxwell PH, Clatworthy MR, Nathan JA, Bradley JR, Lyons PA, Burrows N, Smith KGC.",
     "authorAffiliations": "",
-    "journalTitle": "International journal of population data science",
-    "pubYear": "2019",
-    "date": "2019-04-02",
+    "journalTitle": "EBioMedicine",
+    "pubYear": "2022",
+    "date": "2022-02-19",
     "isOpenAccess": "Y",
-    "keywords": "",
+    "keywords": "Hypoxia; B cells; Lymphopenia; Covid-19",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>Analysis of linked health data can generate important, even life-saving, insights into population health. Yet obstacles both legal and organisational in nature can impede this work.<h4>Approach</h4>We focus on three UK infrastructures set up to link and share data for research: the Administrative Data Research Network, NHS Digital, and the Secure Anonymised Information Linkage Databank. Bringing an interdisciplinary perspective, we identify key issues underpinning their challenges and successes in linking health data for research.<h4>Results</h4>We identify examples of uncertainty surrounding legal powers to share and link data, and around data protection obligations, as well as systemic delays and historic public backlash. These issues require updated official guidance on the relevant law, approaches to linkage which are planned for impact and ongoing utility, greater transparency between data providers and researchers, and engagement with the patient population which is both high-profile and carefully considered.<h4>Conclusions</h4>Health data linkage for research presents varied challenges, to which there can be no single solution. Our recommendations would require action from a number of data providers and regulators to be meaningfully advanced. This illustrates the scale and complexity of the challenge of health data linkage, in the UK and beyond: a challenge which our case studies suggest no single organisation can combat alone. Planned programmes of linkage are critical because they allow time for organisations to address these challenges without adversely affecting the feasibility of individual research projects.",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR, Wellcome Trust.",
     "laySummary": "",
-    "urls": "pdf:https://ijpds.org/article/download/1093/1035; doi:https://doi.org/10.23889/ijpds.v4i1.1093; html:https://europepmc.org/articles/PMC7482514; pdf:https://europepmc.org/articles/PMC7482514?pdf=render"
+    "urls": "pdf:http://www.thelancet.com/article/S2352396422000627/pdf; 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": "36522333",
@@ -34016,23 +34033,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-022-35454-4.pdf; doi:https://doi.org/10.1038/s41467-022-35454-4; html:https://europepmc.org/articles/PMC9753891; pdf:https://europepmc.org/articles/PMC9753891?pdf=render"
   },
-  {
-    "id": "35189575",
-    "doi": "https://doi.org/10.1016/j.ebiom.2022.103878",
-    "title": "The impact of hypoxia on B cells in COVID-19.",
-    "authorString": "Kotagiri P, Mescia F, Hanson AL, Turner L, Bergamaschi L, Pe\u00f1alver 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, G\u00f6ttgens B, Toshner M, Hess C, Maxwell PH, Clatworthy MR, Nathan JA, Bradley JR, Lyons PA, Burrows N, Smith KGC.",
-    "authorAffiliations": "",
-    "journalTitle": "EBioMedicine",
-    "pubYear": "2022",
-    "date": "2022-02-19",
-    "isOpenAccess": "Y",
-    "keywords": "Hypoxia; B cells; Lymphopenia; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR, Wellcome Trust.",
-    "laySummary": "",
-    "urls": "pdf:http://www.thelancet.com/article/S2352396422000627/pdf; 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": "32184442",
     "doi": "https://doi.org/10.1038/s42003-020-0857-9",
@@ -34747,23 +34747,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-019-08797-8.pdf; doi:https://doi.org/10.1038/s41467-019-08797-8; html:https://europepmc.org/articles/PMC6379402; pdf:https://europepmc.org/articles/PMC6379402?pdf=render"
   },
-  {
-    "id": "31666709",
-    "doi": "https://doi.org/10.1038/s41433-019-0657-y",
-    "title": "Comment on: 'Quantification of anterior chamber reaction after intravitreal injections of conbercept and ranibizumab: a pilot study'.",
-    "authorString": "Minocha A, Liu X, Denniston AK, Petrushkin H, Solebo AL.",
-    "authorAffiliations": "",
-    "journalTitle": "Eye (London, England)",
-    "pubYear": "2020",
-    "date": "2019-10-30",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41433-019-0657-y.pdf; doi:https://doi.org/10.1038/s41433-019-0657-y; html:https://europepmc.org/articles/PMC7376231; pdf:https://europepmc.org/articles/PMC7376231?pdf=render; doi:https://doi.org/10.1038/s41433-019-0657-y"
-  },
   {
     "id": "31013802",
     "doi": "https://doi.org/10.3390/ijerph16081325",
@@ -34781,6 +34764,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/1660-4601/16/8/1325/pdf?version=1555077276; doi:https://doi.org/10.3390/ijerph16081325; html:https://europepmc.org/articles/PMC6517898; pdf:https://europepmc.org/articles/PMC6517898?pdf=render"
   },
+  {
+    "id": "31666709",
+    "doi": "https://doi.org/10.1038/s41433-019-0657-y",
+    "title": "Comment on: 'Quantification of anterior chamber reaction after intravitreal injections of conbercept and ranibizumab: a pilot study'.",
+    "authorString": "Minocha A, Liu X, Denniston AK, Petrushkin H, Solebo AL.",
+    "authorAffiliations": "",
+    "journalTitle": "Eye (London, England)",
+    "pubYear": "2020",
+    "date": "2019-10-30",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41433-019-0657-y.pdf; doi:https://doi.org/10.1038/s41433-019-0657-y; html:https://europepmc.org/articles/PMC7376231; pdf:https://europepmc.org/articles/PMC7376231?pdf=render; doi:https://doi.org/10.1038/s41433-019-0657-y"
+  },
   {
     "id": "36180121",
     "doi": "https://doi.org/10.1136/bmjopen-2021-057712",
@@ -35155,23 +35155,6 @@
     "laySummary": "",
     "urls": "pdf:https://ebm.bmj.com/content/ebmed/early/2023/02/20/bmjebm-2023-112253.full.pdf; doi:https://doi.org/10.1136/bmjebm-2023-112253; html:https://europepmc.org/articles/PMC10579468; pdf:https://europepmc.org/articles/PMC10579468?pdf=render"
   },
-  {
-    "id": "36498739",
-    "doi": "https://doi.org/10.3390/jcm11237163",
-    "title": "Biopsychosocial Response to the COVID-19 Lockdown in People with Major Depressive Disorder and Multiple Sclerosis.",
-    "authorString": "Siddi S, Gin\u00e9-V\u00e1zquez 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, S\u00f8rensen PS, Montalban X, Lavelle G, Ivan A, Oetzmann C, White KM, Difrancesco S, Locatelli P, Mohr DC, Aguil\u00f3 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.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of clinical medicine",
-    "pubYear": "2022",
-    "date": "2022-12-01",
-    "isOpenAccess": "Y",
-    "keywords": "Stress; Heart rate; Multiple sclerosis; Physical Activity; Social Activity; Major Depressive Disorder; Depression Severity; Decentralized; Covid-19; Sars-cov-2",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://www.mdpi.com/2077-0383/11/23/7163/pdf?version=1670311452; doi:https://doi.org/10.3390/jcm11237163; html:https://europepmc.org/articles/PMC9738639; pdf:https://europepmc.org/articles/PMC9738639?pdf=render"
-  },
   {
     "id": "30819382",
     "doi": "https://doi.org/10.1016/j.jchf.2019.01.009",
@@ -35189,6 +35172,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jchf.2019.01.009; doi:https://doi.org/10.1016/j.jchf.2019.01.009"
   },
+  {
+    "id": "36498739",
+    "doi": "https://doi.org/10.3390/jcm11237163",
+    "title": "Biopsychosocial Response to the COVID-19 Lockdown in People with Major Depressive Disorder and Multiple Sclerosis.",
+    "authorString": "Siddi S, Gin\u00e9-V\u00e1zquez 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, S\u00f8rensen PS, Montalban X, Lavelle G, Ivan A, Oetzmann C, White KM, Difrancesco S, Locatelli P, Mohr DC, Aguil\u00f3 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.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of clinical medicine",
+    "pubYear": "2022",
+    "date": "2022-12-01",
+    "isOpenAccess": "Y",
+    "keywords": "Stress; Heart rate; Multiple sclerosis; Physical Activity; Social Activity; Major Depressive Disorder; Depression Severity; Decentralized; Covid-19; Sars-cov-2",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://www.mdpi.com/2077-0383/11/23/7163/pdf?version=1670311452; doi:https://doi.org/10.3390/jcm11237163; html:https://europepmc.org/articles/PMC9738639; pdf:https://europepmc.org/articles/PMC9738639?pdf=render"
+  },
   {
     "id": "34320164",
     "doi": "https://doi.org/10.1093/cvr/cvab239",
@@ -35274,23 +35274,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.13517; doi:https://doi.org/10.1002/ehf2.13517; html:https://europepmc.org/articles/PMC8712846; pdf:https://europepmc.org/articles/PMC8712846?pdf=render"
   },
-  {
-    "id": "37343968",
-    "doi": "https://doi.org/10.1136/bmj-2022-072976",
-    "title": "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.",
-    "authorString": "Hippisley-Cox J, Khunti K, Sheikh A, Nguyen-Van-Tam JS, Coupland CAC.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ (Clinical research ed.)",
-    "pubYear": "2023",
-    "date": "2023-06-21",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>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.<h4>Design</h4>Cohort study.<h4>Setting</h4>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.<h4>Participants</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>Of 1\u2009297\u2009922 people with a positive test result for SARS-CoV-2 infection in the derivation cohort, 18\u2009756 (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.<h4>Conclusion</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://www.bmj.com/content/bmj/381/bmj-2022-072976.full.pdf; doi:https://doi.org/10.1136/bmj-2022-072976; html:https://europepmc.org/articles/PMC10282241; pdf:https://europepmc.org/articles/PMC10282241?pdf=render"
-  },
   {
     "id": "35977952",
     "doi": "https://doi.org/10.1038/s41467-022-29931-z",
@@ -35309,21 +35292,38 @@
     "urls": "pdf:https://www.nature.com/articles/s41467-022-29931-z.pdf; doi:https://doi.org/10.1038/s41467-022-29931-z; html:https://europepmc.org/articles/PMC9385867; pdf:https://europepmc.org/articles/PMC9385867?pdf=render"
   },
   {
-    "id": "37757828",
-    "doi": "https://doi.org/10.1016/j.cell.2023.08.028",
-    "title": "Influence of autozygosity on common disease risk across the phenotypic spectrum.",
-    "authorString": "Malawsky DS, van Walree E, Jacobs BM, Heng TH, Huang QQ, Sabir AH, Rahman S, Sharif SM, Khan A, Mirkov MU, 23andMe Research Team, Genes & Health Research Team, Kuwahara H, Gao X, Alkuraya FS, Posthuma D, Newman WG, Griffiths CJ, Mathur R, van Heel DA, Finer S, O'Connell J, Martin HC.",
+    "id": "37343968",
+    "doi": "https://doi.org/10.1136/bmj-2022-072976",
+    "title": "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.",
+    "authorString": "Hippisley-Cox J, Khunti K, Sheikh A, Nguyen-Van-Tam JS, Coupland CAC.",
     "authorAffiliations": "",
-    "journalTitle": "Cell",
+    "journalTitle": "BMJ (Clinical research ed.)",
     "pubYear": "2023",
-    "date": "2023-09-26",
+    "date": "2023-06-21",
     "isOpenAccess": "Y",
-    "keywords": "Consanguinity; Medical genetics; Recessive; Autozygosity; Common Diseases; Diverse Cohorts",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F<sub>ROH</sub>) and common diseases in Genes\u00a0& Health (n\u00a0= 23,978 British South Asians), UK Biobank (n\u00a0= 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of F<sub>ROH</sub>. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between F<sub>ROH</sub> and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n\u00a0= 480,282). We estimated that autozygosity due to consanguinity accounts for 5%-18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity.",
+    "abstract": "<h4>Objectives</h4>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.<h4>Design</h4>Cohort study.<h4>Setting</h4>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.<h4>Participants</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>Of 1\u2009297\u2009922 people with a positive test result for SARS-CoV-2 infection in the derivation cohort, 18\u2009756 (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.<h4>Conclusion</h4>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.",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.cell.2023.08.028; html:https://europepmc.org/articles/PMC10580289; pdf:https://europepmc.org/articles/PMC10580289?pdf=render"
+    "urls": "pdf:https://www.bmj.com/content/bmj/381/bmj-2022-072976.full.pdf; doi:https://doi.org/10.1136/bmj-2022-072976; html:https://europepmc.org/articles/PMC10282241; pdf:https://europepmc.org/articles/PMC10282241?pdf=render"
+  },
+  {
+    "id": "31331193",
+    "doi": "https://doi.org/10.1161/circulationaha.119.041546",
+    "title": "Impact of <i>ADCY9</i> Genotype on Response to Anacetrapib.",
+    "authorString": "Hopewell JC, Ibrahim M, Hill M, Shaw PM, Braunwald E, Blaustein RO, Bowman L, Landray MJ, Sabatine MS, Collins R, HPS3/TIMI55\u2013REVEAL Collaborative Group.",
+    "authorAffiliations": "",
+    "journalTitle": "Circulation",
+    "pubYear": "2019",
+    "date": "2019-07-23",
+    "isOpenAccess": "Y",
+    "keywords": "Randomized controlled trial; Pharmacogenetics; Anacetrapib; Cholesterol Ester Transfer Protein; Adenylate Cyclase 9",
+    "nationalPriorities": "Better, Faster and More Efficient Clinical Trials",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Exploratory analyses of previous randomized trials generated a hypothesis that the clinical response to cholesteryl ester transfer protein (CETP) inhibitor therapy differs by <i>ADCY9</i> 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 <i>ADCY9</i> genotype on response to anacetrapib in the REVEAL trial.<h4>Methods</h4>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 <i>ADCY9</i> rs1967309 genotype.<h4>Results</h4>Among 19\u2009210 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 <i>ADCY9</i> 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 <i>P</i> for interaction = 0.96. Furthermore, there were no associations between <i>ADCY9</i> genotype and the proportional reductions in the separate components of major vascular events or meaningful differences in lipid response to anacetrapib.<h4>Conclusions</h4>The REVEAL trial is the single largest study to date evaluating the <i>ADCY9</i> pharmacogenetic interaction. It provides no support for the hypothesis that <i>ADCY9</i> 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.<h4>Clinical trial registration</h4>URL: https://www.<h4>Clinicaltrials</h4>gov. Unique identifier: NCT01252953. URL: http://www.isrctn.com. Unique identifier: ISRCTN48678192. URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1161/circulationaha.119.041546; doi:https://doi.org/10.1161/CIRCULATIONAHA.119.041546; html:https://europepmc.org/articles/PMC6749971; pdf:https://europepmc.org/articles/PMC6749971?pdf=render"
   },
   {
     "id": "32880390",
@@ -35343,21 +35343,21 @@
     "urls": "pdf:https://academic.oup.com/jcem/article-pdf/105/12/e4230/41829325/dgaa627.pdf; doi:https://doi.org/10.1210/clinem/dgaa627; html:https://europepmc.org/articles/PMC7499588; pdf:https://europepmc.org/articles/PMC7499588?pdf=render"
   },
   {
-    "id": "31331193",
-    "doi": "https://doi.org/10.1161/circulationaha.119.041546",
-    "title": "Impact of <i>ADCY9</i> Genotype on Response to Anacetrapib.",
-    "authorString": "Hopewell JC, Ibrahim M, Hill M, Shaw PM, Braunwald E, Blaustein RO, Bowman L, Landray MJ, Sabatine MS, Collins R, HPS3/TIMI55\u2013REVEAL Collaborative Group.",
+    "id": "37757828",
+    "doi": "https://doi.org/10.1016/j.cell.2023.08.028",
+    "title": "Influence of autozygosity on common disease risk across the phenotypic spectrum.",
+    "authorString": "Malawsky DS, van Walree E, Jacobs BM, Heng TH, Huang QQ, Sabir AH, Rahman S, Sharif SM, Khan A, Mirkov MU, 23andMe Research Team, Genes & Health Research Team, Kuwahara H, Gao X, Alkuraya FS, Posthuma D, Newman WG, Griffiths CJ, Mathur R, van Heel DA, Finer S, O'Connell J, Martin HC.",
     "authorAffiliations": "",
-    "journalTitle": "Circulation",
-    "pubYear": "2019",
-    "date": "2019-07-23",
+    "journalTitle": "Cell",
+    "pubYear": "2023",
+    "date": "2023-09-26",
     "isOpenAccess": "Y",
-    "keywords": "Randomized controlled trial; Pharmacogenetics; Anacetrapib; Cholesterol Ester Transfer Protein; Adenylate Cyclase 9",
-    "nationalPriorities": "Better, Faster and More Efficient Clinical Trials",
+    "keywords": "Consanguinity; Medical genetics; Recessive; Autozygosity; Common Diseases; Diverse Cohorts",
+    "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>Exploratory analyses of previous randomized trials generated a hypothesis that the clinical response to cholesteryl ester transfer protein (CETP) inhibitor therapy differs by <i>ADCY9</i> 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 <i>ADCY9</i> genotype on response to anacetrapib in the REVEAL trial.<h4>Methods</h4>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 <i>ADCY9</i> rs1967309 genotype.<h4>Results</h4>Among 19\u2009210 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 <i>ADCY9</i> 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 <i>P</i> for interaction = 0.96. Furthermore, there were no associations between <i>ADCY9</i> genotype and the proportional reductions in the separate components of major vascular events or meaningful differences in lipid response to anacetrapib.<h4>Conclusions</h4>The REVEAL trial is the single largest study to date evaluating the <i>ADCY9</i> pharmacogenetic interaction. It provides no support for the hypothesis that <i>ADCY9</i> 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.<h4>Clinical trial registration</h4>URL: https://www.<h4>Clinicaltrials</h4>gov. Unique identifier: NCT01252953. URL: http://www.isrctn.com. Unique identifier: ISRCTN48678192. URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",
+    "abstract": "Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F<sub>ROH</sub>) and common diseases in Genes\u00a0& Health (n\u00a0= 23,978 British South Asians), UK Biobank (n\u00a0= 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of F<sub>ROH</sub>. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between F<sub>ROH</sub> and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n\u00a0= 480,282). We estimated that autozygosity due to consanguinity accounts for 5%-18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity.",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1161/circulationaha.119.041546; doi:https://doi.org/10.1161/CIRCULATIONAHA.119.041546; html:https://europepmc.org/articles/PMC6749971; pdf:https://europepmc.org/articles/PMC6749971?pdf=render"
+    "urls": "doi:https://doi.org/10.1016/j.cell.2023.08.028; html:https://europepmc.org/articles/PMC10580289; pdf:https://europepmc.org/articles/PMC10580289?pdf=render"
   },
   {
     "id": "33174830",
@@ -35886,23 +35886,6 @@
     "laySummary": "",
     "urls": "pdf:https://care.diabetesjournals.org/content/diacare/42/9/1700.full.pdf; doi:https://doi.org/10.2337/dc18-2423; html:https://europepmc.org/articles/PMC6706279; pdf:https://europepmc.org/articles/PMC6706279?pdf=render; doi:https://doi.org/10.2337/dc18-2423"
   },
-  {
-    "id": "34563995",
-    "doi": "https://doi.org/10.1016/j.schres.2021.09.006",
-    "title": "The impact of cigarette smoking on life expectancy in schizophrenia, schizoaffective disorder and bipolar affective disorder: An electronic case register cohort study.",
-    "authorString": "Chesney E, Robson D, Patel R, Shetty H, Richardson S, Chang CK, McGuire P, McNeill A.",
-    "authorAffiliations": "",
-    "journalTitle": "Schizophrenia research",
-    "pubYear": "2021",
-    "date": "2021-09-23",
-    "isOpenAccess": "Y",
-    "keywords": "Mortality; Schizophrenia; Tobacco; Smoking; Life expectancy; Bipolar Affective Disorder",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Severe mental disorders are associated with a life expectancy that is 10-20\u00a0years shorter than the general population's. The prevalence of cigarette smoking in these populations is very high. We examined the effect of smoking on life expectancy and survival in patients with a diagnosis of schizophrenia, schizoaffective disorder or bipolar affective disorder from 2007 to 2018 in South East London, UK. Smoking status was determined using unstructured text data extracted from electronic health records. A total of 21,588 patients were identified of which 16,717, (77.4%) were classified as current smokers and 3438 (15.9%) as non-smokers. In female participants, life expectancy at birth was 67.6\u00a0years in current smokers (95% CI: 66.4-68.8) and 74.9\u00a0years in non-smokers (95% CI: 72.8-77.0), a difference of 7.3\u00a0years. In male participants, life expectancy at birth was 63.5\u00a0years in current smokers (95% CI: 62.5-64.5) and 68.5\u00a0years in non-smokers (95% CI, 64.4-72.6), a difference of 5.0\u00a0years. Adjusted survival models found that current smoking status was associated with an increased mortality risk for both females (aHR: 1.42, 95% CI: 1.21-1.66, p\u00a0<\u00a00.001) and males (aHR: 1.49; 95% CI: 1.25-1.79, p\u00a0<\u00a00.001). In terms of the effect sizes, these risks were similar to those associated with a diagnosis of co-morbid alcohol or opioid use disorder. Smoking may account for a substantial proportion of the reduced life expectancy in patients with psychotic disorders. Increased emphasis on reducing cigarette smoking in these populations may be the most effective way to reduce the mortality gap with the general population.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.schres.2021.09.006; doi:https://doi.org/10.1016/j.schres.2021.09.006; html:https://europepmc.org/articles/PMC8653908"
-  },
   {
     "id": "31995663",
     "doi": "https://doi.org/10.1111/cts.12725",
@@ -35920,6 +35903,23 @@
     "laySummary": "",
     "urls": "pdf:https://ascpt.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cts.12725; doi:https://doi.org/10.1111/cts.12725; html:https://europepmc.org/articles/PMC7070790; pdf:https://europepmc.org/articles/PMC7070790?pdf=render"
   },
+  {
+    "id": "34563995",
+    "doi": "https://doi.org/10.1016/j.schres.2021.09.006",
+    "title": "The impact of cigarette smoking on life expectancy in schizophrenia, schizoaffective disorder and bipolar affective disorder: An electronic case register cohort study.",
+    "authorString": "Chesney E, Robson D, Patel R, Shetty H, Richardson S, Chang CK, McGuire P, McNeill A.",
+    "authorAffiliations": "",
+    "journalTitle": "Schizophrenia research",
+    "pubYear": "2021",
+    "date": "2021-09-23",
+    "isOpenAccess": "Y",
+    "keywords": "Mortality; Schizophrenia; Tobacco; Smoking; Life expectancy; Bipolar Affective Disorder",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Severe mental disorders are associated with a life expectancy that is 10-20\u00a0years shorter than the general population's. The prevalence of cigarette smoking in these populations is very high. We examined the effect of smoking on life expectancy and survival in patients with a diagnosis of schizophrenia, schizoaffective disorder or bipolar affective disorder from 2007 to 2018 in South East London, UK. Smoking status was determined using unstructured text data extracted from electronic health records. A total of 21,588 patients were identified of which 16,717, (77.4%) were classified as current smokers and 3438 (15.9%) as non-smokers. In female participants, life expectancy at birth was 67.6\u00a0years in current smokers (95% CI: 66.4-68.8) and 74.9\u00a0years in non-smokers (95% CI: 72.8-77.0), a difference of 7.3\u00a0years. In male participants, life expectancy at birth was 63.5\u00a0years in current smokers (95% CI: 62.5-64.5) and 68.5\u00a0years in non-smokers (95% CI, 64.4-72.6), a difference of 5.0\u00a0years. Adjusted survival models found that current smoking status was associated with an increased mortality risk for both females (aHR: 1.42, 95% CI: 1.21-1.66, p\u00a0<\u00a00.001) and males (aHR: 1.49; 95% CI: 1.25-1.79, p\u00a0<\u00a00.001). In terms of the effect sizes, these risks were similar to those associated with a diagnosis of co-morbid alcohol or opioid use disorder. Smoking may account for a substantial proportion of the reduced life expectancy in patients with psychotic disorders. Increased emphasis on reducing cigarette smoking in these populations may be the most effective way to reduce the mortality gap with the general population.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.schres.2021.09.006; doi:https://doi.org/10.1016/j.schres.2021.09.006; html:https://europepmc.org/articles/PMC8653908"
+  },
   {
     "id": "31647808",
     "doi": "https://doi.org/10.1371/journal.pgen.1008405",
@@ -36108,21 +36108,21 @@
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00395-020-00828-6.pdf; doi:https://doi.org/10.1007/s00395-020-00828-6; html:https://europepmc.org/articles/PMC7666586; pdf:https://europepmc.org/articles/PMC7666586?pdf=render"
   },
   {
-    "id": "37794492",
-    "doi": "https://doi.org/10.1186/s13073-023-01233-z",
-    "title": "Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.",
-    "authorString": "Neumann A, Ohlei O, K\u00fc\u00e7\u00fckali F, Bos IJ, Timsina J, Vos S, Prokopenko D, Tijms BM, Andreasson U, Blennow K, Vandenberghe R, Scheltens P, Teunissen CE, Engelborghs S, Frisoni GB, Blin O, Richardson JC, Bordet R, Lle\u00f3 A, Alcolea D, Popp J, Marsh TW, Gorijala P, Clark C, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Van Broeckhoven C, Tanzi RE, Ten Kate M, Lill CM, Barkhof F, Cruchaga C, Lovestone S, Streffer J, Zetterberg H, Visser PJ, Sleegers K, Bertram L, EMIF-AD & ADNI study group.",
+    "id": "32283057",
+    "doi": "https://doi.org/10.1016/j.jid.2020.03.957",
+    "title": "Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study.",
+    "authorString": "Loeff FC, Tsakok T, Dijk L, Hart MH, Duckworth M, Baudry D, Russell A, Dand N, van Leeuwen A, Griffiths CEM, Reynolds NJ, Barker J, Burden AD, Warren RB, de Vries A, Bloem K, Wolbink GJ, Smith CH, Rispens T, BADBIR, BSTOP Study Groups, PSORT consortium.",
     "authorAffiliations": "",
-    "journalTitle": "Genome medicine",
-    "pubYear": "2023",
-    "date": "2023-10-04",
-    "isOpenAccess": "Y",
-    "keywords": "Principal component analysis; Biomarkers; Alzheimer\u2019s disease; Dementia; Cerebrospinal fluid (CSF); multivariate analysis; Structural Equation Modeling; Mediation; Genome-wide Association Study (Gwas)",
+    "journalTitle": "The Journal of investigative dermatology",
+    "pubYear": "2020",
+    "date": "2020-04-10",
+    "isOpenAccess": "N",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (\u03b2-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.<h4>Methods</h4>We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n\u2009=\u2009205 controls, n\u2009=\u2009546 mild cognitive impairment, n\u2009=\u2009222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects.<h4>Results</h4>Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses\u00a0of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers.<h4>Conclusions</h4>These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.",
+    "abstract": "Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI]\u00a0= 3.2-4.2) and in 10.6% (95% CI\u00a0= 7.9-13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (-0.62 \u03bcg/ml [95% CI\u00a0=\u00a0-1.190 to\u00a0-0.30] and\u00a0-0.74 \u03bcg/ml [95% CI\u00a0=\u00a0-1.09 to\u00a0-0.47], respectively) and higher absolute PASI (6.6 [95% CI\u00a0= 3.0-9.9] and 1.9 [95% CI\u00a0= 0.4-4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI\u00a0= 3.9-8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.",
     "laySummary": "",
-    "urls": "pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-023-01233-z; doi:https://doi.org/10.1186/s13073-023-01233-z; html:https://europepmc.org/articles/PMC10548686; pdf:https://europepmc.org/articles/PMC10548686?pdf=render"
+    "urls": "pdf:http://www.jidonline.org/article/S0022202X20313701/pdf; doi:https://doi.org/10.1016/j.jid.2020.03.957"
   },
   {
     "id": "34812717",
@@ -36142,21 +36142,21 @@
     "urls": "doi:https://doi.org/10.1099/mgen.0.000700; doi:https://doi.org/10.1099/mgen.0.000700; html:https://europepmc.org/articles/PMC8743558; pdf:https://europepmc.org/articles/PMC8743558?pdf=render"
   },
   {
-    "id": "32283057",
-    "doi": "https://doi.org/10.1016/j.jid.2020.03.957",
-    "title": "Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study.",
-    "authorString": "Loeff FC, Tsakok T, Dijk L, Hart MH, Duckworth M, Baudry D, Russell A, Dand N, van Leeuwen A, Griffiths CEM, Reynolds NJ, Barker J, Burden AD, Warren RB, de Vries A, Bloem K, Wolbink GJ, Smith CH, Rispens T, BADBIR, BSTOP Study Groups, PSORT consortium.",
+    "id": "34561430",
+    "doi": "https://doi.org/10.1038/s41467-021-25703-3",
+    "title": "Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease.",
+    "authorString": "Schmidt AF, Hunt NB, Gordillo-Mara\u00f1\u00f3n 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.",
     "authorAffiliations": "",
-    "journalTitle": "The Journal of investigative dermatology",
-    "pubYear": "2020",
-    "date": "2020-04-10",
-    "isOpenAccess": "N",
+    "journalTitle": "Nature communications",
+    "pubYear": "2021",
+    "date": "2021-09-24",
+    "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI]\u00a0= 3.2-4.2) and in 10.6% (95% CI\u00a0= 7.9-13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (-0.62 \u03bcg/ml [95% CI\u00a0=\u00a0-1.190 to\u00a0-0.30] and\u00a0-0.74 \u03bcg/ml [95% CI\u00a0=\u00a0-1.09 to\u00a0-0.47], respectively) and higher absolute PASI (6.6 [95% CI\u00a0= 3.0-9.9] and 1.9 [95% CI\u00a0= 0.4-4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI\u00a0= 3.9-8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.",
+    "abstract": "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\u00a0observed 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.",
     "laySummary": "",
-    "urls": "pdf:http://www.jidonline.org/article/S0022202X20313701/pdf; doi:https://doi.org/10.1016/j.jid.2020.03.957"
+    "urls": "pdf:https://www.nature.com/articles/s41467-021-25703-3.pdf; doi:https://doi.org/10.1038/s41467-021-25703-3; html:https://europepmc.org/articles/PMC8463530; pdf:https://europepmc.org/articles/PMC8463530?pdf=render"
   },
   {
     "id": "37043172",
@@ -36176,21 +36176,21 @@
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s12325-023-02511-3.pdf; doi:https://doi.org/10.1007/s12325-023-02511-3; html:https://europepmc.org/articles/PMC10092909; pdf:https://europepmc.org/articles/PMC10092909?pdf=render"
   },
   {
-    "id": "34561430",
-    "doi": "https://doi.org/10.1038/s41467-021-25703-3",
-    "title": "Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease.",
-    "authorString": "Schmidt AF, Hunt NB, Gordillo-Mara\u00f1\u00f3n 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.",
+    "id": "37794492",
+    "doi": "https://doi.org/10.1186/s13073-023-01233-z",
+    "title": "Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.",
+    "authorString": "Neumann A, Ohlei O, K\u00fc\u00e7\u00fckali F, Bos IJ, Timsina J, Vos S, Prokopenko D, Tijms BM, Andreasson U, Blennow K, Vandenberghe R, Scheltens P, Teunissen CE, Engelborghs S, Frisoni GB, Blin O, Richardson JC, Bordet R, Lle\u00f3 A, Alcolea D, Popp J, Marsh TW, Gorijala P, Clark C, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Van Broeckhoven C, Tanzi RE, Ten Kate M, Lill CM, Barkhof F, Cruchaga C, Lovestone S, Streffer J, Zetterberg H, Visser PJ, Sleegers K, Bertram L, EMIF-AD & ADNI study group.",
     "authorAffiliations": "",
-    "journalTitle": "Nature communications",
-    "pubYear": "2021",
-    "date": "2021-09-24",
+    "journalTitle": "Genome medicine",
+    "pubYear": "2023",
+    "date": "2023-10-04",
     "isOpenAccess": "Y",
-    "keywords": "",
+    "keywords": "Principal component analysis; Biomarkers; Alzheimer\u2019s disease; Dementia; Cerebrospinal fluid (CSF); multivariate analysis; Structural Equation Modeling; Mediation; Genome-wide Association Study (Gwas)",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "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\u00a0observed 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.",
+    "abstract": "<h4>Background</h4>Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (\u03b2-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.<h4>Methods</h4>We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n\u2009=\u2009205 controls, n\u2009=\u2009546 mild cognitive impairment, n\u2009=\u2009222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects.<h4>Results</h4>Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses\u00a0of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers.<h4>Conclusions</h4>These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.",
     "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41467-021-25703-3.pdf; doi:https://doi.org/10.1038/s41467-021-25703-3; html:https://europepmc.org/articles/PMC8463530; pdf:https://europepmc.org/articles/PMC8463530?pdf=render"
+    "urls": "pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-023-01233-z; doi:https://doi.org/10.1186/s13073-023-01233-z; html:https://europepmc.org/articles/PMC10548686; pdf:https://europepmc.org/articles/PMC10548686?pdf=render"
   },
   {
     "id": "31408153",
@@ -37059,23 +37059,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/s1473-3099(19)30410-4; doi:https://doi.org/10.1016/S1473-3099(19)30410-4; html:https://europepmc.org/articles/PMC7185492"
   },
-  {
-    "id": "34316022",
-    "doi": "https://doi.org/10.1038/s41416-021-01505-8",
-    "title": "Assessing the role of cortisol in cancer: a wide-ranged Mendelian randomisation study.",
-    "authorString": "Larsson SC, Lee WH, Kar S, Burgess S, Allara E.",
-    "authorAffiliations": "",
-    "journalTitle": "British journal of cancer",
-    "pubYear": "2021",
-    "date": "2021-07-27",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Cortisol's immunosuppressive, obesogenic, and hyperglycaemic effects suggest that it may play a role in cancer development. However, whether cortisol increases cancer risk is not known. We investigated the potential causal association between plasma cortisol and risk of overall and common site-specific cancers using Mendelian randomisation.<h4>Methods</h4>Three genetic variants associated with morning plasma cortisol levels at the genome-wide significance level (P\u2009<\u20095\u2009\u00d7\u200910<sup>-8</sup>) in the Cortisol Network consortium were used as genetic instruments. Summary-level genome-wide association study data for the cancer outcomes were obtained from large-scale cancer consortia, the UK Biobank, and the FinnGen consortium. Two-sample Mendelian randomisation analyses were performed using the fixed-effects inverse-variance weighted method. Estimates across data sources were combined using meta-analysis.<h4>Results</h4>A standard deviation increase in genetically predicted plasma cortisol was associated with increased risk of endometrial cancer (odds ratio 1.50, 95% confidence interval 1.13-1.99; P\u2009=\u20090.005). There was no significant association between genetically predicted plasma cortisol and risk of other common site-specific cancers, including breast, ovarian, prostate, colorectal, lung, or malignant skin cancer, or overall cancer.<h4>Conclusions</h4>These results indicate that elevated plasma cortisol levels may increase the risk of endometrial cancer but not other cancers. The mechanism by which this occurs remains to be investigated.",
-    "laySummary": "",
-    "urls": "pdf:http://uu.diva-portal.org/smash/get/diva2:1617122/FULLTEXT01; doi:https://doi.org/10.1038/s41416-021-01505-8; html:https://europepmc.org/articles/PMC8476513; pdf:https://europepmc.org/articles/PMC8476513?pdf=render; doi:https://doi.org/10.1038/s41416-021-01505-8"
-  },
   {
     "id": "31115347",
     "doi": "https://doi.org/10.2196/12412",
@@ -37094,21 +37077,21 @@
     "urls": "pdf:https://www.jmir.org/2019/5/e12412/PDF; doi:https://doi.org/10.2196/12412; html:https://europepmc.org/articles/PMC6547770"
   },
   {
-    "id": "37681566",
-    "doi": "https://doi.org/10.1161/jaha.123.030280",
-    "title": "Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204\u2009244 Postmenopausal Women.",
-    "authorString": "Tschiderer L, Peters SAE, van der Schouw YT, van Westing AC, Tong TYN, Willeit P, Seekircher L, Moreno-Iribas C, Huerta JM, Crous-Bou M, S\u00f6derholm M, Schulze MB, Johansson C, Sj\u00e4lander S, Heath AK, Macciotta A, Dahm CC, Ibsen DB, Pala V, Mellemkj\u00e6r L, Burgess S, Wood A, Kaaks R, Katzke V, Amiano P, Rodriguez-Barranco M, Engstr\u00f6m G, Weiderpass E, Tj\u00f8nneland A, Halkj\u00e6r J, Panico S, Danesh J, Butterworth A, Onland-Moret NC.",
+    "id": "34316022",
+    "doi": "https://doi.org/10.1038/s41416-021-01505-8",
+    "title": "Assessing the role of cortisol in cancer: a wide-ranged Mendelian randomisation study.",
+    "authorString": "Larsson SC, Lee WH, Kar S, Burgess S, Allara E.",
     "authorAffiliations": "",
-    "journalTitle": "Journal of the American Heart Association",
-    "pubYear": "2023",
-    "date": "2023-09-08",
-    "isOpenAccess": "Y",
-    "keywords": "Stroke; Age At Menopause; Mendelian Randomization Analysis; Observational Analysis",
+    "journalTitle": "British journal of cancer",
+    "pubYear": "2021",
+    "date": "2021-07-27",
+    "isOpenAccess": "N",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204\u2009244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196\u2009361 from the UK Biobank). Pooled mean baseline age was 58.9\u2009years (SD, 5.8), and pooled mean age at menopause was 47.8\u2009years (SD, 6.2). Over a median follow-up of 12.6\u2009years (interquartile range, 11.8-13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5\u2009years younger age at menopause were 1.09 (95% CI, 1.07-1.12) for stroke, 1.09 (95% CI, 1.06-1.13) for ischemic stroke, 1.10 (95% CI, 1.04-1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08-1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84-1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. Conclusions In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.",
+    "abstract": "<h4>Background</h4>Cortisol's immunosuppressive, obesogenic, and hyperglycaemic effects suggest that it may play a role in cancer development. However, whether cortisol increases cancer risk is not known. We investigated the potential causal association between plasma cortisol and risk of overall and common site-specific cancers using Mendelian randomisation.<h4>Methods</h4>Three genetic variants associated with morning plasma cortisol levels at the genome-wide significance level (P\u2009<\u20095\u2009\u00d7\u200910<sup>-8</sup>) in the Cortisol Network consortium were used as genetic instruments. Summary-level genome-wide association study data for the cancer outcomes were obtained from large-scale cancer consortia, the UK Biobank, and the FinnGen consortium. Two-sample Mendelian randomisation analyses were performed using the fixed-effects inverse-variance weighted method. Estimates across data sources were combined using meta-analysis.<h4>Results</h4>A standard deviation increase in genetically predicted plasma cortisol was associated with increased risk of endometrial cancer (odds ratio 1.50, 95% confidence interval 1.13-1.99; P\u2009=\u20090.005). There was no significant association between genetically predicted plasma cortisol and risk of other common site-specific cancers, including breast, ovarian, prostate, colorectal, lung, or malignant skin cancer, or overall cancer.<h4>Conclusions</h4>These results indicate that elevated plasma cortisol levels may increase the risk of endometrial cancer but not other cancers. The mechanism by which this occurs remains to be investigated.",
     "laySummary": "",
-    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030280; doi:https://doi.org/10.1161/JAHA.123.030280; html:https://europepmc.org/articles/PMC10547274; pdf:https://europepmc.org/articles/PMC10547274?pdf=render"
+    "urls": "pdf:http://uu.diva-portal.org/smash/get/diva2:1617122/FULLTEXT01; doi:https://doi.org/10.1038/s41416-021-01505-8; html:https://europepmc.org/articles/PMC8476513; pdf:https://europepmc.org/articles/PMC8476513?pdf=render; doi:https://doi.org/10.1038/s41416-021-01505-8"
   },
   {
     "id": "35360896",
@@ -37128,21 +37111,21 @@
     "urls": "pdf:https://pubs.acs.org/doi/pdf/10.1021/acs.analchem.1c03592; doi:https://doi.org/10.1021/acs.analchem.1c03592; html:https://europepmc.org/articles/PMC9008693; pdf:https://europepmc.org/articles/PMC9008693?pdf=render"
   },
   {
-    "id": "36792666",
-    "doi": "https://doi.org/10.1038/s41467-023-36486-0",
-    "title": "SVEP1 is an endogenous ligand for the orphan receptor PEAR1.",
-    "authorString": "Elenbaas JS, Pudupakkam U, Ashworth KJ, Kang CJ, Patel V, Santana K, Jung IH, Lee PC, Burks KH, Amrute JM, Mecham RP, Halabi CM, Alisio A, Di Paola J, Stitziel NO.",
+    "id": "37681566",
+    "doi": "https://doi.org/10.1161/jaha.123.030280",
+    "title": "Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204\u2009244 Postmenopausal Women.",
+    "authorString": "Tschiderer L, Peters SAE, van der Schouw YT, van Westing AC, Tong TYN, Willeit P, Seekircher L, Moreno-Iribas C, Huerta JM, Crous-Bou M, S\u00f6derholm M, Schulze MB, Johansson C, Sj\u00e4lander S, Heath AK, Macciotta A, Dahm CC, Ibsen DB, Pala V, Mellemkj\u00e6r L, Burgess S, Wood A, Kaaks R, Katzke V, Amiano P, Rodriguez-Barranco M, Engstr\u00f6m G, Weiderpass E, Tj\u00f8nneland A, Halkj\u00e6r J, Panico S, Danesh J, Butterworth A, Onland-Moret NC.",
     "authorAffiliations": "",
-    "journalTitle": "Nature communications",
+    "journalTitle": "Journal of the American Heart Association",
     "pubYear": "2023",
-    "date": "2023-02-15",
+    "date": "2023-09-08",
     "isOpenAccess": "Y",
-    "keywords": "",
+    "keywords": "Stroke; Age At Menopause; Mendelian Randomization Analysis; Observational Analysis",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes vascular disease and associates with platelet reactivity in humans. Here, using a human genomic and proteomic approach, we identify a high affinity, disease-relevant, and potentially targetable interaction between SVEP1 and the orphan receptor Platelet and Endothelial Aggregation Receptor 1 (PEAR1). This interaction promotes PEAR1 phosphorylation and disease associated AKT/mTOR signaling in vascular cells and platelets. Mice lacking SVEP1 have reduced platelet activation, and exogenous SVEP1 induces PEAR1-dependent activation of platelets. SVEP1 and PEAR1 causally and concordantly relate to platelet phenotypes and cardiovascular disease in humans, as determined by Mendelian Randomization. Targeting this receptor-ligand interaction may be a viable therapeutic strategy to treat or prevent cardiovascular and thrombotic disease.",
+    "abstract": "Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204\u2009244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196\u2009361 from the UK Biobank). Pooled mean baseline age was 58.9\u2009years (SD, 5.8), and pooled mean age at menopause was 47.8\u2009years (SD, 6.2). Over a median follow-up of 12.6\u2009years (interquartile range, 11.8-13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5\u2009years younger age at menopause were 1.09 (95% CI, 1.07-1.12) for stroke, 1.09 (95% CI, 1.06-1.13) for ischemic stroke, 1.10 (95% CI, 1.04-1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08-1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84-1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. Conclusions In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.",
     "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41467-023-36486-0.pdf; doi:https://doi.org/10.1038/s41467-023-36486-0; html:https://europepmc.org/articles/PMC9932102; pdf:https://europepmc.org/articles/PMC9932102?pdf=render"
+    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030280; doi:https://doi.org/10.1161/JAHA.123.030280; html:https://europepmc.org/articles/PMC10547274; pdf:https://europepmc.org/articles/PMC10547274?pdf=render"
   },
   {
     "id": "30842207",
@@ -37161,6 +37144,23 @@
     "laySummary": "",
     "urls": "pdf:https://discovery.dundee.ac.uk/ws/files/30348534/Author_Accepted_Manuscript.pdf; doi:https://doi.org/10.1136/heartjnl-2019-314763"
   },
+  {
+    "id": "36792666",
+    "doi": "https://doi.org/10.1038/s41467-023-36486-0",
+    "title": "SVEP1 is an endogenous ligand for the orphan receptor PEAR1.",
+    "authorString": "Elenbaas JS, Pudupakkam U, Ashworth KJ, Kang CJ, Patel V, Santana K, Jung IH, Lee PC, Burks KH, Amrute JM, Mecham RP, Halabi CM, Alisio A, Di Paola J, Stitziel NO.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature communications",
+    "pubYear": "2023",
+    "date": "2023-02-15",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes vascular disease and associates with platelet reactivity in humans. Here, using a human genomic and proteomic approach, we identify a high affinity, disease-relevant, and potentially targetable interaction between SVEP1 and the orphan receptor Platelet and Endothelial Aggregation Receptor 1 (PEAR1). This interaction promotes PEAR1 phosphorylation and disease associated AKT/mTOR signaling in vascular cells and platelets. Mice lacking SVEP1 have reduced platelet activation, and exogenous SVEP1 induces PEAR1-dependent activation of platelets. SVEP1 and PEAR1 causally and concordantly relate to platelet phenotypes and cardiovascular disease in humans, as determined by Mendelian Randomization. Targeting this receptor-ligand interaction may be a viable therapeutic strategy to treat or prevent cardiovascular and thrombotic disease.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41467-023-36486-0.pdf; doi:https://doi.org/10.1038/s41467-023-36486-0; html:https://europepmc.org/articles/PMC9932102; pdf:https://europepmc.org/articles/PMC9932102?pdf=render"
+  },
   {
     "id": "34307493",
     "doi": "https://doi.org/10.3389/fcvm.2021.677574",
@@ -39218,23 +39218,6 @@
     "laySummary": "",
     "urls": "pdf:https://europepmc.org/articles/pmc6974403?pdf=render; doi:https://doi.org/10.1038/s41588-019-0549-x; html:https://europepmc.org/articles/PMC6974403; pdf:https://europepmc.org/articles/PMC6974403?pdf=render"
   },
-  {
-    "id": "35387486",
-    "doi": "https://doi.org/10.1161/circulationaha.121.057888",
-    "title": "Genetic Landscape of the ACE2 Coronavirus Receptor.",
-    "authorString": "Yang Z, Macdonald-Dunlop E, Chen J, Zhai R, Li T, Richmond A, Klari\u0107 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, Vi\u00f1uela A, Gilly A, Elmst\u00e5hl S, Dedoussis G, Petrie JR, Pola\u0161ek O, Folkersen L, Chen Y, Yao C, V\u00f5sa U, Pairo-Castineira E, Clohisey S, Bretherick AD, Rawlik K, GenOMICC Consortium\u2020, IMI-DIRECT Consortium\u2020, Esko T, Enroth S, Johansson \u00c5, 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, Micha\u00eblsson K, Pawitan Y, Joshi PK, Baillie JK, M\u00e4larstig A, Reiner AP, Wilson JF, Shen X.",
-    "authorAffiliations": "",
-    "journalTitle": "Circulation",
-    "pubYear": "2022",
-    "date": "2022-04-07",
-    "isOpenAccess": "Y",
-    "keywords": "Cardiovascular diseases; Angiotensin-converting Enzyme 2; Genome-wide Association Study; Covid-19; Sars-cov-2",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28\u2009000 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.<h4>Results</h4>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]; <i>P</i>=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; <i>P</i>=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; <i>P</i>=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.<h4>Conclusions</h4>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.",
-    "laySummary": "",
-    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.057888; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.057888; html:https://europepmc.org/articles/PMC9047645; pdf:https://europepmc.org/articles/PMC9047645?pdf=render"
-  },
   {
     "id": "31770382",
     "doi": "https://doi.org/10.1371/journal.pmed.1002974",
@@ -39252,6 +39235,23 @@
     "laySummary": "This paper investigates the mortality of mothers of infants with Neonatal abstinence syndrome. This population has a greatly increased mortality compared to mothers who don't have NAS. The paper highlights the lack of long term support for this group.",
     "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1002974&type=printable; doi:https://doi.org/10.1371/journal.pmed.1002974; html:https://europepmc.org/articles/PMC6879118; pdf:https://europepmc.org/articles/PMC6879118?pdf=render"
   },
+  {
+    "id": "35387486",
+    "doi": "https://doi.org/10.1161/circulationaha.121.057888",
+    "title": "Genetic Landscape of the ACE2 Coronavirus Receptor.",
+    "authorString": "Yang Z, Macdonald-Dunlop E, Chen J, Zhai R, Li T, Richmond A, Klari\u0107 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, Vi\u00f1uela A, Gilly A, Elmst\u00e5hl S, Dedoussis G, Petrie JR, Pola\u0161ek O, Folkersen L, Chen Y, Yao C, V\u00f5sa U, Pairo-Castineira E, Clohisey S, Bretherick AD, Rawlik K, GenOMICC Consortium\u2020, IMI-DIRECT Consortium\u2020, Esko T, Enroth S, Johansson \u00c5, 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, Micha\u00eblsson K, Pawitan Y, Joshi PK, Baillie JK, M\u00e4larstig A, Reiner AP, Wilson JF, Shen X.",
+    "authorAffiliations": "",
+    "journalTitle": "Circulation",
+    "pubYear": "2022",
+    "date": "2022-04-07",
+    "isOpenAccess": "Y",
+    "keywords": "Cardiovascular diseases; Angiotensin-converting Enzyme 2; Genome-wide Association Study; Covid-19; Sars-cov-2",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>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.<h4>Methods</h4>We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28\u2009000 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.<h4>Results</h4>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]; <i>P</i>=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; <i>P</i>=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; <i>P</i>=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.<h4>Conclusions</h4>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.",
+    "laySummary": "",
+    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.057888; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.057888; html:https://europepmc.org/articles/PMC9047645; pdf:https://europepmc.org/articles/PMC9047645?pdf=render"
+  },
   {
     "id": "36084076",
     "doi": "https://doi.org/10.1371/journal.pone.0273687",
@@ -40969,23 +40969,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02486-y; doi:https://doi.org/10.1186/s12916-022-02486-y; html:https://europepmc.org/articles/PMC9449300; pdf:https://europepmc.org/articles/PMC9449300?pdf=render"
   },
-  {
-    "id": "37595128",
-    "doi": "https://doi.org/10.1097/hep.0000000000000361",
-    "title": "The global fatty liver disease Sustainable Development Goal country score for 195 countries and territories.",
-    "authorString": "Lazarus JV, Han H, Mark HE, Alqahtani SA, Schattenberg JM, Soriano JB, White TM, Zelber-Sagi S, Dirac MA, GBD Fatty Liver Disease Sustainable Development Goal Collaborators.",
-    "authorAffiliations": "",
-    "journalTitle": "Hepatology (Baltimore, Md.)",
-    "pubYear": "2023",
-    "date": "2023-04-18",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background and aims</h4>Fatty liver disease is highly prevalent, resulting in overarching wellbeing and economic costs. Addressing it requires comprehensive and coordinated multisectoral action. We developed a fatty liver disease Sustainable Development Goal (SDG) country score to provide insights into country-level preparedness to address fatty liver disease through a whole-of-society lens.<h4>Approach and results</h4>We developed 2 fatty liver disease-SDG score sets. The first included 6 indicators (child wasting, child overweight, noncommunicable disease mortality, a universal health coverage service coverage index, health worker density, and education attainment), covering 195 countries and territories between 1990 and 2017. The second included the aforementioned indicators plus an urban green space indicator, covering 60 countries and territories for which 2017 data were available. To develop the fatty liver disease-SDG score, indicators were categorized as \"positive\" or \"negative\" and scaled from 0 to 100. Higher scores indicate better preparedness levels. Fatty liver disease-SDG scores varied between countries and territories (n = 195), from 14.6 (95% uncertainty interval: 8.9 to 19.4) in Niger to 93.5 (91.6 to 95.3) in Japan; 18 countries and territories scored > 85. Regionally, the high-income super-region had the highest score at 88.8 (87.3 to 90.1) in 2017, whereas south Asia had the lowest score at 44.1 (42.4 to 45.8). Between 1990 and 2017, the fatty liver disease-SDG score increased in all super-regions, with the greatest increase in south Asia, but decreased in 8 countries and territories.<h4>Conclusions</h4>The fatty liver disease-SDG score provides a strategic advocacy tool at the national and global levels for the liver health field and noncommunicable disease advocates, highlighting the multisectoral collaborations needed to address fatty liver disease, and noncommunicable diseases overall.",
-    "laySummary": "",
-    "urls": "html:https://journals.lww.com/hep/Abstract/9900/The_global_Fatty_Liver_Disease_Sustainable.395.aspx; doi:https://doi.org/10.1097/HEP.0000000000000361; html:https://europepmc.org/articles/PMC10442089; pdf:https://europepmc.org/articles/PMC10442089?pdf=render"
-  },
   {
     "id": "32654539",
     "doi": "https://doi.org/10.1161/circulationaha.119.045526",
@@ -41003,6 +40986,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.119.045526; doi:https://doi.org/10.1161/CIRCULATIONAHA.119.045526; html:https://europepmc.org/articles/PMC7493828; pdf:https://europepmc.org/articles/PMC7493828?pdf=render; doi:https://doi.org/10.1161/circulationaha.119.045526"
   },
+  {
+    "id": "37595128",
+    "doi": "https://doi.org/10.1097/hep.0000000000000361",
+    "title": "The global fatty liver disease Sustainable Development Goal country score for 195 countries and territories.",
+    "authorString": "Lazarus JV, Han H, Mark HE, Alqahtani SA, Schattenberg JM, Soriano JB, White TM, Zelber-Sagi S, Dirac MA, GBD Fatty Liver Disease Sustainable Development Goal Collaborators.",
+    "authorAffiliations": "",
+    "journalTitle": "Hepatology (Baltimore, Md.)",
+    "pubYear": "2023",
+    "date": "2023-04-18",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background and aims</h4>Fatty liver disease is highly prevalent, resulting in overarching wellbeing and economic costs. Addressing it requires comprehensive and coordinated multisectoral action. We developed a fatty liver disease Sustainable Development Goal (SDG) country score to provide insights into country-level preparedness to address fatty liver disease through a whole-of-society lens.<h4>Approach and results</h4>We developed 2 fatty liver disease-SDG score sets. The first included 6 indicators (child wasting, child overweight, noncommunicable disease mortality, a universal health coverage service coverage index, health worker density, and education attainment), covering 195 countries and territories between 1990 and 2017. The second included the aforementioned indicators plus an urban green space indicator, covering 60 countries and territories for which 2017 data were available. To develop the fatty liver disease-SDG score, indicators were categorized as \"positive\" or \"negative\" and scaled from 0 to 100. Higher scores indicate better preparedness levels. Fatty liver disease-SDG scores varied between countries and territories (n = 195), from 14.6 (95% uncertainty interval: 8.9 to 19.4) in Niger to 93.5 (91.6 to 95.3) in Japan; 18 countries and territories scored > 85. Regionally, the high-income super-region had the highest score at 88.8 (87.3 to 90.1) in 2017, whereas south Asia had the lowest score at 44.1 (42.4 to 45.8). Between 1990 and 2017, the fatty liver disease-SDG score increased in all super-regions, with the greatest increase in south Asia, but decreased in 8 countries and territories.<h4>Conclusions</h4>The fatty liver disease-SDG score provides a strategic advocacy tool at the national and global levels for the liver health field and noncommunicable disease advocates, highlighting the multisectoral collaborations needed to address fatty liver disease, and noncommunicable diseases overall.",
+    "laySummary": "",
+    "urls": "html:https://journals.lww.com/hep/Abstract/9900/The_global_Fatty_Liver_Disease_Sustainable.395.aspx; doi:https://doi.org/10.1097/HEP.0000000000000361; html:https://europepmc.org/articles/PMC10442089; pdf:https://europepmc.org/articles/PMC10442089?pdf=render"
+  },
   {
     "id": "33069326",
     "doi": "https://doi.org/10.1016/s0140-6736(20)30925-9",