bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in English medication safety indicators throughout the COVID-19 pandemic: a federated analysis of 57 million patients’ primary care records in situ using OpenSAFELY
Authors: Fisher Louis , Hopcroft Lisa E. M. , Rodgers Sarah , Barrett James , Oliver Kerry , Avery Anthony J. , Evans Dai , Curtis Helen , Croker Richard , Macdonald Orla , Morley Jessica , Mehrkar Amir , Bacon Seb , Davy Simon , Dillingham Iain , Evans David , Hickman George , Inglesby Peter , Morton Caroline E. , Smith Becky , Ward Tom , Hulme William , Green Amelia , Massey Jon , Walker Alex J. , Bates Chris , Cockburn Jonathan , Parry John , Hester Frank , Harper Sam , O’Hanlon Shaun , Eavis Alex , Jarvis Richard , Avramov Dima , Griffiths Paul , Fowles Aaron , Parkes Nasreen , Goldacre Ben , MacKenna Brian 
Published: May 2022

AbstractObjectiveTo describe the impact of the COVID-19 pandemic on safe prescribing, using the PINCER prescribing indicators; to implement complex prescribing indicators at national scale using GP data.DesignPopulation based cohort study, with the approval of NHS England using the OpenSAFELY platform.SettingElectronic health record data from 56.8 million NHS patients’ general practice records.ParticipantsAll NHS patients registered at a GP practice using TPP or EMIS computer systems and recorded as at risk of at least one potentially hazardous PINCER indicator between September 2019 and September 2021.Main outcome measureMonthly trends and between-practice variation for compliance with 13 PINCER measures between September 2019 and September 2021.ResultsThe indicators were successfully implemented across GP data in OpenSAFELY. Hazardous prescribing remained largely unchanged during the COVID-19 pandemic, with only small reductions in achievement of the PINCER indicators. There were transient delays in blood test monitoring for some medications, particularly ACE inhibitors. All indicators exhibited substantial recovery by September 2021. We identified 1,813,058 patients at risk of at least one hazardous prescribing event.ConclusionGood performance was maintained during the COVID-19 pandemic across a diverse range of widely evaluated measures of safe prescribing.Summary boxWHAT IS ALREADY KNOWN ON THIS TOPICPrimary care services were substantially disrupted by the COVID-19 pandemic.Disruption to safe prescribing during the pandemic has not previously been evaluated.PINCER is a nationally adopted programme of activities that aims to identify and correct hazardous prescribing in GP practices, by conducting manual audit on subgroups of practices.WHAT THIS STUDY ADDSFor the first time, we were able to successfully generate data on PINCER indicators for almost the whole population of England, in a single analysis.Our study is the most comprehensive assessment of medication safety during the COVID-19 pandemic in England, covering 95% of the population using well-validated measures.Good performance was maintained across many PINCER indicators throughout the pandemic.Delays in delivering some medication-related blood test monitoring were evident though considerable recovery was made by the end of the study period.
DeepPheWAS: an R package for phenotype generation and association analysis for phenome-wide association studies
Authors: Packer R , Williams AT , Hennah W , Eisenberg MT , Fawcett KA , Pearson W , Guyatt A , Edris A , Hollox EJ , Rao BS , Bratty JR , Wain LV , Dudbridge F , Tobin MD 
Published: May 2022

AbstractSummaryDeepPheWAS is an R package for phenome wide association studies that creates clinically-curated composite phenotypes, and integrates quantitative phenotypes from primary care data, longitudinal trajectories of quantitative measures, disease progression, and drug response phenotypes. Tools are provided for efficient analysis of association with any genetic input, under any genetic model, with optional sex-stratified analysis, and for developing novel phenotypes.Availability and ImplementationThe DeepPheWAS R package is freely available under GNU general public licence v3.0 from at https://github.com/Richard-Packer/DeepPheWAS.Contactrichard.packer@leicester.ac.ukSupplementary informationSupplementary methods and results are available at Bioinformatics online.
Routine Saliva Testing for SARS-CoV-2 in Children: Partnering with Childcare Centers in the Greater New Haven Community
Authors: Rayack Erica J. , Askari Hibah Mahwish , Zirinsky Elissa , Lapidus Sarah , Sheikha Hassan , Peno Chikondi , Kazemi Yasaman , Yolda-Carr Devyn , Liu Chen , Grubaugh Nathan D. , Ko Albert I. , Wyllie Anne L. , Spatz Erica S. , Oliveira Carlos R. , Bei Amy K. 
Published: May 2022

AbstractBackgroundWhile considerable attention was placed on SARS-CoV-2 testing and surveillance programs in the K-12 setting, younger age groups in childcare centers were largely overlooked. Childcare facilities are vital to communities, allowing parents/guardians to remain at work and providing safe environments for both children and staff. Therefore, early in the COVID-19 pandemic, we established a PCR-based COVID-19 surveillance program in childcare facilities, testing children and staff with the goal of collecting actionable public health data and aiding communities in the progressive resumption of standard operations and ways of life. In this study we describe the development of a weekly saliva testing program and provide early results from our experience implementing this in childcare centers.MethodsWe enrolled children (aged 6 months to 7 years) and staff at 8 childcare facilities and trained participants in saliva collection using video chat technology. Weekly surveys were sent out to assess exposures, symptoms, and vaccination status changes. Participants submitted weekly saliva samples at school. Samples were transported to a partnering clinical laboratory for RT-PCR testing using SalivaDirect and results were uploaded to each participant’s online patient portal within 24 hours.ResultsThis study fostered a cooperative partnership with participating childcare centers, parents/guardians, and staff with the goal of mitigating COVID-19 transmission in childcare centers. Age-related challenges in saliva collection were overcome by working with parents/guardians to conceptualize new collection strategies and by offering parents/guardians continued virtual guidance and support.ConclusionSARS-CoV-2 screening and routine testing programs have focused less on the childcare population, resulting in knowledge gaps in this critical age group, especially as many are still ineligible for vaccination. SalivaDirect testing for SARS-CoV-2 provides a feasible method of asymptomatic screening and symptomatic testing for children and childcare center staff. Given the relative aversion to nasal swabs in the childcare age group, especially as a routine surveillance tool, an at-home saliva collection method provides an attractive alternative. Results can be shared rapidly electronically through participants’ private medical chart portals, and video chat technology allows for discussion and instruction between investigators and participants.
Impact of COVID-19 non-pharmaceutical interventions on pneumococcal carriage prevalence and density in Vietnam
Authors: Nation Monica Larissa , Manna Sam , Tran Hau Phuc , Nguyen Cattram Duong , Vy Le Thi Tuong , Uyen Doan Y , Phuong Tran Linh , Dai Vo Thi Trang , Ortika Belinda Daniela , Wee-Hee Ashleigh Christina , Beissbarth Jemima , Hinds Jason , Bright Kathryn , Smith-Vaughan Heidi , Nguyen Thuong Vu , Mulholland Kim , Temple Beth , Satzke Catherine 
Published: May 2022

AbstractNon-pharmaceutical interventions (NPIs) implemented to contain SARS-CoV-2 have decreased invasive pneumococcal disease. We undertook an observational study to evaluate the impact of NPIs on pneumococcal carriage and density, drivers of transmission and disease, during the COVID-19 pandemic in Ho Chi Minh City, Vietnam. While NPIs did not significantly impact pneumococcal carriage, mean capsular pneumococcal density decreased by up to 91.5% (1.07 log10genome equivalents/mL, 95% Confidence Interval: 0.74-1.41) after NPI introduction compared with the pre-COVID-19 period. As higher pneumococcal density is a risk factor for disease, the observed decline provides a plausible mechanism for the reductions in invasive pneumococcal disease.
Clinical prediction models for treatment outcome in newly-diagnosed epilepsy: Protocol for a systematic review
Authors: Ratcliffe Corey , Marson Anthony , Keller Simon S. , Bonnett Laura J. 
Published: May 2022

AbstractEpilepsy, characterised by a predisposition towards unprovoked seizures, is one of the most common neurological disorders globally. Whilst 60-70% of individuals diagnosed with epilepsy will gain seizure control through anti-seizure medication, the mechanisms underlying seizure persistence are unclear. Intractability can significantly degrade a patient’s quality of life amongst other things; the use of predictive modelling of epilepsy outcomes in deciding on treatment therefore offers a tangible benefit to the patient. Early indicators of pharmacoresistance may discourage certain treatment options, and save time in what has been indicated to be a critical stage for newly-diagnosed epilepsy. Primarily, this paper aims to evaluate existing predictive models to identify demographic, clinical, physiological (e.g. EEG), and neuroimaging (e.g. MRI) factors that may be predictive of treatment outcomes in newly-diagnosed epilepsy. Two electronic databases, MEDLINE and EMBASE, will be searched with terms related to prognosis in newly-diagnosed epilepsy, and identified studies will be included for review if they have combined at least two demographic, clinical, neuroimaging, and/or physiological factors to predict treatment outcome in people with newly-diagnosed epilepsy. Papers will be screened by two independent reviewers via titles, abstracts and then full text against the inclusion criteria for eligibility. Data will be extracted by reviewers using standardised forms, assessed for risk of bias using the PROBAST tool and synthesised narratively. If considered appropriate the authors will carry out a meta-analysis on the available data.Prospero registration number– CRD42022329936
Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom
Authors: Zöllner Julia , Finer Sarah , Linton Kenneth J. ,   Genes and Health Research Team, van Heel David A. , Williamson Catherine , Dixon Peter H. 
Published: May 2022

AbstractObjectivesThis study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people in the United Kingdom as they are an understudied genetic ancestry group with disproportionate disease burden.MethodsFive genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by low/mid whole 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. Rare variant burden analysis was conducted. Variants associated with a phenotype or predicted to be likely pathogenic (LP) underwent protein structure and modelling analysis in silico.ResultsOut of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and were mostly heterozygous unless specified. 90 were novel and unique to this cohort and not previously reported in the GnomAD database. Of those novel variants, 22 were considered LP 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 inABCB11. A total of 73 variants were assessed for impact at the protein level. Protein modelling demonstrated variants that appeared to likely cause significant structural damage.ConclusionsThis 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.WHAT IS KNOWNCholestatic liver diseases encompass a broad range of conditions.Intrahepatic cholestasis of pregnancy (ICP) is the commonest gestational liver disease.Genetic and environmental factors contribute to the aetiology of cholestatic disease.South Asian populations are disproportionally affected.WHAT IS NEW HEREExome sequencing analysis in a British Pakistani and Bangladeshi population discovered new genetic mutations.Pathogenic variants were identified that increase risk of cholestatic liver disease.Novel variants that contribute to ICP were identified.
Variability of Tissue Mechanical Response in Sus Domesticus Porcine Models from in vivo to ex vivo Conditions
Authors: Malik Faizan A. , Drahos Bradley A. , Safdari Amer , Mazzeo Mark V. , Norfleet Jack E. , Sweet Robert M. , Kowalewski Timothy M. 
Published: May 2022

AbstractHealthcare simulators have been demonstrated to be a valuable resource for training several technical and nontechnical skills. A gap in the fidelity of tissues has been acknowledged as a barrier to application for current simulators; especially for interventional procedures. Inaccurate or unrealistic mechanical response of a simulated tissue to a given surgical tool motion may result in negative training transfer and/or prevents the “suspension of disbelief” necessary for a trainee to engage in the activity. Thus, where it is relevant to training outcomes, there should be an effort to create healthcare simulators with simulated tissue mechanical responses that match or represent those of biological tissues. Historically, this data is most often gathered from preserved (post mortem) tissue; however, there is a concern that the mechanical properties of preserved tissue, that lacks blood flow, may lack adequate accuracy to provide the necessary training efficacy of simulators. This work explores the effect of the “state” of the tissue testing status on liver and peritoneal tissue by using a customized handheld grasper to measure the mechanical responses of representative porcine (Sus domesticus) tissues in N=5 animals across five test conditions: in vivo, postmortem (in-situ), ex vivo (immediately removed from fresh porcine cadaver), post-refrigeration, and post-freeze-thaw cycle spanning up to 72 hours after death. No statistically significant difference was observed in the mechanical responses due to grasping between in vivo and post-freeze conditions for porcine liver and peritoneum tissue samples (p = 0.05 for derived stiffness at grasping force values F = 5N and 6.5N). Furthermore, variance between in vivo and post-thaw conditions within each animal, was comparable to the variance of the in vivo condition between animals. Thus, the use of thawed, preserved tissue for the further study and emulation of mechanical perturbation of the liver and peritoneum can be considered.
Uganda Genome Resource: A rich research database for genomic studies of communicable and non-communicable diseases in Africa
Authors: Fatumo Segun , Mugisha Joseph , Soremekun Opeyemi S , Kalungi Allan , Mayanja Richard , Kintu Christopher , Makanga Ronald , Kakande Ayoub , Abaasa Andrew , Asiki Gershim , Kalyesubula Robert , Newton Robert , Nyirenda Moffat , Sandhu Manj S. , Kaleebu Pontiano 
Published: May 2022

AbstractThe Uganda Genome Resource (UGR) is a well characterised genomic database, with a range of phenotypic communicable and non-communicable diseases and risk factors generated from the Uganda General Population Cohort (GPC) - a population-based open cohort study established in 1989 by the Medical Research Council (MRC) UK in collaboration with the Uganda Virus Research Institute (UVRI).In 2011, UGR was launched with genotype data on ∼5000 and whole genome sequence data on ∼2000 Ugandan individuals from 9 ethno-linguistic groups. Leveraging other available platforms at the MRC Uganda such as Biorepository centre for sample storage, Clinical Diagnostic Laboratory Service (CDLS) for sample diagnostic testing, sequencing platform for DNA extraction, Uganda Medical informatics Unit (UMIC) for large-scale data analysis, GPC for additional sample collection, UGR is strategically poised to expand and generate scientific discoveries.Here, we describe UGR and highlight the important genetic findings thus far including how UGR is providing opportunities to: (1) discover novel disease susceptibility genetic loci; (2) refine association signals at new and existing loci; (3) develop and test Polygenic Risk Score (PRS) to determine individual’s disease risk; 4) assess how some risk factors including infectious diseases are causally related to non-communicable diseases (NCDs) in Africa; (5) develop research capacity for genomics in Africa; and (6) enhance African participation in the global genomics research arena. Leveraging established research infrastructure, expertise, local genomic leadership, global collaboration and strategic funding, we anticipate that UGR can develop further to a comparable level of European and Asian large-scale genomic initiatives.
Reduced motor unit discharge rates in gastrocnemius lateralis, but not in gastrocnemius medialis or soleus, in runners with Achilles tendinopathy
Authors: Fernandes Gabriel L. , Orssatto Lucas B. R. , Sakugawa Raphael L. , Trajano Gabriel S. 
Published: May 2022

AbstractObjectivesDeficits in muscle performance could be a consequence of a reduced ability of a motor neuron to increase the rate in which it discharges. This study aimed to investigate motor unit (MU) discharge properties of each Triceps surae muscle (TS), and TS torque steadiness during submaximal intensities in runners with Achilles tendinopathy (AT).MethodsWe recruited runners with (n=12) and without (n=13) mid-portion AT. MU discharge rate was analysed for each of the TS muscles, using High-Density surface electromyography during 10 and 20% isometric plantar flexor contractions.ResultsMU mean discharge rate was lower in the Gastrocnemius lateralis (GL) in AT compared to controls. In AT, GL MU mean discharge rate did not increase as torque increased from 10% peak torque, 8.24pps (95%CI: 7.08 to 9.41) to 20%, 8.52pps (7.41 to 9.63, p=0.540); however, in controls, MU discharge rate increased as torque increased from 10%, 8.39pps (7.25 to 9.53) to 20%, 10.07pps (8.89 to 11.25, p<0.001). There were no between-group difference in Gastrocnemius medialis (GM) or Soleus (SOL) MU discharge rates. We found no between-groups differences in coefficient of variation of MU discharge rate in any of the TS muscles nor in TS torque steadiness.ConclusionOur data demonstrates that runners with AT may have a reduced neural drive to GL, failing to increase MU discharge rate to adjust for the increase in torque demand. Further research is needed to understand how interventions focusing on increasing neural drive to GL would affect muscle function in runners with AT.
Substance abuse and the risk of severe COVID-19: Mendelian randomization confirms the causal role of opioids but hints a negative causal effect for cannabinoids
Authors: Jabalameli M.Reza , Zhang Zhengdong D 
Published: May 2022

AbstractSince the start of the COVID-19 global pandemic, our understanding of the underlying disease mechanism and factors associated with the disease severity has dramatically increased. A recent report investigated the relationship between substance use disorders (SUD) and the risk of severe COVID-19 in the United States and concluded that the risk of hospitalization and death due to COVID-19 is directly correlated with substance abuse, including opioid use disorder (OUD) and cannabis use disorder (CUD). While we found this analysis fascinating, we believe this observation may be biased due to comorbidities (such as hypertension, diabetes, and cardiovascular disease) confounding the direct impact of SUD on severe COVID-19 illness. To objectively answer this question, we sought to investigate the causal relationship between substance abuse and medication-taking history (as a proxy trait for comorbidities) with the risk of COVID-19 adverse outcomes. Our Mendelian randomization analysis confirms the causal relationship between SUD and severe COVID-19 illness but hints at a negative causal effect for cannabinoids. Given that a great deal of COVID-19 mortality is attributed to disturbed immune regulation, the possible modulatory impact of cannabinoids in alleviating cytokine storms merits further investigation.
Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron Variant of Concern
Authors: Mazzaferri Fulvia , Mirandola Massimo , Savoldi Alessia , De Nardo Pasquale , Morra Matteo , Tebon Maela , Armellini Maddalena , De Luca Giulia , Calandrino Lucrezia , Sasset Lolita , D’Elia Denise , Sozio Emanuela , Danese Elisa , Gibellini Davide , Monne Isabella , Scroccaro Giovanna , Magrini Nicola , Cattelan Annamaria , Tascini Carlo ,   MANTICO Working Group, Tacconelli Evelina 
Published: May 2022

BackgroundRecent in-vitro data have shown that the activity of monoclonal antibodies (mAbs) targeting SARS-CoV-2 varies according to the Variant of Concern (VOC). No studies have compared the clinical efficacy of different mAbs against Omicron VOC.MethodsThe MANTICO trial is a non-inferiority randomised controlled trial comparing the clinical efficacy of bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab in outpatients aged 50 or older with early COVID-19. As the patient enrolment was interrupted for possible futility after the onset of the Omicron wave, the analysis was performed according to the SARS-CoV-2 VOC. The primary outcome was COVID-19 progression (hospitalisation, need of supplemental oxygen therapy, or death through day 14). Secondary outcomes included the time to symptom resolution, assessed using the product-limit method. Kaplan-Meier estimator and Cox proportional hazard model were used to assess the association with predictors. Log rank test was used to compare survival functions.ResultsOverall, 319 patients were included. Among 141 patients infected with Delta, no disease progression was recorded and the time to symptom resolution did not differ significantly between treatment groups (Log-rank Chi-square 0.22, p 0.895). Among 170 patients infected with Omicron (80.6% BA.1, 19.4% BA.1.1), two disease progressions were recorded in the bamlanivimab/etesevimab group and the median time to symptom resolution was 5 days shorter in the sotrovimab group compared to bamlanivimab/etesevimab and casirivimab/imdevimab (HR 0.526 and HR 0.451, 95% CI 0.359 - 0.77 and 95% CI 0.303 - 0.669, p 0.001 and 0.0001, respectively).ConclusionsThese results confirm the in-vitro data of superiority of sotrovimab versus casirivimab/imdevimab and bamlanivimab/etesivamab in reducing the time to recovery in patients infected with Omicron BA.1 and BA.1.1, while no difference was detected in Delta infections. Casirivimab/imdevimab seems to maintain a role in preventing severe COVID-19 in the Omicron population. Adaptive clinical trials comparing mAbs by VOC should be pursued to promptly inform clinical recommendations.FundingThis trial was funded by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The VOC identification was funded by the ORCHESTRA (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic) project, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101016167.Clinical trial numberNCT05205759