bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of a glucagon-like peptide-1 agonist and restrictive versus liberal oxygen supply in patients undergoing coronary artery bypass grafting or aortic valve replacement: study protocol for a 2-by-2 factorial designed, randomised clinical trial
Authors: Wiberg Sebastian , Kjaergaard Jesper , Møgelvang Rasmus , Møller Christian Holdflod , Kandler Kristian , Ravn Hanne , Hassager Christian , Køber Lars , Nilsson Jens Christian 
Published: November 2021

IntroductionCoronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR) are associated with risk of death, as well as brain, heart and kidney injury. Glucagon-like peptide-1 (GLP-1) analogues are approved for treatment of type 2 diabetes, and GLP-1 analogues have been suggested to have potential organ-protective and anti-inflammatory effects. During cardiopulmonary bypass (CPB), consensus on the optimal fraction of oxygen is lacking. The objective of this study is to determine the efficacy of the GLP-1-analogue exenatide versus placebo and restrictive oxygenation (50% fractional inspired oxygen, FiO2) versus liberal oxygenation (100% FiO2) in patients undergoing open heart surgery.Methods and analysisA randomised, placebo-controlled, double blind (for the exenatide intervention)/single blind (for the oxygenation strategy), 2×2 factorial designed single-centre trial on adult patients undergoing elective or subacute CABG and/or surgical AVR. Patients will be randomised in a 1:1 and 1:1 ratio to a 6-hour and 15 min infusion of 17.4 µg of exenatide or placebo during CPB and to a FiO2 of 50% or 100% during and after weaning from CPB. Patients will be followed until 12 months after inclusion of the last participant. The primary composite endpoint consists of time to first event of death, renal failure requiring renal replacement therapy, hospitalisation for stroke or heart failure. In addition, the trial will include predefined sub-studies applying more advanced measures of cardiac- and pulmonary dysfunction, renal dysfunction and cerebral dysfunction. The trial is event driven and aims at 323 primary endpoints with a projected inclusion of 1400 patients.Ethics and disseminationEligible patients will provide informed, written consent prior to randomisation. The trial is approved by the local ethics committee and is conducted in accordance with Danish legislation and the Declaration of Helsinki. The results will be presented in peer-reviewed journals.Trial registration numberNCT02673931.
Extraocular muscle resection, recession length and surgery outcome modelling in strabismus treatment: a pilot study
Authors: Paduca Ala , Arnaut Oleg , Bendelic Eugeniu , Bruenech Jan Richard , Lundmark Per Olof 
Published: November 2021

BackgroundMany surgical formulas have been developed and proposed based on the experience of surgeons to improve the predictability of strabismus surgery. However, the consent among strabismus surgeons regarding the dose effect of the extraocular muscle (EOM) recession or resection was not achieved yet and the disagreement about the appropriate amount of strabismus surgery still exists.ObjectiveOur study aimed to propose an instrument for EOM resection (RsL) and recession length (RcL) estimation before the surgery and second to elaborate an postoperative angle of deviation (PAD) predictive model using simple potential predictors.Methods and AnalysisThe analytical prospective clinical study was conducted from April 2016 to July 2019, on a sample of 216 patients (aged between 2–58) with concomitant strabismus who underwent strabismus surgery in Clinical Republican Hospital ‘Timofei Mosneaga’and Children Hospital ‘Em Cotaga’ from Republic of Moldova. The correlations of patients’ age, strabismus type, amblyopia degree, RsL, RcL, preoperative angle of deviation (PreAD) with PAD were estimated using Pearson’s correlation analysis. Multiple linear regression analysis, multicollinearity analysis and residual analysis were performed.ResultsThe EOM RsL was predicted using strabismus type, patient’s age, PreAD and EOM RcL. EOM RcL, in turn, was estimated by the similar covariates set, instead of RcL being RsL. PAD modelling showed the PreAD, EOM RsL and EOM RcL predictive ability for strabismus surgery outcome prediction.ConclusionIn our study, we propose four mathematical models as potential instruments for EOM RsL, EOM RcL and PAD modelling in esotropia and exotropia surgery.
At risk child: a contemporary analysis of injured children in London and the South East of England: a prospective, multicentre cohort study
Authors: Elbourne Ceri , Cole Elaine , Marsh Stephen , Rex Dean , Makin Erica , Salter Rebecca , Brohi Karim , Edmonds Naomi , Cleeve Stewart , O'Neill Breda 
Published: November 2021

BackgroundInjury is a leading health burden in children yet relatively little is reported about the contemporary risks they face. Current national registry data may under-represent the true burden of injury to children. We aim to analyse contemporary patterns of paediatric trauma and identify current factors putting children at risk of injury.MethodsA 3-month prospective multicentre cohort evaluation of injured children across the London Major Trauma System was performed. All children receiving a trauma team activation; meeting National Institute for Health and Care Excellence CT head criteria; or admitted/transferred out due to trauma were included. Data were collected on demographics, mechanism and location of injury, and body region injured. The primary outcome was in-hospital mortality and secondary outcome was safeguarding concerns.Results659 children were included. Young children were more likely to be injured at home (0–5 years old: 70.8%, n=167 vs adolescents: 15.6%, n=31). Adolescents were more likely to be injured in the street (42.7%, n=85). Head trauma caused over half of injuries in 0–5 years old (51.9%, n=121). Falls were common and increasingly prevalent in younger children, causing 56.6% (n=372) of injuries. In adolescents, penetrating violence caused more than one in five injuries (21.9%, n=50). Most injured children survived (99.8%, n=658), however, one in four (26.1%, n=172) had safeguarding concerns and a quarter of adolescents had police, third sector or external agency involvement (23.2%, n=53).ConclusionsThis study describes modern-day paediatric trauma and highlights the variance in injury patterns in young children and adolescents. Importantly, it highlights differences in actual rates of injuries compared with those reported from current national registry data. We must understand real risks facing 21st century children to effectively safeguard future generations. The results provide an opportunity to reassess the current approach to injury prevention, child and adolescent safeguarding, and public health campaigns for child safety.
Development of a conceptual model of childhood asthma to inform asthma prevention policies
Authors: Adibi Amin , Turvey Stuart E , Lee Tae Yoon , Sears Malcolm R , Becker Allen B , Mandhane Piush J , Moraes Theo J , Subbarao Padmaja , Sadatsafavi Mohsen 
Published: November 2021

BackgroundThere is no definitive cure for asthma, as prevention remains a major goal. Decision analytic models are routinely used to evaluate the value-for-money proposition of interventions. Following best practice standards in decision-analytic modelling, the objective of this study was to solicit expert opinion to develop a concept map for a policy model for primary prevention of asthma.MethodsWe reviewed currently available decision analytic models for asthma prevention. A steering committee of economic modellers, allergists and respirologists was then convened to draft a conceptual model of paediatric asthma. A modified Delphi method was followed to define the context of the problem at hand (evaluation of asthma prevention strategies) and develop the concept map of the model.ResultsConsensus was achieved after three rounds of discussions, followed by concealed voting. In the final conceptual model, asthma diagnosis was based on three domains of lung function, atopy and their symptoms. The panel recommended several markers for each domain. These domains were in turn affected by several risk factors. The panel clustered all risk factors under three groups of ‘patient characteristic’, ‘family history’ and ‘environmental factors’. To be capable of modelling the interplay among risk factors, the panel recommended the use of microsimulation, with an open-population approach that would enable modelling phased implementation and gradual and incomplete uptake of the intervention.ConclusionsEconomic evaluation of childhood interventions for preventing asthma will require modelling of several codependent risk factors and multiple domains that affect the diagnosis. The conceptual model can inform the development and validation of a policy model for childhood asthma prevention.
Personalised risk prediction following emergency department assessment for syncope
Authors: Thiruganasambandamoorthy Venkatesh , Yan Justin W , Rowe Brian H , Mercier Éric , Le Sage Natalie , Hegdekar Mona , Finlayson Anne , Huang Paul , Mohammad Hassan , Mukarram Muhammad , Nguyen Phuong Anh (Iris) , Syed Shahbaz , McRae Andrew D , Nemnom Marie-Joe , Taljaard Monica , Silviotti Marco LA 
Published: November 2021

BackgroundPublished risk tools do not provide possible management options for syncope in the emergency department (ED). Using the 30-day observed risk estimates based on the Canadian Syncope Risk Score (CSRS), we developed personalised risk prediction to guide management decisions.MethodsWe pooled previously reported data from two large cohort studies, the CSRS derivation and validation cohorts, that prospectively enrolled adults (≥16 years) with syncope at 11 Canadian EDs between 2010 and 2018. Using this larger cohort, we calculated the CSRS calibration and discrimination, and determined with greater precision than in previous studies the 30-day risk of adjudicated serious outcomes not identified during the index ED evaluation depending on the CSRS and the risk category. Based on these findings, we developed an on-line calculator and pictorial decision aids.Results8233 patients were included of whom 295 (3.6%, 95% CI 3.2% to 4.0%) experienced 30-day serious outcomes. The calibration slope was 1.0, and the area under the curve was 0.88 (95% CI 0.87 to 0.91). The observed risk increased from 0.3% (95% CI 0.2% to 0.5%) in the very-low-risk group (CSRS −3 to –2) to 42.7% (95% CI 35.0% to 50.7%), in the very-high-risk (CSRS≥+6) group (Cochrane-Armitage trend test p<0.001). Among the very-low and low-risk patients (score −3 to 0), ≤1.0% had any serious outcome, there was one death due to sepsis and none suffered a ventricular arrhythmia. Among the medium-risk patients (score +1 to+3), 7.8% had serious outcomes, with <1% death, and a serious outcome was present in >20% of high/very-high-risk patients (score +4 to+11) including 4%–6% deaths. The online calculator and the pictorial aids can be found at:https://teamvenk.com/csrsConclusions30-day observed risk estimates from a large cohort of patients can be obtained for management decision-making. Our work suggests very-low-risk and low-risk patients may be discharged, discussion with patients regarding investigations and disposition are needed for medium-risk patients, and high-risk patients should be hospitalised. The online calculator, accompanied by pictorial decision aids for the CSRS, may assist in discussion with patients.
COVID-19 rapid diagnostics: practice review
Authors: Reynard Charles , Allen Joy A , Shinkins Bethany , Prestwich Graham , Goves Johnathan , Davies Kerrie , Body Richard 
Published: November 2021

Point-of-care tests for SARS-CoV-2 could enable rapid rule-in and/or rule-out of COVID-19, allowing rapid and accurate patient cohorting and potentially reducing the risk of nosocomial transmission. As COVID-19 begins to circulate with other more common respiratory viruses, there is a need for rapid diagnostics to help clinicians test for multiple potential causative organisms simultaneously.However, the different technologies available have strengths and weaknesses that must be understood to ensure that they are used to the benefit of the patient and healthcare system. Device performance is related to the deployed context, and the diagnostic characteristics may be affected by user experience.This practice review is written by members of the UK’s COVID-19 National Diagnostic Research and Evaluation programme. We discuss relative merits and test characteristics of various commercially available technologies. We do not advocate for any given test, and our coverage of commercially supplied tests is not intended to be exhaustive.
Alcohol-impaired driving among adults—USA, 2014–2018
Authors: Barry Vaughn , Schumacher Amy , Sauber-Schatz Erin 
Published: November 2021

IntroductionAlcohol-impaired driving (AID) crashes accounted for 10 511 deaths in the USA in 2018, or 29% of all motor vehicle-related crash deaths. This study describes self-reported AID in the USA during 2014, 2016 and 2018 and determines AID-related demographic and behavioural characteristics.MethodsData were from the nationally representative Behavioral Risk Factor Surveillance System. Adults were asked ‘During the past 30 days, how many times have you driven when you have had perhaps too much to drink?’ AID prevalence, episode counts and rates per 1000 population were estimated using annualised individual AID episodes and weighted survey population estimates. Results were stratified by characteristics including gender, binge drinking, seatbelt use and healthcare engagement.ResultsNationally, 1.7% of adults engaged in AID during the preceding 30 days in 2014, 2.1% in 2016 and 1.7% in 2018. Estimated annual number of AID episodes varied across year (2014: 111 million, 2016: 186 million, 2018: 147 million) and represented 3.7 million, 4.9 million and 4.0 million adults, respectively. Corresponding yearly episode rates (95% CIs) were 452 (412–492) in 2014, 741 (676–806) in 2016 and 574 (491–657) in 2018 per 1000 population. Among those reporting AID in 2018, 80% were men, 86% reported binge drinking, 47% did not always use seatbelts and 60% saw physicians for routine check-ups within the past year.ConclusionsAlthough AID episodes declined from 2016 to 2018, AID was still prevalent and more common among men and those who binge drink. Most reporting AID received routine healthcare. Proven AID-reducing strategies exist.
Lessons learnt from multifaceted diagnostic approaches to the first 150 families in Victoria’s Undiagnosed Diseases Program
Authors: Cloney Thomas , Gallacher Lyndon , Pais Lynn S , Tan Natalie B , Yeung Alison , Stark Zornitza , Brown Natasha J , McGillivray George , Delatycki Martin B , de Silva Michelle G , Downie Lilian , Stutterd Chloe A , Elliott Justine , Compton Alison G , Lovgren Alysia , Oertel Ralph , Francis David , Bell Katrina M , Sadedin Simon , Lim Sze Chern , Helman Guy , Simons Cas , Macarthur Daniel G , Thorburn David R , O'Donnell-Luria Anne H , Christodoulou John , White Susan M , Tan Tiong Yang 
Published: November 2021

BackgroundClinical exome sequencing typically achieves diagnostic yields of 30%–57.5% in individuals with monogenic rare diseases. Undiagnosed diseases programmes implement strategies to improve diagnostic outcomes for these individuals.AimWe share the lessons learnt from the first 3 years of the Undiagnosed Diseases Program-Victoria, an Australian programme embedded within a clinical genetics service in the state of Victoria with a focus on paediatric rare diseases.MethodsWe enrolled families who remained without a diagnosis after clinical genomic (panel, exome or genome) sequencing between 2016 and 2018. We used family-based exome sequencing (family ES), family-based genome sequencing (family GS), RNA sequencing (RNA-seq) and high-resolution chromosomal microarray (CMA) with research-based analysis.ResultsIn 150 families, we achieved a diagnosis or strong candidate in 64 (42.7%) (37 in known genes with a consistent phenotype, 3 in known genes with a novel phenotype and 24 in novel disease genes). Fifty-four diagnoses or strong candidates were made by family ES, six by family GS with RNA-seq, two by high-resolution CMA and two by data reanalysis.ConclusionWe share our lessons learnt from the programme. Flexible implementation of multiple strategies allowed for scalability and response to the availability of new technologies. Broad implementation of family ES with research-based analysis showed promising yields post a negative clinical singleton ES. RNA-seq offered multiple benefits in family ES-negative populations. International data sharing strategies were critical in facilitating collaborations to establish novel disease–gene associations. Finally, the integrated approach of a multiskilled, multidisciplinary team was fundamental to having diverse perspectives and strategic decision-making.
Bi-allelic loss-of-function variants inKIF21Acause severe fetal akinesia with arthrogryposis multiplex
Authors: Falb Ruth J , Müller Amelie J , Klein Wolfram , Grimmel Mona , Grasshoff Ute , Spranger Stephanie , Stöbe Petra , Gauck Darja , Kuechler Alma , Dikow Nicola , Schwaibold Eva M C , Schmidt Christoph , Averdunk Luisa , Buchert Rebecca , Heinrich Tilman , Prodan Natalia , Park Joohyun , Kehrer Martin , Sturm Marc , Kelemen Olga , Hartmann Silke , Horn Denise , Emmerich Dirk , Hirt Nina , Neumann Armin , Kristiansen Glen , Gembruch Ulrich , Haen Susanne , Siebert Reiner , Hentze Sabine , Hoopmann Markus , Ossowski Stephan , Waldmüller Stephan , Beck-Wödl Stefanie , Gläser Dieter , Tekesin Ismail , Distelmaier Felix , Riess Olaf , Kagan Karl-Oliver , Dufke Andreas , Haack Tobias B 
Published: November 2021

BackgroundFetal akinesia (FA) results in variable clinical presentations and has been associated with more than 166 different disease loci. However, the underlying molecular cause remains unclear in many individuals. We aimed to further define the set of genes involved.MethodsWe performed in-depth clinical characterisation and exome sequencing on a cohort of 23 FA index cases sharing arthrogryposis as a common feature.ResultsWe identified likely pathogenic or pathogenic variants in 12 different established disease genes explaining the disease phenotype in 13 index cases and report 12 novel variants. In the unsolved families, a search for recessive-type variants affecting the same gene was performed; and in five affected fetuses of two unrelated families, a homozygous loss-of-function variant in thekinesin family member 21Agene (KIF21A) was found.ConclusionOur study underlines the broad locus heterogeneity of FA with well-established and atypical genotype–phenotype associations. We describeKIF21Aas a new factor implicated in the pathogenesis of severe neurogenic FA sequence with arthrogryposis of multiple joints, pulmonary hypoplasia and facial dysmorphisms. This hypothesis is further corroborated by a recent report on overlapping phenotypes observed in Kif21a null piglets.
Sexual exposure and sexual behaviour in the interval between gonorrhoea treatment and test of cure: a cross-sectional cohort study
Authors: Ayinde Oluseyi , Ross Jonathan D C 
Published: November 2021

ObjectivesWe explored sexual contact in the interval between the treatment for gonorrhoea and attending for a test of cure (ToC) and identified factors associated with sexual contact in this period.MethodsMultivariable analysis of demographic, behavioural and clinical data with self-reported sexual contact prior to attending for a gonorrhoea ToC evaluation among participants recruited into the ‘Gentamicin for the Treatment of Gonorrhoea’ trial in England, between October 2014 and November 2016. Associations with sexual contact were expressed as prevalence ratios (PR) and their corresponding 95% CI.ResultsThe median time to ToC was 15 days (interquartile range 14–20 days). 197/540 (37%) participants reported sexual contact in the time between treatment and ToC. Of these, 173/197 (88%) participants reported inconsistent condom use, including with previous partners (133/197 (68%)). A history of gonorrhoea (adjusted PR (aPR) 1.32 (1.03 to 1.69)) or syphilis (aPR 1.19 (1.08 to 1.32)), being in regular (aPR 1.71 (1.41 to 2.09)) sexual relationships, high number of partners in the last 3 months (aPR 1.77 (1.25 to 2.51))—‘more than 5 partners’ vs ‘0 to 1 partner’, and attending for a ToC more than 14 days after treatment (aPR 1.40 (1.08 to 1. 81)) were associated with reporting sexual contact before the ToC appointment. However, age (aPR (1.00 (0.99 to 1.01)) and presenting with specific symptoms at baseline (aPR 1.17 (0.95 to 1.44)) were not associated with sexual contact by the ToC attendance.ConclusionSexual activity after receiving treatment for gonorrhoea and prior to a ToC evaluation was common. This was associated with previous infection history and specific behavioural characteristics. Knowledge of these factors can help guide safe sex counselling at the time of treatment.
Weed emergence and seedbank after three years of repetitive shallow cultivation in a muck soil field
Authors: Simard Marie-Josée , Nurse Robert E. , Minville Audrey-Kim , Maheux Lydia , Laforest Martin , Obeid Kristen 
Published: November 2021

Frequent cultivation is often used to control weeds in crops such as lettuce. The efficacy of this technique on weed populations has been evaluated, but the effect on weed emergence and seedbanks is less documented. Studies in mineral soil indicate that soil disturbance can increase both weed emergence and seed persistence depending on where seeds are redistributed in the soil profile. Evaluations done in muck soil are scarce. This study evaluated the effect of two and four repetitive shallow (3.4 to 7.1 cm deep) cultivations on weed emergence and the weed seedbank in muck soil. Cultivation treatments (0, 2, and 4 cultivations using a inter-row rototiller) were done in lettuce plots from 2017 to 2019. Weed density was evaluated by species before each cultivation date and after crop harvest. Viable seedbanks were evaluated by collecting soil samples before and after each growing season and placing them in greenhouse flats. Statistical analyses were based on mixed models. Results showed that shallow cultivation modified the emergence patterns of weeds but did not reduce total emergence during the subsequent years or viable seedbanks. After two seasons without seed inputs, total emergence was reduced by 46.6% and the seedbank was reduced by 31.7% regardless of the cultivation treatment. However, the seedbank of the very abundant common purslane (Portulaca oleracea) remained high.