bluuebunny/crossref_metadata_2025_split huggingface dataset:
Childhood seizures after prenatal exposure to maternal influenza infection: a population-based cohort study from Norway, Australia and Canada
Authors: Oakley Laura L , Regan Annette K , Fell Deshayne B , Spruin Sarah , Bakken Inger Johanne , Kwong Jeffrey C , Pereira Gavin , Nassar Natasha , Aaberg Kari M , Wilcox Allen J , Håberg Siri E 
Published: June 2021

ObjectiveTo assess whether clinical and/or laboratory-confirmed diagnosis of maternal influenza during pregnancy increases the risk of seizures in early childhood.DesignAnalysis of prospectively collected registry data for children born between 2009 and 2013 in three high-income countries. We used Cox regression to estimate country-level adjusted HRs (aHRs); fixed-effects meta-analyses were used to pool adjusted estimates.SettingPopulation-based.Participants1 360 629 children born between 1 January 2009 and 31 December 2013 in Norway, Australia (New South Wales) and Canada (Ontario).ExposureClinical and/or laboratory-confirmed diagnosis of maternal influenza infection during pregnancy.Main outcome measuresWe extracted data on recorded seizure diagnosis in secondary/specialist healthcare between birth and up to 7 years of age; additional analyses were performed for the specific seizure outcomes ‘epilepsy’ and ‘febrile seizures’.ResultsAmong 1 360 629 children in the study population, 14 280 (1.0%) were exposed to maternal influenza in utero. Exposed children were at increased risk of seizures (aHR 1.17, 95% CI 1.07 to 1.28), and also febrile seizures (aHR 1.20, 95% CI 1.07 to 1.34). There was no strong evidence of an increased risk of epilepsy (aHR 1.07, 95% CI 0.81 to 1.41). Risk estimates for seizures were higher after influenza infection during the second and third trimester than for first trimester.ConclusionsIn this large international study, prenatal exposure to influenza infection was associated with increased risk of childhood seizures.
Dutch multidisciplinary guideline on Achilles tendinopathy
Authors: de Vos Robert-Jan , van der Vlist Arco C , Zwerver Johannes , Meuffels Duncan Edward , Smithuis Frank , van Ingen Ronald , van der Giesen Florus , Visser Edwin , Balemans Astrid , Pols Margreet , Veen Natasja , den Ouden Mirre , Weir Adam 
Published: June 2021

ObjectiveTo provide a comprehensive, evidence-based overview of the risk factors, prevention, diagnosis, imaging, treatment and prognosis for Achilles tendinopathy. To make clinical recommendations for healthcare practitioners and patients.DesignComprehensive multidisciplinary guideline process funded by the Quality Foundation of the Dutch Federation of Medical Specialists. This process included a development, commentary and authorisation phase. Patients participated in every phase.Data sourcesMultiple databases and existing guidelines were searched up to May 2019. Information from patients, healthcare providers and other stakeholders were obtained using a digital questionnaire, focus group interview and invitational conference.Study eligibility criteriaStudies on both insertional and/or midportion Achilles tendinopathy were eligible. Specific eligibility criteria were described per module.Data extraction and synthesisTo appraise the certainty of evidence, reviewers extracted data, assessed risk of bias and used the Grading of Recommendations Assessment, Development and Evaluation method, where applicable. Important considerations were: patient values and preferences, costs, acceptability of other stakeholders and feasibility of implementation. Recommendations were made based on the results of the evidence from the literature and the considerations.Primary outcome measureThe primary and secondary outcome measures were defined per module and defined based on the input of patients obtained in collaboration with the Netherlands Patient Federation and healthcare providers from different professions.ResultsSix specific modules were completed: risk factors and primary prevention, diagnosis, imaging, treatment prognosis and secondary prevention for Achilles tendinopathy.Summary/conclusionOur Dutch multidisciplinary guideline on Achilles tendinopathy provides six modules developed according to the standards of the Dutch Federation of Medical Specialists. Evidence-based recommendations for clinical practice are given for risk factors, prevention, diagnosis, imaging, treatment and prognosis. This guideline can assist healthcare providers and patients in clinical practice.
Randomised controlled trial to establish the clinical and cost-effectiveness of expectant management versus preoperative imaging with magnetic resonance cholangiopancreatography in patients with symptomatic gallbladder disease undergoing laparoscopic cholecystectomy at low or moderate risk of common bile duct stones (The Sunflower Study): a study protocol
Authors: Clout Madeleine , Blazeby Jane , Rogers Chris , Reeves Barnaby , Lazaroo Michelle , Avery Kerry , Blencowe Natalie S , Vohra Ravi , Jennings Neil , Hollingworth William , Thorn Joanna , Jepson Marcus , Collingwood Jane , Guthrie Ashley , Booth Elizabeth , Pathak Samir , Beckingham Ian , Culliford Lucy , Griffiths Ewen A , Albazaz Raneem , Toogood Giles 
Published: June 2021

IntroductionSurgery to remove the gallbladder (laparoscopic cholecystectomy (LC)) is the standard treatment for symptomatic gallbladder disease. One potential complication of gallbladder disease is that gallstones can pass into the common bile duct (CBD) where they may remain dormant, pass spontaneously into the bowel or cause problems such as obstructive jaundice or pancreatitis. Patients requiring LC are assessed preoperatively for their risk of CBD stones using liver function tests and imaging. If the risk is high, guidelines recommend further investigation and treatment. Further investigation of patients at low or moderate risk of CBD stones is not standardised, and the practice of imaging the CBD using magnetic resonance cholangiopancreatography (MRCP) in these patients varies across the UK. The consequences of these decisions may lead to overtreatment or undertreatment of patients.Methods and analysisWe are conducting a UK multicentre, pragmatic, open, randomised controlled trial with internal pilot phase to compare the effectiveness and cost-effectiveness of preoperative imaging with MRCP versus expectant management (ie, no preoperative imaging) in adult patients with symptomatic gallbladder disease undergoing urgent or elective LC who are at low or moderate risk of CBD stones. We aim to recruit 13 680 patients over 48 months. The primary outcome is any hospital admission within 18 months of randomisation for a complication of gallstones. This includes complications of endoscopic retrograde cholangiopancreatography for the treatment of gallstones and complications of LC. This will be determined using routine data sources, for example, National Health Service Digital Hospital Episode Statistics for participants in England. Secondary outcomes include cost-effectiveness and patient-reported quality of life, with participants followed up for a median of 18 months.Ethics and disseminationThis study received approval from Yorkshire & The Humber – South Yorkshire Research Ethics Committee. Results will be submitted for publication in a peer-reviewed journal.Trial registration numberISRCTN10378861.
Effect of an online healthy lifestyle psychoeducation programme to improve cardiometabolic outcomes and affective symptoms in youth receiving mental health care: study protocol for a pilot clinical trial.
Authors: Wilson Chloe , Nichles Alissa , Zmicerevska Natalia , Carpenter Joanne Sarah , Song Yun Ju Christine , McHugh Catherine , Hamilton Blake , Hockey Samuel , Scott Elizabeth M , Hickie Ian B 
Published: June 2021

IntroductionWorsened cardiometabolic profiles in youth with mental ill health have been associated with a number of modifiable lifestyle risk factors. It is becoming increasingly evident that clinical interventions need to be multimodal in focus to improve mental health symptoms and the physical health symptoms in this already at-risk cohort.Methods and analysisThis 12-week pilot clinical trial examines the efficacy, feasibility and acceptability of an adjunctive online psychoeducation programme for improving cardiometabolic risk parameters and affective symptoms in a transdiagnostic sample of at least 44 young people aged 16–25 years presenting for mental healthcare for mood and/or psychotic syndromes (including anxiety, depression, bipolar disorder and psychosis). Individuals will be invited to participate in a pilot clinical trial for a structured online psychoeducation programme incorporating nutritional, physical activity, sleep–wake and healthy lifestyle information, delivered fortnightly over six online modules. Participants will undergo a series of assessments including: (1) self-report and clinician administered assessments determining mental health symptomatology; (2) fasting blood tests to assess cardiometabolic markers (fasting insulin, fasting glucose and blood lipids); (3) anthropometric assessments (height, weight, waist circumference and blood pressure); and (4) sleep–wake behaviours and circadian rhythm assessments. Changes in scores for all cardiometabolic and affective measures will be assessed via paired samples t-tests, and correlations between change scores will be assessed via Pearson’s or Spearman’s correlations. Feasibility will be assessed via completion rates, and the acceptability of the programme will be assessed via programme satisfaction measures.Ethics and disseminationThis pilot clinical trial has been approved by the Sydney Local Health District Research Ethics and Governance Office (X20-0228 & 2020/ETH01201). The results of this pilot clinical trial will be disseminated into the scientific and broader community through peer-reviewed journals, conference presentations, social media and university websites.Trial registration numberAustralian New Zealand Clinical Trials Registry (ANZCTR) Number: ACTRN12620000772943, Date 28 August 2020.
Efficacy and safety of nintedanib in Japanese patients with early-stage idiopathic pulmonary fibrosis: a study protocol for an observational study
Authors: Sakamoto Noriho , Hamada Naoki , Okamoto Masaki , Tobino Kazunori , Ichiyasu Hidenori , Ishii Hiroshi , Ichikado Kazuya , Morimoto Shimpei , Hosogaya Naoki , Mukae Hiroshi 
Published: June 2021

IntroductionIdiopathic pulmonary fibrosis (IPF) is a fibrotic disease of unknown aetiology with a poor prognosis. Several clinical trials of nintedanib in patients with IPF have reported its inhibitory effect on reduced lung function, incidence of acute exacerbation of IPF and worsened health-related quality of life. Although nintedanib has a manageable safety and tolerability profile over long-term use, it was discontinued in over 20% of patients because of adverse events such as diarrhoea and liver dysfunction. This might explain why nintedanib use in patients with IPF is not widespread, especially among patients with early-stage IPF. In the present study, we aimed to clarify the efficacy, safety and tolerability of nintedanib in patients with stage I/II IPF, based on the Japanese IPF disease severity staging classification system.Methods and analysisThis is an ongoing, prospective, multicentre observational cohort study of patients with stage I/II IPF who will start receiving nintedanib. Totally, 215 patients at 35 sites in Kyushu and Okinawa, Japan will be enrolled and followed up for 3 years. Nintedanib therapy would be initiated at the discretion of the investigator. The primary endpoint, change in forced vital capacity (FVC) at 156 weeks, will be shown as the mean change in FVC from baseline to week 156 with 95% CIs estimated using the Wald method. The safety endpoint—occurrence of adverse events—will be assessed in each system organ class/preferred term.Ethics and disseminationThe study protocol and informed consent documents were approved by the Institutional Review Board at Nagasaki University Hospital (approval number 19102146) and each participating site. Written informed consent was obtained from all participants. Patient recruitment has begun. The results will be disseminated through scientific peer-reviewed publications and national and international conferences.Trial registration numberUMIN000038192.
Immersive technology in ophthalmology education: a systematic review
Authors: Lowe Shakeel , Mares Kathryn , Khadjesari Zarnie 
Published: June 2021

BackgroundDespite the increasing use of immersive technology (IT) in ophthalmology, the effectiveness of this approach compared to other teaching practices is unclear. This systematic review aimed to determine the value of IT to teach students ophthalmic skills and whether it can supplement or replace conventional teaching practices.MethodsA systematic search was performed of CENTRAL, MEDLINE, EMBASE, ERIC and PsychINFO databases. Randomised controlled trials comparing IT interventions versus (1) no training, (2) standard training, (3) different types of IT interventions, (4) different doses of IT interventions were eligible for inclusion.ResultsSeven trials involving 177 participants were included. IT offered some benefit compared to standard training as most trials demonstrated evidence of learning represented by composite performance score and performance time. Repetitive training with IT displayed similar results.ConclusionIT appears to improve the ophthalmic skill of healthcare trainees and should be considered as a supplement to training.
Heterogeneity of reasons for attendance in frequent attenders of emergency departments and its relationship to future attendance
Authors: Hotham Richard , O'Keeffe Colin , Stone Tony , Mason Suzanne M , Burton Christopher 
Published: June 2021

BackgroundEDs globally are under increasing pressure through rising demand. Frequent attenders are known to have complex health needs and use a disproportionate amount of resources. We hypothesised that heterogeneity of patients’ reason for attendance would be associated with multimorbidity and increasing age, and predict future attendance.MethodWe analysed an anonymised dataset of all ED visits over the course of 2014 in Yorkshire, UK. We identified 15 986 patients who had five or more ED encounters at any ED in the calendar year. Presenting complaint was categorised into one of 14 categories based on the Emergency Care Data Set (ECDS). We calculated measures of heterogeneity (count of ECDs categories and entropy of categories) and examined their relationship to total number of ED visits and to patient characteristics. We examined the predictive value of these and other features on future attendance.ResultsMost frequent attenders had more than one presenting complaint type. Heterogeneity increased with number of attendances, but heterogeneity adjusted for number of attendances did not vary substantially with age or sex. Heterogeneity was associated with the presence of one or more contacts for a mental health problem. For a given number of attendances, prior mental health contact but not heterogeneity was associated with further attendance.ConclusionsHeterogeneity of presenting complaint can be quantified and analysed for ED use: it is increased where there is a history of mental disorder but not with age. This suggests it reflects more than the number of medical conditions.
Airborne infection risk during open-air cardiopulmonary resuscitation
Authors: Dbouk Talib , Aranda-García Silvia , Barcala-Furelos Roberto , Rodríguez-Núñez Antonio , Drikakis Dimitris 
Published: June 2021

AimCardiopulmonary resuscitation (CPR) is an emergency procedure where interpersonal distance cannot be maintained. There are and will always be outbreaks of infection from airborne diseases. Our objective was to assess the potential risk of airborne virus transmission during CPR in open-air conditions.MethodsWe performed advanced high-fidelity three-dimensional modelling and simulations to predict airborne transmission during out-of-hospital hands-only CPR. The computational model considers complex fluid dynamics and heat transfer phenomena such as aerosol evaporation, breakup, coalescence, turbulence, and local interactions between the aerosol and the surrounding fluid. Furthermore, we incorporated the effects of the wind speed/direction, the air temperature and relative humidity on the transport of contaminated saliva particles emitted from a victim during a resuscitation process based on an Airborne Infection Risk (AIR) Index.ResultsThe results reveal low-risk conditions that include wind direction and high relative humidity and temperature. High-risk situations include wind directed to the rescuer, low humidity and temperature. Combinations of other conditions have an intermediate AIR Index and risk for the rescue team.ConclusionsThe fluid dynamics, simulation-based AIR Index provides a classification of the risk of contagion by victim’s aerosol in the case of hands-only CPR considering environmental factors such as wind speed and direction, relative humidity and temperature. Therefore, we recommend that rescuers perform a quick assessment of their airborne infectious risk before starting CPR in the open air and positioning themselves to avoid wind directed to their faces.
Natriuretic peptide level at heart failure diagnosis and risk of hospitalisation and death in England 2004–2018
Authors: Taylor Clare J , Lay-Flurrie Sarah L , Ordóñez-Mena José M , Goyder Clare R , Jones Nicholas R , Roalfe Andrea K , Hobbs FD Richard 
Published: June 2021

ObjectiveHeart failure (HF) is a malignant condition requiring urgent treatment. Guidelines recommend natriuretic peptide (NP) testing in primary care to prioritise referral for specialist diagnostic assessment. We aimed to assess association of baseline NP with hospitalisation and mortality in people with newly diagnosed HF.MethodsPopulation-based cohort study of 40 007 patients in the Clinical Practice Research Datalink in England with a new HF diagnosis (48% men, mean age 78.5 years). We used linked primary and secondary care data between 1 January 2004 and 31 December 2018 to report one-year hospitalisation and 1-year, 5-year and 10-year mortality by NP level.Results22 085 (55%) participants were hospitalised in the year following diagnosis. Adjusted odds of HF-related hospitalisation in those with a high NP (NT-proBNP >2000 pg/mL) were twofold greater (OR 2.26 95% CI 1.98 to 2.59) than a moderate NP (NT-proBNP 400–2000 pg/mL). All-cause mortality rates in the high NP group were 27%, 62% and 82% at 1, 5 and 10 years, compared with 19%, 50% and 77%, respectively, in the moderate NP group and, in a competing risks model, risk of HF-related death was 50% higher at each timepoint. Median time between NP test and HF diagnosis was 101 days (IQR 19–581).ConclusionsHigh baseline NP is associated with increased HF-related hospitalisation and poor survival. While healthcare systems remain under pressure from the impact of COVID-19, research to test novel strategies to prevent hospitalisation and improve outcomes—such as a mandatory two-week HF diagnosis pathway—is urgently needed.
Multiple sclerosis: structural and functional integrity of the visual system following alemtuzumab therapy
Authors: Wang Chenyu , Barton Joshua , Kyle Kain , Ly Linda , Barnett Yael , Hartung Hans-Peter , Reddel Stephen W , Beadnall Heidi , Taha Marinda , Klistorner Alexander , Barnett Michael Harry 
Published: June 2021

ObjectiveTo investigate potential neuroprotective and pro-remyelinating effects of alemtuzumab in multiple sclerosis (MS), using the visual pathway as a model.MethodsWe monitored clinical, multifocal visual evoked potential (mfVEP) and MRI outcomes in 30 patients commencing alemtuzumab for relapsing MS, and a reference group of 20 healthy controls (HCs), over 24 months. Change in mfVEP latency was the primary endpoint; change in optic radiation (OR) lesion diffusion metrics and Mars letter contrast sensitivity over the course of the study were secondary endpoints.ResultsIn patients, we observed a mean shortening of mfVEP latency of 1.21 ms over the course of the study (95% CI 0.21 to 2.21, p=0.013), not altered by correction for age, gender, disease duration or change in OR T2 lesion volume. Mean mfVEP latency in the HC group increased over the course of the study by 0.72 ms (not significant). Analysis of chronic OR T2 lesions (patients) showed an increase in normalised fractional anisotropy and axial diffusivity between baseline and 24 months (both p<0.01). Mean Mars letter contrast sensitivity was improved at 24 months vs baseline (p<0.001), and driven by an early improvement, in both patients and HC.ConclusionWe found evidence of partial lesion remyelination after alemtuzumab therapy, indicating either natural restoration in the context of a ‘permissive’ local milieu; or potentially an independent, pro-reparative mechanism of action. The visual system presents a unique opportunity to study function-structure specific effects of therapy and inform the design of future phase 2 MS remyelination trials.
GFAP as a biomarker in frontotemporal dementia and primary psychiatric disorders: diagnostic and prognostic performance
Authors: Katisko Kasper , Cajanus Antti , Huber Nadine , Jääskeläinen Olli , Kokkola Tarja , Kärkkäinen Virve , Rostalski Hannah , Hartikainen Paivi , Koivisto Anne M , Hannonen Sanna , Lehtola Juha-Matti , Korhonen Ville E , Helisalmi Seppo , Koivumaa-Honkanen Heli , Herukka Sanna-Kaisa , Remes Anne M , Solje Eino , Haapasalo Annakaisa 
Published: June 2021

BackgroundFrontotemporal lobar degeneration (FTLD) and primary psychiatric disorders (PPD) are characterised by overlapping clinical features but different aetiologies. Here, we assessed for the first time the potential of blood glial fibrillar acidic protein (GFAP), marker of astrogliosis, as a discriminative and prognostic tool in FTLD and PPD.MethodsThe levels of GFAP in serum (sGFAP) of patients with FTLD (N=107) and PPD (N=44) and GFAP in whole blood samples (bGFAP) from FTLD (N=10), PPD (N=10) and healthy controls (N=18) were measured. We evaluated whether the sGFAP levels associate with C9orf72 repeat expansion, survival of FTLD and PPD patients, and brain atrophy assessed cross-sectionally and longitudinally by structural T1W MRI. We also examined the correlation between sGFAP and bGFAP levels in a subset of patients.ResultssGFAP and bGFAP levels were elevated in the FTLD group compared with the PPD or control groups. Receiver operating characteristic analysis indicated an excellent diagnostic performance between FTLD and PPD (the area under the curve (AUC)=0.820, 95% CI 0.745 to 0.896). sGFAP and bGFAP levels showed a strong correlation and elevated sGFAP levels significantly associated with atrophy rate in the temporal cortex and predicted shorter survival time in patients with FTLD. No association with C9orf72 repeat expansion was detected.ConclusionssGFAP enabled differentiation of patients with FTLD and PPD and associated with shorter survival and more severe brain atrophy rate in patients with FTLD. These results suggest that blood-based GFAP represents a minimally invasive and useful biomarker in the differential diagnostics between patients with FTLD and PPD and in evaluating disease progression and astrogliosis in FTLD.