bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for the development of a core outcome set for cauda equina syndrome: systematic literature review, qualitative interviews, Delphi survey and consensus meeting
Authors: Srikandarajah Nisaharan , Noble Adam J , Wilby Martin , Clark Simon , Williamson Paula R , Marson Anthony Guy 
Published: May 2019

IntroductionCauda equina syndrome (CES) is a serious neurological condition most commonly due to compression of the lumbosacral nerve roots, which can result in significant disability. The evidence for acute intervention in CES is mainly from retrospective studies. There is heterogeneity in the outcomes chosen for analysis in these studies, which makes it difficult to synthesise the data across studies. This study will develop a core outcome set for use in future studies of CES, engaging with key stakeholders and using transparent methodology. This will help ensure that relevant outcomes are used in future and will facilitate attempts to summarise data across studies in systematic reviews.Methods and analysisA systematic literature review will document all the outcomes for CES after surgery mentioned in the literature. The qualitative interviews with patients with CES will be semistructured, audio recorded, transcribed and thematically analysed with the use of NVivo V.10 to identify outcomes and determine the themes described. The outcomes from the literature review and patient interviews will be combined and prioritised to determine what the most important outcomes are in CES research studies to patients and healthcare professionals. The prioritisation will be done through a two-round iterative Delphi survey and a consensus meeting. This process will decide the core outcome set for patients with CES.Ethics and disseminationREC and HRA approval was obtained on the 6/12/16 for the qualitative interviews from South Central—Hampshire A REC. REC reference 16/SC/0587. REC and HRA approval was obtained on 26/3/18 for the Delphi process and consensus meeting from North West—Greater Manchester Central REC. REC reference was 18/NW/0022. The final core outcome set will be published and freely available.Trial registration numberThis study is registered with the Core Outcome Measures in Effectiveness Trials database as study 824.
Is neutrophil CD11b a special marker for the early diagnosis of sepsis in neonates? A systematic review and meta-analysis
Authors: Qiu Xia , Li Jinhui , Yang Xiaoyan , Tang Jun , Shi Jing , Tong Yu , Qu Yi , Mu Dezhi 
Published: May 2019

ObjectivesOur study aimed to synthesise and analyse the early diagnostic value of neutrophil CD11b (nCD11b) for neonatal sepsis.DesignSystematic review and meta-analysis.MethodsPubmed, Embase, the Cochrane Library and Web of Science Databases were searched up to June 2018. We used Stata software (V.14.0) to conduct the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic OR (DOR), pretest probability, post-test probability and summary receiver operating characteristic (SROC) curve for diagnostic efficiency of n CD11b.ResultsNine studies, accounting for 843 neonates, were included. The overall pooled sensitivity, specificity, PLR, NLR, DOR, post-test positive probability and post-test negative probability and the area under the SROC curve were 0.82 (95% CI 0.71 to 0.90), 0.93 (95% CI 0.62 to 0.99), 11.51 (95% CI 1.55 to 85.62), 0.19 (95% CI 0.10 to 0.36), 59.50 (95% CI 4.65 to 761.58), 74%, 5% and 0.90, which had accuracy in diagnosing neonatal sepsis.ConclusionThe present evidence indicated that nCD11b is a promising biomarker for the early diagnosis of neonatal sepsis.
Gestational route to healthy birth (GaRBH): protocol for an Indian prospective cohort study
Authors: Gupta Vipin , Saxena Ruchi , Walia Gagandeep Kaur , Agarwal Tripti , Vats Harsh , Dunn Warwick , Relton Caroline , Sovio Ulla , Papageorghiou Aris , Davey Smith George , Khadgawat Rajesh , Sachdeva Mohinder Pal 
Published: May 2019

IntroductionPregnancy is characterised by a high rate of metabolic shifts from early to late phases of gestation in order to meet the raised physiological and metabolic needs. This change in levels of metabolites is influenced by gestational weight gain (GWG), which is an important characteristic of healthy pregnancy. Inadequate/excessive GWG has short-term and long-term implications on maternal and child health. Exploration of gestational metabolism is required for understanding the quantitative changes in metabolite levels during the course of pregnancy. Therefore, our aim is to study trimester-specific variation in levels of metabolites in relation to GWG and its influence on fetal growth and newborn anthropometric traits at birth.Methods and analysisA prospective longitudinal study is planned (start date: February 2018; end date: March 2023) on pregnant women that are being recruited in the first trimester and followed in subsequent trimesters and at the time of delivery (total 3 follow-ups). The study is being conducted in a hospital located in Bikaner district (66% rural population), Rajasthan, India. The estimated sample size is of 1000 mother-offspring pairs. Information on gynaecological and obstetric history, socioeconomic position, diet, physical activity, tobacco and alcohol consumption, depression, anthropometric measurements and blood samples is being collected for metabolic assays in each trimester using standardised methods. Mixed effects regression models will be used to assess the role of gestational weight in influencing metabolite levels in each trimester. The association of maternal levels of metabolites with fetal growth, offspring’s weight and body composition at birth will be investigated using regression modelling.Ethics and disseminationThe study has been approved by the ethics committees of the Department of Anthropology, University of Delhi and Sardar Patel Medical College, Rajasthan. We are taking written informed consent after discussing the various aspects of the study with the participants in the local language.
Influenza-like illness and antimicrobial prescribing in Australian general practice from 2015 to 2017: a national longitudinal study using the MedicineInsight dataset
Authors: Bernardo Carla De Oliveira , Gonzalez-Chica David , Stocks Nigel 
Published: May 2019

ObjectivesTo investigate the epidemiology of influenza-like illness (ILI) by general practice and patient characteristics, and explore whether sociodemographic variables or comorbidities affect antiviral or antibiotic prescribing.DesignOpen cohort study.SettingA representative sample of 550 Australian general practices contributing data to the MedicineInsight programme.Participants4 228 149 patients of all age groups who had at least one consultation between 2015 and 2017. Median age was 37 years (Interquartile range: 21–57), 54.4% women, 16.4% aged ≥65 years, 2.2% Aboriginal or Torres Strait Islander, 17.6% had a chronic disease and 18.1% a mental health condition.Primary and secondary outcome measuresILI consultation rates (per 1000 consultations) were calculated using all ILI diagnoses for all clinical encounters with a general practitioner between 2015 and 2017. Antiviral and antibiotic prescribing for ILI cases were investigated and logistic regression models adjusted for practice and patient characteristics used to analyse associations.ResultsILI consultation rates in 2017 were higher than in previous years. Antiviral prescribing increased from 20.6% in 2015, to 23.7 in 2016 and 29.7% in 2017, while antibiotic prescribing decreased from 30.3% to 28.0% and 26.7%, respectively (p<0.05 in both cases). Practices located in high socioeconomic areas had higher ILI consultation rates (4.3 vs 2.5 per 1000 consultations, p<0.05), antibiotic (30.7% vs 23.4%, p<0.05) and antiviral (34.2% vs 13.5%, p<0.05) prescribing than those in lower socioeconomic areas. The coexistence of chronic or mental health conditions was associated with lower ILI consultation rates, higher antibiotic use, but not with antiviral prescribing. However, those with chronic respiratory conditions had a higher frequency of antibiotic and antiviral prescribing in 2017 than individuals with other comorbidities.ConclusionsAlthough the apparent decline in antibiotic prescribing for ILI is welcome, the increase in antiviral use may not be targeting those at high risk of complications from infection.
Racial differences of heart failure with midrange ejection fraction (HFmrEF): a large urban centre-based retrospective cohort study in the USA
Authors: Li Dan Leslie , Quispe Renato , Onyekwelu Chioma , Faillace Robert T , Taub Cynthia C 
Published: May 2019

ObjectivesWe aimed to study the racial differences in clinical presentations, survival outcomes and outcome predictors among patients with heart failure (HF) with midrange ejection fraction (HFmrEF, EF 40%–49%).DesignThis is a retrospective study.SettingAdults with HF diagnosis at Montefiore Medical Center, Bronx, New York between 2008 and 2012, with an inpatient echocardiogram showing left ventricular ejection fraction of 40%–49% were included as HFmrEF population.Participants1,852 HFmrEF patients are included in the study (56% male, mean age 67 years). There were 493 (26.5%) non-Hispanic whites, 541 (29.2%) non-Hispanic black, 489 (26.4%) Hispanics and 329 (17.8%) other racial populations.Outcome measuresCumulative probabilities of all-cause mortality among different racial groups were estimated and multivariable adjusted Cox proportional regressions were performed to assess predictors of mortality.ResultsAmong the HFmrEF patients, white patients were older and were less likely to be on guideline-directed medications. Blacks had a lower prevalence of prior myocardial infarction comparing to other groups. Hispanics had more chronic diseases and yet better survival comparing to whites and blacks after adjustment for age, sex and comorbidities. Distinct sets of survival predictors were revealed in individual racial groups. Baseline use of mineralocorticoid receptor antagonist (MRA) was associated with lower mortality among HFmrEF patients in general (HR 0.61, 95% CI 0.37 to 0.99).ConclusionsThere are significant racial/ethnic differences in clinical phenotypes, survival outcomes and mortality predictors of HFmrEF. Furthermore, the use of MRA predicted a reduced mortality in HFmrEF patients.
Protocol for a controlled human infection with genetically modifiedNeisseria lactamicaexpressing the meningococcal vaccine antigen NadA: a potent new technique for experimental medicine
Authors: Gbesemete Diane , Laver Jay Robert , de Graaf Hans , Ibrahim Muktar , Vaughan Andrew , Faust Saul , Gorringe Andrew , Read Robert Charles 
Published: May 2019

IntroductionNeisseria lactamicais a commensal organism found in the human nasopharynx and is closely related to the pathogenN. meningitidis(meningococcus). Carriage ofN. lactamicais associated with reduced meningococcal carriage and disease. We summarise an ethically approved protocol for an experimental human challenge study using a genetically modified strain ofN. lactamicathat expresses the meningococcal antigen NadA. We aim to develop a model to study the role of specific bacterial antigens in nasopharyngeal carriage and immunity, to evaluate vaccines for their efficacy in preventing colonisation and to provide a proof of principle for the development of bacterial medicines.Methods and analysisHealthy adult volunteers aged 18–45 years will receive an intranasal inoculation of either the NadA containing strain ofN. lactamicaor a genetically modified, but wild-type equivalent control strain. These challenge volunteers will be admitted for 4.5 days observation following inoculation and will then be discharged with strict infection control rules. Bedroom contacts of the challenge volunteers will also be enrolled as contact volunteers. Safety, colonisation, shedding, transmission and immunogenicity will be assessed over 90 days after which carriage will be terminated with antibiotic eradication therapy.Ethics and disseminationThis study has been approved by the Department for Environment, Food and Rural Affairs and South Central Oxford A Research Ethics Committee (reference: 18/SC/0133). Findings will be published in peer-reviewed open-access journals as soon as possible.Trial registration numberNCT03630250; Pre-results.
Genetic associations between genes in the renin-angiotensin-aldosterone system and renal disease: a systematic review and meta-analysis
Authors: Smyth Laura Jane , Cañadas-Garre Marisa , Cappa Ruaidhri C , Maxwell Alexander P , McKnight Amy Jayne 
Published: May 2019

BackgroundChronic kidney disease (CKD) is defined by abnormalities in kidney structure and/or function present for more than 3 months. Worldwide, both the incidence and prevalence rates of CKD are increasing. The renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance through the kidney. RAAS activation is associated with hypertension, which is directly implicated in causation and progression of CKD. RAAS blockade, using drugs targeting individual RAAS mediators and receptors, has proven to be renoprotective.ObjectivesTo assess genomic variants present within RAAS genes,ACE,ACE2,AGT,AGTR1,AGTR2andREN, for association with CKD.Design and data sourcesA systematic review and meta-analysis of observational research was performed to evaluate the RAAS gene polymorphisms in CKD using both PubMed and Web of Science databases with publication date between the inception of each database and 31 December 2018. Eligible articles included case–control studies of a defined kidney disease and included genotype counts.Eligibility criteriaAny paper was removed from the analysis if it was not written in English or Spanish, was a non-human study, was a paediatric study, was not a case–control study, did not have a renal disease phenotype, did not include data for the genes, was a gene expression-based study or had a pharmaceutical drug focus.ResultsA total of 3531 studies were identified, 114 of which met the inclusion criteria. Genetic variants reported in at least three independent publications for populations with the same ethnicity were determined and quantitative analyses performed. Three variants returned significant results in populations with different ethnicities at p<0.05:ACEinsertion,AGTrs699-T allele andAGTR1rs5186-A allele; each variant was associated with a reduced risk of CKD development.ConclusionsFurther biological pathway and functional analyses of the RAAS gene polymorphisms will help define how variation in components of the RAAS pathway contributes to CKD.
Impact of persistent anaemia on mortality in patients hospitalised with acute pulmonary embolism: an Australian retrospective observational study
Authors: Chow Wallace , Wong Christopher , Lau Jerrett K , Chow Vincent , Kritharides Leonard , Ng Austin C C 
Published: May 2019

ObjectivesAnaemia is associated with increased mortality in acute pulmonary embolism (PE) patients. However, prior studies have not examined the prognostic impact of trends in plasma haemoglobin during admission. This study investigates the impact of changes in haemoglobin level on mortality during hospital stay in acute PE.Study designA retrospective observational study.SettingTertiary-referral centre in Australia.ParticipantsConsecutive patients from 2000 to 2012 admitted with confirmed acute PE were identified from a dedicated PE database. Haemoglobin levels on days 1, 3–4, 5–6 and 7 of admission were retrieved. Patients without both baseline haemoglobin and subsequent haemoglobin levels were excluded (n=327), leaving 1099 patients as the study cohort. Anaemia was defined as haemoglobin <130 g/L for men and <120 g/L for women. There were 576 patients without anaemia throughout admission, 65 with transient anaemia (anaemic on day 1, but subsequently normalised during admission), 122 with acquired anaemia (normal on day 1 but developed anaemia during admission) and 336 with persistent anaemia. A total of 71 patients received blood transfusion during admission.Main outcome measure6-month mortality was tracked from a state-wide death database and analysed using multivariable modelling.ResultsAfter adjusting for transfusion, patietns with persistent anaemia had a significantly increased 6-month mortality risk (adjusted HR 1.97, 95% CI 1.26 to 3.09, p=0.003) compared with patients without anaemia. There was no difference in mortality between patients with transient or acquired anaemia and patients without anaemia.ConclusionAmong patients who had anaemia during their admission for acute PE, only the subgroup with persistent anaemia demonstrated worse outcomes.
Rationale and design of the HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) Trial: a protocol for an international randomised controlled trial evaluating early surgery for hip fracture patients
Authors: Borges Flavia K , Bhandari Mohit , Patel Ameen , Avram Victoria , Guerra-Farfán Ernesto , Sigamani Alben , Umer Masood , Tiboni Maria , Adili Anthony , Neary John , Tandon Vikas , Sancheti Parag K , Lawendy AbdelRahman , Jenkinson Richard , Ramokgopa Mmampapatla , Biccard Bruce M , Szczeklik Wojciech , Wang Chew Yin , Landoni Giovanni , Forget Patrice , Popova Ekaterine , Wood Gavin , Nabi Nur Aamer , John Bobby , Ślęczka Paweł , Feibel Robert J , Balaguer-Castro Mariano , Deheshi Benjamin , Winemaker Mitchell , de Beer Justin , Kolesar Richard , Teixidor-Serra Jordi , Tomas-Hernandez Jordi , McGillion Michael , Shanthanna Harsha , Moppett Iain , Vincent Jessica , Pettit Shirley , Harvey Valerie , Gauthier Leslie , Alvarado Kim , Devereaux P J 
Published: May 2019

IntroductionAnnually, millions of adults suffer hip fractures. The mortality rate post a hip fracture is 7%–10% at 30 days and 10%–20% at 90 days. Observational data suggest that early surgery can improve these outcomes in hip fracture patients. We designed a clinical trial—HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) to determine the effect of accelerated surgery compared with standard care on the 90-day risk of all-cause mortality and major perioperative complications.Methods and analysisHIP ATTACK is a multicentre, international, parallel group randomised controlled trial (RCT) that will include patients ≥45 years of age and diagnosed with a hip fracture from a low-energy mechanism requiring surgery. Patients are randomised to accelerated medical assessment and surgical repair (goal within 6 h) or standard care. The co-primary outcomes are (1) all-cause mortality and (2) a composite of major perioperative complications (ie, mortality and non-fatal myocardial infarction, pulmonary embolism, pneumonia, sepsis, stroke, and life-threatening and major bleeding) at 90 days after randomisation. All patients will be followed up for a period of 1 year. We will enrol 3000 patients.Ethics and disseminationAll centres had ethics approval before randomising patients. Written informed consent is required for all patients before randomisation. HIP ATTACK is the first large international trial designed to examine whether accelerated surgery can improve outcomes in patients with a hip fracture. The dissemination plan includes publishing the results in a policy-influencing journal, conference presentations, engagement of influential medical organisations, and providing public awareness through multimedia resources.Trial registration numberNCT02027896; Pre-results.
The TEAM (Trauma Evaluation and Management) course: medical student knowledge gains and retention in the USA versus Ghana
Authors: Berndtson Allison E , Morna Martin , Debrah Samuel , Coimbra Raul 
Published: May 2019

IntroductionTrauma and injury are significant contributors to the global burden of disease, with 5 million deaths and 250 million disability-adjusted life years lost in 2015. This burden is disproportionally borne by low- and middle-income countries (LMICs). Solutions are complex, but one area for improvement is basic trauma education. The American College of Surgeons has developed the Trauma Evaluation and Management (TEAM) course as an introduction to trauma care for medical students. We hypothesized that the TEAM course would be an effective educational program in LMICs and result in increased knowledge gains and retention similar to students in high-income countries (HICs).MethodsThe TEAM course was taught and students evaluated at two sites, one LMIC (Ghana) and one HIC (USA), after obtaining approval from the HIC Institutional Review Board and medical schools at both sites. Participation was optional for all students and results were de-identified. The course was administered by a single educator for all sessions. Multiple-choice exams were given before and after the course, and again 6 months later.ResultsA total of 62 LMIC and 64 HIC students participated in the course and completed initial testing. Demographics for the two groups were similar, as was participant attrition over time. LMIC students started with a relative knowledge deficit, scoring lower on both pre-course and post-course tests than HIC students, but gained more knowledge during the initial teaching session. After 6 months, the LMIC students continued to improve, whereas the HIC students’ knowledge had regressed. Most students recommended course expansion.ConclusionThe TEAM course is a useful tool to provide the basic principles of trauma care to students in LMICs, and should be expanded. Further study is needed to determine the impact of TEAM education on patient care in LMICs.Level of evidenceLevel III; Care Management
Randomised controlled trial of fractionated and unfractionated prednisolone regimens for dogs with immune‐mediated haemolytic anaemia
Authors: Swann James W , Szladovits Balazs , Threlfall Anna J , Garden Oliver A , Chang Yu‐Mei , Church David B , Glanemann Barbara 
Published: May 2019

MethodsA randomised non‐blinded non‐inferiority trial was conducted to determine whether treatment with an unfractionated regimen of oral prednisolone was inferior to a fractionated regimen for dogs with primary immune‐mediated haemolytic anaemia. Dogs received the same total daily dose of prednisolone as unfractionated (group 1, starting at 4 mg/kg orally once daily) or fractionated (group 2, starting at 2 mg/kg orally twice daily) doses. Questionnaires were administered to owners to assess adverse effects and quality of life (QoL). End points included survival to eight weeks, and changes in QoL and clinicopathological parameters over time.ResultsThirty‐nine dogs were enrolled in the study, of which 5 were withdrawn and 17 were assigned to each group. The number of cases recruited was insufficient to determine whether unfractionated treatment was inferior to fractionated. Total serum bilirubin decreased more rapidly in dogs in group 2, whereas polydipsia improved more rapidly in group 1. Blood pressure and score for polyuria were higher in dogs in group 2 over time, whereas lymphocyte concentration was lower.ConclusionAdministration of the same total daily dose of prednisolone as an unfractionated dose resulted in fewer adverse effects but the effect on survival could not be assessed in this study.