bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cologne rebubbling study: a reappraisal of 624 rebubblings after Descemet membrane endothelial keratoplasty
Authors: Siebelmann Sebastian , Kolb Katharina , Scholz Paula , Matthaei Mario , Franklin Jeremy , Händel Alexander , Schrittenlocher Silvia , Hayashi Takahiko , Guell Jose L , Bachmann Björn , Cursiefen Claus 
Published: August 2020

Background/AimsTo analyse graft detachments prior to rebubbling, the influence of rebubbling on the postoperative outcome after Descemet membrane endothelial keratoplasty (DMEK) and the need for rebubbling on the contralateral eye.MethodsIn this retrospective cohort study, out of 1541 DMEKs, optical coherence tomography scans and clinical records of 499 eyes undergoing rebubbling after DMEK at the University Hospital of Cologne, Cologne, Germany, were examined. Main Outcome measures were (a) number, localisation and size of graft detachments; (b) influence of rebubbling/s on postoperative outcome after 12 months; and (c) rebubbling risk of the contralateral eye after DMEK.ResultsMean number of detachment areas was 2.02±0.9. Mean lateral diameter of all detachments was 4534.76±1920.83 μm. Mean axial diameter was 382.53±282.02 μm. Detachments were equally distributed over all regions of the cornea. Best spectacle corrected visual acuity ( BSCVA) after 12 months was 0.197±0.23 logarithm of the minimum angle of resolution, endothelial cell density (ECD) was 1575.21±397.71 cells/mm2 and mean central corneal thickness (CCT) was 566.37±68.11 μm. BSCVA, CCT, ECD or endothelial cell loss of all rebubbled patients were not influenced by the number of rebubblings or the time between DMEK and rebubbling. Of the rebubbled patients, which received a DMEK subsequently on the other eye, 193 (58.8%) also received a rebubbling, which was significantly higher, when compared to the overall rebubbling rate of 32.3% (p=0.000).ConclusionsThe overall number of rebubblings has no influence on the postoperative outcome after DMEK, if a rebubbling becomes necessary. Patients who received a rebubbling on one eye have an elevated risk for a rebubbling on the fellow eye.
Cross-sectional study of Australian medical student attitudes towards older people confirms a four-factor structure and psychometric properties of the Australian Ageing Semantic Differential
Authors: Wilson Mark , Tran Yvonne , Wilson Ian , Kurrle Susan E 
Published: August 2020

ObjectivesThe Australian Ageing Semantic Differential (AASD) survey was developed to quantify medical student attitudes towards older people. The purpose of this study is to examine psychometric properties of the survey and confirm its factor structure of four composites.DesignA cross-sectional study.SettingThree medical schools in three Australian states: Victoria, Western Australia and South Australia.ParticipantsThird-year or fourth-year medical students (n=188, response rate=79%).Outcome measuresIn the previous AASD study, exploratory factor analysis supported a four-factor model consisting of ‘Instrumentality’ (I), ‘Personal Appeal’ (PA), ‘Experience’ (E) and ‘Sociability’ (S). Congeneric one-factor confirmatory factor analysis (CFA) were used to examine model fit for factors using a new student sample (n=188).Psychometric properties of survey items and factors.Post-hoc analysis of pooled data from this study and earlier AASD study (n=509).ResultsIndices of fit (Comparative Fit Index (CFI), Tucker-Lewis Index (TLI), root mean square error of approximation (RMSEA), standardised root mean square residual (SRMR)) for data to the factor model were: PA adequate fit (CFI=0.94, TLI=0.89, RMSEA=0.11 and SRMR=0.05), I good fit (CFI=0.99, TLI=0.99, RMSEA=0.04 and SRMR=0.03), S good fit (CFI=0.98, TLI=0.95, RMSEA=0.06 and SRMR=0.03) and E excellent fit (CFI=1.0, TLI=1.0, RMSEA=0.00 and SRMR=0.01).The AASD was internally consistent (Cronbach’s alpha=0.84), without difference in mean student scores by institution. Mean AASD score was positive for medical students outside New South Wales (73.2/114).Mean I score for all Australian students was negative, with female respondents’ mean E score significantly higher than their counterparts. A positive correlation between student age and I score was noted.ConclusionsThe AASD is internally consistent and generalisable within Australia, with acceptable structural validity for measuring medical student attitudes towards older people within a four-factor model. Student attitudes were positive globally and within all factors except I. Female students rated older persons E more positively. Older students recorded more positive attitudes towards I of older people.
Low-density lipoprotein cholesterol and all-cause mortality: findings from the China health and retirement longitudinal study
Authors: Zhou Liang , Wu Ying , Yu Shaobo , Shen Yueping , Ke Chaofu 
Published: August 2020

ObjectivesTo investigate the relationship between low-density lipoprotein cholesterol (LDL-C) and all-cause mortality among middle-aged and elderly Chinese population.DesignProspective cohort study.SettingThis study used data from the China Health and Retirement Longitudinal Study.ParticipantsMiddle-aged and elderly participants with complete data were enrolled for a 4-year follow-up of total mortality and plasma levels of LDL-C, including 4981 male respondents and 5529 female respondents.ResultsDuring a 4-year follow-up, there were 305 and 219 deaths in men and women, respectively. Compared with the first quintile (Q1) of LDL-C, the adjusted HRs (95% CIs) were 0.818 (0.531 to 1.260) for Q2, 0.782 (0.507 to 1.208) for Q3, 0.605 (0.381 to 0.962) for Q4 and 0.803 (0.506 to 1.274) for Q5 in men. The results from restricted cubic spine (RCS) showed that when the 20th percentile of LDL-C levels (84 mg/dL) was used as the reference, a lower LDL-C concentration (<84 mg/dL) was associated with a higher 4-year all-cause mortality risk. By contrast, both quintile analysis and RCS analysis did not show a statistically significant association in women.ConclusionsCompared with moderately elevated LDL-C (eg, 117–137 mg/dL), a lower plasma level of LDL-C (eg, ≤84 mg/dL) was associated with an increased risk of 4-year all-cause mortality in middle-aged and elderly Chinese men. The results suggest the potential harmful effect of a quite low level of LDL-C on total mortality.
Is untargeted iron supplementation harmful when iron deficiency is not the major cause of anaemia? Study protocol for a double-blind, randomised controlled trial among non-pregnant Cambodian women
Authors: Fischer Jordie AJ , Pei Lulu X , Goldfarb David M , Albert Arianne , Elango Rajavel , Kroeun Hou , Karakochuk Crystal D 
Published: August 2020

IntroductionThe WHO recommends daily oral iron supplementation for 12 weeks in women and adolescents where anaemia prevalence is greater than 40%. However, if iron deficiency is not a major cause of anaemia, then, at best, untargeted iron supplementation is a waste of resources; at worst, it could cause harm. Further, different forms of iron with varying bioavailability may present greater risks of harm.Methods and analysisA 12-week three-arm, double-blind, randomised controlled supplementation trial was conducted in Cambodia to determine if there is potential harm associated with untargeted iron supplementation. We will recruit and randomise 480 non-pregnant women (ages 18–45 years) to receive one of three interventions: 60 mg elemental iron as ferrous sulfate (the standard, commonly used form), 18 mg ferrous bisglycinate (a highly bioavailable iron amino acid chelate) or placebo. We will measure ferritin concentrations (to evaluate non-inferiority between the two forms of iron), as well as markers of potential harm in blood and stool (faecal calprotectin, gut pathogen abundance and DNA damage) at baseline and 12 weeks. Mixed-effects generalised linear models will be used to assess the effect of iron on ferritin concentration and markers of potential harm at 12 weeks.Ethics and disseminationEthical approval was obtained from the University of British Columbia Clinical Research Ethics Board (H18-02610), the Children's and Women's Health Centre of British Columbia Research Ethics Board (H18-02610) and the National Ethics Committee for Health Research in Cambodia (273-NECHR). Findings will be published in peer-reviewed journals, presented to stakeholders and policymakers globally and shared within participants’ communities.Trial registration numberClinicalTrials.gov Registry (NCT04017598).
What clinical challenges are associated with diagnosing and managing work-related mental health conditions? A qualitative study in general practice
Authors: Chakraborty Samantha Paubrey , Dermentzis Jacinta , Brijnath Bianca , Ivey Eli , Mazza Danielle 
Published: August 2020

ObjectiveWhen providing care for patients with work-related mental health conditions (MHCs), the general practitioner’s (GP) role includes clinical care, patient advocacy and assessment of a patient’s ability to work. GPs can experience difficulty representing these competing roles. As clinical guidelines were being developed to assist GPs in providing this care, our aim was to identify the clinical challenges GPs experience when diagnosing and managing patients with work-related MHCs.DesignQualitative research.SettingThis study was conducted in general practice and workers’ compensation settings across Australia.ParticipantsTwenty-five GPs, seven psychiatrists and nine compensation scheme workers. GPs were eligible to participate if they were actively treating (or treated within the previous three years) patient(s) who had submitted a workers’ compensation claim for a MHC. Psychiatrists and compensation scheme workers were eligible to participate if they were active in these roles, as they are best placed to identify additional clinical challenges GPs themselves did not raise.MethodParticipants were invited by letter to participate in qualitative semi-structured telephone interviews. Prior to each interview, participants were asked to reflect on two case vignettes, each depicting a patient’s illness trajectory over 12 months. Data were thematically analysed using inductive and deductive techniques and then categorised by stages of clinical reasoning.ResultsParticipants reported clinical challenges across four key areas: (1) Diagnosis (identifying appropriate diagnostic tools, determining the severity and work-relatedness of a MHC, and managing the implications of labelling the patient with MHC). (2) Management (determining optimal treatment, recommending work participation). (3) Referral (ambiguity of communication pathways within compensation schemes). (4) Procedure (difficulties navigating compensation systems).ConclusionWe found that GPs experienced clinical challenges at all stages of care for people with work-related MHCs. We were also able to identify systemic and procedural issues that influence a GP’s ability to provide care for patients with work-related MHCs.
Incubation period of COVID-19: a rapid systematic review and meta-analysis of observational research
Authors: McAloon Conor , Collins Áine , Hunt Kevin , Barber Ann , Byrne Andrew W , Butler Francis , Casey Miriam , Griffin John , Lane Elizabeth , McEvoy David , Wall Patrick , Green Martin , O'Grady Luke , More Simon J 
Published: August 2020

ObjectivesThe aim of this study was to conduct a rapid systematic review and meta-analysis of estimates of the incubation period of COVID-19.DesignRapid systematic review and meta-analysis of observational research.SettingInternational studies on incubation period of COVID-19.ParticipantsSearches were carried out in PubMed, Google Scholar, Embase, Cochrane Library as well as the preprint servers MedRxiv and BioRxiv. Studies were selected for meta-analysis if they reported either the parameters and CIs of the distributions fit to the data, or sufficient information to facilitate calculation of those values. After initial eligibility screening, 24 studies were selected for initial review, nine of these were shortlisted for meta-analysis. Final estimates are from meta-analysis of eight studies.Primary outcome measuresParameters of a lognormal distribution of incubation periods.ResultsThe incubation period distribution may be modelled with a lognormal distribution with pooled mu and sigma parameters (95% CIs) of 1.63 (95% CI 1.51 to 1.75) and 0.50 (95% CI 0.46 to 0.55), respectively. The corresponding mean (95% CIs) was 5.8 (95% CI 5.0 to 6.7) days. It should be noted that uncertainty increases towards the tail of the distribution: the pooled parameter estimates (95% CIs) resulted in a median incubation period of 5.1 (95% CI 4.5 to 5.8) days, whereas the 95th percentile was 11.7 (95% CI 9.7 to 14.2) days.ConclusionsThe choice of which parameter values are adopted will depend on how the information is used, the associated risks and the perceived consequences of decisions to be taken. These recommendations will need to be revisited once further relevant information becomes available. Accordingly, we present an R Shiny app that facilitates updating these estimates as new data become available.
Impact of COVID-19 pandemic on surgical neuro-oncology multi-disciplinary team decision making: a national survey (COVID-CNSMDT Study)
Authors: Price Stephen John , Joannides Alexis , Plaha Puneet , Afshari Fardad Taghizadeh , Albanese Erminia , Barua Neil U , Chan Huan Wee , Critchley Giles , Flannery Thomas , Fountain Daniel M , Mathew Ryan K , Piper Rory J , Poon Michael TC , Rajaraman Chittoor , Rominiyi Ola , Smith Stuart , Solomou Georgios , Solth Anna , Surash Surash , Wykes Victoria , Watts Colin , Bulbeck Helen , Hutchinson Peter , Jenkinson Michael D 
Published: August 2020

ObjectivesPressures on healthcare systems due to COVID-19 has impacted patients without COVID-19 with surgery disproportionally affected. This study aims to understand the impact on the initial management of patients with brain tumours by measuring changes to normal multidisciplinary team (MDT) decision making.DesignA prospective survey performed in UK neurosurgical units performed from 23 March 2020 until 24 April 2020.SettingRegional neurosurgical units outside London (as the pandemic was more advanced at time of study).ParticipantsRepresentatives from all units were invited to collect data on new patients discussed at their MDT meetings during the study period. Each unit decided if management decision for each patient had changed due to COVID-19.Primary and secondary outcome measuresPrimary outcome measures included number of patients where the decision to undergo surgery changed compared with standard management usually offered by that MDT. Secondary outcome measures included changes in surgical extent, numbers referred to MDT, number of patients denied surgery not receiving any treatment and reasons for any variation across the UK.Results18 units (75%) provided information from 80 MDT meetings that discussed 1221 patients. 10.7% of patients had their management changed—the majority (68%) did not undergo surgery and more than half of this group not undergoing surgery had no active treatment. There was marked variation across the UK (0%–28% change in management). Units that did not change management could maintain capacity with dedicated oncology lists. Low volume units were less affected.ConclusionCOVID-19 has had an impact on patients requiring surgery for malignant brain tumours, with patients receiving different treatments—most commonly not receiving surgery or any treatment at all. The variations show dedicated cancer operating lists may mitigate these pressures.Study registrationThis study was registered with the Royal College of Surgeons of England’s COVID-19 Research Group (https://www.rcseng.ac.uk/coronavirus/rcs-covid-research-group/).
What effective ways of motivation, support and technologies help people with cystic fibrosis improve and sustain adherence to treatment?
Authors: Calthorpe Rebecca J , Smith Sherie J , Rowbotham Nicola J , Leighton Paul A , Davies Gwyneth , Daniels Tracey , Gathercole Katie , Allen Lorna , Elliott Zoe C , Smyth Alan R 
Published: August 2020

Introduction“What effective ways of motivation, support and technologies help people with cystic fibrosis improve and sustain adherence to treatment?” was identified as one of the James Lind Alliance Priority Setting Partnership’s top 10 research questions in cystic fibrosis (CF). Using electronic questionnaires, we aimed to gain a deeper understanding of this research priority.MethodThe work was led by the steering group representative of the UK CF community consisting of patients, carers and healthcare professionals (HCPs). Electronic questionnaires were completed over a 4-week period and promoted via online forums such as Twitter, the UK CF Trust and US CF Foundation websites and via professional networks. Analysis of the closed questions was completed using Microsoft Excel, with keyword analysis and the final thematic analysis completed using NVivo software.ResultsThere were 313 respondents; 176/313 (56%) were from people with CF and their families. HCPs comprised of 10 professional groups accounting for 137/313 (44%) of respondents, with global involvement of participants with the majority from the UK. Common themes identified as impacting on adherence included: having no time, treatment burden, competing life demands, fatigue and the patient’s general health. Having a routine was identified as the most frequently used motivational strategy, valued by both the patient and professional community. However, some strategies were valued more by HCPs than used in practice by patients; these included the use of short-term goal setting and technology use.ConclusionAdherence to treatment is crucial, however it is often suboptimal and strategies valued by HCPs to promote adherence are not always shared by patients. To promote adherence clinicians and researchers should be mindful that in a condition where treatment burden and time pressures are considerable, any interventions should focus on simplifying care and reducing treatment burden.
Variation in CT use for paediatric head injuries across different types of emergency departments in Australia and New Zealand
Authors: Wilson Catherine L , Tavender Emma J , Phillips Natalie T , Hearps Stephen JC , Foster Kelly , O'Brien Sharon L , Borland Meredith L , Watkins Gina O , McLeod Lorna , Putland Mark , Priestley Stephen , Brabyn Christine , Ballard Dustin W , Craig Simon , Dalziel Stuart R , Oakley Ed , Babl Franz E 
Published: August 2020

ObjectivesCT of the brain (CTB) for paediatric head injury is used less frequently at tertiary paediatric emergency departments (EDs) in Australia and New Zealand than in North America. In preparation for release of a national head injury guideline and given the high variation in CTB use found in North America, we aimed to assess variation in CTB use for paediatric head injury across hospitals types.MethodsMulticentre retrospective review of presentations to tertiary, urban/suburban and regional/rural EDs in Australia and New Zealand in 2016. Children aged <16 years, with a primary ED diagnosis of head injury were included and data extracted from 100 eligible cases per site. Primary outcome was CTB use adjusted for severity (Glasgow Coma Scale) with 95% CIs; secondary outcomes included hospital length of stay and admission rate.ResultsThere were 3072 head injury presentations at 31 EDs: 9 tertiary (n=900), 11 urban/suburban (n=1072) and 11 regional/rural EDs (n=1100). The proportion of children with Glasgow Coma Score ≤13 was 1.3% in each type of hospital. Among all presentations, CTB was performed for 8.2% (95% CI 6.4 to 10.0) in tertiary hospitals, 6.6% (95% CI 5.1 to 8.1) in urban/suburban hospitals and 6.1% (95% CI 4.7 to 7.5) in regional/rural. Intragroup variation of CTB use ranged from 0% to 14%. The regional/rural hospitals admitted fewer patients (14.6%, 95% CI 12.6% to 16.9%, p<0.001) than tertiary and urban/suburban hospitals (28.1%, 95% CI 25.2% to 31.2%; 27.3%, 95% CI 24.7% to 30.1%).ConclusionsIn Australia and New Zealand, there was no difference in CTB use for paediatric patients with head injuries across tertiary, urban/suburban and regional/rural EDs with similar intragroup variation. This information can inform a binational head injury guideline.
Construction of a reference material panel for detectingKRAS/NRAS/EGFR/BRAF/METmutations in plasma ctDNA
Authors: Xu Jun , Qu Shoufang , Sun Nan , Zhang Wenxin , Zhang Juanli , Song Qingtao , Lin Mufei , Gao Wei , Zheng Qiaosong , Han Mipeng , Na Chenglong , Xu Ren , Chang Xiaoyan , Yang Xuexi , Huang Jie 
Published: August 2020

BackgroundThe absence of high-quality next-generation sequencing (NGS) reference material (RM) has impeded the clinical use of liquid biopsies with plasma cell-free DNA (cfDNA) in China.ObjectiveThis study aimed to develop a national RM panel for external quality assessment and performance evaluation during kit registration of non-small-cell lung cancer (NSCLC)-related Kirsten rat sarcoma viral oncogene (KRAS)/neuroblastoma ras oncogene (NRAS)/epidermal growth factor receptor (EGFR)/B-type Raf kinase (BRAF)/mesenchymal–epithelial transition factor (MET) genetic assays using plasma circulating tumor DNA (ctDNA).MethodsMutation cell lines detected by NGS and validated by Sanger sequencing were selected to establish the RM. Cell line genomic DNA was sheared and used to spike basal plasma cfDNA at 10% concentration. Then, the calibration accuracy was determined by four sequencing platforms. Average values were adopted and diluted to 0.1%, 0.3%, 1% and 3% concentrations with basal plasma as the RM panel. Then, five manufacturers were invited to evaluate the performance of the RM panel.Results20 cell lines with 23 clinically important mutations were selected, including six mutations inKRAS, two mutations inNRAS, three inBRAF, four in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), six inEGFR, oneEGFRGain (4-5 copy) andone METGain (2-5 copy). The RM panel consisted of 87 samples, including these 21 mutations at four concentrations (0.1%, 0.3%, 1% and 3%), oneMETgain, oneEGFRgain and one wild type. The detection rate was 100% for the 3%, 1% and 0.3% samples at all five companies. For the 0.1% concentration, 15 samples had inconsistent results, but at least three companies had correct results for each mutation.ConclusionRM for aKRAS/NRAS/EGFR/BRAF/METmutation panel for plasma ctDNA was developed, which will be essential for quality control of the performance of independent laboratories.
Advanced pathological study for definite diagnosis of mitochondrial cardiomyopathy
Authors: Takeda Atsuhito , Murayama Kei , Okazaki Yasushi , Imai-Okazaki Atsuko , Ohtake Akira , Takakuwa Emi , Yamazawa Hirokuni , Izumi Gaku , Abe Jiro , Nagai Ayako , Taniguchi Kota , Sasaki Daisuke , Tsujioka Takao , Basgen John M 
Published: August 2020

AimsMitochondrial cardiomyopathy (MCM) is difficult to make a definite diagnosis because of various cardiovascular phenotypes and no diagnostic criteria in the pathology examination. We aim to add myocardial pathology to the diagnostic criteria for mitochondrial respiratory chain disorders.MethodsQuantitative analysis of mitochondria using electron microscopy and immunohistopathological analysis with respiratory chain enzyme antibodies were performed in 11 patients with hypertrophic or restrictive cardiomyopathy who underwent endomyocardial biopsy for possible MCM . Respiratory chain enzymatic assay in biopsied myocardium and genetic studies were also performed in all the subjects to define MCM.ResultsFour patients were diagnosed with MCM according to the recent criteria of mitochondrial respiratory chain disorders. Using electron microscopy with quantitative analysis, the volume density of mitochondria within cardiac muscle cells was significantly increased in the MCM group compared with the non-MCM group (p=0.007). Immunohistopathological results were compatible with the result of the respiratory chain enzymatic assay.ConclusionsPathological diagnosis of MCM could be confirmed by a quantitative study of electron microscopy and immunohistopathological analysis using the mitochondrial respiratory chain enzyme subunit antibody.