Wellcome Open Research最新文献

{"title":"Statistical analysis plan for the LAST ACT clinical trial; a Leukotriene A4 hydrolase Stratified non-inferiority Trial of Adjunctive Corticosteroids for HIV-negative adults with Tuberculous meningitis.","authors":"Joseph Donovan, Marcel Wolbers, Nguyen Thuy Thuong Thuong, Dong Huu Khanh Trinh, Le Thanh Hoang Nhat, Guy E Thwaites, Ronald B Geskus","doi":"10.12688/wellcomeopenres.22498.1","DOIUrl":"10.12688/wellcomeopenres.22498.1","url":null,"abstract":"<p><p>Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Corticosteroids are currently recommended as an adjunctive therapy in HIV-negative adults with TBM. However, benefit from corticosteroids in TBM may depend upon host <i>leukotriene A4 hydrolase</i> ( <i>LTA4H</i>) genotype and the corresponding inflammatory phenotypes. This article describes the planned analyses for the primary publication of the results of the LAST ACT clinical trial (NCT03100786): 'Leukotriene A4 hydrolase Stratified Trial of Adjunctive Corticosteroids for HIV-negative adults with Tuberculous meningitis'. The primary hypothesis addressed by the trial is that <i>LTA4H</i> genotype, in particular CC or CT genotype, determines whether adjunctive dexamethasone benefits or harms adults with TBM. The trial was an <i>LTA4H</i> genotype stratified, parallel group, randomised, double blind, placebo-controlled multi-centre Phase III trial of dexamethasone given for 6-8 weeks in addition to standard anti-tuberculosis drugs. <i>LTA4H</i> genotype (CC, CT, TT) was determined in all participants prior to randomisation; only those with CC or CT genotype were randomised to dexamethasone or placebo. All TT genotype participants received dexamethasone because prior data indicated survival was increased by dexamethasone in this genotype. The primary endpoint was all-cause death or new neurological event over the first 12 months after randomisation. We took a hybrid trial-design approach which aims to prove non-inferiority of placebo first but also allows claiming superiority of placebo in case dexamethasone causes substantial harm. This statistical analysis plan expands upon and updates the analysis plan outlined in the published study protocol.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"9 ","pages":"695"},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep duration, sleep disturbances and skeletal muscle mass change over time: A population-based longitudinal analysis in Peru.","authors":"Renzo A Agurto-García, Enrique S Nuñez-Del-Arco, Rodrigo M Carrillo-Larco, J Jaime Miranda, Antonio Bernabe-Ortiz","doi":"10.12688/wellcomeopenres.23077.3","DOIUrl":"10.12688/wellcomeopenres.23077.3","url":null,"abstract":"<p><strong>Background: </strong>The skeletal muscle has mainly a structural function and plays a role in human's metabolism. Besides, the association between sleep quality and muscle mass, in the form of sarcopenia, has been reported. This study aimed to assess whether changes of skeletal muscle mass (SMM) over time are associated with baseline sleep duration and disturbances in a resource-constrained adult Peruvian population.</p><p><strong>Materials and methods: </strong>Secondary analysis using information of a population-based intervention. The outcome was SMM assessed using bioimpedance and the second version of the Lee's formula. The exposures were baseline self-reported sleep duration (normal, short and long sleepers) and disturbances (sleep difficulties and awakening at nights). Crude and adjusted linear mixed models were used to assess the associations of interest, and coefficients (β) and 95% confidence intervales (95% CI) were reported.</p><p><strong>Results: </strong>Data from 2,310 individuals at baseline, mean age 43.4 (SD: 17.2), and 1,163 (50.4%) females were analyzed. Sleep duration was 7.8 (SD: 1.3) hours/day, with 15.3% short sleepers and 11.6% long sleepers, whereas 24.2% reported sleep difficulties and 25.1% awakening at nights. In multivariable model, SMM among short and long sleepers did not vary significantly over time using the Lee's formula; however, SMM was lower at the end of follow-up for long sleepers using bioimpedance (-0.26 kg; 95% CI: -0.47 to -0.06). Sleep disturbances were associated with a gradual SMM reduction: 0.36 kg using bioimpedance and 0.25 kg using the formula at the end of follow-up.</p><p><strong>Conclusions: </strong>Using bioimpedance and formula estimations, sleep disturbances were associated with a reduction of SMM over a period of 2.4 years. Regarding sleep duration, no SMM changes over time were seen in short sleepers, but findings were discordant in long sleepers: a reduction of SMM using bioimpedance, but no change using the formula.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"9 ","pages":"565"},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence, aetiology, and service mapping of dementia in rural Uganda. <i>Part of DEPEND Uganda (Dementia Epidemiology, unmet Need and co-Developing Solutions in Uganda).</i>","authors":"Josephine Prynn, Racheal Alinaitwe, Beatrice Kimono, Tunde Peto, Nicholas J Ashton, Claire J Steves, Joseph Mugisha, Martin Prince","doi":"10.12688/wellcomeopenres.22944.1","DOIUrl":"10.12688/wellcomeopenres.22944.1","url":null,"abstract":"<p><strong>Background: </strong>Dementia prevalence in low- and middle-income countries is increasing, yet epidemiological data from African populations remain scarce. Crucial risk factors differ in Africa from more intensively studied global areas, including a higher burden of cerebrovascular disease and HIV, but lower rates of other risk factors like physical inactivity.Understanding dementia aetiology in African settings has been limited by the expensive and invasive nature of biomarker testing. This study leverages developments in blood-based and retinal imaging biomarker technology to examine the drivers of dementia in older Ugandans.People with dementia have complex needs benefiting from multi-dimensional support. Understanding current services will allow identification of barriers and opportunities to strengthen support available to people with dementia and their families.</p><p><strong>Methods: </strong>The study is nested within the General Population Cohort run by the Medical Research Council/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Research Unit. All adults aged 60+ (around 1400) are undergoing brief cognitive screening.In Part 1, cohort participants are selected based on screening scores to undergo detailed cognitive assessment, using methods developed by the 10/66 Dementia Research Group. Part 2 is a case control study of people with and without dementia using antecedent data, questionnaires, physical assessment, retinal imaging, and Alzheimer's blood-based biomarkers. We will also compare disability, frailty, quality of life, and social engagement in people with and without dementia.Part 3 assesses current formal support structures for people with dementia through review of publicly available literature and expert interviews.</p><p><strong>Conclusions: </strong>This is the first study in Africa using blood-based and retinal imaging biomarkers to examine pathological processes underlying dementia, and systematically map services available for people with dementia. This paves the way for effective policy strategies and further focused research regarding both dementia prevention and support for affected people and their families.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"9 ","pages":"544"},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genome sequence of the tawny cockroach, Ectobius (Ectobius) pallidus (Olivier, 1789).","authors":"Tony Hunter","doi":"10.12688/wellcomeopenres.23463.1","DOIUrl":"10.12688/wellcomeopenres.23463.1","url":null,"abstract":"<p><p>We present a genome assembly from a specimen of <i>Ectobius pallidus</i> (tawny cockroach; Arthropoda; Insecta; Blattodea; Ectobiidae). The assembly contains two haplotypes with total lengths of 2,087.55 megabases and 2,124.67 megabases, respectively. Most of haplotype 1 (98.55%) is scaffolded into 11 chromosomal pseudomolecules, while haplotype 2 is assembled to scaffold level. The mitochondrial genome has also been assembled and is 15.75 kilobases in length.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"10 ","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genome sequence of a leafhopper, <i>Allygus modestus</i> Scott, 1876.","authors":"Keith Fowler","doi":"10.12688/wellcomeopenres.23451.1","DOIUrl":"10.12688/wellcomeopenres.23451.1","url":null,"abstract":"<p><p>We present a genome assembly from an individual male specimen of <i>Allygus modestus</i> (leafhopper; Arthropoda; Insecta; Hemiptera; Cicadellidae). The genome sequence has a total length of 1,819.90 megabases. Most of the assembly (99.86%) is scaffolded into 7 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 16.69 kilobases in length.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"10 ","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genome sequence of a sawfly, <i>Abia candens</i> Konow, 1887.","authors":"Andrew Cunningham, Andrew Halstead","doi":"10.12688/wellcomeopenres.23449.1","DOIUrl":"10.12688/wellcomeopenres.23449.1","url":null,"abstract":"<p><p>We present a genome assembly from an individual male specimen of <i>Abia candens</i> (sawfly; Arthropoda; Insecta; Hymenoptera; Cimbicidae). The genome sequence has a total length of 261.00 megabases. Most of the assembly (82.7%) is scaffolded into 16 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 19.72 kilobases in length.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"10 ","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the impact of implementing routine rotavirus vaccination on the number of paediatric admissions due to diarrhoea and dehydration in Kenyan hospitals: A study using interrupted time series analysis.","authors":"Daisy Chelangat, Lucas Malla, Reuben C Langat, Samuel Akech","doi":"10.12688/wellcomeopenres.17420.2","DOIUrl":"10.12688/wellcomeopenres.17420.2","url":null,"abstract":"<p><strong>Background: </strong>Dehydration secondary to diarrhoea is a major cause of hospitalization and mortality in children aged less than five years. Most diarrhoea cases in childhood are caused by rotavirus, and routine introduction of rotavirus vaccine is expected to reduce the incidence and severity of dehydration secondary to diarrhoea in vaccinated infants. Previously, studies have examined changes in admissions with stools positive for rotavirus but this study reports on all admissions with dehydration secondary to diarrhoea regardless of stool rotavirus results. We aimed to assess the changes in all-cause severe diarrhoea and dehydration (DAD) admissions following the vaccine's introduction.</p><p><strong>Methods: </strong>We examined changes in admissions of all clinical cases of DAD before and after introduction of routine vaccination with rotavirus vaccine in July 2014 in Kenya. We use data from 13 public hospitals currently involved in a clinical network, the Clinical Information Network (CIN). Routinely collected data for children aged 2-36 months were examined. We used a segmented mixed effects model to assess changes in the burden of diarrhoea and dehydration after introduction of rotavirus vaccine. For sensitivity analysis, we examined trends for non-febrile admissions (surgical or burns).</p><p><strong>Results: </strong>There were 17,708 patients classified as having both diarrhoea and dehydration. Average monthly admissions due to DAD for each hospital before vaccine introduction (July 2014) was 35 (standard deviation: ±22) and 17 (standard deviation: ±12) after vaccine introduction. Segmented mixed effects regression model showed there was a 33% (95% CI, 30% to 38%) decrease in DAD admissions immediately after the vaccine was introduced to the Kenya immunization program in July 2014. There was no change in admissions due to non-febrile admissions pre-and post-vaccine introduction.</p><p><strong>Conclusion: </strong>The rotavirus vaccine, after introduction into the Kenya routine immunization program resulted in reduction of all-cause admissions of diarrhoea and dehydration in children to public hospitals.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"7 ","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical care services in Bagmati province of Nepal: A cross sectional survey.","authors":"Diptesh Aryal, Subekshya Luitel, Sushila Paudel, Roshni Shakya, Janaki Pandey, Isha Amatya, Prashant Acharya, Suman Pant, Hem Raj Paneru, Abi Beane, Rashan Haniffa, Pradip Gyanwali","doi":"10.12688/wellcomeopenres.19932.3","DOIUrl":"10.12688/wellcomeopenres.19932.3","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to assess the current status of critical care services in 13 districts of Bagmati Province in Nepal, with a focus on access, infrastructure, human resources, and intensive care unit (ICU) services.</p><p><strong>Methods: </strong>A cross-sectional survey was conducted among healthcare workers employed in 87 hospitals having medical/surgical ICUs across Bagmati Province. Data were collected through structured questionnaires administered via face-to-face and telephone interviews. Descriptive analysis was used for data analysis, involving frequencies and percentages.</p><p><strong>Results: </strong>From 87 hospitals, a total of 123 ICUs were identified in the province, providing 1167 beds and 615 functioning ventilators. The average ICU bed availability per 100,000 population was 19, ranging from 3.6 in Makwanpur to 33.9 in Kathmandu. Out of 13 districts, 95% of beds were concentrated in just four districts, while six had no ICU facilities. Of the available facilities, 69.9% were owned by private entities. One-to-one nurse-to-ventilated bed ratio was maintained by 63.4% of ICUs during daytime, and 62.6% at nighttime. Furthermore, 74.8% of ICUs had consultants trained in critical care medicine. While essential equipment availability was higher in Bagmati province, gaps existed in the availability of oxygen plants and isolation rooms. Similarly, many ICUs offered continuous medical education and cardiopulmonary resuscitation (CPR) training, but improvements were necessary in clinical audits, antibiotic stewardship programs, and research engagement.</p><p><strong>Conclusions: </strong>Disparities in critical care resources were evident across districts in Bagmati Province, highlighting the need for a balanced and decentralized approach to ensure equitable access to care. Although there were disparities, numerous ICUs were effectively carrying out multiple critical care procedures. This study suggests conducting a nationwide mapping of ICU resources, prioritizing infrastructure development, optimizing resource allocation, and establishing national protocols.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"8 ","pages":"575"},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genome sequence of the striped dolphin, <i>Stenella coeruleoalba</i> (Meyen, 1833).","authors":"Nicholas J Davison, Phillip A Morin","doi":"10.12688/wellcomeopenres.23374.1","DOIUrl":"10.12688/wellcomeopenres.23374.1","url":null,"abstract":"<p><p>We present a genome assembly from an individual male <i>Stenella coeruleoalba</i> (the striped dolphin; Chordata; Mammalia; Artiodactyla; Delphinidae). The genome sequence has a total length of 2,691.40 megabases. Most of the assembly is scaffolded into 23 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 16.39 kilobases in length.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"9 ","pages":"727"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of multimorbidity research in India: a scoping review protocol.","authors":"Parul Puri, Siaa Girotra, Arpita Ghosh","doi":"10.12688/wellcomeopenres.21378.2","DOIUrl":"https://doi.org/10.12688/wellcomeopenres.21378.2","url":null,"abstract":"<p><strong>Background: </strong>Due to demographic and epidemiological shifts, people are living until older ages with more morbidities. These morbidities often have shared pathophysiology, which leads to a rise in coexisting health issues known as 'multimorbidity'. Primary care studies and disease burden surveys have multiplied, unveiling varied aspects of multimorbidity, yet with inconsistent definitions and methods. This protocol aims to guide an in-depth and comprehensive exploration of multimorbidity research in India through a scoping review, to understand the extent, range, and nature of research on multimorbidity in India.</p><p><strong>Methods: </strong>This study will comprehensively search the PubMed/Medline, Cochrane, and Embase databases employing a well-defined strategy. All studies published in English will be considered, provided the focus is multimorbidity and there is information specifically from India. Two reviewers will independently screen the search outcomes, and data extraction will include multimorbidity definitions, data and methods, patterns, risk factors and outcomes. The research will follow the Joanna Briggs Institute framework and adhere to PRISMA-P 2015 guidelines for reporting. Descriptive statistics and narrative synthesis will be used to summarize findings.</p><p><strong>Conclusions: </strong>Findings from this review will shed light on the extent and nature of multimorbidity research in India and help guide future research.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"9 ","pages":"302"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}