To assess the prevalence of dyslipidaemia and associated risk factors, and evaluate low-density lipoprotein cholesterol (LDL-C) target attainment among adults in the Western Province of Sri Lanka.

Cross-sectional epidemiological study.

Western province, Sri Lanka.

Participants were recruited through a community-based survey of non-institutionalised adults aged ≥20 years residing in the Western Province for at least 1 year (n=1800), using multistage stratified random cluster sampling.

Dyslipidaemia was defined according to the National Cholesterol Education Programme/Adult Treatment Panel III guidelines. Prevalence estimates are presented with 95% CIs. Multiple logistic regression results are reported as adjusted ORs with 95% CIs.

Cardiovascular risk in participants aged ≥40 years was assessed using the WHO laboratory-based cardiovascular disease (CVD) risk chart for South-East Asia. Achievement of LDL-C targets was evaluated according to the Sri Lankan guidelines on management for dyslipidaemia management.

Data from 1333 subjects were analysed. Mean age was 49.8 (±14.9) years. The majority were females (63.6%). The age-sex standardised prevalence of any form of dyslipidaemia was 73.3% (95% CI 70.9% to 75.7%). Age standardised prevalence in females was 77.1% (95% CI 74.3% to 79.9) and males was 69.3% (95% CI 65.3% to 73.3%). The most prevalent type of dyslipidaemia was low high-density lipoprotein cholesterol (HDL-C) (46.6%, 95% CI 43.9% to 49.3%), followed by high LDL-C (32.5%, 95% CI 30.0% to 35.0%) and high triglycerides (21.7%, 95% CI 19.5% to 23.9%). Low HDL-C was positively associated with smoking (OR: 1.89, 95% CI 1.16 to 3.18) and inversely with male sex (OR: 0.29, 95% CI 19 to 0.45) and physical activity (OR: 0.71, 95% CI 0.51 to 0.99). Elevated LDL-C was associated with male sex (OR: 1.84, 95% CI 1.2 to 2.89), diabetes (OR: 5.34, 95% CI 3.53 to 8.08), and hypertension (OR: 1.62, 95% CI 1.18 to 2.23). Male sex (OR: 1.85, 95% CI 1.08 to 3.18), diabetes (OR: 1.9, 95% CI 1.4 to 2.58) and hypertension (OR: 1.81, 95% CI 1.12 to 2.91) were positively associated with elevated triglycerides, whereas urban sector (OR: 0.54, 95% CI 0.32 to 0.91) was protective. Physical activity (OR: 0.65, 95% CI 0.44 to 0.98) and male sex (OR: 0.52, 95% CI 0.31 to 0.89) inversely associated with any form of dyslipidaemia, whereas diabetes (OR: 7.08, 95% CI 3.99 to 12.55), hypertension (OR: 1.93, 95% CI 1.36 to 2.73), and body mass index (OR: 1.06, 95% CI 1.01 to 1.2) were positively associated. The majority of participants (66.6%) had a

Three-fourths of adults in Western Province, Sri Lanka had any form of dyslipidaemia, more common in females. Low HDL-C was the most frequent abnormality. Most participants aged above 40 years were at low cardiovascular risk, yet two-thirds failed to meet LDL-C targets. Non-communicable disease prevention in Sri Lanka should expand through population-wide strategies, including awareness campaigns, promoting self-monitoring, targeted education and surveillance to evaluate interventions.

Accurate assessment of insulin resistance, sensitivity and β-cell function is essential for early detection and management of metabolic disorders. However, reference intervals (RIs) commonly used in Nepal have been adapted from Western populations, which may not accurately reflect local physiological characteristics. Thus, this study aimed to establish population-specific RIs for fasting insulin and key insulin-related indices using a direct priori method in healthy adults from Gandaki Province, Nepal.

This cross-sectional study recruited 135 healthy adults (20–69 years, body mass index 18.5–24.9 kg/m²) representing different districts of Gandaki Province, Nepal. Fasting blood samples were analysed for glucose, insulin and lipids using standardised assays. Insulin was measured using the chemiluminescence immunoassay method. Nineteen different insulin-derived indices (Homeostasis Model Assessment 1 of Insulin Resistance (HOMA1-IR), Homeostasis Model Assessment 2 of Insulin Resistance (HOMA2-IR), Homeostasis Model Assessment for Triglycerides, Fasting Insulin to Glucose Ratio, Fasting Insulin Resistance Index, Metabolic Score for Insulin Resistance (METS-IR), InsuTAG, HOMA1-%S, HOMA2-%S, Quantitative Insulin Sensitivity Check Index (QUICKI), McAuley, Bennett, Raynaud, Glucose-to-Insulin Ratio, Fasting Insulin Sensitivity Index, Single Point Insulin Sensitivity Estimator (SPISE), reciprocal insulin, HOMA1-%B and HOMA2-%B) were calculated. Non-parametric 95% double-sided RIs (2.5th–97.5th percentiles) were established following outlier removal per Clinical and Laboratory Standards Institute-International Federation of Clinical Chemistry and Laboratory Medicine EP28-A3c guidelines.

The RI for fasting insulin was 2.63–14.56 µIU/mL (median 7.69 µIU/mL). Among the 19 mathematically correlated insulin-derived indices which are calculated from core measurements (fasting serum insulin and glucose), consistent patterns emerged across functional categories. Insulin resistance indices (HOMA1-IR: 0.56–3.50; HOMA2-IR: 0.30–1.70; METS-IR: 25.14–38.94) exhibited concordant right-skewed distributions with elevated upper limits. Conversely, insulin sensitivity indices (QUICKI: 0.32–0.42; HOMA2-%S: 58.83–233.20; SPISE: 5.75–10.86) demonstrated inverse, left-skewed patterns. Beta-cell function indices (HOMA1-%B: 0.54–322.21; HOMA2-%β: 40.74–159.52) also exhibited right skewed characteristics and revealed wide interindividual variability, reflecting preserved pancreatic reserve despite varying insulin resistance. Composite indices incorporating lipid parameters showed broader ranges, capturing additional metabolic heterogeneity.

This is the first study to define the RIs of fasting insulin and a spectrum of insulin derived indices in a Nepalese population. These findings offer a valuable framework for early detection and management of metabolic disorders in South Asian populations.

People with body mass index (BMI) ≥35 kg/m² have an approximately 19-fold increased risk of undergoing total knee replacement (TKR); however, many UK integrated care boards (37%) have restrictive policies which limit access to TKR for people based on BMI. Therefore, access to both surgical and non-surgical treatments varies widely, exacerbating existing health inequalities. It remains unclear how decisions about offering TKR are made in people with severe knee osteoarthritis, which weight-loss interventions are provided in practice and how different management pathways relate to patient outcomes among individuals with high BMI.

This study will recruit 400 participants with severe Kellgren-Lawrence grade four knee osteoarthritis from eight secondary care centres in England. All participants, irrespective of BMI, will provide baseline clinical data and patient-reported outcome measures (PROMs), enabling characterisation of baseline associations between BMI, knee function and body image.

A prespecified subgroup of participants with BMI ≥35 kg/m² (minimum n=105) will undergo longitudinal follow-up at 6 months, 12 months and 24 months, including repeat BMI measurement, PROMs and detailed data on access to surgical and non-surgical interventions, including weight-loss strategies and TKR. For those with BMI ≥35 kg/m², statistical modelling will be used to explore associations between baseline factors and longitudinal outcomes including Oxford Knee Score and weight change at 12 months (n≥105). Structural equation modelling will be used to quantify associations between BMI and knee pain/function mediated by psychosocial factors using data from all participants (n=400). A nested qualitative study of surgeons and patients will explore obstacles and preferences in the management of severe knee osteoarthritis.

The study received ethical approval from the West of Scotland REC 5 (Ref: 24/WS/0146) on 10 October 2024. Results will be disseminated through peer-reviewed publications.

ISRCTN42984928.

Artificial intelligence (AI) is rapidly evolving, offering an expanding suite of capabilities that go beyond the traditional focus on prediction and classification. Generative AI (GenAI) and agentic AI could create transformative practices to support real-world evidence (RWE) generation for health research by streamlining studies, accelerating insights and improving decision-making. However, there is no published overview available describing the range of applications in RWE generation. This review aims to describe where and how genAI and agentic AI are applied across the domains of healthcare research tasks for RWE generation. Additionally, to map applications by tasks and methods across the product lifecycle continuum, and to identify emerging gaps and opportunities.

This Living Scoping Review (LSR) will include studies reporting an application and/or evaluation of genAI or agentic AI applied to one or more RWE generation research tasks. Searches will be conducted in Embase, MEDLINE and additional sources (eg, grey literature). Citations will be independently screened by two human senior reviewers for a substantive training dataset and a commercially available screening algorithm (Robot Screener) will complete screening with a human reviewer. The LSR will include reports of studies (primary or reviews) describing and/or evaluating the application of any genAI model for RWE generation in healthcare, in English, published from 1 January 2025 to the date of search. Data will be extracted from all studies included in the LSR by one independent senior reviewer using a piloted template, with 10% quality check by a second senior reviewer. Descriptive statistics will be used to summarise the applications of genAI per RWE research task, and the results of genAI evaluations. Thematic analysis will be used to describe genAI application patterns, trends, gaps and opportunities. The LSR protocol and reports will be updated annually, and findings will be published on a publicly available website (eg, ISPE—the International Society for Pharmacoepidemiology).

Ethical approval is not required due to use of previously published data. Planned dissemination includes peer-reviewed publication, presentation and short summaries.

This study assessed the feasibility of implementing a phase 3 field-based clinical trial protocol to evaluate paediatric praziquantel (PED-PZQ) for the treatment of Schistosoma mansoni infection in children aged 3 months to 6 years in endemic areas of Brazil, focusing on operational aspects such as recruitment logistics, documentation management, investigational product handling and protocol adherence.

Pilot and feasibility study for a phase 3 clinical trial, comprising two components: a randomised, open-label, parallel-group, two-arm trial and a single-arm trial.

Conde, Bahia, Brazil, from December 2024 to January 2025.

Two trials aim to screen 5774 participants from three rural areas in Bahia and three in Sergipe, states in northeastern Brazil, and enrol 403 children eligible for either randomisation or allocation. Trial 1 will randomise (1:1 ratio) 240 children aged 4–6 years into the PED-PZQ treatment arm or the standard praziquantel (PZQ) 1. Trial 2 will enrol 163 children aged 3 months to 3 years, all receiving PED-PZQ. Both trials are open label. Eligible participants shall meet age criteria, test positive for S. mansoni and fulfil other inclusion criteria. In the first recruiting centre, Conde (Bahia), it was estimated that 650 participants would need to be screened for trial 1 and 552 for trial 2, assuming schistosomiasis prevalence of 5% and 4%, respectively. This pilot study reports on the first 60 participants enrolled.

The primary outcome of this pilot study is the feasibility of implementing the research protocol in a real-world field setting, focusing on key aspects such as study documentation challenges, participant safety, investigational medicinal product custody chain and protocol adherence. In addition to providing preliminary data on the parasitological cure rate, secondary outcomes include the prevalence of S. mansoni infection and the reduction in S. mansoni egg count (Kato-Katz method). Furthermore, the occurrence and severity of drug-related adverse events are monitored from drug administration to day 21 post-treatment, alongside changes in renal, hepatic and cardiac functions assessed through biochemical markers.

A total of 60 participants were recruited, and 55 provided stool samples for screening. The pilot phase demonstrated the feasibility of implementing the clinical protocol under field conditions, with successful completion of all planned procedures and minimal protocol deviations. Operational challenges were identified mainly in documentation processes, participant recruitment and investigational product management and were addressed through preventive and corrective quality assurance actions. The experience also highlighted logistical and infrastructural barriers typical of field-based trials in remote endemic areas, which informed adjustments for the subsequent phase 3 study. Preliminary parasitological results indicated an overall S. mansoni prevalence of 9.1% (5/55), with 21% in trial 1 and 2.8% in trial 2. All infected participants met the eligibility criteria, received treatment and completed follow-up. Four achieved a parasitological cure, and one case of treatment failure was observed (trial 1, PZQ group). Two mild adverse events (diarrhoea) were reported, with no serious complications or clinically significant changes in biochemical parameters.

This pilot study demonstrated the feasibility of implementing a field-based phase 3 clinical trial protocol for PED-PZQ in endemic areas of Brazil. The findings confirm that the protocol can be successfully applied in primary care settings, despite operational challenges related to recruitment, logistics and documentation. The study also provided preliminary evidence supporting the safety and effectiveness of the paediatric formulation and highlighted the need to revise prevalence assumptions to improve future screening strategies. Overall, the experience offers valuable insights to guide the large-scale phase 3 trial and supports the incorporation of PED-PZQ into national schistosomiasis control policies.

Brazilian Clinical Trials Registry; RBR-86kcy37.

Earlier heart failure (HF) diagnosis in the community could allow timely treatment initiation and prevent unnecessary hospitalisation, but identifying those at risk remains challenging. We aimed to summarise the performance of risk prediction models for a new diagnosis of HF.

Systematic review of multivariable incident HF risk prediction models in the community setting.

MEDLINE and Embase were searched from inception to 9 November 2023.

Observational, community-based studies reporting prediction model performance for incident HF within a 5-year time horizon.

Two reviewers independently screened and extracted data. Where possible, C-statistics (or area under the receiver operating characteristic curve) with 95% CIs were extracted. Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool and certainty of evidence by the Grading of Recommendations, Assessment, Development and Evaluation.

Eighteen studies described 45 prediction models, 27 used traditional statistical methods and 18 applied machine learning. Most (39/45) demonstrated acceptable discrimination (C-statistic >0.70). Overall, C-statistics ranged from 0.675 to 0.954, typically with narrow 95% CIs. External validation was performed for 31 models, but only two—the modified PCP-HF models for white men and women—were validated in three cohorts, the highest among all the models. Exploratory random-effects meta-analysis of these models showed pooled C-statistics of 0.82 (95% CI 0.82 to 0.82) for men and 0.85 (95% CI 0.82 to 0.88) for women, indicating excellent discrimination but more heterogenous performance among women. Model performance was at high risk of bias due to unreported or inappropriate handling of missing data, and the certainty of evidence was very low.

Risk prediction models for a new diagnosis of HF in the community performed well, but were at high risk of bias and lacked external validation. Future model development requires appropriate data sources, robust handling of missing data, external validation and clinical testing to assess their impact on earlier HF diagnosis and outcomes.

CRD42022347120.

The global population of older adults has grown at an unprecedented rate, and projections indicate that the number of older adults will continue to increase considerably in the coming decades. The clinical complexity of older adults living in retirement homes, also known as assisted living settings, is also increasing, and the regulations to ensure quality and safety standards in retirement homes are highly variable. The purpose of this scoping review is to map and summarise the methods used to monitor and measure the safety of older adults living in retirement homes, providing an overview of existing approaches and areas requiring further investigation.

This scoping review will follow the five stages of the Arksey and O’Malley scoping review process. We will report this review using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. A comprehensive search of four electronic databases (MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and Web of Science Core Collection) will be performed, and reference lists of included articles will be searched. We will conduct a two-step screening process, data extraction and analysis of the included studies. We will include all primary study designs that report on safety measurement and monitoring of any type of harms. Relevant grey literature will also be identified. We will exclude studies that only report results from facilities providing 24-hour skilled nursing care or specialised care services, and those not published in English or French. This protocol is registered on the Open Science Framework (osf.io/8rheq).

No ethical approval is needed for the review, and we plan to present the results at research conferences and in a peer-reviewed article. Our findings may inform future research studies that seek to support and improve safety practices in retirement homes.

Our primary objectives were (1) to develop and validate an administrative data algorithm for the identification of hand trauma cases using clinical diagnoses documented in medical records as the reference standard and (2) to estimate the incidence of hand trauma in a universal public healthcare system from 1993 to 2023 using a population-based research cohort constructed using a validated case identification algorithm.

A population-based retrospective validation study.

Ontario, Canada, from 2022 to 2023 (validation) and from 1993 to 2023 (estimation).

Our reference standard was the known hand trauma status of 301 patients (N=147 with hand trauma) who presented to an urban tertiary-care hand trauma centre in Toronto, Ontario.

(1) The sensitivity, specificity, positive and negative predictive values of the optimal algorithm to identify hand trauma using provincial health administrative data and (2) age-standardised and sex-standardised incidence rates of hand trauma among men and women, by age, and by area of patient residence.

The optimal algorithm had a sensitivity of 73.8% (95% CI 66.6% to 81.0%), specificity of 80.1% (95% CI 73.8% to 86.5%), positive predictive value of 78.1% (95% CI 71.2% to 85.0%) and negative predictive value of 76.1% (95% CI 69.5% to 82.7%). Over the study period, the age-standardised and sex-standardised incidence of hand trauma increased from 384 to 530 per 100 000. The greatest increase was observed in males and individuals aged 0–19 and 80+, with higher incidence rates in Southern compared with Northern Ontario.

Our algorithm enabled identification of hand trauma cases using health administrative data suitable for population-level surveillance and health services research, revealing a rising burden of hand trauma from 1993 to 2023. These findings can support improved surveillance, resource allocation and care delivery for this public health problem.

Gram negative bloodstream infections (GN BSI) are a leading cause of mortality worldwide, and antibiotic treatment approaches remain understudied. BALANCE+ is a perpetual Bayesian adaptive platform trial to test multiple treatment questions for hospitalised patients with GN BSI. The vanguard phase objective was to test the feasibility of the main trial.

Adaptive platform trial with five initial domains of investigation, each with open label 1:1 randomisation.

Ten hospitals across four Canadian provinces.

Individuals admitted to hospital with blood cultures yielding Gram negative bacteria.

The five initial domains of investigation included: antibiotic de-escalation versus no de-escalation; oral transition to beta-lactam versus non-beta-lactam treatment; routine versus no routine follow-up blood cultures (FUBCs); central vascular catheter replacement versus retention; and, ceftriaxone versus carbapenem treatment for low risk AmpC organisms.

Domain-specific recruitment rates and protocol adherence.

During the vanguard phase, 719 patients were screened, of whom 563 (78.3%) were eligible, with 179 (31.8%) enrolled into the platform. The platform recruitment rate was 1.37 patients/site-week. Recruitment varied by domain: routine versus no FUBC domain 1.23 patients/site-week; oral beta-lactam versus non-beta-lactam domain 0.48; de-escalation versus no de-escalation domain 0.28; low risk AmpC domain 0.02; catheter replacement versus retention domain 0.01. Domain specific protocol adherence rates were 145/158 (91.8%) for routine versus no routine FUBC, 53/60 (88.3%) for oral beta-lactam versus non-beta-lactam, 26/33 (78.8%) for de-escalation versus no de-escalation, 3/3 (100%) for low risk AmpC, and 0/1 (0%) for line replacement versus retention. There was complete ascertainment of all study outcomes in hospital 170/170 (100%) and near complete ascertainment at 90 days 162/170 (95.3%).

The vanguard phase demonstrated overall trial feasibility by recruitment rate and protocol adherence, with differences across interventions, leading to a transition to the main BALANCE+ platform trial with minimal protocol modifications.

NCT05893147.

Herpes zoster (HZ) vaccinations effectively prevent HZ and may decrease dementia, but HZ vaccine uptake remains poor in China. Rapid verbal persuasion is an innovative intervention, in which physicians offered brief advice to encourage individuals to accept vaccination. This study aims to tailor this intervention to promote HZ vaccination among older adults.

The proposed study will be a two-arm randomised controlled trial and conducted across four community health centres in Shenzhen, China. A total of 388 participants aged 50 and above will be recruited and assigned to either the intervention arm or the standard-care arm. The primary outcome will be first-dose uptake, recorded within 3 weeks after intervention. The primary outcome will be calculated for each arm and compared using ² test.

This trial has been approved by the Ethics Committee of Southern Medical University (Ethical Approval (2024) No. 90). Our findings will be disseminated to patients, healthcare providers and stakeholders through outreach activities and published in peer-reviewed journals, as well as presented in scientific conferences to inform future research or evidence-based practices for public health promotion.

Chinese Clinical Trial Registry (No. ChiCTR2500100798). Registered on 15 April 2025.

Haemophilia is a rare inherited bleeding disorder with complex support and costly treatment. Comprehensive care for people with haemophilia (PwH) must take place in structured and continuously evaluated treatment centres. The aim of the Public Assistance for People with Haemophilia in Brazil Project (PATCH Project) is to assess the infrastructure, human resources and healthcare delivery processes of Brazilian Blood Centres (BC) involved in the provision of haemophilia care.

This is a nationwide cross-sectional study involving 98 BC across Brazil’s 26 states and the Federal District, focusing on the care provided to PwH. A self-administered structured questionnaire was prepared, based on national and international recommendations for management, treatment and outcomes assessment in PwH. The criteria of the World Federation of Haemophilia and the European Association for Haemophilia and Allied Disorders will be used to define standards of quality.

Ethical approval for this study was granted by the Human Research Ethics Committee of the Federal University of Goiás, the coordinating centre (protocol CAAE 53863221.8.0000.5078), and subsequently by all participating institutions. Written informed consent is obtained from all participants prior to enrolment. Study findings will be disseminated through publication in peer-reviewed journals and presentation at international scientific conferences. Research data will be managed in accordance with ethical and legal standards and will be made available on reasonable request to support future investigations.

Not applicable

Older age is one of the greatest risk factors of dementia, and the rural demographic is ageing in Canada. Compared with their urban counterparts, rural older adults often face unique challenges in accessing cognitive healthcare, which is exacerbated by a shortage of healthcare specialists, public transportation, finances, education, services and dispersed geography. This scoping review protocol outlines the methodology that will be used to examine the literature about the care priorities, service needs and lived experiences from the perspectives of rural older adults living with cognitive impairment and dementia in Canada.

Our scoping review protocol will follow the guidance of Arksey and O’Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extensions for Scoping Reviews checklist. Our search strategy will identify relevant peer-reviewed literature in databases including Cumulated Index in Nursing and Allied Health Literature (CINAHL), EMBASE, PsycINFO, PubMed, Web of Science and Scopus. The database search dates for this scoping review will be from 1 January 2015 to 1 January 2025. The data will be charted by two reviewers using a standardised data extraction table. Inductive content analysis will be performed using a three-step process.

Given this scoping review will be an examination of the published literature, human subjects will not be included in this research. Therefore, ethics approval is not required. Knowledge mobilisation and dissemination strategies will include peer-reviewed journal articles, conference presentations, community workshops, newsletter articles and webinars. This study may provide valuable information for healthcare practitioners, community leaders and policymakers working to support people living with cognitive impairment and dementia in rural communities.

Photobiomodulation (PBM) has shown promising effects in managing postoperative pain following conventional periapical surgery, although current evidence remains limited. This study aims to assess the effect of PBM on postoperative pain 24 hours after periapical surgery.

A randomised, controlled, double-blind trial will include 34 patients undergoing periapical surgery in the maxillary region, randomly assigned to an experimental group (n=17) or control group (n=17). The experimental group will receive PBM (GaAlAs diode laser, 808 nm, 100 mW, 4 J/cm², applied at five vestibular points) and placebo ibuprofen immediately and 24 hours postoperatively. The control group will receive simulated PBM and active ibuprofen. The primary outcome is postoperative pain assessed by the visual analogue scale at 24 hours. Secondary outcomes include pain at the seventh day, paracetamol intake, oedema, ecchymosis, soft tissue status and temperature at 24 hours and 7 days. Radiographic evaluation of healing will be performed at 1 and 3 months. Statistical analysis will be conducted based on data distribution, using repeated measures ANOVA (Analysis of Variance) or non-parametric equivalents for longitudinal outcomes, and appropriate tests for categorical variables. Significance will be set at p

The study was approved by the Human Research Ethics Committee of Universidad Católica del Uruguay (process no. 220914). Results will be disseminated to participants, healthcare professionals, the public and scientific communities.

NCT05935306.

TransformUs is a multicomponent school-based programme that offers teachers professional learning and resources aligned with the Australian curriculum to promote physically active teaching and learning, a supportive environment and physical activity opportunities during recess and lunch. The programme was originally developed for students in mainstream primary schools and has been proven efficacious for increasing physical activity and reducing sedentary behaviour in children without disability. The programme has been adapted for delivery with students with disabilities in primary and secondary schools (TransformUs All Abilities). This project aims to determine the implementation at scale and effectiveness of the TransformUs All Abilities programme to increase physical activity among primary and secondary school children and adolescents with disability. This protocol describes the hybrid implementation-effectiveness trial that will be used for this evaluation.

This study employs a hybrid type II implementation-effectiveness trial to evaluate the TransformUs All Abilities programme, targeting all government and independent, primary and secondary schools in Victoria, as well as special and mainstream secondary schools in Queensland and South Australia (n=2173 eligible schools). The effectiveness trial will focus on a subgroup of government/independent special schools for students with mild to moderate intellectual disability in Victoria, involving up to three intervention and three waitlist control schools (n=61 eligible schools). In both trials, outcomes will be guided by the RE-AIM framework focusing on reach, adoption and implementation (implementation trial) and effectiveness (effectiveness trial), with data collected at baseline and 6 months. The effectiveness trial will focus on students’ device-measured physical activity and sedentary behaviour—primary outcomes—and sleep, physical literacy and cognitive functions—secondary outcomes. Teacher feedback on the programme’s adaptation and their experience with programme implementation will also be collected, alongside qualitative feedback from a subsample of students regarding engagement/enjoyment and suggestions for improvements. Implementation data will be analysed descriptively and using linear mixed models to test changes over time. Effectiveness outcomes will be analysed using linear mixed models to compare intervention and waitlist control, accounting for confounding and school/classroom clustering. Interview data will be thematically analysed.

Ethical approval for this trial was obtained from the Deakin University Human Research Ethics Committee (2021-368). Clearance to conduct research in schools was also obtained from the Education Departments of Victoria (2023-004726), Queensland (550/27/2592) and South Australia (2022-0020). Informed consent is required for participation in the study. School staff can enrol in the implementation trial via the TransformUs website, while the effectiveness trial requires organisational, staff, parental/carer consent and student assent. Results will be disseminated through academic publications, scientific conference presentations and summary reports to schools, parents and partner organisations.

ACTRN12622001082796; Universal Trial Number: U1111-1281-1103; ACTRN12622001050741: U1111-1280-8828.

Many patients who are extubated after receiving mechanical ventilation for acute respiratory failure experience extubation failure (ie, require reintubation hours to days after extubation). High-quality evidence shows that extubating patients directly to non-invasive ventilation (NIV) or high-flow nasal cannula oxygen (HFNC), rather than conventional low-flow oxygen, can prevent extubation failure. These guideline-recommended interventions, however, require care coordination involving multiple intensive care unit (ICU) team members and are infrequently used. Interprofessional education (IPE), which teaches members of multiple professions together, could effectively address this implementation gap in complex, team-based, critical care settings, particularly when paired with a customisable protocol.

This batched, stepped-wedge, cluster-randomised, type 2 hybrid effectiveness–implementation trial will test three hypotheses: (1) when compared with traditional online education (OE), IPE increases implementation of preventive postextubation respiratory support, (2) the benefits of IPE are increased when paired with a clinical protocol and (3) preventive postextubation NIV for high-risk patients and preventive postextubation HFNC for low-risk patients reduce in-hospital mortality when compared with conventional postextubation oxygen therapy. The trial will recruit 24 clusters made up of one or more ICUs that care for at least 100 mechanically ventilated patients per year in a large multihospital health system in the USA. All clusters will receive OE, IPE and a clinical protocol, with timing determined by randomisation. We will also randomise half of the clusters to education promoting postextubation NIV for patients at high risk of extubation failure and preventive, postextubation HFNC for patients at lower risk, whereas the other half will be randomised to education promoting postextubation HFNC for all eligible patients. We will include all patients who are invasively mechanically ventilated for at least 24 hours. The primary implementation endpoint is the rate of use of postextubation NIV or HFNC among eligible participants. The primary clinical endpoint is in-hospital mortality truncated at 60 days from intubation.

This study was approved by the institutional review board of the University of Pittsburgh and an independent data safety monitoring board. We describe the methods herein using the Standard Protocol Items for Randomised Trials framework and discuss key design decisions. We will disseminate results to participating healthcare providers, through publication in a peer-reviewed medical journal and via presentations at international conferences.

NCT05523479.

To develop, evaluate and validate the musculoskeletal health climate questionnaire (MHCQ), a multidimensional questionnaire for measuring musculoskeletal health climate.

Cross-sectional test–retest study including systematic scale development and psychometric validation.

The questionnaire was developed following the best practice recommendations for scale development outlined by Boateng et al (2017), including item development, scale development and scale evaluation with input from experts, stakeholders and the target population. Validation was conducted among employees in three physically demanding occupations in Denmark (care workers, slaughterhouse workers and residential painters), where a total of 1420 participants were recruited through labour unions. Of these, 796 completed the retest survey 30 days later. Exploratory and confirmatory factor analyses (EFA and CFA, respectively), internal consistency (Cronbach’s α), test–retest reliability (intraclass correlation coefficients (ICC)) and SEM were used to assess the psychometric properties. Criterion validity was examined via associations with pain points, pain medication use and sickness absence. Construct validity was assessed using correlations with the prevent for work questionnaire (P4Wq).

EFA and CFA supported a four-factor model (supervisor’s practices, workplace practices, worker involvement practices and workers’ pain practices) with good to excellent fit (comparative fit index, 0.96–0.99; root mean square error of approximation, 0.04–0.06). All scales showed high internal consistency (α=0.80–0.88) and excellent test–retest reliability (ICC=0.86–0.92). Associations with musculoskeletal outcomes supported criterion validity. Weak to moderate correlations with the P4Wq subscales (rho

The MHCQ provides a validated, multidimensional tool to assess workplace climate related to musculoskeletal health. It can support workplace assessments and prevention efforts by capturing shared perceptions of leadership, support, involvement and pain-related norms. Further longitudinal research and the use of objective outcome data are needed to assess predictive validity and strengthen the instrument’s applicability across settings.

Progress at the intersection of artificial intelligence and paediatric neuroimaging necessitates large, heterogeneous datasets to generate robust and generalisable models. Retrospective analysis of clinical brain MRI scans offers a promising avenue to augment prospective research datasets, leveraging the extensive repositories of scans routinely acquired by hospital systems in the course of clinical care. Here, we present a systematic protocol for identifying ‘scans with limited imaging pathology’ through machine-assisted manual review of radiology reports.

The protocol employs a standardised grading scheme developed with expert neuroradiologists and implemented by non-clinician graders. Categorising scans based on the presence or absence of significant pathology and image quality concerns facilitates the repurposing of clinical brain MRI data for brain research. Such an approach has the potential to harness vast clinical imaging archives—exemplified by over 250 000 brain MRIs at the Children’s Hospital of Philadelphia—to address demographic biases in research participation, to increase sample size and to improve replicability in neurodevelopmental imaging research. Ultimately, this protocol aims to enable scalable, reliable identification of clinical control brain MRIs, supporting large-scale, generalisable neuroimaging studies of typical brain development and neurogenetic conditions.

Studies using datasets generated from this protocol will be disseminated in peer-reviewed journals and at academic conferences.

Adolescence is a critical period marked by rapid brain development and the onset of many mental health disorders. Brain MRI studies during adolescence, especially when paired with behavioural phenotypes and information about genetic risk factors, hold promise to advance early identification of mental health risk and spur the creation of targeted treatments to improve patient function, prognosis and quality of life. However, prospective neuroimaging is costly and time-intensive, and individuals who participate may not be reflective of the general population. These challenges are compounded when examining adolescents, as many families lack the time, energy or resources to participate in studies that use research-grade imaging. Repurposing clinical MRIs obviates many of the challenges of neuroimaging research. Here, we describe the brain-behaviour-genetics study protocol. This protocol describes procedures used to recruit participants with recent high-quality clinical brain MRIs and prospectively acquire genetic and sociobehavioural data, resulting in a highly cost-efficient design that harnesses a vast and underused neuroscientific resource.

The brain-behaviour-genetics protocol aims to recruit 1000 adolescents who have clinical brain MRIs contained in Children’s Hospital of Philadelphia’s electronic health record. One or both parents of the adolescent proband will be recruited when possible. Parents and adolescents will complete a series of self-report scales spanning the domains of mental health, trauma, risk and resilience. Saliva samples will be collected from the adolescent and at least one biological parent, using an at-home saliva collection kit. Subsequent analysis will examine associations between brain development, genetics and behavioural measures in adolescence.

Approval for the study had been obtained from the Children’s Hospital of Philadelphia’s institutional review board (IRB #23–0 20 851). Results will be published in peer-reviewed journals.

Advancements in technology for treating diabetes mellitus (DM) are progressing rapidly. With the growing availability and use of continuous glucose monitoring (CGM) systems and continuous subcutaneous insulin infusion (CSII), glucose regulation is improved in individuals with DM, which will lead to less long-term complications and reduce the overall disease burden on patients with DM. Collecting vast amount of biomedical data, these devices combined with clinical outcome data provide more insight into the development and treatment of the disease. The objective of the DIABASE initiative is to collect and examine real-world data from medical devices and clinical practice in a registry.

The ongoing study is structured as an observational study registry. Clinical data and real-world data from diabetes wearable devices, such as CGM and CSII, are aggregated in the database. Clinical data is automatically extracted from the hospital’s electronic health record. Data from wearables is periodically collected manually from the various online data platforms for sharing and automatically added to the database.

This study is exempted from ethics approval by the Medical Research Ethics Committees United (MEC-U) since participants are not subject to procedures and are not required to follow rules of behaviour (approval ID: AW23.009/W20.197). The execution of this study has been approved by the board of the study site Hospital Group Twente (ZGT) (ZGT20-40). Results will be shared through scientific meetings and publications and through articles for the general public.

NCT05584293; Pre-results.

Most oral cancers in India present in advanced stages and tend to have poor oncological outcomes. Chemotherapy has been associated with improved oncological outcomes in various cancers, but its role in oral cancer is still not well-defined in curative settings beyond radiosensitisation. Despite an excellent response rate, neoadjuvant chemotherapy trials have failed to show an oncological advantage. Earlier studies were limited by their heterogeneous patient population, including all head and neck subsites, and included both inoperable cancer and early-stage operable cases. Due to such patient selection, the intended results were never met. Patients with biologically aggressive diseases (advanced nodal disease) may derive greater benefit from induction chemotherapy (ICT). Therefore, we aim to determine the oncological advantage of adding ICT to oral squamous cell cancer with advanced nodal disease (N2–N3).

The study is an open-label, multicentre, randomised controlled trial, with an allocation ratio of 1:1, being conducted at seven leading cancer centres in India. The primary objective is to compare survival outcomes with and without ICT before surgery in patients with oral squamous cell carcinoma (OSCC) and advanced nodal disease, specifically focusing on 2-year disease-free survival (DFS). Secondary objectives include assessing overall survival (OS), clinical and pathological response rates, treatment compliance, treatment completion rates, adverse events, treatment-related toxicity (using Common Terminology Criteria for Adverse Events, V.5.0), quality of life (measured with Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck) and postoperative complications (using the modified Clavien-Dindo classification).

The study population consists of patients with operable OSCC and advanced nodal disease (N2–N3), adequate organ function, aged 18–65 years and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–2. The treatment arms are the standard arm Surgery arm (SURG), which involves surgery followed by adjuvant radiotherapy with or without concurrent chemotherapy, and the experimental arm (ICT), in which patients will receive two cycles of ICT using either cisplatin, docetaxel and 5-fluorouracil or cisplatin, docetaxel and capecitabine, followed by surgery and adjuvant radiotherapy with or without concurrent chemotherapy. The sample size was calculated to detect an HR of 0.67 with 80% power. A total of 184 events are required, and with an accrual rate of 15 patients per month, 300 patients will be recruited. DFS analysis will occur 32 months after the trial begins, and follow-up will continue for 5 years. OS analysis will be conducted when 184 deaths are observed. Taking 10% of the withdrawal of consent, a total of 346 patients need to be included.

This trial aims to establish the potential superiority of ICT or definitively determine its futility in OSCC with advanced nodal disease. A positive outcome could provide practice-changing data, particularly for Indian patients, whereas negative results could halt the use of ICT in this setting, directing research efforts towards more effective treatment strategies.

CTRI/2024/03/064586; NCT06737822; Institutional Ethics Committee (IEC) number: AIIMS/IEC/2023/4622 (lead site).