This project, in adult surgical patients, will evaluate whether the creation of a customised checklist, driven by a clinical decision support tool, is able to improve anaesthesia providers’ adherence to consensus guidelines and standardised practice recommendations for the prevention of postoperative nausea and vomiting (PONV).

The intervention will be evaluated using a sequential, repeated crossover design at the institutional level, with designated washout, control and intervention periods. The surgical case will serve as the unit of analysis. The primary outcome is adherence to appropriate PONV prophylaxis administration guidelines. Secondary outcomes include the incidence of PONV and length of stay in the postanaesthesia care unit (PACU).

This protocol and statistical analysis plan provide an outline of the study design, primary and secondary end points and analytic approach. The Advancing Strategies to Optimise the PerIopeRativE Management of PostOperative Nausea and Vomiting trial has received approval from the Vanderbilt University Institutional Review Board (IRB: 250773). The results will be disseminated through peer-reviewed publications and presentations at national conferences. Findings from this trial will inform best practices for timely antiemetic prophylaxis, with the goal of reducing PONV incidence and shortening PACU stay.

NCT07152249.

Due to the multisystemic nature of sickle cell disease (SCD), complications can occur together and thus discerning costs associated with individual complications requires a methodology that can estimate the costs of a given complication while accounting for the presence of other complications. In this study, we aimed to estimate period-based incremental costs associated with specific chronic complications in patients with SCD in England while accounting for multimorbidity.

All-cause primary and secondary care healthcare resource utilisation (HCRU) was obtained for a retrospective cohort of patients with SCD using Clinical Practice Research Datalink (CPRD) Aurum linked to Hospital Episode Statistics (HES) datasets. Annualised HCRU and costs were calculated, dividing patient-level events by patient-level time (in years) to obtain per person per year estimates. A series of generalised linear models were used with adjustment for demographic factors and proportion of follow-up time with each complication to estimate the costs associated with 10 chronic SCD-related complications of interest. For these costs, annual equivalent costs can be obtained by dividing by the median follow-up time of 4.74 years.

Patients with a diagnosis of SCD, with or without complications, in CPRD or HES with at least 12 months follow-up.

Period-based all-cause direct healthcare costs.

Of the 1271 patients with SCD included in the study, 49.9% (n=634) had at least one complication and of these 41.3% (n=262) had two or more complications either at baseline or during follow-up. Patients with complications had higher all-cause healthcare costs compared with patients without complications (mean (SD) annualised cost £16 058 (£21 488) vs £4399 (£6635)). Patients with complications had four times the number of annualised inpatient admissions (6.1 vs 1.5 admissions) and more than double the number of annualised bed days in hospital (8.3 vs 3.8 days) over a median 4.74 years of follow-up. Of the complications evaluated, end-stage renal disease had the highest estimated incremental cost of £252 083 (95% CI £214 478 to £283 745) over 4.74 years; this is in addition to the £18 547 period-based cost among patients with SCD without complications. Osteonecrosis was the most common complication with an estimated incremental cost of £27 399 (95% CI £6417 to £43 319) over the same period.

Estimating the cost of complications, while accounting for multimorbidity, is essential to determine the true direct cost of SCD. The modelling method presented in our study provides period-based estimates of cost and hospital admissions for individual complications in patients with SCD, accounting for multimorbidity. This approach can be used and extended to other diseases with multisystemic complications to estimate the direct HCRU and costs of individual complications.

Statins are a cornerstone of cardiovascular disease prevention yet remain underused among eligible patients. Clinical decision support systems embedded in electronic health records (EHRs) are commonly used to encourage guideline-concordant prescribing. Interruptive reminders (eg, pop-ups) may be effective but interfere with clinical workflows and contribute to alert fatigue. Non-interruptive alerts are less intrusive, but their effectiveness remains unclear. The Interruptive versus Non-Interruptive Reminders for Statin tHerApy in Primary Care (INIRSHA-PC) trial is designed to evaluate the comparative effectiveness of interruptive and non-interruptive reminders on statin-prescribing rates.

INIRSHA-PC is a single-centre, pragmatic, three-arm, parallel-group randomised controlled trial embedded in the EHR at Vanderbilt University Medical Center. The trial will enrol adults aged 18–74 seen in primary care who are eligible for, but not currently prescribed, statin therapy. The planned sample size is 3000 patients (1000 per arm). Enrolled patients will be randomised 1:1:1 to (1) interruptive reminder, (2) non-interruptive reminder or (3) no reminder (usual care). The primary outcome is statin prescription within 24 hours of enrolment. Secondary outcomes are statin prescribing within 12 months and low-density lipoprotein cholesterol levels measured between 30 days and 12 months after enrolment. Enrolment began on 14 August 2024. The study is expected to be completed on 19 November 2025.

The trial has been approved by the Vanderbilt University Medical Center Institutional Review Board with waiver of patient informed consent (IRB number: 240419). Results will be disseminated through peer-reviewed publication and presentation at scientific conferences.

NCT06456658.

The objective of this study was to test whether an airtime reward increased tuberculosis (TB) Check screening uptake. This served as a feasibility study for the planned Phase 2, which aimed to test behavioural messaging to boost take-up of TB testing among users who were advised to get tested by TB Check.

The study was a randomised controlled trial with a parallel design.

This study assessed mHealth support to boost TB testing in high-burden Cape Town clinics.

Patients aged 18 or above with a valid mobile phone number that had been added within the last 5 years were invited by the Western Cape Department of Health and Wellness through unsolicited text messages to screen for TB using TB Check.

Patients in the intervention group (n=1250) were additionally offered R15 airtime for completing the screening and participating in the research study. Patients were allocated to the intervention or control group through parallel randomisation with equal group size.

The primary outcome was the number of TB Check screenings completed within 1 week of the SMS invitation being sent.

Messages were successfully delivered to 616 patients in the control group and 633 patients in the intervention group. Uptake of the invitation by the intended recipients was very low. Eight users in the control group and 20 users in the intervention group initiated a self-screening (1.3% vs 3.2% of delivered messages; 95% CI of difference (0.2 to 3.5)), but only three users in the control group and seven users in the intervention group successfully completed a self-screening (0.49% vs 1.11% of delivered messages; 95% CI of difference (–0.4 to 1.6)). Low delivery of text message invitations (50.0%) and low completion of users who started the screening (35.7%) posed additional challenges. No adverse events were recorded.

The addition of a small airtime participation reward to unsolicited text message invitations did not appear to be an effective tool to reach targeted individuals in this context. The results of Phase 1 reported here suggested that Phase 2 would not be feasible, so we did not proceed with the planned Phase 2. However, uptake of incentivised self-screening was unexpectedly high among users who were not originally invited (presumably known contacts of the original invitees). Within 5 days of the invitations being sent, 1962 unique self-screenings had taken place using the incentive code; only 7 of these users were originally invited. The lessons learnt from this study can help to inform future efforts to promote TB self-screening, mHealth initiatives and attempts to engage with patients via text message. 

The study was pre-registered with the South African National Clinical Trials Registry (Phase 1 trial no DOH-27-112023-9045, Phase 2 trial no DOH-27-112023-4944) and the Pan African Clinical Trials Registry (Phase 1 trial no PACTR202311529334858).

Tobacco use is the most significant modifiable risk factor for adverse health outcomes, and early research indicates there are also significant harms associated with vaping. National targets aim to reduce smoking and vaping during pregnancy for Aboriginal and Torres Strait Islander people. While most Aboriginal and Torres Strait Islander people want to quit, cessation is frequently attempted without support, increasing the chance of relapse. Group-based smoking cessation programmes increase quit success by 50%–130% in the general population; however, they have never been evaluated in Aboriginal and/or Torres Strait Islander communities.

The Gulibaa study is an Indigenous-led and community-embedded project that will co-design, implement and evaluate a group-based model of care to support Aboriginal and Torres Strait Islander women to be smoke- and vape-free. Staff of Health Services in New South Wales, Australia, will receive training to deliver a face-to-face group-based smoking and vaping cessation intervention. Aboriginal and/or Torres Strait Islander people who identify as a woman or non-binary, are pregnant or of reproductive age (16 to 49 years), currently smoke or vape at least once per day and are willing to attend the programme are eligible to participate. Up to 500 participants will be recruited. A mixed method evaluation approach will be implemented guided by the RE-AIM framework. Outcomes will include intervention reach, intervention effectiveness (determined primarily by self-reported 7-day point prevalence abstinence at 6 months follow-up), acceptability and feasibility of the intervention, programme fidelity and maintenance and cost effectiveness.

Embedding culturally safe support to quit during pregnancy can result in improved outcomes for both mother and child and immediately improve intergenerational health and well-being. Ethics approval has been provided by the Aboriginal Health and Medical Research Council and the University of Newcastle. Study findings will be disseminated to Aboriginal and Torres Strait Islander communities in ways that are meaningful to them, as well as through Aboriginal health services, key national bodies, relevant state and federal government departments.

ACTRN12625001050448.

Duchenne and Becker muscular dystrophies (DMD and BMD) are devastating conditions characterised by progressive muscle degeneration and weakness. Despite advances in understanding their pathogenetic processes, there is a critical need for reliable biomarkers to aid in patient stratification and inform clinical decision-making, predict disease progression and evaluate therapeutic responses. Several promising protein biomarkers have been investigated as potential diagnostic/prognostic tools, but, to date, this evidence has not been systematically synthesised. We aim to comprehensively and critically review and summarise published studies reporting the use of protein signatures of muscular damage in DMD and BMD.

We will systematically search Ovid MEDLINE (PubMed), OVID Embase, OVID Evidence-Based Medicine Reviews and Cochrane Library to retrieve all relevant articles. For ongoing trials, we will search WHO International clinical trials registry and ClinicalTrials.gov registry. We will include studies that measure circulating and urine levels of established and/or promising protein biomarkers associated with skeletal muscular damage and disease progression, such as creatine kinase, myoglobin, skeletal troponin I fast-twitch (type II), myostatin, creatine/creatinine ratio, creatinine and titin. We will consider randomised controlled trials, observational studies and longitudinal cohort studies with serial sampling, without restrictions on sample size, geographic location or language, while excluding animal and in vitro studies. Two independent reviewers will screen articles for inclusion using predefined eligibility criteria and extract data of retained articles. A third author will be consulted in case of disagreement. The approach recommended by the Agency for Healthcare Research and Quality’s Methods Guide for Effectiveness and Comparative Effectiveness Reviews will be used. The risk of bias and reporting quality will be assessed with standardised scales. The analysis will involve a structured narrative synthesis and evidentiary tables. If a meta-analysis is possible, biomarker data for each outcome will be pooled using random effects models. Subgroup analyses have been planned as a function of age, genetic mutation, disease severity, imaging and clinical assessment, length of the observation and risk of bias.

Ethics approval is not required for this study as no original data will be collected. The findings will be shared through peer-reviewed publications and conference presentations. Additionally, this systematic review will guide the recommendations of the Duchenne Regulatory Science Consortium. This work will provide a rigorous, exhaustive and accessible evidence synthesis to identify candidate biomarkers of potential clinical value. Furthermore, it is expected that these results could be used to facilitate the development of future research strategies and guidelines, inform resource allocation decisions and accelerate the route towards clinical implementation of biomarkers for DMD and BMD.

CRD42024549471. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024549471

As care and rehabilitation poststroke are increasingly moving into persons’ home environment, the importance of support from social networks in self-management and rehabilitation has emerged as an important topic for research and practice. While there are instruments used to assess social support and collective efficacy, a clearer scope of the availability and quality of these instruments is needed. This clarification will enable the development of interventions integrating social network perspectives in poststroke rehabilitation.

To assess the availability and quality of instruments assessing social support and collective efficacy, a scoping review will be conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews guidelines (PRISMA-ScR). Literature searches conducted between 14 November 2024 and 15 November 2024 in the CINAHL and PubMed/Medline databases resulted in 4631 articles potentially eligible. After removing duplicates, 4121 articles’ titles and abstracts were initially screened. Full-text screening, searches of reference lists and data extraction started in June 2025. Starting August 2025, two reviewers will assess the full texts against the inclusion criteria in Covidence using a coding template. Identified instruments will be appraised following the COSMIN (Consensus-based Standards for the selection of health Measurement INstruments guidelines) and analysed using a narrative descriptive method. Results will be reported in February 2026 according to PRISMA-ScR guidelines.

Ethical approval is not required for this scoping review, as it does not involve primary data. However, this review follows established ethical guidelines and best practices, and included studies will be reviewed to ensure that they received ethical approval and included informed consent. Results from the review will be disseminated through an article in a scientific journal, at relevant conferences and surmised to stroke organisations. A policy brief will be developed for health and social care professionals and policy makers.

Child undernutrition is linked to substantial national economic and health losses in low- and middle-income countries, including Rwanda. Although the causal and contextual factors contributing to chronic malnutrition in children in Rwanda have been explored, the role of the mothers’ mental health has not been fully investigated. This study aims to determine the prevalence of major depressive disorders, generalised anxiety and suicide risk among mothers in Rwanda and to explore their association with child stunting.

This study used a cross-sectional, population-based design.

Participants included children aged 1–36 months (n=601) and their mothers (n=601) in Rwanda’s Northern Province. Mothers’ mental health was assessed using four modules from the Mini International Neuropsychiatric Interview, based on the Diagnostic and Statistical Manual of Mental Disorders. Child anthropometric measurements followed WHO guidelines.

The primary outcome of the study was child stunting that was defined as a height-for-age Z (HAZ) score

Among the 601 mothers assessed, generalised anxiety disorder had the highest prevalence (36.6%), followed by recurrent major depressive disorder (27.3%), current major depressive disorder (22.7%) and current suicide risk (18.2%). Among the children, 27.1% were stunted, with prevalence rising from 9.8% in infants (1–12 months) to 39.9% in toddlers (25–36 months). Current major depressive disorders in mothers were associated with child stunting (adjusted OR 1.67; 95% CI 1.06 to 2.61). Affected children had lower HAZ scores (–1.68±1.36 vs –1.30±1.09; p=0.004), and excess relative risk (ERR) analysis confirmed depression as a significant risk factor (ERR: 1.56; p=0.005).

Mental health disorders in mothers, especially depression, showed a significant association with child stunting. Addressing mental health disorders in mothers is essential for improving child nutritional outcomes.

The use of digitally enabled technology is considered a promising platform to prevent morbidity and enhance youth mental health as youth are growing up in the digital world and accessing the Internet at increasingly younger age. This scoping review will identify, describe and categorise the models, frameworks and strategies that have been used to study the implementation of digital mental health interventions targeted at youth aged 15–34 years.

We will conduct a scoping review following the Arksey-O’Malley five-stage scoping review method and the Scoping Review Methods Manual by the Joanna Briggs Institute. Implementation methods will be operationalised according to pre-established aims: (1) process models that describe or guide the implementation process; (2) evaluation frameworks evaluating or measuring the success of implementation; and (3) implementation strategies used in isolation or combination in implementation research and practice. Primary research studies in all languages will be identified in CINAHL, Cochrane Central Register of Controlled Trials, Embase, ERIC, Education Research Complete, MEDLINE and APA PsycINFO on 6 January 2025. Two reviewers will calibrate screening criteria and the data charting form and will independently screen records and abstract data. We will use the Evidence Standards Framework for Digital Health Technologies by the National Institute for Health and Care Excellence to classify digital interventions based on functions, and a pre-established working taxonomy to synthesise conceptually distinct implementation outcomes. Convergent integrated data synthesis will be performed.

Ethical approval is not applicable as this scoping review will be conducted only on data presented in the published literature. Findings will be published and directly infused into our multidisciplinary team of academic researchers, youth partners, health professionals and knowledge users (healthcare and non-governmental organisation decision makers) to co-design and pilot test a digital psychoeducational health intervention to engage, educate and empower youth to be informed stewards of their mental health.

To develop and validate educational clinical vignettes (CVs) based on real-life patients with serious pathology from the disciplines of oncology, internal medicine and orthopaedics that are relevant for physiotherapists (PTs) working in a non-direct access system.

A mixed-methods study using an iterative design was employed to develop and validate CVs that focused on serious pathology.

Academic and clinical settings within health faculties at three universities in Austria and the UK.

Medical doctors (MD) (n=3) and PTs (n=4) developed CVs in the disciplines of internal medicine, oncology and orthopaedics. Validation of the CVs was undertaken in three stages: internal validation by the research team (n=7), external validation by MDs (n=3) and external validation by PTs (n=18).

25 CVs focusing on internal medicine (9), oncology (8) and orthopaedics (8) were developed. Results of the consensus method of Haute Autorité de Santé ranged between 7 and 9 in the internal validation stage. In the external validation stage with MDs, one orthopaedic CV was excluded, resulting in a final total of 24 validated CVs.

This is the first time educational CVs have been developed and validated across such a broad range of pathologies for countries without direct access to physiotherapy, for use in the education of PTs. Furthermore, the approach described in the Methods section of this paper may serve as a template in similar future projects.

Dysmenorrhoea (period pain) is a global public health issue affecting up to 91% of the 1.8 billion individuals who menstruate. While research has emphasised the improvement of menstrual health in low-middle-income countries, undertreated dysmenorrhoea remains an issue in high-income countries (HICs), where individuals often assume their pain experiences are normal. Studies report that individuals with dysmenorrhoea delay seeking medical care, avoid it entirely or are subjected to diagnostic and treatment delays. Difficulties accessing care are troubling, as individuals may suffer without access to evidence-based techniques, as well as the potential for underlying pathologies (eg, endometriosis, pelvic inflammatory disease) to go undiagnosed.

Many HICs have launched strategies for women’s health to address gaps in care access and knowledge around menstruation. Guided by Levesque and colleagues' (2013) Conceptual Framework of Access to Healthcare, this review will contribute to these strategies by providing an overview of factors affecting healthcare access for dysmenorrhoea in HICs from the point of perceiving a healthcare need to engaging with care, as well as factors affecting perceived quality of care.

This scoping review will follow the Joanna Briggs Institute’s (JBI) guidance for scoping reviews and will be conducted with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist extension for Scoping Reviews. Guided by Levesque and colleagues’ (2013) Conceptual Framework of Access to Healthcare, searching will seek to locate both peer-reviewed studies across PubMed, CINAHL, PsycINFO and Web of Science databases, as well as using web scraping to locate relevant grey literature. Results will be synthesised and mapped to construct a pathway to care, highlighting factors affecting the healthcare access for dysmenorrhoea, as well as factors related to the quality of healthcare interactions.

This review does not require ethical approval, as only existing data will be analysed. Results will be shared using peer-reviewed publications and conference presentations. Datasets emerging from the study will be made available on Open Science Framework.

This review was initially registered on Open Science Framework (https://osf.io/2dsrc/) in February 2024, with an updated protocol registered in February 2025.

Intrusive nightmares are a hallmark symptom of post-traumatic stress disorder (PTSD), contributing significantly to psychiatric comorbidities, impaired physical health and diminished social functioning. Currently, no pharmacological treatments are specifically approved for managing PTSD-related nightmares. However, emerging evidence suggests that adrenoceptor-targeting agents may offer therapeutic potential. Notably, clonidine and doxazosin have demonstrated efficacy in reducing PTSD-associated nightmares, as indicated by findings from open-label studies and small randomised controlled trials.

This study is a multicentre, double-blind, randomised (1:1:1), placebo-controlled, parallel-group interventional trial. A total of 189 eligible patients will be randomly assigned to receive clonidine, doxazosin or placebo, with a once-daily oral dose administered at bedtime for 10 weeks. The primary efficacy endpoint is the Clinician-Administered PTSD Scale B2 score at week 10, which measures the frequency and intensity of nightmares. Secondary efficacy endpoints include other PTSD-specific symptoms. Additionally, the safety of clonidine and doxazosin will be assessed.

The study was approved by the Ethics Committee of the State of Berlin (Ethik-Kommission des Landes Berlin) (Reference: 21-683-Haupt-IV E 13), on 14 March 2022 and by the relevant federal authority, the Bundesinstitut für Arzneimittel und Medizinprodukte, reference 4044931. The study was conducted in accordance with the relevant guidelines and regulations. The study results will be published in peer-reviewed journals and presented at both national and international conferences.

NCT05360953, EudraCT 2021-000319-21.

School environments that encourage children to be physically active can embed lifelong positive health behaviours and contribute towards reducing health inequalities. The Health and Activity of Pupils in the Primary Years (HAPPY) study aims to: (1) explore the extent to which the WHO criteria for creating active school environments are implemented by primary schools and (2) examine associations between active school environments and children’s physical activity, mental health and educational performance.

The HAPPY study is a quasi-experimental study comprising: (1) a survey of state-funded Greater London primary schools to identify implementation of the WHO’s six criteria and (2) a cross-sectional study to examine associations between schools’ active environment score (derived from the school survey) and pupils’ physical activity, mental health and educational performance. For our cross-sectional study, we will recruit up to 1000 year-three children (aged 7–8 years). Our primary outcome is accelerometer (GENEActiv) assessed physical activity, our secondary outcomes are parent-reported child mental health (Strengths and Difficulties Questionnaire) and teacher-reported educational performance (age-related expectations). Using multilevel mixed-effects regression models, we will examine associations between the active environment score and physical activity. Physical activity will be included as a measure of acceleration and also different intensities (light, moderate, vigorous). We will repeat this analysis to examine associations between the active environment score and mental health and educational performance. We will adjust for school characteristics and area-level deprivation and include pupil characteristics (eg, sex, ethnic group) as covariates. Clustering at the school level will be included as a random effect.

Ethical approval has been obtained from Imperial College Research Ethics Committee (ref: 6800895). Findings will be disseminated through a summary report to all participating schools, peer-reviewed publications, presentations at national and international conferences and National Institute for Health and Care Research policy briefings.