To develop and user-test a patient decision aid for people diagnosed with degenerative cervical myelopathy and who are considering surgery.

Mixed-methods study describing the development of a patient decision aid.

A draft decision aid was developed by a multidisciplinary steering group (including study authors with degenerative cervical myelopathy, health professionals and researchers) informed by the best available evidence, authorship consensus and existing patient decision aids.

Patient-participants and health professional-participants who manage people with degenerative cervical myelopathy were recruited through social media and the steering group’s research and practice network. Quantitative questionnaires were used to gather baseline data, descriptive feedback, refine the decision aid and assess its acceptability. Qualitative semi-structured interviews were conducted online to gather feedback on the decision aid and were analysed using reflexive thematic analysis.

We conducted 32 interviews: 19 patient-participants and 13 health professional-participants who manage people with degenerative cervical myelopathy (neurosurgeons, neurologists, physiotherapists, orthopaedic surgeons, general practitioners, rehabilitation and pain specialists and consultant occupational physicians and chiropractors). Participants were from 10 countries (Australia, Canada, Cyprus, Germany, Ireland, New Zealand, Sweden, Switzerland, United Kingdom and USA). Most participants rated the decision aid’s acceptability as good-to-excellent and agreed with most aspects of the decision aid (eg, defining degenerative cervical myelopathy, management recommendations, potential benefits and harms, questions to consider asking a health professional).

Our patient decision aid was rated as an acceptable tool by both health professional-participants who treat degenerative cervical myelopathy and patient-participants with lived experience of degenerative cervical myelopathy. This decision aid can be used by clinicians and people with degenerative cervical myelopathy to help with shared decision making following a diagnosis of degenerative cervical myelopathy. A study testing the potential benefits of this decision aid in a clinical setting is recommended.

Chagas disease affects millions of individuals across Latin America and imposes a substantial economic burden on healthcare systems, particularly in rural and underserved regions. Chronic Chagasic cardiomyopathy remains one of the leading causes of heart failure-related mortality in endemic countries. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has emerged as a potential biomarker of myocardial fibrosis in cardiomyopathies. This study was designed to investigate the association between TIMP-1 and myocardial fibrosis in chronic Chagas disease and to assess its potential as an early biomarker of fibrotic remodelling.

Bottom of form: The PTICH trial is a single-centre, prospective observational cohort study conducted at a government reference clinic in Pernambuco, Brazil. The study aims to enrol 210 adults with Chagas heart disease: 140 without ventricular dysfunction (left ventricular ejection fraction (LVEF) ≥52% in women and ≥54% in men) and 70 with ventricular dysfunction (LVEF

The Research Ethics Committee (REC) of Chagas disease and heart failure outpatient clinic—PROCAPE approved the PTICH trial (CAAE number: 65746322.8.1001.5192). Written informed consent has been obtained from all participants enrolled to date, and data handling is in compliance with applicable privacy and data protection regulations. Study findings will be disseminated through targeted outreach to civil society, the scientific community, healthcare professionals and Brazilian Unified Health System (SUS) policymakers; school-based science communication activities conducted in collaboration with state education departments (potentially including oral health educational materials); policy briefs and targeted reports for public health managers; technical meetings and institutional presentations; a plain-language summary published on the institutional website; and submissions to peer-reviewed journals and presentations at academic and health policy conferences.

RBR-3dcrj98.

Spirituality has gained increasing attention in healthcare, particularly in palliative care, as it supports meaning, purpose and connection during illness. While literature extensively explores patients’ spiritual needs, growing evidence highlights the importance of addressing the spiritual needs of caregivers and healthcare professionals. Caregivers and relatives often face emotional, ethical and practical challenges during prolonged care pathways, impacting their well-being. Limited training and tools can hinder spiritual care, contributing to distress and burnout among professionals and unmet needs for families. Addressing spirituality in neurodegenerative disease palliative care is essential for holistic, person-centred approaches that foster coping, hope and ethical decision-making. This scoping review aims to map evidence on spiritual needs and challenges of caregivers, relatives and healthcare staff in end-stage neurodegenerative disease care.

This review will follow the Joanna Briggs Institute framework (JBI) for scoping reviews. The search and reporting process will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist. Inclusion criteria followed JBI’s population, concept and context framework with no date or geographical limits; only English and Italian sources ensured accurate interpretation. Searches will use university-access databases and grey literature to capture policy and non-peer-reviewed sources. Databases selected: PubMed, CINAHL, APA PsycINFO and Scopus for comprehensive, multidisciplinary coverage. This inclusive approach is aligned with the purpose of scoping reviews, which aim to map the breadth and depth of available literature. Researchers independently screened titles/abstracts in Rayyan software with blinding, resolved discrepancies collaboratively, piloted and refined extraction tables, and jointly synthesised themes through iterative meetings to ensure rigour and consensus. Findings will highlight existing knowledge, identify gaps and inform future research and practice.

Since secondary data will be analysed, no ethical approval is required. The results will be disseminated through publications subject to peer review. The protocol has been registered with the Open Science Framework https://doi.org/10.17605/OSF.IO/X9275

Regular physical activity declines with age, particularly among older adults with health conditions. Digital tools, including wearable devices, mobile applications, virtual reality systems and tele-exercise platforms, offer promising ways to promote physical activity. However, the technological components of these tools and their reported associations with motivation, adherence and physical activity levels remain underexplored. This scoping review aims to map the characteristics and functionalities of digital tools used to promote physical activity among older adults with health conditions and to examine how these components are described in relation to psychobehavioural outcomes.

This review will follow the Joanna Briggs Institute methodological guidance. Searches will be conducted in PubMed, Web of Science, PsycInfo and SportDiscus. The reference lists of included studies will also be screened to identify additional relevant articles. Eligible studies will include adults aged 60 years or older with health conditions using digital tools for physical activity. Two reviewers will independently select studies and extract data on the components of digital tools. A descriptive synthesis will summarise the key technological characteristics, and a content analysis will identify and categorise tool components, describing how they are reported in relation to psychobehavioural outcomes and theoretical constructs.

This review does not involve human participants, so ethical approval is not required. Findings will be disseminated through peer-reviewed publications, conference presentations and stakeholder summaries.

Video-assisted thoracoscopic surgery (VATS) lobectomy is a commonly employed surgical technique for the management of operable early stage non-small cell lung cancer (NSCLC). This procedure, however, is dependent on the patient’s ability to tolerate surgery. In light of this, stereotactic ablative radiotherapy (SABR) has emerged as a viable alternative treatment strategy for patients who are inoperable or who refuse surgery. Considering the lack of randomised controlled trials and the increased risk of bias in observational cohort studies, this study protocol proposes an emulated target trial design to investigate the causal effect of SABR, in comparison to VATS, on overall survival in operable early stage NSCLC patients.

Data on NSCLC patients will be collected from routinely collected university hospital records linked with German cancer registry data. This study protocol was developed using the target trial methodology outlined by Hernan et al. The protocol establishes specific parameters for key trial components in order to mitigate bias in the analysis of observational data and to facilitate the calculation of causal estimands. The target trial design that would be emulated is a multicentre open-label two-parallel arm superiority randomised trial. Mediators and confounding variables were determined through the use of a directed acyclic graph. The statistical analysis aims to measure the per-protocol and intention to treat effect of SABR versus VATS within 3 months of diagnosis, on survival, through the difference in restricted mean survival times, using weighted non-parametric Kaplan-Meier curves.

The Ethics Committee of the Medical Faculty of Martin Luther University Halle-Wittenberg with an approved addendum with Dnr 2023–112 has approved this study. The study uses anonymised routinely collected hospital and cancer registry data in accordance with applicable data protection regulations. Results will be disseminated through peer-reviewed publications and presentations at scientific conferences.

Non-communicable diseases (NCDs) have become the leading cause of mortality globally, with a sharp rise in Iran due to lifestyle changes and urbanisation. Although many NCD risk factors are modifiable, limited understanding of their determinants hinders effective prevention. To address this, the Prospective Epidemiological Research Studies in Iran (PERSIAN) Cohort was established in 2014 to study NCDs nationwide. The Sabzevar PERSIAN Cohort Study (SPECS) is the first in northeastern Iran, aiming to investigate environmental and social factors influencing NCDs in a unique regional context.

SPECS enrolled 5174 adults (aged 35–70 years) in northeastern Iran between January 2018 and January 2019 through a census and an online registration process. The baseline data collection included demographic verification, informed consent, health questionnaires, anthropometric measurements and biological samples (blood, urine, hair, nails). The annual follow-up began in April 2019, with full reassessments every 5 years over a 15-year period. The data is gathered via an active and passive follow-up, supported by trained staff and registry linkages.

Of the 5174 participants, 4241 (81%) remained in the study. Among the cohort, 54.5% were female, with a mean age of 50.5 years. The majority were married (93.5%), and nearly half had at least high-school education (46.5%) and moderate socioeconomic status (49.4%). Drug abuse history (smoking/drugs) was reported by about 15% of the sample. The mean body mass index was 26.9 kg/m², and the average blood pressure was higher in males (118.1/74.0 mm Hg) than in females (111.5/70.2 mm Hg). The common conditions included hypertension (22.8%), kidney stones (22.4%), fatty liver (15.4%) and diabetes (13.8%). Cancer had the highest treatment rate (100%), while fatty liver had the lowest (70.1%). Stroke had the highest mean age of onset (51.2 years), and epilepsy the lowest (23.7 years). All health data were self-reported.

SPECS, part of the national PERSIAN cohort initiative, is the only adult NCD-focused study in Khorasan Razavi. Its 15-year follow-up aims to generate region-specific insights into the incidence of NCDs and their risk factors. The ethnically homogeneous sample enhances statistical power, and the findings may inform culturally tailored health policies. While self-reported data have limitations due to bias, high initial participation and access to free healthcare support long-term engagement, especially among lower-income groups.

Patient decision aids (PtDAs) are effective interventions to support patient involvement in health decisions and have the potential to impact favourably on health inequities by reducing gender bias in clinical practice. The aim was to explore sex and gender reporting and differences in randomised controlled trials (RCTs) evaluating PtDAs for adults making treatment or screening decisions.

Secondary analysis of the Cochrane review of PtDAs of RCTs that reported sex and/or gender. The original review searched MEDLINE, Embase, PsychINFO and EBSCO from journal inception to March 2022. Two team members independently screened citations, extracted data and assessed risk of bias. For this secondary analysis, we only included primary outcomes from the original review. We assessed appropriate use of terminology for sex (biological attribute) and gender (social construct). When terms were used interchangeably, it was considered inaccurate. Findings were synthesised descriptively, and we used meta-analysis when two or more RCTs were conducted with females/women or males/men using similar outcome measures.

Informed values-choice congruence and the quality of the decision-making process (eg, knowledge, accurate risk perceptions, feeling informed, clear values, participation in decision making, undecided) and adverse events (eg, decision regret, emotional distress) by sex and gender.

Of 209 RCTs in the original review, 206 reported sex and/or gender, with 35 (17%) using accurate terminology. Of 206 RCTs, 70 were with females/women only, 27 males/men only, 12 analysed by sex/gender and 97 RCTs did not disaggregate findings by sex or gender. Meta-analysis comparing RCTs for females/women to usual care and RCTs for males/men only compared with usual care showed similar mean differences in knowledge scores (10.84 vs 9.38 out of 100; p=0.44). Males/men had significantly higher self-reported participation in decision making compared with females/women (RR 3.16 vs 0.95; p

In PtDA RCTs, sex and gender terms are used interchangeably and 6% analysed outcomes by sex or gender. Meta-analysis of males/men only given PtDAs showed higher self-reported decision making participation in clinical practice compared to usual care versus females/women only compared with usual care. Researchers must improve reporting sex and gender in PtDA RCTs to assess how it influences health inequities.

To assess the mental health status and identify associated factors among rural adult women in Bangladesh.

Cross-sectional study using face-to-face interviews with a semistructured questionnaire.

Data were collected between January and February 2025 in three rural upazilas (Dhamrai, Nawabganj and Sreepur) using multistage systematic sampling. The semistructured questionnaire included sociodemographic characteristics, household assets and the Depression Anxiety Stress Scale-21 (DASS-21). The wealth index was calculated using principal component analysis. Cases with mild to extreme levels of depression, anxiety and stress were grouped together to indicate the presence of any level of the three mental health problems. Statistical analyses included descriptive statistics, bivariate analyses using ², Fisher’s exact test and Welch two-sample t-test, and multivariable binary logistic regression to identify predictive factors of mental problems. A Venn diagram was generated to display the proportion of patients with anxiety, depression and stress. Data analysis was performed using SPSS (V.26) and R Studio (V.2025.05) with a significance level of p

A total of 1350 women aged 18 years or older who were available at home during the data collection period and gave consent to participate. Women who were unable to participate due to illness were excluded.

Participants had a mean (±SD) age of 36.35 (±12.58) years. The prevalence of depression, anxiety and stress was 47.7%, 60.7% and 23.2%, respectively. Moderate severity was most common among patients with depression (20.34%), anxiety (24.20%) and stress (8.03%). 20% of participants experienced all three conditions simultaneously, with 22% having both depression and anxiety. Multivariable analysis revealed that factors associated with an increased odds of depression, anxiety and stress were chronic diseases (ORs (95% CIs): 2.02 (1.50 to 2.73), 1.44 (1.05 to 1.99) and 1.91 (1.35 to 2.71), respectively) and history of abuse (1.84 (1.28 to 2.66); 3.15 (2.06 to 4.93) and 1.91 (1.28 to 2.83), respectively). Family history of mental illness was associated with an increased odds of anxiety (1.71 (95% CI 1.12 to 2.87)) and stress (1.61 (95% CI 1.01 to 2.52)). So was the presence of a caregiving role (1.68 (95% CI 1.18 to 2.42) and 1.50 (95% CI 1.02 to 2.19) for anxiety and stress, respectively). Having a financial problem was associated with an increased odds of anxiety (1.52 (95% CI 1.16 to 2.00)). A happy family relationship was associated with decreased odds of depression (0.28 (95% CI 0.20 to 0.93)), anxiety (0.22 (95% CI 0.06 to 0.60)) and stress (0.50 (95% CI 0.25 to 1.00)). Conjugal satisfaction was protective against anxiety (0.42 (95% CI 0.18 to 0.80) and stress (0.32 (95% CI 0.17 to 0.59)). Unexpectedly, higher wealth status (being rich) increased depression (1.56 (95% CI 1.04 to 2.34) and anxiety (1.57 (95% CI 1.03 to 2.41) risk.

A major segment of rural adult women of Bangladesh experiences mental health problems. The findings recommend community-based comprehensive mental health screening programmes, interventions and integration of mental healthcare into primary health systems to address this critical public health challenge.

Despite the availability of curative treatments, hepatitis C diagnosis and treatment coverage is suboptimal globally with few countries on track to achieve the WHO’s 2030 elimination targets. In 2022, an estimated 50 million people were living with hepatitis C, with 1 million new infections annually. Most people living with hepatitis C reside in low- and middle-income countries, and people who inject drugs are disproportionately affected by hepatitis C.

Continuing simplification of diagnostic pathways and treatment care models is required to improve linkage to care and reduce costs associated with hepatitis C treatment and cure.

This study is a multi-country non-randomised, quasi-experimental, prospective comparative two-arm trial. It aims to assess the feasibility of implementation, retention in hepatitis C care and achievement of cure and cost-effectiveness outcomes, comparing two simplified hepatitis C testing and treatment pathways.

Arm 1 is a standard simplified test and treat model of care following global guidance, and arm 2 is an innovative rapid, same-day treatment initiation model of care using a presumptive treatment approach based on shortened read-time of the point-of-care OraQuick hepatitis C antibody test result. Secondary outcomes include assessing the accuracy of the OraQuick hepatitis C antibody test in predicting viraemia and the acceptability of each pathway.

This study will be implemented in Armenia, Georgia and Tanzania. Treatment-naïve people who inject drugs aged over 18 years in each country will be eligible for enrolment.

Recruitment commenced in October 2024 in Armenia, June 2025 in Georgia and August 2025 in Tanzania and is anticipated to close by December 2026.

This trial has been reviewed by WHO Ethics Review Committee (ERC), Alfred Hospital Ethics Committee (Australia) and local country ERCs. Alongside journal publications and conferences, the results from this study will be disseminated through summary reports and workshops with key stakeholders and with communities of people affected by HCV through relevant organisations/networks, including the global Community Advisory Board (CAB). The study results will inform national scale-up of simplified care models and inform potential pathways for further simplification of care models, including the potential for one-step diagnostic pathways and same-day treatment in particular scenarios for the three study countries, and other low- and middle-income countries globally.

NCT06159504.

Target trial emulation (TTE) has emerged as a methodological framework to strengthen causal inference from observational health data when randomised controlled trials are infeasible. The credibility of TTE studies depends not only on rigorous design and transparent reporting, but also on their relevance and acceptability to patients and the public. Patient and public involvement and engagement (PPIE) has been shown to enhance the relevance, transparency and impact of health research by shaping research priorities, informing study design and ensuring outcomes reflect patient perspectives. However, the extent to which PPIE has been incorporated into TTE studies remains unclear. This scoping review aims to systematically map the use and reporting of PPIE in published TTE studies.

This review will follow the Joanna Briggs Institute methodology for scoping reviews and will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews checklist. We will search MEDLINE (Ovid) and Embase (Ovid) from January 2011 to present, limited to English-language publications. Eligible studies will be studies that self-identify as using the TTE framework and report empirical analyses of health outcomes using observational or trial data. We will exclude protocols, methodological or simulation-only studies, preprints, conference abstracts and grey literature. Three reviewers will independently screen titles and abstracts, and then full texts, with disagreements resolved by discussion or adjudication. Data extraction will include study characteristics and PPIE information guided by the Guidance for Reporting Involvement of Patients and the Public 2-Short Form checklist. Findings will be summarised using descriptive statistics, tables, figures and narrative synthesis.

Ethics approval is not required, as this review will use publicly available data. Results will be disseminated through a peer-reviewed publication and presented at conferences.

The global prevalence of type 2 diabetes (T2D) is rising and disproportionately affects South Asian adults, including those in the United Kingdom. South Asians develop T2D at a higher rate and at a younger age than their white British counterparts, at a lower body mass index. Active efforts to reduce adiposity can improve glycaemic control and in some cases achieve T2D remission. However, a substantial proportion of lean mass is lost while achieving weight loss, which may have physiological and metabolic consequences, affecting long-term health outcomes and quality of life for people living with T2D and obesity. We are examining the impact of a combined low energy diet and supervised exercise intervention versus a low energy diet alone for the preservation of lean mass in an understudied South Asian population living with T2D and excess adiposity.

This prospective, randomised, two-arm parallel-group, open-label, blinded-endpoint trial is being conducted in Leicester, UK. 36 South Asian adults aged 40–65 years within 10 years of T2D diagnosis and not on insulin therapy will be enrolled. Both intervention arms will receive an 800–900 kcal/day low energy diet for 12 weeks. Those randomised to the exercise group will additionally receive a mixture of supervised and home-based resistance and aerobic exercise training three times per week. The primary outcome is the difference in the change of lean mass between groups measured using dual-energy X-ray absorptiometry at baseline and 12 weeks and will be analysed using linear regression modelling.

The trial was approved by the NHS research ethics service (23/WM/0201). All participants will provide informed consent prior to enrolment, and the study will be conducted in accordance with the Declaration of Helsinki. Findings will be shared widely (publications, presentations, press releases, social media platforms) and will inform an effectiveness trial.

ISRCTN11175684.

Medication errors pose a significant threat to public health. Despite efforts by health agencies and the implementation of various interventions, such as staff training, medication reconciliation and automation, the persistence of these incidents highlights the need for more effective, scalable solutions. In recent years, machine learning (ML) has emerged as a promising approach in healthcare, offering potential to detect and predict medication errors through data-driven insights. This scoping review aims to systematically map the existing literature on ML-based approaches to predict or detect medication errors across all stages of the medication use process. The review seeks to identify the range of ML applications in this domain, characterise methodological trends and highlight current knowledge gaps. The findings will provide a structured and accessible overview for both clinicians and researchers, supporting the development of safer, more data-informed medication practices.

The review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guideline. Structured searches will be performed in PubMed, Embase and Web of Science, covering publications from 1 January 2015 to 28 April 2025. Predefined inclusion and exclusion criteria will be used to identify eligible studies. Key information—including ML models, data sources and type, evaluation methods and clinical contexts—will be extracted and analysed using descriptive statistics, visualisations, thematic analysis and narrative synthesis.

This study involves a review of existing literature and does not involve human participants, personal data or unpublished secondary data. As such, ethical approval was not required. All data analysed were obtained from publicly available sources. Findings of the scoping review will be disseminated through professional networks, conference presentations and publications in scientific journals.

This protocol has been registered on the Open Science Framework (https://doi.org/10.17605/OSF.IO/38SFY).

To describe (1) the proportion of deaths that were in recently hospitalised children and (2) causes of mortality among deceased children aged 0–59 months with preceding hospitalisations who enrolled in a mortality surveillance programme.

Descriptive study using prospectively collected data.

Eight Child Health and Mortality Prevention Surveillance (CHAMPS) community and healthcare sites in sub-Saharan Africa and South Asia.

Deaths among children aged 0–59 months enrolled in CHAMPS 2016–2023.

None.

Deaths with antecedent hospitalisations within 180 days of death. Causes of death determined by expert panels who reviewed clinical data and histopathologic and microbiologic results from postmortem minimally invasive tissue sampling.

CHAMPS enrolled 8548 deaths; we excluded 3688 neonates who died before discharge or ≤24 hours of birth and 482 with unclear information on antecedent hospitalisations. Out of the 4378 remaining deaths, 16.7% (95% CI 15.7% to 17.9%) were deaths that occurred within 180 days of a hospitalisation (n=733/4378). Of these, 55.7% (95% CI 52.0% to 59.3%) occurred outside healthcare facilities. Among included deaths with minimally invasive tissue sampling completed (n=337), lower respiratory tract infections (41.2%, 95% CI 36.0% to 46.7%), sepsis (39.8%, 95% CI 34.5% to 45.2%) and undernutrition (n=92, 27.3%, 95% CI 22.7% to 32.4%) were most common causes of death among cases with antecedent hospitalisations. The greatest proportion of deaths with antecedent hospital admissions occurred among cases aged 1–11 months (48.0%, 95% CI 44.4% to 51.7%), compared with those aged 0–1 months (21.7%, 95% CI 18.8% to 24.9%) and those aged 1–5 years (30.3%, 95% CI 27.0% to 33.8%). Moreover, the greatest proportion of deaths with antecedent hospital admissions occurred among infants/children with weight-for-age Z-score of

We observed a high proportion of deaths with antecedent hospitalisations within 180 days among young children across eight sites in sub-Saharan Africa and Asia. Among those deaths, children aged 1–11 months and undernourished infants were over-represented, suggesting early follow-up as a potential point to focus targeted support and future research.

Vital signs such as heart rate (HR) and respiratory rate (RR), crucial for clinical assessment, are often challenging to measure in paediatric populations. Remote photoplethysmography (rPPG), a video-based measurement tool, has demonstrated accuracy in adults. The objective of this study is to compare HR and RR measurements obtained using rPPG with those from standard clinical monitoring in a paediatric population.

This is a monocentric, prospective study enrolling 600 paediatric participants. Each participant will have standard monitoring electrodes (ECG/impedance) placed on the chest while seated facing a camera for rPPG recording. Simultaneous HR and RR measurements will be recorded over periods of 30 and 60 s using both the standard monitor and the rPPG device. The intraclass correlation coefficient will be calculated to assess agreement between the rPPG and standard monitor measurements.

The study protocol has been approved by the French Agency for the Safety of Health Products (ANSM (Agence nationale de sécurité du médicament) registration no. IDRCB 2023-A02524-41) and by a French ethics committee (CPP Sud Méditerranée III at 29 August 2024, n°2024-A01324-43). The study’s findings will be published in peer-reviewed journals and disseminated at national and international conferences and through press releases.

Clinical Trials Registry (NCT06231654).

To evaluate the effectiveness of early administration of excitatory amino acid (EAA) inhibitors on long-term neurological outcomes in adults with acute moderate to severe traumatic brain injury (TBI).

Systematic review and meta-analysis of randomised controlled trials (RCTs).

MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, WHO International Clinical Trials Registry Platform and ClinicalTrials.gov from inception to January 2026.

RCTs comparing EAA inhibitors with placebo, standard care or any other interventions were included. Trials enrolled adult patients (≥18 years) with moderate to severe TBI (Glasgow Coma Scale score ≤12) receiving the intervention within the acute phase of care (first week).

Pairs of reviewers independently screened trials, extracted data, assessed the risk of bias (RoB) with the Cochrane RoB tool 2 and graded the certainty of evidence using the Grades of Recommendation, Assessment, Development and Evaluation approach. Random effects models were used for all effect measures and trial sequential analyses (TSA) were performed for each outcome.

The primary outcome was long-term neurological function at 6 months (or the nearest earlier time point), assessed with the Glasgow Outcome Scale (GOS) or extended version (GOS-E), using the classical definitions of an unfavourable outcome (GOS 1–3 or GOS-E 1–4).

28 trials enrolling 4238 patients were included. Early administration of EAA inhibitors was not associated with reduced unfavourable neurological outcomes (relative risk 0.93 (95% CI (0.84 to 1.03); I²=40%; 15 trials, n=3613, moderate certainty). No statistically significant difference was observed based on EAA inhibitor type, timing or duration of administration, RoB or TBI severity. Mortality, intensive care unit lengths of stay and mean intracranial pressure were not statistically different between groups, but hospital length of stay was reduced in the EAA inhibitors group. The early use of EAA inhibitors was not associated with adverse events (low certainty). TSA showed insufficient power for the primary outcome.

In adults with moderate to severe TBI, the early administration of EAA inhibitors was not associated with a reduction of unfavourable neurological outcomes. Further high-quality and adequately powered RCTs are required to clarify their role in TBI management.

CRD42025635527.

Patients with haematological malignancies undergoing intensive chemotherapy with or without haematopoietic cell transplantation (HCT) are at high risk of complications that may require intensive care. While some studies advocate for early admission of these patients to the intensive care unit (ICU), it has not been formally demonstrated that admission to the ICU as soon as patients have organ injury may improve their outcomes. To demonstrate the efficacy of implementing the National Early Warning System (NEWS) with immediate ICU admission for patients with NEWS ≥7 to decrease hospital mortality and organ failure.

ALHERT is a randomised cluster, controlled trial carried out in 10 French centres. With their informed consent, adult patients undergoing induction therapy for acute lymphoblastic or myeloblastic leukaemia, autologous or allogeneic HCT in one of the participating centres will be included. Five centres will follow local guidelines for ICU admission (control group) while five centres will assess the NEWS at least three times per day with immediate ICU admission for patients with NEWS ≥7 (interventional group). The primary outcome is hospital mortality without organ sustaining therapy. Secondary objectives will be to study the relative weight of each parameter used to calculate the NEWS for predicting the risk of organ failure requiring life-sustaining organ support, to evaluate the feasibility of implementing early warning scores in routine practice by analysing the proportion of patients with NEWS ≥7 effectively admitted to the ICU in the investigational arm, to assess quality of life with EQ-5D-5L (five level European Quality of Life five Dimensions) and assess the cost-effectiveness of this strategy.

The protocol has been approved by the Comité de Protection des Personnes Ile de France I (Ethics Review ID-RCB: 2024-A00969-38). It is carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The findings of this study will be presented in peer-reviewed journals and at scientific conferences.

NCT06409767.

Non-specific low back pain (NSLBP) is one of the leading causes of disability worldwide. Emerging evidence suggests that altered diaphragmatic function may be associated with lumbar pain, impaired trunk stabilisation and functional disability. Manual diaphragmatic techniques have been proposed as an intervention to modulate diaphragmatic tension, mobility and neuromyofascial relationships; however, their effectiveness has not yet been synthesised using rigorous systematic review methods.

This protocol follows Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidance and has been prospectively registered in PROSPERO. Randomised controlled trials evaluating manual techniques specifically applied to the diaphragm in adults with NSLBP will be eligible. The primary outcomes will include pain intensity and functional disability; secondary outcomes will include lumbar mobility, respiratory function, quality of life and adverse events. Searches will be performed in PubMed/MEDLINE, Cochrane CENTRAL, PEDro, CINAHL, Scopus, Embase and clinical trial registries without language or date restrictions. Two reviewers will independently perform study selection, data extraction and risk-of-bias (RoB) assessment using the Cochrane RoB 2 tool. Where appropriate, a random-effects meta-analysis will be conducted; the certainty of evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation approach. Substantial clinical and methodological heterogeneity is anticipated across trials, which may limit the feasibility of quantitative data pooling.

As this study uses data from previously published trials, ethical approval is not required. Findings will be disseminated through peer-reviewed publication, conference presentations and a plain-language summary for clinical stakeholders.

CRD420251172616.

This study was to estimate the potential social value and net benefit of OpenUp, a 24/7 text-based online counselling service for youth in Hong Kong, and draw policy-relevant conclusions for service provision.

A retrospective, model-based cost–benefit analysis using social return on investment (SROI) methods. Adopting a societal perspective, service, health and social outcomes were valued over a 1-year period, and productivity gains associated with avoided suicide deaths were valued over a 10-year period. Costs are reported in 2022 HK dollars (HK$; US$1=HK$7.8). Reporting was guided by Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) Statement.

A text-based, synchronous online emotional support counselling platform in Hong Kong was accessible through WhatsApp, Facebook, SMS and the official web portal.

A total of 19 543 users aged 11–35 years accessed OpenUp services during the study period (1 December 2020 to 31 May 2022).

These included total social value (HK$), net social benefit (social value minus investment) and the SROI ratio. The secondary outcomes included monetised savings in medical and social services and productivity gains from avoiding suicide attempts and death.

The total social value was estimated to be HK$226 119 729 against an investment of HK$47 655 000 (SROI=4.74). Suicide risk reduction (productivity gains from avoided attempts and deaths) accounted for 75.4% of the social value. Deterministic one-way sensitivity analyses yielded SROI values ranging from 3.62 to 6.99 aggregated across the three groups, with results being most sensitive to assumptions about the duration of productivity impacts for avoided attempts and avoidable mortality.

Based on conservative assumptions, OpenUp can generate potential social value by providing an online emotional support service. Given the study’s reliance on modelling and proxy monetisation, these estimates should be interpreted with caution. Further integration of offline services with online intervention strategies requires continuous investment and evaluation.