BMJ Open

ABSTRACT Introduction Traditional in-person fracture clinics are often overcrowded and inconvenient for patients. Virtual fracture clinics aim to address some of these concerns by improving the efficiency of the orthopaedic service and reducing unnecessary interventions while maintaining safety and quality of care. The RECITAL trial is a non-inferiority randomised controlled trial comparing follow-up care provided at a virtual fracture clinic for people with acute simple fractures to follow-up care provided at an in-person fracture clinic. This study describes the protocol for an economic evaluation of RECITAL where the primary aim is to investigate the cost-effectiveness of a virtual fracture clinic compared with traditional in-person fracture clinic care from a health system perspective. Methods and analysis The RECITAL trial recruited 312 participants with acute simple fractures and randomised them to receive follow-up care provided at a virtual fracture clinic or follow-up care provided at an in-person fracture clinic. We will conduct a within-trial analysis from a health system perspective (primary analysis), as well as a health service, patient and societal perspective. The economic evaluation will estimate the difference in the cost of resource inputs on an intention to treat basis used by participants in the two arms of the trial, allowing comparisons to be made between the in-person and virtual fracture clinics. Data for intervention costs and healthcare utilisation will be collected from trial records, hospital electronic medical records and district performance units. The results of the economic evaluation will be expressed in terms of incremental cost per utility weight gained at 12 weeks and will be plotted on a cost-effectiveness plane. Bootstrapping by resampling will be used to estimate 95% confidence intervals around costs and outcomes, and to calculate the confidence intervals around the incremental cost-effectiveness ratio. A cost-effectiveness acceptability curve (CEAC) will be plotted, which will provide information about the probability that an intervention is cost-effective, given the level of a decision makers willingness to pay for each additional outcome. Ethics and Dissemination The trail was approved by the SLHD Ethics Review Committee (RPAH Zone) (X23-0200 and 2023/ETH01038). The findings will be disseminated through a peer-reviewed journal and conference presentations. Trial registration number The trial was prospectively registered on the Australian New Zealand Clinical Trials Registry (ANZCTR; 12623000934640)

Abstract Background: The current coverage of MCCD in India is only 22%. This is due to incomplete coverage of hospitals under MCCD and also lack of a system for non-institutional deaths in the country. The quality of MCCD in the country is also poor. One of the main reasons for this is the lack of review and feedback at the district level. This study would be the first of its kind study in the country to test the effectiveness and feasibility of involving the district level CRS/Health dept officials in review of MCCD Objectives: To assess the feasibility and effectiveness of a district level review system for MCCD in improving the coverage and quality of MCCD Methods: The study would be conducted in Chikkaballapura district for a period of 2 years. Local Registrars would do a first level of review of MCCD forms for completeness, use of abbreviations, legibility. They would also ensure that form 4/4A is written for all registered deaths in their area. A MCCD review committee would assess the quality of MCCD forms on a monthly basis and provide feedback to the certifying doctors. Comparison of the pre-test and post-test coverage and quality of MCCD will be done. Results: Constitution of the audit committee, training of local registrars, doctors and committee members and baseline assessment have been completed. Intervention has been started from Nov 2025. Expected Outcomes: Improved coverage and quality of MCCD and as a result cause of death data of the district

Background: In Canada, there is a lack of data relating sociodemographic characteristics to the likelihood of consent and clinical trial participation. Objective: The overall objective of this study is to examine the association of hospital-level sociodemographic variables with a priori informed consent rates for participation in the REVISE trial. Design: This study is a retrospective observational analysis of Canadian sites participating in the international REVISE trial. Methods: Sociodemographic characteristics for 42 hospitals participating in the REVISE trial will be supplemented by national data from the 2021 Canadian Census of Population Profile at the census tract level corresponding to the hospital's location. Hospital level information for Ontario sites will be derived from the Institute for Clinical Evaluate Sciences (ICES) database. Site clustering will be performed using latent class analysis, a flexible clustering technique that identifies meaningful subgroups based on sociodemographic variables purposively selected from data available through the Statistics Canada 2021 census profile, ICES, and hospital-reported data. Clustering analysis will be performed for all Ontario hospitals with available ICES data, followed by a separate analysis for all Canadian REVISE sites using Statistics Canada data. Concordance in the clustering of REVISE sites will be examined by comparing the assignment of hospitals to the latent classes separately identified using ICES and Statistics Canada data. If there is a high degree of agreement between the two datasets, sociodemographic predictors will be analyzed using the clusters identified through ICES for Ontario sites with the concordant classes based on Statistics Canada data for Canadian sites outsite Ontario. If there is disagreement in cluster assignment between the two datasets, separate analyses of sociodemographic factors will be conducted for Ontario sites using ICES data and for all Canadian sites using the 2021 Census Profile. Multivariate linear regression models will be used to analyze the association between hospital-level characteristics and the likelihood of a priori and deferred consent. Results: Results of this study will generate information about the relationship between informed consent to participate in a low-risk critical care clinical trial using different consent models, and socioeconomic patient characteristics at the hospital site level (e.g., educational attainment, knowledge of official languages, citizenship rates, family income, poverty, rurality and immigration patterns). Conclusions: This study will fill an evidence gap by generating information on the relationship between sociodemographic variables and the likelihood of informed consent to participate in a critical care clinical trial in Canada.

DREAM is a randomised, superiority, parallel-group, placebo-controlled, participant, clinician, and assessor blinded trial with an adaptive group sequential design that allows early stopping for efficacy or futility. The purpose is to investigate whether taking 60 mg of duloxetine daily for 12 weeks in addition to guideline-recommended advice, compared with placebo in addition to guideline-recommended advice, can reduce leg pain intensity in individuals with chronic sciatica. The primary outcome is leg pain intensity measured on a 0-10 numerical pain rating scale. It will be analysed using a repeated-measures linear mixed model. This statistical analysis plan pre-specifies the methods of analysis to be used in the interim analysis and the final analysis for the outcomes and key variables collected in the trial. It includes planned sensitivity analyses for the final analysis, including covariate adjustments and subgroup analyses, as well as the health economics analysis plan.

There remains considerable uncertainty around the safety of a trial of labour after more than one caesarean delivery. This large retrospective cohort study will investigate the safety of a trial of labour using a large United States dataset of all registered births from 2011 to the most recent year with available data. A multivariable fitted model will be used to predict the probability of uterine rupture in women with two or more previous caesarean deliveries, with a minimum 21-month interpregnancy interval. This will provide important information to clinicians in counselling women wanting to attempt a vaginal birth after more than one caesarean delivery.

Background Advanced Practitioners (APs) are a growing multi-professional workforce within the National Health Service (NHS) in England, spanning nursing, pharmacy, allied health, and healthcare science disciplines. Despite their policy prominence, no national quantification of this workforce using routinely collected administrative data has been published. Existing intelligence relies on regional surveys, employer self-reports, and bespoke data requests, each limited in coverage and comparability. This protocol describes a secondary analysis of NHS Workforce Statistics to address this gap, to support national workforce planning and service redesign. Methods The Measuring Advanced Practitioner Presence, Patterns, and Evolving Distribution (MAPPED) study is a secondary analysis of NHS Workforce Statistics derived from the Electronic Staff Record (ESR), examining the AP workforce in Hospital and Community Health Services (HCHS) in England. The study combines longitudinal analysis of national trends from September 2014 to April 2026 (13 time points) with cross-sectional geographic analysis at NHS England region and Integrated Care System (ICS) levels in April 2026. APs are identified using National Workforce Dataset Job Role codes. The analytical framework comprises descriptive statistics, Mann-Kendall trend tests, Kruskal-Wallis tests, Gini coefficients, and Wilson score confidence intervals; trainee Advanced Practitioners are analysed separately. Reporting follows the REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement and the STandardisierte BerichtsROutine fur SekundardatenAnalysen 2 (STROSA-2) checklist for secondary data analyses. Results and analysis This paper presents the study protocol; no results are reported. Planned outputs include national trend figures, distribution tables by staff group and Area of Work, geographic inequality measures using Lorenz curves, and sensitivity analyses addressing classification-version effects and generic code persistence. Discussion This study will provide the first national, longitudinal quantification of the AP workforce from routinely collected administrative data. The principal limitation is that Job Role coding accuracy varies across trusts, and the transition to profession-specific codes from the year 2022 creates a measurement discontinuity that sensitivity analyses address but cannot fully eliminate.

Introduction and aims Dementia is a growing public health challenge affecting millions of people worldwide. It is a progressive condition that increases the risk of infections, falls, hospital admissions, dependence in activities of daily living, safety issues such as wandering, care home transfers, and death. New ways of supporting people living with dementia (PLWD) at home are urgently needed. We describe the MinderCare study which evaluates a digitally enabled care model that integrates low-burden sensor-based remote monitoring within a nurse-led clinical service. Methods and analysis In this mixed-methods study, we will recruit 100 people with confirmed or suspected dementia living at home and deploy the Minder remote monitoring system for at least 12 months. A detailed characterisation of the cohort will be obtained, including cognition, frailty, participant and carer wellbeing, functioning, and quality of life. The feasibility, acceptability, sustainability, and resource requirements of the service will also be assessed. Low-cost sensors provide information about behaviour, environment and physiology from the home. Machine-learning algorithms have been used to develop digital biomarkers of infection, sleep, night-time behaviours, daily activities and routines, and the effects of clinical events and treatment. These will be assessed through clinical reports of sensor-derived data that include anomaly alerts provided to the clinical teams. Algorithms will be assessed for their clinical utility and acceptability. The comparative-effectiveness component will be designed as a target trial emulation using linked electronic health-record data to construct a time-indexed external usual-care control cohort. The primary comparative outcome will be Days Alive and Out of Hospital (DAOH) over 12 months from the activation-index date, with healthcare utilisation, costs, institutionalisation and mortality assessed as secondary outcomes. DAOH and estimated MinderCare effects will also be examined across prespecified strata of baseline inpatient utilisation. Ethics and dissemination Ethical approval has been granted by the North East Newcastle and North Tyneside 2 Research Ethics Committee, and the study has received confirmation of capacity and capability by the Imperial College Healthcare NHS Trust. Study findings will be disseminated to patients, health and social care professionals, and policymakers through peer-reviewed publications and conference presentations. Study registration number: ISRCTN14997677 and NIHR portfolio CPMSID 63023.

The CATION study is a parallel two-arm randomised controlled trial on the prevention of catheter-associated urinary tract infections (CAUTI) in hospitalised patients. The intervention is the use of a sterile wipe containing 0.1% chlorhexidine solution for meatal cleaning prior to urinary catheter insertion as part of usual care; the intervention will be compared with the use of a sterile wipe containing 0.9% normal saline as the control. This document is the Statistical Analysis Plan for evaluating primary, secondary and tertiary effectiveness outcomes. The trial was preregistered on the Australian and New Zealand Clinical Trials registry (ACTRN12625000278437). A copy of the study protocol and a signed version of this Statistical Analysis Plan are available on request from the corresponding author (BM).

Objective: To assess the feasibility of a definitive randomised controlled trial comparing halved versus routine-concentration oxytocin infusion during active phase of the first stage of labour in women undergoing induction of labour. Design: Multicentre, double-blind, randomised feasibility trial with 1:1 allocation. Participants: Women & birthing people aged 18 years or older undergoing planned induction of labour in two public maternity hospitals in Sydney, Australia, between September 2023 and September 2025 were eligible. Key exclusions included previous caesarean delivery, pre-existing diabetes, major fetal anomaly, abnormal fetal cardiotocography, malpresentation, suspected cephalopelvic disproportion, suspected chorioamnionitis, intrapartum pyrexia, and other predefined maternal or fetal safety concerns. Interventions: All participants commenced induction with standard oxytocin during the latent phase (10 IU in 1 L crystalloid). At established active labour, participants were randomised to receive either halved-concentration oxytocin (5 IU in 1 L crystalloid) or routine-concentration oxytocin (10 IU in 1 L normal saline), titrated according to the New South Wales (NSW) Health oxytocin protocol between one and 40 mIUmin-1. Main outcome measures: Feasibility outcomes were recruitment, consent, randomisation, retention, protocol adherence, unblinding, and treatment separation, assessed by total oxytocin dose and infusion rates. Secondary outcomes included maternal, neonatal, and participant-reported outcomes. Results: Of 771 women assessed for eligibility in two centres, 572 were approached and 293 (51%) consented to participate, of whom 101 (34%) were randomised. During active recruitment, randomised participants represented 9.2% of all births. Baseline characteristics were similar between groups. No between-group differences were observed in maternal, neonatal, or participant-reported outcomes, although the trial was not powered to assess clinical effectiveness. Satisfaction outcomes were ascertained for 69% (70/101) participants. There was 100% ascertainment for short-term clinical outcomes and for readmissions to the hospital of delivery. Twenty-nine participants were interested in providing feedback and in being involved in developing a larger study across multiple hospitals. Conclusions: A blinded randomised controlled trial of oxytocin dose reduction in active labour is feasible in a real-world labour ward. Trial registration: This trial was registered on the ANZCTR (ACTRN12622001342707)

Introduction The overuse and prolonged use of antibiotics in residential aged care (RAC) increases the risk of adverse effects and contributes to the global threat of antimicrobial resistance. Behavioural science-informed interventions have effectively reduced antibiotic prescribing in primary care but have rarely been implemented in RAC settings. We co-developed a behavioural science intervention bundle named Smarter, Shorter, Safer with RAC providers. We aim to assess the effectiveness of the intervention on rates of antibiotic use, measure effect persistence 6-months after the final intervention round, and investigate stakeholder experiences of the intervention. Methods and analysis We will conduct a stepped-wedge cluster randomised controlled trial with an embedded qualitative process evaluation. RAC homes (n=46) will be stratified into tertiles of baseline antibiotic use and randomly allocated to three intervention roll-out steps. Each RAC home will receive a bundled intervention consisting of social norm feedback, public commitment messaging and consumer information, staggered by step. Three rounds of the intervention will be delivered to each home at quarterly intervals. The primary outcome is antibiotic days of therapy per 1000 resident days (DOT/1000 days). Secondary outcomes are the percentage of antibiotic courses with a duration longer than guidelines and the percentage of residents on an antibiotic. Qualitative interviews will investigate staff and consumer experiences of the intervention bundle over time and by high, median and low baseline antibiotic use rates. Ethics and dissemination We obtained ethical approval from the Macquarie University Human Research Ethics Committee. Our findings will be disseminated through a range of forums including the publication of results in peer-reviewed journals and presentations at national and international conferences. Trial registration number Australian New Zealand Clinical Trials Registry ACTRN12625001132437 (https://anzctr.org.au/ACTRN12625001132437.aspx)

Background: Psychological distress is common among people living with chronic kidney disease (CKD), yet access to structured psychological support within routine kidney care remains limited and varied. iADJUST is a primarily self-guided digital psychological intervention designed to support adjustment and emotional well-being in people living with CKD. Delivered over 12 weeks, iADJUST is hosted on the Kidney BEAM platform and supported by brief therapist contact to facilitate engagement. Before a definitive evaluation can be undertaken, it is necessary to establish the feasibility and acceptability of intervention delivery and study procedures. Aim: To assess the feasibility and acceptability of delivering iADJUST to people living with CKD. Methods: This study is a parallel-group, randomised, waitlist-controlled feasibility trial. Approximately 40-50 adults with CKD who are not receiving renal replacement therapy and have not received a kidney transplant will be randomised 1:1 to receive either iADJUST plus usual care or usual care alone. iADJUST is a six-session digital psychological intervention delivered over 12 weeks and supported by brief therapist contact. Feasibility outcomes include recruitment, retention, intervention uptake, engagement, completion of outcome measures, and acceptability of study procedures. Exploratory outcome measures include psychological distress, fatigue, functional impairment and quality of life collected to estimate variability, assess data completeness, and inform outcome selection for a future definitive trial. Following the primary endpoint assessment at 12 weeks, participants in both groups will receive access to the exercise-based Kidney BEAM programme. Kidney BEAM engagement and completion will be assessed at 24 weeks. The study is not powered to detect statistically significant between-group differences in clinical outcomes. Conclusion: This study will provide evidence regarding the feasibility and acceptability of delivering iADJUST within UK kidney care pathways and inform the design of a future definitive trial. Trial Registration: ISRCTN91507822

Introduction Current treatments for multiple sclerosis (MS) do not address the pathological processes of neurodegeneration and chronic demyelination. This, coupled with the significant challenges of translating promising phase 2 results to phase 3 trial success, highlights the need for more efficient trial designs, such as platform multi-arm multi-stage (MAMS) trial approaches. MAMS trials have demonstrated success in areas such as oncology and infectious diseases. They are typified by a statistically robust core trial design that allows the addition of further treatment arms and utilisation of interim outcome analyses at pre-defined timepoints, to determine whether to terminate a treatment arm early or proceed to the final outcome analysis. To address the challenges in progressive multiple sclerosis (PMS) treatment discovery, the Optimal Clinical Trials Platform for PMS (OCTOPUS) trial was developed. It currently utilises MRI whole-brain atrophy as its interim outcome measure and the clinically relevant composite Expanded Disability Status Scale Plus (EDSS-Plus) as its final outcome measure. A rigorous and systematic drug selection process that assessed preclinical in vitro and animal model evidence, along with additional human data, led to the prioritisation of R/S-alpha lipoic acid (R/S-ALA) and metformin for testing against placebo, targeting pathobiological mechanisms relevant to PMS. All participants will be eligible to receive the current standard of care, including disease-modifying treatments (DMTs). Method and analysis OCTOPUS will be a multi-centre, randomised, placebo-controlled, double-blind, phase 3, MAMS trial of participants aged 25 to 70 years (inclusive) with PMS and an EDSS score of 4.0 to 8.0 (inclusive). Steady progression must be the major cause of increasing disability rather than relapse in the preceding 2 years. In the trial s first candidate drug cycle, participants will be allocated to R/S-ALA, metformin, or placebo in a 1:1:1 ratio. Cycle 1 active treatments will start as R/S-ALA 600 mg once daily, increased after 4 weeks to 600 mg twice daily, or metformin 1 g once daily, increased after 4 weeks to 1 g twice daily. The trial will be multinational, with participation from 28 hospitals across the UK and 10 hospitals in Australia. Clinician-reported measures will include: the EDSS-Plus and the individual components: EDSS, Timed 25 Foot Walk (T25FW); 9 Hole Peg Test (9HPT); Symbol Digit Modalities Test (SDMT); Sloan Low Contrast Visual Acuity (SLCVA); and Relapse assessment. Patient-reported outcomes include MS specific walking, fatigue, pain, and impact scales. We will include a health economic analysis. Analysis stage 1 will require randomisation of 125 participants per arm and utilise MRI percentage brain volume change (PBVC) with the Structural Image Evaluation using Normalisation of Atrophy (SIENA) technique from baseline to 78 weeks. A positive outcome in analysis stage 1 will detect a 0.15% per year whole brain atrophy difference with a one-sided alpha of 0.35 and power of 95%, ensuring a low probability of erroneously rejecting a treatment arm at this stage. Any arms that show a positive effect will proceed to final analysis stage 2. Analysis stage 2 will require 600 participants per arm. Participants included in stage 1 will also be included in the stage 2. Analysis stage 2 will evaluate time to 6-month confirmed disability progression in the EDSS-Plus, in order to detect a 25% hazard ratio reduction with 90% power and an alpha of 0.05. Assuming one treatment arm proceeds to analysis stage 2, the trial will recruit approximately 1,200 participants and last about 6 years. This is approximately two-thirds the size and half the duration of separately conducted two-arm phase 2 and 3 trials. Ethics and dissemination The protocol was approved by the London Hampstead REC (22/LO/0622). This manuscript is based on protocol version 8.0, 28th August 2025. The findings of this trial will be disseminated through peer-reviewed publications and conference presentations. There will be a close communication strategy developed with the UK MS Society (MSS) and full patient and public involvement and engagement (PPIE). Trial registration ISRCTN: 14048364 EudraCT number: 2021-003034-37 CTA 20363/0445 IRAS number: 1003943 Secondary identifying numbers: ND001, CPMS 54274 Strengths and limitations - The OCTOPUS trial will be the first platform multi-arm multi-stage phase 3 trial in PMS, offering the potential to significantly expedite clinical trial processes with advantages in cost- and time-efficiency, focusing specifically on the poorly treated pathobiological processes of chronic neurodegeneration and demyelination - It will begin by assessing two promising drug candidates, immediate-release metformin and R/S-ALA, and will expand over the duration of the trial to include more drug arms under the same trial master protocol - The flexible and statistically robust trial design means that several components of the design (such as the early analysis stage 1 interim outcome) can be updated in line with evolving scientific knowledge - It will ultimately be the largest ever investigator-initiated phase 3 trial in PMS - It will include a range of national and international trial sites, including neuroscience centres and district general hospitals - It will have a high inclusion limit for age (up to 70 years) and disability (up to EDSS 8.0) - Several components (the telephone EDSS and virtual patient-reported outcome measures) will be amenable to remote collection increasing inclusivity and thus addressing public and participant suggestions, while minimising the risk of missing data - The main challenges in this trial design are the statistical and methodological complexity involved in design and implementation, and interpretation of interim trial results. Conclusion The trial launched cycle 1 in January 2023. Analysis stage 1 recruitment of 375 participants was achieved in November 2024, enabling planned interim analysis stage 1 to be conducted by late 2026 (Figure 1). On the 1st of June 2026, in the UK, 24 sites are active with a further 4 in set-up as part of stage 2, and in the Australian extension, Platform Adaptive Trial for Remyelination and Neuroprotection in Multiple Sclerosis (PLATYPUS), 1 site is active, with 9 additional sites in set-up.

Introduction: Oxytocin is commonly used in the process of induction of labour and is associated with uterine hyperstimulation and abnormal fetal heart rate patterns that can increase the risk of adverse perinatal outcomes. Cessation of oxytocin in the active phase of induced labour has been shown in randomised trials to reduce uterine tachysystole and abnormal fetal heart rate traces, and may reduce caesarean section. We introduced a policy recommending cessation of oxytocin infusion in the active phase of the first stage of induced labour at a tertiary hospital in Sydney, Australia, and collated both clinical outcomes and maternal satisfaction following implementation. Methods: This was a prospective audit of a policy change at Royal Prince Alfred Hospital, comparing 600 women induced with oxytocin in the 6 months before the policy (November 2019 to May 2020) with 556 women induced in the 6 months after implementation (June to December 2020). Eligible women had a cervix [≥] 5cm, an oxytocin infusion, and regular uterine contractions. The primary clinical outcome was caesarean delivery. The primary patient-centred outcome, maternal satisfaction, measured using the Six Simple Questions questionnaire, was collected in a subset of participants. Secondary outcomes included mode of birth, length of labour, uterine hyperstimulation, and perinatal outcomes. Results: Caesarean delivery occurred in 29% of women before and 28% after policy implementation (p=0.77). Instrumental birth increased from 25% to 27%; and instrumental birth for maternal indications increased from 6.8% to 13% (p=0.0005). Median length of labour increased by one hour (5.4 vs 6.4 hours, p=0.006). Oxytocin was ceased for at least two hours or until birth in 13% of women before the policy versus 35% after. Maternal satisfaction scores were modestly lower after implementation (median 41 vs 38, p=0.03). Perinatal outcomes, including abnormal cord gases, Apgar scores, and NICU admission, were similar between groups. Conclusions: Implementing a policy of recommending cessation of oxytocin in the active phase of induced labour did not reduce caesarean delivery rates in a real-world tertiary hospital setting, despite trial-level evidence supporting the intervention. Poor uptake, negative staff perceptions, and a modest reduction in maternal satisfaction highlight barriers to translating trial efficacy into routine clinical practice. Adequately powered trials are needed to clarify optimal protocols for oxytocin cessation and its effects on maternal and perinatal outcomes.

Background Liver transplantation is a complex surgical procedure featuring prolonged operative time and extensive surgical trauma, which results in a high anesthetic risk. Especially during anesthesia induction and the anhepatic-to-reperfusion phases, where marked hemodynamic fluctuations may readily lead to malignant cardiovascular events. Liver transplantation is associated with numerous postoperative complications, including pulmonary complications, postoperative delirium, acute kidney injury, and delayed emergence, all of which may adversely affect patient prognosis. Studies on remimazolam besylate (hereafter referred to as remimazolam) have suggested that it has minimal impact on patient hemodynamics. In theory, this renders remimazolam an ideal sedative agent for liver transplantation. This study aims to verify the hypothesis that the use of remimazolam during liver transplantation can reduce the incidence of postreperfusion syndrome (PRS). In addition, we further explored the effects of remimazolam on postoperative complications in liver transplant recipients, particularly focusing on perioperative liver and kidney function, pulmonary complications, and postoperative delirium. Methods This study is a prospective randomized controlled trial. 120 participants aged 18-60 years who are scheduled to undergo liver transplantation under general anesthesia will be enrolled. In the intervention group, remimazolam besylate will be used for anesthesia induction and maintenance at doses of 0.2-0.4 mg/kg and 1-3 mg/kg/h until the end of surgery. In the control group, propofol will be used for anesthesia induction and maintenance at doses of 1-2 mg/kg and 4-12 mg/kg/h until the end of surgery. In both groups, anesthetic drug doses or sevoflurane administration for intravenous-inhalational combined anesthesia will be adjusted based on vital signs and BIS values. All other anesthetic medications will be conducted according to the anesthetist's preference and remain consistent. Discussion This trial will investigate whether remimazolam besylate can be used during liver transplantation to reduce the incidence of postreperfusion syndrome. It will also examine whether the drug provides potential benefits regarding perioperative complications such as postoperative delirium and acute kidney injury. Trial Registration: Chinese Clinical Trial Registry,ChiCTR2500095774, registered on January 13, 2025 Keywords: liver transplantation, remimazolam, postreperfusion syndrome, complications

Introduction Education is a core social determinant of health for children and adolescents. Unfortunately, academic achievement, health, and wellbeing of adolescents have decreased in many developed countries in the past decade. The purpose of the Wellbeing and Education linkages in school-aged children (WELL-ED) study is to examine associations of school absences and academic achievement with use of school-based and community-based health and social welfare services. In addition, we will assess user experiences and multi-sector services pathways of school-aged children for a better understanding of how the service system could respond to the needs of children. Methods and analysis WELL-ED is a large population-based study that combines register data on school absences and educational support from municipalities with register data on healthcare and social service use collected from wellbeing services counties in Finland. The study cohort includes all children who attended mandatory education in public schools in Southern Finland in school year 2023-2024. A smaller cohort of adolescents in school year 8 was invited to complete a user experience survey. The primary outcomes of this study are related to equity of service use. Ethics and dissemination The Regional Committee on Medical Research Ethics of the Helsinki and Uusimaa Hospital District (2803/2024) has approved the WELL-ED study protocol. For the survey, adolescents in year 8 and parents of adolescents younger than 15 provided informed consent. Results will be published in peer-reviewed journals, summaries will be sent to participating municipalities and wellbeing services counties and press releases will be written on key findings.

Introduction Stillbirth prevention requires reliable detection of potential causes for timely interventions. Currently, there is no effective screening strategy to identify fetuses at risk of stillbirth. Prognostic models have been proposed as a potential solution, but there is a shortage of robust, clinically applicable models in low- and middle-income countries. Early birth is frequently initiated without proper risk stratification, leading to increased neonatal and infant morbidity and mortality. This study aims to develop and validate multi modal multivariable prediction models for stillbirth and pathologies that lead to stillbirth (preeclampsia & fetal growth restriction) using widely accessible and cost-effective markers. Stakeholder perspectives will also be assessed. Methods and analysis This multi-center prospective cohort study is running in four high volume regional referral hospitals in Uganda: Kawempe, Hoima, Lira, and Mbale. We will enroll at least 6,075 pregnant women attending routine antenatal care (ANC), above 13 years of age, and greater than or equal to11 weeks of gestation. Data and biological samples will be collected at 11-23 weeks, 35-37 weeks and at birth in all women. In a subset of women, additional measurements will be obtained between 24-34 weeks and 38-42 weeks to allow for spread of the data across the full spectrum of pregnancy. This data will enable us to investigate the physiological changes with gestational development in healthy or unhealthy pregnancies, to guide future monitoring and management of women and establishment of reference values for novel markers. The placenta will be collected for histopathological analysis in women diagnosed with intrauterine fetal demise at greater than or equal to 20 weeks of gestation, stillbirth nearmiss and their corresponding controls. Data on socio-demographics, obstetric history, current pregnancy conditions, and tests such as maternal hemodynamics, ultrasound, and biochemical markers will be collected from each participant, and used to develop regression and machine learning prediction models. Models will be validated and evaluated by comparing their calibration plots, precision and recall, F1 scores and accuracy, aiming for less complexity and reliable predictions. Emerging models will be translated into software as a medical device (SAMD), while taking into account user experiences, regulatory requirements, data pipelines in clinical workflows and user-friendly interfaces that facilitate access and the interpretation of outputs, to allow for seamless integration into existing electronic health information systems and decision support tools. To assess stakeholder perceptions, we will employ an exploratory qualitative component using focus group discussions, semi-structured and key informant interviews. The sample will include 81 purposively selected women and their partners who use maternity care services, local leaders and healthcare providers in and out of the four hospitals implementing iTECH in Uganda. Qualitative data will be audio recorded, transcribed verbatim and thematic analysis performed using Nvivo 12.

Background. Hypertension is a leading cause of cardiovascular morbidity and premature death in low- and middle-income countries (LMICs), where blood-pressure control remains poor because of suboptimal medication adherence, unhealthy lifestyle behaviours, and structural barriers to care. Theory-driven Health Belief Model (HBM) interventions have shown promise, but most treat the six HBM constructs as interchangeable predictors. Formative mixed-methods work by our group in the same population indicates that the constructs do not operate uniformly: perceived barriers and cues to action are associated with systolic blood pressure (SBP) through medication adherence, self-efficacy through pathways other than adherence, and perceived severity--though near-universally endorsed--is motivationally inert. This trial will evaluate an HBM-based, mediation-informed, PRECEDE-PROCEED-guided intervention prioritised by that evidence. Methods. This parallel-group, 1:1 cluster randomised controlled trial will assign twelve clusters in Kamalganj sub-district, north-east Bangladesh, to an HBM-based intervention or usual care (480 participants, 40 per cluster). The intervention, delivered over 12 months by trained community health workers, comprises five components: group education weighted toward barriers and self-efficacy; individual barrier-mapping and motivational counselling; enabling strategies including community blood-pressure monitoring corners, drug-supply advocacy, and cultural-practice substitution; reinforcing strategies through family engagement; and provider training on gender-perception bias. Primary outcomes are change in mean SBP and the proportion achieving controlled blood pressure at 12 months. Secondary outcomes include HBM construct scores, medication adherence (Bangladesh Medication Adherence Scale), lifestyle behaviours, and folk-remedy use, assessed at baseline, 6 and 12 months. Analyses follow intention-to-treat using mixed-effects models accounting for clustering; an exploratory longitudinal mediation analysis will test whether trial-induced change in adherence mediates trial-induced change in SBP. Discussion. This trial will provide a prospective test of a mediation-prioritised HBM intervention and, if effective, a culturally tailored, scalable model for hypertension control in comparable low-resource settings. Trial registration. This protocol is registered in ClinicalTrials.gov. Identifier: NCT07426978 (Date: 16/02/2026), Unique Protocol ID- PR-1440 (https://register.clinicaltrials.gov/prs/beta/records)

Background: Zoonotic infectious disease risk arises at human-animal-environment interfaces where pathogen spillover can occur. Rural communities living in biodiverse settings may experience frequent contact with wildlife and shared environments through livelihoods, food practices, and economic activities. Reducing spillover risk and strengthening pandemic prevention requires both structural and individual-level change. Community-based interventions that promote awareness, risk perception, self-efficacy, pro-environmental behaviour, and safe coexistence with wildlife may support prevention by shifting behavioural determinants of zoonotic disease risk. The Saan Suk intervention was co-developed with rural communities in Thailand using a Human-Centred Design approach and is grounded in the Health Belief Model and One Health principles. The intervention is intended to be feasible, acceptable, and deliverable through Thailands established Village Health Volunteer (VHV) system. Methods: This protocol describes a parallel-arm, cluster-randomised controlled superiority trial that will be conducted during July - October 2026, in Chanthaburi Province, Thailand. 24 villages will be equally randomised to the Saan Suk intervention or the current practice (control). In intervention villages, trained VHVs will deliver, once a week over four weeks, a multimodal One Health educational intervention designed to improve knowledge of zoonotic spillover, promote protective behaviours, reduce risky wildlife-related contacts, and support respectful coexistence with wildlife. Trained outcome assessment teams will conduct structured interviews with 42 adult participants per village, yielding a total sample size of 1,008 participants. The sample size was calculated for the primary outcome, accounting for clustering, with 90% power to detect a medium effect size (6 points on the 0-100 knowledge scale) at a significance level of 0.05, accounting for a design effect with an ICC of 0.028. The primary outcome is knowledge of zoonotic spillover, transmission pathways, risk factors, protective and risky behaviours, and safe coexistence with wildlife. Secondary outcomes include attitudes, self-efficacy, preventive and risky behaviours, and reported contacts with major local reservoir hosts. A structured questionnaire was developed, expert-reviewed, and piloted for the outcome assessment. Outcomes will be analysed using mixed-effects regression models with random effects for village and adjustment for relevant pre-specified confounders. Primary analyses will follow the intention-to-treat principle. Discussion: This trial will evaluate whether a co-designed, VHV-delivered One Health educational programme can improve knowledge of zoonotic disease prevention and behavioural determinants in rural communities living in close contact with wildlife and shared ecosystems. If effective and feasible, Saan Suk could inform integration into routine VHV training and community-based zoonotic disease and pandemic prevention strategies. Trial Registration: The Saan Suk trial is registered with the German Clinical Trials Register (DRKS). Registration ID: DRKS00038582; date of registration: 11 May 2026.

Background: Early relational health (ERH) constructs are derived fromresearch observations rather than lived experiences. This study foregrounds diverse parent voices to examine how they describeconnectionwith their young children. Methods: Usingcommunity-based participatory research (CBPR),this study was co-designed withparent leadersfromReach Out and Read. A semi-structured interview guidewas co-designed,and parent leaderssubsequentlyconducted and transcribed 18 interviews with parents from their networks.Researchersanalyzed transcripts using Reflexive Thematic Analysis.Member checking sessions with parent leadersinformedthe analytic framework. Results:Sixorganizing principleswereidentified.(1) Parent-child connection begins with an instinctual sense of responsibility.(2)Connectionebbs and flows as parent and child adapt to one another through dailyactivities.(3) Family circumstances, including family structure, cultural expectations, and intergenerational values, directly shape this connection. (4) Parents' own upbringings and past relationships indirectly shape how they connect with their child. (5) Forconnectionto grow, parents must show up physically and emotionally for their children despite competing demands. (6) Parentsgrow through engaged parenting, and that growth feeds back into the connection, creating a self-sustaining cycle of relational health.Conclusions:Our analysis generated twoconstructs underspecified in ERH frameworks.Parents described their sense of responsibility as immediate and instinctual, preceding an emotional bond.Parentsdemonstratedtheir agency in deciding what to carry forward from their relational histories, a pattern this study termsrelational legacy. Integrating parent-generated language into ERH measurementresearchmay shape a more comprehensive picture of ERHreflectinghow families experience connection.

Background: Perioperative hypotension is associated with postoperative organ injury. However, trials of hypotension avoidance have not found meaningful improvements in postoperative cardiovascular, renal, neurological or functional outcomes. One possible explanation is that organ perfusion depends on patients individual autoregulatory ranges. Hence, technology enabling monitoring of the autoregulatory status of vital organs, e.g. the brain, could provide a physiologic basis for personalising of blood pressure targets. However, current established methodologies for monitoring cerebral autoregulation in noncardiac surgery, e.g. the cerebral oximetry index (COx), are limited by performance and usability. The Medtronic Cotrending algorithm has been developed to provide automated, near real-time assessment of cerebral autoregulation. While feasibility was demonstrated in cardiac surgery, its applicability in major noncardiac surgery remains unknown. This study aims to evaluate the technical feasibility and clinical implications of Cotrending-based cerebral autoregulation monitoring in major noncardiac surgery. Objectives: Primary objective: To evaluate the technical feasibility of using the Medtronic Cotrending algorithm to monitor intraoperative cerebral autoregulation in real-time during major noncardiac surgery, drawing comparisons to the COx algorithm. Secondary objectives: to investigate the potential clinical implications of Cotrending-based cerebral autoregulation monitoring. Design: Single-centre, prospective cohort study. Setting: Swiss tertiary care centre Patients: Patients enrolled in AUTOREGULATE-NONCARDIAC who were monitored intraoperatively with the Medtronic INVOS(TM) 5100 near-infrared spectroscopy (NIRS) system. Outcomes: Technical feasibility outcomes include success rate of determination of the lower limit of cerebral autoregulation, intraoperative uptime, time to first estimate of the lower limit of cerebral autoregulation, sensitivity to external factors and to data artefacts; agreement of Cotrending-derived lower limit of cerebral autoregulation with COx-derived lower limit of cerebral autoregulation. Conclusions: N/A Trial registration: Clinicaltrials.gov NCT07630129