BMJ Open

IntroductionRandomised controlled trials (RCTs) investigate the safety and efficacy of interventions. It has become clear however that some RCTs include fabricated data. The INSPECT-SR tool assesses the trustworthiness of RCTs in systematic reviews of healthcare-related interventions. However, where individual participant data (IPD) can be obtained, a more thorough assessment of trustworthiness is possible. Consequently, INSPECT-SR recommends obtaining IPD to resolve uncertainties, though there is no consensus on appropriate methods for forensic analysis of raw data. Our aim is to evaluate IPD checks to establish which are worthwhile, and how they can be implemented in a new tool, INSPECT-IPD (Investigating Problematic Clinical Trials with Individual Participant Data). Methods and analysisUsing international expert consensus and empirical evidence, the INSPECT-IPD tool will be developed using five stages: (1) compiling a list of IPD trustworthiness checks, (2) evaluating the usefulness and ease of interpretation of the checks when applying them to a collection of presumed authentic and fabricated IPD datasets, (3) a Delphi survey to determine which checks are supported by expert consensus, (4) a series of consensus meetings for selection of checks to be included in the draft tool and finally (5) prospective testing of the draft tool in: a) the production of systematic reviews, and b) the journal editorial process for RCT submissions, leading to refinement based on user feedback. Ethics and disseminationThe University of Manchester ethics decision tool determined that ethical approval was not required (18 June 2024). This project includes secondary research and surveys of healthcare researchers on topics relating to their work. All results will be published as preprints and open-access articles, and the final tool will be freely available. STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIAn international consensus process and empirical evidence will be used to develop the tool. C_LIO_LIThe development and dissemination of the tool will involve key stakeholders. C_LIO_LIIn the absence of a gold-standard test for problematic data, this tool should not be interpreted as a diagnostic instrument for trustworthiness. Instead, it will assist researchers in assessing the trustworthiness of a study. C_LIO_LIThe tool will only be applicable when individual participant data (IPD) can be accessed. Where IPD can be accessed, the ability to assess trustworthiness will be improved. C_LI

IntroductionThe growing burden of cardiovascular disease (CVD) threatens the sustainability of our healthcare systems. In the Netherlands, two-thirds of CVD-related healthcare is delivered in primary care practices, primarily by practice nurses. Given the increasing staffing shortages and the substantial heterogeneity of the population of primary care patients at increased risk of CVD, cardiovascular risk management strategies should be better tailored to individual patients needs and risk profiles. Therefore, we developed the PROSPERA program, aimed at the population of patients enrolled in integrated care programs for cardiovascular risk management in primary care. Methods and analysisThe PROSPERA study is a pragmatic 1:1 cluster randomized controlled trial in 22 primary care practices in the greater Leiden and the Hague region in The Netherlands, investigating real-world effectiveness of the PROSPERA program with care as usual. The PROSPERA program is a multilevel complex intervention, including a population-level risk stratification and three individual patient-level components: a healthcare professional training program in cardiovascular risk communication, a lifestyle questionnaire (Lifestylecheck), and a clinical decision support tool (U-Prevent). Patients between 40-90 years of age enrolled in integrated care programs for increased cardiovascular risk are included. The primary outcome is defined as successful achievement of all protocol-defined cardiovascular preventive treatment goals, measured as the difference between the proportion of patients who meet the outcome in the intervention versus the control group at 18 months. Secondary outcomes include implementation outcomes, healthcare professionals satisfaction on usability of the PROSPERA program, patient experience with shared decision making and decisional conflict, and outcomes on cost-effectiveness. Ethics and disseminationConsent for the use of routine healthcare data is obtained through an opt-out procedure for participating practices. Digital informed consent will be obtained for the study questionnaires for patients and healthcare professionals. Main findings on effectivity, efficacy and implementation will be disseminated via peer-reviewed journals and via (inter)national conferences. Trial registration numberNCT06593704 Strengths and limitations of this studyO_LIThe PROSPERA program was co-developed with stakeholders and refined via a preceding qualitative study, ensuring better integration with clinical workflows. C_LIO_LIThe pragmatic design of this study allows for broad inclusion at the level of the population at increased risk of CVD, enhancing representativeness and inclusivity. C_LIO_LIUse of the Extramural Leiden Medical Center Academic Network (ELAN) data infrastructure enables comprehensive collection of healthcare data. C_LIO_LIThe complexity of the current information- and technology (IT) infrastructure prototype is a constraint, but is expected to be simplified in the future. C_LIO_LIPotential cross-over contamination cannot be prevented, as control practices may have informal access to some PROSPERA components, although these are not yet widely implemented. C_LI

PurposeThe Nepal Turnaway Study was designed to understand abortion care experiences and the longitudinal wellbeing of abortion-seekers and their families. ParticipantsThe Nepal Turnaway Study is a nation-wide cohort of abortion seekers recruited from public and private facilities across all seven provinces between April 2019 and December 2020. It contains 1,832 abortion seekers followed for up to five years. Repeated measures of socioeconomic status, health and wellbeing--including maternal physical and mental health and child health (under age three)--were collected every six months or annually, alongside detailed pregnancy and abortion-seeking histories. Findings to dateAbortion seekers in this context can be recruited at health facilities (96% participation) and successfully followed for up to five years (87% retention). Nearly half (49%, n=856) of abortion seekers were initially denied their abortion, and 16% (n=275) ultimately carried the pregnancy to term and gave birth. Those who were denied were more likely to be socioeconomically disadvantaged prior to abortion seeking. Future plansThe Nepal Turnaway Study will be used to understand the longitudinal health and socioeconomic effects of receiving a wanted abortion in this setting. Exposure-balancing weights can be applied to ensure rigorous estimation of the effects of abortion denial on longitudinal outcomes. This cohort can also be used more broadly to examine the trajectories of women and their families in the years following abortion-seeking. RegistrationThis study has been registered at clinicaltrials.gov (NCT03930576) STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIThe primary strength of the Nepal Turnaway Study is the recruitment of individuals at the time of abortion seeking, with prospective follow-up. This design ensures accurate measurement of pregnancy outcomes and establishes temporality between abortion receipt and subsequent longitudinal outcomes. C_LIO_LIThe five-year follow-up period enables assessment of both immediate and longer-term health and wellbeing among abortion seekers. It also allows examination of outcomes for children born before and in the years following abortion seeking, capturing broader family-level implications. C_LIO_LIFuture collaborations are welcome, and researchers may rigorously examine the effects of receiving a wanted abortion by applying exposure-balancing weights that have already been derived using propensity score methods C_LIO_LILoss to follow-up and administrative censoring at study end may limit statistical power for some analyses and could introduce bias. C_LIO_LIAlthough the study seeks to emulate a target trial, participants were not randomized to pregnancy outcome groups; therefore, unmeasured or unknown confounding may affect longitudinal analyses. C_LI

IntroductionMusculoskeletal conditions have high, and increasing, incidence and prevalence. Although there are many clinical guidelines available for common conditions, most are poor quality and sparsely adopted into practice. We aim to improve patient outcomes by developing robust Best Practice Guidelines (BPG) to get research findings into practice for a range of common musculoskeletal conditions. Methods and analysisMixed methods with systematic review of high-quality studies and qualitative elicitation of both patients perspectives and expert clinical reasoning through in-depth interviews will form the basis for the BPGs. A segregated convergent synthesis, informed throughout by stakeholder engagement, will guide the format and structure of the BPGs. Ethics, outputs and disseminationEthical approval for the qualitative studies and implementation events will be obtained from university and health service research ethics committees. Educational packages for each BPG condition will be hosted online and be available for students, clinicians, and education providers. Dissemination will follow traditional routes including publications and presentations; alongside innovative approaches such as collaboration with higher education institutions, online hosting, adoption by professional bodies, and a social media campaign. Implementation will occur adaptively in multiple national contexts to reflect local requirements and resources, deploying participatory and implementation methods that are contextually and culturally appropriate. KEY MESSAGESO_LIWhat is already known on this topic - Clinical guidelines for the management of musculoskeletal conditions are common, but have limitations regarding quality, applicability, editorial independence, and patient perspective. They are rarely adopted into clinical practice. C_LIO_LIWhat this study adds - We have developed a robust (supported by Patient and Participant Involvement) mixed-methods approach that integrates the three components of evidence-based medicine: synthesis of high-quality evidence, patients perspectives/values, and expert clinical reasoning. We have also developed an education, dissemination, and implementation approach to facilitate international adoption of these guidelines. C_LIO_LIHow this study might affect research, practice or policy - The guideline development methods will integrate the three pillars of evidence-based practice and ensure they are robust and clinically applicable. Creation of educational material combined with an implementation and dissemination plan will support adoption into clinical practice of different countries and cultures, designed to lead to improved patient outcomes. C_LI

IntroductionAcross Europe, many people with HIV are diagnosed late despite repeated contact with hospital services for HIV indicator conditions. These conditions flag a possible underlying HIV infection for which HIV testing is recommended. They provide an opportunity to identify people with HIV, yet implementation of indicator condition based testing remains insufficient in hospital practice. The #aware.hiv Europe study was developed to address this gap by embedding HIV teams into routine care to normalise HIV testing. Methods and analysis#aware.hiv Europe is a stepped-wedge cluster randomised trial in 30 hospitals across ten European countries. Five clusters of 6 hospitals each will sequentially transition from control to implementation periods when local HIV teams led by an infectious diseases specialist will be installed. Intervention activities include hospital-wide peer audit and feedback on missed testing opportunities, targeted education, stigma reduction activities, and strengthening of linkage to HIV prevention and care. Patients with predefined HIV indicator conditions are identified using International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes, confirmed through manual review. The primary outcome is the change in HIV testing rate among patients with confirmed HIV indicator conditions. Secondary outcomes include HIV case detection, cascades of diagnosis, care and prevention, variation in testing practices, healthcare professional knowledge and stigma, and implementation outcomes. Analyses will use mixed effects regression models accounting for clustering and time within the stepped-wedge design. Ethics and disseminationThe study has ethical approval in all hospitals to use routinely collected clinical data under exemption from informed consent for patient level data. Results will be disseminated through peer reviewed publications, conferences, and collaboration with clinical and community partners with the goal to inform HIV testing policies. Trial registrationClinicalTrials.gov NCT06900829. https://clinicaltrials.gov/study/NCT06900829 Strengths and limitations of this study+ Large, multinational, real-world, stepped-wedge, cluster randomized trial design. + Primary outcome derived from routinely collected clinical data, using a GDPR- and GCP-compliant approach with exemption from informed consent. + Hospital-wide intervention targeting care professionals, delivered through proactive expert HIV teams across departments powered to conclude on hard HIV care cascade clinical endpoints and stigma reducing interventions. + Implementation science design informed by established frameworks (CFIR and RE-AIM) to strengthen cross-continental generalisability. - Variation in healthcare systems and baseline testing practices across countries may contribute to heterogeneity in implementation and outcomes. - Despite standardised SOPs, local clinical judgement influences the assessment of HIV indicator conditions.

1. PurposeSpontaneous preterm birth (sPTB), particularly early preterm birth and mid-trimester loss, remains poorly understood and difficult to predict. The INSIGHT cohort was established to create a deeply phenotyped, longitudinal pregnancy dataset integrating clinical data and biological sampling to investigate the mechanisms of cervical shortening and sPTB, with a focus on linking innate immune responses, the vaginal microbiome, and host biology to identify early biomarkers of risk. 2. Participants2272 pregnant women (8+0 -28+0 weeks gestation) were enrolled as high or low risk of preterm birth based on obstetric history, cervical length, cervical procedures, multiple pregnancy, or Mullerian anomalies. Serial clinical data and biological samples, including cervicovaginal specimens and blood, were collected throughout pregnancy. 3. Findings to dateThe cohort has generated comprehensive multi-omic data, including transcriptomic, microbiome, metabolomic, proteomic, and immune profiling. Key findings demonstrate that maternal plasma cfRNA can predict early sPTB months before clinical presentation, and that integration of cervicovaginal microbiota, metabolites, and host immune markers improves risk prediction and provides mechanistic insight into inflammatory pathways leading to sPTB. 4. Future plansRecruitment concluded in 2023, with final visits occurring in 2024. Ongoing analyses focus on refining predictive models, defining biological subtypes of preterm birth, and translating integrated biomarker panels into clinically scalable risk stratification tools. STRENGTHS AND LIMITATIONS OF THIS STUDYO_LILarge, prospective longitudinal cohort (Strength): Ten years of recruitment with repeat sampling enabled detailed study of biological pathways leading to sPTB. C_LIO_LIBroad risk spectrum with clear definitions (Strength): Inclusion of both high and low-risk women using pre-specified clinical criteria supported robust comparative analyses and biomarker discovery. C_LIO_LIMulticentre NHS recruitment (Strength): Inclusion of several sites, particularly the diverse Lambeth population at St Thomas, enhanced population diversity and external validity. C_LIO_LIHospital-based, high-risk enrichment (Limitation/Strength): Recruitment from specialist preterm birth clinics and secondary/tertiary care may limit generalisability to lower-risk or primary care populations. However, it did ensure many preterm birth events were captured prospectively in this study. C_LIO_LIIncomplete follow-up and limited late sampling (Limitation): Attrition and sampling only up to a prespecified gestation (defined by standard clinical pathway) reduced full pregnancy coverage of longitudinal data. C_LI

IntroductionIn many Low- and Middle-Income countries (LMIC), access to psychological therapies for psychosis remains extremely limited, contributing to significant treatment gaps and persistent inequalities in care. Novel interventions that are effective, scalable, and culturally acceptable across diverse settings are urgently needed. AVATAR therapy is an innovative digital intervention for distressing voices in psychosis, developed in the UK. The therapy enables voice-hearers to engage in a series of facilitated dialogues with a customized computer-based representation of their main distressing voice. AVATAR3 represents the first initiative to contextually adapt AVATAR therapy and evaluate its acceptability in two LMIC settings (Ethiopia and India). Methods and analysisWe will establish Innovation and Implementation Hubs in Addis Ababa, Ethiopia (Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa) at Addis Ababa University (AAU) and Mental Health Service Users Association (MHSUA), Ethiopia) and New Delhi, India (All India Institute of Medical Sciences). Phase 1 employs formative work and diverse stakeholder engagement to inform context-specific adaptations. Reflexive thematic analysis will be used, with data synthesis informed by the Cultural Adaptation of Scalable Psychological Interventions (CASPI) framework and Ecological Validity Model (EVM). Phase 2 tests adapted AVATAR therapy through a parallel case series (n=15 per site, targeting 70% completion rate) measuring feasibility, acceptability, and safety indicators at baseline, 12-weeks, and 24-weeks. Qualitative research will explore the experiences of participants (n=10) and therapists (n=8) at each site. Ethics and disseminationEthical approval has been obtained from Addis Ababa University College of Health Science Institutional Review Board, All India Institute of Medical Sciences (AIIMS) Institutional Review Board and the Kings College London (study sponsor) Research Ethics Committee. Findings will be disseminated to inform the implementation of AVATAR therapy across diverse international settings. Strengths and limitations of this studyO_LIInterdisciplinary and participatory approach C_LIO_LIContextual adaptation of a digital innovation C_LIO_LIExpert by experience leadership and involvement from the conception of the study C_LIO_LIThe study will develop tools and share learning to support future digital mental health innovation across diverse international settings C_LIO_LIThe case-series at each site will not have a control group C_LI

IntroductionSkin-to-skin contact during the first hour of birth is recommended for healthy newborn infants and their mothers and improves early stabilisation and breastfeeding outcomes. Kangaroo Mother Care (KMC), involving prolonged skin-to-skin contact (SSC) and exclusive breastfeeding, provides an optimal physiological transition from intrauterine to extrauterine life for preterm and low birth weight infants, improving survival by 32% and conferring multiple clinical and neurodevelopmental benefits. Extending the duration of SSC contact beyond the first hour may similarly confer underexplored benefits to normal birth weight infants, including improved stabilisation, breastfeeding, growth, and maternal-infant bonding. The study aims to evaluate the effect of KMC during the first 72 hours on early weight loss, weight gain velocity and breastfeeding quality in normal birthweight infants. Methods and AnalysisThis multicentre, individually randomised, controlled, open-label superiority trial will enrol 516 healthy singleton neonates with birth weight [&ge;]2500 grams and their mothers with uncomplicated vaginal deliveries from 3 public health facilities in Uttar Pradesh, India. Dyads will be randomised (1:1) and stratified by site to either intervention or control groups. The intervention involves prolonged KMC ([&ge;]8 hours of daily SSC with exclusive breastfeeding in the KMC position) during the initial 3 days after birth, with a recommendation to continue KMC at home throughout the newborn period. Both intervention and control groups will receive a common minimum care package, including breastfeeding initiation through uninterrupted SSC in the first hour, essential newborn care counselling, vaccinations and other standard facility care. The primary outcomes are: 1) mean percentage weight loss at 48 hours; 2) weight gain velocity up to 28 days; and 3) the proportion of dyads with moderate-to-poor quality breastfeeding scores (BBAT <7) at age 7 completed days. Secondary outcomes include exclusive breastfeeding rates, maternal breastfeeding experience, incidence of possible serious bacterial infection, maternal depression, and maternal-infant bonding. Data will be collected electronically using standardised tools with quality control measures. Primary outcomes will be analysed using Linear Mixed-Effects Models (continuous) and Mixed-Effects Logistic Regression (binary) on an Intention-to-Treat basis, adjusting for study site, parity, infant sex, and baseline birth weight. A p-value <0.05 will be considered statistically significant. Ethics and DisseminationThe study is approved by the institutional ethics committees of the Community Empowerment Lab and King Georges Medical University. Written informed consent will be obtained from participating mothers. All findings will be disseminated regardless of the outcome, through publication in peer-reviewed journals, presentations at international conferences, and policy briefings to local health authorities. Data will be deposited in an open-access repository to promote data sharing and transparency. The results are intended to inform national and international guidelines on essential newborn care for the global population of healthy, term infants. Strengths and limitations of the studyO_LIThis study fills an important evidence gap, being the first multi-centre randomised controlled trial to evaluate prolonged KMC benefits for normal birthweight infants, a group that has largely been excluded from prior KMC research. C_LIO_LIThe study will conduct a rigorous and objective assessment of a range of important newborn and maternal outcomes, including physical growth, quality of breastfeeding and exclusive breastfeeding, maternal mental health and mother-infant bonding, providing a holistic understanding of KMCs effects on the newborn-mother dyad. C_LIO_LIThe visible nature of KMC makes blinding participants and implementers impossible, however, extensive measures have been undertaken to minimise bias. Being the first study of its kind, it excludes Caesarean section and complicated births to simplify the intervention, analysis and subsequent interpretation. C_LI Administrative informationO_ST_ABSTitleC_ST_ABSEffect of Kangaroo Mother Care during the first 72 hours of life on early growth and breastfeeding in normal birth weight newborns: Protocol for a Randomised Controlled Trial Trial registrationThis trial has been registered with the Clinical Trials Registry of India CTRI/2024/01/062057 (date: 30/01/2024) and International Standard Randomised Controlled Trial Number ISRCTN14346778 (date: 19/12/2024). Protocol date and versionSeptember 10, 2024; CEL/KMC_NormalBW/V3.1. The full study protocol and statistical analysis plan will be available as supplementary material accompanying the published manuscript. The protocol has also been uploaded to the CTRI registry. Funding & Role of sponsorThis work was supported by Indian Council of Medical Research (Project number: IIRP-2023-7329). The sponsor has no role in the design, conduct, analysis and reporting of the trial, but provides study oversight through a scientific review committee. Sponsor contact informationIndian Council of Medical Research (ICMR), New Delhi - 110029, India Email: icmrhqds@sansad.nic.in

ObjectivesUsing qualitative methods, this study aimed to provide a comparative overview of the similarities and differences in perspectives towards AI in healthcare in two different stakeholder groups: healthcare practitioners and patients. It also aimed to investigate whether these perspectives may influence the adoption of AI in healthcare. DesignThis study was conducted using semi-structured interviews. Qualitative data from the interviews were analyzed using both deductive and inductive coding, followed by a thematic analysis to identify the prevailing categories for further discussion. SettingThe study was conducted within the Department of Surgical Oncology and Gastrointestinal Surgery of Erasmus Medical Center in Rotterdam, the Netherlands. ParticipantsA total of 30 participants were recruited using purposive sampling based on predefined inclusion characteristics. This included 18 healthcare professionals (subdivided into 10 surgeons and 8 nurses), and 12 patients. The inclusion criterion for healthcare professionals included surgeons specializing in gastro-intestinal surgery, while the inclusion criterion for patients included those patients who had undergone gastro-intestinal surgery within the past 12 months at the time interviews were conducted. Exclusion criteria involved excluding patients with major health complications. Outcome measuresThe studys central objective was to develop a set of thematic domains that characterize how both groups of stakeholders view the integration of AI in healthcare, encompassing their attitudes towards trust, acceptance, and responsibility. Additionally, it aimed to compare perspectives between healthcare professionals and patients in order to identify areas of convergence and divergence. ResultsThe analysis comprised a total of 3 main thematic categories, with 10 subcategories. The main thematic categories which emerged were AI Knowledge, Ethics, and Operational and Clinical Implications. While clinicians largely focused on validation, monitoring, administrative labor, and clinical integration, patients emphasized the importance of human attention, of being heard, and of maintaining trust in their clinician. ConclusionComparing the attitudes and perspectives of both healthcare practitioners and patients revealed the importance of taking into consideration both groups of stakeholders. While both groups tend to raise concerns about similar themes connected to responsibility, it is clear that this concern involves complex dynamics present in the epistemic environment of healthcare. Strengths and limitationsO_LIThis study uniquely compared healthcare practitioners and patients perspectives within a single qualitative design, using similar interview guides to enable direct cross-stakeholder comparison. C_LIO_LIThe study examined perceptions of an AI model that had been designed and validated for clinical use, enhancing the practical relevance of the findings. C_LIO_LIThe relatively small sample size may have limited the diversity of perspectives captured and reduced transferability. C_LIO_LIAs the study was conducted in a single academic hospital in the Netherlands, the findings may not be generalizable to other healthcare settings or national contexts. C_LI

IntroductionPrediabetes, a key precursor to type 2 diabetes, is highly prevalent and underdiagnosed, particularly among adults aged [&ge;]45 years with elevated body mass index (BMI). Early detection is critical because lifestyle interventions can delay or prevent progression to type 2 diabetes. The Glow Up (GLucose Observation and Wearable Use for Prevention) study aims to (1) test the feasibility of a digital biomarker for prediabetes screening using wearable- and smartphone-derived lifestyle factors (e.g., sleep, physical activity, and nutrition patterns), in daily life and to (2) characterize individual- and metabolic subgroup-level variability in lifestyle factors and glycemic control. Specifically, we aim to examine how lifestyle factors relate to diabetes risk and identify personalized predictors of early metabolic dysregulation. Methods and analysisGlow Up is a prospective, single-center, observational case-control study conducted in Switzerland. Adults (N=200) aged [&ge;]45 years with BMI [&ge;]25 kg/m{superscript 2} will be recruited, including n=100 individuals with prediabetes and n=100 age- and sex-matched case-control normoglycemic controls. Participants will undergo four weeks of continuous monitoring using a blinded continuous glucose monitor (CGM), and commercial- and medical-grade wearables; e.g. capturing physical activity, sleep, and physiological markers (heart rate variability, heart rate and skin temperature); in addition to completing daily image-based meal logs, using smartphones. Glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and body anthropometrics will be collected at baseline and follow-up, four weeks apart. Primary outcomes include HbA1c and FPG, measured at approximately four week follow-up. Secondary outcomes include CGM metrics, lifestyle profiling (sleep, physical activity, stress, and nutrition), and adherence to image-based meal logging. Ethics and disseminationThe study has received ethics approval from the Ethics Committee of Eastern Switzerland (BASEC ID.: 2025-00972). Results will be published in international peer-reviewed journals and at national and international conferences as posters, presentations, and articles. Summaries will be provided to the funders and personalized reports to participants. Trial registration numberNCT07373418 Article SummaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIGlow Up presents the first study in Switzerland to investigate glycaemic and lifestyle profiling among individuals with normoglycaemia and prediabetes in an observational, free-living setting. C_LIO_LITo our knowledge, Glow Up is the first dataset to combine continuous glucose monitoring, commercial- and medical-grade wearable sensors, smartphone-based questionnaires, image-based dietary logging under free-living conditions, and clinical biomarkers, HbA1c and FPG; allowing for rich digital phenotyping. C_LIO_LIInclusion of baseline and follow-up clinical biomarkers (HbA1c and FPG) provides clinically validated ground truth measures, strengthening outcome validity and anchoring digital and wearable-derived markers to established clinical, diagnostic standards. C_LIO_LIThe absence of direct measures of insulin resistance, lipid metabolism, and gut microbiome compositions may limit more mechanistic investigation of glucose dysregulation patterns and metabolic sub phenotyping. C_LIO_LIThe four-week follow-up period may limit inference on longer-term glycaemic trajectories and progression to T2D. C_LIO_LIFindings may not be generalisable beyond at-risk adults living in Switzerland who meet the study eligibility criteria. C_LI

BackgroundDespite national efforts to improve research inclusion, people from underserved communities remain underrepresented in dementia trials. Barriers occur at the point of initial engagement and also within the participation pathway itself, as the structure and burden of early screening procedures can discourage continuation. ACCESS D (Advancing Community Collaboration and Engagement Strategies in Dementia) aims to address these challenges by testing a community-based model that combines co-produced engagement events, low-burden research activities, and real-time support from the South Central Ambulance Service (SCAS), a trusted, community-visible healthcare workforce. Methods and analysisACCESS D is a 12-month mixed-methods feasibility study recruiting 100 adults aged 50-90 years with either (i) a diagnosis of mild cognitive impairment or dementia or (ii) a self- or proxy-reported memory concern affecting daily life. The study will deliver 12-18 co-produced community outreach events in non-clinical settings, supported by SCAS research paramedics and nurses. Following consent, participants will complete a core questionnaire and may optionally take part in one or more low-burden research activities designed to provide supported, first-hand experience of dementia research. Feasibility outcomes, including pathway progression and opt-in to future dementia research contact, will be descriptively summarised and stratified using NIHR INCLUDE-aligned underserved characteristics. Qualitative interviews and focus groups with participants and staff will examine acceptability, perceived value, barriers and enablers, and implementation learning, analysed using thematic analysis and integrated with quantitative findings. Ethics and disseminationThe study has received a favourable opinion from the Southwest Frenchay Research Ethics Committee and Health Research Authority approval (IRAS 361074). Findings will be disseminated via peer-reviewed publications, conference presentations and co-produced lay outputs for community partners and participants. These outputs will be accompanied by an implementation toolkit for research teams and a visual summary for potential participants. Strengths and limitations of this studyO_LIThis study tests a community based, co-produced delivery model that embeds real research participation within outreach, addressing both awareness and structural barriers to dementia research participation. C_LIO_LIOutreach is delivered by a trusted, community visible healthcare workforce, enabling real time support and reducing psychological, practical and digital barriers for underserved groups. C_LIO_LIThe mixed methods feasibility design combines quantitative indicators of reach, progression and resource use with qualitative insights into participant and staff experience, generating actionable learning for scale up. C_LIO_LIOutcomes are explicitly equity-stratified using NIHR INCLUDE aligned characteristics, allowing early assessment of differential reach and engagement across underserved populations. C_LIO_LIAs a single region feasibility study, findings may have limited immediate generalisability. However, the study is designed to generate transferable implementation insights and inform a future multi-site evaluation. C_LI

ObjectiveTo explore emergency medical dispatchers (EMD) experiences of prioritising patients and stewarding ambulance resources when system capacity is constrained. DesignQualitative interview study using inductive qualitative content analysis. SettingEmergency medical communication centres (EMCCs) in Sweden operated by the national emergency call provider, responsible for receiving 112 calls and dispatching ambulances. ParticipantsThirteen purposively sampled EMDs with at least one year of professional experience. Data analysisInterviews were analysed inductively using qualitative content analysis (Elo and Kyngas) through open coding, grouping into subcategories and abstraction into generic categories and one main category. ResultsDispatchers described prioritisation under scarcity as system work that simultaneously addresses individual patient acuity and population-level readiness. One main category captured this work: Stewarding scarce response capacity. Three interrelated generic categories characterised stewardship: (1) prioritising by clinical urgency within geographic and operational constraints; (2) producing availability through anticipation, reassessment and queue governance in a virtual waiting room; and (3) coordinating response through information infrastructures and interprofessional collaboration. Across categories, dispatchers described redistributing risk across patients and time while attempting to avoid both under-response to urgent need and over-allocation that would leave areas without coverage. ConclusionsDispatch under scarcity is best understood as active stewardship of a safety-critical dispatch queue. Strengthening patient safety therefore requires organisational support for reassessment and escalation during prolonged waits, and governance that makes queue dynamics and geographic coverage trade-offs visible, rather than relying solely on initial triage decisions or aggregate response-time targets. Strengths and limitations of this studyO_LIStrengths and limitations of this study C_LIO_LIAn inductive qualitative content analysis allowed categories to emerge from dispatchers own descriptions, rather than imposing predefined theoretical frameworks. C_LIO_LIInclusion of emergency medical dispatchers with varied ages, professional experience and EMCC locations enhanced the richness of the data and potential transferability. C_LIO_LIAnalyst triangulation, an explicit abstraction pathway and data-to-category quotations strengthened analytic transparency and trustworthiness. C_LIO_LIInterviews were conducted via video, which may have limited access to non-verbal cues compared with in-person interviews. C_LIO_LIThe study was conducted within a single national dispatch system, and participation was voluntary, which may limit transferability and introduce self-selection of more experienced or engaged dispatchers. C_LI

ImportanceThe United States is facing a projected shortage of 40,000 primary care physicians by 2034. Student-run clinics (SRCs) are widely regarded as service-learning environments that may encourage students to enter a primary care specialty, but prior studies have yielded conflicting results and are limited to non-generalizable, single site analyses. ObjectiveTo compare likelihood of practice in a primary care specialty between students who did and did not participate in an SRC via pooled meta-analysis of U.S.-based studies. Study SelectionStudies were first identified through a comprehensive library of U.S.-based SRC literature. The inclusion criteria were publications on SRCs in the United States with MD/DO students, from all time until March 1, 2024. Exclusion criteria were: full text not available; published abstract/textbook/dissertation/thesis; not in English. Two authors independently screened the database for publications on SRC participation and practice in primary care specialties. To identify relevant literature after March 1, 2024, the authors performed iterative snowball sampling of the bibliographies of included studies and their Google Scholar "cited by" lists until saturation. Finally, we included original data from the single largest study on this topic. Data Extraction and SynthesisWe evaluated study quality using the NIH Study Quality Appraisal Tool. We used a random-effects model to account for heterogeneity. Main Outcomes and MeasuresThe primary outcome was the relative likelihood (risk ratio) of pursuing a primary care specialty among SRC volunteers versus non-volunteers. We used a funnel plot and sensitivity analysis to assess for bias. ResultsSeven studies met inclusion criteria with a cumulative sample size of 7,468 students. SRC volunteers pursued primary care at 102% to 160% the rate of non-volunteers. The pooled risk ratio was 1.25 (95% CI: 1.09-1.44). Funnel plot and multiple sensitivity analyses did not suggest publication bias or undue influence from included studies. Conclusions and RelevanceSRC participation is associated with a statistically-significant 25% increased likelihood of practicing in a primary care specialty. These findings may inform national and institutional strategies to support service-learning and address the national primary care workforce shortage. KEY POINTSO_ST_ABSQuestionC_ST_ABSIs participation in a student-run clinic during medical school associated with increased likelihood of practicing in a primary care specialty? FindingsDespite conflicting results in the literature among small and single-site studies, in this meta-analysis of 7,468 medical students, participation in a student-run clinic was associated with a statistically significant 25% increased likelihood of practicing in a primary care specialty. MeaningStudent-run clinics may be a potential strategy for strengthening the pipeline into primary care and reducing the projected shortage of 40,000 primary care physicians.

ObjectivesTo evaluate the effect of surgical hubs on the volume of surgeries, patient waiting times, and length of hospital stay for elective hip and knee replacements in the English NHS. DesignA retrospective longitudinal study using a difference-in-differences approach to compare changes in outcomes at NHS trusts that opened surgical hubs with those that did not. SettingThe study was set in the English NHS, using administrative data from NHS acute trusts providing elective hip and knee replacements between April 2014 and September 2024. ParticipantsThe study included 76 NHS trusts. The treatment group consisted of 29 trusts that opened a surgical hub for trauma and orthopaedic surgery during the study period. The control group consisted of 47 trusts that did not. 48 trusts that performed fewer than 1,000 relevant procedures over the ten-year period or that reported data for fewer than 41 of the 42 quarters in the sample period were excluded. InterventionThe phased introduction of surgical hubs dedicated to elective procedures at 29 NHS trusts between Q1 2020 and Q3 2024. Main outcome measuresThe three main outcomes were, measured at the trust-quarter level: the total number of elective primary hip and knee replacements (surgical volume), the average length of stay in hospital, and the average waiting time from being added to the waiting list to hospital admission. ResultsThe opening of a surgical hub was associated with an increase of 43.75 hip and knee replacement surgeries per quarter (95% CI: 22.22 to 65.28), which represents a 19.1% increase compared to the pre-hub mean. Length of stay was reduced by 0.32 days (95% CI: - 0.48 to -0.16), a 7.8% reduction. There was no statistically significant effect on average waiting times (-14.96 days, 95% CI: -33.11 to 3.19). ConclusionsSurgical hubs appear to be effective at increasing the number of hip and knee replacements and reducing the time patients spend in hospital. However, in this study, they did not lead to a statistically significant reduction in waiting times overall.

IntroductionSevere mental illness is associated with high mortality rates and cardiovascular disease. Obesity and dysmetabolism associated with antipsychotic treatment comprise modifiable risk factors, which remain undertreated. Interventions such as antipsychotic-switching, lifestyle-interventions and weight-reducing medication have shown varying results indicating a need for a more individualized approach. The Meta-Care Trial aims to assess the effectiveness of a pragmatic, individualized, evidence- and guideline-based cardiometabolic intervention. Methods and analysisMeta-Care is an open-label randomized controlled trial (RCT). Patients between 18-45 years with schizophrenia spectrum disorders or bipolar disorder will be recruited from in- and outpatient Mental Health Services in the Capital Region of Denmark. Inclusion criteria include treatment with antipsychotics and: either i) [&ge;]5% body weight gain or [&ge;]5cm waist circumference increase since initiation of antipsychotic therapy, or ii) a body mass index (BMI) [&ge;]30 kg/m2, or iii) BMI [&ge;]27 kg/m2 and related cardiovascular risk factors. Patients are randomized to a pragmatic, individualized metabolic clinic using evidence- and guideline-based care in a mental health center or standard care. Allocation-ratio is 1:1. The primary outcome is the proportion of patients achieving weight loss [&ge;]5% of initial body weight after 12 months. Secondary and exploratory outcomes cover cardiometabolic risk factors, cognition, personal recovery, and quality of life. Qualitative interviews will explore patient experience and contextual factors. Recruitment started in October 2023 and will include a total of 84 patients. Ethics and disseminationThe Meta-Care trial is funded by The Independent Research Fund Denmark and The Worzner Memorial Fund for Research in Mental Illness. The trial has been approved by the Regional Ethics Committee and Data Protection Agency in the Capital Region of Denmark. Positive, negative, and inconclusive results will be published in scientific peer-reviewed journals, presented at conferences, and dispersed to patient organisations and media. Strengths and limitations- The Meta-Care Trial is the first randomized control trial (RCT) to investigate the effectiveness and acceptability of a pragmatic, individualized metabolic clinic located in a mental health center using evidence- and guideline-based care to treat obesity and cardiometabolic risk factors in patients with severe mental illness - The pragmatic design with limited exclusion criteria and simple outcome measures will generate results that are generalizable to clinical practice - The complex Meta-Care multi-intervention limits inferences of effects explained by specific modifications of pharmacotherapy or lifestyle changes - Potential knowledge exchange from treating personnel in the Meta-Care Trial to caregivers in the standard care group may lead to contamination bias - Although the Meta-Care trial has an open label design, measurements of primary and secondary outcomes will be carried out by blinded assessors

IntroductionAs antibiotic resistant organisms and infections continue to proliferate globally, it becomes increasingly difficult to select empiric antibiotic therapy, particularly in patients who stand to benefit from early adequate treatment. The inappropriate treatment of suspected infection, including sepsis, can be both too narrow and too broad. There is a need to optimize and tailor selection of antibiotic therapy to each patient, such that those at risk for infections due to antibiotic resistant organisms receive broader therapy, and those that are not at risk receive narrower antibiotic therapy. By helping clinicians select the right antibiotic for each individual patient we can potentially reduce unnecessarily broad antibiotic prescribing while preserving (and potentially improving) adequacy of treatment. Individualized clinical prediction models and decision support interventions are promising approaches that can meet these needs by better defining patient risk for antibiotic resistant or susceptible infections, but rigorous prospective evaluations are needed to confirm their utility. MethodsWe propose a two-period two-sequence non-blinded cross-sectional cluster randomized cross-over trial of an individualized antibiotic prescribing decision support intervention, administered by antibiotic stewardship pharmacists, for providers treating hospitalized patients with suspected infection including sepsis. The trial is taking place at 3 hospitals in Ontario, Canada, with clusters defined as medical, surgical, and critical care services. Eligible patients are adults with suspected infection characterized by initiation of a broad-spectrum antibiotic and recent collection of blood cultures. This decision support intervention will be based on a combination of proven decision heuristics (for Gram-positive organisms), modelled predicted susceptibilities (for Gram-negative organisms), and well-defined syndromes, that are individualized to the patient. Our primary outcome will be whether or not patients are de-escalated from their initial empiric regimen at 48 hours. The target sample size is 18 clusters with anticipated data from 1,440 patients, designed to achieve 80% power to detect an absolute increase in de-escalation at 48 hours of 7.5%. Secondary outcomes include adequacy of therapy, process measures, and safety. AnalysisThe primary and secondary outcomes will be analyzed at the patient-level using generalized linear mixed effects regression with fixed effects for treatment and period to account for the cross-over design, as well as fixed effects for the stratification factors and a priori patient risk factors to improve power and efficiency. Cluster and cluster-period random effects will be included to account for within-period and between-period intracluster correlation and the Kenward-Roger correction will be applied to minimize small sample bias. The primary effect estimate will be presented as a risk ratio with 95% confidence interval. Ethics and DisseminationThis trial has research ethics board approval at all participating sites and adheres to the Ottawa Statement ethics guidelines. The study is registered with clinicaltrials.gov, and the results will be published open access in a peer-reviewed journal. RegistrationClinicaltrials.gov, NCT06103500. STRENGTHS AND LIMITATIONSO_LIIDEAS-CRXO is a cluster randomized cross-over trial of a pharmacist administered decision support intervention for antibiotic prescribing in patients with suspected infection. C_LIO_LIThe intervention is based upon a generalizable algorithm incorporating Gram-positive heuristics, Gram-negative modelled susceptibility, and local well-defined syndrome treatment guidelines. C_LIO_LIThe primary outcome is a relevant measure for antibiotic stewardship - antibiotic de-escalation from the initial empiric index regimen at 48 hours from receipt of antibiotics. Secondary outcomes are focused on other clinical, process, and safety measures. C_LIO_LIThis rigorous cluster randomized cross-over trial will be conducted with 18 clusters (across three institutions) which will achieve 80% power in a two-period two-sequence design to detect a clinically important absolute difference of 7.5% in the primary outcome at a 5% two-sided significance level. C_LIO_LIThis study could be impacted by treatment contamination, however the cluster design will limit this potential source of bias. C_LI

Aim To examine ethnic inequalities in recruitment outcomes and workforce representation across pay bands among nursing and midwifery staff, and to assess whether routinely collected administrative data can generate reproducible indicators for workforce equality monitoring. Design Retrospective observational study. Methods We analyzed routinely collected administrative data from one NHS Board in Scotland. This included annual staff-in-post data for 2021/22 to 2024/25 and pooled recruitment data on interviewed candidates and conditional job offers for 2021/22 to 2023/24. Ethnicity was grouped as White and non-White. Analyses focused on Bands 5, 6 and 7. Recruitment outcomes were assessed using relative risks for receipt of a conditional job offer among interviewed candidates, comparing White and non-White applicants. Workforce representation across pay bands was assessed using representation quotients. Analyses were descriptive and unadjusted. Results White applicants were more likely than non-White applicants to receive a conditional job offer following interview across all pay bands examined. Inequalities were also evident at Band 5, the usual entry point to registered practice. Workforce composition analyses showed a corresponding gradient in representation, with non-White staff overrepresented in Band 5 and underrepresented in Bands 6 and 7, with little change over the study period. Conclusion Routinely collected administrative data can generate reproducible indicators of ethnic inequality in recruitment and workforce representation. Embedded within existing workforce systems, such analyses could strengthen workforce equality monitoring, support benchmarking and enhance accountability across healthcare settings. Impact Utilising routine administrative data for workforce equality monitoring can support policy and practice aimed at improving accountability, retention and workforce sustainability across health systems. Reporting Method This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines. Patient or Public Involvement This study did not include patient or public involvement in its design, conduct, or reporting.

IntroductionBreastfeeding supports multiple aspects of child development and maternal health. However, research findings are often inconsistent due to methodological limitations, including inadequate control for sociodemographic factors, variation in feeding practices, health conditions across the life course, and heterogeneity in human milk (HM) composition. The Manitoba Interdisciplinary Lactation Center (MILC) is a globally accessible, bench-to-population research platform that enables integrated study of HM composition, maternal-child health, and the societal and structural determinants of lactation and HM feeding. Methods and AnalysisMILC combines cross-sectional questionnaire data and HM sample collection with longitudinal administrative data derived from provincial government databases. MILC recruits lactating parents currently feeding their HM to at least one child. Participants follow a standardized full breast expression protocol. All collected HM samples have their macronutrient profiles characterized and are bio-banked for unspecified future research. Questionnaires capture child and parent demographic, dietary and health characteristics, and detailed HM feeding practices. Administrative data include over 90 databases spanning health and social services utilization and education; these de-identified records are housed at the Manitoba Population Research Data Repository and linked with MILC study samples and data. MILC questionnaires and HM collection protocols can be customized to accommodate specific research projects (e.g. additional surveys or questions; snap freezing, addition of preservatives, cell or extra-cellular vesicle isolation, etc.). MILC began recruiting participants in October 2024 and is currently ongoing. Researchers may access MILC data and biospecimens subject to appropriate ethical approvals and data-sharing agreements. Ethics and disseminationMILC is approved by the University of Manitoba Human Research Ethics Board and the Provincial Health Research Privacy Committee. Participation is voluntary and based on informed consent. Research updates and findings will be disseminated via peer-reviewed journal publications, academic and clinical conferences, social media, public knowledge sharing events (e.g. information booths and virtual "Ask Me Anything" sessions), the MILC website (https://www.milcresearch.com) and the MILC Club (monthly meetings among researchers, trainees, healthcare providers, and community partners). MILC members also engage with agenda-setting organizations (e.g. Breastfeeding Committee for Canada, North American Board for Breastfeeding and Lactation Medicine) to accelerate translation of research knowledge into policy and practice. STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIMILC combines low-burden cross-sectional human milk samples and questionnaire data with lifelong/longitudinal administrative data. C_LIO_LIParent-child dyad human milk feeding practices and history are captured in a high level of detail, filling a gap frequently experienced in human milk and lactation research. C_LIO_LIOur questionnaires have been partially harmonized with other biorepositories and/or utilize valid and reliable measurement scales. C_LIO_LIThe initial MILC study pilot population lacks diversity; this will be intentionally addressed going forward. C_LIO_LIThe cost to maintain a long-term biorepository facility is high. C_LI

BackgroundWithin the UK, more than a million people cannot speak English well or at all. The lack of data on English proficiency means that the link between English proficiency and health status and care utilisation is not comprehensively quantified. ObjectiveDescribe the association between English proficiency and patients health status and healthcare utilisation, and demonstrate that GP data can be useful in understanding the health burdens of those with poor language proficiency. MethodsThe Northwest London (NWL) Discover-NOW database contains linked, deidentified records from General Practices (GPs), hospitals, and social care in NWL. Using this data, we examined health outcomes and healthcare utilisation of people in Brent who are not proficient in English. ResultsPrevalence of age-sex-adjusted cardiometabolic conditions was higher in groups that were not proficient in English or spoke a main language other than English. Primary and secondary healthcare utilisation was also higher in groups that were not proficient in English. ConclusionThis work is the first to quantify healthcare utilisation of those not proficient in English using a large, representative sample in a UK setting. It highlights poorer health outcomes in this group. There is a need to improve provision of language support, starting at registration, which would allow for this group to be better understood.

IntroductionWith global populations ageing, demand for palliative care is increasing. Population-level assessments of unmet palliative care needs are essential for strategic planning, yet rigorous methods to estimate unmet needs are lacking. This study aimed to develop methods and estimate current and future population-level prevalence of unmet palliative care needs among adults in England and Wales. MethodsSecondary analyses of data from a nationally representative post-bereavement survey in England and Wales in 2022 (n=1,194). Unmet needs in the survey sample were estimated using two methods: (1) reported unresolved symptoms and concerns using Integrated Palliative care Outcome Scale scores, cutoff [&ge;]34/68; and (2) reported insufficient care provision from general practitioners. These methods were combined to further provide a conservative estimate (1 and 2) and a broad estimate (1 or 2). We examined associations with unmet needs using modified Poisson regression. Age-, gender- and nation-specific sample estimates were applied to mortality data for 2022 and projections from the Office for National Statistics to calculate population-level estimates and prevalence from 2025 to 2050. ResultsIn 2022, 247,993 (46%) adult decedents in England and 17,209 (49%) in Wales had unmet palliative care needs using method 1; 244,612 (46%) and 15,280 (43%), respectively, using method 2. According to conversative and broad estimates, 32% and 61% could have unmet needs in England, and 29% and 62% in Wales. By 2050, prevalence of unmet needs are projected to rise by 21-26% in England and 14-19% in Wales depending on estimate used, with the largest absolute increase among those aged [&ge;]85 years. ConclusionsUnmet palliative care needs are high in England and Wales and projected to increase by 2050, regardless of method. We contrast methods based on unresolved symptoms and concerns or insufficient care provision, or both, to inform the planning and evaluating of equitable care. Key MessagesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIAlthough understanding population-level unmet palliative care needs is critical for effective service planning, robust and standardised methods to estimate these needs remain limited. C_LI What this study addsO_LIWe use two methods to provide four estimates of population-level prevalence of unmet palliative care needs and discuss their strengths and limitations. C_LIO_LIRegardless of estimate, prevalence of unmet palliative care needs is high, ranging 32-61% in England and in 29-62% in Wales; the number of people with unmet needs is anticipated to increase by 21-26% in England and 14-19% in Wales by 2050. C_LI How this study might affect research, practice or policyO_LIThis advancement in methods to estimate unmet palliative care needs can inform the development and evaluation of population-level strategies to improve end-of-life care. C_LIO_LIOur population-level estimates do not account for multiple long-term conditions which are rising and will likely increase the complexity of needs. C_LIO_LIThere needs to be more investment in primary and community-based services to ensure high-quality symptom management and support for people and their families towards the end of life. C_LI