There are approximately 700 000 autistic people in the UK, and autism is increasingly being diagnosed in adulthood. Diagnosis on its own does not provide adequate information to plan post-diagnostic support for autistic people, and clinicians often plan support without the use of validated standardised tools which may exacerbate inequities in care. This study will evaluate a novel strengths and needs assessment, based on the WHO’s International Classification of Functioning, Disability and Health CoreSet for Autism, for use in adult diagnostic services immediately on receipt of an autism diagnosis. Potential issues, including the length of the assessment, timing of delivery and selection bias, will be explored as part of the trial process evaluation.

A two-arm, multisite, randomised pilot trial design will be used to evaluate the ICF CoreSets for Autism Strengths and Needs Assessment in three diagnostic services in England. A total of 72 newly diagnosed autistic adults will be recruited across the three sites over a 6-month period and randomised into an assessment group (strengths and needs assessment plus standard care) and a treatment as usual group (standard care only). The assessment group will receive a summary report of their strengths and needs on completion of the assessment. Both groups will complete measures of mental health and quality of life at baseline and 3 months follow-up (Patient Health Questionnaire-9, Generalised Anxiety Disorder questionnaire-7, Recovering Quality of Life questionnaire-10, EuroQoL-5D). Acceptability and feasibility will be measured for the strengths and needs assessment and for trial procedures using standardised measures, progression criteria and qualitative data from clinician focus groups and interviews with a subsample of autistic participants. The study design and procedures are being co-produced with an autistic advisor/patient and public involvement lead and with a steering group of autistic adults.

This study was reviewed by the East Midlands—Nottingham 2 Research Ethics Committee and was given Health Research Authority approval on 18 March 2025 (REC reference:25/EM/0041). The results will be disseminated via reports to the funder (NIHR), a peer-reviewed journal paper and academic conferences. We will email a summary report of findings to study participants and will invite participants to an information dissemination event at the end of the study. Links to reports and a lay summary will be provided on the research group’s website: https://sharl.sites.sheffield.ac.uk/home

ISRCTN10283350.

Some people with HIV (PWH) experience brain changes that affect neurocognition, but little is known about how HIV impacts social cognition or related brain regions. Social cognition, the ability to perceive, understand and respond to social information, is important for maintaining relationships and quality of life. This article provides the protocol for the first comprehensive study examining social brain function in PWH and people without HIV (PWoH). With three aims, this study will: (1) examine neural circuits related to social cognition; (2) examine social cognitive performance across two social cognitive domains and (3) examine the role of social cognition in everyday social functioning.

Referred to as Social Brain Health Study in HIV Study, this cross-sectional study will enrol 105 PWH and 105 demographically matched PWoH aged 18–65 years. The study administers a comprehensive assessment battery across two visits within a 2-week period. Visit 1 includes behavioural measures of social cognition (Perceiving Social Cues and Understanding Others), neurocognition and social functioning (social network size and loneliness). Visit 2 involves functional MRI procedures with three social cognitive tasks designed to activate key brain regions (ie, fusiform face area, superior temporal gyrus, temporo-parietal junction, dorsal medial prefrontal cortex).

This study was funded by the National Institute of Mental Health (MH139613) and approved by the Institutional Review Board of the University of Alabama at Birmingham (IRB-300013394). Data collection is ongoing. The first results are expected to be submitted for publication in 2030. Findings of this study will be published in peer-reviewed journals and presented at local, national and international conferences as well as patient organisations such as AIDS service organisations and community talks.

Healthcare utilisation (HU) is key to improving the health of residents in urban informal settlements. This study aimed to explore household-level factors influencing HU among informal settlement households in Freetown, Sierra Leone.

Cross-sectional survey.

Three informal settlements (Cockle Bay, Dwarzark and Moyiba) in Freetown, Sierra Leone.

Primary data from 4871 households were collected during the Health and Wellbeing survey conducted between April and May 2023, targeting households with adults aged 18 years and older.

The primary outcomes were households HU both within and outside informal settlements. Household-level predisposing and enabling explanatory variables were derived from Andersen’s Behavioural Model of HU.

Disability in households increases HU within settlements (especially in Dwarzark, 13% and Moyiba, 10%) but is less likely outside. Households engaged in income-generating activities are more likely to seek healthcare within settlements, but 12% less likely outside in Cockle Bay and Dwarzark. Food insecurity decreases HU within Dwarzark (9%) and increases HU outside by 174% in Moyiba. Longer water fetching times and water shortages were associated with higher HU (between 6% and 16%) within settlements, especially in Cockle Bay and Dwarzark. Clean water sources (eg, piped dwelling, bowser, surface, bottled) were consistently associated with higher HU both within and outside settlements. Shared sanitation facilities (such as shared toilets) were positively associated with HU both within and outside settlements, particularly in Dwarzark and Moyiba. Households with income from fishing, informal salaried work and bike riding showed higher HU both within and outside settlements, especially in Dwarzark and Moyiba.

We identified strong settlement-specific patterns of household-level factors that influence HU both within and outside Freetown’s informal settlements. These findings provide a foundation for developing targeted policies such as strengthening local services, addressing affordability and accessibility barriers and supporting vulnerable occupation groups.

Multidrug-resistant tuberculosis (MDR-TB) is an urgent public health challenge in Namibia, with profound socioeconomic consequences. The high burden of both tuberculosis and HIV complicates treatment and underscores the need for optimised drug therapies. Precision medicine, which leverages patient-specific genetic and molecular information, offers promise for improving MDR-TB outcomes. However, its effective application relies on population-specific data, particularly understanding how individuals metabolise tuberculosis drugs and how genetic diversity drives variability in treatment response. Currently, no pharmacokinetic (PK) or pharmacogenetic (PG) data on TB treatment exist for Namibian populations. This gap is particularly concerning, given the country’s genetic diversity, environmental factors and comorbidities that may uniquely influence drug metabolism. This study aims to generate PK and PG data to inform dose optimisation and support personalised treatment strategies for MDR-TB in Namibia. The findings will contribute to improved patient care and inform health system strengthening based on locally relevant evidence.

This cross-sectional study will consist of 100 Namibian participants with matched human DNA and PK data of MDR-TB cases receiving isoniazid, clofazimine, bedaquiline and the fluoroquinolones (levofloxacin or moxifloxacin). PK sampling will be divided as follows: 30 individuals will undergo intensive PK sampling, while the remaining (n=70) will undergo sparse PK sampling. DNA will be extracted at Stellenbosch University (SU), and samples will be genotyped using the H3Africa microarray. Sequences will be aligned to the human reference genome, hg38 (GRCh38p13), using the freely available Burrows-Wheeler Aligner. A subset of the samples (n=20–30) will undergo whole genome sequencing (WGS) to verify imputation results and identify novel genetic variants potentially affecting PK in this population.

Quality control and variant call format file generation will be performed using the Genome Analysis Toolkit best practices (V.3.5). Intensive and sparse PK data will be pooled for the development of a population PK (popPK) model using a non-linear mixed-effects modelling approach. The popPK model will characterise the relationship between TB drug dose and exposure, including quantifying covariates, including genetic variation, explaining PK variability, providing a foundation for dose optimisation and personalised treatment strategies.

Ethics approval was obtained from the University of Namibia Human Research Ethics Committee for Health (Ref. SOM18/2024), the Ministry of Health and Social Services (Ref. 22/4/2/3), the SU Health Research Ethics Committee (Ref. N21/11/136) and the University of Cape Town Human Research Ethics Committee (Ref. 500/2022).

Status epilepticus (SE) in adults is a serious neurological emergency that can lead to high morbidity and mortality rates. Although functional outcomes are often assessed using general scoring systems, limited data on health-related quality of life (HRQoL) in patients admitted to intensive care units (ICUs) are still limited. Furthermore, comprehensive evaluations of patient-reported physical, cognitive, mental health and psychological outcomes are lacking in this population. POSEIDON 2 aims to assess HRQoL and cognitive, physical and psychological impairments at 3 and 12 months after ICU discharge following SE and quantify caregiver burden.

POSEIDON 2 is a prospective, multicentre, longitudinal study conducted in 19 French ICUs. The study combines data from the SE ICTAL Registry with data from patients who survived admission to the ICU for SE, who will be recruited for the study. The study also includes patient-reported outcome (PRO) data collected 3 (M3) and 12 (M12) months after discharge from the ICU using validated instruments. The Zarit scale will be used to measure the burden on caregivers at M3 and M12. The primary endpoint is the prevalence of overall HRQOL impairment at M3 and M12, as defined by dichotomous scores on the physical and mental components of the 36-Item Short Form Health Survey compared with those of the general population. Secondary endpoints include domain-specific impairments, such as cognitive function, dependence, mental health and patient experiences. The sample size has been calculated based on an estimated prevalence of 75% for HRQoL impairment, with a planned sample size of 140 patients.

The POSEIDON 2 study protocol received ethical approval from the ethics committee ‘Comité de Protection des Personnes Ouest VI’ on 5 October 2023 (#2023-A01223-42). The study is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice and the regulatory requirements of France. Written informed consent is obtained from participants, who are able to decline participation or withdraw from the study at any time. Findings will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences.

NCT06100978.

Common mental health outcomes among children in conflict with the law in correctional facilities in Africa are an under-researched area with significant public health implications. This review will synthesise available and accessible evidence on the prevalence and associated factors of common mental health outcomes among children in conflict with the law in Africa.

Comprehensive electronic searches will date from 01 January 2015 to 31 December 2025 and will be conducted in PubMed, Sabinet, Scopus, EBSCOhost, Web of Science and PsycINFO. Articles will be screened using defined inclusion and exclusion criteria and assessed for eligibility by three independent reviewers. Discrepancies will be reviewed by a ninth reviewer. The selection process of included articles will be reported by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses will be used. The Mixed Methods Appraisal Tool will assess study quality, and data will be synthesised using meta-analysis or a narrative synthesis approach, depending on heterogeneity levels.

This study will not require ethical approval from an institutional review board, as it does not entail the direct collection of data from children in conflict with the law, nor does it pose any risk to their privacy. Once finalised, the full review report will be submitted for publication in a peer-reviewed journal. The key findings will also be shared at both local and international conferences, highlighting common mental health outcomes among children in conflict with the law.

CRD420251011484.

To explore how well the primary care system in Scotland works for adults with intellectual disabilities (ID), using the rate of unplanned hospital admissions for ambulatory care sensitive conditions (ACSC) as a proxy indicator. As part of this, to investigate those rates and rate ratios among adults with ID and without ID, adjusting for the prevalence of a given ACSC in each population. The secondary aim was to explore deaths due to ACSC among the ID and no-ID populations.

A population-based retrospective cohort data linkage study of adult respondents to Scotland’s 2011 Census. Self-reported or proxy-reported ID status from the Census was linked to hospital admissions data and deaths data. The cohort was followed until the end of 2019. The prevalence of ACSCs in each population was calculated from aggregate-level data published by the National Health Service, as it was not possible to use the linked dataset for this purpose.

Whole population of Scotland.

People aged 18+ on census day (27 March 2011), including all adults with ID (n=16 840) and a 15% randomly selected comparator sample of adults without ID (n=566 074).

Crude and age-sex standardised incidence rates and ratios; cumulative incidence; prevalence ratios. The exposure was ID status, and the outcomes were (1) unplanned ACSC hospital admission, (2) death with an ACSC condition listed as the main cause on the death certificate and (3) death with an ACSC condition listed as one of the causes on the death certificate.

Adults with ID under the age of 55 had only a slightly higher risk of an unplanned ACSC hospitalisation than their general population counterparts (standardised incidence ratio 1.11; 95% CI 1.03 to 1.20). After adjusting for different ACSC prevalence in ID and non-ID cohorts, this difference in risk disappeared. These findings contrast with existing evidence from England, where a much higher unadjusted risk of unplanned ACSC hospitalisations was found among people with ID. Adults with ID had a higher risk of dying due to ACSC than adults without ID (standardised mortality ratio 2.54; 95% CI 2.19 to 2.95).

Our findings on unplanned ACSC hospitalisations suggest that the primary care system in Scotland appears to be similarly effective for adults with ID than for adults without ID. However, the higher risk of dying from ACSC among people with ID suggests that this system is less effective for people with ID. Future research should investigate this tension and aim to understand why the operation of the primary healthcare system seems to be worse with regards to ACSC mortality than with regards to unplanned ACSC hospitalisations.

Stroke is one of the top causes of disability in Malaysia, yet caregivers have limited access to structured, culturally tailored education to support poststroke care.

To develop and validate the CaknaStrok Education Package (CEP), a blended learning intervention comprising a printed guidebook and a trilingual mobile health application for informal stroke caregivers in Malaysia.

Methodological study involving the development and validation of a caregiver education programme guided by the Analyse, Design, Develop, Implement, Evaluate (ADDIE) instructional design framework.

Development and validation were conducted in Malaysia between January 2022 and December 2023. Both experts and caregivers were recruited from two tertiary hospitals on the East Coast of Malaysia, with caregivers identified from inpatient wards and outpatient clinics at these hospitals.

Content validation involved 10 multidisciplinary experts. Face validation involved 14 informal stroke caregivers who met eligibility criteria, and all completed the study.

CEP was developed based on prior needs assessment and expert input. Content validation was undertaken using the Content Validity Index (CVI) and face validation using the Face Validity Index (FVI), both assessed on a four-point Likert scale. Qualitative feedback was also obtained from the participants.

CEP consists of six modules delivered via a printed guidebook and a trilingual app with videos, assessment tools and local resources. Experts rated the content highly valid (Scale-level (S)-CVI/the average method (Ave): 0.97–0.99 across domains). Caregivers reported strong acceptability (S-FVI/Ave: 0.95–0.99). Qualitative feedback from experts and caregivers informed refinements to content clarity, usability and presentation, including improved navigation, consistent language use and enhanced visual design. Suggestions requiring substantial structural changes were documented for future iterations.

The CEP shows strong content and face validity as a blended caregiver education tool. By combining printed and digital formats, CEP addresses cultural and access challenges and provides a scalable model for stroke caregiver education in Malaysia. Further pilot or feasibility studies are warranted to evaluate usability, engagement and implementation in real-world settings prior to effectiveness evaluation.

To use best practices in pharmacoepidemiology to assess the association between new use of brain-penetrant calcium channel blockers (BP-CCBs) compared with use of non-brain-penetrant CCBs (NP-CCBs) and the incidence of neuropsychiatric outcomes.

Retrospective comparative cohort study.

Secondary data from nine claims and electronic health record databases from across the globe were used.

First use of a CCB was the index date. There were 1.2 million BP-CCB patients and 9.3 million NP-CCB patients identified across all databases, with 881 758 matched in each group.

Patients were categorised as either initiating BP-CCBs or NP-CCBs. On-treatment and intention-to-treat analyses were conducted. Large-scale propensity models were used to match cohorts and control for observed confounding. Cox models were used to analyse the time to incident neuropsychiatric disorders. Negative control outcomes were used to calibrate estimates, CIs and p values to account for residual confounding. Diagnostics were used to assess the validity of the analysis.

The time to first diagnosis of schizophrenia, schizoaffective disorder, major depressive disorder (MDD) and bipolar disorder was assessed independently. HRs compared the BP-CCB group to the NP-CCB group.

For the outcome of incident MDD in the intention-to-treat design, the meta-analytic HR (95% CI) was 1.02 (0.97, 1.08). Meta-analytic HRs for bipolar disorder (1.04 (0.96, 1.13)), schizophrenia (1.05 (0.94, 1.18)) and schizoaffective disorder (1.04 (0.87, 1.23)) showed similar null effects. The on-treatment analysis was largely consistent: MDD (1.01 (0.96, 1.06)), bipolar (1.05 (0.86, 1.27)), schizophrenia (1.09 (0.87, 1.38)) and schizoaffective (1.00 (0.71, 1.40)).

There was no evidence of an association with any of the neuropsychiatric conditions of interest between use of BP-CCB and NP-CCB. This does not rule out the potential beneficial effect of CCB formulations and doses targeted specifically for the brain rather than the cardiovascular system.

To evaluate the prognostic significance of tumour deposit (TD) across different N stages in patients with stage III colon cancer and to develop and validate a novel N staging system that incorporates TD count to improve prediction of cancer-specific survival (CSS).

Retrospective cohort study based on population-based data and external validation.

Secondary and tertiary care settings; data from the SEER database, a population-based cancer registry capturing cancer incidence and survival information (USA, 2010–2017); and a single-centre validation cohort from South China (2015–2019).

A total of 8739 stage III colon cancer patients from the SEER database who underwent curative surgery were included; 1335 (15.3%) had TD. Patients with

The outcome was cancer-specific survival (CSS). The prognostic impact of tumour deposit (TD) and the comparative performance of the novel N staging system versus the AJCC system were evaluated using the Fine-Gray competing risks model, time-dependent area under the curve (AUC) and Brier score.

TD was independently associated with poorer CSS: 1 TD (SHR=1.23, 95% CI 1.04 to 1.47, p=0.017), 2–3 TDs (SHR=1.36, 95% CI 1.17 to 1.58, p3 TDs (SHR=2.02, 95% CI 1.73 to 2.35, pet al, TDs were converted to metastatic lymph nodes (mLNs) using the following weighting: 1 TD=3 mLNs (N1c), 1 TD=2 mLNs (N1) and 1 TD=1 mLN (N2). The novel N staging system stratified patients as nN1a (1 nLN), nN1b (2–3 nLNs), nN2a (4–6 nLNs) and nN2b (≥7 nLNs). This approach showed improved prognostic accuracy compared with AJCC N staging: 3-year AUC (0.623 vs 0.614) and Brier score (0.151 vs 0.157, p

TD significantly worsens prognosis in stage III colon cancer, particularly in lower N stages. Incorporating TD counts into the N staging system with different weightings based on N stage enhances prognostic accuracy and risk stratification within stage III disease, particularly for the heterogeneous AJC N1c category. This novel staging system provides better prognostic value and more accurate treatment guidance and should be considered for broader clinical use, subject to further (eg, prospective) validation.

Acute pain following pulmonary surgery can affect the recovery process of patients. The use of intrathecal morphine (ITM) injections offers a long-lasting analgesic effect, but its clinical application remains controversial. This study aims to investigate the impact of combining bupivacaine with ITM injections on the quality of postoperative recovery in patients who have undergone pulmonary surgery.

This multicentre, randomised, double-blind, controlled trial will enrol 254 patients undergoing elective lung surgery, who will be randomly assigned in a 1:1 ratio to either group IT (receiving an intrathecal injection of 3 mg bupivacaine and 0.25 mg morphine before general anaesthesia induction) or the control group (C group). The primary outcome includes postoperative recovery quality on day 1 (quality of recovery, QoR-15), with secondary outcomes encompassing postoperative recovery quality on days 2 and 3 (QoR-15), pain scores within 72 hours postoperatively, analgesic rescue, intraoperative haemodynamic parameters, opioid consumption, postoperative adverse reactions, recovery metrics, complications, chronic pain incidence and sleep quality.

The results will be disseminated through peer-reviewed publications. This study protocol (V.2.0, 30 October 2024) involves human participants and has been approved by the Ethics Committee of Affiliated Hospital of Yangzhou University (number 2024-08-02-2), Taicang Hospital Affiliated to Soochow University (number 2025 SR-041) and Yichang Central People’s Hospital (number 2024-513-02). Each individual who agrees to participate in the research will provide written informed consent after the objectives and procedures of this study are explained to them.

ChiCTR2400092935. Registered on 26 November 2024.

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

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

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

To assess the acceptability and adoption of multiparameter point-of-care testing (POCT) devices for the diagnosis and management of non-communicable diseases (NCDs) at the primary healthcare level in a resource-limited region of Peru.

Qualitative case-control process evaluation.

Eight primary healthcare facilities in northern Peru, including both urban and rural centres, where routine chronic care and laboratory services are provided.

Sixty-three participants: 36 patients, 12 laboratory technicians, 10 healthcare professionals and five facility heads. Eligible patients were ≥18 years, residing in the catchment area, with or without prior NCD diagnoses. Healthcare workers, including physicians, nurses, laboratory staff and facility managers.

Multiparameter POCT devices were installed in four intervention facilities, accompanied by staff training and community awareness activities, while four control facilities continued with conventional laboratory diagnostics.

Primary outcome: perceptions of patients and healthcare workers regarding the acceptability and adoption of POCT devices. Secondary outcomes: identification of facilitators and barriers to implementation, including infrastructure, supply chains and training gaps.

(1) Individuals: POCT was valued for speed and comfort, but concerns over accuracy were mentioned. (2) Intervention characteristics: laboratory staff valued POCT’s practicality in emergencies, but noted limitations in handling multiple samples. (3) Outer setting: urban centres outperformed rural facilities, with more staff and longer operating hours. (4) Inner setting: calibration gaps impacted POCT and conventional test reliability, requiring quality control and training. (5) Process: clear staff communication boosted patient confidence in POCT, but inconsistent training could lead to reliability doubts.

Multiparameter POCT devices show promise for enhancing NCD care in resource-limited primary healthcare settings, particularly in rural areas. However, their sustainability depends on broader health system reforms, including reliable supply chains, expanded training and stronger quality assurance mechanisms. Further research should examine strategies for embedding POCT within national regulatory and policy frameworks.

Microcirculatory dysfunction drives the end-organ pathophysiology of circulatory shock but is not reflected within existing clinical indices of perfusion, such as blood pressure. The choroidal vasculature of the retina can be measured non-invasively and we hypothesised that this may reflect dysfunction in other organs. We tested the feasibility of measuring the choroid in intensive care and explored associations between choroidal measurements and clinical parameters.

A pilot study of optical coherence tomography conducted in a sample of general intensive care unit (ICU) patients.

A tertiary mixed ICU within the UK.

15 patients were recruited. One patient was excluded following withdrawal of active treatment. 12/14 (86%) of the remaining patients had successful baseline imaging and 6 (40%) of these had follow-up imaging within intensive care. These patients had a mean age of 56.3 years, were 71% (10/14) male and mean Acute Physiology and Chronic Health Evaluation 2 (APACHE2) score on ICU admission was 20.4.

Choroidal anatomy, including choroidal and suprachoroidal thickness, as well as volumetric analysis of intrachoroidal blood vessels, was assessed using automated image segmentation along with clinical, physiological and biochemical data at ICU admission and after an interval of 12–72 hours. Feasibility and safety data were assessed throughout ICU admission.

Baseline choroidal vascular index and choroidal thickness were positively associated with fluid balance, and negatively with APACHE2 score, haematocrit and albumin content. A measurable suprachoroidal space was seen in nine (75%) patients (range 25.0–110.0 microns) and was inversely associated with heart rate. There was substantial intraindividual variation in choroidal measurements over time. There were no safety concerns.

Measuring the choroid is feasible in patients with Intensive Care Society Level 2 or Level 3 requirements. The suprachoroidal space may be markedly enlarged in these patients. Exploratory associations with systemic variables suggest that the choroid may provide information about the microvascular function of other major organs. Size and change of choroidal measurements may reflect perfusion pressure and vascular leakage.

Adnexal torsion is a gynaecological emergency in which prompt diagnosis and management are critical to preserving ovarian function. However, the clinical presentation is often non-specific, and diagnosis primarily relies on pelvic ultrasound, a modality with limited sensitivity that can lead to misdiagnosis and unnecessary surgery. Contrast-enhanced ultrasound (CEUS) has emerged as a promising imaging technique that may enhance diagnostic accuracy by better characterising adnexal vascularisation.

The aim of this study is to assess whether the addition of CEUS to standard diagnostic procedures can reduce the rate of unnecessary emergency surgeries. Specifically, we compare two diagnostic strategies in cases of high clinical suspicion of adnexal torsion: the current standard approach versus an experimental strategy incorporating CEUS. The primary outcome is the rate of inappropriate surgical interventions, defined as emergency surgery performed within 6 hours without intraoperative confirmation of torsion.

This is a prospective, open-label, multicentre, randomised (1:1), controlled, superiority trial. A total of 256 women presenting with a high clinical suspicion of adnexal torsion will be enrolled over a period of 36 months. Participants will be randomly assigned to either the standard diagnostic strategy or an experimental strategy that includes CEUS. The primary endpoint is the proportion of emergency surgical procedures (performed within 6 hours of hospital admission) in which adnexal torsion is not confirmed.

The study was approved by the French Ethics Committee, the CPP (Comité de Protection des Personnes) on 28 October 2024. The results of this study will be published in peer-reviewed journals and presented at relevant national and international conferences. The ethical approval number from the CPP is 6115.

NCT06677554; 2024-511720-13-00.

Sodium-glucose cotransporter (SGLT) inhibitors have shown substantial benefit in reducing cardiovascular and kidney events across diverse clinical populations, but the underlying physiological mechanisms remain unclear. However, existing mechanistic studies on renal and cardiovascular haemodynamics show variability in design, have limited statistical power and yield inconsistent outcomes, thus limiting the ability to draw generalisable conclusions. To address this gap, we conducted a systematic review and proposed the first meta-analysis to aggregate individual participant-level data from mechanistic studies to identify consistent physiological patterns and enhance understanding of the therapeutic effects of SGLT inhibition.

Gold-standard measured glomerular filtration rate (mGFR) was selected as the primary outcome for this systematic review, which aimed to identify all completed mechanistic studies investigating the effects of SGLT inhibition. Electronic databases including Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; and Cochrane Central Register of Controlled Trials were searched using a detailed search strategy. In total, 24 studies (n=1296) were identified. This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Key variables including demographics, medical history, concomitant medications, vital signs, mGFR, renal haemodynamics, urine and plasma biochemistry, tubular sodium handling, echocardiography, cardiac output monitoring, arterial stiffness and fluid volume will be extracted. A one-stage individual participant data meta-analysis under a Bayesian framework will be conducted, using hierarchical models to simultaneously analyse data from all eligible studies. The risk of bias due to missing results will be assessed. Sensitivity analyses and subgroup evaluations will be incorporated to explore sources of heterogeneity and assess robustness of findings.

Ethics approval was obtained from University Health Network, Toronto, Canada. Findings from the Mechanisms of SGLT Inhibitor Action and Physiological Mediators (MOSAIC) meta-analysis will be published in peer-reviewed journals and results will be disseminated at scientific conferences.

CRD420251001413.

To estimate tuberculosis (TB) incidence trends in the high-altitude Xizang, China, and to explore the key intervention strategies on achieving the WHO 2030 TB control target.

We developed a susceptible–exposed–infectious–recovered transmission model using routinely reported TB surveillance data from 2004 to 2022. Scenario-based simulations were conducted to project future TB incidence under alternative intervention strategies. Model assumptions are as follows: (1) a stable population, (2) lifelong vaccine-induced immunity, (3) infectiousness of active TB cases, (4) relapse risk after recovery and (5) homogeneous mixing within the population.

Seven prefectures of Xizang Autonomous Region on the Tibetan Plateau, China.

An estimated population of approximately 3 million individuals residing in Xizang.

We assessed the epidemiological impact of four interventions implemented independently: increasing vaccine efficacy rate, reducing transmission rates of susceptible individuals, decreasing progression rate from latent TB infection to active disease and reducing relapse rate among successfully treated patients, compared with continuation of current control measures.

The estimated basic reproduction number (R₀ ) for TB in Xizang was 0.39 (95% CI 0.21 to 0.71) in the absence of additional interventions, which was the highest among all regions of China. Model simulations indicated that all four evaluated interventions were each likely to reduce TB incidence, but only reducing the latent-to-active TB progression had a substantial effect. A 50% reduction in the progression rate was predicted to lower TB incidence from 66.56 (62.00–70.11) to 40.54 (37.15–43.77) cases per 100 000 population, meeting the WHO 2030 TB control target.

Targeted management of individuals with latent TB infection should be strengthened to substantially reduce TB transmission in high-altitude areas.

Urgent and emergency care (UEC) systems in England face unprecedented pressures, with record accident and emergency attendances, persistent breaches of ambulance response targets and poorer outcomes for time-sensitive conditions. National UEC recovery plans have introduced multiple innovations—such as same-day emergency care, virtual wards and specialty hubs—to manage these pressures and improve patient flow. Rural coastal areas are particularly vulnerable to excessive demand due to higher levels of deprivation, older populations with complex health needs, seasonal surges that generate unpredictable demand and challenges in attracting and retaining staff. Following the Chief Medical Officer’s 2021 Annual Report, funding research and developing bespoke solutions to manage UEC demand and address geographical disparities has been recognised as a national priority. The Elevate study responds to this priority by identifying and evaluating innovative models of UEC in rural coastal communities in England.

The Elevate study is a 30-month, mixed-methods evaluation that comprises three interlinked work packages: (1) National service mapping—outlining provision of innovative models of UEC in rural coastal areas of England. This will be developed through document review and interviews with regional and national service leaders. (2) Quantitative analysis—quasiexperimental and longitudinal approaches will use National Health Service (NHS) England’s Emergency Care Data Set and linked routine NHS datasets to evaluate the impact of UEC models on health and process outcomes. Standard and bespoke metrics will be developed and used to assess performance. (3) Qualitative case studies—up to 12 case studies of UEC models in rural coastal communities. Interviews with patients and staff and non-participant observation will explore how and why different UEC models influence patient experience, clinical outcomes, resource use and the workforce. Findings will be integrated using the Consolidated Framework for Implementation Research to identify components of UEC models that are effective, scalable and sensitive to local context,

Ethical approval for qualitative components was granted by the North of Scotland Research Ethics Committee (25/NS/0099). Dissemination will include peer-reviewed publications, policy briefs, creative media and community engagement activities to ensure findings are communicated inclusively and effectively to policymakers, health and social care practitioners and the public.

Research Registry (researchregistry11126).

In rural sub-Saharan Africa (sSA), the burden of antimicrobial resistance (AMR) remains high. As AMR continues to rise, there is a strong need for practical, implementable surveillance to monitor and mitigate risks, as well as inform timely, evidence-based clinical decision-making. Emerging evidence points to possible community-level drivers, such as transmission between human, animal and environmental reservoirs as contributing factors, yet microbiological surveillance or opportunities for wastewater-based surveillance are often limited and insufficient in these settings. Therefore, alternative sustainable and affordable approaches are needed. We intend to build on the demonstrated potential of metagenomic profiling of pooled faecal material, which accurately predicted population-level AMR prevalence in invasive Enterobacterales infections.

We aim to validate this metagenomic pooled approach on additional populations, and to evaluate whether AMR patterns could be similarly predicted from surveillance of community One Health reservoirs. We will assemble existing data from hospital-based microbiology diagnostic laboratories in rural Burkina Faso and Kenya, and determine to what extent community-level metagenomic data, and/or faecal material of patients on hospital admission, can predict AMR in clinical isolates. We will perform community-level surveys in eight clusters per country, randomly selecting 15 households per cluster. We will systematically sample suspected environmental AMR exposure sites in and around households (soil, drinking water, latrines, chicken faeces) and collect data on community-level antibiotic use, hygiene practices, contact with domestic animals and sanitary facilities. Samples and data will be collected twice: during the dry and during the rainy season.

In addition to evaluating the accuracy of predicting resistance in clinical isolates, we will quantify community-level exposure risks. We will conduct metagenomic profiling on pooled DNA extracts from human stool samples (hospital and community-level) and from household environments. Bayesian statistical models will quantify relationships between AMR gene abundance in the environment and in human stool, and invasive bacteria identified among clinical patients, accounting for geography and seasonality. A cost-utility analysis will determine under what circumstances the use of pooled metagenomic data to inform empirical antibiotic policies would represent an efficient use of resources.

The proposed surveillance protocol is developed in partnership with local communities and local and international researchers and has received ethical approval in Kenya and Burkina Faso. It will assess whether intermittent, pooled-sample metagenomics provides a viable, low-cost and practical approach for population-level AMR surveillance in settings that—like many in rural sSA—lack systematic microbiological diagnostics and where sewage systems for wastewater-based surveillance are absent. By providing an alternative to routine microbiological-based surveillance where this proves challenging to implement, this approach may help improve treatment outcomes, contribute to equity and public health. Findings will be disseminated through peer-reviewed publications and academic conferences and will contribute to the recently proposed WHO AMR surveillance strategy, which combines survey-based approaches with routine AMR surveillance.