Tuberculosis is the leading cause of death globally from a single infectious agent. Early diagnosis is critical to reducing morbimortality. In cases of negative smear microscopy or limited sputum production, bronchoalveolar lavage (BAL) samples offer an alternative for diagnosis. Culture, the gold standard, requires a high bacterial load, extensive infrastructure and is time-consuming. Xpert MTB/RIF provides faster results with a higher cost. Previous systematic reviews present substantial limitations, including significant heterogeneity. Therefore, the diagnostic utility of Xpert MTB/RIF using BAL samples in adults with negative or scant sputum for pulmonary tuberculosis (PTB) needs to be reassessed.

A systematic search of MEDLINE, Embase, LILACS and Web of Science will be conducted without language or publication date restriction. Cross-sectional diagnostic studies of negative or sputum-scarce adults with presumptive PTB who underwent bronchoscopy to obtain samples for Xpert MTB/RIF and culture will be included. Screening and data extraction will be performed independently. Methodological quality will be assessed using the QUADAS-2 tool. A bivariate hierarchical random-effects model will synthesise sensitivity and specificity. Meta-analysis will be performed using Meta-DiSc 2.0. Heterogeneity will be assessed using I² and Cochrane thresholds. Subgroup analyses will be performed based on study design, population differences, country, culture method and risk of bias. Publication bias will be investigated using a funnel plot. The certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. There was no patient or public involvement in the development of the systematic review protocol.

Ethical approval is not required as this study will use publicly available data. Findings will be disseminated through peer-reviewed publication.

CRD42025639440.

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment through targeted disruption of the physiological pathways that maintain tissue tolerance, but which are co-opted by cancers to evade immunosurveillance. Thus, the resultant T-cell activity often causes immune-related adverse events including immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA). ICI-IA results in functional impairment that frequently persists, even after ICI discontinuation, with substantial quality-of-life impacts for cancer survivors.

A high-quality body of evidence to guide ICI-IA management remains an unmet need. Pharmacological treatment may be prolonged, typically begins with non-specific immunosuppression, including systemic steroids, and is usually only rationalised to more targeted therapy in resistant cases. Moreover, retrospective data suggest the high dose glucocorticoids sometimes used in new-onset ICI-IA may be associated with worse cancer outcomes.

Tumour necrosis factor (TNF) inhibition strategies are well established with excellent efficacy and safety profiles in ‘spontaneous’ inflammatory arthritides including rheumatoid and psoriatic arthritis. Mechanistic evidence from ex vivo and murine studies also supports the utility of anti-TNF therapy for steroid-refractory cases of ICI-IA. Although good clinical responses have been reported in this setting, the REACT trial (REmission induction of Arthritis caused by Cancer ImmunoTherapy) aims to provide randomised and robust clinical evidence for deploying targeted therapy earlier in ICI-IA management. It will test whether up-front anti-TNF therapy can more effectively and quickly control symptoms, reduce glucocorticoid exposure, prevent early ICI discontinuation and increase the frequency of drug-free ICI-IA remission.

REACT is a prospective, multicentre, open-label, superiority, two-arm, randomised controlled clinical trial to guide initial therapy for patients with ICI-IA. The trial will compare the current standard of care (initial prednisolone; Arm A) with the anti-TNF drug, adalimumab without glucocorticoids (Arm B).

The primary outcome is glucocorticoid-free arthritis remission rate at 24 weeks where remission is defined as: (i) No use of systemic or intra-articular glucocorticoids (except when used for adrenal insufficiency) within 4 weeks prior to assessment at 24 weeks; and (ii) absence of synovitis on clinical examination.

The protocol was approved by East Midlands—Leicester South Research Ethics Committee on 31-Oct-2024 (Ref: 24/EM/0202). Participants are required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

ISRCTN18217497.

Among the five hepatitis viruses, the hepatitis B virus (HBV) is a major cause of serious acute and chronic liver infections worldwide. The major public health impact of HBV infection arises from chronic liver disease, including cirrhosis and hepatocellular carcinoma, which predominantly affects young and middle-aged adults of both sexes. Therefore, preventive interventions focusing on mothers and infants are critical due to vertical and early childhood transmission dynamics.

HBV prevalence largely varies among pregnant women in Ethiopia because of multiple interrelated factors. This umbrella review will consolidate all existing systematic reviews and create a more reliable picture of HBV infection and its determinants among pregnant women in Ethiopia.

This umbrella review will be conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses reporting standards. The review will focus on identifying and integrating evidence from eligible systematic reviews and meta-analyses, with methodological quality appraised using the MeaSurement Tool to Assess systematic Reviews instrument. A comprehensive literature search strategy will be developed using relevant Medical Subject Headings alongside free-text keywords. Electronic searches will be conducted in PubMed/MEDLINE, African Journals Online, Web of Science, Scopus and Google Scholar. Statistical heterogeneity among the included reviews will be quantified using the I² statistic. Data management and meta-analytic procedures will be performed using STATA version 17, and effect estimates will be presented with corresponding 95% CIs to determine statistical precision.

This review uses only published or publicly available data, so ethics approval is not required. Findings will be disseminated via peer-reviewed publications, conference presentations and shared with policymakers, healthcare partners, clinicians and patients to inform policy, enhance education and guide future research.

PROSPERO (CRD420251118982).

To assess the impact of a National Enhanced Service (NES) incentive for weight management that financially rewarded practices for each eligible patient referred to a weight management programme.

Interrupted time-series analysis to examine the rate of weight management referral and weight management advice.

Primary healthcare records from January 2018 to December 2024 in the Oxford Clinical Informatics Digital Hub, covering 8.3 million patients in 1198 primary care clinics around England.

NES payments to practices for weight management were introduced in April 2021.

The rate of referral increased from 1 referral per 1000 patients per month before the incentive to around 4 referrals per 1000 patients per month afterwards. There was no evidence that the increase differed by age, gender, ethnic group or socioeconomic status. The occurrence of weight management advice was unchanged by the introduction of the NES and was at least three times more common than referral to weight management services.

The NES was associated with a fourfold increase in referrals to weight management services. However, clinicians are much more likely to offer advice rather than a referral to a weight management programme. There is a clear opportunity to improve outcomes for patients by encouraging greater use of referrals to effective weight management services in place of advice.

To investigate associations between body composition indices and metabolic status among normal-weight adults.

Cross-sectional study using data from the Tehran Lipid and Glucose Study (phaseVII: 2019–2021).

Primary care and community health services in an urban Tehran population.

1298 adults (40.5% men, 59.5% women), aged 18–80years, body mass index (BMI) 18.5–24.9 kg/m². Exclusions: known diabetes, cardiovascular disease, kidney failure, malignancy, pregnancy or lactation, diuretic or glucocorticoid use. Participants were classified as metabolically healthy normal weight (MHNW) or unhealthy (MUHNW).

The primary outcome was the association between body composition and anthropometric indices with metabolic status. The secondary outcome was identification of the strongest predictors of MUHNW. Body composition was assessed by bioelectrical impedance analysis to obtain fat mass (FM), body fat percentage (BFP), skeletal muscle mass percentage (SMM%), fat mass index (FMI), fat-free mass index, skeletal muscle indices and the fat-to-muscle mass ratio (FMR). Anthropometric measures included waist circumference (WC) and waist-to-hip ratio (WHR). Associations were examined using logistic regression adjusted for age, smoking and physical activity.

Mean age: 37.5±12.8 y; MUHNW participants were older than MHNW (44.5±13.2 vs 35.8±12.1 years, p

BMI, WC, WHR and body fat indices were positively associated with metabolically unhealthy status among normal-weight adults of both sexes. WHR was the strongest predictor, highlighting its value for identifying at-risk individuals where advanced body composition tools are unavailable.

Cycling can be beneficial for health, well-being and the environment; however, cycling participation in the UK remains low. Effective and cost-effective strategies are needed to support people in the community to increase cycling. The Cycle Nation Communities randomised controlled trial (RCT) will evaluate whether a 9 week multi-component cycling programme (Cycle Nation) is more effective and cost-effective than an existing national cycle training session on cycling participation, transport use and health and well-being.

This pragmatic, single-blinded, two-arm RCT will recruit ≥268 adults who cycle infrequently. Participants will be randomised to the 9 week multi-component individual/social-level group-based Cycle Nation programme or an existing national standard single group-based cycle training session. Both arms will be delivered by community-based cycling organisations in Glasgow. Participants will complete self-reported measurements at baseline, 12 weeks and 12 months. The primary outcome is the proportion of participants cycling at least weekly at 12 months. Secondary outcomes include proportion of participants cycling at least weekly at 12 weeks; change in weekly number of rides and minutes of cycling and use of private car, taxi, public transport and walking at 12 weeks and 12 months; change in motivation, perceptions of cycling safety, confidence to cycle, self-esteem, vitality, health-related quality of life and perceived general physical health at 12 weeks and 12 months. A within-trial economic evaluation from a National Health Service/personal social service and a broader societal perspective will be undertaken. Pending within-trial results, a long-term model may be developed. An embedded process evaluation will use participant and facilitator interviews, participant acceptability questionnaires, facilitator delivery proforma and session observations.

Ethical approval has been obtained from the University of Glasgow Medical, Veterinary and Life Sciences Ethics Committee (11 April 25). Findings will be published in peer-reviewed journals and communicated to stakeholders and the public.

NCT07005674.

To determine the prevalence of potentially inappropriate prescribing (PIP), potentially inappropriate medication (PIM), potential prescription omission (PPO), potentially harmful drug–drug interactions (PDDI) and identify associated factors among older Ethiopians.

Systematic review and meta-analysis

We searched PubMed, HINARI, Scopus and Web of Science databases to identify eligible studies published up to 31 October 2025.

Observational studies reported the prevalence of PIP, PIM, PPO and PDDI among older adults from any healthcare settings were screened.

Two independent reviewers selected studies, extracted data and assessed the risk of bias. The quality and risk of bias of the studies were assessed using the Newcastle-Ottawa scale and Hoy risk of bias tool, respectively, while the certainty of evidence of outcomes was assessed using Grading of Recommendations, Assessment, Development and Evaluation based on Cochrane recommendations. We used a random-effects model for analyses to estimate the pooled prevalence and associated factors. All data analyses were done using Stata V.17 software.

The national prevalence of PIP, PIM, PPO and PDDI was estimated as main outcomes. Variations were estimated based on regions, age groups, outcome evaluation tool, disease type and healthcare setting.

The review included 25 studies (n=5662 participants) for PIP or PIM, 14 studies (n=2706 participants) for PDDI and 6 studies (n=1342 participants) for PPO. The pooled prevalence estimate was 41% (95% CI 33% to 48%), I²=96.87% for PIP, 37% (95% CI 31% to 44%), I²=96.33% for PIM, 55% (95% CI 36% to 73%), I²=99.00% for PDDI and 14% (95% CI 6% to 24%), I²=95.07% for PPO. The majority of the studies have very good quality (very good=13, good=1, satisfactory=11 for PIP and PIM; very good=11, satisfactory=3 for PDDI; very good=6 for PPO) and low risk of bias (low risk=18, moderate risk=7 for PIP and PIM; low risk=12, moderate risk=2 for PDDI and low risk=6 for PPO), while all studies for each outcome have low certainty of evidence. Subgroup analyses revealed significant regional and contextual variations. Polypharmacy was significantly associated with PIP (OR=3.72, 95% CI 2.53 to 5.46, p2=69.56%), PIM (OR=4.20, 95% CI 2.91 to 6.06, p2=57.83%) and PDDI (OR=4.51, 95% CI 3.05 to 6.69, p2=0.00%), while hypertension (OR=2.46, 95% CI 1.38 to 4.36, p2=0.00%) was associated with PIP.

This review found a high prevalence of PIP, PIM, PDDI and PPO among older adults in Ethiopia, with notable heterogeneity across regions. Polypharmacy was associated with PIP, PIM and PDDI, while hypertension showed association with PIP. Despite generally good study quality, the certainty of evidence was low for the included studies due to the cross-sectional design nature, with high heterogeneity. Therefore, these findings should be interpreted cautiously. This study indicates a high burden of inappropriate medication prescribing and its associated factors, underscoring the importance of further robust studies to clarify prescribing practices and associated factors.

CRD42024556744.

Incidental pulmonary nodules (IPNs) are commonly encountered on chest radiographs (CXRs) performed for routine clinical indications and may represent early manifestations of significant pulmonary pathology, including lung cancer. While low-dose CT screening has mortality benefits in selected high-risk populations, its implementation remains limited in many healthcare settings. Artificial intelligence (AI)-assisted CXR interpretation has the potential to enhance pulmonary nodule detection. However, evidence from Malaysian clinical practice is scarce. This study aims to evaluate the diagnostic performance of AI-assisted CXR interpretation for detecting IPNs across healthcare facilities in the Klang Valley, Malaysia.

This prospective, multicentre study will include 2452 CXRs from patients aged ≥35 years over a 6-month period across four Klang Valley healthcare facilities. Each CXR will be independently interpreted by an experienced radiologist (>5 years of experience) and analysed separately using an AI system (qXR-LNMS). An independent thoracic radiologist will determine the final classification for analysis if there is IPN detection discordance. Diagnostic performance metrics (sensitivity, specificity, positive and negative predictive values, and overall accuracy) will be calculated using a 2x2 classification matrix. Agreement between AI-assisted interpretation and radiologist reports will be assessed using Cohen’s kappa statistic. The prevalence of IPNs detected by AI-assisted interpretation and radiologist reporting will be compared using a two-proportion z-test. AI discriminative performance will be evaluated using receiver operating characteristic curve analysis and area under the curve estimation. Statistical analyses will be conducted using Statistical Package for the Social Sciences V.29, with p

Ethical approval has been obtained from the Universiti Kebangsaan Malaysia Research Ethics Committee and the Ministry of Health Malaysia Medical Research and Ethics Committee. Written informed consent will be obtained from all participants. The findings will be disseminated through peer-reviewed publications, scientific conferences and engagement with relevant stakeholders.

This study intended to investigate barriers to implementing evidence-based intrapartum care during vaginal births, from maternity care providers’ point of view.

A descriptive qualitative study was conducted using in-depth interviews, with data analysed through thematic analysis.

The labour room of a major tertiary care hospital in Central Sri Lanka.

Purposively selected 17 maternity care providers including doctors, nurse managers, nurse-midwives and midwives.

Three major themes and twelve sub-themes were generated: (1) barriers related to care providers (lack of human resources, negative attitudes of care providers, poor relationship among care providers, poor relationship between women and care providers, lack of knowledge on evidence-based practice in childbirth care); (2) barriers related to organisational environment (gaps in management, heavy workload, inadequate physical resources, insufficient in-service training and lack of availability/use of updated guidelines) and (3) barriers related to women’s birth preparedness (women’s limited knowledge on childbirth and intrapartum practices and women’s limited engagement during labour and childbirth). Many maternity care providers perceived that prevailing challenges to implement evidence-based childbirth care were one of the major reasons that impacted the quality of current childbirth care in the labour room.

The findings showed that an integrative approach may be essential to address the diverse barriers to the implementation of evidence-based intrapartum care. It is necessary to engage healthcare administrators, healthcare professionals and care recipients to enhance the quality of current childbirth care in the setting through the successful implementation of evidence-based care.

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.

Forced migrants (i.e., asylum seekers and refugees) experience greater mental health disparities and inequities in care. Mental health services and systems lack clear policy on integrated mental healthcare. Understanding the causal mechanisms of integrated mental health for migrants can promote a resilient and adaptive health and social care system. However, to achieve a functional mental health service integration, there is a need to understand how and why mental health system integration works and under what health systems conditions. The purpose of this realist review protocol will be to outline a process for refining an initial programme theory (IPT), developed through deliberative dialogues with key interest groups in British Columbia, Canada, and to test the IPT against the global evidence base.

A realist review is an interpretive methodological approach to synthesising the literature based on the realist philosophy of science. Realist reviews are pragmatic approaches to theory development because they involve the participation of real-world actors or people who work within complex systems. Realist reviews are particularly useful for synthesising complex knowledge. We plan to conduct a seven-step review process, with iteration between each step. Steps 1–3 have already been completed in our previous work and included the development of an IPT, which will be refined systematically by exploring the global literature and consulting with an international advisory group. These will be used iteratively to identify, test and refine the programme theory. The quality of included literature will be appraised using the relevance, richness and rigour criteria and the realist quality appraisal tool, TAPUPASM (transparency, accessibility, propriety, utility, purposiveness, accuracy, specificity and modified objectivity). Steps 4–7 will include data extraction and realist analysis through retroductive theorising using the ICAMO (intervention, context, actor, mechanism and outcome) heuristic to help distinguish actors and resources from contexts, mechanisms and outcomes.

Ethics approval for the deliberative dialogue interviews that inform this realist review and IPT were obtained by the University of British Columbia (ref: REB Number: H22-03195). Study recruitment occurred between 21 November 2023 and 16 January 2024. All participants provided informed consent to take part in deliberative dialogues and to have their interviews audio recorded and transcribed for the purpose of this research. We will disseminate results of the review through academic papers, conference presentations and through iterative interest group workshops and discussions.

CRD42024580083.

Since the 1970s, telemedicine has transformed significantly, becoming a critical component of modern healthcare delivery. Over time, technological innovation has increasingly emphasised the integration of the human body with digital systems to develop non-invasive methods for monitoring physiological parameters. Among these technologies, wearable sensors demonstrate substantial potential for continuous patient monitoring. These devices can facilitate real-time data collection, enable more rapid clinical decision-making and promote active patient participation in health management. Such capabilities are particularly valuable in emergency contexts, including prehospital care provided by ambulance services and telephone triage systems. Despite the growing interest in wearable health technologies, their integration into emergency medical services (EMS) remains insufficiently explored and warrants further investigation. We aim to map current research, explore the use of wearables in EMS settings and identify gaps in knowledge regarding their use in EMS.

This scoping review will follow the Joanna Briggs Institute’s (JBI) methodology for scoping reviews. A systematic search of relevant databases (MEDLINE, EMBASE, Cochrane Library, CINAHL, ProQuest and Web of Science) will be conducted, from inception to March 2026. All types of study designs, including quantitative and qualitative studies, will be considered in this scoping review. The inclusion is limited to studies published in English. Two independent reviewers (RA and AA) will conduct a thorough screening of titles and abstracts against the predefined inclusion criteria. Studies that meet the inclusion criteria will be reviewed in full text. Quality and risk of bias will be assessed using the JBI’s critical appraisal tools for the relevant study types. The findings will be presented using diagrams or tables, supplemented by narrative summaries following the JBI guidelines.

Ethical approval is not required. The findings of this study will be disseminated via publication in a peer-reviewed journal.

Open Science Framework (10.17605/OSF.IO/MUEFX).

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.

To identify the individual and community-level factors associated with barriers to accessing healthcare services among currently married women in Somalia.

A cross-sectional analysis using data from the 2020 Somalia Demographic and Health Survey.

Somalia.

A nationally representative sample of 30 311 currently married women aged 15–49 years with complete data on outcome and explanatory variables.

The primary outcome was ‘reporting at least one barrier to accessing healthcare’, a composite binary variable based on four specific problems: obtaining permission to go for treatment, getting money for treatment, distance to the health facility and not wanting to go alone.

A substantial majority (77.06%) of married women reported experiencing at least one barrier to accessing healthcare. Financial cost was the most common barrier (69.91%), followed by distance to health facilities (65.95%), reluctance to go alone (49.64%) and the requirement for permission (46.03%). Multilevel analysis confirmed that higher household wealth was strongly protective (richest vs poorest: adjusted OR (aOR)=0.27, 95% CI 0.24 to 0.32). Paradoxically, factors typically considered protective were associated with increased barriers: women with secondary education (aOR=1.19, 95% CI 1.00 to 1.41) and those with educated husbands (aOR=1.23, 95% CI 1.14 to 1.33) reported more obstacles. Similarly, urban residents faced higher odds of barriers than their nomadic counterparts (aOR=1.40, 95% CI 1.27 to 1.55). Significant regional disparities were evident, with community-level context explaining 26.30% of the total variance in reporting barriers.

Access to healthcare for married women in Somalia is predominantly hindered by economic, educational and community-level constraints. Targeted interventions addressing socioeconomic disparities, infrastructural deficits and specific community contexts are essential to alleviate these barriers.

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).

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.

Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures.

This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.

Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, ³Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA.

This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.

Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.

Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration.