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 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.

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.

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).

Identifying the factors that increase the likelihood of medical graduates choosing rural medical careers is key to addressing the global shortage of rural doctors. Using linked graduate-workforce outcomes data, this study aimed to identify predictors of rural medical practice in Aotearoa New Zealand (NZ).

A national prospective cohort study linking data from the longitudinal Medical School Outcomes Database to workforce location data. Univariate and multivariate analyses were conducted to generate ORs for putative predictors of rural medical career.

All NZ medical graduates from 2011 to 2019 were followed for a minimum of 3 years.

During the study period, there were a total of 4152 medical graduates nationally. Included in the analysis were 3291 graduates who had linked longitudinal medical school and workforce data, of whom 133 (4%) doctors were classified as having decided on a career in rural medicine. Independent predictors of rural practice included being of rural origin (OR 2.13, 95% CI 1.19 to 3.81, p=0.011), age older than 25 years at entry to medical school (OR 2.88, 95% CI 1.54 to 5.36, p

This is the first national study linking medical school data to rural medical workforce outcomes. It demonstrates that previously known predictors of rural practice intention are borne out with actual career outcomes, and these also hold true at a national level. However, this research highlights that diverse pathways into rural practice are vital, given that urban-origin students and those with no early rural career intention make up a substantial number of the early-career rural medical workforce.

This community-led research study protocol emphasises placing black youth impacted by the legal system, their families and their communities at the forefront of substance use treatment development research and decision-making. The study, the Cultural Adaptation of a Substance Use Treatment (CAST) Project, challenges traditional top-down approaches to treatment creation, advocating for a grassroots model that centres community knowledge, values and active participation.

The CAST project is a US-based mixed-methods study with an exploratory design that examines the impact of racial discrimination on substance use in black youth impacted by the legal system. The study participants are black youth impacted by the legal system (N=15), parents of black youth impacted by the legal system (N=10) and community members who serve black youth (N=10) (total N=35 study participants). Study participants from each group (youth, parents and community members) will participate in three separate focus groups, respectively, to provide feedback on the culturally responsive content needed to best support black youth impacted by the legal system around substance use and mental health. The eight-step Assess, Decision, Adaptation, Production, Topical Expert, Integration, Training, Testing framework will be used as a guide to inform adaptations to the Motivational Enhancement Therapy and Cognitive Behavioural Therapy (MET/CBT12) for black youth impacted by the legal system. Once the cultural adaptation process has been completed, the study will conclude with an open feasibility and accessibility trial of the culturally adapted MET/CBT12 manual. The primary outcomes of this study are the feasibility and acceptability of the culturally adapted manual, measured by treatment attendance and participant feedback. Secondary outcomes include reductions in substance use and discrimination distress, and improvements in mental health symptoms.

This study was approved by the Institutional Review Board (IRB) at the University of California, San Francisco (IRB Protocol Number: 23-40126). All study procedures will be conducted in accordance with the ethical standards outlined by the institutional review board. The results from this study will be shared through peer-reviewed publications, academic conferences, community forums and policy briefs to support broader implementation of culturally adapted adolescent substance use interventions that address discrimination-related stress and substance use among black individuals impacted by the legal system.

NCT06003725.