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).

Parental psychological challenges and poor well-being are key factors in shaping both the quality of parent-child interactions and child development. Specifically, maternal psychological distress is a central determinant of child development. Elevated levels of distress in mothers are associated with poorer child cognitive, behavioural and social-emotional outcomes, with effects persisting into adolescence and adulthood. While this highlights the critical importance of early prevention and intervention efforts to support parents, postpartum mental healthcare remains limited, despite ongoing and evident needs.

This protocol outlines a 2-year longitudinal follow-up study investigating the impact of a secondary perinatal programme (ie, Toi, Moi, Bébé), completed by mothers during pregnancy, and its impact on children’s cognitive and social-emotional functioning at 24 and 48 months. Further, the study aims to explore whether maternal self-efficacy and emotion regulation may serve as potential mediators or moderators of the relationship between programme participation and child development outcomes. The research aims to leverage the Toi, Moi, Bébé programme, by recruiting mother-child dyads (n=250) in which the mothers participated in the programme during pregnancy. Mothers were randomly assigned to complete the parenting well-being intervention either independently or with added telephone support. Participants who consent will be invited to take part in a two-wave follow-up at 24 months (T1) and 48 months postpartum (T2). At both time points, mothers will complete demographic questionnaires and standardised measures assessing maternal well-being (Generalised Anxiety Disorder-7, Edinburgh Postnatal Depression Scale and Perceived Stress Scale), child cognitive functioning (Ages and Stages Questionnaire-3 and MacArthur-Bates Communicative Development Inventory), child social-emotional functioning (Ages and Stages Questionnaire, Social Emotional—second Edition-2 and Child Behaviour Checklist for Ages 1.5–5), maternal emotion regulation (Cognitive Emotion Regulation Questionnaire) and maternal self-efficacy (Parental Cognitions and Conduct Towards the Infant Scale & Me as a Parent Scale). Parents’ perceptions of their parenting experience will be measured using the Parental Reflective Functioning Questionnaire. Mother-child interaction, parenting quality and cognitive stimulation in the home environment will be measured using a brief virtual interview (StimQ₂-Toddler) and a naturalistic observation assessment (Parenting Interactions with Children: Checklist of Observations Linked to Outcomes). Using RStudio, linear mixed models will be used to assess the impact of the intervention (online intervention only vs only with telephone support) on child cognitive and social-emotional development at T1 and T2. In parallel, separate models will be conducted to examine associations between maternal emotion regulation and self-efficacy on the child development outcomes at the same timepoints. Exploratory analyses will be conducted to examine potential moderating effects of child sex and group assignment on the associations between maternal emotion regulation and self-efficacy and child developmental (cognitive and socioemotional) outcomes, using causal inference models.

The current study has been registered, reviewed and approved (MP-37-2025-10894) by the Research Institute of the McGill University Health Centre Research Ethics Board. Findings from this research will be disseminated through peer-reviewed open access publications, and presentations at national and international conferences.

NCT05110456.

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.

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.

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.

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.

Laser corneal refractive surgery is a widely adopted approach for correcting refractive errors, but postoperative dry eye remains a common side effect. Intense pulsed light (IPL) and low-level light therapy (LLLT) are two emerging treatments that have shown potential in managing dry eye disease. However, their role as a prophylactic treatment in patients without pre-existing symptomatic dry eye undergoing refractive surgery has not been explored.

This is a single-blind, randomised controlled trial comparing the prophylactic efficacy of combined IPL and LLLT treatment versus standard care in preventing dry eye after laser corneal refractive surgery (FS-LASIK, SMILE or PRK). Eligible patients aged 18 or older scheduled for surgery will be randomly assigned in a 1:1 ratio to either the treatment or control group. The primary endpoint is the French version of Ocular Surface Disease Index score at 1 month postoperatively. Secondary outcomes include Fluorescein Break-Up Time, Schirmer I test, Oxford score and Meibomian Gland Dropout. Data will be analysed using a mixed-effects linear model adjusted for surgery type and baseline dry eye parameters. The study started in June 2023 and end in April 2025 but data have not been yet analysed.

The study has been approved by the Institutional Review Board Est III, France, and registered on ClinicalTrials.gov (NCT05803798). All participants will provide written informed consent. Results will be disseminated through peer-reviewed publications and presentations at scientific conferences.

NCT05803798.

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.

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.

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.

The mental health impacts of COVID-19 on frontline healthcare workers have been reported globally; however, there is limited evidence from low-income countries such as Ethiopia. We reviewed the literature to understand how COVID-19 impacted the mental health of frontline healthcare workers, including the associated risk and protective factors.

A scoping review of peer-reviewed research was conducted between 2020–2025 to explore the mental health and well-being of frontline healthcare workers in Ethiopia during COVID-19. The process adhered to the guidelines for data extraction outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Our search identified 35 studies, of which 29 studies were included in the final synthesis.

Three online databases, PubMed, Web of Science and PsycInfo, were systematically searched for data.

Studies were considered for inclusion in the review if they focused on mental health conditions and psychosocial well-being among healthcare workers during COVID-19 in Ethiopia. Studies were only included if published in English and excluded if they were conference abstracts, case studies, reviews, commentaries, contained incomplete data or lacked variables of interest.

Data extraction was conducted manually by two reviewers by using a data extraction sheet created in Excel.

Most frontline healthcare workers experienced symptoms of insomnia, psychological distress, stress, anxiety, post-traumatic stress disorder and depression during COVID-19. Female frontline healthcare workers, nurses, midwives and laboratory technicians reported higher rates of adverse mental health outcomes. Our results found that being married, living together with a spouse and having a high educational level were risk factors for adverse mental health outcomes.

The mental health and well-being of frontline healthcare workers is at risk during a global health crisis; however, there is a limited understanding of how to protect the mental health of frontline healthcare workers in low-income countries, such as Ethiopia, at such a critical time. Additional research is needed to better inform mental health preparedness interventions for frontline healthcare workers in these contexts, particularly given predictions of another pandemic occurring within the next decade.

Virtual Wards (VWs) facilitate hospital-level monitoring, diagnostics and treatment within patients’ homes, while the hospital team retains responsibility for care. International research indicates that VWs decrease hospital length of stay without increasing readmissions; however, the feasibility and key operational determinants within Dutch care remain uncertain. This protocol outlines the VW for Early Discharge in Patients Receiving Inpatient Care (VIP Care) study.

The VIP Care study is a single-centre prospective feasibility cohort study conducted at Erasmus University Medical Center (Erasmus MC), Rotterdam, the Netherlands. The study encompasses seven predefined subcohorts with n=51 eligible patients per subcohort: (1) bacterial, fungal or parasitic infections; (2) viral respiratory infections; (3) dehydration; (4) decompensated heart failure; (5) high-dose corticosteroid treatment; (6) post-transsphenoidal pituitary surgery follow-up and (7) severe inflammatory skin disease with or without bacterial or viral superinfection. Adults who require hospital-level monitoring and/or therapy may qualify for early discharge to the VW.

The VW integrates scheduled, patient-performed measurements using (European Conformity) CE-marked devices with structured symptom assessment submitted via a patient application, and data review in an electronic health record-integrated clinician cockpit. Submissions are evaluated by VW tele-nurses using prespecified Early Warning Score based thresholds and an escalation protocol. Patients receive a daily physician telephone review. Diagnostics and treatments are administered at home to hospital standards through established home-care services.

The primary outcome (feasibility) is adherence to transfer, defined as the proportion of eligible inpatients who provide written informed consent and are subsequently successfully transferred to the VW. The prespecified feasibility threshold is 30%. Secondary outcomes include reach (eligibility, invitation and consent rates among admitted patients), operational performance during the VW episode (alert frequency and handling, contact volumes and actions), length of stay on the ward and in the VW, emergency department reassessments and 30-day readmissions. Qualitative interviews will be conducted to identify implementation determinants.

The study received approval from the Erasmus MC Medical Ethics Committee (MEC-2024–0060; amendment MEC-2024–0060 A0001). Incremental risk is considered minimal. Written informed consent is obtained. Findings will be disseminated through peer-reviewed publications, conference presentations and an accessible lay summary.

ClinicalTrials.gov NCT06936891; CCMO NL85516.078.24. Recruitment began in May 2025 and is ongoing.

Post-COVID-19 syndrome (PCS) is characterised by persistent symptoms, such as fatigue, dyspnoea, depression and sleep problems, following SARS-CoV-2 infection. The long-term course and impact on quality of life remain unclear. This review aims to synthesise evidence on longitudinal changes in symptom prevalence, severity and health-related quality of life (HRQoL) in adults with PCS.

This systematic review will include longitudinal studies (randomised controlled trials, non-randomised trials, prospective and retrospective cohort studies) of adults (≥18 years) with PCS, defined by symptoms persisting beyond 4 weeks after acute infection. Eligible studies must report changes in prevalence or severity of fatigue, dyspnoea, depression, sleep problems or HRQoL from baseline to at least one follow-up visit.

We will systematically search MEDLINE, Embase, PsycINFO, Web of Science, Scopus, CINAHL and Epistemonikos, with no restrictions on language, date or publication status. Two reviewers will independently screen studies, extract data and assess risk of bias using validated tools appropriate to study design. Disagreements will be resolved by consensus or a third reviewer.

A narrative synthesis will summarise study characteristics and symptom trajectories. Where sufficient data are available, random-effects meta-analyses will be conducted to estimate pooled changes in symptom prevalence (ORs), severity ((standardised) mean differences) and HRQoL ((standardised) mean differences). Meta-regression and subgroup analyses will explore potential effect modifiers. Certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

No ethical approval is required. Findings will be disseminated via peer-reviewed publication, conference presentations and plain language summaries.

CRD420251011612.

The prognostic value of left atrial (LA) strain in patients with heart failure with reduced ejection fraction (HFrEF) has not been fully elucidated. Therefore, this study investigated the prognostic value of LA strain in HFrEF patients in relation to all-cause mortality.

A total of 822 echocardiograms from HFrEF patients admitted to a heart failure clinic were analysed offline. To calculate left atrial reservoir strain (LA RS) and left atrial contractile strain (LA CS), LA two-dimensional speckle tracking was performed in the 4-chamber, 2-chamber and 3-chamber view. The end-point was all-cause mortality. The association between LA strain parameters and outcome was examined using Cox regression.

The median follow-up time was 40 months and follow-up was 100% complete. During follow-up, a total of 137 patients (16.7%) died of all causes. In a final multivariable model adjusted for clinical and echocardiographic parameters including global longitudinal strain, LA RS and LA CS were significantly associated with all-cause death during follow-up (LA RS, HR 0.96, 95% CI 0.92 to 0.99, p=0.014, pr. 1% increase) (LA CS, HR 0.95, 95% CI 0.92 to 0.98, p=0.002, pr. 1% increase).

When added to the final multivariable model, both LA RS and LA CS contributed with incremental prognostic value as determined by C-statistic (LA RS: C-stat difference 0.007, 95% CI 0.000 to 0.020, p=0.050) (LA CS: C-stat difference 0.009, 95% CI 0.000 to 0.023, p=0.030).

In HFrEF patients, LA RS and LA CS were associated with all-cause mortality and contributed incremental prognostic value in addition to established prognostic measures.

Postoperative acute pain following video-assisted thoracoscopic surgery (VATS) impedes patient rehabilitation. While multimodal analgesia effectively mitigates postoperative acute pain and facilitates the postoperative rehabilitation process, the efficacy of preventive precision multimodal analgesia (PPMA) remains uncertain. This study designs a PPMA strategy targeting incisional pain, inflammatory pain and visceral pain in VATS. It aims to investigate the impact of the PPMA strategy on the postoperative acute pain process and rehabilitation outcomes.

This multicentre, single-blinded, randomised controlled trial will enrol adult patients scheduled for elective thoracoscopic lobectomy or segmentectomy. A total of 1372 participants will be recruited and randomly allocated in a 1:1 ratio to either the preventive precision multimodal analgesia group (PPMA Group) or the conventional multimodal analgesia group (CMA Group). Patients in the PPMA Group will receive a regimen consisting of local anaesthetic infiltration of surgical incision (for incisional pain), intravenous injection of oxycodone (for visceral pain) and parecoxib sodium (for inflammatory pain) before surgery initiation. Patients in the CMA Group will receive the same regimen after specimen isolation. This trial will be conducted across 13 medical centres in China from 2023 to 2026. The primary outcome is the duration of postoperative acute pain. Secondary outcomes include postoperative analgesic consumption, postoperative pain scores, intraoperative haemodynamic parameters and the Indexes of Consciousness (IoC₁ and IoC₂), as well as intraoperative arterial blood gas and ventilation parameters, intraoperative dosages of general anaesthesia, inflammatory markers at predefined time points, postoperative rehabilitation process and perioperative adverse events and complications.

This study has been approved by the Ethics Committee of Xuanwu Hospital, Capital Medical University (Linyanshen[2023]-NO.012-003-Revised Vision 1). The results will be published in a peer-reviewed journal.

Chinese Clinical Trial Registry (ChiCTR2300072176).