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.

Despite the minimally invasive nature of video-assisted thoracoscopic surgery (VATS), moderate-to-severe postoperative pain remains frequent and impairs recovery. Intravenous lidocaine possesses multimodal analgesic, antihyperalgesic and anti-inflammatory properties that may improve pain control and functional outcomes, but robust evidence in thoracic surgery is lacking. Moreover, its potential to attenuate neuropathic pain, a key component of chronic post-thoracic pain syndromes, has not been adequately investigated. This trial will determine whether continuous perioperative intravenous lidocaine infusion improves recovery, reduces acute pain intensity and prevents the development of neuropathic pain after VATS.

This single-centre, randomised, double-blind, placebo-controlled trial will enrol 84 adult patients undergoing elective VATS. Participants will be randomised (1:1) to receive either intravenous lidocaine (bolus 1 mg/kg at induction followed by continuous infusion at 1.5 mg/kg/hour intraoperatively and postoperatively for 24 hours) or matched normal saline postoperatively, with identical intraoperative management in both groups. The primary outcome is the incidence of moderate-to-severe movement-evoked pain at 24 hours postoperatively. Secondary outcomes include pain at 48 and 72 hours, opioid consumption, pulmonary complications, sleep quality, quality of recovery, neurocognitive outcomes and chronic neuropathic pain at 3 months. Analyses will follow the intention-to-treat principle.

The study protocol was approved by the Institutional Review Board of Tongji Hospital (Reference No. TJ-IRB202509102) and registered in the Chinese Clinical Trial Registry (ChiCTR2500111163). Written informed consent will be obtained from all participants. Results will be submitted to peer-reviewed journals and academic conferences.

ChiCTR2500111163.

Indian immigrants experience significant dietary acculturation post-migration, shifting from traditional diets to more westernised eating patterns influenced by socioeconomic and environmental factors. This transition, often marked by increased processed food consumption and reduced intake of traditional staples, contributes to elevated risks of obesity and type 2 diabetes. Despite the growing Indian diaspora in Australia, Canada, New Zealand and the UK, the evidence on their dietary acculturation remains limited.

This review will adopt the Joanna Briggs Institute (JBI) methodology for scoping reviews. A three-step search strategy will be applied across databases including MEDLINE (via PubMed), CINAHL, Scopus and Web of Science. Google Scholar will be used as a supplementary search tool to identify additional relevant studies. The search will include peer-reviewed studies and grey literature published in English between 1 January 2000 and 22 May 2025. First-generation Indian immigrants of all ages will be included, while second-generation immigrants, refugee populations and studies linked to non-communicable disease interventions will be excluded. Screening will be conducted in Covidence by two independent reviewers, with discrepancies resolved by a third reviewer. Data will be extracted using a standard JBI tool, charted in tabular form, and synthesised narratively and thematically.

As this review will use published and publicly available data, formal ethics approval is not required. Findings will be disseminated through peer-reviewed publication, conference presentations and community engagement.

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.

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.

Postoperative pain is common after surgery, with a high incidence and risk of becoming chronic. Current multimodal analgesia has drawbacks, including limited efficacy from single agents and opioid side effects and addiction risk. These issues have led to opioid-sparing multimodal analgesia. Transcutaneous auricular vagus nerve stimulation (taVNS) is non-invasive and convenient. Studies have shown it can reduce postoperative pain, improve mood and lower adverse events. However, taVNS lacks a comprehensive evaluation and standardised protocols, so further research is needed to provide reliable evidence.

This study strictly adheres to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. To identify suitable randomised controlled trials (RCTs), eight credible databases will be searched, including four English databases (Web of Science, PubMed, Cochrane Central Register of Controlled Trials, EMBASE) and four Chinese databases (China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Database, Chinese Biomedical Literature Database). RevMan V.5.3 will be employed to integrate the retrieved data and conduct meta-analyses. The methodological quality of included RCTs will be evaluated using the Cochrane Risk of Bias Assessment 2.0 tool. Additionally, the Grading of Recommendations, Assessment, Development and Evaluation system will be applied to assess the strength and certainty of the evidence. We will also conduct publication bias analyses, sensitivity analyses and subgroup analyses.

No ethical review is required as no private or confidential patient data will be included. Results of this study will be disseminated through a peer-reviewed journal.

CRD420251207651.

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.

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

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

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

NCT06100978.

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.

Nigeria has one of the highest maternal mortality burdens globally. Improving maternal outcomes requires a better understanding of how women experience care across pregnancy, childbirth and the postnatal period. This study explored women’s maternal healthcare experiences across the perinatal continuum in Nigeria, with a focus on how challenges emerge and interact over time.

Longitudinal qualitative study using patient journey mapping.

Public primary, secondary and tertiary healthcare facilities in Abuja, Nigeria.

12 pregnant women were purposively sampled. Each woman participated in two rounds of in-depth interviews: once in late pregnancy and again 2–6 weeks postpartum. All participants completed both interview rounds.

Data were collected through 24 semistructured in-depth interviews conducted longitudinally to capture changes in women’s experiences before and after childbirth. Interview guides were informed by existing maternal health frameworks. Transcripts were analysed using reflexive thematic analysis and organised across five stages of the maternal healthcare journey: Awareness, Consideration, Access, Treatment and Recovery.

This study introduces a five-stage framework: Awareness, Consideration, Access, Treatment and Recovery, to comprehensively explore maternal healthcare experiences. The findings reveal systemic inefficiencies at every stage of the pregnancy journey, from limited awareness of pregnancy test kits to unreliable booking systems and inadequate postpartum mental health support. This study highlights how early-stage barriers cascade into later phases, unlike traditional research that focuses only on clinical interactions. This study emphasises the importance of maternal care accessibility and recovery support, moving beyond a treatment-centric lens. 

This study presents a transformative framework for understanding maternal healthcare as a continuum of interconnected experiences. The research offers actionable insights to enhance maternal health outcomes through stage-specific strategies. The globally adaptable framework provides policymakers and healthcare practitioners with a roadmap to improve maternal healthcare systems in Nigeria and beyond. This holistic approach lays the foundation for reducing maternal mortality while ensuring equitable care for all.

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.

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.

Osteoporosis (OP) is a systemic skeletal disorder that increases fragility and susceptibility to fractures. Despite the availability of teriparatide for the treatment of patients with acute fractures with better efficacy, its long-term daily injection and high cost limit its broader use among a wider patient population, especially for those living in low- and middle-income countries. This study aims to evaluate the efficacy of a novel sequential treatment with teriparatide daily for 6 months followed by denosumab every 6 months for another 18 months, in comparison with denosumab monotherapy every 6 months for 24 months, in reducing the risk of fractures in patients with newly diagnosed osteoporotic fractures. The study will also explore the possible difference between two sequential treatments (shifting to denosumab treatment at 6 or 12 months) in their effect on increasing bone mineral density (BMD).

This study is designed as a multicentre, open-label, randomised controlled trial among 2478 patients with newly diagnosed osteoporotic fractures from 58 hospitals across China. Participants will be randomly assigned in a 10:10:1 ratio to three treatment groups: 24 months of denosumab monotherapy, early sequential treatment (teriparatide for 6 months followed by denosumab for 18 months) and late sequential treatment (teriparatide for 12 months followed by denosumab for 12 months). The primary outcome is the incidence of vertebral fractures over 24 months of treatment. Secondary outcomes include changes in BMD at the lumbar spine, total hip and femoral neck, changes in bone turnover markers (β-carboxy-terminal telopeptide of type 1 collagen and procollagen type 1 N-terminal propeptide), treatment adherence and cost-effectiveness. Follow-up assessments are scheduled at 3, 6, 9, 12, 18 and 24 months post-randomisation for primary and secondary outcomes, and biannually afterwards for the primary outcome.

The study protocol has been registered on ClinicalTrials.gov and has received ethical approval from the Peking Union Medical College Hospital Medical Science Research Ethics Committee (1-22PJ939). The findings will be disseminated through peer-reviewed scientific journals.

NCT05866029.

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.

Black women in early midlife experience disproportionate exposure to stress and elevated cardiovascular risk, including hypertension. Despite this, few stress management interventions are designed with and for this population. This study aims to explore the lived experiences of stress and coping among black women in early midlife with elevated blood pressure to inform the codesign of a culturally relevant, multilevel stress management intervention.

We will conduct one-time, semistructured focus groups with black women aged 35–50 who have elevated blood pressure, recruited from a large safety-net health system. Data will be analysed using a constructivist grounded theory approach, with inductive theme development supported by line-by-line, focused and theoretical coding. The Social Determinants of Cardiovascular Disease framework will serve as a sensitising guide to multilevel contextual factors rather than a prescriptive coding structure. An artificial intelligence (AI)-assisted analytic component will complement human-led analysis by supporting preliminary theme exploration and enhancing transparency.

Approved by the Indiana University Institutional Review Board (Protocol #21785). All participants will provide written informed consent. Findings will be shared via peer-reviewed publications, conference presentations and lay summaries for stakeholders.

Previous reviews have investigated the relationship between empathy and burnout. However, these are now out of date, did not capture the effect of the pandemic, did not include healthcare professionals other than doctors and nurses or medical students, did not assess the impact of differences in profession and did not pool the data, which made estimating the strength of the association unclear. We therefore aim to address these shortcomings in an up-to-date, rigorous, systematic review and meta-analysis.

Findings will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and flowchart.

We will search American Psychological Association (APA) PsycINFO, APA PsycArticles, Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library, PubMed and Scopus. We will also search ResearchSquare and Social Science Research Network (SSRN) for preprints; ProQuest Dissertations and Theses and Electronic Theses Online Service for relevant theses. Forward and backward citation searches will identify additional studies. Two independent reviewers will screen titles, abstracts and full texts and extract data. Two independent reviewers will assess risk of bias using Risk of Bias 2 (RoB 2) for randomised controlled trials, Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) for non-randomised interventional studies and Risk of Bias in Non-randomised Studies of Exposures (ROBINS-E) for observational studies.

For all included studies, we will summarise the study characteristics, including number of participants; health profession, specialty and career stage; country and gender. If data are suitable, we will pool results and conduct subgroup analyses (including by health profession, career stage and clinical specialty). We will also explore the relationships between subscales of empathy and burnout. We will use metaregression to explore the impact of theoretically derived factors (such as study design and profession) on the strength of the association. Sensitivity analyses will assess the impact of low-quality research. In our discussion, we will summarise results, the limitations and provide a general interpretation of the results and implications.

Ethical approval is not required for this review, as primary data will not be collected. The review will be disseminated through peer-reviewed publication and presentation at conferences.

CRD420251075618.