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.

This study aimed to investigate the effects of long-term and habitual physical activity on mortality and long-term care insurance (LTCI) certification among cancer survivors using a population database.

5-year retrospective study.

13 Japanese municipalities participated in the Longevity Improvement & Fair Evidence study.

Among 471 511 participants who underwent health check-ups, 39 435 met the following eligible criteria: documented in the cancer claims database without a suspected diagnosis and participated in a health check-up at least once in a 12-month period, had no missing exercise data and had already been certified for LTCI.

Outcomes were new LTCI certification and all-cause mortality. LTCI certification was assigned by a trained local government official through a systematic process (involving various items—physical function, daily activity function, cognitive function, behavioural disorders, adjustment to social life and daily use of medical services—as well as overall consideration of computer-based and specialist team assessments), and the LTCI severity level correlates with the Barthel index. LTCI certification reflects some impairment in activities of daily living. All-cause mortality was defined based on claims data.

Three physical activity categories, ‘exercise and walking’, ‘exercise or walking’ and ‘no physical activity’, were used. Among survivors aged 65–74 years, the ‘no physical activity’ group had a higher risk of mortality and LTCI certification than the ‘exercise and walking’ group (adjusted model HR: 1.72, 95% CI 1.52 to 1.94). Among survivors aged ≥75 years, the low physical activity groups had a higher risk of mortality and LTCI certification than the ‘exercise and walking’ group (adjusted model: ‘exercise or walking’, HR: 1.51, 95% CI 1.29 to 1.85; ‘no physical activity’, HR: 1.66, 95% CI 1.43 to 1.92). The effects of physical activity differed according to cancer type.

Habitual physical activity had positive effects on cancer survivors. These effects differed according to age and cancer type.

While diabetes prevention programmes (DPPs) effectively reduce the risk of type 2 diabetes, optimising referral to these programmes is challenging. Our prior research (a qualitative study on the pilot of the National Diabetes Prevention Programme (NDPP) and a systematic review) identified a range of barriers and facilitators to referral from healthcare workers’ perspectives. This study aims to gain consensus on the main factors influencing referral to a newly established NDPP and using the Behaviour Change Wheel (BCW) to select behaviour change techniques (BCTs) for an implementation strategy to improve referral to the programme in the future.

A two-round modified online Delphi survey prioritised 17 barriers and facilitators of the referral process, followed by a mapping exercise with the BCW, which guided the identification of techniques to change referral behaviour from general practice.

The survey took place online with healthcare professionals working in the primary care setting in Ireland (April to June 2024). The NDPP was in the pilot phase and was not available in all areas. This study sought to learn from this pilot phase to inform the referral process, which was not yet fully established.

Healthcare professionals eligible to refer or involved in referral to the NDPP in Ireland (general practitioners, practice nurses and dietitians delivering the NDPP) took part in the Delphi survey. Recruitment was through a number of gatekeepers, a health service manager and professional groups who shared invitations to participate with eligible healthcare professionals.

In the Delphi survey round 1, respondents were asked to rate the importance of 17 factors (nine facilitators and eight barriers) influencing referral on a 5-point Likert scale (not important to very high importance) and an open text box captured other suggested important factors. Barriers included limited practical information about the availability of the programme, concerns about workload, competing priorities and concern about patient motivation, the time commitment for patients and referral delays. Facilitators included electronic referral and feedback, promotion of the programme by healthcare professionals and consultation with patients before referral. Consensus was defined as agreement of ≥70% for each factor in the combined categories of high importance/very high importance, low/moderate importance or not important. Factors not reaching consensus after the first round were included in round 2 with any new factors from round 1. Factors that did not reach consensus or reached consensus as not important or of low/moderate importance were excluded. Only factors reaching consensus as being of high importance/very high importance across the two rounds were included in the final prioritised list.

The Delphi survey had 37 responses to round 1 and 23 (62%) responses to round 2. 12 factors reached consensus as being of high/very high importance to improve referral. The 12 factors are mapped to seven intervention functions in the BCW and to nine key BCTs (feedback on the outcome of the behaviour, social support, instruction on how to perform a behaviour, information about the health consequences, information about social and environmental consequences, demonstration of the behaviour, prompts/cues, credible source and restructuring the physical environment). The strategy to improve referrals should include education delivered by educators to referrers, educational materials on the DPP and practical support to facilitate referrals. The health service should continue to provide electronic referrals and electronic prompts to refer could be considered as part of the electronic health record.

This study systematically prioritises factors perceived to influence referral and identifies BCTs to improve referral to an NDPP. The BCTs are a starting point for a strategy to improve referral to DPPs. Further consultation with stakeholders is recommended to discuss the acceptability, feasibility and operationalisation of the BCTs in the Irish setting.

Inadequate production of the essential stress hormone, cortisol, results in adrenal insufficiency (AI), which is associated with significant morbidity and mortality. The current standard diagnostic test for AI is the Short Synacthen Test (SST), but this is both invasive and resource-intensive, involving cannulation and blood sampling. A novel formulation, Nasacthin, has been developed in which the same Active Pharmaceutical Ingredient can be delivered intranasally, with the resultant glucocorticoid levels either measured in serum, or in saliva samples to render the test non-invasive, thus creating a potentially more cost-effective test. The Salivary Test of Adrenal Response to Liquid Intranasal Tetracosactide (STARLIT-3) study aims to determine the diagnostic utility of the test in patients with AI.

STARLIT-3 is a randomised 2-way crossover trial which aims to collect data from 32 AI patients allocated to receive both Synacthen and Nasacthin in a random order across two study visits. Paired blood and saliva samples will be collected from participants at baseline, and then at 30 and 60 min after drug administration. Glucocorticoid levels in study samples will be quantified with the aim to determine whether the Nasacthin test is able to correctly diagnose patients with AI by estimating the positive percent agreement with the standard SST using serum cortisol at 30 and 60 min. Data on any reported harms and on the acceptability, usability and tolerability of the Nasacthin test will also be collected.

The study and subsequent amendments have been reviewed and approved by South Central—Hampshire A Research Ethics Committee. Results will be published in peer-reviewed journals and presented at national and international conferences. Plans for dissemination of results to trial participants will be developed in collaboration with patient and public involvement and engagement groups.

ISRCTN26461337.

To identify outcome domains of importance to adults undergoing prosthetic rehabilitation following lower limb amputation in low- and middle-income countries (LMICs), based on their lived experiences described in qualitative literature.

Systematic review and qualitative synthesis informed by a critical realist perspective and reported according to ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) guidelines.

CINAHL, PsycInfo, Web of Science and Trip databases were searched from inception to April 2024.

We included qualitative studies exploring the views and experiences of adults (≥18 years) using lower limb prosthesis in LMICs (World Bank definition). Studies including upper limb amputees, non-prosthetic users, mixed samples that could not be disaggregated or not reporting first-person accounts were excluded.

Two reviewers independently screened studies using predefined criteria. Data were extracted from results sections, including participant quotations and author interpretations. Reflexive thematic analysis was conducted to identify outcome domains across studies. Study quality was appraised using the CASP (Critical Appraisal Skills Programme) qualitative checklist; no studies were excluded based on quality.

Five studies involving 55 participants from Nepal, Kenya, Cambodia, Bangladesh and Kiribati met the inclusion criteria. Four outcome domains were identified: (1) The importance of a prosthesis: highlighting access, socket comfort, durability and functional suitability; (2) valued activities: particularly the importance of work and participation in daily living tasks; (3) acceptance following limb loss: encompassing community participation and self and social acceptance; and (4) independence: including reduced reliance on family and greater control over daily life. Across settings, participants emphasised prosthesis durability, work participation and culturally relevant function.

Evidence on meaningful outcomes of prosthetic rehabilitation in LMICs is extremely limited. Findings indicate that access to a comfortable and durable prosthesis enabling work and daily living is central to recovery, alongside social acceptance and independence. These domains may provide initial insights into outcome measurement and development in low-resource settings. Further primary research across diverse LMIC contexts is urgently needed.

The objective was to assess whether frailty is associated with an increased risk of postoperative delirium (POD) in intensive care unit (ICU) patients aged 65 years and older.

A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. MEDLINE (via PubMed) and the Cochrane Library were searched for studies published between August 2014 and January 2025, assessing frailty with validated instruments and reporting POD during ICU stay. While the search strategy was not limited to a specific study design, only observational studies met the inclusion criteria. Study quality was appraised using the Newcastle-Ottawa Scale (NOS). Due to methodological heterogeneity, results were synthesised narratively.

This review targeted the intensive care setting specifically, including studies conducted in hospital-based ICUs in various countries.

Of 655 records, five studies (n=3045) met inclusion criteria. Frailty prevalence ranged from 10% to 34.9%. Tools used included the Fried Frailty Scale, modified Frailty Index (mFI), FRAIL Scale (Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight), Comprehensive Assessment of Frailty and Edmonton Frailty Scale. Frail patients had higher POD incidence and experienced more complications such as acute kidney injury, prolonged mechanical ventilation and reoperation. NOS scores ranged from 5 to 7, indicating moderate quality.

Frailty appears to be associated with an increased risk of POD in ICU patients aged 65 and older. Given the limited number and heterogeneity of studies, further research is needed to validate this relationship and to inform targeted prevention strategies in critical care.

https://doi.org/10.17605/OSF.IO/7TWQ8

To assess prevalence and associated factors of adverse childhood experiences (ACEs) among patients with severe mood disorders (SMDs).

An institution-based cross-sectional study.

Gedeo Zone Public Hospitals, Southern Ethiopia.

374 patients with SMDs were recruited using a systematic sampling technique.

The data were collected using an interview-administered questionnaire and medical chart review. The outcome variable was assessed using the ACEs questionnaire. Data were coded and entered into Epi Data 3.1 and analysed using SPSS V.26. Bivariate and multivariable logistic regression analyses were performed to identify factors associated with ACEs. The presence of an association was examined using an adjusted OR (AOR) with a 95% CI. Variables with P-values less than 0.05 were considered a statistically significant association.

The overall prevalence of ACEs among patients with SMDs was 51.6% (95% CI 49.2 to 53.9), and the prevalence of ACEs among patients with severe bipolar disorders and depressive disorders was 14.7% with (95% CI 46.8 to 52.4) and 36.9% with (95% CI 46.7 to 55.8), respectively. Having low socioeconomic status (SES) (AOR=2.04 (95% CI 1.40 to 3.45), poor social support (AOR=2.43 (95% CI 1.74 to 4.17)), low resilient coping strategies (AOR=1.48 (95% CI 1.21 to 2.83)) and severity of depressive symptoms (AOR=3.82 (95% CI 2.89 to 6.00)) were significantly associated with ACEs.

This study reveals a high prevalence of ACEs among patients with SMDs, with more than half of the participants reporting at least one ACE. Low SES, low resilient coping strategies and poor social support were factors significantly associated with ACEs, and severe depressive symptoms were significantly associated with ACEs. Therefore, these findings underscore the importance of early screening and appropriate intervention for SMDs and ACEs, and providing more holistic mental healthcare for SMDs and ACEs, improving access to education and economic support, strengthening social support networks, enhancing resilience-building programmes and integrating routine ACEs assessments into mental health evaluations could potentially contribute to improved clinical outcomes and support long-term recovery.

Not applicable

Strengthening research capacity in Africa is vital for tackling pressing health, educational and socioeconomic challenges facing the continent. At the core of this effort is the cultivation of innovative research leaders through postgraduate training programmes that incorporate mentorship-infused supervision. Such models have demonstrated potential in improving research skills, boosting academic productivity and fostering leadership development among emerging scholars. This systematic review and meta-synthesis protocol aims to examine existing mentorship-infused supervision practices across African higher education institutions. The review seeks to identify effective models, uncover common challenges and barriers, and generate evidence-based recommendations to develop sustainable, contextually relevant strategies. Insights from this work will inform policies and practices to enhance postgraduate research training, advance research leadership and contribute to the broader goal of strengthening research ecosystems across Africa.

A systematic review and thematic meta-synthesis will be undertaken, focusing on qualitative research studies as well as the qualitative components of mixed-methods studies. Relevant studies published in English will be identified through a comprehensive search strategy. The electronic databases, including Medline/PubMed, Scopus, Web of Science, African Journals Online, EMBASE and CINAHL, will be searched to capture a wide range of peer-reviewed articles and grey literature. Databases will be searched from March 2026. Two reviewers will independently perform study selection, data extraction, quality assessment and evaluation of risk of bias, using the Critical Appraisal Skills Programme checklist.

This systematic review and meta-synthesis will analyse publicly available literature and does not require ethical approval, as it involves no primary data collection. It will adhere to established ethical and methodological standards, including proper citation and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The findings will be widely disseminated through open-access journal publication, conference presentations and targeted reports for universities, research institutions and policymakers to inform and support mentorship-based postgraduate research supervision across Africa.

CDR420251049878. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD420251049878.

Women doctors face considerable challenges navigating family planning, pregnancy and motherhood. Their experiences can have relevance for health system functioning, including doctor retention. This scoping review synthesises research on family planning, fertility, pregnancy and motherhood among women doctors in the EU and the UK.

Scoping review conducted according to JBI best practice guidance.

MEDLINE, CINAHL, Academic Search Complete, PsycInfo and Web of Science were searched, and supplemented with backwards and forwards citation chasing.

Peer-reviewed, original research, in English, focusing on either fertility and family planning, pregnancy and/or motherhood among women doctors in an EU country(s) and/or the UK.

Data were extracted independently by two authors. Data were synthesised using deductive content analysis and collated using narrative synthesis.

In total, 34 studies were identified. Family planning appears complicated by medical careers. Medical specialty choice is particularly impacted, with certain specialties (eg, General Practice) considered particularly family friendly and others markedly less so. Pregnancy complications among women doctors, especially surgeons, were documented. However, women doctors’ and non-doctors’ pregnancy outcomes were overall not significantly different. Notably, doctor-mothers had fewer children and were more likely to report making compromises or facing negative consequences when balancing family and career than doctor-fathers.

Women doctors in the EU and UK report challenges in balancing work and motherhood. With the potential for their experiences to impact on health system functioning and patient outcomes, training bodies and health organisations should take proactive action to better support women doctors and ensure they can remain in the profession and practice in their desired specialty. Future research examining working practices/schedules during pregnancy, breastfeeding experiences, parenting and childcare and maternal mental health will support a better understanding of women doctors’ experiences and facilitate implementation of effective supports.

Harms due to methamphetamine use disorder (MAUD) are rising globally. Untreated withdrawal symptoms perpetuate the cycle of dependence and are a barrier to treatment. There is no pharmacotherapy approved for methamphetamine withdrawal. Lisdexamfetamine (LDX) dimesylate has potential as an agonist therapy to ameliorate symptom severity during acute methamphetamine withdrawal and increase duration of initial abstinence and retention in treatment.

We will conduct a double-blind, randomised, controlled trial to evaluate the efficacy of LDX in reducing symptom severity during acute methamphetamine (MA) withdrawal. One hundred eighty-four adults with moderate to severe MAUD presenting to a health service requesting MA withdrawal treatment who report use of MA within the last 72 hours will be recruited. Participants will be randomised 1:1 to receive a tapering dose of lisdexamfetamine (250 mg on day 1, reducing by 50 mg per day to 50 mg on day 5, followed by 2 days of placebo washout on days 6 and 7), or placebo for 7 days. The study will be conducted over 7 days in an inpatient unit, and all participants will also receive standard inpatient withdrawal care. Participants will be followed up in the community to day 84. The primary outcome is efficacy, defined as the between-group difference in average withdrawal severity measured over the 7-day admission by the Amphetamine Withdrawal Questionnaire. Secondary outcomes are retention in treatment, treatment satisfaction, sleep and concomitant medication use (symptomatic medications and medications for other indications to day 7); safety, craving for MA, post-treatment withdrawal symptoms, depression, anxiety and stress, insomnia and cost effectiveness (to day 28) and MA use, mental, physical and social health and post-withdrawal treatment utilisation (to day 84). A First Nations qualitative substudy will assess the experiences of Aboriginal and Torres Strait Islander participants, ensuring the treatment meets the needs of First Nations people.

This protocol was first approved by the St Vincent’s Hospital Human Research Ethics Committee on 15/05/2024 (2024/ETH00788). All participants will be provided with a participant information sheet and consent form, be fully informed about the study and given ample time to consider participation. Results will be published in peer-reviewed journals and presented at national and international conferences. Findings will be presented such that individual participants will not be identifiable.

ACTRN12624001061527.

Cardiac surgical procedures are associated with a high incidence of postoperative infection, a risk attributed to their inherently invasive nature and extended duration. The goal of this study is to evaluate the efficacy of negative pressure wound therapy (NPWT) compared with standard dressings in preventing sternal scar dehiscence in patients undergoing cardiac surgery via complete vertical midline sternotomy, comparing a 3 day change system (NPWT 3/7 d) versus a 7 day wear system (NPWT 7d) versus standard dressings.

The PRISTER study is a prospective open-label multicentre, randomised, controlled, three-arm trial. Patients aged ≥18 years and meeting all the following inclusion criteria: patients undergoing scheduled or semiurgent cardiac surgery, with or without extracorporeal circulation, and patients managed by complete vertical median sternotomy will be recruited. Total sample size will consist of 660 patients. The primary outcome, surgical wound dehiscence after complete median sternotomy, expressed as occurrence or non-occurrence during the first 30 postoperative days, will be assessed by tablet calibrated photos analysed by an independent blinded staff. The secondary outcomes will be the number of dressing repairs between D7 (excluding initial protocol) and D90, length of initial hospital stay, occurrence of surgical site infection and its classification collected on day 90 (D90), use of an anti-infectious treatment and its duration, incidence of postoperative mediastinitis defined by dehiscence of the sternum with positive sternal samples, incidence of surgical revision for dehiscence of the surgical wound at D90 and collection of all operations involving surgical revision of the sternotomy wound, number of rehospitalisations (including hospital consultations) and their duration (evaluated at D90). Medicoeconomic assessment will be assessed by evaluation of hospital and extrahospital costs (number of days in hospital, consultations, rehospitalisations, imaging, biology and drugs), dressing costs and patient quality of life by EQ-5D-5L.

The study was approved by the French Agency for the Safety of Health Products (ANSM, Agence National de Sécurité du Médicament) as well as by the Ethics Committee (CPP Ile de France VIII) N°ID-RCB: 2023-A01782-43. Recruitment began in April 2024 and ended on 26 May 2025.

clinicaltrials.gov NCT06207630.

Practice guidelines recommend addressing patient non-medical drivers of health such as access to nutritious food and transportation as part of whole-person care. Emergent electronic health record (EHR)-based tools can enable non-medical needs care coordination, but adoption commonly faces workflow and infrastructure barriers. Targeted implementation support strategies (eg, training, practice facilitation) can enhance technology adoption in healthcare settings, but no prior research has assessed if implementation strategies can improve how care managers use enabling technologies for non-medical needs care coordination. This study will test whether providing implementation support to primary care health centre care management teams improves the adoption of EHR-based enabling technologies to address patients’ non-medical needs.

This hybrid implementation-effectiveness type 2 pragmatic trial has a mixed methods design. The primary outcomes include: (1) Whether patients enrolled in care management programmes have been screened for unmet non-medical health-related needs and (2) Whether patients with identified unmet non-medical health-related needs received a referral to a community organisation to address their need. The secondary outcomes include: (1) Whether referrals for financial-related non-medical needs had a documented outcome in the EHR, such as successful connection to services, service unavailability or other disposition statuses, (2) Whether the referral outcomes indicated ‘successful connection to services’ and (3) Clinical markers including hypertension and diabetes control. Formative evaluation of barriers and facilitators to using EHR tools to conduct non-medical needs screening, referrals and tracking of receipt of services will include semi-structured interviews and a ‘guided tour’ of enabling technology used by care managers. A modified Delphi process will then inform the development of a set of implementation strategies for inclusion in the intervention. The intervention will be piloted in three health centres, refined, then tested in a stepped-wedge cluster-randomised trial in 20 health centres.

We obtained ethics approval for all study activities from Advarra Institutional Review Board (registration number #00000971). Results will be disseminated to Health Centres and Health Centre network nationally at meetings and we will disseminate to researchers via manuscripts in peer-reviewed journals and scientific meetings.

NCT06489002.

Despite the continued burden of opioid overdose in communities in the USA, effective treatments for opioid use disorder (OUD), such as medication for opioid use disorder (MOUD), remain underused. Motivational interviewing techniques and linkage to MOUD via digital health are innovative practices developed to overcome persistent barriers to accessing MOUD treatment. These practices are merged in a comprehensive digital health platform, RecoveryPad (developed by the Center for Progressive Recovery). Our study, ‘Using System Dynamics Modeling to Foster Real-time Connections to Care’ (NIH Award #: 1R61DA057675-01), is a pilot to assess the feasibility and behaviour change potential of RecoveryPad for our target audience of people experiencing OUD.

This study will recruit 40 participants in Connecticut and New York through online platforms, such as social media and digital advertising, and direct access via quick-response (QR) codes distributed by local community partners. Eligibility assessment and enrolment will be conducted virtually. Individuals reporting symptoms indicating moderate to severe OUD who are at least 18 years of age are eligible for the study, excluding those who are currently receiving MOUD, pregnant or incarcerated. Enrolled participants will interact with an automated chatbot, live recovery coaches and, if desired, be referred to a telehealth MOUD provider via the RecoveryPad platform. Participants will have access to the platform for 30 days and will be asked to complete brief surveys to assess MOUD engagement and secondary outcomes at 30 and 90 days. Additionally, system dynamics (SD) models will be developed at the individual level to simulate participant interactions with RecoveryPad, and at the community level to improve understanding of the systems affecting OUD and MOUD access.

This project received approval from the Yale University Human Investigation Committee in 2024 (HIC # 2000034414). All participants will complete an electronic consent form with detailed study information and release of information to obtain data related to MOUD appointment attendance. Findings and conclusions from this pilot will be disseminated via peer-reviewed publication, advisory board meetings and meetings with community partners.

NCT05832879.