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.

Medication non-adherence in older adults with long-term conditions contributes to significant morbidity, mortality and healthcare costs. While adherence support tools exist, many interventions fail to reach those most at risk. Automated medication dispensers (AMDs) show promise in improving adherence and health outcomes, but their integration into routine community pharmacy practice remains underexplored. This study aims to assess the effectiveness of an AMD intervention with SMS reminders in enhancing medication adherence among older adults and to evaluate how this technology can be integrated into community pharmacy workflows.

This randomised controlled trial involves 144 participants recruited from eight community pharmacies who will be randomised to receive either the AMD intervention or usual care. Primary outcomes include medication adherence, measured through pharmacy records and self-report at baseline, 3 and 6 months. Secondary outcomes include Morisky Medication Adherence Scale, health-related quality of life (SF-12), and healthcare resource use. A nested mixed methods process evaluation will explore uptake, acceptability and implementation.

The study protocol has been approved by the University of Bedfordshire Institute for Health Research Ethics Committee (IHREC1039), the NHS and the local authority Research Governance and Research Ethics Committee (NHS REC reference: 25/EE/0026). The findings will be disseminated via a final report, peer-reviewed journal publications and presentations at relevant conferences.

ISRCTN18849739.

Each year, millions of people experience recurrent diverticulitis episodes. Elective sigmoid colon resection reduces the risk of recurrence, but The American Society of Colon and Rectal Surgeons recommends individualising surgical decisions based on the impact of the condition on a patient’s quality of life (QoL). However, no threshold for QoL impairment has been established to guide decision-making, and evidence comparing elective colectomy with medical management in terms of QoL limitation is limited. To address these gaps and to guide treatment decision-making, we designed the Comparison of Surgery and Medicine on the Impact of Diverticulitis (COSMID) trial.

The COSMID trial is a large, pragmatic randomised trial including patients with QoL-limiting diverticulitis that aims to determine if partial colectomy is superior to medical management and explore subgroups that are more likely to respond to each treatment.

COSMID will recruit 250 English-speaking and Spanish-speaking adults with imaging-confirmed and QoL-limiting diverticulitis (defined using a modified diverticulitis-related QoL survey). Participants are randomly assigned to undergo elective partial colectomy or receive comprehensive medical management (eg, selected from options including fibre, probiotics, mesalamine and rifaximin). A total of 100 patients who decline randomisation but consent to follow-up will be included in a parallel observational cohort. The primary outcome is the time-averaged score of the Gastrointestinal Quality of Life Index at 6, 9 and 12 months after randomisation. Secondary outcomes include clinical adverse events, healthcare utilisation, recurrent episodes of diverticulitis and additional patient-reported outcomes like the Diverticulitis Quality of Life instrument, decisional regret and work productivity. Exploratory analyses aim to identify differential treatment effects based on patients’ characteristics.

This trial was approved by the Vanderbilt Institutional Review Board (IRB) on 26 August 2019 (IRB #191217). Vanderbilt serves as the institutional review board of record for the following study sites: Albany Medical College, Allegheny Health, Atrium Health Carolinas Medical Center, Virginia Mason Medical Center, Boston University Medical Center, Cedars-Sinai Medical Center, UT Health Lyndon B. Johnson Hospital, Medical University of South Carolina, New York-Presbyterian Queens, Stanford University, University of Pennsylvania, University of California San Diego, University of California San Francisco, University of Colorado Denver, University of Florida, University of Iowa, University of Utah, University of Washington Medical Center, University of South Florida, University of Rochester Medical Center, University of Texas Southwestern Medical Center, Virginia Commonwealth University, Lahey Hospital & Medical Center, Weill Cornell Medical Center and Northwell Health. Rush University Medical Center (approved 8 January 2020), Columbia University Medical Center (approved 28 January 2020), Northwestern University (approved 19 March 2020), Mount Carmel Health System (approved 5 May 2020) and Memorial Health University Medical Center (approved 4 April 2022) are regulated and were approved by their respective IRBs. Results from this trial will be presented at international conferences and published in peer-reviewed journals.

NCT04095663.

Pain in patients with rheumatoid arthritis (RA) is an unmet clinical need. Targeting joint inflammation with disease-modifying antirheumatic drugs has not resulted in the anticipated reduction in pain for many patients. This can partly be explained by the concept of central sensitisation whereby spinal and supraspinal pathways have a lower threshold of activation, leading to increased perception of pain. Synovial stromal cells, such as fibroblasts, are also thought to play a role through peripheral sensitisation of nerves in the joint. Synovial fibroblasts are known to produce pro-algesic mediators such as interleukin 6 and nerve growth factor at the messenger RNA level. These pro-algesic mediators could activate sensory nerve fibres that send signals from the joint to the spinal cord, thereby driving persistent pain in RA. The purpose of this study is to evaluate which pro-algesic mediators are produced by lining versus sub-lining fibroblasts and whether the level of these mediators correlates with clinical measures of pain in patients with RA.

FiND-Pain RA is a multicentre observational study which will recruit 50 patients with seropositive RA who attend the rheumatology department of Guy’s and St Thomas’ Hospital, London, and the Nuffield Orthopaedic Centre, Oxford. Clinical examination, pain-focused patient-reported outcome measures, ultrasound examination and ultrasound-guided synovial biopsy of the knee will be performed. The levels of known and putative pro-algesic mediators will be measured in fibroblasts from the lining and sub-lining layer of the synovium. The location and spatial morphology of sensory nerve fibres and their proximity to lining and sub-lining fibroblasts will be characterised. The primary outcome will be to determine whether the knee pain scores of participants correlate with the level of leukaemia inhibitory factor, a novel putative pain-mediator expressed in sub-lining fibroblasts. The secondary outcomes will be to determine whether other pro-algesic mediators produced by lining or sub-lining fibroblasts correlate with clinical measures of pain and to assess the location and proximity of sensory nerve fibres to lining versus sub-lining fibroblasts.

The study is a sub-study of the PUMIA (Pain Phenotypes and their Underlying Mechanisms in Inflammatory Arthritis) study, which has been approved by the Bromley Research Ethics Committee (REC: 21/LO/0712). The findings of this study will be disseminated through open-access publications, as well as scientific and clinical conferences.

Infection prevention and control (IPC) interventions are multifactorial and are used to prevent healthcare-associated infections in healthcare facilities. However, patient views and enabling patient and public involvement (PPI) in their development has been minimal.

This systematic review aims to identify peer-reviewed publications reporting patient satisfaction outcomes in the context of IPC interventions, to document the methods used to assess patient satisfaction and to conduct a meta-analysis on reported satisfaction outcomes.

Systematic review and meta-analysis following the Joanna Briggs Institute (JBI) methodology and the PRISMA statement, with oversight from a steering group including PPI partners. Studies in peer-reviewed journals were included based on eligibility criteria.

MEDLINE, Scopus, Web of Science, EMBASE, Cochrane Library, CINAHL and PsycINFO were searched in June 2024.

Included studies investigated satisfaction among hospitalised patients in acute care settings following IPC measures, including isolation, cohorting, screening, hand hygiene, antimicrobial stewardship, patient flagging, education, personal protective equipment use, visiting restrictions and treatment delays

Titles and abstracts were screened independently by two reviewers; disagreements were resolved by a third. Study quality was assessed using the JBI manual for evidence synthesis. A meta-analysis was conducted where four or more studies used comparable designs and methods within the same areas of IPC, with heterogeneity evaluated using Cochran’s Q statistic and I² and pooled estimates calculated with 95% CIs using the Wilson (score) method.

Twenty-nine studies were identified. Among IPC measures, isolation precautions were the most commonly reported intervention (11 studies, 38%). The Likert scale was the predominant assessment method (13 studies, 45%). Patient satisfaction with IPC interventions ranged from 58.3% to 97.2%. Meta-analysis of four studies using the Hospital Consumer Assessment of Healthcare Providers and Systems survey showed substantial heterogeneity (I², 55%, p=0.08) and a pooled patient satisfaction level of 69% (95% CI 63.6% to 74.4%) for isolation precautions.

Sixty-nine percent of isolated patients reported satisfaction with their care. Patient satisfaction with IPC interventions varies widely, highlighting limitations in current measurement approaches. Strengthening PPI in the design and evaluation of satisfaction measures is essential to capture meaningful data and improvements in IPC programmes.

IS 2024 CRD42024558385.

Stroke is a leading cause of death and disability in the Caribbean, yet there is limited published information on the availability and utilisation of diagnostic imaging and treatment methods. Inequities in healthcare infrastructure, access to neuroimaging and acute treatment options may contribute to poorer outcomes following stroke, particularly in the low-resource settings that characterise most of the Caribbean region. The objective of this review is to map the literature on access to diagnostic and therapeutic modalities for adult stroke care in the Caribbean to identify potential limitations in acute treatment and examine how restricted access may impact outcomes. The resulting data can help inform strategies for improving access to stroke care in resource-limited communities.

We will apply a three-step strategy based on the Joanna Briggs Institute methodological framework: first, a limited search to identify relevant articles; second, selection of key search terms; third, implementation into a comprehensive search strategy. The query will range from 1 January 1995 to 1 June 2025 (date of final search). Search results will be extracted and screened by two independent reviewers, and findings will be presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. We will consider studies focusing on ischaemic and haemorrhagic stroke in the Caribbean, emphasising access to diagnostic imaging, stroke centres, prehospital management and emergent treatment. Studies examining acute stroke management capacity within the region will be considered. Studies will be excluded if they: focus exclusively on primary stroke prevention, postacute care, longitudinal care pathways for stroke victims or paediatric populations; are unrelated to stroke diagnosis or treatment or are conducted outside the Caribbean.

This protocol aims to perform secondary analysis of previously published literature; therefore, ethical approval is not required. The results of this review will be disseminated through academic conferences and peer-reviewed publication.

Tobacco use is the most significant modifiable risk factor for adverse health outcomes, and early research indicates there are also significant harms associated with vaping. National targets aim to reduce smoking and vaping during pregnancy for Aboriginal and Torres Strait Islander people. While most Aboriginal and Torres Strait Islander people want to quit, cessation is frequently attempted without support, increasing the chance of relapse. Group-based smoking cessation programmes increase quit success by 50%–130% in the general population; however, they have never been evaluated in Aboriginal and/or Torres Strait Islander communities.

The Gulibaa study is an Indigenous-led and community-embedded project that will co-design, implement and evaluate a group-based model of care to support Aboriginal and Torres Strait Islander women to be smoke- and vape-free. Staff of Health Services in New South Wales, Australia, will receive training to deliver a face-to-face group-based smoking and vaping cessation intervention. Aboriginal and/or Torres Strait Islander people who identify as a woman or non-binary, are pregnant or of reproductive age (16 to 49 years), currently smoke or vape at least once per day and are willing to attend the programme are eligible to participate. Up to 500 participants will be recruited. A mixed method evaluation approach will be implemented guided by the RE-AIM framework. Outcomes will include intervention reach, intervention effectiveness (determined primarily by self-reported 7-day point prevalence abstinence at 6 months follow-up), acceptability and feasibility of the intervention, programme fidelity and maintenance and cost effectiveness.

Embedding culturally safe support to quit during pregnancy can result in improved outcomes for both mother and child and immediately improve intergenerational health and well-being. Ethics approval has been provided by the Aboriginal Health and Medical Research Council and the University of Newcastle. Study findings will be disseminated to Aboriginal and Torres Strait Islander communities in ways that are meaningful to them, as well as through Aboriginal health services, key national bodies, relevant state and federal government departments.

ACTRN12625001050448.

Hearing loss is highly prevalent and impacts many aspects of a person’s life, including communication, social engagement, employment, general health and well-being. Yet, many people do not access hearing healthcare and are unaware of the range of hearing healthcare options available. Barriers to hearing healthcare include poor understanding of hearing loss and its impact; poor knowledge of help-seeking for hearing healthcare options; minimal support to help decide which option is best; and stigma related to hearing loss. These barriers lead to many people not receiving the hearing healthcare they need. Guided by theories of behaviour change and implementation science, HearChoice, an online tailored decision support intervention, has been co-developed to empower adults with hearing difficulties by offering them choice and control over their own hearing healthcare. HearChoice aims to facilitate informed decisions, accessibility and uptake of hearing healthcare, including a wide range of interventions, for adults with hearing difficulties. The objectives of the trial are to evaluate the effectiveness, health economics and feasibility of HearChoice.

This online randomised controlled trial will recruit participants with hearing difficulties across Australia, with an anticipated sample size of 640. Participants will be randomised to either HearChoice (treatment) or an Australia-specific Hearing Option Grid (active control), both delivered online. Outcomes will be assessed at baseline when the interventions will be offered, at 7 days post-intervention (primary endpoint) and at 3 months post-intervention. An email reminder will be sent at 1-month post-intervention. The primary outcome is decisional conflict. Secondary outcomes include measures of readiness and self-efficacy to take action, hearing-related quality of life and empowerment, assessment of the value and impact of HearChoice, work performance and health, and feasibility measures. Primary analysis will compare outcomes between HearChoice and the active control at the primary endpoint.

The study was approved by the Curtin University Human Ethics Committee (HRE2023-0024). All participants will provide written informed consent prior to participation. A broad dissemination plan of the study findings includes peer-reviewed publications, scientific conference presentations, articles and presentations for the wider community and public written in lay and accessible language, and social media.

Australian New Zealand Clinical Trials Registry (ACTRN12624001139561).

Endometriosis is a chronic condition affecting up to 11% of people presumed female at birth by the age of 44 years, characterised by the growth of tissue similar to the lining of the uterus on other organs. Endometriosis significantly impacts health-related quality of life (HRQoL) and imposes a substantial burden on both individuals and the healthcare system. International guidelines recommend the interdisciplinary management of endometriosis due to its significant biopsychosocial burden; however, research aimed at exploring psychological approaches for endometriosis is limited. This trial aims to evaluate the effectiveness of CodeEndo, an online co-designed interdisciplinary supportive care program, compared with a waitlist control (WLC), on HRQoL and biopsychosocial outcomes in people with a diagnosis of endometriosis.

A hybrid type 1 effectiveness and implementation randomised controlled trial (RCT) will be conducted. Eligible participants will be randomly allocated to either the CodeEndo program (n=176) or WLC group (n=176) for 8 weeks. The primary outcome will be HRQoL, and secondary outcomes will include psychological symptoms (anxiety, depression, stress), self-efficacy, menstrual, bladder and gastrointestinal symptoms, pain, fatigue, sleep, exercise, diet, symptom bothersomeness and physical and psychological well-being, measured at 8 weeks post-randomisation (T2) and 6-month follow-up (T3). Cost-effectiveness will also be examined. Longitudinal qualitative individual interviews (up to n=40) will be conducted with participants who complete the CodeEndo program to explore benefits, barriers and facilitators of ongoing use. Additionally, the CodeEndo program will undergo evaluation by a group of endometriosis healthcare providers, who will assess potential barriers and facilitators to its real-world implementation. Various process evaluation strategies will also be measured to inform future implementation. Data analyses will incorporate mixed-effects regression models on an intention-to-treat basis, cost-consequences and cost-utility, dietary and qualitative thematic analysis.

This protocol received ethics approval from Deakin University Research Ethics Committee (DUREC Ref: 2024-157). Dissemination is expected to include peer-reviewed journal articles, reports, conference presentations as well as websites or social media platforms of relevant chronic pain organisations. Participants will be sent a summary of trial results.

ACTRN12623000598684p.

People identified as higher risk by a machine learning algorithm (Future Innovations in Novel Detection of Atrial Fibrillation [FIND-AF]) are at increased risk of cardio-renal-metabolic-pulmonary disease and cardiovascular death. The OPTIMISE-1 randomised controlled trial aims to test the effect of community-based specialist-led identification and management of cardio-renal-metabolic-pulmonary (CRMP) disease and risk factors compared with usual care on the use of therapeutic interventions over a follow-up of 6 months among high FIND-AF risk community-dwelling individuals.

OPTIMISE-1 is a multicentre, pragmatic, prospective, randomised, open-label, blinded-endpoint strategy trial that will recruit 138 participants aged 30 years or older, with a high FIND-AF risk score and previously enrolled in the FIND-AF pilot study (NCT05898165), to be randomised 1:1 to a specialist-led care intervention or usual care. The primary endpoint is a composite of initiation or increase of guideline-directed CRMP therapies. The secondary endpoints are the components of the primary endpoint, time to primary endpoint, diagnosis of new CRMP diseases or risk factors, time to diagnosis of new CRMP diseases or risk factors, initiation or increase of guideline-directed CRMP therapies for participants with recorded CRMP disease, initiation or increase of guideline-directed CRMP therapies for participants with newly diagnosed CRMP disease and change in participant-reported quality of life.

The study has ethical approval (the North East & North Tyneside 2 Research Ethics Committee reference 24/NE/0188). Findings will be announced at relevant conferences and published in peer-reviewed journals in line with the Funder’s open access policy.

Clinicaltrials.gov NCT06444711.

Advancing equity, diversity and inclusion in health research trials is essential for improving health outcomes among priority populations. While evidence increasingly highlights the importance of cultural diversity in research trial leadership and participation, evidence-based strategies for enhancing this remain limited. This article outlines approaches to strengthen Aboriginal and Torres Strait Islander involvement in health research trials, drawing on insights from community engagement at the Darwin (Northern Territory) trial site of the Australian Fans in Training (Aussie-FIT) project.

Community engagement at this site aimed to (1) build mutually beneficial relationships with community leaders, specifically Aboriginal and Torres Strait Islander men; (2) codesign engagement standards to enhance the quality of engagement with these leaders and more broadly with local community members and stakeholders. A culturally diverse community advisory group was established, which codesigned engagement standards tailored to community needs and preferences.

While the codesigned standards supported Aboriginal and Torres Strait Islander trial leadership and participation during the trial, the extensive consultation needed to build cross-cultural relationships and develop the standards meant they were finalised only after trial recruitment had ceased. As a result, researchers were unable to fully implement them in the early stages of the trial.

This paper shared and critically discussed approaches used in the early stages of the Aussie-FIT trial to foster more equitable and inclusive practices in research trials. Implementation of these approaches and community-informed recommendations has the potential to enhance research quality, build trust with priority populations and address participation inequities, thus supporting effective trial design and improved health outcomes.

This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623000437662).

To describe diagnostic and management characteristics of acute rheumatic fever (ARF) among participants in the ‘Searching for a Technology-Driven Acute Rheumatic Fever Test’ study, in order to answer clinical questions and determine epidemiological and practice differences in different settings.

Multisite, prospective cohort study.

One hospital in northern Australia and two hospitals in New Zealand, 2018–2021.

143 episodes of definite, probable or possible ARF among 141 participants (median age 10 years, range 5–23; 98% Indigenous).

Participant characteristics, clinical, biochemical and echocardiographic data were explored using descriptive data. Associations with length of stay were determined using multivariable regression analysis.

ARF presentations were heterogeneous with the most common ARF ‘phenotype’ in 19% of cases being carditis with joint manifestations (polyarthritis, monarthritis or polyarthralgia), fever and PR prolongation. The total proportion of children with carditis was 61%. Australian compared with New Zealand participants more commonly had ARF recurrence (22% vs 0%), underlying RHD (48% vs 0%), possible/probable ARF (23% vs 9%) and were underweight (64% vs 16%). Erythrocyte sedimentation rate (ESR) provided an incremental diagnostic yield of 21% compared with C reactive protein. No instances of RHD were diagnosed among participants in New Zealand. Positive throat Group A Streptococcus culture was more common in New Zealand than in Australian participants (69% vs 3%). Children often required prolonged hospitalisation, with median hospital length-of-stay being 7 days (range 2–66). Significant predictors for length of stay in a multivariable regression model were valve disease (adjusted OR (aOR) 1.56, 95% CI 1.23 to 1.98, p

This study provides new knowledge on ARF characteristics and management and highlights international variation in diagnostic and management practice. Differing approaches need to be aligned. Meanwhile, locally specific information can help guide patient expectations after ARF diagnosis.