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.

To use best practices in pharmacoepidemiology to assess the association between new use of brain-penetrant calcium channel blockers (BP-CCBs) compared with use of non-brain-penetrant CCBs (NP-CCBs) and the incidence of neuropsychiatric outcomes.

Retrospective comparative cohort study.

Secondary data from nine claims and electronic health record databases from across the globe were used.

First use of a CCB was the index date. There were 1.2 million BP-CCB patients and 9.3 million NP-CCB patients identified across all databases, with 881 758 matched in each group.

Patients were categorised as either initiating BP-CCBs or NP-CCBs. On-treatment and intention-to-treat analyses were conducted. Large-scale propensity models were used to match cohorts and control for observed confounding. Cox models were used to analyse the time to incident neuropsychiatric disorders. Negative control outcomes were used to calibrate estimates, CIs and p values to account for residual confounding. Diagnostics were used to assess the validity of the analysis.

The time to first diagnosis of schizophrenia, schizoaffective disorder, major depressive disorder (MDD) and bipolar disorder was assessed independently. HRs compared the BP-CCB group to the NP-CCB group.

For the outcome of incident MDD in the intention-to-treat design, the meta-analytic HR (95% CI) was 1.02 (0.97, 1.08). Meta-analytic HRs for bipolar disorder (1.04 (0.96, 1.13)), schizophrenia (1.05 (0.94, 1.18)) and schizoaffective disorder (1.04 (0.87, 1.23)) showed similar null effects. The on-treatment analysis was largely consistent: MDD (1.01 (0.96, 1.06)), bipolar (1.05 (0.86, 1.27)), schizophrenia (1.09 (0.87, 1.38)) and schizoaffective (1.00 (0.71, 1.40)).

There was no evidence of an association with any of the neuropsychiatric conditions of interest between use of BP-CCB and NP-CCB. This does not rule out the potential beneficial effect of CCB formulations and doses targeted specifically for the brain rather than the cardiovascular system.

Peritoneal dialysis (PD) is a widely used renal replacement therapy for chronic kidney disease patients, yet malnutrition remains a common complication linked to poor outcomes. Nearly 40% of PD patients in China are malnourished, with serum albumin levels below 35 g/L. Amino acid-based peritoneal dialysis solutions (AA-PDS), which replace glucose with amino acids as the osmotic agent, have been used globally for decades to improve nutrition and reduce peritoneal damage, but they were introduced to mainland China only in 2022. This study aims to evaluate the efficacy and safety of AA-PDS in improving nutritional status and clinical outcomes among malnourished PD patients in mainland China, providing a potential new therapeutic option for this population.

This multicentre, open-label, prospective, parallel-controlled study will enrol patients with end-stage kidney disease who were stable on PD for more than 3 months. A total of 500 eligible patients will be divided into the intervention group undergoing PD once every morning using 2.0 L of amino acid (15) PD solution and the control group using conventional PD solution (lactate) in a 4:1 ratio based on their willingness and clinical needs. Our primary outcome is serum albumin, while other nutritional indicators, including serum prealbumin, serum transferrin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and ultrafiltration volumes are considered secondary outcomes. Information such as demographics, clinical and biochemical characteristics, examination indicators, anthropometry measurements and Subjective Global Assessment scores will be collected at baseline, 1 month, 3 month and 6 month follow-up. Statistical analysis will be conducted using SAS V.9.4 or higher versions. All statistical tests are conducted through the two-tailed test, and a p value≤0.05 will be considered statistically significant. The description of quantitative indicators will be used in calculating the number of cases, mean, SD, median and IQR method. The classification indicators will be used to describe the number of cases and percentages (frequency and frequency rate).

This multicentre study obtained ethical approval from the lead ethics committee at the First Affiliated Hospital of Zhejiang Chinese Medical University (approval no.: 2024-KLS-379-02). Additionally, each participating site provided local ethical approval or a formal waiver, as required by their institutional policies. The results will be reported in a peer-reviewed journal and a relevant academic conference.

ChiCTR2400090896.

Acute pain following pulmonary surgery can affect the recovery process of patients. The use of intrathecal morphine (ITM) injections offers a long-lasting analgesic effect, but its clinical application remains controversial. This study aims to investigate the impact of combining bupivacaine with ITM injections on the quality of postoperative recovery in patients who have undergone pulmonary surgery.

This multicentre, randomised, double-blind, controlled trial will enrol 254 patients undergoing elective lung surgery, who will be randomly assigned in a 1:1 ratio to either group IT (receiving an intrathecal injection of 3 mg bupivacaine and 0.25 mg morphine before general anaesthesia induction) or the control group (C group). The primary outcome includes postoperative recovery quality on day 1 (quality of recovery, QoR-15), with secondary outcomes encompassing postoperative recovery quality on days 2 and 3 (QoR-15), pain scores within 72 hours postoperatively, analgesic rescue, intraoperative haemodynamic parameters, opioid consumption, postoperative adverse reactions, recovery metrics, complications, chronic pain incidence and sleep quality.

The results will be disseminated through peer-reviewed publications. This study protocol (V.2.0, 30 October 2024) involves human participants and has been approved by the Ethics Committee of Affiliated Hospital of Yangzhou University (number 2024-08-02-2), Taicang Hospital Affiliated to Soochow University (number 2025 SR-041) and Yichang Central People’s Hospital (number 2024-513-02). Each individual who agrees to participate in the research will provide written informed consent after the objectives and procedures of this study are explained to them.

ChiCTR2400092935. Registered on 26 November 2024.

Artificial intelligence (AI) is rapidly evolving, offering an expanding suite of capabilities that go beyond the traditional focus on prediction and classification. Generative AI (GenAI) and agentic AI could create transformative practices to support real-world evidence (RWE) generation for health research by streamlining studies, accelerating insights and improving decision-making. However, there is no published overview available describing the range of applications in RWE generation. This review aims to describe where and how genAI and agentic AI are applied across the domains of healthcare research tasks for RWE generation. Additionally, to map applications by tasks and methods across the product lifecycle continuum, and to identify emerging gaps and opportunities.

This Living Scoping Review (LSR) will include studies reporting an application and/or evaluation of genAI or agentic AI applied to one or more RWE generation research tasks. Searches will be conducted in Embase, MEDLINE and additional sources (eg, grey literature). Citations will be independently screened by two human senior reviewers for a substantive training dataset and a commercially available screening algorithm (Robot Screener) will complete screening with a human reviewer. The LSR will include reports of studies (primary or reviews) describing and/or evaluating the application of any genAI model for RWE generation in healthcare, in English, published from 1 January 2025 to the date of search. Data will be extracted from all studies included in the LSR by one independent senior reviewer using a piloted template, with 10% quality check by a second senior reviewer. Descriptive statistics will be used to summarise the applications of genAI per RWE research task, and the results of genAI evaluations. Thematic analysis will be used to describe genAI application patterns, trends, gaps and opportunities. The LSR protocol and reports will be updated annually, and findings will be published on a publicly available website (eg, ISPE—the International Society for Pharmacoepidemiology).

Ethical approval is not required due to use of previously published data. Planned dissemination includes peer-reviewed publication, presentation and short summaries.

Microcirculatory dysfunction drives the end-organ pathophysiology of circulatory shock but is not reflected within existing clinical indices of perfusion, such as blood pressure. The choroidal vasculature of the retina can be measured non-invasively and we hypothesised that this may reflect dysfunction in other organs. We tested the feasibility of measuring the choroid in intensive care and explored associations between choroidal measurements and clinical parameters.

A pilot study of optical coherence tomography conducted in a sample of general intensive care unit (ICU) patients.

A tertiary mixed ICU within the UK.

15 patients were recruited. One patient was excluded following withdrawal of active treatment. 12/14 (86%) of the remaining patients had successful baseline imaging and 6 (40%) of these had follow-up imaging within intensive care. These patients had a mean age of 56.3 years, were 71% (10/14) male and mean Acute Physiology and Chronic Health Evaluation 2 (APACHE2) score on ICU admission was 20.4.

Choroidal anatomy, including choroidal and suprachoroidal thickness, as well as volumetric analysis of intrachoroidal blood vessels, was assessed using automated image segmentation along with clinical, physiological and biochemical data at ICU admission and after an interval of 12–72 hours. Feasibility and safety data were assessed throughout ICU admission.

Baseline choroidal vascular index and choroidal thickness were positively associated with fluid balance, and negatively with APACHE2 score, haematocrit and albumin content. A measurable suprachoroidal space was seen in nine (75%) patients (range 25.0–110.0 microns) and was inversely associated with heart rate. There was substantial intraindividual variation in choroidal measurements over time. There were no safety concerns.

Measuring the choroid is feasible in patients with Intensive Care Society Level 2 or Level 3 requirements. The suprachoroidal space may be markedly enlarged in these patients. Exploratory associations with systemic variables suggest that the choroid may provide information about the microvascular function of other major organs. Size and change of choroidal measurements may reflect perfusion pressure and vascular leakage.

Adnexal torsion is a gynaecological emergency in which prompt diagnosis and management are critical to preserving ovarian function. However, the clinical presentation is often non-specific, and diagnosis primarily relies on pelvic ultrasound, a modality with limited sensitivity that can lead to misdiagnosis and unnecessary surgery. Contrast-enhanced ultrasound (CEUS) has emerged as a promising imaging technique that may enhance diagnostic accuracy by better characterising adnexal vascularisation.

The aim of this study is to assess whether the addition of CEUS to standard diagnostic procedures can reduce the rate of unnecessary emergency surgeries. Specifically, we compare two diagnostic strategies in cases of high clinical suspicion of adnexal torsion: the current standard approach versus an experimental strategy incorporating CEUS. The primary outcome is the rate of inappropriate surgical interventions, defined as emergency surgery performed within 6 hours without intraoperative confirmation of torsion.

This is a prospective, open-label, multicentre, randomised (1:1), controlled, superiority trial. A total of 256 women presenting with a high clinical suspicion of adnexal torsion will be enrolled over a period of 36 months. Participants will be randomly assigned to either the standard diagnostic strategy or an experimental strategy that includes CEUS. The primary endpoint is the proportion of emergency surgical procedures (performed within 6 hours of hospital admission) in which adnexal torsion is not confirmed.

The study was approved by the French Ethics Committee, the CPP (Comité de Protection des Personnes) on 28 October 2024. The results of this study will be published in peer-reviewed journals and presented at relevant national and international conferences. The ethical approval number from the CPP is 6115.

NCT06677554; 2024-511720-13-00.

Sodium-glucose cotransporter (SGLT) inhibitors have shown substantial benefit in reducing cardiovascular and kidney events across diverse clinical populations, but the underlying physiological mechanisms remain unclear. However, existing mechanistic studies on renal and cardiovascular haemodynamics show variability in design, have limited statistical power and yield inconsistent outcomes, thus limiting the ability to draw generalisable conclusions. To address this gap, we conducted a systematic review and proposed the first meta-analysis to aggregate individual participant-level data from mechanistic studies to identify consistent physiological patterns and enhance understanding of the therapeutic effects of SGLT inhibition.

Gold-standard measured glomerular filtration rate (mGFR) was selected as the primary outcome for this systematic review, which aimed to identify all completed mechanistic studies investigating the effects of SGLT inhibition. Electronic databases including Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; and Cochrane Central Register of Controlled Trials were searched using a detailed search strategy. In total, 24 studies (n=1296) were identified. This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Key variables including demographics, medical history, concomitant medications, vital signs, mGFR, renal haemodynamics, urine and plasma biochemistry, tubular sodium handling, echocardiography, cardiac output monitoring, arterial stiffness and fluid volume will be extracted. A one-stage individual participant data meta-analysis under a Bayesian framework will be conducted, using hierarchical models to simultaneously analyse data from all eligible studies. The risk of bias due to missing results will be assessed. Sensitivity analyses and subgroup evaluations will be incorporated to explore sources of heterogeneity and assess robustness of findings.

Ethics approval was obtained from University Health Network, Toronto, Canada. Findings from the Mechanisms of SGLT Inhibitor Action and Physiological Mediators (MOSAIC) meta-analysis will be published in peer-reviewed journals and results will be disseminated at scientific conferences.

CRD420251001413.

To investigate the associations of oxidative balance score (OBS) with all-cause mortality, cardiovascular mortality and cardiovascular disease (CVD) incidence in two large, population-based cohorts.

Cohort study and cross-sectional study were used.

The US National Health and Nutrition Examination Survey (NHANES) and the UK Biobank.

A total of 33 566 adults from NHANES (1998–2018) and 55 760 adults from the UK Biobank were included.

All-cause mortality, cardiovascular mortality and CVD. Mortality outcomes were ascertained through national death registries. Prevalent CVD was identified in NHANES through questionnaire, and incident CVD events were identified in the UK Biobank using linked hospital admission and death registry data.

Higher OBS was consistently associated with lower all-cause and cardiovascular mortality in both cohorts. In NHANES, participants in the highest OBS quartile (Q4) had a 39% lower risk of all-cause mortality (adjusted HR: 0.61, 95% CI 0.52 to 0.72) and a 45% lower risk of cardiovascular mortality (adjusted HR: 0.55, 95% CI 0.41 to 0.74) compared with those in Q1. Similarly, in the UK Biobank, Q4 was associated with an 18% lower risk of all-cause mortality (adjusted HR: 0.82, 95% CI 0.74 to 0.91) and a 41% lower risk of cardiovascular mortality (adjusted HR: 0.59, 95% CI 0.4 to 0.87). In NHANES, Q4 was associated with lower odds of prevalent CVD (adjusted OR: 0.56, 95% CI 0.46 to 0.67), whereas in the UK Biobank, Q4 was associated with a 19% lower risk of incident CVD during follow-up (adjusted HR: 0.81, 95% CI 0.74 to 0.9). Subgroup analyses in NHANES indicated heterogeneity by ethnicity and socioeconomic status, whereas associations in the UK Biobank followed an L-shaped pattern with a flattening of estimated risk at moderate OBS levels.

Higher OBS was associated with more favourable mortality and cardiovascular outcomes. These findings indicate that OBS is a composite indicator associated with cardiovascular health at the population level.

Urgent and emergency care (UEC) systems in England face unprecedented pressures, with record accident and emergency attendances, persistent breaches of ambulance response targets and poorer outcomes for time-sensitive conditions. National UEC recovery plans have introduced multiple innovations—such as same-day emergency care, virtual wards and specialty hubs—to manage these pressures and improve patient flow. Rural coastal areas are particularly vulnerable to excessive demand due to higher levels of deprivation, older populations with complex health needs, seasonal surges that generate unpredictable demand and challenges in attracting and retaining staff. Following the Chief Medical Officer’s 2021 Annual Report, funding research and developing bespoke solutions to manage UEC demand and address geographical disparities has been recognised as a national priority. The Elevate study responds to this priority by identifying and evaluating innovative models of UEC in rural coastal communities in England.

The Elevate study is a 30-month, mixed-methods evaluation that comprises three interlinked work packages: (1) National service mapping—outlining provision of innovative models of UEC in rural coastal areas of England. This will be developed through document review and interviews with regional and national service leaders. (2) Quantitative analysis—quasiexperimental and longitudinal approaches will use National Health Service (NHS) England’s Emergency Care Data Set and linked routine NHS datasets to evaluate the impact of UEC models on health and process outcomes. Standard and bespoke metrics will be developed and used to assess performance. (3) Qualitative case studies—up to 12 case studies of UEC models in rural coastal communities. Interviews with patients and staff and non-participant observation will explore how and why different UEC models influence patient experience, clinical outcomes, resource use and the workforce. Findings will be integrated using the Consolidated Framework for Implementation Research to identify components of UEC models that are effective, scalable and sensitive to local context,

Ethical approval for qualitative components was granted by the North of Scotland Research Ethics Committee (25/NS/0099). Dissemination will include peer-reviewed publications, policy briefs, creative media and community engagement activities to ensure findings are communicated inclusively and effectively to policymakers, health and social care practitioners and the public.

Research Registry (researchregistry11126).

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

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

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

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

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

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

To assess the levels of knowledge, attitudes and practices (KAP) toward skin cancer prevention among Malaysian adults and to examine differences in KAP across socio-demographic groups.

Cross-sectional online survey.

Community-based study conducted in Malaysia using social media recruitment.

A total of 386 adults aged ≥18 years residing in Malaysia. Most participants were young adults (86.3%), female (55.4%) and of Chinese ethnicity (65.5%). Healthcare professionals were excluded.

Primary outcomes were levels of knowledge, attitude and preventive practices toward skin cancer, measured using the validated KAP-SC-Q (Knowledge, Attitude and Practice of Skin Cancer Questionnaire) and categorised as poor, moderate or good. Secondary outcomes included differences in KAP across socio-demographic and clinical characteristics, analysed using independent t-tests and ² tests.

Over half of participants demonstrated poor knowledge of skin cancer (56.0%) and the vast majority showed inadequate preventive practices (84.2%), while attitudes toward skin cancer were predominantly positive (62.4%). Significant differences in mean KAP scores and categorical levels were observed across several socio-demographic variables. Participants with tertiary education had higher knowledge (14.32 vs 12.61) and attitude scores (20.01 vs 15.95; p

Malaysian adults exhibited limited knowledge and very poor preventive practices toward skin cancer despite generally positive attitudes. These findings highlight substantial gaps between awareness and behaviour and support the need for targeted public health interventions to correct misconceptions, improve risk perception especially in high-risk groups and promote effective ultraviolet protection behaviours.

Disasters can have a disproportionate impact on highly vulnerable hospitalised patients. Managers preparing hospital networks for disasters play an important role in enhancing networks’ readiness by creating disaster plans and imparting that knowledge through training and simulation exercises. The objective of this research was to uncover how those working in disaster preparedness roles in Australian hospital networks perceived the challenges that they face while ensuring adequate preparation for disasters.

A qualitative study design was employed which involved purposive sampling of Australian hospital network professionals responsible for disaster preparedness. Thematic analysis of data collected through individual online interviews generated prominent challenges of disaster preparedness in Australian hospital networks.

Local hospital networks across Australia

Twenty-six disaster preparedness managers, including hospital executives, disaster managers, emergency management coordinators and business continuity managers from 23 hospital networks located in five Australian states and one territory, participated in semi-structured online interviews. Interview transcripts were coded through an iterative inductive thematic analysis process to synthesise the predominant challenges faced by these participants when preparing their hospital networks for disasters.

Participants reported four challenges: staff’s limited interest in preparedness, budgetary constraints, staffing issues and ambiguous relationships with state and national health departments. They also presented four related solutions: capitalising on interest after disasters, attracting funding with evidence from prior disasters, facilitating staff’s availability for disaster training and specifying network-government relationships for accountability.

Disasters, although infrequent, are known to occur and can be catastrophic, yet those working in hospital network disaster preparedness roles encounter limited availability of wider staff for training and low interest in disaster planning. The sudden onset of a disaster can take a heavy toll on patients if hospitals’ staff are not sufficiently trained in disaster response or are not aware of the disaster plan. By identifying the perceptions of managers to disaster preparedness, this research presents specific challenges that hospital networks can address to improve awareness and preparation.