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.

Sympathetic activation is the hallmark of cardiac disease, driving disease progression and triggering ventricular arrhythmia (VA). Despite optimal medical therapy, many patients experience recurrent VAs refractory to medical therapy, leading to repetitive implantable cardioverter defibrillator (ICD) therapy, worse quality of life and adverse outcomes. Cardiac sympathetic denervation (CSD) through surgical removal of the stellate ganglia is an effective treatment for refractory VAs but carries a high complication rate. We hypothesise that high precision image guided radiotherapy can be used to target the stellate ganglia to achieve CSD non-invasively.

RADIO-STAR (hypofractionated radiotherapy to the stellate ganglia for ventricular arrhythmia) is a first-in-human, phase 1 safety and dose finding study of radiotherapy to the stellate ganglia in patients with recurrent VAs. Patients with structural heart disease requiring recurrent ICD therapy for VAs are invited to undergo radiotherapy bilaterally to their stellate ganglia with a predetermined sample size of n=13. Radiotherapy dose will be determined by a prespecified dose escalation protocol. The primary outcome is safety defined as any treatment-related grade 3–5 toxicity occurring within 6 months of radiotherapy treatment, as defined by the Common Terminology Criteria for Adverse Events or any treatment-related side effects detected on patient symptom questionnaires and clinical examination during study visits. Secondary outcome measures to evaluate feasibility and efficacy include ability to safely deliver radiotherapy and consequent changes in circulating catecholamines and neuropeptide-Y, heart rate variability, structural changes in the stellate ganglia on MRI imaging and ICD therapy burden.

This study has received ethical approval by the South Central—Oxford B Research Ethics Committee (REC/SC/0005). Study findings will be submitted for publication in peer-reviewed scientific journals and presented at national and/or international scientific conferences.

ISRCTN49861434.

Type 2 diabetes mellitus has been associated with an increased risk of cognitive decline and dementia, with patients being 1.5–2 times more likely to develop these conditions. While both sodium-glucose co-transporter 2 (SGLT2) inhibitors and thiazolidinediones (TZDs) have shown potential neuroprotective effects in previous studies, their comparative effectiveness for preventing neurodegenerative outcomes has not been established. This study aimed to compare the risk of stroke, dementia and Alzheimer’s disease (AD) between patients treated with SGLT2 inhibitors and those treated with TZDs.

Multicentre, retrospective, observational, new-user, active-comparator cohort study.

Electronic health record-based databases from 11 secondary and tertiary institutions in South Korea from 1 January 2014 to 31 July 2025. The study period began in 2014, following the post-marketing surveillance initiation of SGLT2 inhibitors in Korea (November 2013), to ensure adequate drug availability and clinical adoption.

Patients aged 40 years or older who were newly prescribed either SGLT2 inhibitors or TZDs without prior exposure.

Propensity score matching (1:1) was performed using sex as the primary covariate due to data availability constraints in the Observational Medical Outcomes Partnership Common Data Model framework. The HRs with 95% CIs were measured via Cox regression analysis.

The study analysed 24 172 matched pairs for stroke outcomes (40 483 person-years in the SGLT2 inhibitor group and 39 363 person-years in the TZD group), 25 111 matched pairs for dementia (41 924 person-years in the SGLT2 inhibitor group and 40 726 person-years in the TZD group) and 25 237 matched pairs for AD (42 139 person-years in the SGLT2 inhibitor group and 40 895 person-years in the TZD group) across 11 participating hospitals. After a 1:1 propensity score matching, the SGLT2 inhibitors showed no significant difference in stroke risk (HR 1.18, 95% CI 0.62 to 2.23, p=0.62), while having significant reductions in dementia risk (HR 0.66, 95% CI 0.45 to 0.98, p=0.04) and AD risk (HR 0.54, 95% CI 0.35 to 0.83, p=0.005). Moreover, these protective effects for neurodegenerative outcomes were shown to be consistent across multiple hospital sites.

SGLT2 inhibitors are associated with a reduced risk of dementia and AD compared with TZDs in patients aged 40 years or older with type 2 diabetes and have neutral effects on stroke risk. These findings confirm the potential selective neuroprotective benefits of SGLT2 inhibitors for neurodegenerative outcomes, which may inform therapeutic decision-making for diabetic patients at risk of cognitive decline.

Patients in intensive care units (ICUs) and their families face existential physical, psychosocial and spiritual distress. Integrating palliative care (PC) into ICU care may benefit patients, relatives and ICU clinicians. Prior PC studies have shown a reduction in ICU length of stay (LOS) and distressing symptoms without altering overall mortality. A shorter ICU LOS may alleviate the burden for patients and relatives and help optimise the use of limited intensive care resources. PC in the ICU, however, remains underused, partly due to limited access and knowledge of ICU clinicians. Also, robust data regarding the effectiveness and cost-effectiveness of PC treatment in the ICU are scarce. We established the ‘enhancing palliative care in ICUs’ (EPIC) study to implement a system-based harmonised practice model across European ICUs. The aim is to investigate if early integration of PC via telemedicine, clinician education and bedside tools is effective and cost-effective, ultimately benefiting patients, relatives and ICU clinicians.

This multicentre, controlled, cluster-randomised, non-blinded stepped-wedge design trial with crossover phase aims to recruit around 2,000 patients from five European countries. All adult patients admitted to participating ICUs—with an ICU LOS exceeding 72 hours, where cancer is not the primary cause of critical illness, and who are not expected to die within the next 24 hours—are screened for the need for specialised PC based on the attending physician’s judgement. This judgement is triggered by the presence of one or more of the following: (1) significant disagreement among ICU team members and/or relatives about the appropriateness of current ICU treatment, (2) considerations of limiting life-sustaining therapy or (3) the anticipation that a specialised PC consultation may benefit the patient, their relatives or the ICU team. Patients identified as needing specialised PC and their relatives are then enrolled after obtaining written informed consent.

The complex intervention consists of (a) a blended-learning programme to foster knowledge and attitude about PC among ICU clinicians, (b) bedside tools, including a checklist to identify patients in need of PC and a factsheet and (c) standardised telemedical consultations from trained EPIC interventionists. Patient and relative follow-up is conducted 3 months post-ICU discharge. Outcomes include clinical measures (including ICU LOS (primary outcome), severity of critical illness, invasive treatments and health-related quality of life), economic endpoints (resource use, costs, cost–consequence situation, cost-effectiveness), ICU clinician burnout and distress, and patient and family perception about the quality of symptom management, care and communication. Endpoint analyses will employ generalised linear mixed models, accounting for the clustered data structure and stepped wedge design.

EPIC complies with the Declaration of Helsinki and has been approved by all local ethics committees. A decision-making structure is established to ensure trial procedures are carried out according to Good Clinical Practice. Study findings will be published in peer-reviewed journals and communicated to participants, healthcare professionals and the public. Sets of anonymised study data will be made available following Findable, Accessible, Interoperable, and Reusable principles.

NCT06605079.

Clinical learning is central to undergraduate nursing education, with preceptors translating theoretical knowledge into practical competence. Preceptors’ clinical teaching behaviours (CTBs) shape students’ confidence, skill development and professional identity. While CTBs have been studied globally, evidence from Pakistan is limited, highlighting the need for research that offers a comprehensive, integrated perspective.

To investigate preceptors’ CTBs by evaluating students’ perceptions, exploring preceptors’ experiences, and integrating these insights to identify points of agreement and discrepancy for a thorough understanding of CTB.

Convergent mixed-methods study, with quantitative and qualitative data collected concurrently, analysed independently, and integrated using the Pillar Integration Process.

A tertiary teaching hospital in Islamabad, Pakistan, providing clinical placements for undergraduate nursing students.

All undergraduate nursing students (n=50) engaged in clinical practicum and their preceptors (n=14) were included through census sampling. Students completed the CTB Inventory (CTBI) following student-preceptor interactions. Preceptors participated in semistructured face-to-face interviews.

Quantitative data from 44 undergraduate nursing students, based on 88 student–preceptor encounter observations, showed generally positive ratings of preceptors’ CTBs across all six CTBI domains (mean scores range: 3.48–3.97 on a 5-point scale). The highest-rated domain was guiding interprofessional communication (M=3.97, SD=0.89), with 85.2% of students agreeing that preceptors demonstrated professional role modelling. The lowest-rated domain was showing concern and support (M=3.48, SD=0.89), with only 31.8% of students agreeing that preceptors expressed concern about students’ lives outside work. Qualitative interviews with 14 preceptors identified six categories reflecting clinical teaching practices, including commitment to teaching, learning environment creation, instructional strategies, communication facilitation, feedback and evaluation, and supportive behaviours. Integration of quantitative and qualitative findings yielded six overarching themes, demonstrating convergence in professional role modelling, structured teaching, scaffolded learning, feedback and communication practices. Divergence was observed in the area of personalised support, with qualitative findings explaining lower quantitative ratings through heavy workloads, competing clinical responsibilities and limited protected teaching time.

Preceptors play a critical role in shaping undergraduate nursing students’ clinical competence and professional identity. Enhancing preceptor training, institutional recognition and supportive policies can strengthen teaching effectiveness and optimise student learning outcomes.

Racialised immigrant communities in Western nations face disproportionate risks for sexually transmitted and blood-borne infections (STBBIs) due to systemic barriers, including racism, stigma and limited access to culturally appropriate care. While the need is well-established, a comprehensive synthesis of effective, culturally responsive sexual health interventions is lacking. This scoping review aims to map the available evidence on sexual health intervention needs and protective factors of racialised immigrants, and to identify and describe existing culturally appropriate programmes in Western nations.

The review will follow the JBI methodology for scoping reviews and be reported as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A systematic search strategy, developed and peer-reviewed by a health sciences librarian, will be executed in MEDLINE, Embase, CINAHL and Scopus, alongside grey literature sources, with no date limit. Two independent reviewers will screen titles/abstracts and full texts against the inclusion criteria. Data will be extracted using a standardised tool, analysed via narrative synthesis and framed by a socio-ecological model to categorise interventions across individual, interpersonal, community and structural levels.

Ethical approval is not required for this review. Findings will be disseminated through a peer-reviewed publication, academic presentations and tailored summaries for community organisations and policy-makers to ensure practical application.

Open Science Framework (https://osf.io/9qah6).

The functional resonance analysis method (FRAM) is increasingly used to analyse healthcare processes. FRAM uses four steps to analyse a process and its potential variability. We systematically reviewed studies using FRAM in healthcare on how the four steps in FRAM are reported, defined and supported by data.

Systematic review following the preferred reporting items for systematic reviews and meta-analyses 2020 guidelines.

Web of Science, PubMed, Embase, Scopus, PsycINFO, Dimensions and Lens were searched up to December 2025.

All peer-reviewed studies using FRAM in a healthcare context that presented a FRAM visualisation were included. The papers had to be written in English.

Two independent reviewers screened titles and abstracts, and subsequently the full text of selected papers. Data was extracted reporting on the steps of FRAM, how functions were supported by data, and the functions and couplings of the visualisations.

Sixty-eight papers were included, of which 20 (29%) reported at least one aspect of all four steps in FRAM. While most studies (85%) described how functions were supported by data, the methods used varied widely. Terminology was interpreted differently concerning variability, the output of variability and the effect of combined variability.

Most FRAM studies in healthcare do not report all steps of FRAM, and interpretations of key terms differ. FRAM studies should more clearly describe which steps of the method are conducted, and how data is collected and analysed. Refinement of FRAM guidelines, particularly on data use and terminology, would enhance consistency and comparability across studies.

CRD42024592858.

Obesity affects over a quarter of the UK population and can lead to serious health issues. NHS Specialist Weight Management Services (WMS) offer treatments including lifestyle advice, psychological support and medications, but access and availability vary by region. Although around 4 million people could be eligible for NHS Specialist WMS annually, capacity is limited to 35 000, severely limiting overall access for those who need it. While digital technology has started to be used in WMS, more evidence is needed to confirm its long-term effectiveness, acceptability and cost-effectiveness. This study explores the use of Gro Health W8Buddy, a digital platform and app providing remote Specialist WMS. It aims to determine the long-term health benefits of remote WMS pathway Gro Health W8Buddy compared with standard NHS WMS delivered in hospitals, and to improve patients access to services.

The study is a real-world evaluation with observational data collection. We will recruit 450 study participants from four NHS specialist WMS who will choose either standard NHS WMS or the digital pathway Gro Health W8Buddy. Participants are being given the option to choose their pathway to generate real-world evidence. We will measure and analyse health outcomes including weight loss, time taken to be treated and cost-effectiveness, at 18 months and follow up at 24 months for later analysis (outside of this core funding). We will gather experiential data from patients and healthcare professionals through surveys, observation and interviews.

Ethical approval has been obtained from NHS Health Research Authority (HRA) and Health and Care Research Wales (HCRW) (Supplementary Figure 3) (REC reference: 25/EM/0147). Our findings will be disseminated through academic publications, conference presentations and stakeholder engagement.

ISRCTN89168871; Pre-results.

Maternal and child mortality has markedly decreased worldwide over the past few decades. Despite this success, the decline remains unequal across countries and is overall insufficient to meet the Sustainable Development Goals. South Asia and sub-Saharan Africa bear most of the burden of maternal and child morbidity and mortality. Major gaps persist in our understanding of the causes, timing, diagnostic thresholds and risk factors for adverse outcomes in these regions. Addressing these gaps requires new ways to prevent and treat disease, from novel diagnostics to precision public health strategies, all of which rely on high-quality clinical data from diverse populations. The Pregnancy Risk, Infant Surveillance, and Measurement Alliance (PRISMA) Maternal and Newborn Health Study aims to estimate population-level prevalence of morbidities and mortality and to assess biological, clinical and sociodemographic risk among mother–infant pairs in India, Pakistan, Kenya, Ghana and Zambia.

This study is a prospective, open cohort study with a planned recruitment of about 6000 women annually across six research sites in five countries. Participants are pregnant women enrolled less than 20 weeks gestation, as determined by ultrasound, identified through active house-to-house and facility-based surveillance. Robust clinical data will be collected at 12 scheduled study visits during antenatal care, labour and delivery, and through 1 year postpartum. A total of 34 outcomes will be captured. The primary analysis will estimate the burden of adverse outcomes and examine associated risk factors to inform future intervention strategies. Data will also be used to develop normative values for pregnant and postpartum women, as well as predictive models to assess pregnancy risk.

PRISMA received institutional and national ethical approvals. Findings will be published in peer-reviewed open-access journals and disseminated at national and international forums to inform clinical guidelines and public health practice.

NCT05904145.

To explore maternity care providers’ attitudes toward regional centralisation of vaginal breech birth (VBB) care and gather their recommendations for maintaining clinical proficiency.

Exploratory qualitative study using semi-structured interviews and thematic analysis.

10 hospital-based maternity care professionals (nine obstetricians and one clinical midwife), purposively sampled to represent experience and institutional diversity.

10 hospital maternity units in a metropolitan region of the Netherlands.

Key themes describing provider attitudes towards two proposed models of centralised care (mobile breech team, designated referral centre) and alternative strategies.

Three core themes emerged: (1) proficiency—providers valued regular exposure, formal training and peer support, expressing concern that centralisation would reduce overall workforce readiness; (2) organisation—concerns included unequal access, staffing burden, legal risks and inefficiencies in mobile teams and (3) alternatives—participants preferred a regional breech network with shared training, joint video review and expert on-call support.

Maternity care providers opposed full centralisation of VBB, favouring a networked model that distributes expertise and preserves local access. These insights highlight the importance of involving frontline providers in service redesign.

Not applicable.

Values and preferences are key determinants of optimal care, and variability in patient values and preferences often dictates differences in patient management. Clinicians’ views of patients’ values and preferences may differ across cultural aspects and stage of training, but the extent to which this is the case remains uncertain. One key value and preference issue is the trade-off between quantity and quality of life, and this issue is particularly prominent among patients with dementia. We therefore propose to investigate the extent to which physicians’ perceptions of optimal management for patients living with advanced dementia may differ due to cross-cultural factors and stage of medical training.

We will conduct a sequential explanatory mixed-methods study (QUAN -> qual). First, we will administer paper-based or electronic surveys during educational sessions, conferences and rounds to medical students, residents and physicians in ten countries, either in person or online. Following that, a qualitative inquiry, guided by the findings of the quantitative study and the principles of the interpretive description design, will inform an in-depth exploration of the predictive factors identified in the quantitative data analysis.

The Hamilton Integrated Research Ethics Board at McMaster University has approved this study (approval number 2024-17651). We will disseminate our findings in peer-reviewed publications and present results at conferences as oral and poster presentations.