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.

Effective prevention of maternal-fetal transmission of hepatitis B virus (HBV) in highly endemic settings depends on targeting vaccination efforts to key priority groups, including pregnant women. However, the extent of HBV vaccination and determinants of uptake in sub-Saharan Africa (SSA) have not been systematically examined. This systematic review aims to estimate HBV vaccination among pregnant women in SSA and identify the broader factors influencing uptake.

This review will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) guidelines. A comprehensive literature search will be conducted in MEDLINE, Embase, Web of Science, Scopus, African Journals Online and Google Scholar in November 2025. We will include published observational studies that assess HBV vaccination among pregnant women in SSA countries from database inception to October 2025. A meta-analysis will be conducted using random-effects models to pool estimates of HBV vaccination and multivariable-adjusted ORs for vaccination-associated factors. Statistical heterogeneity will be assessed using the I² statistic.

Ethical approval is not required as this review will not involve primary data collection. Findings will be published in a peer-reviewed journal, presented at regional and international public health conferences, and, where applicable, shared with policymakers and health authorities in SSA.

This protocol is registered with the International Prospective Register of Systematic Reviews, registration number CRD420251120357.

To compare elective surgeries rates and waiting times between Indigenous and non-Indigenous patients in Queensland.

Aggregated annual data analysis from July 2013 to December 2022 on elective surgeries and waiting times.

Public hospitals across Queensland.

All patients who had elective surgery in Queensland public hospitals between 2013 and 2022.

Rates and clinically recommended timeframes for elective surgeries.

Between 2013 and 2022, the overall estimated average rate of elective surgeries for Indigenous patients was 286 per 100 000 population, compared with 221 per 100 000 for non-Indigenous patients. Indigenous patients had higher rates of most elective surgeries except plastic and urological surgeries, where non-Indigenous patients had higher rates. Across all urgency categories, the percentages of elective surgery performed within clinically recommended timeframes were similar between Indigenous and non-Indigenous patients.

Our findings may point to the efficacy of specific policy and service delivery innovations undertaken in Queensland. Due to the limitations of our aggregated data, this inference warrants careful interpretation. More studies with disaggregated data are needed.

The rapidly growing population of older adults (individuals aged 65 years and older) presents a new set of challenges for healthcare providers in the emergency department (ED), given the prevalence of severe and life-threatening conditions among this group, such as chronic cancer, Alzheimer’s disease/dementia and congestive heart failure. ED encounters often represent a critical point in an older patient’s trajectory of care and can thus be an important opportunity for various interventions such as palliative care consultation. Therefore, identifying those who will benefit most from palliative care is of high importance, especially in determining the course of future treatment. Thus, we aim to conduct a systematic review assessing the efficacy of palliative care screening in the ED by assessing inpatient length of stay as the primary outcome and quality of life, percentage of hospitalisation and cost of care as secondary outcomes.

This study will use Ovid MEDLINE, Embase, EBSCO CINAHL, Web of Science and Cochrane as databases. The study population comprises adults aged 60 years and older, with no focus on any specific clinical specialty or disease. Patients who have not received palliative care screening will serve as the comparator. Only studies with an applicable comparator will be considered. Studies published from 1 January 2000 to 1 July 2025 will be included.

All articles will be reviewed independently and in duplicate, and every author will participate in the review, data abstraction and conflict resolution process.

Ethical approval is not required as it is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations.

CRD42024562389.

To identify and understand the barriers and enablers influencing medical students’ engagement with research and consideration of academic careers.

This was a mixed-methods explanatory sequential study comprising two surveys (Phase 1 and Phase 2), followed by semistructured interviews (Phase 3).

The School of Medicine at Newcastle University.

All students from all year groups at The School of Medicine, Newcastle University (UK) were invited to participate, with data collected from 343 survey respondents and 25 students in semistructured interviews.

Survey responses from 188 students in Phase 1 (exploratory survey) and 155 students in Phase 2 (general student survey) identified barriers which reflect personal experience (eg, lack of knowledge and confidence), practical constraints (eg, time constraints and academic pressures) and institutional contexts (eg, insufficient research teaching and lack of formal opportunities). Enablers included mentors and other sources of information about research.

Interview data emphasised that academic mentoring relationships are often emergent rather than planned. The limited visibility of research opportunities and of mentors was a significant barrier and perpetuated a culture where research was not normalised within the curriculum. Conversely, enablers included intrinsic motivations (eg, intellectual curiosity and desire to contribute to knowledge) and extrinsic motivations (eg, career advancement). Social dynamics between peer groups emerged, whereby these could act as either a barrier or an enabler, depending on the normalisation of research within their networks.

To enhance engagement with research and promote the attractiveness of a clinical academic career, research should become a ‘normal’ part of undergraduate medical education. Visible integration of research into the undergraduate curriculum, providing structured mentorship programmes and ensuring equitable access to research opportunities will aid this. Addressing these factors may sustain the pipeline of students pursuing clinical academic careers.

To quantify the costs associated with a stepped model of depression care—Integrated Chronic Care Clinics-Depression Module (IC3D)—in rural Malawi.

Cross-sectional cost analysis.

Integrated chronic care clinics (n=14) throughout Neno District, Malawi.

The stepped model of depression care provided behavioural therapy (Problem Management Plus (PM+)) to adults (aged 18+) with moderate depression and joint PM+ and antidepressant therapy (ADT) to those with moderate-to-severe and severe depression. The model incorporated two cost-saving features: treatment was integrated into existing chronic care services within the health system, and PM+ was group-based rather than one-on-one.

We conducted time-driven activity-based costing to quantify the marginal economic cost of implementing PM+ and ADT, inclusive of training and supervision. We measured all costs in 2025 US dollars and quantified costs from a societal perspective—including human resources, infrastructure, equipment, consumables, indirect costs and opportunity costs.

The marginal cost of PM+ was $90 per patient treated for five sessions over 2 months, while ADT was $138 for eight sessions over 8 months. In both instances, human resources (45% from PM+, 52% for ADT) and consumables (30% for PM+, 31% for ADT) represented primary health system cost drivers. In the first year of implementation, 15 002 depression screenings were conducted, 724 adults were evaluated with a diagnostic tool and 398 adults subsequently received care: 263 received PM+ alone, 31 received ADT alone and 104 received both PM+ and ADT. The total cost of introducing operations throughout Neno District was $62 806.

These findings indicate that integrating depression care services into the Malawian health system is financially feasible and successfully reached many individuals with major depressive disorder.

NCT04777006.

The Validating Outcomes by Including Consumer Experience (VOICE) project is developing patient reported experience measure (PREM) tools to collect consumer feedback for Indigenous primary healthcare (IPHC) services’ accreditation and quality improvement processes. This study aimed to explore the views of health service staff about: (1) optimising the feasibility of collection, analysis and interpretation of findings; and (2) resourcing requirements for implementation of the PREM.

A participatory action research qualitative study design, guided by an Indigenous advisory group. Our team of Indigenous and non-Indigenous researchers conducted semistructured focus groups and individual interviews with IPHC staff. Focus groups and interviews were recorded, transcribed and thematically analysed. Multiple sense-making meetings were conducted with the Indigenous advisory group.

Eight partner IPHC services across four Australian states and territories.

All staff were eligible and invited to participate in the study via purposive and snowball sampling. Administrative staff (eg, receptionist, programme facilitator), clinicians/practitioners (eg, general practitioner, nurse, Aboriginal and Torres Strait Islander health workers and practitioners) and service managers (eg, CEO, practice manager) from partner health services participated.

63 staff participated; 44 attended across 13 focus groups, with the remainder participating in individual interviews. The majority of participants were between 35 years and 55 years old (52%), female (66%) and working in frontline IPHC service delivery roles (56%). Equal numbers identified as Indigenous (50%) and non-Indigenous (50%). Many had worked in the Indigenous health and well-being sector for over 10 years (40%). ‘Culturally safe care’ and ‘accountability’ were identified as primary themes and key reasons for gathering consumer feedback. Subthemes identified were ‘Relationships’, ‘trust and respect’, ‘communication about consumer feedback’, ‘timing and frequency of requesting consumer feedback’, ‘health service systems’, ‘health service and staff capacity’, ‘staff skills’ and ‘structure and administration of the PREM’. All themes and subthemes need to be considered for the successful design and implementation of PREMs in IPHC settings.

Many of the issues identified are not currently considered in the process of collecting PREM data for accreditation yet, if addressed, would likely improve the quality and relevance of data collected. The findings from this study will inform the co-design and validation of Indigenous-specific PREM tools to collect consumer feedback. Critically, service and community input will ensure the PREM tools meet service needs for continuous quality improvement and accreditation and reflect the priorities and values of Indigenous peoples.

Over the past decades, interest in second breast-conserving therapy (BCT) has increased due to, among others, advances in radiotherapy techniques. Preoperative partial breast irradiation (PBI) is an experimental treatment for patients with low-risk primary breast cancer. This approach can downstage the tumour and may possibly reduce toxicity and improve cosmetic outcomes compared with postoperative radiotherapy. This study aims to evaluate the feasibility of single-dose preoperative PBI and second breast-conserving surgery (BCS) for patients with an ipsilateral recurrent breast event (IRBE) after previous BCT.

The REPEAT trial is a multicentre, prospective, single-arm trial investigating ablative single-dose preoperative PBI in patients with an IRBE. Eligible patients are ≥50 years, have a unifocal non-lobular invasive breast cancer ≤2 cm, Bloom-Richardson grade 1 or 2, oestrogen receptor-positive, human epidermal growth factor receptor 2-negative and clinically negative axillary lymph nodes. The study plans to enrol 25 patients. Radiotherapy planning will involve the use of CT and MRI in the treatment position. Single-dose PBI of 20 Gy to the tumour and 15 Gy to the surrounding 2 cm of breast tissue will be delivered using a conventional or MR-guided linear accelerator. Tumour response will be monitored preoperatively using MRI and liquid biopsies to identify biomarkers for evaluating radiosensitivity. BCS will be performed 3 (±one) weeks post PBI. The primary endpoint is the incidence of grade 2 or higher treatment-associated acute toxicity within 90 days. Secondary endpoints include the evaluation of acute (grade 1) and late toxicity, radiologic and pathologic response, mastectomy rate, patient-reported outcomes, cosmetic outcome, local, regional and distant recurrence rates, survival outcome and biomarkers in liquid biopsies and tumour tissue. Patients will be followed up to 5 years after PBI.

Ethical approval from the Medical Research Ethics Committee of the Amsterdam UMC has been obtained (NL85983.018.24). The results will be disseminated via peer-reviewed academic journal and presentation at conferences. In addition, summaries will be shared with the participating patients.

The trial was registered prospectively on October 11^th 2024 at clinicaltrials.gov (NCT06640881).