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.

We investigated symptoms reported before and after heart failure (HF) diagnosis and their associations with 3-month hospitalisation and mortality.

To examine associations between symptoms recorded in primary care and short-term hospitalisation and mortality in HF patients.

Landmark analysis using Royston-Parmar survival models at baseline (diagnosis), 6 and 12 months post-diagnosis.

Primary care database (Clinical Practice Research Datalink) linked to hospital and mortality data (1998–2020).

Adults (>40 years) with a first HF diagnosis.

Shortness of breath, ankle swelling, oedema, fatigue, chest pain, depression and anxiety in the 3 months before diagnosis and at 6 and 12 months.

3-month all-cause hospitalisation and mortality; secondary outcomes included HF and non-cardiovascular hospitalisation.

Among 86 882 HF patients (62 742 and 54 555 surviving to 6 and 12 months, respectively), the magnitude of symptom risk varied by timepoint. Specifically, the symptoms with the strongest associations with adverse outcomes were: depression for all-cause hospitalisation at diagnosis (HR: 1.26; 95% CI 1.15 to 1.39) and 6 months (1.46; 1.25 to 1.70); ankle swelling for mortality (1.49; 1.14 to 1.94) at 6 months and SOB for HF hospitalisation (1.18; 1.12 to 1.26) at diagnosis and 12 months (1.99; 1.68 to 2.35).

Symptoms persisted and were more prominent at 6 and 12 months post-diagnosis than at diagnosis.

PRELUCA is a randomised, intervention, non-inferiority study designed to use real-time, longitudinal circulating tumour DNA (ctDNA) measurements to evaluate the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC). The primary outcome is overall survival between the two groups: the standard of care group (computer tomography scan evaluation) and intervention group (ctDNA evaluation).

The inclusion and exclusion criteria align with European Society for Medical Oncology treatment guidelines and permit broad inclusion of NSCLC patients, ensuring ‘real-world’ representativeness. The study uses a tumour-informed method, using baseline next generation sequencing analyses to design patient-specific droplet digital PCR assays, which are run with collected blood samples 1 week prior to the intended treatment, enabling real-time evaluation via ctDNA Response Evaluation Criteria in Solid Tumours.

Inclusion began in July 2023 and patients are now being actively included in five locations across Denmark. Approval by The Committee on Health Research Ethics of Region Zealand was gained on 4 May 2023.

NCT05889247.

To characterise the reporting practices of sequential multiple assignment randomised trials (SMARTs) in human health research.

Scoping review of protocol and primary analysis papers describing SMARTs published between January 2009 and February 2024.

SMARTs are innovative trial designs that allow for multiple stages of randomisation to treatment, with randomization potentially based on a patient’s response(s) to previous treatment(s). They are uniquely designed to develop sequential adaptive interventions (dynamic treatment regimes (DTRs)) to support personalized clinical decision-making over time. Previous reviews have identified inconsistencies in how the design, implementation and results of SMARTs have been reported in published studies. A comprehensive assessment of SMART reporting practices is lacking and necessary for developing standardised SMART-specific reporting guidelines.

We systematically searched multiple databases for SMART-related protocol and primary analysis papers published between January 2009 and February 2024. Title, abstract and full-text screenings were performed by pairs of reviewers, with disagreements resolved by consensus. Data extraction included study characteristics, design elements and analytical approaches for embedded or tailored DTRs. Results were synthesised qualitatively and presented descriptively.

From 5486 screened studies, 103 (59 protocol papers, 16 primary analysis papers, 14 protocol papers with corresponding primary analysis papers) met the inclusion criteria. Most studies targeted adults (62.7% protocols, 62.5% primary analyses, 42.9% protocol+primary analyses) and were primarily conducted in the USA. Behavioural and mental health constituted the most frequent therapeutic domain. While intervention descriptions and re-randomisation criteria were consistently reported, operational characteristics such as blinding (protocols: 64.4%, primary analyses: 62.5%, protocols+primary analyses: 71.4%) and randomisation details (protocols: 55.9%, primary analyses: 37.5%, protocols+primary analyses: 50.0%) were inconsistently documented. Only 46.7% of primary analyses evaluated embedded DTRs, and none explored deeply tailored DTRs.

Despite the increased adoption of SMART designs, substantial reporting variability persists. Most primary analyses underuse the capability of SMARTs to generate data for developing DTRs. SMART-specific standardised reporting guidelines can help accelerate the scientific and clinical impact of SMARTs.

Respiratory infections like influenza and SARS-CoV-2 pose significant global health risks due to their high transmissibility and severity. SARS-CoV-2 has caused over 7 million deaths worldwide, and the Lancet Commission estimates a >20% chance of a similar respiratory virus pandemic within a decade. Schools, often poorly ventilated, are high-risk settings for transmission. While COVID-19 school closures may have reduced transmission, they likely caused learning loss, mental health issues and increased burdens on parents and caregivers. Air purifiers with High Efficiency Particulate Air (HEPA) filters may offer a non-disruptive mitigation strategy, but the evidence to support their effectiveness in reducing viral transmission is weak. This protocol describes a cluster-randomised, parallel, two-arm, group sequential superiority trial with an interim analysis—to allow early stopping for efficacy or futility—to estimate the effect of portable air purifiers with HEPA filters in primary school classrooms on student absenteeism.

This group sequential trial will randomise schools (clusters) 1:1 to intervention or control arms in two stages: winter 2025/2026 (N=32 schools; ~736 students) and winter 2026/2027 (N=30 schools; ~690 students). The study setting is Norway. Eligible schools must have classrooms suitable for portable air purifiers, >10 students in grades 5–7 (typically aged 10–13 years) and principal consent. Intervention and control classrooms will each receive two portable air purifiers with HEPA filters operating at a performance equivalent to 3.0 and 0.3 air changes per hour, respectively, with control purifiers acting as shams. Outcomes will be measured during and at the end of a 12-week period. The primary outcome is student absenteeism, measured as full child days of absence aggregated at the class level. An interim analysis is planned at the end of the first stage, with error-spending O’Brien-Fleming stopping boundaries that are binding for efficacy and non-binding for futility. The primary estimand is the marginal incidence rate ratio of student absences, estimated using generalised estimating equations with a negative binomial model to account for overdispersion. Prespecified stopping boundaries will determine stopping, with efficacy boundaries being binding. Treatment effects will be estimated using cluster-bootstrapped CIs adjusted to provide strong control on overall type I and II error probabilities, and a bias correction will be applied if the trial is stopped early for efficacy. All analyses will follow the intention-to-treat principle. The primary question is whether installing and operating air purifiers with HEPA filters (intervention) reduces student absenteeism due to sickness (primary outcome) compared with sham air purifiers (control). Secondary questions examine whether the intervention reduces teacher absenteeism due to respiratory infections, rate and 12-week risk of self-reported respiratory infections among teachers, and teachers’ perceptions of air quality, compared with sham air purifiers. If the trial estimates a statistically significant effect for the primary outcome, a cost-consequence analysis will evaluate the direct and indirect costs associated with operating air purifiers against the potential benefits of reduced student and teacher absenteeism. A process evaluation will explore mechanisms of effect.

The trial has been approved by the Regional Committees for Medical and Health Research Ethics and the National Research Ethics Committee (ref. 737650). Absence data, routinely collected and fully anonymised at the class level, will serve as the primary outcome and does not require informed consent. Informed consent will be obtained from teachers participating in weekly surveys or interviews. Results will be disseminated to stakeholders, participants and the public through peer-reviewed journals, scientific meetings and social media.

NCT07119333.

Military personnel are a unique population with heightened vulnerability to sexually transmitted infections (STIs), often exhibiting higher prevalence rates than civilians due to demographic, environmental and occupational factors. These vulnerabilities underscore the need for global prevalence estimates to guide effective, evidence-based interventions. This study aims to quantify the global burden of STIs among military personnel, providing a comprehensive and up-to-date assessment.

This systematic review will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines (2020). Using the CoCoPop (Condition, Context, and Population) framework, a comprehensive search strategy will be conducted in MEDLINE, Embase, Global Health and Scopus to retrieve peer-reviewed records published between January 2010 and June 2025. Eligible studies will report numerical STI prevalence data among military personnel. Studies with insufficient information to calculate prevalence or those relying on self-reported STI data will be excluded. Data extraction will include study details, military descriptors, STI prevalence and diagnostic methods. Risk of bias will be assessed using the Joanna Briggs Institute critical assessment tool for prevalence and incidence studies. Prevalence estimates with 95% CIs will be reported for each STI and, where appropriate, pooled for curable STIs. Subgroup analyses will stratify prevalence by geographic region, service status, deployment status and socioeconomic factors. Heterogeneity will be evaluated within predefined subgroups using the I² statistic. Data will be presented in comprehensive tables and visualised with graphical tools, including forest plots for subgroup analyses and pooled estimates.

Ethical approval is not required for this review. The results will be disseminated through a peer-reviewed publication and conference presentations.

CRD42023472113.

The aim of this study was to explore why patients with hard-to-heal ulcers are treated without an aetiological diagnosis, using a grounded theory approach.

The study employed a qualitative semistructured interview design to gain in-depth insights. Data were collected in 2024, and an explanatory model was formed in accordance with grounded theory analysis.

Interviews were conducted with healthcare staff across primary, community and specialist care units in Sweden, encompassing both public and private sectors and representing a wide geographical spread.

The study involved 23 healthcare professionals, including nurses (n=18), assistant nurses (n=2) and physicians (n=3), from 22 healthcare units that participated in a preceding national mapping study. Participants were selected purposively to represent various professional roles and healthcare levels.

The analysis resulted in a theoretical model based on two categories: Healthcare traditions and clinical practices and Clinical governance. The lack of an aetiological diagnosis can be attributed to a traditional division of tasks, where ulcer care falls within the nurses’ domain. As a result, patients often receive treatment without a physician’s involvement, especially in home healthcare. Barriers and enablers for a diagnosis are present on different levels; issues close to the patient as well as structural matters. The results illustrate how healthcare units can be positioned along a scale, from traditional work distribution to evidence-based guidelines.

This study can be used to get a deeper understanding of the challenges of current wound management, where clinical governance can support or undermine the movement from a traditional work distribution towards an evidence-based clinical practice. Furthermore, this study can provide a basis for discussing quality improvement, to obtain good and equal care for patients with hard-to-heal ulcers.

Studies suggest that extreme heat events can have negative effects on mental health. However, characterisation of these effects in urban communities remains limited, and few studies have investigated the potential modifying effects of demographic, clinical and environmental characteristics. The aim of this study is to address this knowledge gap and quantify the impacts of extreme heat on mental health, health service use and mental well-being in vulnerable urban populations.

In this multidisciplinary project, we will assess mental health outcomes in different populations by bringing together two distinct datasets: electronic health record (EHR) data on mental health service users and data from general public participants of Urban Mind, a citizen science project. We will use EHRs from the South London and Maudsley NHS Foundation Trust (SLaM) and the North London NHS Foundation Trust (NLFT), from six boroughs which collectively cover more than 1.8 million residents in Greater London, to capture mental health service use and mortality among people with existing diagnoses of mental illness across 2008–2023. We will use smartphone-based ecological momentary assessment data from Urban Mind to measure mental well-being in the general population (2018–2023). These datasets will be linked to high-resolution spatiotemporal data on temperature, fine and coarse particulate matter (PM_2.5, PM₁₀), nitrogen dioxide (NO₂), Normalised Difference Vegetation Index (NDVI) and density of large mature tree canopy. We will employ novel quasi-experimental designs, including case time series and case-crossover analysis, to examine the impact of extreme heat on mental health and explore effect modification by sociodemographic, clinical and environmental factors, including air pollution and types of green space coverage. We will also develop a microsimulation model combined with the InVEST urban cooling model to assess and forecast the mental health and social care impacts of extreme heat events and the mitigation of these impacts by different green space coverage and pollution-reduction policies. With a core team composed of researchers, community organisations, industry partners and specialist policy experts, this project will consider lived experience, benefit from broad stakeholder engagement and address gaps in policy and practice.

Each component of this project has been approved by the relevant ethics committee (ref RESCM-22/23-6905 for Urban Mind, LRS/DP-23/24-41409 for the co-development of a screening tool, 23/SC/0257 for the SLaM EHRs, and 24/EE/0178 for the NLFT EHRs). Our dissemination plan includes peer-reviewed scientific articles, policy briefs, a practical guide on fostering ecological and human resilience at the neighbourhood level, and a technical guide for planting and improving the growing conditions of large canopy trees.

Patients with acute psychiatric symptoms are often referred to the emergency department (ED) for medical evaluation to exclude medical causes before psychiatric admission. The absence of a prospectively validated medical screening tool leads to wide practice variation. This study aims to develop a new, evidence-based and consensus-based medical screening tool through a collaborative, interdisciplinary, international Delphi approach.

This modified Delphi study will include representatives from emergency medicine and psychiatry societies across four continents, as well as patient representatives with prior experience of medical screening in the ED. A minimum sample size of 24 participants is planned to account for potential dropouts. The Delphi procedure consists of four rounds. Round 1 will present current evidence and identify key items for the new medical screening tool. Round 2 will evaluate and refine statements from Round 1. Round 3 will seek consensus on the variables to be included in a medical screening tool. In Round 4, hypothetical clinical vignettes will be used to assess the agreement on the recommendations of the newly developed medical screening tool in order to test for content and construct validity. Surveys will be conducted via Research Electronic Data Capture (REDCap), with participants rating statements on a 6-point Likert scale. Response stability will be evaluated using the intraclass correlation coefficient, and consensus defined as ≥80% agreement. Results will be reported according to the ACcurate COnsensus Reporting Document guidelines and the Guidance for Reporting Involvement of Patients and the Public 2 short form.

The Ethics Committee of Northwestern and Central Switzerland exempted the project from committee approval under the Human Research Act on 11 September 2024. Written consent will be obtained from all participants. Results of this study will be summarised as a medical screening tool which will be validated in a prospective, multicentre study in a second step.

NCT06936826.

Total diet replacements (TDRs) and weight loss medications (WLMs) have proven effective in producing substantial weight loss for individuals with obesity. Evidence is lacking on whether combining these treatments is effective and cost-effective in primary care for adults with obesity class I (body mass index (BMI) 30–34.9) or uncomplicated obesity class II or higher (BMI≥35 without obesity-related disease).

LightCARE is a 2-year 1:1 randomised, parallel-group, clinical superiority trial with blinded outcome assessment evaluating the benefits and harms of an intensive weight loss (IWL) intervention compared with usual care for adults with obesity in Denmark and the UK. The trial will include 400 participants aged 18–60 years with obesity class I or uncomplicated obesity class II or higher. The IWL programme aims to achieve and maintain a weight loss of ≥20% through a flexible and individualised combination of TDR, behavioural support, including physical activity and sleep guidance, and WLM if needed and will continue for 2 years. The control group will receive usual care offered in each country, typically consisting of brief behavioural support for weight loss. The primary outcome is body weight 2 years after randomisation. Secondary outcomes will include the proportion of participants achieving ≥20% weight loss, Short-Form-36 Mental Component Score, 4-m gait speed and Metabolic Syndrome Severity-Z score. Serious adverse events, the incidence of eating disorders and bone mineral density will be evaluated as safety outcomes. We will also examine the cost-effectiveness of the intervention, within the trial and in the longer term through modelling. We will conduct a process evaluation to inform any future implementation.

Ethical approval was granted in Denmark (December 2023, H-23051332) and the UK (August 2024, 24/SC/0210). Findings from the trial will be disseminated through peer-reviewed journals and scientific conferences.

NCT06321432.