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.

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.

Childhood overweight and obesity pose a growing public health problem with increasing prevalence both in Europe and globally. Reasons can be found in behavioural factors such as a sedentary lifestyle, eating habits or low exercise levels and to a lesser extent in a genetic predisposition or a metabolic disorder. Preventing children with obesity and overweight to grow into obese teenagers is therefore of high importance. However, there are currently no established care and prevention programmes in Germany for the early reduction of overweight and prevention of obesity in children aged 3–6 years. fruehstArt aims to close this gap with a cross-sector outreach and family-centred personal counselling approach, where parents receive support from paediatricians and trained coaches who conduct consultations in the home of the family. The main research question is whether the fruehstArt programme reduces overweight and obesity in children aged 3–6 years within 12 months, as measured by the body mass index-standard deviation score (BMI-SDS).

fruehstArt has been developed as a new form of care, which includes a family intervention with motivational interviews provided by paediatricians and individual home-based counselling provided by a trained coach on eating behaviour, exercising, sleeping behaviour and age-appropriate use of electronic devices. fruehstArt will be accompanied by an efficacy study (summative evaluation of change in BMI-SDS). In addition to German, the project is also offered in Turkish in order to reach families with a migration background and language barriers. 812 children with overweight or obesity and their families in the region North Rhine will be included and observed over 12 months. Recruitment of children occurred from December 2023 to April 2025 with the final visits scheduled for April 2026. The study is conducted as a randomised controlled trial with a social-ecological intervention approach, considering children in their living environment and conditions. Moreover, a formative evaluation at the process level, and the system level will be carried out and complemented by a health economic analysis. Those are carried out to provide information about the intervention’s success and relevant costs. Thus, fruehstArt is realised in the form of an effectiveness–implementation hybrid design that combines the analysis of effectiveness with an evaluation of the implementation process.

The study received ethics approval in a coordinated procedure from the ethics committee of the Medical Faculty University hospital of Cologne and the ethics committee of the North Rhine Medical Association. For all collected data, the relevant national and European data protection regulations will be considered. All personal data (contact details) will be removed for the data analysis in order to ensure pseudonymisation. Dissemination strategies include reports and quality workshops for organisations, peer-reviewed publications and the presentation of results at conferences.

The aim of the unique form of care fruehstArt is to improve the care of preschool children with overweight or obesity through innovative home-based counselling, cross-sectoral service integration and to address the cultural needs of Turkish families.

DRKS00030749 (29-09-2023)