Non-communicable diseases (NCDs) currently contribute to over 50% of the global disease burden. Digital tools bear the potential to mitigate the risk of NCDs by facilitating personalised, preventive healthcare. It is therefore pertinent to examine the specific components that contribute to the success or constrain the impact of digital health interventions (DHIs), with particular attention to the sustainability of their long-term effects. Additionally, it is important to provide an up-to-date perspective on emerging interventions and technologies that have not yet been comprehensively addressed in the literature. This protocol defines the methodology for an umbrella review to synthesise the available high-quality evidence from systematic reviews and meta-analyses regarding effectiveness of DHIs in influencing the primary prevention of NCDs.

Using a rigorous search strategy, the subsequent databases will be searched in December 2025: MEDLINE, Web of Science, CINAHL, Embase, Scopus and Epistemonikos. Following the Joanna Briggs Institute (JBI) methodology, the selected literature will be screened based on predefined inclusion criteria. This includes systematic reviews and meta-analyses published within the last 5 years, without restrictions on country or language, that evaluate the effectiveness of any DHI aimed at the primary prevention of NCDs. Suitable full-text articles will be extracted by four researchers and independently assessed for methodological quality by two researchers using the AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews) tool. The results will be presented in a summary table aligned with the review question and subquestions, accompanied by a narrative synthesis that explores the findings and their relevance to the research aims.

Ethical approval is not required as no primary data will be collected. The findings of this umbrella review will be published in a peer-reviewed journal and presented at academic conferences.

CRD420251139744.

Acute lower limb ischaemia (ALI) is a life- and limb-threatening vascular emergency requiring urgent intervention. Despite advancements in therapeutic strategies, outcome reporting for ALI remains inconsistent, limiting evidence synthesis and guideline development. The CORE-ALI study aims to develop a Core Outcome Set (COS) to standardise outcome reporting and ensure the inclusion of both clinical and patient-centred metrics.

CORE-ALI will use a structured, multi-phase methodology guided by the Core Outcome Measures in Effectiveness Trials (COMET) initiative and the Core Outcome Set-STAndards for Reporting (COS-STAR) guidelines. Phase 1 involves stakeholder engagement through semi-structured interviews with patients, clinicians and policymakers from diverse European healthcare systems. Qualitative data will be analysed using thematic analysis to generate a preliminary list of outcomes. In Phase 2, a multi-round Delphi survey (anticipated two to three rounds) will prioritise and refine outcomes through consensus building, with quantitative data analysed using descriptive and non-parametric statistical methods. Phase 3 will culminate in a consensus meeting to finalise the COS. Multilingual accommodations will ensure inclusivity, and General Data Protection Regulation (GDPR)-compliant platforms will secure data handling.

The study has received ethics approval from the Ethics Committee of the Medical University of Innsbruck (EK Nr: 1082/2025) on 20/05/2025. Additional local ethics approvals are required and will be obtained at all participating sites prior to the initiation of recruitment. The final Core outcome set will be disseminated through peer-reviewed publications, presentations at international conferences and engagement with professional societies and patient organisations.

COMET initiative (Registration No. 3346).

The only supportive therapy for patients with severe acute kidney injury (AKI), a common complication among the critically ill, is dialysis. Based on the literature and current guidelines, continuous renal replacement therapy (CRRT) with a total effluent dose of 20–25 mL/kg/hour and adjustments to ensure such dose is delivered despite down time (eg, due to surgical procedures) is recommended. However, experimental and clinical studies suggest that azotaemia, which can be induced by lowering the effluent dose, may accelerate renal recovery. This clinical study investigates whether a lower effluent dose (10–15 mL/kg/hour) for a maximum of 7 days or until successful (>24 hours) liberation of CRRT in critically ill patients with a dialysis-dependent AKI accelerates renal recovery and reduces time on CRRT compared with guideline-directed standard dose (25–30 mL/kg/hour).

The Ketzerei trial is an international, multicentre randomised, controlled trial, designed to investigate if a lower effluent dose (10–15 mL/kg/hour) accelerates renal recovery and reduces the time on CRRT compared with the guideline directed standard effluent dose (25–30 mL/kg/hour). The study aims to enrol 150 critically ill patients with a dialysis-dependent AKI. Eligible patients will be randomised to receive either a standard effluent dose (control group, 25–30 mL/kg/hour) or lower effluent dose (interventional group, 10–15 mL/kg/hour). The primary endpoint is the number of days free from CRRT and alive (from randomisation through day 28). Key secondary endpoints include the number of (serious) adverse events due to potential uremia, the duration of RRT and intensive care unit survival.

The Ketzerei trial has been approved by the Ethics Committee of the Chamber of Physicians Westfalen-Lippe (2023–343 f-s), the University of Muenster and subsequently by the corresponding Ethics Committee of the participating sites. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research.

clinicaltrials.gov (NCT06021288).