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Weight-loss effects of macronutrient-based diets modified by genetic variants: a protocol for systematic review of randomised controlled trials

Por: Subardjo · Y. P. · Khairunnissa · N. M. · Kusuma · R. J. · Huriyati · E. · Susetyowati · S.
Introduction

Personalised nutrition that incorporates genetic results into dietary interventions holds significant potential to optimise weight management and metabolic outcomes. While traditional calorie-restricted diets remain effective, emerging evidence suggests that variations in macronutrient distribution may offer additional benefits. Genetic variants help explain interindividual differences in dietary responses, with certain alleles showing enhanced weight loss and metabolic improvements with specific macronutrient distributions. However, comprehensive reviews of randomised controlled trials (RCTs) examining genotype-based dietary effects, particularly those focusing on macronutrient distribution metabolic pathway interactions, are lacking, limiting the development of robust evidence-based guidelines for nutrigenetic counselling. This systematic review aims to assess the influence of genetic variants on weight loss outcome in adults in response to varying macronutrient distribution diets (eg, low-fat, low-carbohydrate, high-protein diets) using evidence from RCTs.

Methods and analysis

We will systematically review RCTs examining weight loss outcomes of macronutrient-varied diets in adults with genotype stratifications to risk and protective allele. Multiple databases, PubMed, Cochrane Library, Scopus, Science Direct and Google Scholar, will be used. Reviewers will screen studies, extract data on study characteristics, weight loss, metabolic marker outcomes and genetic data, and assess the risk of bias using the Cochrane Risk of Bias Tool 2.0 tool.

All eligible RCTs will first be summarised in structured tables describing study characteristics, macronutrient distribution and genetic variants and will be analysed with narrative synthesis. For quantitative analysis, interventions will be grouped into three predefined diet types (high-protein, low to moderate carbohydrate and low-fat diet). Because heterogeneity across diet categories is expected, pooled effects will be estimated separately within each diet subgroup using random-effects meta-analysis, expressed as mean differences in weight change (kg). Within each subgroup, and when at least 10 studies or data are available, random-effects meta-regression will be used to examine potential moderators, including intervention duration, physical activity and ancestry. Heterogeneity will be evaluated using I2 and 2, and publication bias assessed when feasible. Evidence certainty will be graded using Grading of Recommendations Assessment, Development and Evaluation.

Ethics and dissemination

Ethical approval is not required for this protocol as it involves the analysis of data from primary studies. The findings will be disseminated through publication in peer-reviewed journals. Any enquiries regarding research integrity of this protocol may be directed to the Head of the Doctoral Program in Medical Health and Sciences, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada via the institutional email address s3fk@ugm.ac.id, as the responsible academic authority for research integrity.

PROSPERO registration number

CRD420251050587.

Protocol for a multi-country retrospective observational paediatric sepsis epidemiological study (SENTINEL International)

Por: Long · E. · Williams · A. · George · S. · Hearps · S. · Yock-Corrales · A. · Pavlicich · V. · Krishnamurthy · K. · Seymour-Hanna · Y. · Raman · R. · Choudhary · B. · Kusuma · W. · Ribaya · V. · Mudithakumara · N. · Lertamornkitti · N. · David · A. · Mohamed · S. · Heye · T. B. · Njiramma
Introduction

Improving outcomes from sepsis in children is a WHO Global Health Priority, yet mortality from sepsis remains high, particularly in low- and middle-income countries (LMICs). This database from children with community-acquired childhood sepsis in LMICs and some high-income countries will allow analysis of the burden of disease, including incidence, severity and outcomes. Understanding these aspects of sepsis care is fundamental for the design and conduct of future international interventional trials to improve childhood sepsis outcomes.

Methods and analysis

This multicountry retrospective observational study will include children up to 18 years of age presenting to emergency departments with suspected sepsis, defined as admission to hospital for treatment with intravenous antibiotics plus (1) a provisional diagnosis of sepsis and/or (2) treatment for suspected sepsis (operationalised as the administration of one or more fluid bolus to treat impaired perfusion or vasoactive infusion). Presenting characteristics, management and outcomes will be collected. These will include vital signs, serum biomarkers, intravenous fluid administration for the first 24 hours of hospitalisation, organ support therapies delivered, antimicrobial use, microbiological diagnoses, hospital and intensive care unit length of stay, and mortality censored at hospital discharge or 30 days from enrolment (whichever occurs first).

Ethics and dissemination

Central ethics approval was received from the Royal Children’s Hospital of Melbourne, Australia Human Research Ethics Committee (HREC/100648/RCHM-2023). Each international site will be required to obtain local Institutional Research Ethics Board approval. The findings will be disseminated in peer-reviewed journals, at academic conferences and through lay media. A cleaned study database and individual site-level data will be made available to site investigators upon completion of the study.

Trial registration number

This study was registered with the Australian and New Zealand Clinical Trials Registry on 23 January 2024 prior to commencement of recruitment (ACTRN12624000052538).

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