Variations in pharmacokinetics and pharmacodynamics among sodium-glucose co-transporter 2 inhibitors (SGLT2i) and SGLT1/2i have not been explored adequately. This gap in knowledge about the differential efficacy and safety is exacerbated by an absence of head-on randomized controlled trials (RCTs). This necessitates a network meta-analysis (NMA) to inform comparisons of SGLT2i and SGLT1/2i among each other. Hence, we reviewed the efficacy and safety of SGLT2i and SGLT1/2i in heart failure (HF). This systematic review and network meta-analysis was conducted according to PRISMA-NMA and registered in PROSPERO (CRD42023435066). PubMed, Embase, Cochrane CENTRAL, and Scopus were searched until 2025/04/10, for RCTs of SGLT2i or SGLT1/2i in HF. We addressed a single question, analyzing efficacy separately within two ejection fraction (EF) strata (< 40
Diabetes mellitus (DM) and diabetic peripheral neuropathy (DPN) are linked to altered gait biomechanics, increasing functional limitations and foot ulcer risk. Although previous studies investigated biomechanical changes, findings are heterogeneous, methodologically limited considering the technological advances in the field, and outdated, with the last meta-analysis published in 2016. An updated synthesis is needed to identify consistent DM- and DPN-related gait patterns. PubMed, Embase, Scopus, Web of Science, Virtual Health Library and, CINAHL were searched for observational studies reporting gait biomechanics outcomes in adults with DM or DPN, compared with healthy individuals. Two independent reviewers assessed the risk of bias (modified Downs and Black checklist) and extracted data. Meta-analyses (random-effects models calculating mean differences [MD] with 95
Anti-obesity medications (AOMs) are increasingly indicated in the management of overweight and obesity. Most international guidelines recommend their co-prescription with companion lifestyle interventions (CLIs), typically modelled on the high-intensity, multi-contact behavioural support evaluated in pre-pharmacotherapy trials. The assumption that this intensity is required alongside an effective AOM has not been formally tested. Service models built on this assumption are resource-intensive, capacity-limited, and represent the principal bottleneck to equitable access in many health systems. This systematic review aims to (i) quantify the upper-bound contribution of CLI to weight change in the placebo arms of randomised placebo-controlled AOM trials; (ii) characterise CLI content, dose and delivery; and (iii) examine between-trial dose–response relationships between CLI intensity, contact time and modality, in order to test whether higher-intensity (“high-touch”) approaches outperform lower-intensity (“light-touch”) approaches alongside effective pharmacotherapy. This protocol follows PRISMA-P guidelines. Randomised placebo-controlled trials in adults with BMI ≥ 25 kg/m2 receiving AOMs licensed for weight management in the UK (tirzepatide, semaglutide, liraglutide, orlistat) will be included, provided that the same CLI is delivered in both arms. Searches will be conducted in four databases: MEDLINE (via PubMed), Embase (via Ovid), CENTRAL, and CINAHL. The primary outcome will be mean weight change (kg) at the longest in-trial follow-up in placebo arms receiving CLI. A secondary outcome will capture weight change at the longest available post-treatment follow-up to address sustained weight loss. CLI engagement and adherence will also be analysed. Subgroup analyses and random-effects meta-regression will examine between-trial associations between CLI characteristics (contact minutes, frequency, modality, professional mix, Behavioural Change content) and weight outcomes (subject to a minimum of ten studies per covariate). This review will provide an upper-bound estimate of CLI-attributable weight change in AOM placebo arms, characterise the behavioural content and intensity of CLIs, and test whether between-trial variation in CLI intensity predicts weight outcomes. The findings will inform whether the prevailing assumption that high behavioural intensity is required alongside AOMs is supported by trial evidence, and will identify the components and minimum effective CLI dose to prioritise in scalable models of obesity care. PROSPERO 2025 CRD420251050251.
The role of HER2-targeted therapy in the perioperative treatment of HER2-positive gastric and gastro-oesophageal junction (GEJ) cancer remains unclear, largely due to inconsistent results and the limited statistical power across individual clinical trials. This systematic review and individual patient data meta-analysis aims to evaluate the impact of HER2-targeted therapy on pathological tumour response and survival outcomes. This review will include randomised controlled trials and single-arm interventional trials evaluating the perioperative HER2-targeted therapy plus chemotherapy in HER2-positive resectable gastric and GEJ cancer. The main comparison will be HER2-targeted therapy plus chemotherapy versus chemotherapy alone, where an internal control arm is available. A comprehensive literature search will be conducted in MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials, and major international oncology conferences proceedings. The primary outcomes are pathological tumour response and time-to-event outcomes, including progression-free survival and overall survival. A one-stage meta-analysis using individual participant data will be performed to assess treatment effects, with prespecified subgroup analyses exploring heterogeneity according to sex, tumour site, geographical region, histological subtype, HER2 status and chemotherapy regimen. By integrating individual-level data across studies, this IPD meta-analysis will provide more precise evidence on the efficacy and safety of adding HER2-targeted therapy to perioperative chemotherapy in HER2-positive gastric and GEJ cancer. The findings are expected to support the design of future clinical trials and contribute to the future development of perioperative treatment strategies for this patient population. PROSPERO CRD420251248294.
Pre-eclampsia remains a significant contributor to maternal and perinatal morbidity and mortality worldwide. Altered maternal iron metabolism during pregnancy, including, but not limited to, elevated iron biomarkers and dysregulated iron handling, has been implicated in the pathophysiology of pre-eclampsia, through mechanisms involving oxidative stress, endothelial injury, inflammatory activation, and placental dysfunction. However, evidence linking maternal iron biomarkers to pre-eclampsia remains inconclusive, partly because markers like ferritin may reflect both iron status and inflammation. The systematic review and meta-analysis will synthesise evidence on the association between maternal iron biomarkers and pre-eclampsia in pregnancy. The primary objective is to determine whether elevated maternal iron biomarkers are associated with pre-eclampsia compared with normotensive pregnancies. Secondary objectives are to examine associations by biomarker type and to explore whether gestational timing of biomarker assessment, study design, diagnostic criteria, and adjustment for inflammation or other confounders contribute to heterogeneity. This protocol was developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guidelines, and the completed review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. A systematic search will be conducted in PubMed/MEDLINE, Scopus, Web of Science, Embase, DOAJ, ProQuest Dissertations Theses and the Cochrane Library for observational studies published from database inception to the final search date. Eligible studies will include pregnant women with measured maternal iron biomarkers and reported pre-eclampsia outcomes. Two reviewers will independently screen studies, extract data, and assess risk-of-bias using an appropriate tool for observational studies. Where appropriate, pooled effect estimates will be calculated using a random-effects model. The certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. This review will synthesise evidence on the association between maternal iron biomarkers and pre-eclampsia and identify gaps and sources of heterogeneity in the literature. Findings may improve understanding of the role of maternal iron dysregulation in pre-eclampsia and inform future research. Strengths include duplicate screening and formal risk-of-bias assessment, while anticipated limitations include reliance on observational evidence and variability in biomarker measurement. PROSPERO CRD420261399815.
