Despite advances in maternity care, stillbirth remains a major burden. It disproportionately affects black and Asian mothers, those with obesity and women over the age of 35 years. Induction of labour may benefit these women, but there is no clear evidence to guide recommendations on optimal timing of induction because of variations in the intervention and insufficient power in primary trials for rare outcomes such as stillbirth and perinatal mortality, or to assess whether effects differ by maternal characteristics. We will conduct an individual participant data (IPD) meta-analysis of randomised trials to assess the overall and differential effect of induction of labour, according to timing of induction and maternal characteristics, on adverse perinatal and maternal outcomes. We will also rank induction of labour timing strategies by their effectiveness to inform clinical and policy decision-making.

We will identify randomised trials on induction of labour by searching MEDLINE, CINAHL, EMBASE, BIOSIS, LILACS, Pascal, SCI, CDSR, ClinicalTrials.gov, ICTRP, ISRCTN registry, CENTRAL, DARE and Health Technology Assessment Database, without language restrictions, from inception to June 2025. Primary researchers of identified trials will be invited to join the OPTIMAL Collaboration and share the original trial data. Data integrity and trustworthiness assessment will be performed on all eligible trials. We will check each study’s IPD for consistency with the original authors before standardising and harmonising the data. Study quality of included trials will be assessed by the Cochrane Risk of Bias tool. We will perform a series of one-and-two-stage random-effects meta-analyses to obtain the summary intervention effect on composite adverse perinatal outcome (stillbirth, neonatal death or severe morbidity requiring admission to neonatal unit) with 95% CIs and summary treatment–covariate interactions (maternal age, ethnicity, parity, socioeconomic status, body mass index and method of conception). Heterogeneity will be summarised using tau², I² and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Small study effects (potential publication bias) will be investigated using funnel plots.

The study is registered on PROSPERO (CRD420251066346) and ethics approval is not required. We will disseminate findings widely to women, healthcare professionals and policymakers through academic, professional bodies and social media channels, and in peer-reviewed journals to achieve impact.

CRD420251066346.

Dietary (poly)phenols have beneficial properties that may play a relevant role in the management of overweight/obesity and cardiometabolic risk factors, modulating physiological and molecular pathways involved in energy metabolism, adiposity and gut microbiota-derived metabolites.

The Prevention/Precision Diet in Araucanía (PREDIET-ARAC) trial is a randomised, single-blind, parallel arm, placebo-controlled, clinical trial designed to assess the potential health benefits of (poly)phenol intake through either diet or supplementation. The study will evaluate the effectiveness of a healthy plant-based diet (PBD) rich in (poly)phenols compared with (poly)phenol supplementation during a caloric restriction intervention.

A total of 99 adults (aged 25–45 years) with overweight or obesity (body mass index: 25–35 kg/m²) and cardiovascular risk factors will be recruited from primary health centres in Temuco, Araucanía Region, Chile. Participants will be randomised (stratified by age:

Dietary data will be collected using dedicated software through three 24-hour dietary recalls at baseline and post-intervention. (Poly)phenol intake will be estimated using the Phenol-Explorer database. The main data collection will include general and lifestyle questionnaires, anthropometric and bioimpedance measurements, blood pressure assessments using sphygmomanometers, physical activity monitoring through accelerometers and strength evaluations via dynamometry. Blood samples will be collected at both baseline and after 12 weeks. For the analysis of plasma metabolites, a large-scale targeted metabolomics approach will be employed, specifically utilising ultra-high performance liquid chromatography coupled to tandem mass spectrometry. The healthy PBD will be primarily supplied by the food industry, encompassing a selection of regional and Latin American foods: blueberries, apple, nuts, olive oil and coffee. A descriptive and inferential statistical plan will be conducted, based on comparison tests, regression models and machine-learning algorithms.

This trial adheres to the Declaration of Helsinki and the CONSORT statement. Signed informed consent will be obtained from all participants. Ethical approval has been granted by the Ethical-Scientific Committee of the Health Service of Araucanía Sur, Chile (Approval No 11250095–58) and the Biosafety Committee of the Catholic University of Temuco. Findings will be disseminated through peer-reviewed publications, conference presentations and engagement with healthcare professionals and policymakers.

NCT06911346.

Time-lapse imaging (TLI) systems for embryo incubation and assessment are hypothesised to improve the success rates of in vitro fertilisation (IVF) treatment by providing undisturbed culture conditions for embryos and/or providing more information on embryo development (morphokinetic parameters) to improve predictive accuracy for embryo selection. Despite numerous aggregate meta-analyses showing uncertainty of benefit, IVF clinics globally continue to invest significant resources into this technology with little translation of evidence into guidelines or policy frameworks. This may be attributed to heterogeneity in participant populations and/or variations in the use of TLI, as highlighted in the aggregate meta-analyses.

Our research proposal for evidence synthesis using individual participant data meta-analysis will provide greater power than aggregate meta-analysis to detect differential treatment effects for effectiveness (live birth, clinical pregnancy) and safety (pregnancy loss, multiple births, congenital malformations) outcomes across three comparisons (overall effect, undisturbed culture and morphokinetic parameters). We will also analyse if there are specific subgroups of women who may benefit from the intervention and if variations in use of the intervention show any benefits. We have incorporated the results of the literature search used for the latest Cochrane review (7 January 2019) into this review and will include all the trials included therein. We will further update the literature search to include new evidence by searching the electronic databases MEDLINE, EMBASE, CINAHL and CENTRAL from 07/01/2019 to date, outcomes for all ongoing trials reported in the 2019 Cochrane review, trial registers for newer ongoing/completed trials and the citation lists of all the newly identified trials for any relevant references. The search strategy will include a combination of subject headings and text words relating to or describing the participants and the intervention, with no language restrictions. Two authors will independently screen the titles and abstracts, and full text of articles retrieved from the search, to finalise a list of trials suitable for inclusion in the review. We will include randomised controlled trials that assess TLI systems for either undisturbed culture and/or use of morphokinetic parameters for embryo selection in women having IVF/ICSI treatment using their own oocytes.

Ethical approval is not required for this study. We plan to disseminate the findings of the research to all stakeholders, including the National Institute for Health and Care Excellence and other international guideline development groups, through publication in peer-reviewed journals, presentation at conferences, newsletters, meetings and websites of the funders, fertility charities and patient support groups.

CRD42024564332.

A synthesis and appraisal of the recommendations for biomarkers in practice guidelines concerning sepsis is required to consolidate evidence-based practice. We generated an evidence gap map (EGM) on the use of biomarkers for managing adults with sepsis.

Scoping review.

MEDLINE, Guidelines International Network, Pan American Health Organization, Trip Database and UpToDate were searched from 2016 to March 2025.

Guidance documents (GD) that searched at least one literature source and provided clinical recommendations for the use of biomarkers for the management (diagnosis and prognosis, including treatment response) of adults with sepsis.

Two reviewers independently applied the eligibility criteria and extracted data. We used the AGREE-II (Appraisal of Guidelines for Research and Evaluation) tool to assess the GD quality. GDs that scored ≥50% on the AGREE-II 'Rigour of development' domain were considered robust. We also applied the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system to evaluate if the recommendations were strong or conditional.

We found 10 GDs, with only half (4/8) having a robust methodology. There were 31 recommendations concerning biomarkers. Among these, 24 (77.4%) recommendations were about single biomarkers, with lactate (23; 74.2%) and procalcitonin (8; 25.8%) most frequently recommended. Biomarker testing focused on prognosis in 28 (90.3%) recommendations. Overall, 16 (51.6%) recommendations were graded strong and 13 (42.0%) were conditional, which we displayed in an EGM.

The methodology of GDs concerning adult sepsis was poor. Our review calls for more prudent use of biomarkers in specific prognostic scenarios and in combination with standard clinical assessments. Enhancing the methodological quality of future GDs is essential to generate more valid and robust recommendations for optimising patient care.