Spermidine administration ameliorates hepatic steatosis and cardiometabolic dysfunction in animal models. However, evidence in humans remains limited. We aimed to explore the 1-year longitudinal associations between changes in dietary spermidine intake and changes in hepatic function indexes and cardiometabolic traits in overweight and obese older adults with metabolic syndrome. We used baseline and 1-year follow-up data from 2664 participants from the PREDIMED-Plus trial. Dietary spermidine intake was estimated using a semi-quantitative food frequency questionnaire. Time series clustering identified temporal patterns of 1-year change in spermidine intake. Linear mixed-effects models assessed the associations between spermidine intake clusters and changes in hepatic and cardiometabolic markers. Three distinct spermidine intake patterns were identified across baseline, six months and 1 year follow-up. Cluster 3, characterized by the highest baseline and increased 1-year spermidine intake, was associated with mean reductions in fatty liver index (− 8.97 [− 9.96 to − 7.97], p-int < 0.001), hepatic steatosis index (− 1.88 [− 2.13 to − 1.63], p-int < 0.001), alanine aminotransferase (− 2.93 [− 3.83 to − 2.02] U/L, p-int < 0.05), aspartate aminotransferase (− 1.11 [− 1.76 to − 0.45] U/L, p-int < 0.05) and glycated hemoglobin levels (− 0.14 [− 0.18 to − 0.10]

BACKGROUND:As survival improves, attention in breast cancer (BC) has shifted from purely oncologic outcomes to quality of life, body image, and value-concordant decision-making. In this context, shared decision-making (SDM) has emerged as a cornerstone of patient-centered BC care, particularly in guiding choices between breast-conserving surgery (BCS) and mastectomy. However, its implementation and impact on patient outcomes remain inconsistently documented. METHODS:Following PRISMA guidelines, a systematic review was conducted across six databases (PubMed, Embase, Web of Science, Scopus, Cochrane Library, and Trip) up to April 2025 (OSF registration: osf. io/fr8ka). Original studies examining SDM in surgical decision-making between BCS and mastectomy were included. Data extraction and quality assessment (using the QualSyst tool) were performed independently by four reviewers. Evidence was synthesized thematically across five SDM domains: determinants of surgical choice, patient perception and outcomes, decision aids, structured SDM models, and barriers and facilitators. RESULTS:Twenty-two studies met the inclusion criteria. Most were observational (59%), with 95% of quantitative studies rated as strong (QualSyst ≥0.80). SDM consistently enhanced patient knowledge, involvement, and satisfaction, significantly reducing decisional conflict (mean reduction 6-10 points, p < 0.01) and improving congruence between treatment choice and personal values. Decision aids, particularly 3D visual and conversational tools, increased observed SDM scores by 24-32 points (OPTION-5 (Observing Patient Involvement-5), p = 0.01) and mitigated knowledge disparities among lower-socioeconomic status patients. While SDM rarely altered overall surgical distributions (BCS approximately 70%, mastectomy 30%), it refined the decision-making process and increased confidence. Implementation barriers included clinician resistance, time constraints, and systemic inequities, whereas structured frameworks and institutional support facilitated success. CONCLUSIONS:SDM in BC surgery strengthens the ethical and psychological integrity of surgical decisions by ensuring that choices between BCS and mastectomy reflect informed, deliberative, and value-concordant preferences. Though its influence on surgical distribution is limited, SDM enhances satisfaction, decisional quality, and equity. Integrating structured SDM frameworks and clinician training into standard breast surgery practice is essential to advance truly patient-centered care.

Objective To assess the feasibility of randomising a sufficiently large number of pregnant women who screen positive for intimate partner violence (IPV) to perform a full-scale effectiveness trial. Methods This pilot randomised trial was nested within a cohort of IPV-positive pregnant women who accepted an e-health package in Spain and Denmark. This study was co-designed with patient input using a modified Zelen’s design and a qualitative evaluation. Eligible women were randomised to an intervention (received the e-health package) or to a control (received it with a delay). The primary outcome was the proportion of women screened positive for IPV who consented to be randomised to receive an e-health package with a delay. Results Twenty-nine of the 51 women in the cohort were randomised. Of these, 12 were allocated to the control group, and 7 (58.3%) consented to receive the e-health package with a delay, i.e., 24.1% of the total randomised and 13.7% of the total cohort. The proportion of randomized women who adhered to treatment was 31.03% (9/29). Complete outcome data were obtained in 7/17 (41.17%) and 2/12 (16.66%) women in the intervention and control groups, respectively. Qualitative interviews indicated that the women perceived the intervention as beneficial and that delaying it was not acceptable. Conclusions This pilot randomised trial indicated that a future full-scale randomised study would likely be unfeasible based on our a priori criteria to stop the trial. If a future large trial is launched, it should include an internal pilot with strict go/no-go criteria monitored by an independent committee. Trial registration NCT04978064. E-health Psychological Intervention in Pregnant Women Exposed to Intimate Partner Violence (eIPV). Registered 15 July 2021, https://clinicaltrials.gov/study/NCT04978064

BACKGROUND:Obesity increases the risk of obstetric and neonatal complications, and adherence to lifestyle interventions during pregnancy presents a challenge. Patient and public involvement (PPI) in trials may foster a more patient-centered approach, potentially improving compliance with intervention and follow up. OBJECTIVE:To assess the extent of PPI in systematic reviews (SRs) and meta-analyses (MAs) focused on lifestyle interventions for pregnant women with obesity and its impact on compliance and follow-up rates of included randomized controlled trials (RCTs). SEARCH STRATEGY:Searches were conducted in PubMed, Scopus, Web of Science, and Embase using terms related to "lifestyle", "obesity", and "pregnancy", along with filters for SRs and MAs. SELECTION CRITERIA:SRs of RCTs, with or without MAs, published from 2013 to 2024, focusing on lifestyle interventions for pregnant women with obesity (BMI ≥30 [calculated as weight in kilograms divided by the square of height in meters]). DATA COLLECTION AND ANALYSIS:SR quality was assessed using AMSTAR 2. PPI reporting was evaluated using the GRIPP2 checklist and the ACTIVE framework. Compliance and follow-up rates were compared between RCTs with and without PPI. MAIN RESULTS:Eleven SRs, 10 with MAs (including 94 RCTs) were included. They were of low quality in 3/11 (27%) and critically low in 8/11 (73%). No SRs reported implementing PPI. Only 6/94 (10%) RCTs reported PPI, 2/29 (7%) directly after the introduction of GRIPP2 (2018) and 4/65 (6%) indirectly before its introduction (P = 0.79). PPI occurred during RCT methodology planning in 2/6 (33%), knowledge translation in 2/6 (33%), or both in 2/6 (33%). Compared with RCTs not reporting PPI (n = 94), the median intervention compliance rate in RCTs reporting PPI (n = 6) was higher (74% versus 68%, P = 0.637), and the follow-up rate was lower (78% versus 89%, P = 0.138), but the difference was not statistically significant. These findings warrant cautious interpretation given the limited number of RCTs reporting PPI. CONCLUSIONS:PPI remains scarce in both SRs and RCTs evaluating lifestyle interventions in pregnant women with obesity. Future research should integrate and clearly report PPI to strengthen the evaluation of lifestyle interventions in this population.

Introduction:Global population ageing is linked to increasing multimorbidity and polypharmacy. This shift places pressure on caregivers, who often lack training and face challenges like medication mismanagement. Our objective was to collate scientific evidence on interventions to enhance medication management among multimorbid older adults living in the community. Methods:We conducted a systematic review and meta-analysis (PROSPERO: CRD42024513056) following PRISMA guidelines. PubMed, Web of Science, CINAHL, and ClinicalTrials.gov were searched up to July 9, 2024. Eligible studies were RCTs or quasi-experimental designs involving home-dwelling adults aged ≥60 years with ≥2 chronic conditions or ≥5 medications, assessing adherence or health outcomes, and ≥30 days of follow-up. Screening, data extraction, and quality assessment were performed in duplicate. Random-effects meta-analyses were conducted using R. ORs (95% CI) were calculated for binary outcomes and SMDs (95% CI) for continuous variables. Results:Of 7,980 citations, 49 articles met the eligibility criteria, corresponding to 48 unique studies. Medication adherence measured with the MMAS-4 indicated a significant effect (OR = 1.55; 95% CI 1.08-2.28; I2 = 32.4%), while continuous measures showed no effect (SMD = 0.00; 95% CI = -0.08-0.09; I2 = 2%). Readmissions decreased at medium-term follow-up (OR = 0.41; 95% CI 0.25-0.69). Results for ED visits were inconclusive due to heterogeneity. Primary care contacts showed a weak, non-significant effect (SMD = 0.06; 95% CI = -0.04-0.16; I2 = 42%). No effect was found for quality of life or mortality. DRPs and costs lacked conclusive evidence. Most studies had a moderate to high risk of bias. Certainty of evidence was very low. Discussion:Interventions showed limited and variable effects. Adherence improvements were identified only for the MMAS-4, while other measures showed no benefit. A short-term reduction in readmissions was observed, but effects were not sustained, and the certainty of evidence was low. This review highlights evidence gaps, particularly the need for standardized outcomes, more sustained and multifactorial interventions, economic evaluation, and higher methodological quality, to support evidence-based policymaking and optimize future interventions. Systematic review registration:The systematic review was registered in PROSPERO (CRD42024513056). The registration link is: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024513056.

Socioeconomic disadvantage is associated with higher obesity risk in older adults, but whether walkable neighborhoods modify these inequalities remains unclear. We examined whether neighborhood walkability moderates the association between area-level socioeconomic status (SES) and adiposity among older adults with overweight or obesity living in Mediterranean cities. This cross-sectional study analyzed baseline data from 1286 urban-dwelling adults aged 55 to 75 years with overweight or obesity and metabolic syndrome residing in six Andalusian cities. Area-level SES was assessed using the 2011 Spanish Deprivation Index, and neighborhood walkability was derived from an open-source index incorporating population density, street intersection density, and access to daily amenities. Adiposity outcomes included waist circumference, waist-to-hip ratio, and a body shape index, all objectively measured. Two-level linear regression models, with individuals nested within census tracts, evaluated SES-walkability interactions while adjusting for demographic and lifestyle factors. No overall differences in adiposity were observed between higher- and lower-SES neighborhoods. However, walkability significantly modified the SES-adiposity association. In highly walkable and dense neighborhoods, participants living in more deprived areas had larger waist circumference and higher body shape index compared with those in less deprived areas, indicating a steeper SES gradient in central adiposity. In low-walkability neighborhoods, SES differences in central adiposity were minimal. No interaction was observed for body mass index. Highly walkable urban environments may therefore amplify socioeconomic inequalities in abdominal obesity among older Mediterranean adults with overweight or obesity. Urban planning strategies promoting walkability should incorporate equity-focused, age-friendly approaches to ensure benefits reach socioeconomically disadvantaged populations.

BACKGROUND:Patient, carer and public involvement (PCPI), an approach being endorsed in research, may also improve research integrity. After prospective registration (https://osf.io/nfgxp), we conducted a scoping umbrella review to collate evidence on the contribution of PCPI toward the integrity of randomized clinical trials (RCTs). METHODS:Three databases were searched on 17 July 2024 with a double-blind selection process. We included systematic reviews that addressed PCPI issues related to clinical research integrity. Quality was appraised with a modified AMSTAR-2 instrument. RESULTS:We identified 27 reviews. The overlap between primary studies was low. The quality of the reviews was rated as high-moderate for two, low for four, and critically low for 21. Findings on adherence to ethical and professional standards emphasized the importance of early citizen engagement in RCTs, the role of PCPI in the ethical approval process, and the need for research integrity training. There was a lack of research on the role of PCPI relating to post-publication issues. CONCLUSION:Our findings supported the need for developing a consensus approach to ascertain the role of PCPI in responsible RCT design, conduct, and reporting, to enhance the credibility and trustworthiness of clinical research.

Recent studies have revealed issues with ethical practice and informed consent in randomized clinical trials (RCTs). We aimed to develop an international, multi-stakeholder consensus statement on human research ethics committee approval and informed participant consent for RCTs. The consensus process encompassed a systematic scoping review, modified two-round Delphi survey, and final consensus meeting of a multi-stakeholder group, including trialists, ethics committee members, methodologists, patient representatives, journal editors, and other experts on RCTs. Delphi consensus deployed the Average Percentage of Majority Opinions (APMO) threshold. There were 36 stakeholders from 12 countries in five continents. Delphi survey response rates were 67% (24/36 stakeholders) and 69% (25/36 stakeholders) in the first and second rounds, respectively. There were 135 statements (18 stakeholder-provided, 117 scoping review-generated) in the initial long list. Three additional statements were provided during the Delphi rounds. APMO threshold was 81.33% and 75.05% for the first and second Delphi rounds, respectively. Through consensus, the final set consolidated 77 statements in the following domains: general aspects (n = 11), journals' instructions and policies (n = 9), research institutions and funders' policies (n = 6), ethics committee regulations (n = 11), ethics committee evaluation and approval (n = 18), monitoring of informed consent procedures (n = 8), monitoring of trials for compliance (n = 3), post-publication concerns on ethics (n = 2), and recommendations for future research and development (n = 9). In conclusion, this international consensus statement provides a comprehensive integrity framework to address the unique challenges in RCT ethics and informed consent. It highlights the importance of robust ethics committee assessments, stakeholder training, patient engagement, and trial monitoring procedures.

OBJECTIVE:Low Glycemic Index (GI) diets improve cardiometabolic risk (CMR) specifically in those with insulin resistance. However, the prospective association between pasta (a low GI staple) consumption and CMR is unclear. We evaluated the longitudinal association of pasta consumption with CMR (after 2 y: body weight, body mass index (BMI), waist circumference (WC), blood pressure (BP); after 1 y: fasting blood glucose, HbA1c, HDL-cholesterol and triglycerides) in ∼6000 older adults (50% women) at high CMR. METHODS:Consumption of pasta and other staples were determined as the cumulative average of reported intakes at baseline and annual follow-up visits from food frequency questionnaires and defined as energy-adjusted (residuals) and the number of daily servings. Longitudinal association between pasta consumption and CMR was assessed in PREDIMED-Plus participants (Trail registry number: ISRCTN89898870). RESULTS:Mean (SD) dry pasta intake was 9(7) g/d at Year 1 and 8(6) g/d at Year 2. In linear regression models, higher pasta intake was associated with greater 2 y decreases in body weight, BMI and WC. When fully adjusted, every additional serving of pasta was associated with significantly greater 2 y decreases in body weight (-2.23(-3.47, -0.98 kg), BMI (-0.86(-1.27, -0.34 kg/m2) and WC (-1.92 (-3.46, -0.38 cm). There was no evidence of association with other outcomes. Additionally, substituting equivalent servings of pasta for white bread or white rice or potato was significantly associated with greater 2 y decreases in body weight and BMI. Replacing white bread with pasta was associated with higher 2 y reductions in WC. Replacing potato with pasta was associated with improvements in diastolic BP and HDL-cholesterol. Conclusions: Equivalent serving substitutions of white bread/white rice/potato with pasta may help reduce CMR in older Mediterranean adults with overweight/obesity. While such substitutions are feasible where pasta consumption aligns with the local gastronomic culture, the feasibility and potential CMR benefit of such interventions should be confirmed in other populations.

BACKGROUND:Randomized clinical trials (RCTs) based on Mediterranean Diet (MedDiet) have reported that higher adherence is associated with better health outcomes. Our aim was to describe the perspectives and experiences of older adults in a MedDiet RCT for cardiovascular disease prevention. METHODS:Three focus groups on 25 participants from a MedDiet RCT, aged from 63 to 76 years old, were conducted after a conference on patient and public involvement in research at the University of Granada (Spain). Each focus group, comprising 8-10 participants, was audio-recorded, transcribed, and thematically analysed. RESULTS:Participants were motivated by research team commitment during follow-up, improved health status and chronic disease management, weight loss, and enhanced health literacy. Health benefits among cohabitants were highlighted by female participants. A more personalized counselling and transparency with disclosure of the results of their tests and on-going study findings were missed. Participants were willing to collaborate in the dissemination of findings. Involving patients in RCTs would align the interventions with their needs and health conditions. CONCLUSION:In the context of an RCT, participants could join the research team, identifying key questions, planning study design, contributing to the intervention protocol, and helping disseminate results by selecting the best platforms for sharing findings.

The number of retractions of randomized clinical trials (RCTs) following post-publication allegations of misconduct is increasing. To address this issue, we aimed to establish an international multistakeholder consensus on post-publication integrity concerns related to RCTs. After prospective registration (https://osf.io/njksm), we assembled a multidisciplinary stakeholder group comprising 48 participants from 18 countries across six continents, recruited using a curated list of journal editors and snowballing. An underpinning evidence synthesis collated 89 articles related to post-publication integrity concerns. Integrity statements related to RCTs created were subjected to anonymized two-round Delphi survey. A hybrid face-to-face-online consensus development meeting was convened to consolidate the consensus. The response rates of the two Delphi survey rounds were 65% (31/48) and 67% (32/ 48), respectively. There were 101 and 41 statements in the first and second Delphi rounds, respectively. After the two Delphi rounds and the consensus development meeting, consensus was achieved on 104 statements consolidated to 84 after merging, editing, and removing duplicates. This set of statements included general aspects (n = 9), journal instructions (n = 14), editorial and peer review (n = 7), correspondence and complaints (n = 4), investigations for integrity concerns (n = 16), decisions and sanctions (n = 9), critical appraisal guidance (n = 1), systematic reviews of RCTs (n = 8), and research recommendations (n = 16). In conclusion, this international multistakeholder consensus statement aimed to underpin policies for preventing post-publication integrity concerns in RCT publications and assist in improving investigations of misconduct allegations.

OBJECTIVES:Using Bandura's self-efficacy theory and the health belief model, the aim of this study is identify the information sources related to the promotion of healthy lifestyles during pregnancy, analysing their accessibility, relevance, and reliability. STUDY DESIGN:Qualitative Study. METHODS:A thematic analysis of 25 semi-structured interviews with pregnant women at different stages of pregnancy was carried out, considering sociodemographic and clinical variables such as age, educational level, parity, and access to social networks, among others. The discourses and data were processed through coding and categorization, as per the objectives of the study. Validation was carried out through researcher triangulation. RESULTS:Health professionals, the internet, and social media are among the variety of information sources used by pregnant women, with substantial variability in the accessibility and reliability of the sources and their direct influence on the acceptance and adherence to recommendations. The results of the study showed a strong reliance and trust in the recommendations from healthcare professionals, but also a growing influence of social media. CONCLUSIONS:Information provided by healthcare professionals is considered the most reliable and accepted, but pregnant women supplement this information by consulting other sources, where social networks are gaining ground, especially among young pregnant women. This highlights the need to develop strategies to improve the quality of online information.

BACKGROUND:Limited research has been done to evaluate the combined effect of energy reduction, Mediterranean diet (MedDiet), and physical activity on type 2 diabetes incidence. OBJECTIVE:To evaluate whether an energy-reduced MedDiet (erMedDiet) plus physical activity reduces diabetes incidence compared with a standard MedDiet. DESIGN:Prespecified secondary outcome analysis in the PREDIMED (Prevención con Dieta Mediterránea)-Plus randomized, single-blinded, controlled trial. (ISRCTN Registry: ISRCTN89898870). SETTING:23 centers across Spain. PARTICIPANTS:4746 adults aged 55 to 75 years with metabolic syndrome and overweight or obesity, without prior cardiovascular disease or diabetes. INTERVENTION:Participants were randomly assigned 1:1 to an intervention group receiving an erMedDiet (planned reduction of 600 kcal per day), increased physical activity, and behavioral strategies for reducing weight, or a control group receiving ad libitum MedDiet advice. MEASUREMENTS:Diabetes incidence was based on the American Diabetes Association criteria. Anthropometric measurements were obtained annually. Cox regression models were used to assess the intervention effect. RESULTS:The 6-year absolute risk was 12.0% (95% CI, 11.9% to 12.1%) in the control group (349 cases) and 9.5% (CI, 9.4% to 9.5%) in the intervention group (280 cases). Over a median 6-year follow-up, diabetes incidence was 31% (CI, 18% to 41%) relatively lower in the intervention group compared with the control group, with an absolute risk reduction of -2.6 cases (CI, -2.7 to -2.4) per 1000 person-years. The intervention group attained better adherence to the erMedDiet, higher physical activity levels, and greater reductions in body weight and waist circumference. LIMITATION:Secondary outcome, single-blinded design, and self-reported dietary adherence. CONCLUSION:An intensive intervention with the MedDiet adding caloric reduction, physical activity, and modest weight loss was more effective than only an ad libitum MedDiet in reducing diabetes incidence in overweight/obese persons with metabolic syndrome. PRIMARY FUNDING SOURCE:Instituto de Salud Carlos III.

BACKGROUND:Men and women tend to follow different dietary patterns, but this is often disregarded when relating diet to health outcomes. OBJECTIVE:Our aim was to analyze (poly)phenol intake patterns and their association with cardiovascular risk (CVR) according to sex. METHODS:6633 participants were included in this cross-sectional study. The intake of 26 (poly)phenol classes/subclasses was included in the factor analysis obtaining for the total sample, men and women. Linear regression models were performed with the estimation of absolute CVR (Framingham equation) as the dependent variable, and each (poly)phenol pattern categorized into quintiles as the independent variable. RESULTS:For the total sample, (poly)phenol pattern three (olives and olive oil) was positively associated with CVR (βQ5vs.Q1 = 2.71%, 95% CI = 1.45, 3.96), presenting a higher risk of diabetes prevalence, smoking more and consuming more salt. In men, pattern three (olives and olive oil) was also positively associated with CVR (βQ5vs.Q1 = 3.17%, 95% CI = 1.58, 5.64), exhibiting higher prevalence of diabetes and higher sodium intake. Also in men, pattern four (coffee) was positively associated (βQ5vs.Q1 = 1.99 %, 95% CI = 0.26, 3.73) presenting a higher diabetes and current smokers prevalence and higher sugar intake. In women, greater adherence to pattern four (coffee) was associated with higher CVR (βQ5vs.Q1 = 2.19%, 95% CI = 1.05, 3.34). CONCLUSIONS:We found sex differences in (poly)phenol intake patterns and in their associations with CVR. These differences may be explained by the fact that subjects at higher risk at baseline may be motivated to improve their dietary habit (reverse causality). CLINICAL TRIAL REGISTRY NUMBER:The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN89898870).

BACKGROUND:Clinical Practice Guidelines (CPGs) are essential for promoting evidence-based maternal and neonatal care, but inconsistencies in recommendations can be confusing. OBJECTIVES:To analyse the quality and reporting of international CPGs for normal birth and summarise the recommendations. SEARCH STRATEGY:Registered on PROSPERO (CRD42021269488), the study identified CPGs on normal birth through systematic searches in databases like MEDLINE, Cochrane, Scopus and WOS, along with direct outreach to international organisations. SELECTION CRITERIA:CPGs published from 2010 to December 2024 were included, with no language restrictions. DATA COLLECTION AND ANALYSIS:The quality and reporting of CPGs were evaluated using the AGREE II and RIGHT tools, and recommendations were summarised. MAIN RESULTS:Of the 25 CPGs analysed, the median AGREE II quality score was 54%, and the median RIGHT reporting score was 50%. The highest scores were from WHO (2018), CINETS (2013) and the Spanish normal childbirth CPG (2010). Notably, 56% of CPGs had poor reporting, while only 8% were adequately informed. Common recommendations included the presence of support persons, avoiding routine interventions (e.g., enemas, shaving), encouraging fluid intake, allowing movement during labour and promoting skin-to-skin contact. CONCLUSIONS:Most CPGs on normal childbirth are outdated and exhibit poor quality and reporting. There is a pressing need for improvements to ensure valid, consistent and updated recommendations that enhance maternal and neonatal health.

Objective:To identify and synthesize evidence on Coronavirus-two infection (SARS-CoV-2) among adults diagnosed by polymerase chain reaction. Methods:The protocol was registered on Open Science Forum (doi: 10.17605/OSF.IO/2837X). Three bibliographic databases (Medline, SCOPUS, and Web of Science) were searched from July 2024 to December 2024. Peer-reviewed, quantitative studies with participants aged 18 and over were eligible to enlist potential risk factors of SARS-CoV-2 infection confirmed by Polymerase Chain Reaction PCR). The evidence was summarized as illustrations and tabulations with risk factors grouped into various categories. EndNote 20 was used for deduplications and organization of the literature. Results:Of 28,688 unique entries searched, 299 were shortlisted and 32 full-text manuscripts selected from 17 countries. There were two (6.2%) manuscripts based on real-time surveillance of at-risk populations. A total of 42 individual risk factors were examined in the evidence. Conclusion:Low socioeconomic status and occupation were consistent risk factors of SARS-CoV-2 infection, with minimal representation from low- and middle-income countries in the evidence body. Future research should prioritize standardized methods and inclusion of underrepresented regions to enhance global applicability and inform targeted public health interventions.

Objectives Frailty has emerged as a key indicator of biological aging. This study aimed to assess the relationship between MedDiet adherence and frailty prevalence in the context of metabolic syndrome (MetS). Design Cross-sectional study. Baseline data from PREDIMED-Plus trial Setting Primary care health, 23 recruitment sites (2013–2016). Participants A total of 6874 participants with overweight/obesity and ≥3 MetS components. Measurements Adherence to the MedDiet: 17-item MedDiet score. Frailty and prefrailty (3 or 1–2 criteria): modified Fried Frailty Index (FFI), considering exhaustion, physical activity and functional capacity. Main independent variable was analysed: as a continuous variable (range: 0–17); in quartiles of adherence using univariate and multivariate logistic regression models adjusted for potential confounders. Results Prefrailty and frailty prevalence were 49.7% and 2.9%, respectively. Compared to those with the lowest MedDiet adherence (0–6), participants with the highest adherence (11–17) had significantly lower odds of meeting frailty criteria. Fully adjusted models showed ORs of 0.479 (p = 0.097) for frailty, 0.705 (p = 0.001) for prefrailty, and 0.694 (p = 0.001) for frailty or prefrailty in participants with higher/greater MedDiet adherence. Each 1-point increase in the 17-item score was associated with an OR ranging from 0.878 to 0.977 (p < 0.05 for all comparisons, except functional capacity: p = 0.100). When adherence was dichotomized, the adjusted ORs ranged from 0.406 to 0.834 (p < 0.05 for all comparisons). Conclusions Higher adherence to MedDiet was associated with a lower prevalence of frailty and prefrailty in older adults with overweight/obesity and MetS, reinforcing its potential role in promoting healthy aging despite cardiometabolic comorbidities.

BackgroundThe rising number of retracted randomised clinical trials (RCTs) is a concern over their trustworthiness. In today's digital landscape electronic observational data is easily accessible for research purposes. This emerging perspective, in tandem with the growing scrutiny of RCT credibility, may steer some researchers towards favouring non-randomized studies. It is crucial to emphasize the ongoing need for robust RCTs, shedding light on the areas within trial design that require enhancements and addressing existing gaps in trial execution.Main bodyEvidence-based medicine pivots on the nexus between empirical medical research and the theoretical and applied facets of clinical care. Healthcare systems regularly amass patient data, creating a vast reservoir of information. This facilitates large-scale observational studies, which may appear as potential substitutes for RCTs. These large-scale studies inherently possess biases that place them a notch below randomized evidence. Honest errors, data manipulation, lapses in professionalism, and methodological shortcomings tarnish the integrity of RCTs, compromising trust in trials. Research institutions, funding agencies, journal editors and other stakeholders have the responsibility to establish robust frameworks to prevent both deliberate and inadvertent mishandling of RCT design, conduct and analysis. Systematic reviews that collate robust RCTs are invaluable. They amalgamate superior evidence instrumental in improving patient outcomes via informed health policy decisions. For systematic reviews to continue to retain trust, validated integrity assessment tools must be developed and routinely applied. This way it will be possible to prevent false or untrustworthy research from becoming part of the recommendations based on the evidence.ConclusionHigh-quality RCTs and their systematic reviews play a crucial role in acquiring valid and reliable evidence that is instrumental in improving patient outcomes. They provide vital information on healthcare effectiveness, and their trustworthiness is key to evidence-based medicine.

Objective: To estimate the environmental impact of a dietary intervention based on an energy -reduced Mediterranean diet (MedDiet) after one year of follow-up. Methods: Baseline and 1 -year follow-up data were used for 5800 participants aged 55 -75 years with metabolic syndrome in the PREDIMED-Plus study. Food intake was estimated through a validated semiquantitative food consumption frequency questionnaire, and adherence to the MedDiet was estimated through the Diet Score. Using the EAT -Lancet Commission tables we assessed the influence of dietary intake on environmental impact (through five indicators: greenhouse gas emissions (GHG), land use, energy used, acidification and potential eutrophication). Using multivariable linear regression models, the association between the intervention and changes in each of the environmental factors was assessed. Mediation analyses were carried out to estimate what extent changes in each of 2 components of the intervention, namely adherence to the MedDiet and caloric reduction, were responsible for the observed reductions in environmental impact. Results: We observed a significant reduction in the intervention group compared to the control group in acidification levels (-13.3 vs. -9.9 g SO2-eq), eutrophication (-5.4 vs. -4.0 g PO4-eq) and land use (-2.7 vs. -1.8 m2). Adherence to the MedDiet partially mediated the association between intervention and reduction of acidification by 15 %, eutrophication by 10 % and land use by 10 %. Caloric reduction partially mediated the association with the same factors by 55 %, 51 % and 38 % respectively. In addition, adherence to the MedDiet fully mediated the association between intervention and reduction in GHG emissions by 56 % and energy use by 53 %. Conclusions: A nutritional intervention based on consumption of an energy -reduced MedDiet for one year was associated with an improvement in different environmental quality parameters.