Resumen de Sex and gender considerations in clinical research on sepsis: sex-and gender-based analysis and prognostic effect
Background: Historically, western-oriented research knowledge and approaches have often reproduced the dynamics of different structural oppression systems. The evidence derived from these methodologies is at risk of disregarding the needs of health care and values and preferences of most of the population that, in turn, is composed of a mosaic in which groups experiencing multiple axes of disadvantage. Sepsis is a leading cause of mortality worldwide. The degree of sex- and gender-related inclusion analysis and reporting in studies underpinning clinical recommendations for sepsis, as well as the role of sex as an independent prognostic factor for mortality among critically ill adults with sepsis, remain unclarified. Objective: To synthesise and evaluate the role of sex and gender in clinical research on sepsis and elaborate a methodological approach to sex-and gender-based analysis in systematic reviews (SR). Methods: Article-based thesis composed of three main studies. First study: A bibliometric study examining the female Participation-to-Prevalence Ratio (PPR) in primary studies underpinning recommendations from clinical guidelines and SRs for sepsis. Second study: A revision process of sex and gender appraisal tool for SR (SGAT-SR). We revised the items to consider additional factors associated with health inequities and appraised sex and gender considerations using the SGAT-SR-2 and PPR in Cochrane sepsis reviews. Third study: SR and meta-analysis. We included studies evaluating independent associations between sex and mortality in critically ill adults with sepsis controlling for at least one of five core covariate domains pre-specified following a literature search and consensus amongst experts. Results: Among 277 sepsis primary studies examined, females were under-enrolled. Among 71 Cochrane reviews assessed, possible similarities and differences across sex and gender were rarely appraised. Prognostic SR included 13 studies. Meta-analysis found no sex-based differences in all-cause hospital mortality and all-cause ICU mortality (very low-certainty evidence). Females presented higher 28-day all-cause mortality (very low-certainty evidence) and lower 1- year all-cause mortality (low-certainty evidence). Interpretation: Representation of participants by sex in sepsis studies can be assessed by using PPR. The SGAT-SR-2 tool can support the design and appraisal of SR to assess sex and gender considerations. Clinical research should embrace sex- and gender-based analysis to understand to whom the evidence applies, given the potential implications for clinical practice, research, and policy-making. High-quality research is needed to test the adjusted prognostic value of sex for predicting mortality in critically ill adults with sepsis.
