Integrating gender analysis into research: reflections from the Gender-Net Plus workshop.

Gender equality has been a crosscutting issue in Horizon 2020 with three objectives: gender balance in decision-making, gender balance and equal opportunities in project teams at all levels, and inclusion of the gender dimension in research and innovation content. Between 2017 and 2022, the EU funded, in collaboration with national agencies, 13 transnational projects under "GENDER-NET Plus" that explored how to best integrate both sex and gender into studies ranging from social sciences, humanities, and health research. As the projects neared completion, forty researchers from these interdisciplinary teams met in November 2022 to share experiences, discuss challenges, and consider the best ways forward to incorporate sex and gender in research. Here, we summarize the reflections from this workshop and provide some recommendations for i) how to plan the studies (e.g., how to define sex and/or gender and their dimensions, rationale for the hypotheses, identification of data that can best answer the research question), ii) how to conduct them (e.g., adjust definitions and dimensions, perform pilot studies to ensure proper use of terminology and revise until consensus is achieved), and iii) how to analyze and report the findings being mindful of any real-world impact.

Sex Differences in the Association Between Vascular Risk Factors and Cognitive Decline: A UK Biobank Study.

Background: Age-related cognitive decline is accelerated by vascular risk factors for cerebral small vessel disease. However, the association of vascular risk factors with cerebral small vessel disease contributing to the sex differences in cognitive decline remains unclear. Objectives: The purpose of this study was to evaluate sex differences in cognitive decline and the association between vascular risk factors and cognitive decline by sex. Methods: We used data from the UK Biobank (>55 years of age; n = 19,067) to assess cognitive tests (executive function, processing speed, and memory) while adjusting for baseline measurements to examine how vascular risk factors affect cognition. A univariate regression analysis was used to assess sex differences at the first time point (2014). A repeated measure analysis with a mixed effect model was used to determine cognitive decline (between 2014 and 2019). Any significant interaction between vascular risk factors and sex was investigated. Results: Females had lower scores in all 3 domains at the first cognitive tests (2014). We found a significant sex-by-time interaction over a 5-year period in matrix pattern completion (P = 0.03). After adjusting for vascular risk factors, this interaction was reduced (P = 0.08). High low-density lipoprotein, low education, and high blood pressure had a greater effect on the rate of cognitive decline in the executive function for females compared to males for the sex∗vascular risk factor interaction (P < 0.05). Conclusions: The rate of cognitive decline did not differ significantly between males and females. However, the impact of several vascular risk factors on cognitive decline was greater in females than in males.

Sex and gender-based analysis and diversity metric reporting in acute care trials published in high-impact journals: a systematic review.

OBJECTIVE: To characterise sex and gender-based analysis (SGBA) and diversity metric reporting, representation of female/women participants in acute care trials and temporal changes in reporting before and after publication of the 2016 Sex and Gender Equity in Research guideline. DESIGN: Systematic review. DATA SOURCES: We searched MEDLINE for trials published in five leading medical journals in 2014, 2018 and 2020. STUDY SELECTION: Trials that enrolled acutely ill adults, compared two or more interventions and reported at least one clinical outcome. DATA ABSTRACTION AND SYNTHESIS: 4 reviewers screened citations and 22 reviewers abstracted data, in duplicate. We compared reporting differences between intensive care unit (ICU) and cardiology trials. RESULTS: We included 88 trials (75 (85.2%) ICU and 13 (14.8%) cardiology) (n=111 428; 38 140 (34.2%) females/women). Of 23 (26.1%) trials that reported an SGBA, most used a forest plot (22 (95.7%)), were prespecified (21 (91.3%)) and reported a sex-by-intervention interaction with a significance test (19 (82.6%)). Discordant sex and gender terminology were found between headings and subheadings within baseline characteristics tables (17/32 (53.1%)) and between baseline characteristics tables and SGBA (4/23 (17.4%)). Only 25 acute care trials (28.4%) reported race or ethnicity. Participants were predominantly white (78.8%) and male/men (65.8%). No trial reported gendered-social factors. SGBA reporting and female/women representation did not improve temporally. Compared with ICU trials, cardiology trials reported significantly more SGBA (15/75 (20%) vs 8/13 (61.5%) p=0.005). CONCLUSIONS: Acute care trials in leading medical journals infrequently included SGBA, female/women and non-white trial participants, reported race or ethnicity and never reported gender-related factors. Substantial opportunity exists to improve SGBA and diversity metric reporting and recruitment of female/women participants in acute care trials. PROSPERO REGISTRATION NUMBER: CRD42022282565.

Gender-Related Factors Associated With Outcomes of Acute Coronary Syndrome in Young Female Patients.

Acute coronary syndrome (ACS) remains a significant global health concern, with a growing recognition of its impact on young adults, particularly young female adults. Although gender-related factors, defined as a social construct that encompasses 4 distinct dimensions (gender roles, gender identity, gender relations, and institutionalized gender) are undoubtedly relevant across age groups, young female patients with ACS face specific challenges and disparities in outcomes, compared to other populations. This narrative review examines the role of gender-related factors-specifically, gender roles, gender identity, gender relations, and institutionalized gender-in influencing objective and subjective ACS outcomes in young female patients. In the 5 articles identified, the objective outcomes included hospital readmission, "door-to-electrocardiography" time, and coronary atherosclerosis progression. Subjective outcomes, such as physical and mental functional status, quality of life, physical limitations, and vital exhaustion, were also examined. Being employed, which is a gender role, emerged as a protective factor against hospital readmission. Gender identity factors such as depression and stress were correlated with negative outcomes, and anxiety influenced "door-to-electrocardiography" times. Institutional factors, including income disparities, affected readmission likelihood. Strong social support decreased physical limitations post-ACS, whereas financial challenges and lower education negatively impacted quality of life and vital exhaustion. These findings underscore the intricate interplay of gender dimensions in shaping ACS outcomes among young female patients. Integrating these insights into clinical practice and research can enhance care, mitigate disparities, and foster improved cardiovascular health in this vulnerable population.

Le syndrome coronarien aigu (SCA) demeure un problème de santé préoccupant à l'échelle mondiale, avec une reconnaissance croissante de ses conséquences chez les jeunes adultes, plus particulièrement les jeunes femmes adultes. Les facteurs liés au genre, définis comme un construit social à quatre dimensions distinctes (les rôles liés au genre, l'identité de genre, les relations de genre et le genre institutionnalisé) sont indéniablement d'une grande importance dans tous les groupes d'âge, mais les jeunes patientes atteintes d'un SCA font face à des disparités et des défis particuliers à l'égard des résultats de santé par rapport à d'autres populations. La présente synthèse narrative propose un examen de l'influence des facteurs liés au genre (plus particulièrement les rôles liés au genre, l'identité de genre, les relations de genre et le genre institutionnalisé) sur les issues objectives et subjectives du SCA chez les jeunes patientes. Dans les 5 articles retenus, les issues objectives incluaient la réadmission à l'hôpital, le temps écoulé entre l'arrivée à l'hôpital et la réalisation de l'électrocardiographie et l'évolution de l'athérosclérose coronarienne. Les issues subjectives, comme le statut fonctionnel physique et mental, la qualité de vie, les limitations physiques et le syndrome d'épuisement, ont également été examinées. Être employé, qui est un rôle de genre, est apparu comme facteur de protection contre la réadmission à l'hôpital. Des facteurs liés à l'identité de genre, comme la dépression et le stress, étaient corrélés à des issues négatives et l'anxiété était liée au temps écoulé entre l'arrivée à l'hôpital et la réalisation de l'électrocardiographie. Les facteurs liés aux institutions, y compris les disparités de revenus, influençaient la probabilité de réadmission à l'hôpital. La présence d'un bon réseau social était associée à de plus faibles limitations physiques après le SCA, alors que les problèmes financiers et un faible niveau d'éducation avaient une influence néfaste sur la qualité de vie et le syndrome d'épuisement. Ces résultats font ressortir les interactions complexes entre les différentes dimensions du genre qui façonnent les issues du SCA chez les jeunes patientes. L'intégration de ces renseignements dans la pratique clinique et dans la recherche scientifique pourrait permettre d'améliorer les soins, de limiter les disparités auxquelles font face ces patientes et de favoriser une meilleure santé cardiovasculaire au sein de cette population vulnérable.

Are Socioeconomic Factors Associated With Atrial Fibrillation Sex-Dependent? A Narrative Review.

Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, poses a significant public health and economic burden. Although socioeconomic factors such as income and education have been implicated in AF incidence and outcomes, the potential sex-specific associations remained underexplored. This narrative review aimed to fill this gap by synthesizing existing literature on the sex-specific impact of socioeconomic factors on AF incidence, treatment, and outcome. Among these socioeconomic factors, we identified income and education as the most frequently cited determinants. Nevertheless, the magnitude and direction of these sex differences remained inconsistent across studies. The review uncovered that many studies did not include sex in the analysis when assessing the impact of socioeconomic factors on AF. We highlighted that there is a paucity of studies employing sex-stratified reporting and sex interaction analyses, thereby hindering a deeper understanding of these relationships.

Administrative data ICD-10 diagnostic codes identifies most lab-confirmed SARS-CoV-2 admissions but misses many discharged from the Emergency Department.

We estimated the operating characteristics of ICD-10 code U07.1, introduced by the World Health Organization in 2020, to identify lab-confirmed SARS-CoV-2. CCEDRRN is a national research registry of adults (March 2020-August 2021) with suspected/confirmed SARS-CoV-2 identified in Canadian emergency departments (EDs) using chart review (symptoms, clinical information, and lab test results including SARS-CoV-2 polymerase chain reaction, PCR results). CCEDRRN data were linked to administrative hospitalization discharge and ED ICD-10 diagnostic codes (accessed centrally via the Canadian Institute for Health Information). We identified ICD-10 diagnostic codes in CCEDRRN participants. We defined lab-confirmed SARS-CoV-2 based on at least one positive PCR in the 0-14 days before the ED presentation and/or during hospitalization (in those admitted from ED). We performed separate analyses for CCEDRRN participants discharged from ED and those hospitalized from the ED. Additional analyses were stratified by province, sex, age, and (for hospitalized patients) timing of the first PCR test. The sensitivity of ICD-10 code U07.1 for a positive SARS-CoV-2 test was 93.6% (95% CI 93.0-94.1%) in those hospitalized from ED and 83.0% (95% CI 82.1-83.9%) in those discharged from the ED. Sensitivity was similar across provinces and demographics, but in each stratified analysis, values were higher in those hospitalized versus those discharged from ED. The ICD-10 diagnostic code for U07.1 within administrative data identified most lab-confirmed SARS-CoV-2 within persons hospitalized from ED, although a significant number of cases discharged from ED were missed. This should be considered when using administrative data for research and public health planning.

Heterogeneity of coronary vascular function and myocardial oxygenation in women with angina and non-obstructive coronary artery disease.

AIMS: Women with angina and non-obstructive coronary artery disease (ANOCA) have a heightened risk for cardiovascular events, and the pathophysiology for ischaemic symptoms may be related to alterations in microvascular structure and function. We examined the use of breathing-enhanced oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) using vasoactive breathing manoeuvres to assess myocardial oxygenation in women with ANOCA. METHODS AND RESULTS: We recruited women (aged 40-65 years) from two sites in Canada who presented to healthcare with persistent retrosternal chest pain and found to have ANOCA, or without a history of cardiovascular disease. All participants were scanned using a clinical 3T MRI scanner, and OS-CMR images were acquired over a breath hold following paced hyperventilation to measure global and regional measurements of heterogeneity. Fifty-four women with ANOCA (age: 55 ± 6.2 years) and 48 healthy controls (age: 51.2 ± 4.8 years) were recruited. There was no significant difference in volume, function, mass, or global myocardial oxygenation between the two groups [mean %Δ in signal intensity (SI): 4.9 (±7.3) vs. 4.5 (±10.1), P = 0.82]. Women with ANOCA had higher regional variations in myocardial oxygenation in circumferential [median %Δ in SI: 5.1 (2.0-7.6) vs. 2.2 (1.4-3.5), P = 0.0004] and longitudinal directions [median %Δ in SI: 11.4 (5.4-16.7) vs. 6.0 (3.0-7.0), P = 0.001], which remained present in a multivariate model. CONCLUSION: Heterogeneous myocardial oxygenation may explain ischaemic symptoms without any associated epicardial obstructive coronary artery disease. Regional variations in myocardial oxygenation on OS-CMR could serve as an important diagnostic marker for microvascular dysfunction in women with ANOCA.

Association of marital/partner status with hospital readmission among young adults with acute myocardial infarction.

INTRODUCTION: Despite evidence supporting the benefits of marriage on cardiovascular health, the impact of marital/partner status on the long-term readmission of young acute myocardial infarction (AMI) survivors is less clear. We examined the association between marital/partner status and 1-year all-cause readmission and explored sex differences among young AMI survivors. METHODS: Data were from the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), which enrolled young adults aged 18-55 years with AMI (2008-2012). The primary end point was all-cause readmission within 1 year of hospital discharge, obtained from medical records and patient interviews and adjudicated by a physician panel. We performed Cox proportional hazards models with sequential adjustment for demographic, socioeconomic, clinical, and psychosocial factors. Sex-marital/partner status interaction was also tested. RESULTS: Of the 2,979 adults with AMI (2002 women [67.2%]; mean age 48 [interquartile range, 44-52] years), unpartnered individuals were more likely to experience all-cause readmissions compared with married/partnered individuals within the first year after hospital discharge (34.6% versus 27.2%, hazard ratio [HR] = 1.31; 95% confidence interval [CI], 1.15-1.49). The association attenuated but remained significant after adjustment for demographic and socioeconomic factors (adjusted HR, 1.16; 95% CI, 1.01-1.34), and it was not significant after further adjusting for clinical factors and psychosocial factors (adjusted HR, 1.10; 95%CI, 0.94-1.28). A sex-marital/partner status interaction was not significant (p = 0.69). Sensitivity analysis using data with multiple imputation and restricting outcomes to cardiac readmission yielded comparable results. CONCLUSIONS: In a cohort of young adults aged 18-55 years, unpartnered status was associated with 1.3-fold increased risk of all-cause readmission within 1 year of AMI discharge. Further adjustment for demographic, socioeconomic, clinical, and psychosocial factors attenuated the association, suggesting that these factors may explain disparities in readmission between married/partnered versus unpartnered young adults. Whereas young women experienced more readmission compared to similar-aged men, the association between marital/partner status and 1-year readmission did not vary by sex.

Sex Differences in the Association of Age at Hypertension Diagnosis With Brain Structure.

BACKGROUND: Sex differences exist in the likelihood of cognitive decline. The age at hypertension diagnosis is a unique contributor to brain structural changes associated with cerebral small vessel disease. However, whether this relationship differs between sexes remains unclear. Therefore, our objective was to evaluate sex differences in the association between the age at hypertension diagnosis and cerebral small vessel disease-related brain structural changes. METHODS: We used data from the UK Biobank to select participants with a known age at hypertension diagnosis and brain magnetic resonance imaging (n=9430) and stratified them by sex and age at hypertension diagnosis. Control participants with magnetic resonance imaging scans but no hypertension were chosen at random matched by using propensity score matching. For morphological brain structural changes, generalized linear models were used while adjusting for other vascular risk factors. For the assessment of white matter microstructure, principal component analysis led to a reduction in the number of fractional anisotropy variables, followed by regression analysis with major principal components as outcomes. RESULTS: Males but not females with a younger age at hypertension diagnosis exhibited lower brain gray and white matter volume compared with normotensive controls. The volume of white matter hyperintensities was greater in both males and females with hypertension than normotensive controls, significantly higher in older females with hypertension. Compared with normotensive controls, white matter microstructural integrity was lower in individuals with hypertension, which became more prominent with increasing age. CONCLUSIONS: Our study demonstrates that the effect of hypertension on cerebral small vessel disease-related brain structure differs by sex and by age at hypertension diagnosis.