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Abstract 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.

Summary: 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.

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. Résumé: 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.

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.

Abstract Sharing health data for research purposes across international jurisdictions has been a challenge due to privacy concerns. Two privacy enhancing technologies that can enable such sharing are synthetic data generation (SDG) and federated analysis, but their relative strengths and weaknesses have not been evaluated thus far. In this study we compared SDG with federated analysis to enable such international comparative studies. The objective of the analysis was to assess country-level differences in the role of sex on cardiovascular health (CVH) using a pooled dataset of Canadian and Austrian individuals. The Canadian data was synthesized and sent to the Austrian team for analysis. The utility of the pooled (synthetic Canadian + real Austrian) dataset was evaluated by comparing the regression results from the two approaches. The privacy of the Canadian synthetic data was assessed using a membership disclosure test which showed an F1 score of 0.001, indicating low privacy risk. The outcome variable of interest was CVH, calculated through a modified CANHEART index. The main and interaction effect parameter estimates of the federated and pooled analyses were consistent and directionally the same. It took approximately one month to set up the synthetic data generation platform and generate the synthetic data, whereas it took over 1.5 years to set up the federated analysis system. Synthetic data generation can be an efficient and effective tool for enabling multi-jurisdictional studies while addressing privacy concerns.

IntroductionDespite 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.MethodsData 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.ResultsOf 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.ConclusionsIn 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.

Background: Although young women ( aged ≤ 55 years) are at higher risk than similarly aged men for hospital readmission within 1 year after an acute myocardial infarction (AMI), no risk prediction models have been developed for them. The present study developed and internally validated a risk prediction model of 1-year post-AMI hospital readmission among young women that considered demographic, clinical, and gender-related variables. Methods: We used data from the US Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study (n = 2007 women), a prospective observational study of young patients hospitalized with AMI. Bayesian model averaging was used for model selection and bootstrapping for internal validation. Model calibration and discrimination were respectively assessed with calibration plots and area under the curve. Results: Within 1-year post-AMI, 684 women (34.1%) were readmitted to the hospital at least once. The final model predictors included: any in-hospital complication, baseline perceived physical health, obstructive coronary artery disease, diabetes, history of congestive heart failure, low income ( < $30,000 US), depressive symptoms, length of hospital stay, and race (White vs Black). Of the 9 retained predictors, 3 were gender-related. The model was well calibrated and exhibited modest discrimination (area under the curve = 0.66). Conclusions: Our female-specific risk model was developed and internally validated in a cohort of young female patients hospitalized with AMI and can be used to predict risk of readmission. Whereas clinical factors were the strongest predictors, the model included several gender-related variables (ie, perceived physical health, depression, income level). However, discrimination was modest, indicating that other unmeasured factors contribute to variability in hospital readmission risk among younger women. Résumé: Contexte: Bien que les femmes jeunes (≤ 55 ans) présentent un risque plus élevé que les hommes du même âge de réadmission à l’hôpital dans l’année suivant un infarctus aigu du myocarde (IAM), il n’existe pas de modèle de prédiction des risques conçu spécialement pour elles. Dans le cadre de la présente étude, on a créé et validé à l’interne un modèle de prédiction des risques de réadmission à l’hôpital dans l’année suivant un IAM chez les femmes jeunes en tenant compte de variables démographiques, cliniques et associées au genre. Méthodologie: Nous avons utilisé les données de l’étude américaine VIRGO (variation du rétablissement : le rôle du genre dans les résultats des jeunes patientes ayant subi un IAM) (n = 2007 femmes), une étude observationnelle prospective menée auprès de jeunes patientes hospitalisées pour un IAM. Un modèle bayésien d’établissement de la moyenne a été utilisé pour la sélection du modèle et la méthode bootstrap a été utilisée pour la validation interne. L’étalonnage et la discrimination du modèle ont été évalués respectivement au moyen des courbes d’étalonnage et de la surface sous la courbe. Résultats: Dans l’année suivant l’IAM, 684 femmes (34,1 %) ont été réadmises à l’hôpital au moins une fois. Les facteurs prédictifs finaux du modèle sont notamment : toute complication survenue à l’hôpital, l’état de santé physique perçu au départ, la coronaropathie obstructive, le diabète, les antécédents d’insuffisance cardiaque congestive, le faible revenu (< 30 000 $ US), les symptômes dépressifs, la durée du séjour à l’hôpital et l’ethnie (blanc par rapport à noir). Parmi les neuf facteurs prédictifs retenus, trois sont associés au genre. Le modèle est bien étalonné et présente une discrimination modeste (surface sous la courbe = 0,66). Conclusions: Notre modèle de risque propre aux femmes a été conçu et validé à l’interne auprès d’une cohorte de femmes jeunes hospitalisées pour un IAM et peut être utilisé pour prédire le risque de réadmission. Bien que les facteurs cliniques soient les facteurs prédictifs les plus puissants, le modèle inclut plusieurs variables liées au genre (p. ex., état de santé physique perçu, dépression, revenu). Cependant, la discrimination étant modeste, d’autres facteurs non mesurés contribuent à la variabilité du risque de réadmission à l’hôpital chez les femmes plus jeunes.

Background Stress experienced in a marriage or committed relationship may be associated with worse patient‐reported outcomes after acute myocardial infarction (AMI), but little is known about this association in young adults (≤55 years) with AMI. Methods and Results We used data from VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), an observational cohort study that enrolled individuals aged 18 to 55 years with AMI (2008–2012). Marital stress was self‐reported 1 month after AMI using the Stockholm Marital Stress Scale (categorized as absent/mild, moderate, and severe). Outcomes were physical/mental health (Short Form‐12), generic health status (EuroQol‐5 Dimensions), cardiac‐specific quality of life and angina (Seattle Angina Questionnaire), depressive symptoms (Patient Health Questionnaire‐9), and all‐cause readmission 1 year after AMI. Regression models were sequentially adjusted for baseline health, demographics (sex, age, race or ethnicity), and socioeconomic factors (education, income, employment, and insurance). Sex and marital stress interaction was also tested. Among 1593 married/partnered participants, 576 (36.2%) reported severe marital stress, which was more common in female than male participants (39.4% versus 30.4%, P=0.001). Severe marital stress was significantly associated with worse mental health (beta=−2.13, SE=0.75, P=0.004), generic health status (beta=−3.87, SE=1.46, P=0.008), cardiac‐specific quality of life (beta=−6.41, SE=1.65, P0.05). Conclusions The association between marital stress and worse 1‐year health outcomes was statistically significant in young patients with AMI, suggesting a need for routine screening and the creation of interventions to support patients with stress recovering from an AMI.

Background: Poorer health outcomes experienced by young women with acute coronary syndrome may be related to sex differences in the safety and efficacy of antiplatelet agents, such as clopidogrel. Polymorphisms in drug metabolism enzyme (cytochrome P450 [CYP] family) genes are independent factors for the variability in response to clopidogrel. However, a sex-specific impact of genetics to explain worse clinical outcomes in women has not been explored extensively. Therefore, our objective was to determine whether an interaction of sex with CYP variants occurs among users of clopidogrel, and if so, its impact on 1-year adverse clinical outcomes. Methods: We used data from a combined cohort of 2272 patients (median age 49 years; 56% female) hospitalized for acute coronary syndrome. We examined interactions between sex and CYP variants among clopidogrel users at admission and discharge to assess associations with 1-year readmission due to cardiac events. Results: The case-only analysis of 177 participants on clopidogrel at the time of presentation showed that the risk of an atherothrombotic event was greater in female carriers of the CYP2C9∗3 loss-of-function allele (odds ratio = 3.77, 95% confidence interval = 1.54-9.24). The results of the multivariable logistic regression model for users of clopidogrel at discharge (n = 1733) indicated that women had significantly higher risk of atherothrombotic readmissions at 1 year (odds ratio = 1.55, 95% confidence interval = 1.16-2.07), compared to the risk for men, but the loss-of-function alleles, either individually or through a genetic risk score, were not associated with 1-year readmissions. Conclusion: This study highlights the need for an improved understanding of the role of sex-by-gene interactions in causing sex differences in drug metabolism. Résumé: Contexte: Les piètres résultats cliniques observés chez les jeunes femmes atteintes d’un syndrome coronarien aigu pourraient être liés à des différences entre les sexes en ce qui concerne l’innocuité et l’efficacité des antiplaquettaires, comme le clopidogrel. Le polymorphisme génétique des enzymes intervenant dans le métabolisme des médicaments (famille des cytochromes P450 [CYP]) est un facteur indépendant de la variabilité de la réponse au clopidogrel. Cependant, jamais la possibilité d’un effet génétique propre au sexe qui expliquerait les résultats cliniques défavorables chez les femmes n’a été examinée en profondeur. Notre objectif était donc de déterminer s’il se produit une interaction entre le sexe et les variants de CYP chez les personnes prenant du clopidogrel et, si tel est le cas, quels sont ses effets sur les résultats cliniques indésirables après un an. Méthodologie: Nous avons utilisé les données d’une cohorte combinée de 2 272 patients (âge médian : 49 ans; 56 % de femmes) hospitalisés en raison d’un syndrome coronarien aigu. Nous avons examiné les interactions entre le sexe et les variants du CYP chez les utilisateurs de clopidogrel au moment de leur admission à l’hôpital et de leur congé pour évaluer les liens entre ces variables et les réhospitalisations après un an en raison d’événements cardiaques. Résultats: L’analyse de cas de 177 participants prenant du clopidogrel au moment de leur admission à l’hôpital a montré que le risque d’événement athérothrombotique était plus élevé chez les femmes porteuses de l’allèle non fonctionnel CYP2C9∗3 (rapport de cotes = 3,77; intervalle de confiance [IC] à 95 % = 1,54 à 9,24). Les résultats obtenus avec le modèle de régression logistique multivariée pour les utilisateurs de clopidogrel au moment du congé (n = 1 733) indiquent que les femmes présentaient un risque significativement plus élevé de réhospitalisation en raison d’un événement athérothrombotique après un an (rapport de cotes = 1,55; [IC] à 95 % = 1,16 à 2,07), comparativement aux hommes. Toutefois, les allèles non fonctionnels, considérés individuellement ou sur la base d’un score de risque génétique, n’étaient pas liés à la réhospitalisation après un an. Conclusion: Cette étude fait ressortir la nécessité de mieux comprendre le rôle de l’interaction sexe-gène dans les différences entre les sexes relativement au métabolisme des médicaments.

Background Gender‐related factors are psycho‐socio‐cultural characteristics and are associated with adverse clinical outcomes in acute myocardial infarction, independent of sex. Whether sex‐ and gender‐related factors contribute to the substantial heterogeneity in hospital length of stay (LOS) among patients with non–ST‐segment–elevation myocardial infarction remains unknown. Methods and Results This observational cohort study combined and analyzed data from the GENESIS‐PRAXY (Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome study), EVA (Endocrine Vascular Disease Approach study), and VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI [Acute Myocardial Infarction] Patients study) cohorts of adults hospitalized across Canada, the United States, Switzerland, Italy, Spain, and Australia for non–ST‐segment–elevation myocardial infarction. In total, 5219 participants were assessed for eligibility. Sixty‐three patients were excluded for missing LOS, and 2938 were excluded because of no non–ST‐segment–elevation myocardial infarction diagnosis. In total, 2218 participants were analyzed (66% women; mean±SD age, 48.5±7.9 years; 67.8% in the United States). Individuals with longer LOS (51%) were more likely to be White race, were more likely to have diabetes, hypertension, and a lower income, and were less likely to be employed and have completed secondary education. No univariate association between sex and LOS was observed. In the adjusted multivariable model, age (0.62 d/10 y; P

Background PARAGON‐HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) suggested a potential benefit of sacubitril–valsartan in women with preserved ejection fraction. Among patients with heart failure previously treated with angiotensin‐converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), we studied whether effectiveness of treatment with sacubitril–valsartan compared with ACEI/ARB monotherapy differed between men and women for both preserved and reduced ejection fraction. Methods and Results Data were derived from the Truven Health MarketScan Databases between January 1, 2011, and December 31, 2018. We included patients with a primary diagnosis of heart failure on treatment with ACEIs, ARBs, or sacubitril–valsartan on the basis of the first prescription after diagnosis. A total of 7181 patients treated with sacubitril–valsartan, 25 408 patients using an ACEI, and 16 177 patients treated with ARBs were included. A total of 790 readmissions or deaths occurred among 7181 patients in the sacubitril–valsartan group and 11 901 events in 41 585 patients treated with an ACEI/ARB. Adjusted for covariates, the hazard ratio (HR) for treatment with sacubitril–valsartan compared with an ACEI or ARB was 0.74 (95% CI, 0.68–0.80). The protective effect of sacubitril–valsartan was evident for men and women (women: HR, 0.75 [95% CI, 0.66–0.86]; P

Background: Women with physical disabilities are faced with challenges in many aspects of life—education, work, income, relationships, as well as their general health. These women are at a greater risk of developing heart disease. This study aimed to explore the cardiac pain experiences of women with physical disabilities and heart disease within a Canadian healthcare context. Methods: In this qualitative study, 8 women with physical disabilities and heart disease from across Canada were interviewed. They were asked about their pre-, peri-, and post-diagnostic experiences in the Canadian healthcare system. Transcripts of the interviews were analyzed using a hermeneutic phenomenological approach inspired by Ricoeur. Results: Two main themes were uncovered in the analysis of the transcripts, as follows: (i) the diagnostic journey; and (ii) life with cardiac symptoms and a disability. The women indicated that they had experienced difficulties in utilizing the Canadian healthcare system prior to receiving a cardiac diagnosis, including long waitlists, expensive and unreliable transport, issues with accessibility, and dealing with providers’ attitudinal barriers regarding disability. Receiving a diagnosis was challenging due to poor relationships with healthcare providers; however, having a same-sex provider seemed essential to receiving adequate care. Self-managing a disability and heart disease had significant physical and psychological impact, which was lightened by financial and social supports, modified lifestyle choices, and self-advocacy. Conclusions: Women with physical disabilities are often forgotten in discussions encompassing equity and inclusion. The participants’ experiences offer insight into what changes are needed within the Canadian healthcare system in order to improve outcomes for these women. Résumé: Contexte: Les femmes qui présentent une incapacité physique doivent composer avec des défis dans de nombreux aspects de leur vie, notamment en ce qui touche l’éducation, le travail, le revenu, les relations et la santé en général. Le risque de cardiopathie est plus important dans leur cas. Cette étude visait à examiner comment la douleur cardiaque est vécue par les femmes présentant une incapacité physique et une cardiopathie dans le contexte des soins de santé au Canada. Méthodologie: Dans le cadre de cette étude qualitative, huit femmes présentant une incapacité physique et une cardiopathie ont participé à des entrevues menées à l’échelle du Canada. Elles ont été interrogées sur leurs expériences au sein du système de santé canadien au cours des périodes précédant, entourant et suivant le diagnostic. Les transcriptions des entrevues ont été analysées en fonction d’une approche phénoménologique herméneutique inspirée par Ricœur. Résultats: Deux grands thèmes ressortent de l’analyse des transcriptions, à savoir : (i) le parcours diagnostique; (ii) la vie avec des symptômes cardiaques et une incapacité physique. Les femmes interrogées ont indiqué qu’elles avaient éprouvé des difficultés dans leur parcours au sein du système de santé canadien avant de recevoir un diagnostic en cardiologie, évoquant à cet égard les longues listes d’attente, les services de transport coûteux et peu fiables, les problèmes d’accessibilité et les obstacles liés à l’attitude des fournisseurs de soins vis-à-vis de l’incapacité physique. Le fait de recevoir un diagnostic a été éprouvant en raison de rapports difficiles avec les fournisseurs de soins de santé; cependant, le fait d’avoir un fournisseur de soins de sexe féminin semblait être une condition essentielle à une prestation de soins adéquate. L’autoprise en charge d’une incapacité physique et d’une cardiopathie a eu des répercussions physiques et psychologiques importantes qui ont pu être allégées par le soutien financier et social, des modifications des habitudes de vie et l’autonomie sociale. Conclusions: Les femmes qui présentent une incapacité physique sont souvent laissées pour compte dans les discussions portant sur l’équité et l’inclusion. Le vécu des participantes donne un aperçu des changements qui doivent être apportés au sein du système de santé canadien afin d’améliorer les résultats chez ces femmes.

AimsThe aim of this study was to elucidate whether sex and gender factors influence access to health care and/or are associated with cardiovascular (CV) outcomes of individuals with diabetes mellitus (DM) across different countries.MethodsUsing data from the Canadian Community Health Survey (8.4% of respondent reporting DM) and the European Health Interview Survey (7.3% of respondents reporting DM), were analyzed. Self-reported sex and a composite measure of socio-cultural gender was constructed (range: 0–1; higher score represent participants who reported more characteristics traditionally ascribed to women). For the purposes of analyses the Gender Inequality Index (GII) was used as a country level measure of institutionalized gender.ResultsCanadian females with DM were more likely to undergo HbA1c monitoring compared to males (OR = 1.26, 95% CI: 1.01–1.58), while conversely in the European cohort females with DM were less likely to have their blood sugar measured compared to males (OR = 0.88, 95% CI: 0.79–0.99). A higher gender score in both cohorts was associated with less frequent diabetes monitoring. Additionally, independent of sex, higher gender scores were associated with higher prevalence of self-reported heart disease, stroke, and hospitalization in all countries albeit European countries with medium-high GII, conferred a higher risk of all outcomes and hospitalization rates than low GII countries.ConclusionRegardless of sex, individuals with DM who reported characteristics typically ascribed to women and those living in countries with greater gender inequity for women exhibited poorer diabetes care and greater risk of CV outcomes and hospitalizations.

Abstract Background Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality. Methods ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality. Results Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p

Abstract Background Vaccine hesitancy has been a growing challenge for public health in recent decades. Among factors contributing to vaccine hesitancy, concerns regarding vaccine safety and Adverse Events (AEs) play the leading role. Moreover, cognitive biases are critical in connecting such concerns to vaccine hesitancy behaviors, but their role has not been comprehensively studied. In this study, our first objective is to address concerns regarding vaccine AEs to increase vaccine acceptance. Our second objective is to identify the potential cognitive biases connecting vaccine hesitancy concerns to vaccine-hesitant behaviors and identify the mechanism they get triggered in the vaccine decision-making process. Methods First, to mitigate concerns regarding AEs, we quantitatively analyzed the U.S. Vaccine Adverse Event Reporting System (VAERS) from 2011 to 2018 and provided evidence regarding the non-severity of the AEs that can be used as a communicable summary to increase vaccine acceptance. Second, we focused on the vaccination decision-making process. We reviewed cognitive biases and vaccine hesitancy literature to identify the most potential cognitive biases that affect vaccine hesitancy and categorized them adopting the Precaution Adoption Process Model (PAPM). Results Our results show that the top frequent AEs are expected mild reactions like injection site erythema (4.29%), pyrexia (3.66%), and injection site swelling (3.21%). 94.5% of the reports are not serious and the average population-based serious reporting rate over the 8 years was 25.3 reports per 1 million population. We also identified 15 potential cognitive biases that might affect people’s vaccination decision-making and nudge them toward vaccine hesitancy. We categorized these biases based on the factors that trigger them and discussed how they contribute to vaccine hesitancy. Conclusions This paper provided an evidence-based communicable summary of VAERS. As the most trusted sources of vaccine information, health practitioners can use this summary to provide evidence-based vaccine information to vaccine decision-makers (patients/parents) and mitigate concerns over vaccine safety and AEs. In addition, we identified 15 potential cognitive biases that might affect the vaccination decision-making process and nudge people toward vaccine hesitancy. Any plan, intervention, and message to increase vaccination uptake should be modified to decrease the effect of these potential cognitive biases.

Background: There is an upsurge of cardiovascular diseases (CVDs) in sub-Saharan Africa (SSA). Irrespective of biological sex, gender-related factors could be the precursor of these conditions. Objective: To examine the associations between biological sex, gender-related variables, and cardiovascular health (CVH) risk factors in SSA countries. Methods: We used data from the STEPwise approach to surveillance of risk factors for non-communicable disease survey, conducted in adults from Ghana, Gambia, Mali, Guinea, and Botswana. The main outcome was CVH, measured through the health index with values ranging from 0 (worst) to 5 (best or ideal) CVH. Multivariable logistic regression was applied to determine the gender-related factors related to poorer CVH (index less than 4). Results: Data included 15,356 adults (61.4% females, mean age 36.9 years). The prevalence of hypertension (21.6% vs. 13.8%) and overweight/obesity (48.3% vs. 27.5%) was higher among females as compared to males. Females were more likely to be unemployed (17.3% vs. 9.7%) or reported unpaid work (36.8% vs. 15.2%). Overall, females showed worse CVH than males (ORfemale = 0.95, 95% CI:0.91–0.99). Being married was associated with better CVH compared with being single, more so for males (ORmale = 1.09, 95% CI:0.96–1.24, pinteraction < 0.01). Males with unpaid work (ORmale = 1.28, 95% CI:1.12–1.47) had better CVH than their unpaid female counterparts (ORfemale = 1.08, 95% CI:1.01–1.17). Conclusion: In SSA populations, being female was associated with poorer CVH given the disproportionate burden of hypertension and overweight/obesity. Gender-related factors such as marital status and unpaid work were associated with better CVH in males compared to females.

Abstract Influenza immunization protects seniors against influenza and its potentially serious complications. It is uncertain whether standard-dose (SD) quadrivalent vaccine offers better protection over other formulations in the elderly. In this study, we compared the effectiveness of SD-trivalent, high-dose (HD) trivalent, SD-quadrivalent, and adjuvanted trivalent vaccines in seniors (≥65 years) in a real-world setting. We selected over 200,000 individuals in each of 6 influenza seasons from 2012 to 2018 using MarketScan® databases. The two outcomes were hospitalization or emergency room (ER) visit due to (1) influenza or (2) pneumonia. Here, SD-quadrivalent was associated with higher risk of influenza-related hospitalization/ER visit (adjusted hazard ratio (aHR) 1.14 and 95% confidence interval (95% CI) 1.05–1.24) and of pneumonia-related hospitalization/ER visit (aHR 1.04 and 95% CI 1.01–1.07) vs. HD-trivalent. SD-trivalent followed similar trends compared to HD-trivalent (aHR 1.16 and 95% CI 1.06–1.27 for hospitalized/ER visit influenza; aHR 1.07 and 95% CI 1.05–1.10 for hospitalized/ER visit pneumonia). We could not demonstrate risk differences between SD vaccine formulations and between adjuvanted trivalent and one of the other three vaccines. Risk estimates slightly varied across seasons. These findings suggest that SD vaccine formulations vs. HD-trivalent were associated with higher risk of hospitalization/ER visit for influenza and pneumonia in seniors.

Abstract Background Patient attitudes about health and healthcare have emerged as important outcomes to assess in clinical studies. Gender is increasingly recognized as an intersectional social construct that may influence health. Our objective was to determine potential sex differences in self-reported overall health and access to healthcare and whether those differences are influenced by individual social factors in two relatively similar countries. Methods Two public health surveys from countries with high gender equality (measured by UN GII) and universal healthcare systems, Canada (CCHS2014, n = 57,041) and Austria (AT-HIS2014, n = 15,212), were analysed. Perceived health was assessed on a scale of 1 (very bad) to 4 (very good) and perceived unmet healthcare needs was reported as a dichotomous variable (yes/no). Interactions between sex and social determinants (i.e. employment, education level, immigration and marital status) on outcomes were analysed. Results Individuals in both countries reported high perceived health (Scoring > 2, 85.0% in Canada, 79.9% in Austria) and a low percentage reported unmet healthcare needs (4.6% in Canada, 10.7% in Austria). In both countries, sex and several social factors were associated with high perceived health, and a sex-by-marital status interaction was observed, with a greater negative impact of divorce for men. Female sex was positively associated with unmet care needs in both countries, and sex-by-social factors interactions were only detected in Canada. Conclusions The intersection of sex and social factors in influencing patient-relevant outcomes varies even among countries with similar healthcare and high gender equality.

Cardio-pulmonary diseases, which were once regarded as a man's illness, have been one of the leading causes of morbidity and mortality for both men and women in many countries in recent years. Both gender and sex influence the functional and structural changes in the human body and therefore play an important role in disease clinical manifestation, treatment choice, and/or response to treatment and prognosis of health outcomes. The gender dimension integrates sex and gender analysis in health sciences and medical research, however, it is still relatively overlooked suggesting the need for empowerment in the medical research community. Latest advances in the field of cardiovascular research have provided supportive evidence that the application of biological variables of sex has led to the understanding that heart disease in females may have different pathophysiology compared to males, particularly in younger adults. It has also resulted in new diagnostic techniques and a better understanding of symptomatology, while gender analysis has informed more appropriate risk stratification and prevention strategies. The existing knowledge in the pulmonary field shows the higher prevalence of pulmonary disorders among females, however, the role of gender as a socio-cultural construct has yet to be explored for the implementation of targeted interventions. The purpose of this review is to introduce the concept of gender dimension and its importance for the cardiopulmonary continuum with a focus on shared pathophysiology and disease presentation in addition to interrelation with chronic kidney disease. The review presents basic knowledge of what gender dimension means, and the application of sex and gender aspects in cardiovascular medicine with a specific focus on early pulmonary development, pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). Early vascular aging and inflammation have been presented as a potential pathophysiological link, with further interactions between the cardiopulmonary continuum and chronic kidney disease. Finally, implications for potential future research have been provided to increase the impact of gender dimension on research excellence that would add value to everybody, foster toward precision medicine and ultimately improve human health.

Cardiovascular diseases represent the leading cause of mortality and morbidity worldwide, and age is an important risk factor. Preclinical models provide supportive evidence toward age-related cardiac changes, as well as allow for the study of pathological aspects of the disease. In the present work, we evaluated the electrocardiogram (ECG) recording in the O. degus during the aging process in both females and males. Taking into account the age and sex, our study provides the normal ranges for the heart rate, duration and voltage of the ECG waves and intervals, as well as electrical axis deviation. We found that the QRS complex duration and QTc significantly increased with age, whereas the heart rate significantly decreased. On the other hand, the P wave, PR and QTc segments durations, S wave voltage and electrical axis were found to be significantly different between males and females. The heart rhythm was also altered in aged animals, resulting in an increased incidence of arrhythmias, especially in males. Based on these results, we suggest that this rodent model could be useful for cardiovascular research, including impacts of aging and biological sex.

Abstract Background In this paper, we argue for Gender as a Sociocultural Variable (GASV) as a complement to Sex as a Biological Variable (SABV). Sex (biology) and gender (sociocultural behaviors and attitudes) interact to influence health and disease processes across the lifespan—which is currently playing out in the COVID-19 pandemic. This study develops a gender assessment tool—the Stanford Gender-Related Variables for Health Research—for use in clinical and population research, including large-scale health surveys involving diverse Western populations. While analyzing sex as a biological variable is widely mandated, gender as a sociocultural variable is not, largely because the field lacks quantitative tools for analyzing the influence of gender on health outcomes. Methods We conducted a comprehensive review of English-language measures of gender from 1975 to 2015 to identify variables across three domains: gender norms, gender-related traits, and gender relations. This yielded 11 variables tested with 44 items in three US cross-sectional survey populations: two internet-based (N = 2051; N = 2135) and a patient-research registry (N = 489), conducted between May 2017 and January 2018. Results Exploratory and confirmatory factor analyses reduced 11 constructs to 7 gender-related variables: caregiver strain, work strain, independence, risk-taking, emotional intelligence, social support, and discrimination. Regression analyses, adjusted for age, ethnicity, income, education, sex assigned at birth, and self-reported gender identity, identified associations between these gender-related variables and self-rated general health, physical and mental health, and health-risk behaviors. Conclusion Our new instrument represents an important step toward developing more comprehensive and precise survey-based measures of gender in relation to health. Our questionnaire is designed to shed light on how specific gender-related behaviors and attitudes contribute to health and disease processes, irrespective of—or in addition to—biological sex and self-reported gender identity. Use of these gender-related variables in experimental studies, such as clinical trials, may also help us understand if gender factors play an important role as treatment-effect modifiers and would thus need to be further considered in treatment decision-making.

Abstract In addition to biological sex, gender, defined as the sociocultural dimension of being a woman or a man, plays a central role in health. However, there are so far few approaches to quantify gender in a retrospective manner in existing study datasets. We therefore aimed to develop a methodology that can be retrospectively applied to assess gender in existing cohorts. We used baseline data from the Berlin Aging Study II (BASE-II), obtained in 2009–2014 from 1869 participants aged 60 years and older. We identified 13 gender-related variables and used them to construct a gender score by using primary component and logistic regression analyses. Of these, nine variables contributed to a gender score: chronic stress, marital status, risk-taking behaviour, personality attributes: agreeableness, neuroticism, extraversion, loneliness, conscientiousness, and level of education. Females and males differed significantly in the distribution of the gender score, but a significant overlap was also found. Thus, we were able to develop a gender score in a retrospective manner from already collected data that characterized participants in addition to biological sex. This approach will allow researchers to introduce the notion of gender retrospectively into a large number of studies.

Objective To examine sex and gender roles in COVID-19 test positivity and hospitalisation in sex-stratified predictive models using machine learning.Design Cross-sectional study.Setting UK Biobank prospective cohort.Participants Participants tested between 16 March 2020 and 18 May 2020 were analysed.Main outcome measures The endpoints of the study were COVID-19 test positivity and hospitalisation. Forty-two individuals’ demographics, psychosocial factors and comorbidities were used as likely determinants of outcomes. Gradient boosting machine was used for building prediction models.Results Of 4510 individuals tested (51.2% female, mean age=68.5±8.9 years), 29.4% tested positive. Males were more likely to be positive than females (31.6% vs 27.3%, p=0.001). In females, living in more deprived areas, lower income, increased low-density lipoprotein (LDL) to high-density lipoprotein (HDL) ratio, working night shifts and living with a greater number of family members were associated with a higher likelihood of COVID-19 positive test. While in males, greater body mass index and LDL to HDL ratio were the factors associated with a positive test. Older age and adverse cardiometabolic characteristics were the most prominent variables associated with hospitalisation of test-positive patients in both overall and sex-stratified models.Conclusion High-risk jobs, crowded living arrangements and living in deprived areas were associated with increased COVID-19 infection in females, while high-risk cardiometabolic characteristics were more influential in males. Gender-related factors have a greater impact on females; hence, they should be considered in identifying priority groups for COVID-19 infection vaccination campaigns.

Abstract Background Among the unknowns posed by the coronavirus disease 2019 (COVID-19) outbreak, the role of biological sex to explain disease susceptibility and progression is still a matter of debate, with limited sex-disaggregated data available. Methods A retrospective analysis was performed to assess if sex differences exist in the clinical manifestations and transitions of care among hospitalized individuals dying with laboratory-confirmed SARS-CoV-2 infection in Italy (February 27–June 11, 2020). Clinical characteristics and the times from symptoms’ onset to admission, nasopharyngeal swab, and death were compared between sexes. Adjusted multivariate analysis was performed to identify the clinical features associated with male sex. Results Of the 32,938 COVID-19-related deaths that occurred in Italy, 3517 hospitalized and deceased individuals with COVID-19 (mean 78 ± 12 years, 33% women) were analyzed. At admission, men had a higher prevalence of ischemic heart disease (adj-OR = 1.76, 95% CI 1.39–2.23), chronic obstructive pulmonary disease (adj-OR = 1.7, 95% CI 1.29–2.27), and chronic kidney disease (adj-OR = 1.48, 95% CI 1.13–1.96), while women were older and more likely to have dementia (adj-OR = 0.73, 95% CI 0.55–0.95) and autoimmune diseases (adj-OR = 0.40, 95% CI 0.25–0.63), yet both sexes had a high level of multimorbidity. The times from symptoms’ onset to admission and nasopharyngeal swab were slightly longer in men despite a typical acute respiratory illness with more frequent fever at the onset. Men received more often experimental therapy (adj-OR = 2.89, 95% CI 1.45–5.74) and experienced more likely acute kidney injury (adj-OR = 1.47, 95% CI 1.13–1.90). Conclusions Men and women dying with COVID-19 had different clinical manifestations and transitions of care. Identifying sex-specific features in individuals with COVID-19 and fatal outcome might inform preventive strategies.

Background: Current guidelines are relatively general regarding the type of patient with heart failure (HF) who should be considered for catheter ablation (CA) of atrial fibrillation (AF). The aim of the present study was to identify clinical predictors and sex differences for treatment with CA in the AF-HF population. Methods: A population-based AF-HF cohort was created using the Quebec administrative data (2000-2017). Patients were followed from the date of diagnosis of both diseases to the date of CA or death. Predictors for CA, represented by time-varying covariates, were assessed in a multivariable Cox model that accounted for the competing risk of death. Results: Among 101,931 patients with AF-HF with medication information (median age, 80.7 years; interquartile range [IQR], 73.9-86.3; 51.4% were female, median CHA2DS2-VASc, 4; IQR, 3-4), only 432 (0.4%) underwent CA after a median of 0.8 years (IQR, 0.1-2.7). Independent of multiple comorbidities and advanced age, which were associated with a lower likelihood of CA, women were approximately half as likely to undergo a CA (26% were women; adjusted hazard ratio, 0.6; 95% confidence interval, 0.4-0.7). Prior use of direct-acting oral anticoagulants and antiarrhythmics, and the presence of an implantable cardioverter-defibrillator were also predictors for CA treatment (P < 0.05 for all). Conclusion: In a real-world population, CA was infrequently used to treat AF among patients with HF, and the likelihood of CA was further reduced in women. Because patients with CA had few comorbidities, future studies need to be conducted to determine whether CA can be beneficial in subjects whose clinical characteristics are more representative of the AF-HF population. Résumé: Contexte: Les lignes directrices actuelles abordent de façon relativement générale les cas d’insuffisance cardiaque (IC) où les patients devraient être considérés comme des candidats à l’ablation par cathéter (AC) pour le traitement de la fibrillation auriculaire (FA). La présente étude visait à cerner les prédicteurs cliniques et les différences entre les sexes dans le contexte de l’AC au sein de la population atteinte de FA et d’IC. Méthodologie: Une cohorte populationnelle de patients atteints de FA et d’IC a été constituée à partir de données administratives du Québec (2000-2017). Le suivi des patients allait de la date du diagnostic des deux affections à la date de l’AC ou du décès. Les prédicteurs d’AC, représentés par des covariables temporalisées, ont été évalués dans un modèle de Cox multivarié tenant compte du risque concurrent de décès. Résultats: Sur 101 931 patients atteints de FA et d’IC dont la médication était documentée (âge médian : 80,7 ans; intervalle interquartile [IIQ] : 73,9-86,3; proportion de patients de sexe féminin : 51,4 %; score CHA2DS2-VASc médian : 4; IIQ : 3-4), seulement 432 (0,4 %) ont subi une AC au bout d’un laps de temps médian de 0,8 an (IIQ : 0,1-2,7). Indépendamment des maladies concomitantes multiples et de l’âge avancé, associés à une moindre probabilité d’AC, les femmes étaient environ deux fois moins susceptibles de subir une AC (proportion de patients de sexe féminin : 26 %; rapport des risques instantanés corrigé : 0,6; intervalle de confiance à 95 % : de 0,4 à 0,7). Les antécédents de traitement par des anticoagulants oraux à action directe et des antiarythmiques, ainsi que la présence d’un défibrillateur cardioverteur implantable étaient également des prédicteurs d’AC (p < 0,05 dans tous les cas). Conclusion: Au sein d’une population en contexte réel, l’AC a été rarement pratiquée pour traiter la FA chez des patients atteints d’IC. En outre, la probabilité d’une AC était moindre chez les femmes. Étant donné que les patients ayant subi une AC présentaient peu de maladies concomitantes, d’autres études devront être menées pour déterminer si l’AC peut être salutaire chez les personnes présentant des caractéristiques cliniques plus représentatives de la population atteinte de FA et d’IC.

Background The extent to which race influences in‐hospital quality of care for young adults (≤55 years) with acute myocardial infarction (AMI) is largely unknown. We examined racial disparities in in‐hospital quality of AMI care and their impact on 1‐year cardiac readmission. Methods and Results We used data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study enrolling young Black and White US adults with AMI (2008–2012). An in‐hospital quality of care score (QCS) was computed (standard AMI quality indicators divided by the total a patient is eligible for). Multivariable logistic regression was performed to identify factors associated with the lowest QCS tertile, including interactions between race and social determinants of health. Among 2846 young adults with AMI (median 48 years [interquartile range 44–52], 67.4% women, 18.8% Black race), Black individuals, especially women, exhibited a higher prevalence of cardiac risk factors and social determinants of health and were more likely to experience a non–ST‐segment–elevation myocardial infarction than White individuals. Black individuals were more likely in the lowest QCS tertile than White individuals (40.8% versus 34.7%; P=0.003). The association between Black race and low QCS (odds ratio [OR], 1.25; 95% CI, 1.02–1.54) was attenuated by adjustment for confounders. Employment was independently associated with better QCS, especially among Black participants (OR, 0.76; 95% CI, 0.62–0.92; P‐interaction=0.02). Black individuals experienced a higher rate of 1‐year cardiac readmission (29.9% versus 20.0%; P

Background Readmission over the first year following hospitalization for acute myocardial infarction (AMI) is common among younger adults (≤55 years). Our aim was to develop/validate a risk prediction model that considered a broad range of factors for readmission within 1 year. Methods and Results We used data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study, which enrolled young adults aged 18 to 55 years hospitalized with AMI across 103 US hospitals (N=2979). The primary outcome was ≥1 all‐cause readmissions within 1 year of hospital discharge. Bayesian model averaging was used to select the risk model. The mean age of participants was 47.1 years, 67.4% were women, and 23.2% were Black. Within 1 year of discharge for AMI, 905 (30.4%) of participants were readmitted and were more likely to be female, Black, and nonmarried. The final risk model consisted of 10 predictors: depressive symptoms (odds ratio [OR], 1.03; 95% CI, 1.01–1.05), better physical health (OR, 0.98; 95% CI, 0.97–0.99), in‐hospital complication of heart failure (OR, 1.44; 95% CI, 0.99–2.08), chronic obstructive pulmomary disease (OR, 1.29; 95% CI, 0.96–1.74), diabetes mellitus (OR, 1.23; 95% CI, 1.00–1.52), female sex (OR, 1.31; 95% CI, 1.05–1.65), low income (OR, 1.13; 95% CI, 0.89–1.42), prior AMI (OR, 1.47; 95% CI, 1.15–1.87), in‐hospital length of stay (OR, 1.13; 95% CI, 1.04–1.23), and being employed (OR, 0.88; 95% CI, 0.69–1.12). The model had excellent calibration and modest discrimination (C statistic=0.67 in development/validation cohorts). Conclusions Women and those with a prior AMI, increased depressive symptoms, longer inpatient length of stay and diabetes may be more likely to be readmitted. Notably, several predictors of readmission were psychosocial characteristics rather than markers of AMI severity. This finding may inform the development of interventions to reduce readmissions in young patients with AMI.

Gender refers to the socially constructed roles, behaviours, expressions and identities of girls, women, boys, men and gender diverse people. Gender-related factors are seldom assessed as determinants of health outcomes, despite their powerful contribution. The Gender Outcomes INternational Group: to Further Well-being Development (GOING-FWD) project developed a standard five-step methodology applicable to retrospectively identify gender-related factors and assess their relationship to outcomes across selected cohorts of non-communicable chronic diseases from Austria, Canada, Spain, Sweden. Step 1 (identification of gender-related variables): Based on the gender framework of the Women Health Research Network (ie, identity, role, relations and institutionalised gender), and available literature for a certain disease, an optimal ‘wish-list’ of gender-related variables was created and discussed by experts. Step 2 (definition of outcomes): Data dictionaries were screened for clinical and patient-relevant outcomes, using the International Consortium for Health Outcome Measurement framework. Step 3 (building of feasible final list): a cross-validation between variables per database and the ‘wish-list’ was performed. Step 4 (retrospective data harmonisation): The harmonisation potential of variables was evaluated. Step 5 (definition of data structure and analysis): The following analytic strategies were identified: (1) local analysis of data not transferable followed by a meta-analysis combining study-level estimates; (2) centrally performed federated analysis of data, with the individual-level participant data remaining on local servers; (3) synthesising the data locally and performing a pooled analysis on the synthetic data and (4) central analysis of pooled transferable data. The application of the GOING-FWD multistep approach can help guide investigators to analyse gender and its impact on outcomes in previously collected data.

Objectives There are increasing requirements to make research data, especially clinical trial data, more broadly available for secondary analyses. However, data availability remains a challenge due to complex privacy requirements. This challenge can potentially be addressed using synthetic data.Setting Replication of a published stage III colon cancer trial secondary analysis using synthetic data generated by a machine learning method.Participants There were 1543 patients in the control arm that were included in our analysis.Primary and secondary outcome measures Analyses from a study published on the real dataset were replicated on synthetic data to investigate the relationship between bowel obstruction and event-free survival. Information theoretic metrics were used to compare the univariate distributions between real and synthetic data. Percentage CI overlap was used to assess the similarity in the size of the bivariate relationships, and similarly for the multivariate Cox models derived from the two datasets.Results Analysis results were similar between the real and synthetic datasets. The univariate distributions were within 1% of difference on an information theoretic metric. All of the bivariate relationships had CI overlap on the tau statistic above 50%. The main conclusion from the published study, that lack of bowel obstruction has a strong impact on survival, was replicated directionally and the HR CI overlap between the real and synthetic data was 61% for overall survival (real data: HR 1.56, 95% CI 1.11 to 2.2; synthetic data: HR 2.03, 95% CI 1.44 to 2.87) and 86% for disease-free survival (real data: HR 1.51, 95% CI 1.18 to 1.95; synthetic data: HR 1.63, 95% CI 1.26 to 2.1).Conclusions The high concordance between the analytical results and conclusions from synthetic and real data suggests that synthetic data can be used as a reasonable proxy for real clinical trial datasets.Trial registration number NCT00079274.

Preeclampsia is a common hypertensive disorder in pregnant women and whose causes and consequences have focused primarily on cardiovascular outcomes on the mother and offspring, often without taking into consideration the possible effects on the brain. One possible cause of preeclampsia has been attributed to alterations in the renin-angiotensin system, which has also been linked to cognitive decline. In this pilot study, we use a transgenic mouse model that chronically overexpresses human angiotensinogen and renin (R+A+ mice) that displayed characteristics of preeclampsia such as proteinuria during gestation. Offspring of these mothers as well as from control mothers were also examined. We were primarily interested in detecting whether cognitive deficits were present in the mothers and offspring in the long term and used a spatial learning and memory task as well as an object recognition task at three timepoints: 3, 8, and 12 months post-partum or post-natal, while measuring blood pressure and performing urine analysis after each timepoint. While we did not find significant deficits in preeclamptic mothers at the later timepoints, we did observe negative consequences in the pups of R+A+ mice that coincided with hemodynamic alterations whereby pups had higher whisker-evoked oxygenated hemoglobin levels and increased cerebral blood flow responses compared to control pups. Our study provides validation of this preeclampsia mouse model for future studies to decipher the underlying mechanisms of long-term cognitive deficits found in offspring.

Introduction More women experience cardiac pain related to coronary artery disease and cardiac procedures compared with men. The overall goal of this programme of research is to develop an integrated smartphone and web-based intervention (HEARTPA♀N) to help women recognise and self-manage cardiac pain.Methods and analysis This protocol outlines the mixed methods strategy used for the development of the HEARTPA♀N content/core feature set (phase 2A), usability testing (phase 2B) and evaluation with a pilot randomised controlled trial (RCT) (phase 3). We are using the individual and family self-management theory, mobile device functionality and pervasive information architecture of mHealth interventions, and following a sequential phased approach recommended by the Medical Research Council to develop HEARTPA♀N. The phase 3 pilot RCT will enable us to refine the prototype, inform the methodology and calculate the sample size for a larger multisite RCT (phase 4, future work). Patient partners have been actively involved in setting the HEARTPA♀N research agenda, including defining patient-reported outcome measures for the pilot RCT: pain and health-related quality of life (HRQoL). As such, the guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trial Protocols (SPIRIT-PRO) are used to report the protocol for the pilot RCT (phase 3). Quantitative data (eg, demographic and clinical information) will be summarised using descriptive statistics (phases 2AB and 3) and a content analysis will be used to identify themes (phase 2AB). A process evaluation will be used to assess the feasibility of the implementation of the intervention and a preliminary efficacy evaluation will be undertaken focusing on the outcomes of pain and HRQoL (phase 3).Ethics and dissemination Ethics approval was obtained from the University of Toronto (36415; 26 November 2018). We will disseminate knowledge of HEARTPA♀N through publication, conference presentation and national public forums (Café Scientifique), and through fact sheets, tweets and webinars.Trial registration number NCT03800082.

Background Randomized controlled trials showed that newer glucose‐lowering agents are cardioprotective, but most participants were men. It is unknown whether benefits are similar in women. Methods and Results Among adults with type 2 diabetes mellitus not controlled with metformin with no prior use of insulin, we assessed for sex differences in the cardiovascular effectiveness and safety of sodium‐glucose‐like transport‐2 inhibitors (SGLT‐2i), glucagon‐like peptide‐1 receptor agonists (GLP‐1RA), dipeptidyl peptidase‐4 inhibitors, initiated as second‐line agents relative to sulfonylureas (reference‐group). We studied type 2 diabetes mellitus American adults with newly dispensed sulfonylureas, SGLT‐2i, GLP‐1RA, or dipeptidyl peptidase‐4 inhibitors (Marketscan‐Database: 2011–2017). We used multivariable Cox proportional hazards models with time‐varying exposure to compare time to first nonfatal cardiovascular event (myocardial infarction/unstable angina, stroke, and heart failure), and safety outcomes between drugs users, and tested for sex–drug interactions. Among 167 254 type 2 diabetes mellitus metformin users (46% women, median age 59 years, at low cardiovascular risk), during a median 4.5‐year follow‐up, cardiovascular events incidence was lower in women than men (14.7 versus 16.7 per 1000‐person‐year). Compared with sulfonylureas, hazard ratios (HRs) for cardiovascular events were lower with GLP‐1RA (adjusted HR‐women: 0.57, 95% CI: 0.48–0.68; aHR‐men: 0.82, 0.71–0.95), dipeptidyl peptidase‐4 inhibitors (aHR‐women: 0.83, 0.77–0.89; aHR‐men: 0.85, 0.79–0.91) and SGLT‐2i (aHR‐women: 0.58, 0.46–0.74; aHR‐men: 0.69, 0.57–0.83). A sex‐by‐drug interaction was statistically significant only for GLP‐1RA (P=0.002), suggesting greater cardiovascular effectiveness in women. Compared with sulfonylureas, risks of adverse events were similarly lower in both sexes for GLP‐1RA (aHR‐women: 0.81, 0.73–0.89; aHR‐men: 0.80, 0.71–0.89), dipeptidyl peptidase‐4 inhibitors (aHR‐women: 0.82, 0.78–0.87; aHR‐men: 0.83, 0.78–0.87) and SGLT‐2i (aHR‐women: 0.68, 0.59–0.78; aHR‐men: 0.67, 0.59–0.78) (all sex–drug interactions for adverse events P>0.05). Conclusions Newer glucose‐lowering drugs were associated with lower risk of cardiovascular events than sulfonylureas, with greater effectiveness of GLP‐1RA in women than men. Overall, they appeared safe, with a better safety profile for SGLT‐2i than for GLP‐1RA regardless of sex.

Abstract Background Perception of low subjective social status (SSS) relative to others in society or in the community has been associated with increased risk of cardiovascular disease. Our objectives were to determine whether low SSS in society was associated with barriers to access to care or hospital readmission in patients with established cardiovascular disease, and whether perceptions of discordantly high SSS in the community modified this association. Methods We conducted a prospective cohort study from 2009 to 2013 in Canada, United States, and Switzerland in patients admitted to hospital with acute coronary syndrome (ACS). Data on access to care and SSS variables were obtained at baseline. Readmission data were obtained 12 months post-discharge. We conducted multivariable logistic regression to model the odds of access to care and readmission outcomes in those with low versus high societal SSS. Results One thousand ninety patients admitted with ACS provided both societal and community SSS rankings. The low societal SSS cohort had greater odds of reporting that their health was affected by lack of health care access (OR 1.48, 95% CI 1.11, 1.97) and of experiencing cardiac readmissions (1.88, 95% CI 1.15, 3.06). Within the low societal SSS cohort, there was a trend toward fewer access to care barriers for those with discordantly high community SSS though findings varied based on the outcome variable. There were no statistically significant differences in readmissions based on community SSS rankings. Conclusion Low societal SSS is associated with increased barriers to access to care and cardiac readmissions. Though attenuated, these trends remained even when adjusting for clinical and sociodemographic factors, suggesting that perceived low societal SSS has health effects above and beyond objective socioeconomic factors. Furthermore, high community SSS may potentially mitigate the risk of experiencing barriers to access to health care in those with low societal SSS, though these associations were not statistically significant. Subjective social status relative to society versus relative to the community seem to represent distinct concepts. Insight into the differences between these two SSS constructs is imperative in the understanding of cardiovascular health and future development of public health policies.

Abstract Background Despite the growing appreciation of the importance of sex and gender considerations in transplantation research, there is currently no framework or good practice guidelines for the appropriate handling of sex and gender issues in human allotransplantation research. Methods We will conduct a scoping review to synthesize the evidence on how matters of sex and gender have been handled in human allotransplantation research. We will survey the literature discussing sex and gender in relation to transplantation, including adult and pediatric patients, hematopoietic and solid organ transplant recipients as well as organ donors. We will search MEDLINE and Embase for literature discussing sex and gender in relation to transplantation. Two reviewers will independently evaluate the eligibility of all identified titles and abstracts for inclusion in the full text review, as well as data extraction. Descriptive data and information on how sex and gender have been considered in human transplantation research will be reported. Discussion This scoping review will be an important stepping stone towards the development of good practice guidelines on study design and analysis considerations when handling sex and gender issues in human transplantation research. This scoping review can also help identify methodological issues that restrict the translation of transplantation research findings into clinical practice related to underestimation of sex/gender differences. This review will ultimately identify major gaps, inform donor-recipient selection, guide personalized interventions, and prioritize research recommendations in human transplantation research.

Background Clinical practice guideline (CPG) developers have yet to endorse a consistent and systematic approach for considering sex‐specific cardiovascular information in CPGs. This article describes an initiative led by the Canadian Cardiovascular Society to determine the feasibility and outcomes of a structured process for considering sex in a CPG for the management of ST‐segment–elevation myocardial infarction. Methods and Results A sex and gender champion was appointed to the guideline development committee. The feasibility of tailoring the CPG to sex was ascertained by recording (1) the male–female distribution of the study population, (2) the adequacy of sex‐specific representation in each study using the participation/prevalence ratio, and (3) whether data were disaggregated by sex. The outcome was to determine whether recommendations for CPGs based on an assessment of the evidence should differ by sex. In total, 175 studies were included. The mean percentage of female participants reported in the studies was 24.5% (SD: 6.6%; minimum: 0%; maximum: 51%). The mean participation/prevalence ratio was 0.62 (SD: 0.16; minimum: 0.00; maximum: 1.19). Eighteen (10.2%) studies disaggregated the data by sex. Based on the participation/prevalence ratio and the sex‐specific analyses presented, only 1 study provided adequate evidence to confidently inform the applicability of the CPG recommendations to male and female patients. Conclusions Implementing a systematic process for critically appraising sex‐specific evidence for CPGs was straightforward and feasible. Inadequate enrollment and reporting by sex hindered comprehensive sex‐specific assessment of the quality of evidence and strength of recommendations for a CPG on the management of ST‐segment–elevation myocardial infarction.

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner.

Objective. To compare dipeptidyl peptidase-4 (DPP-4) inhibitors with neutral protamine Hagedorn (NPH) insulin, in terms of effectiveness and safety for the management of patients with type 2 diabetes mellitus (DM2) not controlled on metformin and sulfonylureas. Methods. A retrospective cohort study of individuals with DM2 newly dispensed with either DPP-4 inhibitors or NPH as third-line therapy, after metformin and sulfonylurea. Treatment discontinuation, macrovascular outcomes, and hypoglycemia were compared using multivariable Cox regression models, adjusted for sex, age, year of cohort entry, place of residence, hypertension, past history of hypoglycemia, diabetic ketoacidosis, comorbidities, and number of visits to emergency departments, outpatient physician, and hospitalizations. Results. Treatment discontinuation and hypoglycemia occurred more frequently with NPH than with DPP-4 inhibitor users. In the adjusted Cox model, the use of NPH compared to that of DPP-4 inhibitors was associated with a higher risk of discontinuation (HR: 1.33; 95% CI 1.27–1.40) and hypoglycemia (HR: 2.98; 95% CI 2.72–3.28). Risk of cardiovascular events was similar across groups. Conclusions. This real-world analysis suggests that DM2 patients initiating third-line therapy with NPH have poorer control of diabetes when compared to DPP-4 inhibitor initiators.

BACKGROUND:Factors associated with study completion in younger adults are not well understood. This study sought to describe psychosocial, clinical, and demographic features associated with completion of a study of men and women with premature acute coronary syndrome. METHODS:As part of the GENdEr and Sex determInantS of cardiovascular disease: From bench to beyond-Premature Acute Coronary Syndrome (GENESIS-PRAXY) study, demographic, psychosocial, and clinical variables were assessed in 1213 patients hospitalized for acute coronary syndrome (≤ 55 years; 30% women). Patients were followed for 12 months. Dropouts withdrew from the study or were lost to follow-up after 12 months; completers were still enrolled after 12 months. RESULTS:Of 1213 patients initially enrolled, 777 (64.1%) completed 12-month follow-up. Fully adjusted models suggested that being older (OR = 1.04, 95% CI [1.01, 1.06]), higher subjective social status within one's country (OR = 1.11, 95% CI [1.01, 1.22]), being free of type II diabetes, (OR = 0.66, 95% CI [0.45, 0.97]), non-smoking status (OR = 0.70, 95% CI [0.51, 0.95]) and being free of depression (OR = 1.52, 95% CI [1.11, 2.07]) were independently associated with study completion. CONCLUSIONS:Recruitment/retention strategies targeting individuals who smoke, are younger, have low subjective social status within one's country, have diabetes, or have depression may improve participant follow-up in cardiovascular cohort studies.

BACKGROUND:Little is known about potential ethnic differences in stroke incidence. We compared incidence and time trends of ischemic stroke and primary intracerebral hemorrhage in South Asian, Chinese and white persons in a population-based study. METHODS:Population based census and administrative data analysis in the provinces of Ontario and British Columbia, Canada using validated ICD 9/ICD 10 coding for acute ischemic and hemorrhagic stroke (1997-2010). RESULTS:There were 3290 South Asians, 4444 Chinese and 160944 white patients with acute ischemic stroke and 535 South Asian, 1376 Chinese and 21842 white patients with intracerebral hemorrhage. South Asians were younger than whites at onset of stroke (70 vs. 74 years for ischemic and 67 vs. 71 years for hemorrhagic stroke). Age and sex adjusted ischemic stroke incidence in 2010 was 43% lower in Chinese and 63% lower in South Asian than in White patients. Age and sex adjusted intracerebral hemorrhage incidence was 18% higher in Chinese patients, and 66% lower in South Asian relative to white patients. Stroke incidence declined in all ethnic groups (relative reduction 69% in South Asians, 25% in Chinese, and 34% in white patients for ischemic stroke and for intracerebral hemorrhage, 79% for South Asians, 51% for Chinese and 30% in white patients). CONCLUSION:Although stroke rates declined across all ethnic groups, these rates differed significantly by ethnicity. Further study is needed to understand mechanisms underlying the higher ischemic stroke incidence in white patients and intracerebral hemorrhage in Chinese patients.

BackgroundCurrent recommendations for lipoprotein(a) (Lp[a]) focus on the control of other risk factors, including lowering low‐density lipoprotein cholesterol (LDL‐C), with little evidence to support this approach. Identifying interactions between Lp(a) and other risk factors could identify individuals at increased risk for Lp(a)‐mediated disease. Methods and ResultsWe used a case‐only study design and included 939 participants (median age=49 years, interquartile range 46–53, women=33.1%) from the GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond‐Premature Acute Coronary Syndrome (GENESIS‐PRAXY) study, a multicenter prospective cohort study of premature acute coronary syndrome. There was a higher prevalence of elevated Lp(a) levels (>50 mg/dL; 80th percentile) in PRAXY participants as compared to the general population (31% versus 20%; P2.5 mmol/L, indicating a synergistic interaction (adjusted odds ratio 1.51; 95% CI 1.08–2.09; P=0.015). The interaction with high Lp(a) was stronger at increasing LDL‐C levels (LDL‐C >3.5, adjusted odds ratio 1.87; LDL‐C >4.5, adjusted odds ratio 2.72). In a polytomous logistic model comparing mutually exclusive LDL‐C categories, the interaction with high Lp(a) became attenuated at LDL‐C ≤3.5 mmol/L (odds ratio 1.16; 95% CI 0.80–1.68, P=0.447). Other risk factors were not associated with high Lp(a). ConclusionsIn young acute coronary syndrome patients, high Lp(a) is more prevalent than in the general population and is strongly associated with high LDL‐C, suggesting that Lp(a) confers greater risk for acute coronary syndrome when LDL‐C is elevated. Individuals with high Lp(a) and LDL‐C >3.5 mmol/L may warrant aggressive LDL‐C lowering.

Walking and cardiovascular mortality are inversely associated in type 2 diabetes, but few studies have objectively measured associations of walking with individual cardiovascular risk factors. Such information would be useful for "dosing" daily steps in clinical practice. This study aimed to quantify decrements in blood pressure and glycated hemoglobin (A1C) per 1,000 daily step increments.Two hundred and one subjects with type 2 diabetes underwent assessments of step counts (pedometer-measured), blood pressure, A1C and anthropometric parameters. Due to missing data, the final analysis was conducted on 83 women and 102 men, with a mean age of 60 years. Associations of daily steps with blood pressure and A1C were evaluated using sex-specific multivariate linear regression models (adjusted for age, ethnicity, and BMI). Potential sex differences were confirmed in a combined model (women and men) with interaction terms. Mean values for daily steps, blood pressure, A1C and BMI were 5,357 steps/day; 137/80 mm Hg; 7.7% and 30.4 kg/m(2) respectively. A 1,000 daily step increment among women was associated with a -2.6 (95% CI: -4.1 to -1.1) mm Hg change in systolic and a -1.4 (95% CI: -2.2 to -0.6) mm Hg change in diastolic blood pressure. Among men, corresponding changes were -0.7 (95% CI: -2.1 to 0.7) and -0.6 (95% CI: -1.4 to 0.3) mm Hg, respectively. Sex differences were confirmed in combined models. Step counts and A1C did not demonstrate clinically important associations.A 1,000 steps/day increment is associated with important blood pressure decrements among women with type 2 diabetes but the data were inconclusive among men. Targeted "dose increments" of 1,000 steps/day in women may lead to measurable blood pressure reductions. This information may be of potential use in the titration or "dosing" of daily steps. No associations were found between step count increments and A1C.