A comparison of synthetic data generation and federated analysis for enabling international evaluations of cardiovascular health.

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.

Sex and gender aspects in diabetes mellitus: Focus on access to health care and cardiovascular outcomes.

Aims: The 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. Methods: Using 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. Results: Canadian 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. Conclusion: Regardless 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.

Need for improving immunization status and preventive care in diabetes mellitus patients.

BACKGROUND: The incidence and the comorbidities, such as infectious diseases (e.g. pneumonia or influenza) of diabetes mellitus are increasing. Therefore, the purpose of this study is to investigate immunization status and preventive care in diabetes mellitus patients. METHODS: Two groups from the Austrian health interview survey 2014 were identified, a cohort of diabetes mellitus (DM) individuals (n = 678) and a non-diabetes mellitus (non-DM) cohort (n = 15,093). The frequencies of doctors' visits, preventive care and immunization status were compared. Furthermore, the study population was divided by age (> 50 years, < 50 years) and differences between > 50 years old DM with < 50 years old DM and the > 50 years old DM and > 50 years old Non-DM cohort were investigated. RESULTS: In the DM cohort a higher frequency of influenza immunization (13.3% vs. 7.1%, p < 0.001), doctor visits (89.4% vs. 75.4%, p < 0.001), and preventive care, such as colonoscopy (11.2% vs. 6.8%, p < 0.001) and hemoccult tests (32.6% vs. 22.1%, p < 0.001) was observed. Even though older DM individuals have a higher risk for complications, the > 50 years DM cohort has similar frequencies of colonoscopy, hemoccult test and immunization against influenza and TBE (tick-borne encephalitis) compared to > 50 years Non-DM. Although the > 50 years old DM cohort had a higher frequency of doctors' visits, they still had lower frequencies of mammography and dentists' visits compared to > 50 years old Non-DM. In comparison to the < 50 years old DM cohort, the > 50 years DM cohort was related to lower intact immunization status of tetanus, diphtheria, Polio and TBE. Still a higher frequency of intact immunization of pneumococcus, influenza and doctors' visits in the > 50 years old DM cohort compared to the < 50 years old DM cohort can be reported. CONCLUSION: Preventive care and immunization status in the DM cohort just differ slightly from the general cohort but still should be improved.

Sex and Gender Impact Mental and Emotional Well-Being During COVID-19 Pandemic: A European Countries Experience.

Objective: The COVID-19 pandemic influences mental health drastically. Therefore, our aim was to investigate whether biological sex and gender-related factors are associated with mental health during the COVID-19 pandemic. Materials and Methods: The International COVID-19 Awareness and Responses Evaluation Study is an international multiwave cross-sectional observational cohort study of public awareness, attitudes, and responses to public health policies (www.mbmc- cmcm.ca/covid19). The study is led by the Montreal Behavioural Medicine Centre in collaboration with 200 international collaborators from 42 countries. It has received research ethics board approval from the Comité d'éthique de recherche du CIUSSS-NIM (Centre intégré universitaire de santé et de services sociaux du Nord- de-l'île-de-Montréal), approval no.: 2020-2099/25-03-2020. Recruitment began on March 27, 2020, and the survey is available in 34 languages. The associations between biological sex, sociocultural gender, and mental health were assessed in multivariate logistic regression models only for the European population (n = 12,300). Results: Positive correlations were found between female sex and "feeling nervous, anxious or worried" (OR = 3.2, p < 0.001, 95% CI 1.87-5.63) and "feeling sad, depressed or hopeless" (OR 1.8, p = 0.031, CI 1.05-3.05). Male sex was related to more frequently "feeling irritable, frustrated, and angry" (OR = 1.8, p = 0.04, 95% CI 1.03-2.99). Concerning gender, a negative correlation between being employed and "feeling lonely or isolated" (OR = 0.26, p < 0.001, 95% CI 0.11-0.59) was observed in the female cohort. Conclusion: Sex and gender differences exist in the emotional responses during the COVID-19 pandemic. Especially, within the female cohort, unemployment is negatively associated with mental health. Therefore, this study suggests more targeted psychological and social support for females during the pandemic.

Sex-Specific Effects of Vitamin D Status on the Metabolic Profile in Prediabetic Subjects.

INTRODUCTION: We aim to investigate the effect of vitamin D on metabolic parameters in a population with prediabetes and to detect possible sex differences. METHODS: In 621 patients with diagnosed prediabetes, glucose, lipid, and anthropometric parameters were measured. Furthermore, the interaction of 25-OH-vitamin D (25-hydroxyvitamin D) with metabolic and glucose metabolism parameters was analysed in the total prediabetic population, as well as after stratification by sex (female vs. male prediabetic subgroup), by logistic regression. RESULTS: 25-OH-vitamin D was negatively related to cholesterol, BMI, fatty liver index, insulin, and HOMA-IR. Especially in the male prediabetic cohort, 25-OH-vitamin D levels negatively correlated with total cholesterol levels (r = -0.17, p=0.001), with triglycerides (r = -0.17, p=0.001), and with HbA1c levels (r = -0.14, p=0.010). Only in the female cohort with prediabetes, we found a negative correlation of 25-OH-vitamin D levels with systolic (r = -0.18, p=0.005) and diastolic blood pressures (r = -0.23, p < 0.001). CONCLUSION: In this study, in females with prediabetes, 25-OH-vitamin D was notably related to a more favourable metabolic profile, including lower total cholesterol and higher HDL cholesterol levels. On the contrary, in men with prediabetes, there was a stronger association between 25-OH-vitamin D and cholesterol-HDL quotient, as well as fatty liver index was observed in the male prediabetic subgroup. Therefore, sex differences should be considered in future studies on vitamin D and glucose tolerance status.

Determinants of perceived health and unmet healthcare needs in universal healthcare systems with high gender equality.

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.

Sex, Gender, and Cardiovascular Health in Canadian and Austrian Populations.

BACKGROUND: Evidence differentiating the effect of biological sex from psychosociocultural factors (gender) in different societies and its relation to cardiovascular diseases is scarce. We explored the association between sex, gender, and cardiovascular health (CVH) among Canadian (CAN) and Austrian (AT) populations. METHODS: The Canadian Community Health Survey (CCHS) (n = 63,522; 55% female) and Austrian Health Interview Survey (AT-HIS) (n = 15,771; 56% female) were analyzed in a cross-sectional survey design. The CANHEART/ATHEART index, a measure of ideal CVH composed of 6 cardiometabolic risk factors (smoking, physical activity, fruit and vegetable consumption, overweight/obesity, diabetes, and hypertension; range 0-6; higher scores reflecting better CVH) was calculated for both databases. A composite measure of psychosociocultural gender was computed for each country (range 0-1, higher score identifying characteristics traditionally ascribed to women). RESULTS: Median CANHEART 4 (interquartile range 3-5) and CAN gender scores 0.55 (0.49-0.60) were similar to median ATHEART 4 (3-5) and AT gender scores 0.55 (0.46-0.64). Although higher gender scores (CCHS: ß = -1.33, 95% confidence interval [CI] -1.44 to -1.22; AT-HIS: ß = -1.08, 95% CI -1.26 to -0.89)) were associated with worse CVH, female sex (CCHS: ß = 0.35, 95% CI (0.33-0.37); AT-HIS: ß = 0.60, 95% CI (0.55-0.64)) was associated with better CVH in both populations. In addition, higher gender scores were associated with increased prevalence of heart disease compared with female sex. The magnitude of this risk was higher in Austrians. CONCLUSIONS: These results demonstrate that individuals with characteristics typically ascribed to women reported poorer cardiovascular health and higher risk of heart disease, independently from biological sex and baseline CV risk factors, in both countries. Female sex exhibited better CV health and a lower prevalence of heart disease than male in both populations. However, gender factors and magnitude of gender impact varied by country.

Penicillin G Induces H+, K+-ATPase via a Nitric Oxide-Dependent Mechanism in the Rat Colonic Crypt.

BACKGROUND/AIMS: The colonic H+, K+ ATPase (HKA2) is a heterodimeric membrane protein that exchanges luminal K+ for intracellular H+ and is involved in maintaining potassium homeostasis. Under homeostatic conditions, the colonic HKA2 remains inactive, since most of the potassium is absorbed by the small intestine. In diarrheal states, potassium is secreted and compensatory potassium absorption becomes necessary. This study proposes a novel mechanism whereby the addition of penicillin G sodium salt (penG) to colonic crypts stimulates potassium uptake in the presence of intracellular nitric oxide (NO), under sodium-free (0-Na+) conditions. METHODS: Sprague Dawley rat colonic crypts were isolated and pHi changes were monitored through the ammonium prepulse technique. Increased proton extrusion in 0-Na+ conditions reflected heightened H+, K+ ATPase activity. Colonic crypts were exposed to penG, L-arginine (a NO precursor), and N-nitro l-arginine methyl ester (L-NAME, a NO synthase inhibitor). RESULTS: Isolated administration of penG significantly increased H+, K+ ATPase activity from baseline, p 0.0067. Co-administration of arginine and penG in 0-Na+ conditions further upregulated H+, K+ ATPase activity, p <0.0001. Crypt perfusion with L-NAME and penG demonstrated a significant reduction in H+, K+ ATPase activity, p 0.0058. CONCLUSION: Overall, acute exposure of colonic crypts to penG activates the H+, K+ ATPase in the presence of NO. This study provides new insights into colonic potassium homeostasis.

Decompression of Multimorbidity Along the Disease Trajectories of Diabetes Mellitus Patients.

Multimorbidity, the presence of two or more diseases in a patient, is maybe the greatest health challenge for the aging populations of many high-income countries. One of the main drivers of multimorbidity is diabetes mellitus (DM) due to its large number of risk factors and complications. Yet, we currently have very limited understanding of how to quantify multimorbidity beyond a simple counting of diseases and thereby inform prevention and intervention strategies tailored to the needs of elderly DM patients. Here, we conceptualize multimorbidity as typical temporal progression patterns of multiple diseases, so-called trajectories, and develop a framework to perform a matched and sex-specific comparison between DM and non-diabetic patients. We find that these disease trajectories can be organized into a multi-level hierarchy in which DM patients progress from relatively healthy states with low mortality to high-mortality states characterized by cardiovascular diseases, chronic lower respiratory diseases, renal failure, and different combinations thereof. The same disease trajectories can be observed in non-diabetic patients, however, we find that DM patients typically progress at much higher rates along their trajectories. Comparing male and female DM patients, we find a general tendency that females progress faster toward high multimorbidity states than males, in particular along trajectories that involve obesity. Males, on the other hand, appear to progress faster in trajectories that combine heart diseases with cerebrovascular diseases. Our results show that prevention and efficient management of DM are key to achieve a compression of morbidity into higher patient ages. Multidisciplinary efforts involving clinicians as well as experts in machine learning and data visualization are needed to better understand the identified disease trajectories and thereby contribute to solving the current multimorbidity crisis in healthcare.