Sex Differences in CKD-Associated Mortality From 1990 to 2019: Data From the Global Burden of Disease Study

Rationale & Objective: Previous studies have shown chronic kidney disease (CKD) mortality rates to be lower among females than males. We aimed to examine the extent to which sex differences vary over time, among countries, and with age, using Global Burden of Disease (GBD) Study data. Study Design: Observational epidemiological study. Setting & Participants: GBD Study, which used published literature, vital registration systems, kidney replacement therapy registries, and household surveys. Exposures: Sex. Outcomes: CKD-associated mortality rate (per 100,000 population). Analytical Approach: Changes in CKD mortality between 1990 and 2019 were compared between sexes, globally, and separately for the 50 most populous countries. For 2019 only, sex differences in age-standardized and age-specific mortality were compared between countries. Results: There was no change in global age-standardized mortality for either sex between 1990 and 2019, with female mortality consistently 30% lower than male mortality. Percentage changes were less favorable among females than males in two-thirds of the 50 countries examined, with the greatest change disparities observed in Egypt, Thailand, and Malaysia. Although Mexico exhibited the greatest overall percentage increase, the increase was smaller in females (81% vs 138%). In 2019, female mortality varied between 47% lower and 60% higher than male mortality (in Angola and Egypt, respectively). In most countries, female mortality was lower across all age groups, with no narrowing of sex differences with age. Limitations: We were not able to assess the sex differences according to CKD stage and we did not explore other disease metrics (eg, disability-adjusted life years). Conclusions: Percentage changes in age-standardized CKD mortality have tended to be less favorable among females than males, with notable exceptions. Similarly, although female mortality is generally lower than male mortality, there are multiple examples of the opposite. Country-specific assessments of sex differences in CKD-associated outcomes are essential for equitable care

Women's representation as authors of retracted papers in the biomedical sciences

Women are under-represented among authors of scientific papers. Although the number of retractions has been rising over the past few decades, gender differences among authors of retracted papers remain poorly understood. Therefore, this study investigated gender differences in authorship of retracted papers in biomedical sciences available on Retraction- Watch. Among 35,635 biomedical articles retracted between 1970 and 2022, including 20,849 first authors and 20,413 last authors, women accounted for 27.4% [26.8 to 28.0] of first authors and 23.5% [22.9 to 24.1] of last authors. The lowest representation of women was found for fraud (18.9% [17.1 to 20.9] for first authors and 13.5% [11.9 to 15.1] for last authors) and misconduct (19.5% [17.3 to 21.9] for first authors and 17.8% [15.7 to 20.3] for last authors). Women's representation was the highest for issues related to editors and publishers (35.1% [32.2 to 38.0] for first authors and 24.8% [22.9 to 26.8] for last authors) and errors (29.5% [28.0 to 31.0] for first authors and 22.1% [20.7 to 23.4] for last authors). Most retractions (60.9%) had men as first and last authors. Gender equality could improve research integrity in biomedical sciences

Sex differences in CKD-associated mortality from 1990 to 2019: data from the global burden of disease study

Abstract Rationale & Objective: Previous studies have shown chronic kidney disease (CKD) mortality rates to be lower in females than males. We aimed to examine the extent to which sex differences vary over time, among countries and with age, using Global Burden of Disease (GBD) Study data. Study Design: Observational epidemiological study Setting & Participants: GBD Study, which used published literature, vital registration systems, kidney replacement therapy registries and household surveys. Exposures: Sex Outcomes: CKD-associated mortality rate (per 100,000 population) Analytical Approach: Changes in CKD mortality between 1990 and 2019 were compared between sexes, globally and for the 50 most populous countries. For 2019 only, sex differences in age-standardised and age-specific mortality were compared among countries. Results: There was no change in global age-standardised mortality in either sex between 1990 and 2019, with female mortality consistently 30% lower than male mortality. Percentage changes were less favourable in females than males in two-thirds of the 50 countries examined, with the greatest change disparities observed in Egypt, Thailand and Malaysia. In Mexico, which had the greatest overall percentage increase, the increase was smaller in females (81% vs 138%). Female mortality varied between 47% lower and 60% higher than males (in Angola and Egypt, respectively) in 2019. In most countries, female mortality was lower across all age groups, with no narrowing of sex differences with age. Limitations: We were not able to assess sex differences according to CKD stage, nor did we explore other disease metrics (e.g. disability-adjusted life years). Conclusions: Percentage changes in age-standardised CKD mortality have tended to be less favourable in females compared to males, but with some notable exceptions. Similarly, whilst female mortality is generally lower than in males, numerous examples exist where the opposite is true. Country-specific assessments of sex differences in CKD-associated outcomes are essential for equitable care

Sex and Gender in COVID-19 Vaccine Research: Substantial Evidence Gaps Remain

Since the start of the COVID-19 pandemic there has been a global call for sex/gender-disaggregated data to be made available, which has uncovered important findings about COVID-19 testing, incidence, severity, hospitalisations, and deaths. This mini review scopes the evidence base for efficacy, effectiveness, and safety of COVID-19 vaccines from both experimental and observational research, and asks whether (1) women and men were equally recruited and represented in vaccine research, (2) the outcomes of studies were presented or analysed by sex and/or gender, and (3) there is evidence of sex and/or gender differences in outcomes. Following a PubMed search, 41 articles were eligible for inclusion, including seven randomised controlled trials (RCTs), 11 cohort studies, eight cross-sectional surveys, eight routine surveillance studies, and seven case series. Overall, the RCTs contained equal representation of women and men; however, the observational studies contained a higher percentage of women. Of 10 studies with efficacy data, only three (30%) presented sex/gender-disaggregated results. Safety data was included in 35 studies and only 12 (34%) of these presented data by sex/gender. For those that did present disaggregated data, overall, the majority of participants reporting adverse events were women. There is a paucity of reporting and analysis of COVID-19 vaccine data by sex/gender. Research should be designed in a gender-sensitive way to present and, where possible analyse, data by sex/gender to ensure that there is a robust and specific evidence base of efficacy and safety data to assist in building public confidence and promote high vaccine coverage

Sex differences in chronic kidney disease prevalence in Asia: A systematic review and meta-analysis

Background: Previous reports on the prevalence of chronic kidney disease (CKD) in Asia have suggested important sex disparities but have been inconsistent in nature. We sought to synthesize available sex-disaggregated CKD prevalence data in Asia to quantify sex disparities in the region. Methods: We systematically searched MEDLINE and Embase for observational studies involving ≥500 adults who reported sex-disaggregated CKD prevalence data in any of the 26 countries in East, Southeast and South Asia. For each study we calculated the female:male prevalence ratio (PR), with a ratio >1 indicating a higher female prevalence. For each country, log-transformed PRs were pooled using random effects meta-analysis. These were then combined using a fixed effects model, weighting by population size, to estimate a pooled PR for each of East, Southeast and South Asia and Asia overall. Results: Sex-disaggregated data were available from 171 cohorts, spanning 15 countries and comprising 2 550 169 females and 2 595 299 males. Most studies (75.4%) came from East Asia (China, Taiwan, Japan and South Korea). Across Asia, CKD prevalence was higher in females {pooled prevalence 13.0% [95% confidence interval (CI) 11.3-14.9]} compared with males [pooled prevalence 12.1% (95% CI 10.3-14.1)], with a pooled PR of 1.07 (95% CI 0.99-1.17). Substantial heterogeneity was observed between countries. The pooled PRs for East, Southeast and South Asia were 1.11 (95% CI 1.02-1.21), 1.09 (0.88-1.36) and 1.03 (0.87-1.22), respectively. Conclusions: Current evidence suggests considerable between-country and-region heterogeneity in the female:male PR of CKD. However, there remains a large part of the region where data on sex-specific CKD prevalence are absent or limited. Country-level assessment of the differential burden of CKD in females and males is needed to define locally relevant policies that address the needs of both sexes

Prior Cardiovascular Treatments-A Key Characteristic in Determining Medication Adherence After an Acute Myocardial Infarction.

Objective: To investigate long-term adherence to guideline-recommended cardioprotective medications following hospitalization for an acute myocardial infarction (AMI), and identify characteristics associated with adherence. Methods: An Australian population-based cohort study was used to identify participants who had their first AMI between 2006 and 2014 and were alive after 12 months. Linked routinely collected hospital, and prescription medication claims data was used to study adherence over time. Predictors and rates of adherence to both lipid-lowering medication and renin-angiotensin system blockade at 12 months post-AMI was assessed. Results: 14,200 people (mean age 69.9 years, 38.7% female) were included in our analysis. At 12 months post-AMI, 29.5% (95% CI: 28.8-30.3%) of people were adherent to both classes of medication. Individuals receiving treatment with both lipid-lowering medication and renin-angiotensin system blockade during the 6 months prior to their AMI were over 9 times more likely to be adherent to both medications at 12 months post-AMI (66.2% 95% CI: 64.8-67.5%) compared to those with no prior medication use (treatment naïve) (7.1%, 95% CI: 6.4-7.9%). Prior cardiovascular treatment was the strongest predictor of long-term adherence even after adjusting for age, sex, education and income. Conclusions: Despite efforts to improve long-term medication adherence in patients who have experienced an acute coronary event, considerable gaps remain. Of particular concern are people who are commencing guideline-recommended cardioprotective medication at the time of their AMI. The relationship between prior cardiovascular treatments and post AMI adherence offers insight into the support needs for the patient. Health care intervention strategies, strengthened by enabling policies, are needed to provide support to patients through the initial months following their AMI

Canagliflozin and atrial fibrillation in type 2 diabetes mellitus: A secondary analysis from the CANVAS Program and CREDENCE trial and meta-analysis

Aim: To assess the effects of canagliflozin on the incidence of atrial fibrillation/atrial flutter (AF/AFL) and other key cardiorenal outcomes in a pooled analysis of the CANVAS and CREDENCE trials. Materials and Methods: Participants with type 2 diabetes and high risk of cardiovascular disease or chronic kidney disease were included and randomly assigned to canagliflozin or placebo. We explored the effects of canagliflozin on the incidence of first AF/AFL events and AF/AFL-related complications (ischaemic stroke/transient ischaemic attack/hospitalization for heart failure). Major adverse cardiovascular events and a renal-specific outcome by baseline AF/AFL status were analysed using Cox regression models. Results: Overall, 354 participants experienced a first AF/AFL event. Canagliflozin had no detectable effect on AF/AFL (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.67-1.02) compared with placebo. Subgroup analysis, however, suggested a possible reduction in AF/AFL in those with no AF/AFL history (HR 0.78, 95% CI 0.62-0.99). Canagliflozin was also associated with a reduction in AF/AFL-related complications (HR 0.74, 95% CI 0.65-0.86). There was no evidence of treatment heterogeneity by baseline AF/AFL history for other key cardiorenal outcomes (all Pinteraction > 0.14). Meta-analysis of five sodium-glucose cotransporter-2 (SGLT2) inhibitor trials demonstrated a 19% reduction in AF/AFL events with active treatment (HR 0.81, 95% CI 0.72-0.92). Conclusions: Overall, a significant effect of canagliflozin on the incidence of AF/AFL events could not be shown, however, a possible reduction in AF/AFL events in those with no prior history requires further investigation. Meta-analysis suggests SGLT2 inhibition reduces AF/AFL incidence

Effects of canagliflozin compared with placebo on major adverse cardiovascular and kidney events in patient groups with different baseline levels of HbA<inf>1c</inf>, disease duration and treatment intensity: results from the CANVAS Program

Aims/hypothesis: Type 2 diabetes mellitus can manifest over a broad clinical range, although there is no clear consensus on the categorisation of disease complexity. We assessed the effects of canagliflozin, compared with placebo, on cardiovascular and kidney outcomes in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program over a range of type 2 diabetes mellitus complexity, defined separately by baseline intensity of treatment, duration of diabetes and glycaemic control. Methods: We performed a post hoc analysis of the effects of canagliflozin on major adverse cardiovascular events (MACE) according to baseline glucose-lowering treatments (0 or 1, 2 or 3+ non-insulin glucose-lowering treatments, or insulin-based treatment), duration of diabetes (16 years) and HbA1c (≤53.0 mmol/mol [53.0 to 58.5 mmol/mol [>7.0% to 7.5%], >58.5 to 63.9 mmol/mol [>7.5 to 8.0%], >63.9 to 69.4 mmol/mol [8.0% to 8.5%], >69.4 to 74.9 mmol/mol [>8.5 to 9.0%] or >74.9 mmol/mol [>9.0%]). We analysed additional secondary endpoints for cardiovascular and kidney outcomes, including a combined kidney outcome of sustained 40% decline in eGFR, end-stage kidney disease or death due to kidney disease. We used Cox regression analyses and compared the constancy of HRs across subgroups by fitting an interaction term (p value for significance 74.9 mmol/mol (9.0%) and the median duration of diabetes was 12.6 years (interquartile interval 8.0–18 years). Canagliflozin reduced MACE (HR 0.86 [95% CI 0.75, 0.97]) with no evidence that the benefit differed between subgroups defined by the number of glucose-lowering treatments, the duration of diabetes or baseline HbA1c (all p-heterogeneity >0.17). Canagliflozin reduced MACE in participants receiving insulin with no evidence that the benefit differed from other participants in the trial (HR 0.85 [95% CI 0.72, 1.00]). Similar results were observed for other cardiovascular outcomes and for the combined kidney outcome (HR for combined kidney outcome 0.60 [95% CI 0.47, 0.77]), with all p-heterogeneity >0.37. Conclusions/interpretation: In people with type 2 diabetes mellitus at high cardiovascular risk, there was no evidence that cardiovascular and renal protection with canagliflozin differed across subgroups defined by baseline treatment intensity, duration of diabetes or HbA1c. Graphical abstract: [Figure not available: see fulltext.

Nation-Wide Routinely Collected Health Datasets in China: A Scoping Review

Objectives: The potential for using routinely collected data for medical research in China remains unclear. We sought to conduct a scoping review to systematically characterise nation-wide routinely collected datasets in China that may be of value for clinical research. Methods: We searched public databases and the websites of government agencies, and non-government organizations. We included nation-wide routinely collected databases related to communicable diseases, non-communicable diseases, injuries, and maternal and child health. Database characteristics, including disease area, data custodianship, data volume, frequency of update and accessibility were extracted and summarised. Results: There were 70 databases identified, of which 46 related to communicable diseases, 20 to non-communicable diseases, 1 to injury and 3 to maternal and child health. The data volume varied from below 1000 to over 100,000 records. Over half (64%) of the databases were accessible for medical research mostly comprising communicable diseases. Conclusion: There are large quantities of routinely collected data in China. Challenges to using such data in medical research remain with various accessibility. The potential of routinely collected data may also be applicable to other low- and middle-income countries