Centre-level variation in the survival of patients receiving haemodialysis in India: findings from a nationwide private haemodialysis network.

Background: There are no large studies examining survival in patients receiving haemodialysis in India or considering centre-level effects on survival. We measured survival variation between dialysis centres across India and evaluated the extent to which differences are explained by measured centre characteristics. Methods: This is a multilevel analysis of patient survival in centres of the NephroPlus dialysis network consisting of 193 centres across India. Patients receiving haemodialysis at a centre for ≥90 days between April 2014 and June 2019 were included, with analyses restricted to centres with ≥10 such patients. The primary outcome was all-cause mortality, measured from 90 days after joining a centre. Proportional hazards models with shared frailty were used to model centre- and patient-level effects on survival. Findings: Amongst 23,601 patients (median age 53 years; 29% female), the unadjusted centre-specific 180-day Kaplan-Meier survival estimates ranged between 55% (95% confidence interval [CI] 38-80%) and 100%, with a median of 88% (interquartile interval 83%-92%). After accounting for multilevel factors, estimated 180-day survival ranged between 83% (73-89%) and 97% (95-98%), with 90% 180-day survival in the average centre. The mortality rate in patients attending rural centres was 32% (Hazard Ratio 1.32; 95% CI 1.06-1.65) higher than those at urban centres in adjusted analyses. Multiple patient characteristics were associated with mortality. Interpretation: This is the first national benchmark for survival amongst dialysis patients in India. Centre- and patient-level characteristics are associated with survival but there remains unexplained variation between centres. As India continues to widen dialysis access, ongoing quality improvement programs will be an important part of ensuring that patients experience the best possible outcomes at the point of care. Funding: This project received no external funding.

Women's representation in clinical trials of patients with chronic kidney disease.

Background: Sex and gender differences in chronic kidney disease (CKD), including epidemiology and response to treatment, remain poorly understood. This study aimed to investigate how women are represented in CKD clinical trials and whether sex- and gender-disaggregated outcomes were reported. Methods: Clinical trials on CKD were identified from ClinicalTrials.gov. Randomised, phase 3/4 trials with ≥100 participants were selected to quantify women's representation among participants by computing the participation:prevalence ratio (PPR) and investigating whether sex-disaggregated analyses had been performed. Results: In total, 192 CKD trials registered on ClinicalTrials.gov and published between 1995 and 2022 were included. Overall, women accounted for 66 875 (45%) of the 147 136 participants. Women's participation in clinical trials was lower than their representation in the underlying CKD population globally (55%). The PPR was 0.75 (95% confidence interval 0.72-0.78), with no significant variation irrespective of mean age, CKD stage, dialysis, location, type of intervention or funding agency. A total of 39 (20%) trials reported sex-disaggregated efficacy outcomes and none reported sex-disaggregated safety outcomes. Conclusion: Women's participation in CKD clinical trials was lower than their representation in the underlying CKD population. Sex-disaggregated efficacy and safety outcomes were rarely reported. Improving women's enrolment into clinical trials is crucial to enable sex- and gender-disaggregated analysis and thus identify potential differences in treatment response between women and men.

Safety and Effectiveness of Rivaroxaban Versus Warfarin Across GFR Levels in Atrial Fibrillation: A Population-Based Study in Australia and Canada.

Rationale & Objective: The benefit-risk profile of rivaroxaban versus warfarin for atrial fibrillation (AF) in patients with chronic kidney disease is uncertain. We compared rivaroxaban with warfarin across the range of kidney function in adults with AF. Study Design: Multicenter retrospective cohort. Setting & Participants: Adults with AF and a measure of estimated glomerular filtration rate (eGFR); using administrative data from 5 jurisdictions across Australia and Canada (2011-2018). Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. Patients receiving dialysis and kidney transplant recipients were excluded. Exposures: New dispensation of either rivaroxaban or warfarin. Outcomes: Composite (1) effectiveness outcome (all-cause death, ischemic stroke, or transient ischemic attack) and (2) major bleeding events (intracranial, gastrointestinal, or other) at 1 year. Analytical Approach: Cox proportional hazards models accounting for propensity score matching were performed independently in each jurisdiction and then pooled using random-effects meta-analysis. Results: 55,568 patients (27,784 rivaroxaban-warfarin user matched pairs; mean age 74 years, 46% female, 33.5% with eGFR <60 mL/min/1.73 m2) experienced a total of 4,733 (8.5%) effectiveness and 1,144 (2.0%) bleeding events. Compared to warfarin, rivaroxaban was associated with greater or similar effectiveness across a broad range of kidney function (pooled HRs of 0.72 [95% CI, 0.66-0.78], 0.78 [95% CI, 0.58-1.06], 0.70 [95% CI, 0.57-0.87], and 0.78 [95% CI, 0.62-0.99]) for eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively). Rivaroxaban was also associated with similar risk of major bleeding across all eGFR categories (pooled HRs of 0.75 [95% CI, 0.56-1.00], 1.01 [95% CI, 0.79-1.30], 0.87 [95% CI, 0.66-1.15], and 0.63 [95% CI, 0.37-1.09], respectively). Limitations: Unmeasured treatment selection bias and residual confounding. Conclusions: In adults with AF, rivaroxaban compared with warfarin was associated with lower or similar risk of all-cause death, ischemic stroke and transient ischemic attack and similar risk of bleeding across a broad range of kidney function. Plain-Language Summary: This real-world study involved a large cohort of 55,568 adults with atrial fibrillation from 5 jurisdictions across Australia and Canada. It showed that the favorable safety (bleeding) and effectiveness (stroke or death) profile of rivaroxaban compared with warfarin was consistent across different levels of kidney function. This study adds important safety data on the use of rivaroxaban in patients with reduced kidney function, including those with estimated glomerular filtration rate <30 mL/min/1.73 m2 in whom the risks and benefits of rivaroxaban use is most uncertain. Overall, the study supports the use of rivaroxaban as a safe and effective alternative to warfarin for atrial fibrillation across differing levels of kidney function.

Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure.

BACKGROUND: Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. METHODS: We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. RESULTS: A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). CONCLUSIONS: In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.).

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 RetractionWatch. 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.

The sodium-glucose cotransporter-2 inhibitor canagliflozin does not increase risk of non-genital skin and soft tissue infections in people with type 2 diabetes mellitus: A pooled post hoc analysis from the CANVAS Program and CREDENCE randomized double-blind trials.

AIMS: To assess whether the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin affects risk of non-genital skin and soft tissue infections (SSTIs). MATERIALS AND METHODS: We performed a post hoc pooled individual participant analysis of the CANVAS Program and CREDENCE trials that randomized people with type 2 diabetes at high cardiovascular risk and/or with chronic kidney disease to either canagliflozin or placebo. Investigator-reported adverse events were assessed by two blinded authors following predetermined criteria for non-genital SSTIs. Risks of non-genital SSTIs, overall and within prespecified subgroups, and risk of non-genital fungal SSTIs, were analysed using Cox regression models. Factors associated with non-genital SSTIs were assessed using multivariable Cox regression models. RESULTS: Overall, 903 of 14 531 participants (6%) experienced non-genital SSTIs over a median follow-up of 26 months. No difference was observed in non-genital SSTI rates between canagliflozin and placebo (24.0 events/1000 person-years vs. 23.9 events/1000 person-years, respectively; hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.85-1.11; P = 0.70), with consistent results across subgroups (all P interaction > 0.05). The risk of recurrent events and non-genital fungal infection also did not differ significantly between canagliflozin and placebo (HR 1.06, 95% CI 0.94-1.19 [P = 0.32] and HR 1.18, 95% CI 0.88-1.60 [P = 0.27], respectively). Baseline factors independently associated with non-genital SSTIs were younger age, male sex, higher body mass index, higher glycated haemoglobin, lower estimated glomerular filtration rate (eGFR), established peripheral vascular disease, and history of neuropathy. CONCLUSIONS: Canagliflozin did not affect risk of non-genital SSTIs or non-genital fungal SSTIs compared with placebo. These findings suggest that any SGLT2 inhibitor-mediated change in skin microenvironment is unlikely to have meaningful clinical consequences.

Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study.

Objective: To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease. Design: Registry based observational study. Setting: 74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021. Participants: All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients). Main outcome measures: Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease. Results: Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07). Conclusions: In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.

Kidney function and the comparative effectiveness and safety of direct oral anticoagulants vs. warfarin in adults with atrial fibrillation: a multicenter observational study.

AIMS: The aim of this study was to determine the comparative effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin in adults with atrial fibrillation (AF) by level of kidney function. METHODS AND RESULTS: We pooled findings from five retrospective cohorts (2011-18) across Australia and Canada of adults with; a new dispensation for a DOAC or warfarin, an AF diagnosis, and a measure of baseline estimated glomerular filtration rate (eGFR). The outcomes of interest, within 1 year from the cohort entry date, were: (1) the composite of all-cause death, first hospitalization for ischaemic stroke, or transient ischaemic attack (effectiveness), and (2) first hospitalization for major bleeding defined as an intracranial, upper or lower gastrointestinal, or other bleeding (safety). Cox models were used to examine the association of a DOAC vs. warfarin with outcomes, after 1:1 matching via a propensity score. Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. A total of 74 542 patients were included in the matched analysis. DOAC initiation was associated with greater or similar effectiveness compared with warfarin initiation across all eGFR categories [pooled HRs (95% CIs) for eGFR categories: 0.74(0.69-0.79), 0.76(0.54-1.07), 0.68(0.61-0.75) and 0.86(0.76-0.98)], respectively. DOAC initiation was associated with lower or similar risk of major bleeding than warfarin initiation [pooled HRs (95% CIs): 0.75(0.65-0.86), 0.81(0.65-1.01), 0.82(0.66-1.02), and 0.71(0.52-0.99), respectively). Associations between DOAC initiation, compared with warfarin initiation, and study outcomes were not modified by eGFR category. CONCLUSION: DOAC use, compared with warfarin use, was associated with a lower or similar risk of all-cause death, ischaemic stroke, and transient ischaemic attack and also a lower or similar risk of major bleeding across all levels of kidney function.

Angiotensin receptor blockers for the treatment of covid-19: pragmatic, adaptive, multicentre, phase 3, randomised controlled trial.

OBJECTIVE: To determine whether disrupting the renin angiotensin system with angiotensin receptor blockers will improve clinical outcomes in people with covid-19. DESIGN: CLARITY was a pragmatic, adaptive, multicentre, phase 3, randomised controlled trial. SETTING: 17 hospital sites in India and Australia. PARTICIPANTS: Participants were at least 18 years old, previously untreated with angiotensin receptor blockers, with a laboratory confirmed diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection who had been admitted to hospital for management of covid-19. INTERVENTION: Oral angiotensin receptor blockers (telmisartan in India) or placebo (1:1) for 28 days. MAIN OUTCOME MEASURES: The primary endpoint was covid-19 disease severity using a modified World Health Organization Clinical Progression Scale (WHO scale) at day 14. Secondary outcomes were WHO scale scores at day 28, mortality, intensive care unit admission, and respiratory failure. Analyses were evaluated on an ordinal scale in the intention-to-treat population. RESULTS: Between 3 May 2020 and 13 November 2021, 2930 people were screened for eligibility, with 393 randomly assigned to angiotensin receptor blockers (of which 388 (98.7%) to telmisartan 40 mg/day) and 394 to the control group. 787 participants were randomised: 778 (98.9%) from India and nine (1.1%) from Australia. The median WHO scale score at day 14 was 1 (interquartile range 1-1) in 384 participants assigned angiotensin receptor blockers and 1 (1-1) in 382 participants assigned placebo (adjusted odds ratio 1.51 (95% credible interval 1.02 to 2.23), probability of an odds ratio of >1 (Pr(OR>1)=0.98). WHO scale scores at day 28 showed little evidence of difference between groups (1.02 (0.55 to 1.87), Pr(OR>1)=0.53). The trial was stopped when a prespecified futility rule was met. CONCLUSIONS: In patients admitted to hospital for covid-19, mostly with mild disease, not requiring oxygen, no evidence of benefit, based on disease severity score, was found for treatment with angiotensin receptor blockers, using predominantly 40 mg/day of telmisartan. TRIAL REGISTRATION: ClinicalTrials.gov NCT04394117.

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.

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.

Contextualising sex and gender research to improve women's health: An early- and mid-career researcher perspective.

The field of sex and gender research in health and medicine is growing, and many early- and mid-career researchers (EMCRs) are developing skills in this area. As EMCRs specialising in sex and gender research, we aim to better understand sex- and gender-based determinants of human health, challenge long-standing and pervasive gender biases, and contribute to improving the evidence base upon which clinical guidelines and policy interventions are developed. To effectively achieve these goals, we believe that EMCRs would benefit from understanding the challenges of working in this space and participate in driving change in three key areas. First, in creating greater links between the goals of sex and gender research and addressing systemic bias against women and gender minorities, to effectively translate knowledge about sex and gender differences into improved health outcomes. Second, in expanding the reach of sex and gender research to address women's health in an intersectional way and ensure that it also benefits the health of men, transgender and gender-diverse people and those who are intersex. Third, in working with others in the scientific community to improve methods for sex and gender research, including updating data collection practises, ensuring appropriate statistical analyses and shifting scientific culture to recognise the importance of null findings. By improving focus on these three areas, we see greater potential to translate this research to improve women's health and reduce health inequities for all.

Risk Factors for Fracture in Patients with Coexisting Chronic Kidney Disease and Type 2 Diabetes: An Observational Analysis from the CREDENCE Trial.

Background: The fracture pathophysiology associated with type 2 diabetes and chronic kidney disease (CKD) is incompletely understood. We examined individual fracture predictors and prediction sets based on different pathophysiological hypotheses, testing whether any of the sets improved prediction beyond that based on traditional osteoporotic risk factors. Methods: Within the CREDENCE cohort with adjudicated fracture outcomes, we assessed the association of individual factors with fracture using Cox regression models. We used the Akaike information criteria (AIC) and Schwartz Bayes Criterion (SBC) to assess six separate variable sets based on hypothesized associations with fracture, namely, traditional osteoporosis, exploratory general population findings, cardiovascular risk, CKD-mineral and bone disorder, diabetic osteodystrophy, and an all-inclusive set containing all variables. Results: Fracture occurred in 135 (3.1%) participants over a median 2.35 [1.88-2.93] years. Independent fracture predictors were older age (hazard ratio [HR] 1.04, confidence interval [CI] 1.01-1.06), female sex (HR 2.49, CI 1.70-3.65), previous fracture (HR 2.30, CI 1.58-3.34), Asian race (HR 1.74, CI 1.09-2.78), vitamin D therapy requirement (HR 2.05, CI 1.31-3.21), HbA1c (HR 1.14, CI 1.00-1.32), prior cardiovascular event (HR 1.60, CI 1.10-2.33), and serum albumin (HR 0.41, CI 0.23-0.74) (lower albumin associated with greater risk). The goodness of fit of the various hypothesis sets was similar (AIC range 1870.92-1849.51, SBC range 1875.60-1948.04). Conclusion: Independent predictors of fracture were identified in the CREDENCE participants with type 2 diabetes and CKD. Fracture prediction was not improved by models built on alternative pathophysiology hypotheses compared with traditional osteoporosis predictors.

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.

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.

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.

Prevalence of chronic kidney disease in Asia: a systematic review and analysis.

INTRODUCTION: The burden of chronic kidney disease (CKD) is growing rapidly around the world. However, there is limited information on the overall regional prevalence of CKD, as well as the variations in national prevalence within Asia. We aimed to consolidate available data and quantify estimates of the CKD burden in this region. METHODS: We systematically searched MEDLINE, Embase and Google Scholar for observational studies and contacted national experts to estimate CKD prevalence in countries of Asia (Eastern, Southern and South Eastern Asia). CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or the presence of proteinuria. For countries without reported data, we estimated CKD prevalence using agglomerative average-linkage hierarchical clustering, based on country-level risk factors and random effects meta-analysis within clusters. Published CKD prevalence data were obtained for 16 countries (of the 26 countries in the region) and estimates were made for 10 countries. RESULTS: There was substantial variation in overall and advanced (eGFR <30 mL/min/1.73 m2) CKD prevalence (range: 7.0%-34.3% and 0.1%-17.0%, respectively). Up to an estimated 434.3 million (95% CI 350.2 to 519.7) adults have CKD in Asia, including up to 65.6 million (95% CI 42.2 to 94.9) who have advanced CKD. The greatest number of adults living with CKD were in China (up to 159.8 million, 95% CI 146.6 to 174.1) and India (up to 140.2 million, 95% CI 110.7 to 169.7), collectively having 69.1% of the total number of adults with CKD in the region. CONCLUSION: The large number of people with CKD, and the substantial number with advanced CKD, show the need for urgent collaborative action in Asia to prevent and manage CKD and its complications.

Risk factors for incident kidney disease in older adults: an Australian prospective population-based study.

BACKGROUND AND AIM: To determine risk factors for incident chronic kidney disease (CKD) in a large population-based cohort. METHODS: This prospective opt-in population-based cohort study is based on the 45 and Up Study, where New South Wales residents aged ≥45 years were randomly sampled from the Services Australia database and agreed to complete the 45 and Up Study baseline questionnaire and have their responses linked to their health data in routinely collected databases. The primary outcome was the development of incident CKD, defined as eGFR < 60 mL/min/1.73 m2 . CKD incidence was calculated using Poisson regression. Risk factors for incident CKD were assessed using Cox regression in multivariable models. RESULTS: In 39 574 participants who did not have CKD at enrolment, independent factors associated with developing CKD included: older age, regional residence (HR 1.38 (1.27-1.50) for outer regional vs major city), smoking (1.13 (1.00-1.27) for current smoker vs non-smoker), obesity (1.25 (1.16-1.35) for obese vs normal body mass index), diabetes mellitus (1.41 (1.33-1.50)), hypertension (1.53 (1.44-1.62)), coronary heart disease (1.13 (1.07-1.20)), depression/anxiety (1.16 (1.09-1.24)) and cancer (1.29 (1.20-1.39)). Migrants were less likely to develop CKD compared with people born in Australia (0.88 (0.83-0.94)). Gender, partner status and socioeconomic factors were not independently associated with developing CKD. CONCLUSIONS: This large population-based study found multiple modifiable and non-modifiable factors were independently associated with developing CKD. In the Australian setting, the risk of CKD was higher with regional residence. Differences according to socioeconomic status were predominantly explained by age, comorbidities and harmful health-related behaviours.

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.