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

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

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

Kidney, Cardiovascular, and Safety Outcomes of Canagliflozin according to Baseline Albuminuria:A CREDENCE Secondary Analysis

BACKGROUND AND OBJECTIVES: The kidney protective effects of renin-angiotensin system inhibitors are greater in people with higher levels of albuminuria at treatment initiation. Whether this applies to sodium-glucose cotransporter 2 (SGLT2) inhibitors is uncertain, particularly in patients with a very high urine albumin-to-creatinine ratio (UACR; ≥3000 mg/g). We examined the association between baseline UACR and the effects of the SGLT2 inhibitor, canagliflozin, on efficacy and safety outcomes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) randomized controlled trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study enrolled 4401 participants with type 2 diabetes, an eGFR of 30 to 300 to 5000 mg/g. Using Cox proportional hazards regression, we examined the relative and absolute effects of canagliflozin on kidney, cardiovascular, and safety outcomes according to a baseline UACR of ≤1000 mg/g (n=2348), >1000 to 1000 to <3000 mg/g, and 37% (HR, 0.63; 95% CI, 0.47 to 0.84) in the highest subgroup (Pheterogeneity=0.55). Absolute risk reductions for kidney outcomes were greater in participants with higher baseline albuminuria; the number of primary composite events prevented across ascending UACR categories were 17 (95% CI, 3 to 38), 45 (95% CI, 9 to 81), and 119 (95% CI, 35 to 202) per 1000 treated participants over 2.6 years (Pheterogeneity=0.02). Rates of kidney-related adverse events were lower with canagliflozin, with a greater relative reduction in higher UACR categories. CONCLUSIONS: Canagliflozin safely reduces kidney and cardiovascular events in people with type 2 diabetes and severely increased albuminuria. In this population, the relative kidney benefits were consistent over a range of albuminuria levels, with greatest absolute kidney benefit in those with an UACR ≥3000 mg/g. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrials.gov: CREDENCE, NCT02065791. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_02_22_CJN15260920_final.mp3

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

Exploring the spatial epidemiology and population genetics of malaria-protective haemoglobinopathies

Haemoglobinopathies, which include sickle-cell anaemia (SCA) and α- and β-thalassaemia, represent some of our few unequivocal examples of human evolution. The underlying genetic mutations reflect a recurring adaptation against one of the biggest infectious disease killers of humans, Plasmodium falciparum malaria. Inheritance of one copy of a sickle-cell or thalassaemic allele leads to protection against death from malaria, while two copies can result in a severe blood disorder. As a result, haemoglobinopathies have risen in frequency through balancing selection and pose a significant public health problem in parts of the world with a history of malaria transmission. Their study therefore lies at the interface between evolutionary biology and public health. In this thesis, I explore different aspects of the epidemiology and population genetics of haemoglobinopathies around the world. Using pre-existing epidemiological data, statistical and geostatistical methods and Geographic Information System tools, I develop detailed evidence-based maps of the α-thalassaemia allele frequency distribution and genetic diversity in Southeast Asia and sickle-cell allele frequency in India. Pairing these with birth data, I generate sub-national estimates of the number of newborns born with severe forms of α-thalassaemia and SCA in Thailand and India, respectively, together with uncertainty estimates. In addition, I use a flexible population genetic simulation model to explore evolutionary explanations for the contrasting spatial haplotype patterns observed for SCA and the severe form of β-thalassaemia (β0-thalassaemia) in sub-Saharan Africa and the Middle East, and resurrect a 20-year old question surrounding the genetic origin of sickle-cell. Understanding the fine-scale geographical heterogeneities in the distributions of malaria-protective haemoglobinopathies is critical for addressing basic science questions and applied public health queries. Working at the interface between evolutionary biology and public health has provided me with the opportunity to build a more complete overview of the neglected increasing public health burden that this group of human disorders represents.</p

Exploring the spatial epidemiology and population genetics of malaria-protective haemoglobinopathies

Haemoglobinopathies, which include sickle-cell anaemia (SCA) and α- and β-thalassaemia, represent some of our few unequivocal examples of human evolution. The underlying genetic mutations reflect a recurring adaptation against one of the biggest infectious disease killers of humans, Plasmodium falciparum malaria. Inheritance of one copy of a sickle-cell or thalassaemic allele leads to protection against death from malaria, while two copies can result in a severe blood disorder. As a result, haemoglobinopathies have risen in frequency through balancing selection and pose a significant public health problem in parts of the world with a history of malaria transmission. Their study therefore lies at the interface between evolutionary biology and public health. In this thesis, I explore different aspects of the epidemiology and population genetics of haemoglobinopathies around the world. Using pre-existing epidemiological data, statistical and geostatistical methods and Geographic Information System tools, I develop detailed evidence-based maps of the α-thalassaemia allele frequency distribution and genetic diversity in Southeast Asia and sickle-cell allele frequency in India. Pairing these with birth data, I generate sub-national estimates of the number of newborns born with severe forms of α-thalassaemia and SCA in Thailand and India, respectively, together with uncertainty estimates. In addition, I use a flexible population genetic simulation model to explore evolutionary explanations for the contrasting spatial haplotype patterns observed for SCA and the severe form of β-thalassaemia (β0-thalassaemia) in sub-Saharan Africa and the Middle East, and resurrect a 20-year old question surrounding the genetic origin of sickle-cell. Understanding the fine-scale geographical heterogeneities in the distributions of malaria-protective haemoglobinopathies is critical for addressing basic science questions and applied public health queries. Working at the interface between evolutionary biology and public health has provided me with the opportunity to build a more complete overview of the neglected increasing public health burden that this group of human disorders represents.</p

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

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

Estimating the burden of α-thalassaemia in Thailand using a comprehensive prevalence database for Southeast Asia

Severe forms of α-thalassaemia, haemoglobin H disease and haemoglobin Bart’s hydrops fetalis, are an important public health concern in Southeast Asia. Yet information on the prevalence, genetic diversity and health burden of α-thalassaemia in the region remains limited. We compiled a geodatabase of α-thalassaemia prevalence and genetic diversity surveys and, using geostatistical modelling methods, generated the first continuous maps of α-thalassaemia mutations in Thailand and sub-national estimates of the number of newborns with severe forms in 2020. We also summarised the current evidence-base for α-thalassaemia prevalence and diversity for the region. We estimate that 3595 (95% credible interval 1,717–6,199) newborns will be born with severe α-thalassaemia in Thailand in 2020, which is considerably higher than previous estimates. Accurate, fine-scale epidemiological data are necessary to guide sustainable national and regional health policies for α-thalassaemia management. Our maps and newborn estimates are an important first step towards this aim