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

Sex differences in the utilization and outcomes of endovascular treatment after acute ischemic stroke: A systematic review and meta-analysis

BackgroundStudies of sex differences in the use and outcomes of endovascular treatment (EVT) for acute ischemic stroke report inconsistent resultsMethodsWe systematically searched PubMed and Embase databases for studies examining sex-specific utilization of EVT for acute ischemic stroke published before 31 December 2021. Estimates were compared by study type: randomized clinical trials (RCTs) and non-RCTs (hospital-based, registry-based or administrative data). Random effects odds ratios (ORs) were generated to quantify sex differences in EVT use. To estimate sex differences in functional outcome on the modified Rankin scale after EVT, the female:male ratio of ORs and 95% confidence intervals (CIs) were obtained from ordinal or binary analysis.Results6,396 studies were identified through database searching, of which 594 qualified for a full review. A total of 51 studies (36 non-RCT and 15 RCTs) reporting on sex-specific utilization of EVT were included, and of those 10 estimated the sex differences of EVT on functional outcomes. EVT use was similar in women and men both in non-RCTs (OR: 1.03, 95% CI: 0.96–1.11) and RCTs (1.02, 95% CI: 0.89–1.16), with consistent results across years of publication and regions of study, except that in Europe EVT treatment was higher in women than men (1.15, 95% CI: 1.13–1.16). No sex differences were found in the functional outcome by either ordinal and binary analyses (ORs 0.95, 95% CI: 0.68–1.32] and 0.90, 95% CI: 0.65–1.25, respectively).ConclusionsNo sex differences in EVT utilization or on functional outcomes were evident after acute ischemic stroke from large-vessel occlusion. Further research may be required to examine sex differences in long-term outcomes, social domains, and quality of life.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=226100, identifier: CRD42021226100

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

Gender differences in the accuracy of dietary assessment methods to measure energy intake in adults:protocol for a systematic review and meta-analysis

Introduction Diet is an important modifiable risk factor for many chronic diseases. Measurement of dietary intake usually relies on self-report, subject to multiple biases. There is a need to understand gender differences in the self-report of dietary intake and the implications of any differences in targeting nutrition interventions. Literature in this area is limited and it is currently unknown whether self-report dietary assessment methods are equally accurate for women and men. The aim of this systematic review is to determine whether there are differences by gender in reporting energy intake compared with a reference measure of total energy expenditure. Methods and analysis A comprehensive search of published original research studies will be performed in MEDLINE, Scopus, Web of Science, EMBASE, CINAHL and Cochrane library. Original research studies will be included if they were conducted in free-living/unhospitalised adults and included a measure for both women and men of (a) self-reported energy intake and (b) total energy expenditure by doubly labelled water. One author will conduct the electronic database searches, two authors will independently screen studies, conduct a quality appraisal of the included studies using standardised tools and extract data. If further information is needed, then study authors will be contacted. If appropriate, a random-effects meta-analysis will be conducted, with inverse probability weighting, to quantify differences in the mean difference in agreement between reported energy intake and measured energy expenditure between women and men, by self-report assessment method. Subgroup analyses will be conducted by participant factors, geographical factors and study quality. Ethics and dissemination All data used will be from published primary research studies or deidentified results provided at the discretion of any study authors that we contact. We will submit our findings to a peer-reviewed scientific journal and will disseminate results through presentations at international scientific conferences. PROSPERO registration number CRD42019131715

Early decompressive hemicraniectomy in thrombolyzed acute ischemic stroke patients from the international ENCHANTED trial

Abstract Decompressive hemicraniectomy (DHC) can improve outcomes for patients with severe forms of acute ischemic stroke (AIS), but the evidence is mainly derived from non-thrombolyzed patients. We aimed to determine the characteristics and outcomes of early DHC in thrombolyzed AIS participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Post-hoc analyses of ENCHANTED, an international, partial-factorial, open, blinded outcome-assessed, controlled trial in 4557 thrombolysis-eligible AIS patients randomized to low- versus standard-dose intravenous alteplase (Arm A, n = 2350), intensive versus guideline-recommended blood pressure control (Arm B, n = 1280), or both (Arms A + B, n = 947). Logistic regression models were used to identify baseline variables associated with DHC, with inverse probability of treatment weights employed to eliminate baseline imbalances between those with and without DHC. Logistic regression was also used to determine associations of DHC and clinical outcomes of death/disability, major disability, and death (defined by scores 2–6, 3–5, and 6, respectively, on the modified Rankin scale) at 90 days post-randomization. There were 95 (2.1%) thrombolyzed AIS patients who underwent DHC, who were significantly younger, of non-Asian ethnicity, and more likely to have had prior lipid-lowering treatment and severe neurological impairment from large vessel occlusion than other patients. DHC patients were more likely to receive other management interventions and have poor functional outcomes than non-DHC patients, with no relation to different doses of intravenous alteplase. Compared to other thrombolyzed AIS patients, those who received DHC had a poor prognosis from more severe disease despite intensive in-hospital management

Who will benefit more from low-dose alteplase in acute ischemic stroke?

Objectives: Controversy persists over the benefits of low-dose versus standard-dose intravenous alteplase for the treatment of acute ischemic stroke. We sought to determine individual patient factors that contribute to the risk–benefit balance of low-dose alteplase treatment. Methods: Observational study using data from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, randomized, open-label, blinded-endpoint trial that assessed low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase in acute ischemic stroke patients. Logistic regression models were used to estimate the benefit of good functional outcome (scores 0 or 1 on the modified Rankin scale at 90 days) and risk (symptomatic intracerebral hemorrhage), under both regimens for individual patients. The net advantage for low-dose, relative to standard-dose, alteplase was calculated by dividing excess benefit by excess risk according to a combination of patient characteristics. The algorithms were externally validated in a nationwide acute stroke registry database in South Korea. Results: Patients with an estimated net advantage from low-dose alteplase, compared with without, were younger (mean age of 66 vs. 75 years), had lower systolic blood pressure (148 vs. 160 mm Hg), lower National Institute of Health Stroke Scale score (median of 8 vs. 16), and no atrial fibrillation (10.3% vs. 97.4%), diabetes mellitus (19.2% vs. 22.4%), or premorbid symptoms (defined by modified Rankin scale = 1) (16.3% vs. 37.8%). Conclusion: Use of low-dose alteplase may be preferable in acute ischemic stroke patients with a combination of favorable characteristics, including younger age, lower systolic blood pressure, mild neurological impairment, and no atrial fibrillation, diabetes mellitus, or premorbid symptoms.</p

Brain Imaging Signs and Health-Related Quality of Life after Acute Ischemic Stroke: Analysis of ENCHANTED Alteplase Dose Arm.

The influence of specific brain lesions on health-related quality of life (HRQoL) after acute ischemic stroke (AIS) is uncertain. We aimed to identify imaging predictors of poor HRQoL in alteplase-treated participants of the alteplase dose arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). ENCHANTED was an international trial of low- versus standard-dose intravenous alteplase in AIS patients, with functional outcome (modified Rankin scale [mRS]) and HRQoL on the 5-dimension European Quality of Life Scale (EQ-5D) assessed at 90 days post-randomization. Brain images were analyzed centrally by trained assessors. Multivariable logistic regression was undertaken in the study population randomly divided (2:1) into training (development) and validation (performance) groups, with age (per 10-year increase), ethnicity, baseline National Institutes of Health Stroke Scale (NIHSS) score, diabetes mellitus, premorbid function (mRS score 0 or 1), and proxy respondent, forced into all models. Data are presented with odds ratios (ORs) and 95% confidence intervals (CIs). Eight prediction models were developed and validated in 2,526 AIS patients (median age 67.5 years; 38.4% female; 61.7% Asian) with complete brain imaging and 90-day EQ-5D utility score data. The best performance model included acute ischemic changes in the right (OR 1.69, 95% CI: 1.24-2.29) and deep (OR 1.50, 95% CI: 1.03-2.19) middle cerebral artery (MCA) regions. Several background features of brain frailty - atrophy, white matter change, and old infarcts - were significantly associated with adverse physical but not emotional HRQoL domains. In thrombolysed AIS patients, right-sided and deep ischemia within the MCA territory predict poor overall HRQoL, whilst features of old cerebral ischemia are associated with reduced physical HRQoL. [Abstract copyright: © 2020 S. Karger AG, Basel.