Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) updates the KDIGO 2012 guideline and has been developed with patient partners, clinicians, and researchers around the world, using robust methodology. This update, based on a substantially broader base of evidence than has previously been available, reflects an exciting time in nephrology. New therapies and strategies have been tested in large and diverse populations that help to inform care; however, this guideline is not intended for people receiving dialysis nor those who have a kidney transplant. The document is sensitive to international considerations, CKD across the lifespan, and discusses special considerations in implementation. The scope includes chapters dedicated to the evaluation and risk assessment of people with CKD, management to delay CKD progression and its complications, medication management and drug stewardship in CKD, and optimal models of CKD care. Treatment approaches and actionable guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations which followed the "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE) approach. The limitations of the evidence are discussed. The guideline also provides practice points, which serve to direct clinical care or activities for which a systematic review was not conducted, and it includes useful infographics and describes an important research agenda for the future. It targets a broad audience of people with CKD and their healthcare, while being mindful of implications for policy and payment.

Association between serum estradiol and cardiovascular health among transgender adults using gender-affirming estrogen therapy.

Gender-affirming estrogen therapy (GAET) is commonly used for feminization in transgender and nonbinary (TNB) individuals, yet the optimal rate of change (ROC) in estradiol levels for cardiovascular health is unclear. We examined the association between serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and Web of Science were systematically searched (inception-April 2023) for original articles reporting serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Data extraction was completed in duplicate following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Stratified random effect meta-analyses using serum estradiol ROC (serum estradiolbaseline - serum estradiolfollow-up/study duration) was used to assess longitudinal studies (low, 0 < ROC ≤ 1 pg/mL/mo; moderate, 1 < ROC ≤ 3 pg/mL/mo; high, ROC ≥ 3 pg/mL/mo). Thirty-five studies (13 cross-sectional, 19 cohort, and 3 trials) were included. Two studies collectively reported 50 cardiovascular-related deaths, and four collectively reported 23 adverse cardiovascular events. Nineteen studies reporting cardiovascular risk factors were meta-analyzed by ROC stratum (low = 5; moderate = 6; high = 8), demonstrating an association between moderate [0.40, 95% confidence interval (CI): 0.22, 0.59 kg/m2, I2 = 28.2%] and high (0.46, 95% CI: 0.15, 0.78 kg/m2; I2 = 0.0%) serum estradiol ROC and increased body mass index. High (-6.67, 95% CI: -10.65, -2.68 mg/dL; I2 = 0.0%) serum estradiol ROC was associated with decreased low-density lipoproteins. Low (-7.05, 95% CI: -10.40, -3.70 mmHg; I2 = 0.0%) and moderate (-3.69, 95% CI: -4.93, -2.45 mmHg; I2 = 0.0%) serum estradiol ROCs were associated with decreases in systolic blood pressure. In TNB adults using GAET, serum estradiol ROC may influence cardiovascular risk factors, which may have implications for clinical cardiovascular outcomes.NEW & NOTEWORTHY In this systematic review and meta-analysis of 35 studies involving 7,745 participants, high rates of serum estradiol change were associated with small increases in body mass index. Moderate to high rates of change were associated with decreases in low-density lipoprotein. Low rates of change were associated with small decreases in systolic blood pressure. Rate of serum estradiol change in adults using gender-affirming estrogen therapy may influence cardiovascular risk factors, though further research is warranted.

Interventions on gender equity in the workplace: a scoping review.

BACKGROUND: Various studies have demonstrated gender disparities in workplace settings and the need for further intervention. This study identifies and examines evidence from randomized controlled trials (RCTs) on interventions examining gender equity in workplace or volunteer settings. An additional aim was to determine whether interventions considered intersection of gender and other variables, including PROGRESS-Plus equity variables (e.g., race/ethnicity). METHODS: Scoping review conducted using the JBI guide. Literature was searched in MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, ERIC, Index to Legal Periodicals and Books, PAIS Index, Policy Index File, and the Canadian Business & Current Affairs Database from inception to May 9, 2022, with an updated search on October 17, 2022. Results were reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension to scoping reviews (PRISMA-ScR), Sex and Gender Equity in Research (SAGER) guidance, Strengthening the Integration of Intersectionality Theory in Health Inequality Analysis (SIITHIA) checklist, and Guidance for Reporting Involvement of Patients and the Public (GRIPP) version 2 checklist. All employment or volunteer sectors settings were included. Included interventions were designed to promote workplace gender equity that targeted: (a) individuals, (b) organizations, or (c) systems. Any comparator was eligible. Outcomes measures included any gender equity related outcome, whether it was measuring intervention effectiveness (as defined by included studies) or implementation. Data analyses were descriptive in nature. As recommended in the JBI guide to scoping reviews, only high-level content analysis was conducted to categorize the interventions, which were reported using a previously published framework. RESULTS: We screened 8855 citations, 803 grey literature sources, and 663 full-text articles, resulting in 24 unique RCTs and one companion report that met inclusion criteria. Most studies (91.7%) failed to report how they established sex or gender. Twenty-three of 24 (95.8%) studies reported at least one PROGRESS-Plus variable: typically sex or gender or occupation. Two RCTs (8.3%) identified a non-binary gender identity. None of the RCTs reported on relationships between gender and other characteristics (e.g., disability, age, etc.). We identified 24 gender equity promoting interventions in the workplace that were evaluated and categorized into one or more of the following themes: (i) quantifying gender impacts; (ii) behavioural or systemic changes; (iii) career flexibility; (iv) increased visibility, recognition, and representation; (v) creating opportunities for development, mentorship, and sponsorship; and (vi) financial support. Of these interventions, 20/24 (83.3%) had positive conclusion statements for their primary outcomes (e.g., improved academic productivity, increased self-esteem) across heterogeneous outcomes. CONCLUSIONS: There is a paucity of literature on interventions to promote workplace gender equity. While some interventions elicited positive conclusions across a variety of outcomes, standardized outcome measures considering specific contexts and cultures are required. Few PROGRESS-Plus items were reported. Non-binary gender identities and issues related to intersectionality were not adequately considered. Future research should provide consistent and contemporary definitions of gender and sex. TRIAL REGISTRATION: Open Science Framework https://osf.io/x8yae .

A Holistic Framework for the Evaluation of Kidney Function in a Gender-Diverse Landscape.

The most commonly used equations to estimate glomerular filtration rate incorporate a binary male-female sex coefficient, which has important implications for the care of transgender, gender-diverse, and nonbinary (TGD) people. Whether "sex assigned at birth" or a binary "gender identity" is most appropriate for the computation of estimated glomerular filtration rate (eGFR) is unknown. Furthermore, the use of gender-affirming hormone therapy (GAHT) for the development of physical changes to align TGD people with their affirmed gender is increasingly common, and may result in changes in serum creatinine and cystatin C, the biomarkers commonly used to estimate glomerular filtration rate. The paucity of current literature evaluating chronic kidney disease (CKD) prevalence and outcomes in TGD individuals on GAHT makes it difficult to assess any effects of GAHT on kidney function. Whether alterations in serum creatinine reflect changes in glomerular filtration rate or simply changes in muscle mass is unknown. Therefore, we propose a holistic framework to evaluate kidney function in TGD people. The framework focuses on kidney disease prevalence, risk factors, sex hormones, eGFR, other kidney function assessment tools, and the mitigation of health inequities in TGD people.

Social factors associated with self-reported changes in mental health symptoms among youth in the COVID-19 pandemic: a cross-sectional survey.

BACKGROUND: Children and youth experienced marked impacts on day-to-day life in the COVID-19 pandemic that were associated with poorer familial and friend relationships, and greater mental health challenges. Few studies provide self-report data on mental health symptoms from children and youth themselves. We sought to examine the associations between social factors and child and youth self-reported symptoms of worsened mood, anxiety, and irritability during the COVID-19 pandemic. METHODS: A nationally representative cross-sectional survey was administered online to collect self-report data across 10 Canadian provinces among children (11-14 years) and youth (15-18 years), April-May 2022. Age-appropriate questions were based on The Partnership for Maternal, Newborn & Child Health and the World Health Organization of the United Nations H6 + Technical Working Group on Adolescent Health and Well-Being consensus framework and the Coronavirus Health and Impact Survey. Associations between a priori defined social factors (e.g., relationship quality) and respondent self-reported mental health were evaluated using ordinal logistic regression models adjusted for age, sex, and geographic location. RESULTS: We analyzed data from 483 (51.7%) children (11-14 years; 227, 47.0% girls) and 450 (48.3%) youth (15-18 years; 204, 45.3% girls). The parents of most children and youth had resided in Canada for over 20 years (678, 72.7%). Over one-quarter of children and youth self-identified as Black, Indigenous, or a Person of Color (134, 27.7%; 134, 29.8%, respectively). Over one-third of children and youth self-reported symptoms of worsened mood (149, 30.9%; 125, 27.8%, respectively), anxiety (181, 37.5%; 167, 37.1%, respectively), or irritability (160, 33.1%; 160, 35.6%, respectively) during, compared to pre-pandemic. In descending order of odds ratios (OR), for children and youth, worsened familial relationships (during compared to pre-pandemic) was associated with the self-reported symptoms of worsened mood (child: OR 4.22, 95%CI 2.51-6.88; youth: OR 6.65 95%CI 3.98-11.23), anxiety (child: OR 4.24, 95%CI2.69-6.75; youth: OR 5.28, 95%CI 3.17-8.86), and irritability (child: OR 2.83, 95%CI 1.76-4.56; youth: OR 6.46, 95%CI 3.88-10.90). CONCLUSIONS: Self-reported data from a nationally representative sample of children and youth suggest strong associations between social factors and mental health during the COVID-19 pandemic. Interventions targeting child and youth familial relationships may positively impact child and youth mental health.

Well-being approaches targeted to improve child and youth health post-COVID-19 pandemic: a scoping review.

BACKGROUND: Our previous work synthesized published studies on well-being interventions during COVID-19. As we move into a post-COVID-19 pandemic period there is a need to comprehensively review published strategies, approaches, and interventions to improve child and youth well-being beyond deleterious impacts experienced during COVID-19. METHODS: Seven databases were searched from inception to January 2023. Studies were included if they: (1) presented original data on an approach (i.e., approach applied) or (2) provided recommendations to inform development of a future approach (i.e., approach suggested), (3) targeted to mitigate negative impacts of COVID-19 on child and youth (≤18 year) well-being, and (4) published on or after December 2019. RESULTS: 39 studies (n = 4/39, 10.3% randomized controlled trials) from 2021 to 2023 were included. Twenty-two studies applied an approach (n = 22/39, 56.4%) whereas seventeen studies (n = 17/39, 43.6%) suggested an approach; youth aged 13-18 year (n = 27/39, 69.2%) were most frequently studied. Approach applied records most frequently adopted an experimental design (n = 11/22, 50.0%), whereas approach suggested records most frequently adopted a cross-sectional design (n = 13/22, 59.1%). The most frequently reported outcomes related to good health and optimum nutrition (n = 28/39, 71.8%), followed by connectedness (n = 22/39, 56.4%), learning, competence, education, skills, and employability (n = 18/39, 46.1%), and agency and resilience (n = 16/39, 41.0%). CONCLUSIONS: The rapid onset and unpredictability of COVID-19 precluded meaningful engagement of children and youth in strategy development despite widespread recognition that early engagement can enhance usefulness and acceptability of interventions. Published or recommended strategies were most frequently targeted to improve connectedness, belonging, and socialization among children and youth.

Female sex-specific considerations to improve rigor and reproducibility in cardiovascular research.

Cardiovascular disease is the leading cause of death in women. Despite recognition of sex-specific differences in cardiovascular health, females are underrepresented across all aspects of cardiovascular research, playing a key role in reducing rigor and reproducibility in cardiovascular research and contributing to these poorer health outcomes. Therefore, we propose a framework to capture factors associated with the female sex at the preclinical, recruitment, data collection, and data analysis stages. In preclinical cardiovascular research, female experimental models are commonly excluded despite similar variability in findings compared with males. To reduce this sex bias, the inclusion of female models and the incorporation of sex as a biological variable are critical to improve reproducibility and inform clinical research and care. Although funding agencies have mandated the inclusion of women in clinical trials, greater efforts are needed to achieve optimal participation-to-prevalence ratio to increase the generalizability of results to real-world settings. Female participants face more stringent exclusion criteria in research compared with males owing to sex-specific factors. However, their routine exclusion from cardiovascular research is not only unethical but limits generalizability and applicability to clinical practice. Identifying sex assigned at birth, collecting information on female sex-specific and -predominant factors associated with cardiovascular health and risk, and stratifying data by sex, including adverse events, are essential to ensure reproducibility and relevance of findings to target populations. Increasing female representation and the incorporation of female sex-specific cardiovascular risk factors in cardiovascular research will not only lead to enhanced rigor and reproducibility but improved cardiovascular health for all.

Improving the inclusion of transgender and nonbinary individuals in the planning, completion, and mobilization of cardiovascular research.

Cardiovascular disease is the leading cause of morbidity and mortality globally. Transgender and nonbinary (TNB) individuals face unclear but potentially significant cardiovascular health inequities, yet no TNB-specific evidence-based interventions for cardiovascular risk reduction currently exist. To address this gap, we propose a road map to improve the inclusion of TNB individuals in the planning, completion, and mobilization of cardiovascular research. In doing so, the adoption of inclusive practices would optimize cardiovascular health surveillance and care for TNB communities.

Sex and Gender in Randomized Controlled Trials of Adults Receiving Maintenance Dialysis: A Meta-epidemiologic Study.

RATIONALE & OBJECTIVE: How sex and gender concepts are incorporated into randomized controlled trials (RCTs) in adults with kidney failure receiving maintenance dialysis is largely unknown. We describe these practices in published journal articles as well as investigate the proportion of women and female participants in these studies. STUDY DESIGN: Meta-epidemiologic study. SETTING & STUDY POPULATIONS: RCTs in maintenance dialysis. SELECTION CRITERIA FOR STUDIES: Trials published in high-impact journals in 2000-2020. DATA EXTRACTION: Implemented in duplicate with conflicts resolved by a third reviewer. ANALYTICAL APPROACH: Meta-regression was performed to identify trial characteristics independently associated with the proportion of women and female participants. RESULTS: Among 561 included RCTs, 69.7% were parallel and 28.0% were crossover in design; 80.6% were conducted in the hemodialysis population; and 25% of trials compared the treatment of interest with a placebo arm, 25% with a usual care treatment arm, and 50% with an active alternative therapy arm. Of the RCTS, 37.6% were masked. The median size was 60 (IQR, 26-151) participants, and the median follow-up period was 154 (IQR, 42-365) days. The mean proportion of women or female participants was 0.40±0.13 (SD): 39.0% of trials reported sex, and 26.6% reported the gender of the participants. Also, 56.2% referred to participants as females, 25.3% referred to participants as women, and 15.5% referred to both females and women. No trial characteristic other than region (ß of 0.062 [95% CI, 0.007-0.117] for Asia) was associated with the proportion of women or female participants. Considering trial design and conduct, 2.7% of trials used sex and/or gender as an inclusion criterion, 26.6% as an exclusion criterion, 4.5% for randomization, 4.8% for subgroup analyses, and 15.7% for covariate adjustment. LIMITATIONS: Only high-impact journal articles were studied; and the included studies lacked pediatric trials, those addressing chronic kidney disease or kidney transplantation, any trials from Africa and underrepresentation of other regions, and missing data. CONCLUSIONS: RCTs in dialysis are representative of the general dialysis population with regard to sex and gender but they uncommonly report both and often do not include either in their reporting or analysis.

Experiences and Perceptions of Racism and Sexism Among Alberta Physicians: Quantitative Results and Framework Analysis of a Cross-Sectional Survey.

BACKGROUND: The prevalence of harassment and discrimination in medicine differs by race and gender. The current evidence is limited by a lack of intersectional analysis. OBJECTIVE: To evaluate the experiences and perceptions of harassment and discrimination in medicine across physicians stratified by self-identified race and gender identity. DESIGN: Quantitative and framework analysis of results from a cross-sectional survey study. PARTICIPANTS: Practicing physicians in the province of Alberta, Canada (n=11,688). MAIN MEASURES: Participants completed an instrument adapted from the Culture Conducive to Women's Academic Success to capture the perceived culture toward self-identified racial minority physicians (Black, Indigenous, and People of Color (BIPOC)), indicated their perception of gender inequity in medicine using Likert responses to questions about common experiences, and were asked about experiences of reporting harassment or discrimination. Participants were also able to provide open text comments. KEY RESULTS: Among the 1087 respondents (9.3% response rate), 73.5% reported experiencing workplace harassment or discrimination. These experiences were least common among White cisgender men and most common among BIPOC cisgender women (52.4% and 85.4% respectively, p<0.00001). Cisgender men perceived greater gender equity than cisgender women physicians, and White cisgender men physicians perceived greatest racial equity. Participant groups reporting the greatest prevalence of harassment and discrimination experiences were the least likely to know where to report harassment, and less than a quarter of physicians (23.8%) who had reported harassment or discrimination were satisfied with the outcome. Framework analysis of open text responses identified key types of barriers to addressing racism, including denial of racism and greater concern about other forms of discrimination and harassment. CONCLUSIONS: Our results document the prevalence of harassment and discrimination by intersectional identities of race and gender. Incongruent perceptions and experiences may act as a barrier to preventing and addressing harassment and discrimination in the Canadian medical workplace.

Gender-affirming estrogen therapy route of administration and cardiovascular risk: a systematic review and narrative synthesis.

Transgender women (individuals assigned male sex at birth who identify as women) and nonbinary and gender-diverse individuals receiving gender-affirming estrogen therapy (GAET) are at increased cardiovascular risk. Nonoral (i.e., patch, injectable) compared with oral estrogen exposure in cisgender women (individuals assigned female sex at birth who identify as women) may be associated with lower cardiovascular risk, though whether this applies to transgender women and/or gender-diverse individuals is unknown. We sought to determine the association between the route of estrogen exposure (nonoral compared with oral) and cardiovascular risk in transgender women and gender diverse individuals. Bibliographic databases (MEDLINE, Embase, PsycINFO) and supporting relevant literature were searched from inception to January 2022. Randomized controlled trials and observational studies reporting cardiovascular outcomes, such as all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors in individuals using nonoral compared with oral gender-affirming estrogen therapy were included. The search strategy identified 3,113 studies, 5 of which met inclusion criteria (3 prospective cohort studies, 1 retrospective cohort study, and 1 cross-sectional study; n = 259 participants, range of duration of exposure of 2 to 60 mo). One out of five studies reported on all-cause and cardiovascular mortality or adverse cardiovascular events. All five studies reported lipid levels [low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC)], whereas only two studies reported systolic blood pressure (SBP) and diastolic blood pressure (DBP). Limited studies have examined the effect of the route of GAET on all-cause cardiovascular mortality, morbidity, and risk factors. In addition, there is significant heterogeneity in studies examining the cardiovascular effects of GAET.NEW & NOTEWORTHY This study is the first to summarize the potential effect of nonoral versus oral gender-affirming estrogen therapy use on cardiovascular risk factors in transgender women or nonbinary or gender-diverse individuals. Heterogeneity of studies in reporting gender-affirming estrogen therapy formulation, dose, and duration of exposure limits quantification of the effect of gender-affirming estrogen therapy on all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors. This systematic review highlights the needs for large prospective cohort studies with appropriate stratification of gender-affirming estrogen therapy by dose, formulation, administration route, and sufficient follow-up and analyses to limit selection bias to optimize the cardiovascular care of transgender, nonbinary, and gender-diverse individuals.

Female sex-specific and -predominant cardiovascular risk factors and heart failure practice guidelines.

Heart failure (HF) etiology, presentation and prognosis differ by sex, with female sex-specific and -predominant risk factors playing important roles. We systematically reviewed the studies cited by the 2017 American College of Cardiology/ American Heart Association/ Heart Failure Society of America Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. Female cardiovascular risk factors were broadly categorized as female sex-specific (reproductive, pregnancy, menopausal) and female sex-predominant (depression, anthracycline exposure, autoimmune disease) risk factors. Of the 205 cited articles, only 3 studies (1.6%) reported any female sex-specific cardiovascular risk factor in the data analysis or results sections. Oral contraceptive use (n = 1), menopausal status (n = 2) and hormone replacement therapy (n = 2) were the only female sex-specific cardiovascular risk factors reported. No other female sex-specific or -predominant cardiovascular risk factor was reported by any of the eligible studies. Our work highlights that in addition to the need for proportional representation of women in heart failure clinical studies, inclusion of female sex-specific and -predominant risk factors in data collection and analysis is of paramount importance to guide heart failure care in the female population.

Recruitment of patients with chronic kidney disease and obstructive sleep apnoea for a clinical trial.

Obstructive sleep apnoea is common in chronic kidney disease (CKD) and may accelerate the decline in kidney function. Recruitment for a randomised controlled trial to address whether treatment of sleep apnoea with continuous positive airway pressure (CPAP) slows the progression of kidney failure may be challenging because sleep apnoea is often asymptomatic in this patient population. The present report outlines recruitment challenges and how to address them. Adult patients with CKD were recruited for a 12-month randomised, controlled, non-blinded, parallel clinical trial to evaluate the impact of CPAP therapy on kidney function. Patients completed a home sleep apnoea test and those that met pre-specified sleep apnoea and nocturnal hypoxaemia severity criteria were randomised to receive CPAP or no therapy. Although 1,665 patients were eligible to participate in the study over 3 years, only 57 (3.4%) were ultimately randomised. The sequential reasons (and number of patients) for recruitment failure were: no show at clinic appointment (137), insufficient recruiters to approach every eligible patient (461), on therapy for sleep apnoea (122), unable to provide informed consent (67), refused consent (645), home sleep apnoea test not completed (47) or inclusion criteria not met (116), and declined pre-randomisation education session (12). Many challenges limit effective recruitment, which may be addressed by hiring additional recruiters and increasing the awareness of sleep apnoea among patients with CKD. These findings can be used to improve recruitment strategies and the design of future studies.

Restricted visitation policies in acute care settings during the COVID-19 pandemic: a scoping review.

BACKGROUND: Restricted visitation policies in acute care settings because of the COVID-19 pandemic have negative consequences. The objective of this scoping review is to identify impacts of restricted visitation policies in acute care settings, and describe perspectives and mitigation approaches among patients, families, and healthcare professionals. METHODS: We searched Medline, Embase, PsycINFO, Healthstar, CINAHL, Cochrane Central Register of Controlled Trials on January 01/2021, unrestricted, for published primary research records reporting any study design. We included secondary (e.g., reviews) and non-research records (e.g., commentaries), and performed manual searches in web-based resources. We excluded records that did not report primary data. Two reviewers independently abstracted data in duplicate. RESULTS: Of 7810 citations, we included 155 records. Sixty-six records (43%) were primary research; 29 (44%) case reports or case series, and 26 (39%) cohort studies; 21 (14%) were literature reviews and 8 (5%) were expert recommendations; 54 (35%) were commentary, editorial, or opinion pieces. Restricted visitation policies impacted coping and daily function (n = 31, 20%) and mental health outcomes (n = 29, 19%) of patients, families, and healthcare professionals. Participants described a need for coping and support (n = 107, 69%), connection and communication (n = 107, 69%), and awareness of state of well-being (n = 101, 65%). Eighty-seven approaches to mitigate impact of restricted visitation were identified, targeting families (n = 61, 70%), patients (n = 51, 59%), and healthcare professionals (n = 40, 46%). CONCLUSIONS: Patients, families, and healthcare professionals were impacted by restricted visitation polices in acute care settings during COVID-19. The consequences of this approach on patients and families are understudied and warrant evaluation of approaches to mitigate their impact. Future pandemic policy development should include the perspectives of patients, families, and healthcare professionals. TRIAL REGISTRATION: The review was registered on PROSPERO (CRD42020221662) and a protocol peer-reviewed prior to data extraction.

Sex differences in renal hemodynamics and renin-angiotensin system activity post-CPAP therapy in humans with obstructive sleep apnea.

Men have faster loss of kidney function and greater renal renin-angiotensin system (RAS) activity compared with women. Obstructive sleep apnea (OSA) is common in chronic kidney disease; the vascular effects of OSA differ by sex, and OSA-associated glomerular hyperfiltration can be reversed by continuous positive airway pressure (CPAP) therapy. We evaluated sex differences in the effect of CPAP on renal hemodynamics and the renal RAS in OSA. Twenty-nine Na+-replete, otherwise healthy study participants with OSA (10 women and 19 men) with nocturnal hypoxemia were studied pre- and post-CPAP (>4 h/night for 4 wk). Renal hemodynamics [renal plasma flow (RPF), glomerular filtration rate (GFR), and filtration fraction(FF)] were measured at baseline and in response to ANG II challenge, as a marker of renal RAS activity, pre- and post-CPAP therapy for 1 mo. In women, CPAP was associated with increased RPF (626 ± 22 vs. 718 ± 43 mL/min, P = 0.007, pre- vs. post-CPAP), maintained GFR (108 ± 2 vs. 105 ± 3 mL/min, P = 0.8), and reduced FF (17.4 ± 0.8% vs. 15.0 ± 0.7%, P = 0.017). In men, CPAP was associated with maintained RPF (710 ± 37 vs. 756 ± 38 mL/min, P = 0.1), maintained GFR (124 ± 8 vs. 113 ± 6 mL/min, P = 0.055), and reduced FF (18.6 ± 1.7% vs. 15.5 ± 1.1%, P = 0.035). Pre-CPAP, there were no sex differences in renal hemodynamic responses to ANG II. CPAP use was associated with a greater renovasoconstrictive response to ANG II in women (RPF at Δ30 min: -100 ± 27 vs. -161 ± 25 mL/min, P = 0.007, and RPF at Δ60 min: -138 ± 27 vs. -206 ± 32 mL/min, P = 0.007) but not men. CPAP use was associated with improved renal hemodynamics in both sexes and downregulated renal RAS activity in women but not men.

Estradiol and mortality in women with end-stage kidney disease.

BACKGROUND: Young women with end-stage kidney disease (ESKD) have early menopause compared with women in the general population and the highest mortality among the dialysis population. We hypothesized that low estrogen status was associated with death in women with ESKD. METHODS: We measured estradiol and sex hormone levels in female ESKD patients initiating hemodialysis from 2005 to 2012 in four Canadian centers. We divided women into quintiles based on estradiol levels and tested for associations between the estradiol level and cardiovascular (CV), non-CV and all-cause mortality. Participants were further dichotomized by age. RESULTS: A total of 482 women (60 ± 15 years of age, 53% diabetic, estradiol 116 ± 161 pmol/L) were followed for a mean of 2.9 years, with 237 deaths (31% CV). Estradiol levels were as follows (mean ± standard deviation): Quintile 1: 19.3 ± 0.92 pmol/L; Quintile 2: 34.6 ± 6.6 pmol/L; Quintile 3: 63.8 ± 10.6 pmol/L; Quintile 4: 108.9 ± 19.3; Quintile 5: 355 ± 233 pmol/L. Compared with Quintile 1, women in Quintiles 4 and 5 had significantly higher adjusted all-cause mortality {hazard ratio [HR] 2.12 [95% confidence interval (CI) 1.38-3.25] and 1.92 [1.19-3.10], respectively}. Similarly, compared with Quintile 1, women in Quintile 5 had higher non-CV mortality [HR 2.16 (95% CI 1.18-3.96)]. No associations were observed between estradiol levels and CV mortality. When stratified by age, higher quintiles were associated with greater all-cause mortality (P for trend <0.001) and non-CV mortality (P for trend = 0.02), but not CV mortality in older women. CONCLUSIONS: In women with ESKD treated with hemodialysis, higher estradiol levels were associated with greater all-cause and non-CV mortality. Further studies are required to determine the mechanism for the observed increased risk.

Toward Gender Equity in Critical Care Medicine: A Qualitative Study of Perceived Drivers, Implications, and Strategies.

OBJECTIVES: Critical care medicine is a medical specialty where women remain underrepresented relative to men. The purpose of this study was to explore perceived drivers (i.e., influencing factors) and implications (i.e., associated consequences) of gender inequity in critical care medicine and determine strategies to attract and retain women. DESIGN: Qualitative interview-based study. SETTING: We recruited participants from the 13 Canadian Universities with adult critical care medicine training programs. PARTICIPANTS: We invited all faculty members (clinical and academic) and trainees to participate in a semistructured telephone interview and purposely aimed to recruit two faculty members (one woman and one man) and one trainee from each site. Interviews were transcribed verbatim, and two investigators conducted thematic analysis. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Three-hundred seventy-one faculty members (20% women, 80% men) and 105 trainees (28% women, 72% men) were invited to participate, 48 participants were required to achieve saturation. Participants unanimously described critical care medicine as a specialty practiced predominantly by men. Most women described experiences of being personally or professionally impacted by gender inequity in their group. Postulated drivers of the gender gap included institutional and interpersonal factors. Mentorship programs that span institutions, targeted policies to support family planning, and opportunities for modified role descriptions were common strategies suggested to attract and retain women. CONCLUSIONS: Participants identified a gender gap in critical care medicine and provided important insight into the impact for personal, professional, and group dynamics. Recommended improvement strategies are feasible, map broadly onto reported drivers and implications, and are applicable to critical care medicine and more broadly throughout medical specialties.

Determining the research priorities for patients with chronic kidney disease not on dialysis.

BACKGROUND: The importance of engaging key stakeholders, and patients in particular, in determining research priorities has been recognized. We sought to identify the top 10 research priorities for patients with non-dialysis chronic kidney disease (CKD), their caregivers, and the clinicians and policy-makers involved in their care. METHODS: We used the four-step James Lind Alliance process to establish the top 10 research priorities. A national survey of patients with non-dialysis CKD (estimated glomerular filtration rate <45 mL/min/1.73 m 2 ), their caregivers, and the clinicians and policy-makers involved in their care was conducted to identify research uncertainties. A Steering Group of patients, caregivers, clinicians and researchers combined and reduced these uncertainties to 30 through a series of iterations. Finally, a workshop with participants from across Canada (12 patients, 6 caregivers, 3 physicians, 2 nurses, 1 pharmacist and 1 policy-maker) was held to determine the top 10 research priorities, using a nominal group technique. RESULTS: Overall, 439 individuals responded to the survey and identified 1811 uncertainties, from which the steering group determined the top 30 uncertainties to be considered at the workshop. The top 10 research uncertainties prioritized at the workshop included questions about treatments to prevent progression of kidney disease (including diet) and to treat symptoms of CKD, provider- and patient-targeted strategies for managing CKD, the impact of lifestyle on disease progression, harmful effects of medications on disease progression, optimal strategies for treatment of cardiovascular disease in CKD and for early identification of kidney disease, and strategies for equitable access to care for patients with CKD. CONCLUSIONS: We identified the top 10 research priorities for patients with CKD that can be used to guide researchers, as well as inform funders of health-care research.

Sex differences in associations between insulin resistance, heart rate variability, and arterial stiffness in healthy women and men: a physiology study.

Diabetes confers greater cardiovascular risk to women than to men. Whether insulin-resistance-mediated risk extends to the healthy population is unknown. Measures of insulin resistance (fasting insulin, homeostatic model assessment, hemoglobin A1c, quantitative insulin sensitivity check index, glucose) were determined in 48 (56% female) healthy subjects. Heart rate variability (HRV) was calculated by spectral power analysis and arterial stiffness was determined using noninvasive applanation tonometry. Both were measured at baseline and in response to angiotensin II infusion. In women, there was a non-statistically significant trend towards increasing insulin resistance being associated with an overall unfavourable HRV response and increased arterial stiffness to the stressor, while men demonstrated the opposite response. Significant differences in the associations between insulin resistance and cardiovascular physiological profile exist between healthy women and men. Further studies investigating the sex differences in the pathophysiology of insulin resistance in cardiovascular disease are warranted.