Sex-Dependency of T Cell-Induced Salt-Sensitive Hypertension and Kidney Damage.

BACKGROUND: It is established that the immune system, namely T cells, plays a role in the development of hypertension and renal damage in male Dahl salt-sensitive (SS) rats, but far less is known about this relationship in females. Rats with genetically deleted T cells via CD247 gene mutation on the Dahl SS background (SSCD247-/-) were utilized to interrogate the effect of sex and T cells on salt sensitivity. METHODS: We assessed the hypertensive and kidney injury phenotypes in male versus female SS and SSCD247-/- rats challenged with 3 weeks of high salt (4.0% NaCl). Differences in T-cell activation genes were examined in renal T cells from male and female SS rats, and a sex-specific adoptive transfer was performed by injecting male or female splenocytes into either male or female SSCD247-/- recipients to determine the potential contribution of T-cell sex. RESULTS: The lack of functional T cells in SSCD247-/- rats significantly reduced salt-induced hypertension and proteinuria in both sexes, although SSCD247-/- females exhibited greater protection from kidney damage. Adoptive transfer of either Dahl SS male or female splenocytes into SSCD247-/- male recipients exacerbated hypertension and proteinuria compared with controls, while in SSCD247-/- female recipients, exacerbation of disease occurred only upon transfer of male, but not female, SS splenocytes. CONCLUSIONS: The absence of T cells in the SSCD247-/- normalized sex differences in blood pressure, though sex differences in renal damage persisted. Splenocyte transfer experiments demonstrated that salt sensitivity is amplified if the sex of the T cell or the recipient is male.

Do foot type classifications differ between male and female netball players? A cluster analysis.

We must better understand the foot type classifications of netball players to develop sex and size-specific shoe lasts. Five hundred and two representative-level netball players (n = 251 male; n = 251 female) had their feet three-dimensionally scanned. A validated MATLAB code was used to extract six different foot measurements from these scans automatically. We then used a two-step cluster analysis and chi-squared tests to classify foot types and determine the effect of sex on each cluster, respectively. Five foot types were identified (Extra long-and-wide, Long-and-wide, Flat, Tapered and Short-and-narrow), with sex significantly affecting foot type classification. The feet of players wearing smaller shoe sizes were often Short-and-narrow and Tapered, whereas the feet of players wearing larger sizes tended to be more Extra long-and-wide and Long-and-wide. These results highlight that netball players have a wide variety of foot types; manufacturers should use these data to develop future grading systems to improve the fit and functionality of netball-specific footwear.

This study aimed to investigate the foot types of netball players. The results demonstrated that five main foot types should be used to inform future shoe last designs and size grading systems. These findings have implications for improving the fit and functionality of netball shoes, particularly for men.

Enhancing intersex healthcare: A qualitative study of parental perspectives on the role of genetics.

Intersex individuals, encompassing people with diverse sex characteristics that do not fit binary frameworks of sex, have long faced a history of medical secrecy, discrimination, and societal stigma, contributing to their limited social visibility. In recent years, increased awareness of intersex issues and a robust advocacy movement have drawn significant attention to the experiences of intersex individuals and their families. This study contributes to the existing literature by examining the experiences and needs of parents of intersex individuals within genetic healthcare systems, bridging a critical gap, and advocating for more comprehensive and supportive healthcare practices. Semi-structured interviews were conducted with 14 parents of intersex individuals, and reflexive thematic analysis was used to inductively generate four major themes. Themes highlighted the need for improved accessibility of intersex healthcare, the importance of multidisciplinary healthcare teams, and the significance of clinical diagnosis provided by genetics professionals. Furthermore, the study highlighted the necessity of a thoughtful approach to information provision and the impact of genetic investigations on family dynamics. Genetics professionals can play a pivotal role in raising awareness about intersex variations, improving diagnostic processes, collaborating within healthcare teams, and providing specialized support to address psychosocial concerns. The study underscores the importance of treating families as a collective entity and addressing the impact of genetic investigations on the family unit. By addressing the challenges and implementing the recommendations outlined, healthcare institutions can create a more compassionate, inclusive, and effective healthcare environment for the intersex community.

Comparison of enjoyment and energy expenditure of exergame with and without blood flow restriction in men and women.

This study compared the effects of blood flow restriction (BFR) on intensity and perceived enjoyment during an exergame. Fourteen healthy young participants engaged in a boxing exergame for 20 min, with or without BFR, across two sessions. Perceived enjoyment levels were assessed using the Physical Activity Enjoyment Scale. Heart rate was monitored, and energy expenditure (EE) during exercise was calculated. A mixed model analysis of variance with repeated measures was used to evaluate differences in EE and enjoyment between exergame conditions (with and without BFR) as well as the interaction effects of these protocols with gender. Although not statistically significant, perceived enjoyment decreased with BFR inclusion for both genders. No significant differences were observed between men and women for both protocols. Regarding EE, there was no significant difference between the two groups (with and without BFR). However, a significant main effect of gender was found, with men exhibiting higher EE values in both protocols compared to women. In conclusion, exergames incorporating BFR impact perceptual responses, particularly perceived enjoyment. Furthermore, significant gender differences in EE were found, with men displaying higher values.

Understanding Female and Male Insights in Psychology: Who Thinks What?

Evolutionary psychology is the study of human psychological behavior. During childhood, men and women behave similarly; however, as a child approaches puberty, new physical and behavioral changes emerge. Behavioral psychology focuses on understanding the functioning and thought processes of the human mind. The general population lacks knowledge of basic behavioral differences between men and women, leaving them unaware of their role, limitations, societal responsibilities, resulting in an underestimation of their own natural talents and biology. Thus, people tend to follow societal norms rather than exploring and utilizing their natural talents. The current review was designed and conducted to enforce compression on behavioral psychology in both genders as well as to identify variations in hormonal activity and sexual preferences.

Do the feet of male and female netball players differ in shape? Implications for shoe design.

A large proportion of netball players suffer foot-related problems and pain and are dissatisfied with current netball-specific footwear. To improve the fit and functionality of netball-specific shoes, we must understand the shape of these players' feet and determine whether any sex differences exist. Five hundred and two representative-level netball players (n = 251 male; n = 251 female) had their feet three-dimensionally scanned. We then used a validated MATLAB code to automatically extract 10 measurements to characterise each participant's foot shape. Differences between men and women for the absolute values and those normalised to foot length and stature were identified using independent samples t-tests with a Bonferroni adjusted alpha level. The size and shape of male netball players' feet differed significantly from their female counterparts. Males had significantly larger absolute and normalised foot measurements than females, notably at the ball of the foot, heel and instep (p < 0.001). Netball shoe manufacturers should develop unique lasts for each sex and foot size and should offer a more extensive range of shoe lengths and widths to netball players. Such considerations will help optimise shoe fit and comfort and, in turn, reduce foot-related problems and pain associated with ill-fitting footwear.

Sex differences in the pre-hospital ambulance delay, assessment and treatment of patients with acute coronary syndrome: a rapid evidence review.

Background: Chest pain is a frequent symptom suffered by adult patients attended by ambulance. Evidence suggests female patients may suffer different symptoms to their male counterparts, potentiating differences in pre-hospital time delays, assessment and treatment. Objective: To explore the sex differences in the pre-hospital ambulance delay, assessment and treatment of patients with acute coronary syndrome (ACS). Methods: A rapid evidence review was conducted following the Cochrane rapid review guidelines. MEDLINE and CINAHL Complete were searched via EBSCOhost on 2 February 2023, and reference lists of included studies and reviews were screened. The Joanna Briggs Institute checklist for analytical cross-sectional studies was used to perform critical appraisal, and a narrative synthesis was conducted. Results: From 216 articles screened, nine were included, representing over 3.1 million patients from five different countries. Female patients were more likely to suffer delays in time to first electrocardiogram (ECG) and delays in transport time to the emergency department by ambulance. Female patients were also less likely to receive an ECG, aspirin, glyceryl trinitrate and other analgesics. Conclusion: There are sex disparities in the pre-hospital ambulance delay, assessment and treatment of patients with ACS. Future research is urgently needed to fully understand the reasons for these observations.

Educational guidelines on sexual orientation, gender identity and expression, and sex characteristics biases in medical education.

A commitment to diversity, equity, inclusion, and belonging in medical education requires addressing both explicit and implicit biases based on sexual orientation, gender identity and expression, and sex characteristics and the intersectionality with other identities. Heterosexism and heteronormative attitudes contribute to health and healthcare disparities for lesbian, gay, bisexual, transgender and queer or questioning, intersex, asexual individuals. Student, trainee, and faculty competencies in medical education curricula regarding the care of lesbian, gay, bisexual, transgender and queer or questioning, intersex, asexual patients and those who are gender nonconforming or born with differences of sex development allow for better understanding and belonging within the clinical learning environment of lesbian, gay, bisexual, transgender and queer/questioning, intersex, asexual learners and educators. The Association of Professors of Gynecology and Obstetrics issued a call to action to achieve a future free from racism and bias through inclusivity in obstetrics and gynecology education and healthcare, which led to the creation of the Association of Professors of Gynecology and Obstetrics Diversity, Equity, and Inclusion Guidelines Task Force. The task force initially addressed racism, racial- and ethnicity-based bias, and discrimination in medical education and additionally identified other groups that are subject to bias and discrimination, including sexual orientation, gender identity and expression, and sex characteristic identities, persons with disabilities, and individuals with various religious and spiritual practices. In this scholarly perspective, the authors expand on previously developed guidelines to address sexual orientation, gender identity and expression, and sex characteristics bias, heterosexism, and heteronormative attitudes in obstetrics and gynecology educational products, materials, and clinical learning environments to improve access and equitable care to vulnerable individuals of the lesbian, gay, bisexual, transgender and queer or questioning, intersex, asexual community.

Combined effects of binary mixtures of 17ß-estradiol and testosterone in western mosquitofish (Gambusia affinis) after full life-cycle exposure.

Estrogens and androgens are typical steroid hormones and often occur together in contaminated aquatic environments, but their mixed effects in aquatic organisms have been less well reported. In this study, the endocrine disrupting effects of binary mixtures of 17ß-estradiol (E2) and testosterone (T) in western mosquitofish (Gambusia affinis) were assessed by analyzing the sex ratio, secondary sex characteristics, gonadal histology, and transcriptional expression of target genes related to the hypothalamic-pituitary-gonadal (HPG) axis in G. affinis (from embryos) continuously exposed to E2 (50 ng/L), T (T1: 50 ng/L; T2: 200 ng/L), and mixtures of both (E2 + T1: 50 + 50 ng/L; E2 + T2: 50 + 200 ng/L) for 119 d. The results showed that exposure to E2 + T1 and E2 + T2 reduced the length ratio of ray 4/6 ratio in male G. affinis, suggesting feminized phenomenon in male G. affinis. Furthermore, 16.7-38.5 % of female G. affinis showed masculinized anal fins and hemal spines when exposed to T alone and in combination with E2. Importantly, the transcriptional levels of certain target genes related to the HPG axis were significantly altered in G. affinis following exposure to E2 and T alone and in combinations. Moreover, exposure to E2 and T in combinations can lead to combined effects (such as synergistic and antagonistic effects) on the transcriptional levels of some genes. These results collectively suggest that exposure to environmentally relevant concentrations of E2 and T alone and in mixtures can impact the endocrine system of G. affinis, and may pose potential risks in aquatic systems.

Sex Disparities in Rectal Cancer Surgery: An In-Depth Analysis of Surgical Approaches and Outcomes.

Anatomical and physiological differences exist between sex, leading to variations in how diseases, such as rectal cancer, are prevalence and treatment outcomes of diseases including rectal cancer. In particular, in the case of rectal cancer, anatomical differences may be associated with surgical challenges, and these factors are believed to be important contributors to potential disparities in postoperative recovery, associated complications, and oncological outcomes between male and female patients. However, there is still ongoing debate regarding this matter. Significantly, the male pelvic anatomy is distinguished by its narrower dimensions, which can present surgical challenges and impede visual access during operative procedures, rendering it more complex than surgical interventions in the female pelvis. As a result, this anatomical difference leads to a greater occurrence of postoperative complications, such as anastomotic leakage. Moreover, the pelvis houses nerves that are vital for urinary and genital functions, underscoring the need to assess the potential risks of sexual and urinary dysfunction in rectal cancer surgery. These postoperative complications can significantly impact the quality of life; therefore, it is imperative to perform surgery with an understanding of the structural differences between sexes. Therefore, to address the limitations imposed by anatomical structures, new approaches such as robotic surgery, trans-anal total mesorectal excision, and intraoperative neuromonitoring are being introduced. Furthermore, it is essential to conduct research into fundamental mechanisms that may give rise to differences in surgical outcomes and oncological results between sexes. By comprehending the disparities between males and females, we can advance toward personalized treatments. Consequently, this review outlines variations in surgical approaches, complications, and treatments for rectal cancer in male and female patients.

Association of Traditional and Nontraditional Risk Factors in the Development of Strokes Among Young Adults by Sex and Age Group: A Retrospective Case-Control Study.

BACKGROUND: Despite women having fewer traditional risk factors (eg, hypertension, diabetes), strokes are more common in women than men aged ≤45 years. This study examined the contributions of traditional and nontraditional risk factors (eg, migraine, thrombophilia) in the development of strokes among young adults. METHODS: This retrospective case-control study used Colorado's All Payer Claims Database (2012-2019). We identified index stroke events in young adults (aged 18-55 years), matched 1:3 to stroke-free controls, by (1) sex, (2) age±2 years, (3) insurance type, and (4) prestroke period. All traditional and nontraditional risk factors were identified from enrollment until a stroke or proxy-stroke date (defined as the prestroke period). Conditional logistic regression models stratified by sex and age group first assessed the association of stroke with counts of risk factors by type and then computed their individual and aggregated population attributable risks. RESULTS: We included 2618 cases (52% women; 73.3% ischemic strokes) and 7827 controls. Each additional traditional and nontraditional risk factors were associated with an increased risk of stroke in all sex and age groups. In adults aged 18 to 34 years, more strokes were associated with nontraditional (population attributable risk: 31.4% men and 42.7% women) than traditional risk factors (25.3% men and 33.3% women). The contribution of nontraditional risk factors declined with age (19.4% men and 27.9% women aged 45-55 years). The contribution of traditional risk factors peaked among patients aged 35 to 44 years (32.8% men and 39.7% women). Hypertension was the most important traditional risk factor and increased in contribution with age (population attributable risk: 27.8% men and 26.7% women aged 45 to 55 years). Migraine was the most important nontraditional risk factor and decreased in contribution with age (population attributable risk: 20.1% men and 34.5% women aged 18-35 years). CONCLUSIONS: Nontraditional risk factors were as important as traditional risk factors in the development of strokes for both young men and women and have a stronger association with the development of strokes in adults younger than 35 years of age.

Measuring mantled howler monkey (Alouatta palliata) testes via parallel laser photogrammetry: Expanding the use of noninvasive methods.

Parallel laser photogrammetry (PLP), which consists of attaching two or three parallel laser beams at a known inter-beam distance to a camera, can be used to collect morphological measurements of organisms noninvasively. The lasers project onto the photo being taken, and because the inter-beam distance is known, they act as a scale for image analysis programs like ImageJ. Traditionally, this method has been used to measure larger morphological traits (e.g., limb length, crown-rump length) to serve as proxies for overall body size, whereas applications to smaller anatomical features remain limited. To that end, we used PLP to measure the testes of 18 free-living mantled howler monkeys (Alouatta palliata) at La Selva Biological Station, Costa Rica. We tested whether this method could reliably measure this relatively small and globular morphology, and whether it could detect differences among individuals. We tested reliability in three ways: within-photo (coefficient of variation [CV] = 4.7%), between-photo (CV = 5.5%), and interobserver (intraclass correlation = 0.92). We found an average volume of 36.2 cm3 and a range of 16.4-54.4 cm3, indicating variation in testes size between individuals. Furthermore, these sizes are consistent with a previous study that collected measurements by hand, suggesting that PLP is a useful method for making noninvasive measurements of testes.

Challenges in Transition of Care for People with Variations in Sex Characteristics in the European Context.

OBJECTIVE: People with variations in sex characteristics (VSCs) have been receiving inadequate care for many decades. The Chicago consensus statement in 2006 aimed to introduce improved comprehensive care, which would include the transition of care from pediatric to adult services organized by multidisciplinary teams. Yet, the evidence for transitional care is scarce. The aim of this paper is to outline the delivery of transition of care for adolescents and young adults with VSCs. METHOD: Seven focus groups were conducted with health care professionals and peer support groups by care teams in Central, Northern, and Western Europe. The data from the focus groups were examined using reflexive thematic analysis. RESULTS: Even though the transition of care has been implemented in the last two decades, it remains inadequate. There are differences among countries, as the quality of care depends on available resources and variations in sex characteristics. Moreover, there are significant hurdles to adequate transition of care, as there is lack of time and funding. The lack of adult care providers and psychosocial support often leaves young adults with VSCs to navigate the health care system alone. CONCLUSION: The outcome of the study shows that the transition of care is organized through the department of pediatric endocrinology. The quality of care varies due to resources and variations in sex characteristics. A lack of adult specialists, and especially psychosocial support, represents the biggest obstacle for young adults and adults in navigating the health care system and for improvements in the provision of health care to adults. There is a risk of re-traumatization, as adolescents and young adults must often repeat their medical history and educate adult care providers who are insufficiently trained and knowledgeable.

Sex-Specific Association Between Perivascular Inflammation and Plaque Vulnerability.

BACKGROUND: It is not known whether there is a sex difference in the association between perivascular inflammation and plaque vulnerability. The aim of this study was to investigate the sex-specific association between perivascular inflammation and plaque vulnerability. METHODS: Patients who underwent coronary computed tomography angiography and optical coherence tomography were enrolled. All images were analyzed at a core laboratory. The level of perivascular inflammation was assessed by pericoronary adipose tissue attenuation on computed tomography angiography and the level of plaque vulnerability by optical coherence tomography. Patients were classified into 3 groups according to tertile levels of culprit vessel pericoronary adipose tissue attenuation (low inflammation, ≤-73.1 Hounsfield units; moderate inflammation, -73.0 to -67.0 Hounsfield units; or high inflammation, ≥-66.9 Hounsfield units). RESULTS: A total of 968 lesions in 409 patients were included: 184 lesions in 82 women (2.2 plaques per patient) and 784 lesions in 327 men (2.4 plaques per patient). Women were older (median age, 71 versus 65 years; P<0.001) and had less severe coronary artery disease with a lower plaque burden than men. In women, it was found that perivascular inflammation was significantly associated with plaque vulnerability, with a higher prevalence of thin-cap fibroatheroma and greater macrophage grades in the high inflammation group compared with the low inflammation group (low versus moderate versus high inflammation in women: 18.5% versus 31.8% versus 46.9%, P=0.002 for low versus high inflammation; 3 versus 4 versus 12, P<0.001 for low versus high inflammation, respectively). However, no significant differences were observed among the 3 groups in men. CONCLUSIONS: Perivascular inflammation was associated with a higher prevalence of thin-cap fibroatheroma and more significant macrophage accumulation in women but not in men. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.

Sex and Age Differences in the Association Between Metabolic Dysfunction-Associated Fatty Liver Disease and Heart Failure: A Prospective Cohort Study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a risk factor for heart failure (HF) occurrence, but it remains unclear whether the association between MAFLD and HF differs in different sexes and ages. METHODS: A total of 96 576 participants of Kailuan Study were included. MAFLD was defined as presence of hepatic steatosis and metabolic dysfunction and classified as mild and significant by ultrasound. Hazard ratios (HRs) were calculated by Cox regression models. RESULTS: After a median follow-up of 14.0 years, 2939 participants developed HF. Adjusting for confounding factors, mild-MAFLD (HR, 1.27 [95% CI, 1.16-1.39]) and significant-MAFLD (HR, 1.45 [95% CI, 1.31-1.63]) were associated with a higher risk of HF in all participants, and the risk differed by sex (Pinteraction<0.05) and age (Pinteraction<0.001). Compared with non-MAFLD participants, in women, significant-MAFLD was associated with an 84% (HR, 1.84 [95% CI, 1.43-2.37]) increased risk of HF; however, in men, the risk was 36% (HR, 1.36 [95% CI, 1.20-1.53]). In participants under 45 years, mild-MAFLD and significant-MAFLD had a 55% (HR, 1.55 [95% CI, 1.07-2.25]) and 172% (HR, 2.72 [95% CI, 1.87-3.97]) increased risk of HF; however, in participants over 65 years, even significant-MAFLD did not associate with a higher risk of HF (HR, 1.11 [95% CI, 0.92-1.34]). Afterwards, we stratified all participants by both sex and age and found that the risk of MAFLD-associated HF decreased with age in men (Pinteraction<0.05) and women (Pinteraction<0.05), but the sex difference in this risk was only present in participants younger than 45 years (Pinteraction<0.05). CONCLUSIONS: MAFLD greatly increased the risk of HF in women, especially young women. With increasing age, MAFLD-related risk of HF decreased and the difference between men and women disappeared.

Efficacy of Quadruple-coated Probiotics in Patients With Irritable Bowel Syndrome: A Randomized, Double-blind, Placebo-controlled, Parallel-group Study.

Background/Aims: To evaluate the efficacy of quadruple-coated probiotics (gQlab) in patients with irritable bowel syndrome (IBS), focusing on sex differences and IBS subtypes. Methods: One hundred and nine Rome III-diagnosed IBS patients were randomized into either a gQlab or placebo group and received either gQlab or a placebo for 4 weeks. Participants replied to questionnaires assessing compliance, symptoms, and safety. Fecal samples were collected at 0 and 4 weeks to measure the probiotic levels using real-time quantitative polymerase chain reaction (qPCR) and to perform metagenomic analysis via 16S ribosomal DNA sequencing. The primary endpoint was the change in the overall IBS symptoms after 4 weeks of treatment. Results: Ninety-two subjects (47 and 45 in the gQlab and placebo groups, respectively) completed the study protocol. At week 4, there was a higher relief of the overall IBS symptoms in the gQlab group (P = 0.005). The overall IBS symptom improvement was statistically significant (P = 0.017) in female patients of the gQlab group compared with the placebo group. Among the IBS subtypes, constipation-predominant IBS patients showed significant relief of the overall IBS symptoms (P = 0.002). At week 4, the fecal microbiome profiles between the 2 groups did not differ, but the qPCR levels of Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus helveticus, Bifidobacterium longum, and Bifidobacterium breve were increased in the gQlab group (P < 0.05 by repeated measures ANOVA). Conclusions: gQlab administration can improve the overall IBS symptoms, especially in female and constipation-predominant IBS patients. Further research is necessary to clarify the pathophysiology behind sex-related treatment responses in IBS patients.

Sex-Based Analysis of Workflow and Outcomes in Acute Ischemic Stroke Patients Treated With Alteplase Versus Tenecteplase.

BACKGROUND: Understanding sex differences in stroke care is important in reducing potential disparities. Our objective was to explore sex differences in workflow efficiency, treatment efficacy, and safety in the AcT trial (Alteplase Compared to Tenecteplase). METHODS: AcT was a multicenter, registry-linked randomized noninferiority trial comparing tenecteplase (0.25 mg/kg) with alteplase (0.9 mg/kg) in acute ischemic stroke within 4.5 hours of onset. In this post hoc analysis, baseline characteristics, workflow times, successful reperfusion (extended Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracerebral hemorrhage, 90-day functional independence (modified Rankin Scale score, 0-1), and 90-day mortality were compared by sex. Mixed-effects regression analysis was used adjusting for age, stroke severity, and occlusion site for outcomes. RESULTS: Of 1577 patients treated with intravenous thrombolysis (2019-2022), 755 (47.9%) were women. Women were older (median, 77 [68-86] years in women versus 70 [59-79] years in men) and had a higher proportion of severe strokes (National Institutes of Health Stroke Scale score >15; 32.4% versus 24.9%) and large vessel occlusions (28.7% versus 21.5%) compared with men. All workflow times were comparable between sexes. Women were less likely to achieve functional independence (31.7% versus 39.8%; unadjusted relative risk, 0.80 [95% CI, 0.70-0.91]) and had higher mortality (17.7% versus 13.3%; unadjusted relative risk, 1.33 [95% CI, 1.06-1.69]). Adjusted analysis showed no difference in outcomes between sexes. CONCLUSIONS: Differences in prognostic factors of age, stroke severity, and occlusion site largely accounted for higher functional dependence and mortality in women. No sex disparities were apparent in workflow quality indicators. Given the integration of the AcT trial into clinical practice, these results provide reassurance that no major sex biases are apparent in acute stroke management throughout participating Canadian centers. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Sex Disparities in Longitudinal Use and Intensification of Guideline-Directed Medical Therapy Among Patients With Newly Diagnosed Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Guideline-directed medical therapies (GDMTs) are the mainstay of treatment for heart failure with reduced ejection fraction (HFrEF), but they are underused. Whether sex differences exist in the initiation and intensification of GDMT for newly diagnosed HFrEF is not well established. METHODS: Patients with incident HFrEF were identified from the 2016 to 2020 Optum deidentified Clinformatics Data Mart Database, which is derived from a database of administrative health claims for members of large commercial and Medicare Advantage health plans. The primary outcome was the use of optimal GDMT within 12 months of HFrEF diagnosis. Consistent with the guideline recommendations during the time period of the study, optimal GDMT was defined as ≥50% of the target dose of evidence-based beta-blocker plus ≥50% of the target dose of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, or any dose of angiotensin receptor neprilysin inhibitor plus any dose of mineralocorticoid receptor antagonist. The probability of achieving optimal GDMT on follow-up and predictors of optimal GDMT were evaluated with time-to-event analysis with adjusted Cox proportional hazard models. RESULTS: The study cohort included 63 759 patients (mean age, 71.3 years; 15.2% non-Hispanic Black race; 56.6% male). Optimal GDMT use was achieved by 6.2% of patients at 12 months after diagnosis. Female (compared with male) patients with HFrEF had lower use across every GDMT class and lower use of optimal GDMT at each time point at follow-up. In an adjusted Cox model, female sex was associated with a 23% lower probability of achieving optimal GDMT after diagnosis (hazard ratio [HR], 0.77 [95% CI, 0.71-0.83]; P<0.001). The sex disparities in GDMT use after HFrEF diagnosis were most pronounced among patients with commercial insurance (females compared with males; HR, 0.66 [95% CI, 0.58-0.76]) compared with Medicare (HR, 0.85 [95% CI, 0.77-0.92]); Pinteraction sex×insurance status=0.005) and for younger patients (age <65 years: HR, 0.65 [95% CI, 0.58-0.74]) compared with older patients (age ≥65 years: HR, 87 [95% CI, 80-96]) Pinteraction sex×age=0.009). CONCLUSIONS: Overall use of optimal GDMT after HFrEF diagnosis was low, with significantly lower use among female (compared with male) patients. These findings highlight the need for implementation efforts directed at improving GDMT initiation and titration.

Navigating the complexities of adult healthcare for individuals with variations of sex characteristics: from paediatric emergencies to a sense of abandonment.

Intersex people and those with variations of sex characteristics face significant health and social issues. This paper analyses the complexities of adult healthcare for this diverse population, including the root causes of deficiencies in care provision. Many minors with variations of sex characteristics are subjected to irreversible, non-consensual medical interventions, which can have negative effects on their health and wellbeing as adults. This 'emergency' approach to intersex paediatric healthcare has been challenged since the 1990s, but there is still a lack of understanding about how the paradigm affects adult care. This paper aims to raise awareness of the health challenges faced by adults with variations of sex characteristics. It identifies themes related to the challenges associated with accessing appropriate adult care, including the repercussions of childhood treatment, the lack of transitional services and psychological support, the limited general medical knowledge about variations of sex characteristics, and the reluctance to access services due to fear of stigma or past medical trauma. The paper indicates the need for more attention to intersex people's health needs as adults, moving away from attempts to 'fix' them as minors towards approaches which consider and provide for their diverse healthcare needs in a broader temporal context.