Sex Differences In Functional Outcomes Research Articles

Trends in Sex Differences of Functional Outcome after Intravenous Thrombolysis in Patients with Acute Ischemic Stroke.

Intravenous thrombolysis (IVT) is an approved treatment for patients with acute ischemic stroke irrespective of sex. However, the current literature on sex differences in functional outcomes following IVT is inconsistent. So far, a number of studies - including a previous analysis based on data from the Austrian Stroke Unit Registry (ASUR) - detected significant sex-related differences in functional outcome, while others did not report any differences between women and men. In addition, currently there is a lack of data on how sex-related differences evolve over time. To assess time trends of sex-related differences in functional outcome of ischemic stroke in a large nationwide cohort and to investigate associations of patient characteristics with functional outcome post thrombolysis in women and men. These data will offer crucial insights into whether sex differences in functional outcome persist despite the large advances in acute stroke treatment. We analyzed retrospective data of consecutive patients with acute ischemic stroke treated with IVT in 39 stroke centers contributing to the ASUR between 2006 and 2021. We included patients over 18 years of age diagnosed with an acute ischemic stroke who received IVT and with available data on functional outcome at 3 months after treatment. The primary outcome parameter was favorable functional outcome (modified Rankin Scale (mRS) of 0-2) at 3 months. Multivariable logistic regression analysis was performed in the overall population and stratified by sex to assess associations of baseline characteristics with functional outcome. Among 11840 patients receiving IVT, 2489/5503 (45.4%) women achieved favorable functional outcome compared to 3787/6337 (59.8%) men. Overall, female sex was a statistically significant predictor of functional outcome after thrombolysis, but additional predictors of outcome differed between women and men. Female sex was independently associated with decreased chances of achieving functional independency (adjOR 0.87, 95%CI 0.79-0.96, p=0.005) and we detected a statistically significant improvement in functional outcome over time only in men (year of treatment, adjOR (per year) 1.04, 95%CI 1.02-1.06, p<0.001) but not in women (adjOR (per year) 1.01, 95%CI 0.99-1.03, p=0.280). Hypertension, smoking, and longer or unknown onset-to-door times were statistically significant predictors of outcome only in male patients, whereas atrial fibrillation, prior myocardial infarction and longer door-to-needle times were significantly associated with outcome only in women. Sex differences in functional outcome after IVT for acute ischemic stroke are persisting over the past years. Results of our analysis can increase awareness and a resulting focus on sex differences in predictors of outcome could be helpful in mitigating these differences in the future by supporting a more individualized patient care in clinical routine. Follow-up analyses are needed to assess this potential impact and its effect in the future.Data access statement: Data from the Austrian Stroke Unit Registry can only be accessed by the employed statistician (DM), access inquiries have to be addressed to the registry's academic review board.

Sex differences in functional outcomes of intravenous thrombolysis among patients with lacunar stroke.

This study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS). Consecutive patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke. A total of 413 patients with LS were treated with IVT: 177 (42.9%) women and 236 (57.1%) men. Women were older than men (median age 74 years, 25th-75th percentiles 67-84 years versus 70 years, 25th-75th percentiles 60-80 years, value of p 0.001) and, after adjustment for meaningful variables, showed more frequently increased odds of a higher mRS score at 90 days after stroke (adjusted odds ratio 1.49, 95% confidence interval 1.01-2.19, value of p 0.044). This study showed that female sex increased the odds of a worse functional response to IVT in patients with LS. Future studies should further elucidate the mechanisms underlying such sex differences.

Sex Differences in Obstructive Sleep Apnea after Stroke.

ABSTRACT: Background and Objectives: Obstructive sleep apnea (OSA) is prevalent after stroke and associated with recurrent stroke, prolonged hospitalization, and decreased functional recovery. Sex differences in post-stroke OSA remain underexplored. The objective of this study was to evaluate sex differences in functional outcomes, stroke and OSA severity, and clinical manifestations of OSA in stroke patients with OSA. Methods: We retrospectively evaluated data from three previously conducted studies. Study patients had an imaging-confirmed stroke and had been found to have OSA (apnea–hypopnea index [AHI] ≥ 5) on either in-laboratory polysomnography or home sleep apnea testing performed within 1 year of their stroke. Linear regression models were used to evaluate study outcomes. Results: In total, 171 participants with post-stroke OSA (117 males [68.4%] and 54 females [31.6%]) were included. Female sex was an independent predictor for greater functional impairment (β = 0.37, 95% CI 0.029–0.71, p = 0.03), increased stroke severity (β = 1.009, 95% CI 0.032–1.99, p = 0.04), and greater post-stroke depressive symptoms (β = 3.73, 95% CI 0.16–7.29, p = 0.04). Female sex was associated with lower OSA severity, as measured by the AHI (β = –5.93, 95% CI –11.21– –0.66). Sex was not an independent predictor of specific symptoms of OSA such as daytime sleepiness, snoring, tiredness, and observed apneas. Conclusion: Females with post-stroke OSA had poorer functional outcomes and more severe strokes compared to males, despite having lower OSA severity. Females with post-stroke OSA also exhibited more depressive symptoms. Understanding sex differences in patients with post-stroke OSA will likely facilitate better recognition of OSA and potentially improve clinical outcomes.

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

Studies of sex differences in the use and outcomes of endovascular treatment (EVT) for acute ischemic stroke report inconsistent results. We 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. 6,396 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). No 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. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=226100, identifier: CRD42021226100.

Sex differences in the cognitive performance in adults: role of impaired sleep.

ObjectivesPoor sleep quality negatively affects cognitive performance. However, there are limited data on sex differences in functional outcomes of impaired sleep on cognition. Therefore, the aim of this study was to evaluate the association between sleep quality and performance of men and women in cognitive tests.Material and MethodsAfter screening, 97 individuals with and without insomnia complaints participated of this study. Behavioral scales were evaluated using a number of instruments and the sleep pattern was recorded by actigraph. Subsequently, the participants were submitted to visuospatial/verbal working memory (WM), visual attention, and psychomotor vigilance tests (PVT).ResultsThe actigraphic recordings indicated that men sleep later (d=-0.56, p<0.05), fall asleep faster (d=0.42, p<0.05), showed shorter sleep duration (d=0.53, p<0.05), and more sleep fragmentation than women (d=-0.41, p<0.05). The performance in the cognitive tasks also showed sex differences: the men showed better performance in the visuospatial short-term memory (d=-0.78, p<0.05); verbal (d=-0.61, p<0.05), and visuospatial-WM tests (d=-0.84, p<0.05); they also responded faster in the PVT (d=0.69, p<0.05), although made more mistakes (d=-0.85, p<0.01). Longer sleep latency was associated with poor performance in visual attention (r=0.52, p<0.05) and verbal memory tasks (r=-0.30, p<0.05) in men.ConclusionOur results suggest that difficulty in falling asleep was associated with cognitive impairment, especially in men. Sex differences in sleep quality and cognitive skills should be taken into account in future research in this field.

Sex Differences in Functional Outcomes Following Endovascular Treatment for Acute Ischemic Stroke.

Sex disparities have been reported across many aspects of acute ischemic stroke (AIS) care; however, there is a relative paucity of research examining sex differences in outcomes following endovascular treatment (EVT). Some studies report worse functional independence for females following EVT. Few, if any of these studies account for differences in age, baseline function, and comorbidity burden. This retrospective cohort study aimed to assess for sex differences in functional outcomes following EVT by comparing 90-day modified Rankin Scale (mRS) of males and females while controlling for baseline function and comorbidity burden. Baseline demographic and clinical data, and stroke severity were compared for 230 consecutive patients undergoing EVT for AIS between October 2014 and July 2019 at a tertiary stroke centre in Toronto, Canada. Effect of sex on likelihood of functional independence post-EVT was assessed using regression analysis with and without correction for age, baseline mRS, and Charlson Comorbidity Index (CCI). Females undergoing EVT for AIS were older (75 ± 13 vs. 66 ± 15, p < 0.0001), with worse clinical and functional baselines. Unadjusted, males were more functionally independent (90-day mRS < 3) [OR = 1.831, 95%CI 1.082-3.098]. After controlling for age, baseline mRS and CCI, there was no difference between groups [OR 1.21, 95%CI 0.61-2.37]. This study provides evidence that prior findings of sex disparities in function after EVT may be accounted for by differences in age, baseline clinical status and functional independence between males and females when a comprehensive measure of comorbidity burden is utilized.

Sexual dimorphism in neurological function after SCI is associated with disrupted neuroinflammation in both injured spinal cord and brain

Whereas human spinal cord injury (SCI) is more common in men, the prevalence is growing in women. However, little is known about the effect of biological sex on brain dysfunction and injury mechanisms. To model the highest per capita rate of injury (ages between 16 and 30 years old) in humans, in the present study, young adult or a young/middle-aged male and female C57BL/6 mice were subjected to moderate contusion SCI. When mice were injured at 10–12-week-old, transcriptomic analysis of inflammation-related genes and flow cytometry revealed a more aggressive neuroinflammatory profile in male than females following 3 d SCI, ostensibly driven by sex-specific changes myeloid cell function rather than cell number. Female mice were generally more active at baseline, as evidenced by greater distance traveled in the open field. After SCI, female mice had more favorable locomotor function than male animals. At 13 weeks post-injury, male mice showed poor performance in cognitive and depressive-like behavioral tests, while injured female mice showed fewer deficits in these tasks. However, when injured at 6 months old followed by 8 months post-injury, male mice had considerably less inflammatory activation compared with female animals despite having similar or worse outcomes in affective, cognitive, and motor tasks. Collectively, these findings indicate that sex differences in functional outcome after SCI are associated with the age at onset of injury, as well as disrupted neuroinflammation not only at the site of injury but also in remote brain regions. Thus, biological sex should be considered when designing new therapeutic agents.

The Importance of Considering Sex Differences in Translational Stroke Research.

Stroke is the second leading cause of death worldwide, and differences between men and women have been documented in incidence, prevalence, and outcome. Here, we reviewed the literature on sex differences in stroke severity, mortality, functional outcome, and response to therapies after ischemic stroke. Many of the sex differences in stroke severity and mortality are explained by differences in baseline demographics such as older age in women. However, women account for more stroke deaths, consistently suffer from worse stroke outcomes, and are more often institutionalized and permanently disabled than men. These sex differences in functional outcome are equalized after treatment with tissue plasminogen activator (tPA) and women may benefit more from treatment than men. However, this may depend on race, as African-American women have less of a response to tPA than other groups. Regarding endovascular treatments, the few existing studies that have investigated sex differences in stroke outcome point to equal benefit in both sexes; however, many clinical trials are relatively underpowered to detect sex differences. Further, we considered sex-specific effects in animal models of stroke and present recommendations for the performance of stroke studies in female animals. The male-biased use of research animals is distinguished from the clinical situation where there is a disproportionate and growing female stroke population. Stroke in women is greatly understudied, and including both sexes is especially important in both preclinical and clinical studies that evaluate potential stroke therapies.

Abstract WP405: Sex Differences in Post-Stroke Functional Outcomes

Background: Studies consistently show that women have less favorable functional outcomes after stroke than men but the causes are uncertain. Our objective was to assess sex differences in functional outcomes measured 90-days post event in a population-based stroke study and to identify which pre-stroke factors and clinical stroke characteristics explain sex differences. Methods: Ischemic stroke patients (n=398) were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) Project (2008-2011). Data were ascertained from in-person patient or proxy interviews (baseline and 90 days post-stroke) and medical records. Functional outcome at 90 days was measured as total ADL/IADL score (range 22-88, higher scores indicate poorer function). Tobit regression was used to estimate sex differences in outcome. To identify clinically important confounding factors, individual variables were added to age-adjusted models to determine if the sex difference changed by ≥ 5%. A final multivariable model was run including sex, age, ethnicity, and identified confounders. Results: Median age was 69 (IQR: 57, 79) and 52% were women. In crude and age-adjusted models women scored 11.2 points (p&lt;0.001) and 8.7 points (p&lt;0.001) higher on the ADL/IADL score respectively. After accounting for age, stroke severity, pre-stroke functional and cognitive status, pre-stroke comorbidity index, nursing home residence, history of stroke/TIA, BMI and marital status were all clinically important confounders of the sex difference. In the final multivariable model, a sex difference in functional outcome remained, with women scoring 6.2 points higher on the ADL/IADL score than men (p&lt;0.01). Conclusions: Women had poorer functional outcomes post stroke even after accounting for differences in age, pre-stroke confounding factors and stroke severity. Age, pre-stroke factors and stroke severity explained about half of the total observed sex difference. Further research is needed to identify the reasons why women have poorer outcomes in order to design interventions aimed at reducing stroke disability in women.

Male-Female Differences in Scoliosis Research Society-30 Scores in Adolescent Idiopathic Scoliosis

Longitudinal cohort study. To compare functional outcomes between male and female patients before and after surgery for adolescent idiopathic scoliosis (AIS). There is no clear consensus in the existing literature with respect to sex differences in functional outcomes in the surgical treatment of AIS. A prospective, consecutive, multicenter database of patients who underwent surgical correction for adolescent idiopathic scoliosis was analyzed retrospectively. All patients completed Scoliosis Research Society-30 (SRS-30) questionnaires before and 2 years after surgery. Patients with previous spine surgery were excluded. Data were collected for sex, age, Risser grade, previous bracing history, maximum preoperative Cobb angle, curve correction at 2 years, and SRS-30 domain scores. Paired sample t tests were used to compare preoperative and postoperative scores within each sex. Independent sample t tests were used to compare scores between sexes. A P value of <0.05 was considered statistically significant. Seven hundred forty-four patients (621 females and 123 males) were included. On average, males were 1 year older than females. There were no differences between sexes in Risser grade, bracing history, maximum curve magnitude, or correction after surgery. Both males and females had similar improvement in all SRS-30 domains after surgery. Self-image/appearance had the greatest relative improvement. Males had better self-image/appearance scores preoperatively, better pain scores at 2 years, and better mental health and total scores both preoperatively and at 2 years. Both males and females were similarly satisfied with surgery. Males treated with surgery for AIS report better preoperative self-image, less postoperative pain, and better mental health than females. These differences may be clinically significant. For both males and females, the most beneficial effect of surgery is improved self-image/appearance. Overall, the benefits of surgery for AIS are similar for both sexes.

Do women benefit more from systemic thrombolysis in acute ischemic stroke? A Serbian experience with thrombolysis in ischemic stroke (SETIS) study

Objective The female sex is associated with increased stroke severity and relatively poor functional recovery. Several studies have demonstrated that women with stroke benefit more from intravenous thrombolysis compared with men, while others found the nullification of gender effect among women treated with recombinant tissue plasminogen activator (rtPA). The purpose of our study was to determine any gender differences in the efficacy and safety of systemic thrombolysis among patients with acute ischemic stroke in Serbia. Methods Data were from the Serbian experience with intravenous thrombolysis in ischemic stroke (SETIS) study, a prospective, ongoing, multicenter, open, and observational study in Serbia of all patients who have received rtPA for acute ischemic stroke. We analyzed sex differences in the baseline characteristics, functional outcome and treatment complications. Results Among 60 women and 96 men with stroke and treated with intravenous thrombolysis, we found that at day 90, no significant sex differences in excellent functional outcome (50.9% of women vs. 57.0% of men, p = 0.5), favorable functional outcome (61.4% of women vs. 68.8% of men, p = 0.38) or death (8.8% of women vs. 12.9% of men, p = 0.60). These results were constant even after adjustments for age, severity of basal neurological deficit and onset to treatment time. Conclusion There were no sex differences in functional outcome at 90 days after the stroke among patients treated with IV rtPA. This finding might confirm that thrombolytic therapy nullifies usual sex differences in stroke outcome and suggests that women with stroke may benefit more from rtPA treatment.

Towards an understanding of sex differences in functional outcome following moderate to severe traumatic brain injury: a systematic review

Background and aim:A clear understanding of the impact sex differences play in clinical traumatic brain injury (TBI) outcome remains elusive. Animal research suggests that females have better functional outcomes following...

Poster 22: Sex Differences in Functional Outcome After Sustaining a Traumatic Brain Injury

Objective: To examine sex differences in functional outcome after traumatic brain injury (TBI) by operationalizing functional outcome as return to previous meaningful activity (work, school, housework, volunteering). Design: Observational cross-sectional. Setting: Research and training center for community integration of individuals with TBI within a medical setting in a large metropolitan area. Participants: 323 community dwellers with TBI (42.9% female), ranging in age from 18 to 51 years (mean ± SD, 36±9y).