Importance of sex and gender differences in enrollment and interpretation of stroke clinical trials.

OBJECTIVES: This review aims to reinforce the importance of improving sex balance in preclinical trials and sex and gender diversity and proportional balance in clinical trials enrollment and how this influences interpretation of stroke clinical trials. It also aims to identify strategies for improvement in data collection. MATERIALS AND METHODS: A PubMed search was conducted of publications in English, using MeSH terms sex, sex characteristics, gender identity, transgender, gender-nonconforming persons, clinical trials as topic, stroke. Of 249 search results, 217 were human or animal studies related to stroke, the majority of which were reviews, secondary analyses of stroke clinical trials, meta analyses, or retrospective studies, subject to the methods of sex and gender acquisition per the primary data source. Articles were reviewed, noting inclusion or absence of sex and gender definitions and trial design. Selected articles were supplemented with United States Food and Drug Administration, National Institutes of Health, and National Academy of Science, Engineering, and Medicine publications. RESULTS: The majority of preclinical studies continue to report sex as a binary variable, and the majority of stroke clinical trials report sex and gender as interchangeable and binary. Mindful trial design and statistical analysis can improve accuracy in the interpretation of sex and gender differences. Guidance exists to improve reporting on currently accepted sex and gender definitions, recommended data collection instruments, and appropriate statistical analyses. CONCLUSIONS: Despite acknowledgement of having failed to achieve diverse and proportionally balanced enrollment, sex and gender imbalance across the research continuum remains prevalent. Responsible incorporation of sex and gender in stroke clinical trials can be achieved through thoughtful study design, use of contemporary sex and gender definitions, inclusive prospective data collection, balanced enrollment with prespecified goals, and appropriate statistical analysis.

Trends Over Time in Stroke Incidence by Race in the Greater Cincinnati Northern Kentucky Stroke Study.

BACKGROUND AND OBJECTIVES: Understanding the current status of and temporal trends of stroke epidemiology by age, race, and stroke subtype is critical to evaluate past prevention efforts and to plan future interventions to eliminate existing inequities. We investigated trends in stroke incidence and case fatality over a 22-year time period. METHODS: In this population-based stroke surveillance study, all cases of stroke in acute care hospitals within a 5-county population of southern Ohio/northern Kentucky in adults aged ≥20 years were ascertained during a full year every 5 years from 1993 to 2015. Temporal trends in stroke epidemiology were evaluated by age, race (Black or White), and subtype (ischemic stroke [IS], intracranial hemorrhage [ICH], or subarachnoid hemorrhage [SAH]). Stroke incidence rates per 100,000 individuals from 1993 to 2015 were calculated using US Census data and age-standardized, race-standardized, and sex-standardized as appropriate. Thirty-day case fatality rates were also reported. RESULTS: Incidence rates for stroke of any type and IS decreased in the combined population and among White individuals (any type, per 100,000, 215 [95% CI 204-226] in 1993/4 to 170 [95% CI 161-179] in 2015, p = 0.015). Among Black individuals, incidence rates for stroke of any type decreased over the study period (per 100,000, 349 [95% CI 311-386] in 1993/4 to 311 [95% CI 282-340] in 2015, p = 0.015). Incidence of ICH was stable over time in the combined population and in race-specific subgroups, and SAH decreased in the combined groups and in White adults. Incidence rates among Black adults were higher than those of White adults in all time periods, and Black:White risk ratios were highest in adults in young and middle age groups. Case fatality rates were similar by race and by time period with the exception of SAH in which 30-day case fatality rates decreased in the combined population and White adults over time. DISCUSSION: Stroke incidence is decreasing over time in both Black and White adults, an encouraging trend in the burden of cerebrovascular disease in the US population. Unfortunately, however, Black:White disparities have not decreased over a 22-year period, especially among younger and middle-aged adults, suggesting the need for more effective interventions to eliminate inequities by race.

Treatment and Outcomes of Cervical Artery Dissection in Adults: A Scientific Statement From the American Heart Association.

Cervical artery dissection is an important cause of stroke, particularly in young adults. Data conflict on the diagnostic evaluation and treatment of patients with suspected cervical artery dissection, leading to variability in practice. We aim to provide an overview of cervical artery dissection in the setting of minor or no reported mechanical trigger with a focus on summarizing the available evidence and providing suggestions on the diagnostic evaluation, treatment approaches, and outcomes. Writing group members drafted their sections using a literature search focused on publications between January 1, 1990, and December 31, 2022, and included randomized controlled trials, prospective and retrospective observational studies, meta-analyses, opinion papers, case series, and case reports. The writing group chair and vice chair compiled the manuscript and obtained writing group members' approval. Cervical artery dissection occurs as a result of the interplay among risk factors, minor trauma, anatomic and congenital abnormalities, and genetic predisposition. The diagnosis can be challenging both clinically and radiologically. In patients with acute ischemic stroke attributable to cervical artery dissection, acute treatment strategies such as thrombolysis and mechanical thrombectomy are reasonable in otherwise eligible patients. We suggest that the antithrombotic therapy choice be individualized and continued for at least 3 to 6 months. The risk of recurrent dissection is low, and preventive measures may be considered early after the diagnosis and continued in high-risk patients. Ongoing longitudinal and population-based observational studies are needed to close the present gaps on preferred antithrombotic regimens considering clinical and radiographic prognosticators of cervical artery dissection.

Association of Prior Stroke With Health Care Perceptions of Adequate Emergency Care in Women.

BACKGROUND: Women with a history of stroke represent a vulnerable patient population due to their extant disability, morbidity, and risk of recurrence. The association between prior stroke with patient experience and perception of emergency medical care is unknown. METHODS: We utilized data from the Health Care Experiences and Perception cross-sectional, online survey from the American Heart Association Research Goes Red Registry. Ordinal logistic regression models were performed to assess the association between a self-reported history of stroke in the prior 10 years and the perception of not receiving adequate care in an emergency department because of gender or race. Models were adjusted for age at the time of enrollment, race/ethnicity, myocardial infarction within 10 years, and current smoking status. RESULTS: A total of 3498 women participants met inclusion criteria: 89 participants with a history of stroke in the past 10 years (mean age, 49.4 years; 10.1% Black participants and 5.6% Hispanic participants) and 3409 participants without such history (mean age, 45.8 years; 7.8% Black participants and 7.0% Hispanic participants). In multivariate logistic regression models, stroke history was significantly associated with greater odds of answering "to a great extent" that "I will not receive adequate care in an emergency room based on my gender" (odds ratio, 3.23 [95% CI, 1.69-6.17]) and "…race/ethnicity" (odds ratio, 3.88 [95% CI, 1.45-10.39]). Similar results were seen for secondary outcomes. CONCLUSIONS: Women patients with a stroke history felt less likely to receive adequate emergency care based on gender and race/ethnicity. Whether these negative health perceptions are associated with delays in presentation for stroke or other time-sensitive conditions should be the focus of future studies, given that these populations are known to less frequently receive advanced therapies for stroke, in part due to delays in presentation.

Comparison of Diagnostic and Triage Accuracy of Ada Health and WebMD Symptom Checkers, ChatGPT, and Physicians for Patients in an Emergency Department: Clinical Data Analysis Study.

BACKGROUND: Diagnosis is a core component of effective health care, but misdiagnosis is common and can put patients at risk. Diagnostic decision support systems can play a role in improving diagnosis by physicians and other health care workers. Symptom checkers (SCs) have been designed to improve diagnosis and triage (ie, which level of care to seek) by patients. OBJECTIVE: The aim of this study was to evaluate the performance of the new large language model ChatGPT (versions 3.5 and 4.0), the widely used WebMD SC, and an SC developed by Ada Health in the diagnosis and triage of patients with urgent or emergent clinical problems compared with the final emergency department (ED) diagnoses and physician reviews. METHODS: We used previously collected, deidentified, self-report data from 40 patients presenting to an ED for care who used the Ada SC to record their symptoms prior to seeing the ED physician. Deidentified data were entered into ChatGPT versions 3.5 and 4.0 and WebMD by a research assistant blinded to diagnoses and triage. Diagnoses from all 4 systems were compared with the previously abstracted final diagnoses in the ED as well as with diagnoses and triage recommendations from three independent board-certified ED physicians who had blindly reviewed the self-report clinical data from Ada. Diagnostic accuracy was calculated as the proportion of the diagnoses from ChatGPT, Ada SC, WebMD SC, and the independent physicians that matched at least one ED diagnosis (stratified as top 1 or top 3). Triage accuracy was calculated as the number of recommendations from ChatGPT, WebMD, or Ada that agreed with at least 2 of the independent physicians or were rated "unsafe" or "too cautious." RESULTS: Overall, 30 and 37 cases had sufficient data for diagnostic and triage analysis, respectively. The rate of top-1 diagnosis matches for Ada, ChatGPT 3.5, ChatGPT 4.0, and WebMD was 9 (30%), 12 (40%), 10 (33%), and 12 (40%), respectively, with a mean rate of 47% for the physicians. The rate of top-3 diagnostic matches for Ada, ChatGPT 3.5, ChatGPT 4.0, and WebMD was 19 (63%), 19 (63%), 15 (50%), and 17 (57%), respectively, with a mean rate of 69% for physicians. The distribution of triage results for Ada was 62% (n=23) agree, 14% unsafe (n=5), and 24% (n=9) too cautious; that for ChatGPT 3.5 was 59% (n=22) agree, 41% (n=15) unsafe, and 0% (n=0) too cautious; that for ChatGPT 4.0 was 76% (n=28) agree, 22% (n=8) unsafe, and 3% (n=1) too cautious; and that for WebMD was 70% (n=26) agree, 19% (n=7) unsafe, and 11% (n=4) too cautious. The unsafe triage rate for ChatGPT 3.5 (41%) was significantly higher (P=.009) than that of Ada (14%). CONCLUSIONS: ChatGPT 3.5 had high diagnostic accuracy but a high unsafe triage rate. ChatGPT 4.0 had the poorest diagnostic accuracy, but a lower unsafe triage rate and the highest triage agreement with the physicians. The Ada and WebMD SCs performed better overall than ChatGPT. Unsupervised patient use of ChatGPT for diagnosis and triage is not recommended without improvements to triage accuracy and extensive clinical evaluation.

Emergency medicine physician workforce attrition differences by age and gender.

BACKGROUND: Emergency care workforce concerns have gained national prominence given recent data suggesting higher than previously estimated attrition. With little known regarding characteristics of physicians leaving the workforce, we sought to investigate the age and number of years since residency graduation at which male and female emergency physicians (EPs) exhibited workforce attrition. METHODS: We performed a repeated cross-sectional analysis of EPs reimbursed by Medicare linked to date of birth and residency graduation date data from the American Board of Emergency Medicine for the years 2013-2020. Stratified by gender, our primary outcomes were the median age and number of years since residency graduation at the time of attrition, defined as the last year during the study time frame that an EP provided clinical services. We constructed a multivariate logistic regression model to examine the association between gender and EP workforce attrition. RESULTS: A total of 25,839 (70.2%) male and 10,954 (29.8%) female EPs were included. During the study years, 5905 male EPs exhibited attrition at a median (interquartile range [IQR]) age of 56.4 (44.5-65.4) years, and 2463 female EPs exhibited attrition at a median (IQR) age of 44.0 (38.0-53.9) years. Female gender (adjusted odds ratio 2.30, 95% confidence interval 1.82-2.91) was significantly associated with attrition from the workforce. Male and female EPs had respective median (IQR) post-residency graduation times in the workforce of 17.5 (9.5-25.5) years and 10.5 (5.5-18.5) years among those who exhibited attrition and one in 13 males and one in 10 females exited clinical practice within 5 years of residency graduation. CONCLUSIONS: Female physicians exhibited attrition from the EM workforce at an age approximately 12 years younger than male physicians. These data identify widespread disparities regarding EM workforce attrition that are critical to address to ensure stability, longevity, and diversity in the EP workforce.

A Review of Hormone and Non-Hormonal Therapy Options for the Treatment of Menopause.

Understanding the role of both menopausal hormone therapy (MHT) along with non-hormonal options for the treatment of vasomotor symptoms, sleep disruption, and genitourinary symptoms after menopause is critical to the health of women during middle and later life. Recent updates to the evidence for the treatment of menopausal symptoms pertaining to both hormonal and non-hormonal therapies as well as updated guidance from specialty societies can help guide clinicians in their treatment of women going through natural menopause or with estrogen deficiencies due to primary ovarian insufficiency or induced menopause from surgery or medications. The objective of this narrative review is to provide clinicians with an overview of MHT for the use of menopausal symptoms in women, incorporating updated primary evidence for risk versus benefit profiles, recent specialty society recommendations, and alternative, non-hormonal options. In this review, we summarize literature on the use of MHT for menopause-related symptomatology including options for formulations and dosages of MHT, non-hormonal treatment options, and the risk-benefit profile of MHT including long-term health consequences (eg, cardiovascular disease, cognitive decline, venous thromboembolism, and fracture risk). Finally, we highlight areas in which future research is needed to advance care of women after menopause. In summary, both hormonal (MHT) and non-hormonal options exist to treat symptoms of menopause. There is strong evidence for safety and effectiveness of MHT for the treatment of vasomotor symptoms among women who are less than 60 years of age, less than 10 years since menopause, and without significant cardiometabolic comorbidities. For others, treatment with hormonal versus non-hormonal therapies can be considered based on individual risk profiles, as well as other factors such as drug formulation, therapeutic goals, and symptom severity.

Clinical Performance Measures for Emergency Department Care for Adults With Intracranial Hemorrhage.

Though select inpatient-based performance measures exist for the care of patients with nontraumatic intracranial hemorrhage, emergency departments lack measurement instruments designed to support and improve care processes in the hyperacute phase. To address this, we propose a set of measures applying a syndromic (rather than diagnosis-based) approach informed by performance data from a national sample of community EDs participating in the Emergency Quality Network Stroke Initiative. To develop the measure set, we convened a workgroup of experts in acute neurologic emergencies. The group considered the appropriate use case for each proposed measure: internal quality improvement, benchmarking, or accountability, and examined data from Emergency Quality Network Stroke Initiative-participating EDs to consider the validity and feasibility of proposed measures for quality measurement and improvement applications. The initially conceived set included 14 measure concepts, of which 7 were selected for inclusion in the measure set after a review of data and further deliberation. Proposed measures include 2 for quality improvement, benchmarking, and accountability (Last 2 Recorded Systolic Blood Pressure Measurements Under 150 and Platelet Avoidance), 3 for quality improvement and benchmarking (Proportion of Patients on Oral Anticoagulants Receiving Hemostatic Medications, Median ED Length of Stay for admitted patients, and Median Length of Stay for transferred patients), and 2 for quality improvement only (Severity Assessment in the ED and Computed Tomography Angiography Performance). The proposed measure set warrants further development and validation to support broader implementation and advance national health care quality goals. Ultimately, applying these measures may help identify opportunities for improvement and focus quality improvement resources on evidence-based targets.

Changing Trends in Demographics, Risk Factors, and Clinical Features of Patients With Infective Endocarditis-Related Stroke, 2005-2015.

BACKGROUND AND OBJECTIVES: There is a rising incidence of infective endocarditis-related stroke (IERS) in the United States attributed to the opioid epidemic. A contemporary epidemiologic description is necessary to understand the impact of the opioid epidemic on clinical characteristics of IERS. We describe and analyze trends in the demographics, risk factors, and clinical features of IERS. METHODS: This is a retrospective cohort study within a biracial population of 1.3 million in the Greater Cincinnati/Northern Kentucky region. All hospitalized patients with hemorrhagic or ischemic stroke were identified and physician verified from the 2005, 2010, and 2015 calendar years using ICD-9 and ICD-10 codes. IERS was defined as an acute stroke attributed to infective endocarditis meeting modified Duke Criteria for possible or definite endocarditis. Unadjusted comparison of demographics, risk factors, outcome, and clinical characteristics was performed between each study period for IERS and non-IERS. An adjusted model to compare trends used the Cochran-Armitage test for categorical variables and a general linear model or Kruskal-Wallis test for numerical variables. Examination for interaction of endocarditis status in trends was performed using a general linear or logistic model. RESULTS: A total of 54 patients with IERS and 8,204 without IERS were identified during the study periods. Between 2005 and 2015, there was a decline in rates of hypertension (91.7% vs 36.0%; p = 0.0005) and increased intravenous drug users (8.3% vs 44.0%; p = 0.02) in the IERS cohort. The remainder of the stroke population demonstrated a significant rise in hypertension, diabetes, atrial fibrillation, and perioperative stroke. Infective endocarditis status significantly interacted with the trend in hypertension prevalence (p = 0.001). DISCUSSION: From 2005 to 2015, IERS was increasingly associated with intravenous drug use and fewer risk factors, specifically hypertension. These trends likely reflect the demographics of the opioid epidemic, which has affected younger patients with fewer comorbidities.

Sex Hormone-Binding Globulin and Risk of Coronary Heart Disease in Men and Women.

BACKGROUND: The role of sex hormone-binding globulin (SHBG) levels in clinical risk stratification and intervention for coronary heart disease (CHD) remains uncertain. We aimed to examine whether circulating levels of SHBG are predictive of CHD risk in men and women. METHODS: We investigated the association between SHBG and the risk of incident CHD in 128 322 men and 135 103 women free of CHD at baseline in the prospective United Kingdom Biobank (UKB) cohort. The unconfounded associations were estimated using Mendelian randomization (MR) analysis. We further conducted a meta-analysis to integrate currently available prospective evidence. CHD events included nonfatal and fatal myocardial infarction and coronary revascularization. RESULTS: In the UKB, during a median of 11.7 follow-up years, 10 405 men and 4512 women developed CHD. Serum levels of SHBG were monotonically associated with a decreased risk of CHD in both men (adjusted hazard ratio [HR] per log nmol/L increase in SHBG: 0.88 [0.83-0.94]) and women (HR: 0.89 [0.83-0.96]). MR-based analyses suggested causality and a dose-response relationship of SHBG with CHD risk. A cumulative meta-analysis including 216 417 men and 138 282 women from 11 studies showed that higher levels of SHBG were prospectively associated with decreased CHD risk in men comparing the highest with the lowest quartile: pooled relative risk (RR) 0.81 (0.74-0.89) and women (pooled RR: 0.86 [0.78-0.94]). CONCLUSIONS: Higher circulating SHBG levels were directly and independently predictive of lower CHD risk in both men and women. The utility of SHBG for CHD risk stratification and prediction warrants further study.

Diagnosis, Workup, Risk Reduction of Transient Ischemic Attack in the Emergency Department Setting: A Scientific Statement From the American Heart Association.

At least 240 000 individuals experience a transient ischemic attack each year in the United States. Transient ischemic attack is a strong predictor of subsequent stroke. The 90-day stroke risk after transient ischemic attack can be as high as 17.8%, with almost half occurring within 2 days of the index event. Diagnosing transient ischemic attack can also be challenging given the transitory nature of symptoms, often reassuring neurological examination at the time of evaluation, and lack of confirmatory testing. Limited resources, such as imaging availability and access to specialists, can further exacerbate this challenge. This scientific statement focuses on the correct clinical diagnosis, risk assessment, and management decisions of patients with suspected transient ischemic attack. Identification of high-risk patients can be achieved through use of comprehensive protocols incorporating acute phase imaging of both the brain and cerebral vasculature, thoughtful use of risk stratification scales, and ancillary testing with the ultimate goal of determining who can be safely discharged home from the emergency department versus admitted to the hospital. We discuss various methods for rapid yet comprehensive evaluations, keeping resource-limited sites in mind. In addition, we discuss strategies for secondary prevention of future cerebrovascular events using maximal medical therapy and patient education.

Long-term effect of field triage on times to endovascular treatment for emergent large vessel occlusion.

BACKGROUND: Delays to endovascular therapy (EVT) for stroke may be mitigated with direct field triage to EVT centers. We sought to compare times to treatment over a 5.5 year span between two adjacent states, one with field triage and one without, served by a single comprehensive stroke center (CSC). METHODS: During the study period, one of the two states implemented severity-based triage for suspected emergent large vessel occlusion, while in the other state, patients were transported to the closest hospital regardless of severity. We compared times to treatment and clinical outcomes between these two states. We also performed a matched pairs analysis, matching on date treated and distance from field to CSC. RESULTS: 639 patients met the inclusion criteria, 407 in State 1 (with field triage) and 232 in State 2 (without field triage). In State 1, scene to EVT decreased 6% (or 8.13 min, p=0.0004) every year but no decrease was observed for State 2 (<1%, p=0.94). Cumulatively over 5.5 years, there was a reduction of 43 min in time to EVT in State 1, but no change in State 2. Lower rates of disability were seen in State 1, both for the entire cohort (all OR 1.22, 95% CI 1.07 to 1.40, p=0.0032) and for those independent at baseline (1.36, 95% CI 1.15 to 1.59, p=0.0003). CONCLUSIONS: Comparing adjacent states over time, the implementation of severity-based field triage significantly reduced time to EVT.