Tracy E. Madsen

Analysis of Tissue Plasminogen Activator Eligibility by Sex in the Greater Cincinnati/Northern Kentucky Stroke Study

Background and Purpose— Sex differences in recombinant tissue-type plasminogen activator (r-tPA) administration are present in some populations. It is unknown whether this is because of eligibility differences or the modifiable exclusion criterion of severe hypertension. Our aim was to investigate sex differences in r-tPA eligibility, in individual exclusion criteria, and in the modifiable exclusion criterion, hypertension. Methods— We included all ischemic stroke patients ≥18 years among residents of the Greater Cincinnati/Northern Kentucky region who presented to 16-area emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association (AHA) and European Cooperative Acute Stroke Study (ECASS) III guidelines. Results— Of 1837 ischemic strokes, 58% were women, 24% were black. Mean age in years was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex (6.8% men and 6.1% women; P=0.55), even after adjusting for age (7.0% and 5.9%; P=0.32). Similar proportions of women and men arrived beyond 3- and 4.5-hour time windows, but more women had severe hypertension. There were no sex differences in blood pressure treatment rates among those with severe hypertension (14.6% women and 20.8% men; P=0.21). More women were >80 years and had National Institutes of Health Stroke Scale (NIHSS) >25. Conclusions— Within a large, biracial population, eligibility for r-tPA was similar by sex. Women were more likely to have the modifiable exclusion criterion of severe hypertension but were not more likely to be treated. Women were more likely to have 2 of the 5 ECASS III exclusion criteria. Undertreatment of hypertension in women is a potentially modifiable contributor to reported differences in r-tPA administration.

The DISPARITY-II Study: Delays to Antibiotic Administration in Women With Severe Sepsis or Septic Shock

BACKGROUND Early antibiotics reduce mortality in patients with severe sepsis and septic shock. Recent work demonstrated that women experience greater delays to antibiotic administration, but it is unknown if this relationship remains after adjusting for factors such as source of infection. OBJECTIVES The objective was to investigate whether gender and/or source of infection are associated with delays to antibiotics in patients with severe sepsis or septic shock. METHODS This was a retrospective, observational study in an urban academic emergency department and national Surviving Sepsis Campaign (SSC) database study site. Consecutive patients age 18 years and older admitted to intensive care with severe sepsis or septic shock and entered into the SSC database from October 2005 to March 2012 were included. Two trained research assistants, blinded to the primary outcome, used a standardized abstraction form to obtain patient demographic and clinical data, including the Sequential Organ Failure Assessment (SOFA) scores and comorbidities. Time to first antibiotic and presumed source of infection were extracted from the SSC database. Univariate analyses were performed with Pearson chi-square tests and t-tests. Linear regression was performed with time to first antibiotic as the primary outcome. Covariates, chosen a priori by study authors, included age, race, ethnicity, source of infection, SOFA score, and lactate. RESULTS A total of 771 patients were included. Women were 45.3% of the sample, the mean age was 66 years (95% confidence interval [CI] = 65.1 to 67.5 years), 19.4% were nonwhite, and 8% were Hispanic. Mean time to first antibiotic was 153 minutes (95% CI = 143 to 163 minutes) for men and 184 minutes (95% CI = 171 to 197 minutes) for women (p < 0.001). The urinary tract was source of infection for 35.2% of women (95% CI = 30.2% to 40.3%) versus 23.7% (95% CI = 19.6% to 27.8%) of men. Pneumonia was present in 46.9% of men (95% CI = 42.1% to 51.7%) versus 35.8% (95% CI = 30.8% to 40.8%) of women. The mean time to antibiotics in women was longer than in men (adjusted odds ratio [aOR] = 1.18, 95% CI = 1.07 to 1.30), even after adjusting for age, race, ethnicity, presumed source of infection, SOFA score, and lactate (p = 0.001). Those with pneumonia compared to other infections received antibiotics faster (aOR = 0.73, 95% CI = 0.66 to 0.81). There was no significant association between other sources of infection and time to antibiotics in either univariate or multivariate analysis. CONCLUSIONS Women experience longer delays to initial antibiotics among patients with severe sepsis or septic shock, even after adjusting for infectious source. Pneumonia was associated with shorter times to antibiotic administration. Future research is necessary to investigate contributors to delayed antibiotic administration in women.

Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study.

Objective: Recent data suggest stroke incidence is decreasing over time, but it is unknown whether incidence is decreasing in women and men to the same extent. Methods: Within our population of 1.3 million, all incident strokes among residents ≥20 years old were ascertained at all hospitals during July 1993–June 1994 and calendar years 1999, 2005, and 2010. A sampling scheme was used to ascertain out-of-hospital cases. Sex-specific incidence rates per 100,000 among black and white participants, age- and race-adjusted, were standardized to the 2000 US Census population. Trends over time by sex were compared; a Bonferroni correction was applied for multiple comparisons. Results: Over the 4 study periods, there were 7,710 incident strokes; 57.2% (n = 4,412) were women. Women were older than men (mean ± SE 72.4 ± 0.34 vs 68.2 ± 0.32, p < 0.001). Incidence of all strokes decreased over time in men (263 [confidence interval 246–281] to 192 [179–205], p < 0.001) but not in women (217 [205–230] to 198 [187–210], p = 0.15). Similar sex differences were seen for ischemic stroke (men, 238 [223–257] to 165 [153–177], p < 0.01; women, 193 [181–205] to 173 [162–184], p = 0.09). Incidence of all strokes and of ischemic strokes was similar between women and men in 2010. Incidence of intracerebral hemorrhage and subarachnoid hemorrhage were stable over time in both sexes. Conclusions: Decreases in stroke incidence over time are driven by a decrease in ischemic stroke in men. Contrary to previous study periods, stroke incidence rates were similar by sex in 2010. Future research is needed to understand why the decrease in ischemic stroke incidence is more pronounced in men.

The DISPARITY Study: do gender differences exist in Surviving Sepsis Campaign resuscitation bundle completion, completion of individual bundle elements, or sepsis mortality?

PURPOSE Women in the emergency department are less likely to receive early goal directed therapy, but gender differences in the Surviving Sepsis Campaign (SSC) bundle completion have not been studied [1]. We hypothesized that women have lower SSC resuscitation bundle completion rates. MATERIALS AND METHODS This was a retrospective, observational study in a large urban academic ED at a national SSC site. Consecutive patients (age>18 years) admitted to intensive care with severe sepsis or septic shock and entered into the SSC database from October 2005 to February 2012 were included. Data on overall and individual bundle elements were exported from the database. Bivariate analyses were performed with chi-square tests and t-tests. Multiple logistic regression was then performed with gender as an effect modifier. RESULTS Eight hundred fourteen patients were enrolled. The mean age was 66 years;, 44.8% were women. There was no association between gender and bundle completion (aOR 0.83, 95% CI 0.58-1.16), controlling for age, race, Sequential Organ Failure Assessment, congestive heart failure, and coagulopathy. In-hospital mortality did not differ by gender. Women were less likely to receive antibiotics within 3 hours (60.5% vs. 68.8%, p=0.01) and less likely to reach a target ScvO2>70 (31.3% vs. 39.5%, P=.05). CONCLUSIONS There were no gender disparities in bundle completion or in-hospital mortality. Further research is needed to examine individual bundle elements and gender specific factors that may affect bundle completion and mortality.

Potentially Missed Diagnosis of Ischemic Stroke in the Emergency Department in the Greater Cincinnati/Northern Kentucky Stroke Study

OBJECTIVE Missed diagnoses of acute ischemic stroke (AIS) in the ED may result in lost opportunities to treat AIS. Our objectives were to describe the rate and clinical characteristics of missed AIS in the ED, to determine clinical predictors of missed AIS, and to report tissue plasminogen (tPA) eligibility among those with missed strokes. METHODS Among a population of 1.3 million in a five-county region of southwest Ohio and northern Kentucky, cases of AIS that presented to 16 EDs during 2010 were identified using ICD-9 codes followed by physician verification of cases. Missed ED diagnoses were physician-verified strokes that did not receive a diagnosis indicative of stroke in the ED. Bivariate analyses were used to compare clinical characteristics between patients with and without an ED diagnosis of AIS. Logistic regression was used to evaluate predictors of missed AIS diagnoses. Alternative diagnoses given to those with missed AIS were codified. Eligibility for tPA was reported between those with and without a missed stroke diagnosis. RESULTS Of 2,027 AIS cases, 14.0% (n = 283) were missed in the ED. Race, sex, and stroke subtypes were similar between those with missed AIS diagnoses and those identified in the ED. Hospital length of stay was longer in those with a missed diagnosis (5 days vs. 3 days, p < 0.0001). Younger age (adjusted odds ratio [aOR] = 0.94, 95% confidence interval [CI] = 0.89 to 0.98) and decreased level of consciousness (LOC) (aOR = 3.58, 95% CI = 2.63 to 4.87) were associated with higher odds of missed AIS. Altered mental status was the most common diagnosis among those with missed AIS. Only 1.1% of those with a missed stroke diagnosis were eligible for tPA. CONCLUSION In a large population-based sample of AIS cases, one in seven cases were not diagnosed as AIS in the ED, but the impact on acute treatment rates is likely small. Missed diagnosis was more common among those with decreased LOC, suggesting the need for improved diagnostic approaches in these patients.

Analysis of Gender Differences in Knowledge of Stroke Warning Signs

BACKGROUND The impact of gender on knowledge of stroke warning signs and preparedness is poorly understood, and gender-specific factors associated with poor knowledge of stroke warning signs have not been identified. METHODS This was a cross-sectional study of 132,604 participants in the 2009 Behavioral Risk Factor Surveillance System Survey, a national telephone survey. Adults aged 18 years or older who lived in one of 19 states that administered an optional stroke module asking them to correctly identify stroke symptoms and the correct action to take were included. The primary outcome was a low score (≤ 4 of 7) on the Stroke Symptoms Knowledge Scale (SSKS). Logistic regression was performed for the overall sample and then stratified by gender, with adjustments made for age, race, Hispanic ethnicity, income, and whether respondents had a primary doctor (PMD). Data were weighted as recommended by the Centers for Disease Control. RESULTS In all, 51.7% of the weighted sample was women. Less women than men had low scores on the SSKS (21% versus 25%, P < .001). After adjusting for age, race, ethnicity, income, and PMD, men had higher odds of having low scores (adjusted odds ratio, 1.36; 95% confidence interval, 1.28-1.45). After stratifying by gender, Hispanic ethnicity, and age younger than 35 years predicted low scores on the scale in women but not in men. CONCLUSIONS Female gender is associated with better knowledge of stroke warning signs, but a gender-specific approach identified Hispanic women, young women, and black participants as subgroups at risk for having poor knowledge, suggesting the need for targeted stroke education to increase stroke preparedness in these groups.

Foundations for a Novel Emergency Medicine Subspecialty: Sex, Gender, and Women's Health

Sex and gender affect all aspects of health and disease, including pathophysiology, epidemiology, presentation, treatment, and outcomes. Sex- and gender-specific medicine (SGM) is a rapidly developing field rooted in womens health; however, inclusion of SGM in emergency medicine (EM) is currently lacking. Incorporating principles of sex, gender, and womens health into emergency care and training curricula is an important first step toward establishing a novel subspecialty. EM is an ideal specialty to cultivate this new field because of its broad interdisciplinary nature, increasing numbers of patient visits, and support from academic medical centers to promote expertise in womens health. This article describes methods used to establish a new multidisciplinary training program in sex, gender, and womens health based in a department of EM. Womens health and SGM program initiatives span clinical care, patient education, clinical research, resident and fellow training, and faculty development.

Lack of Gender Disparities in Emergency Department Triage of Acute Stroke Patients

Introduction Previous literature has shown gender disparities in the care of acute ischemic stroke. Compared to men, women wait longer for brain imaging and are less likely to receive intravenous (IV) tissue plasminogen activator (tPA). Emergency department (ED) triage is an important step in the rapid assessment of stroke patients and is a possible contributor to disparities. It is unknown whether gender differences exist in ED triage of acute stroke patients. Our primary objective was to determine whether gender disparities exist in the triage of acute stroke patients as defined by Emergency Severity Index (ESI) levels and use of ED critical care beds. Methods This was a retrospective, observational study of both ischemic and hemorrhagic stroke patients age ≥18 years presenting to a large, urban, academic ED within six hours of symptom onset between January 2010, and December 2012. Primary outcomes were triage to a non-critical ED bed and Emergency Severity Index (ESI) level. Primary outcome data were extracted from electronic medical records by a blinded data manager; secondary outcome data and covariates were abstracted by trained research assistants. We performed bivariate and multivariate analyses. Logistic regression was performed using age, race, insurance status, mode of and time to arrival, National Institutes of Health Stroke Scale, and presence of atypical symptoms as covariates. Results There were 537 patients included in this study. Women were older (75.6 vs. 69.5, p<0.001), and more women had a history of atrial fibrillation (39.8% vs. 25.3%, p<0.001). Compared to 9.5% of men, 10.3% of women were triaged to a non-critical care ED bed (p=0.77); 92.1% of women were triaged as ESI 1 or 2 vs. 93.6% of men (p=0.53). After adjustment, gender was not associated with triage location or ESI level, though atypical symptoms were associated with higher odds of being triaged to a non-critical care bed (aOR 1.98, 95%CI [1.03 – 3.81]) and 3.04 times higher odds of being triaged as ESI 3 vs. ESI 1 or 2 (95% CI [1.36 – 6.82]). Conclusion In a large, urban, academic ED at a primary stroke center, there were no gender differences in triage to critical care beds or ESI levels among acute stroke patients arriving within six hours of symptom onset. These findings suggest that ED triage protocols for stroke patients may be effective in minimizing gender disparities in care.

Gender Differences in Neurologic Emergencies Part I: A Consensus Summary and Research Agenda on Cerebrovascular Disease

Cerebrovascular neurologic emergencies including ischemic and hemorrhagic stroke, subarachnoid hemorrhage (SAH), and migraine are leading causes of death and disability that are frequently diagnosed and treated in the emergency department (ED). Although sex and gender differences in neurologic emergencies are beginning to become clearer, there are many unanswered questions about how emergency physicians should incorporate sex and gender into their research initiatives, patient evaluations, and overall management plans for these conditions. After evaluating the existing gaps in the literature, a core group of ED researchers developed a draft of future research priorities. Participants in the 2014 Academic Emergency Medicine consensus conference neurologic emergencies working group then discussed and approved the recommended research agenda using a standardized nominal group technique. Recommendations for future research on the role of sex and gender in the diagnosis, treatment, and outcomes pertinent to ED providers are described for each of three diagnoses: stroke, SAH, and migraine. Recommended future research also includes investigation of the biologic and pathophysiologic differences between men and women with neurologic emergencies as they pertain to ED diagnoses and treatments.

Predictors of Being Unsafe Participation in the Behavioral Risk Factor Surveillance System 2006 Intimate Partner Violence Module

A common reason for not participating in intimate partner violence (IPV) research is thought to be fear for one’s safety. However, little is known about those who do not participate due to safety fears. To better characterize this population, we investigated correlates of being “not safe” to answer the optional IPV module in the 2006 Behavioral Risk Factor Surveillance Survey (BRFSS), a yearly cross-sectional telephone survey in the United States. We compared those who said they were not safe to complete the module with those who were safe and reported (+IPV) or denied (−IPV) IPV. Forward stepwise multivariate logistic regression was performed to identify significant correlates of being not-safe. Those who said they were not safe to answer IPV questions were found to have lower income, lower education levels, and were older than either +IPV or −IPV respondents. They were also more likely to be male than the +IPV group. The not-safe differ from those traditionally identified as being at greatest risk for IPV. However, the percentage of IPV victims in the not-safe group remains unknown. Greater efforts should be made to include this group in future IPV research, both to determine these groups’ true IPV risk and to avoid missing potential IPV victims. The validity, reliability, and comprehensibility of safety questions should also be assessed.