Published online before print February 10, 2009, doi: 10.1161/STROKEAHA.108.543116
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(Stroke. 2009;40:1114.)
© 2009 American Heart Association, Inc.
Go Red for Women |
Do Presenting Symptoms Explain Sex Differences in Emergency Department Delays Among Patients With Acute Stroke?
From the Departments of Epidemiology (J.W.G., M.J.R.) and Neurology and Ophthalmology (S.W.), Michigan State University, East Lansing, Mich.
Correspondence to Julia Warner Gargano, MS, Department of Epidemiology, Michigan State University, B601 West Fee Hall, East Lansing, MI 48824. E-mail jgargano{at}epi.msu.edu
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Abstract |
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Background and Purpose— Previous studies report that women with stroke may experience longer delays in diagnostic workup than men after arriving at the emergency department. We hypothesized that presenting symptom differences could explain these delays.
Methods— Data were collected on 1922 acute stroke cases who presented to 15 hospitals participating in a statewide stroke registry. We evaluated 2 in-hospital time intervals: emergency department arrival to physician examination ("door-to-doctor") and emergency department arrival to brain imaging ("door-to-image"). We used parametric survival models to estimate time ratios, which represent the ratio of average times comparing women to men, after adjusting for symptom presentation and other confounders.
Results— Women were significantly less likely than men to present with any stroke warning sign or suspected stroke (87.5% versus 91.4%) or to report trouble with walking, balance, or dizziness (9.5% versus 13.7%). Difficulty speaking and loss of consciousness were associated with shorter door-to-doctor times. Weakness, facial droop, difficulty speaking, and loss of consciousness were associated with shorter door-to-image times, whereas difficulty with walking/balance was associated with longer door-to-image times. In adjusted analyses, women had 11% longer door-to-doctor intervals (time ratio, 1.11; 95%, CI 1.02 to 1.22) and 15% longer door-to-image intervals (time ratio, 1.15; 95% CI, 1.08 to 1.25) after accounting for presenting symptoms, age, and other confounders. Furthermore, these sex differences remained evident after restricting to patients who arrived within 6 or within 2 hours of symptom onset.
Conclusions— Women with acute stroke experienced greater emergency department delays than men, which were not attributable to differences in presenting symptoms, time of arrival, age, or other confounders.
Key Words: quality of care • sex • stroke • symptoms • thrombolytic therapy
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Introduction |
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Although age-specific stroke incidence rates are higher in men than women, more strokes occur in women because of their longer life expectancy.1 Moreover, many studies have found evidence of poorer stroke outcomes in women compared with men, even after investigators have accounted for differences in age and other potential confounders.2–9 In general, sex differences in the quality of acute stroke care are limited1,3,5; however, several studies have found that women are less likely to receive tissue plasminogen activator for acute stroke than men.10–15 One explanation for these findings is that women are more likely to delay seeking care, but evidence for this has been inconsistent.5,11,16–19 Several studies have also found that women with stroke experience longer delays between the emergency department (ED) arrival and receiving brain imaging,20–24 although other studies have not found a difference.19,25,26 Another study has also reported that the time from ED arrival to first contact with a physician was greater for women than for men.27
Limited evidence suggests that women with stroke may present with a different symptom profile than men,28 analogous to the well-known sex differences in presentation with acute coronary syndromes.29 Although, to our knowledge, no studies have directly linked symptoms with in-hospital delays, the higher prevalence of nontraditional stroke symptoms in women could translate into delays in ED workup and ultimately result in ineligibility for acute stroke treatments. We aimed to (1) assess sex differences in symptoms at presentation; (2) quantify sex differences in in-hospital delays, ie, door-to-doctor and door-to-image times; (3) examine associations between symptoms and door-to-doctor and door-to-image times; and (4) determine whether symptom differences explain sex differences in in-hospital delays.
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Methods |
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Registry Design
The Michigan Acute Stroke Care Overview & Treatment Surveillance System was a statewide, hospital-based, acute stroke registry prototype for the Paul Coverdell National Acute Stroke Registry.30,31 A representative statewide sample of 16 Michigan hospitals was obtained using a modified stratified sampling scheme. One hospital closed before data collection, leaving 15 hospitals in the sample. Institutional Review Board approval was obtained from each hospital.
Data Collection
Acute stroke or transient ischemic attack (TIA) admissions were prospectively identified at each hospital during a 6-month period in 2002. Using a standardized data collection instrument, trained stroke clinical coordinators obtained information on demographics, presenting symptoms, prestroke ambulatory status, medical history, in-hospital care, and discharge status. Detailed information on the timing of critical ED events was collected, including dates and times of symptom onset, ED arrival, ED triage, first contact with a physician, and brain imaging.
Symptom information was recorded in a free-text chief complaint field. We developed an iterative structured query language algorithm to abstract symptom information based on the identification of specific character strings. Suspected strokes were defined as having any mention of stroke or TIA (eg, "RO stroke," "poss. CVA," "TIA") in their chief complaint field. The following individual symptoms were identified: numbness (including tingling and paresthesia), weakness (including paralysis), any unilateral symptom (including a specific reference to one side), facial droop, confusion, difficulty speaking, vision changes, difficulty walking, dizziness, imbalance or lack of coordination, headache, other pain, loss of consciousness, falls, seizure, nausea/vomiting, and respiratory difficulties. We aggregated reported individual symptoms into 5 stroke warning signs consistent with the American Heart Association public health messages (www.americanheart.org), ie, (1) numbness/weakness; (2) confusion/speech; (3) vision; (4) walking/dizziness/balance; and (5) headache. We tested the reliability of this system in a 10% random sample, which was independently classified into the 5 warning signs and suspect stroke by a clinical stroke expert (S.W.) Reliability was excellent (all kappas >0.90).
From the 2566 registry subjects, we excluded cases who did not present to the ED (n=281 direct admissions and n=285 hospital transfers), leaving 2000 ED admissions. Seventy-six cases (4%) were excluded due to missing arrival time data leaving 1922 subjects.
Time Interval Data and Descriptive Statistics
Two key time intervals related to in-hospital stroke evaluation were considered: ED arrival to examination by physician ("door-to-doctor") and ED arrival to brain imaging ("door-to-image"). Interval censoring32 was present in this data set because the exact time of physician examination was not recorded for 193 patients and exact time of brain imaging was not recorded for 702 patients; however, sufficient information was available to infer a time interval in which the event occurred. To generate crude median and interquartile range estimates, we substituted the midpoint between the earliest and latest possible times for subjects without an exact time. The time from symptom onset to arrival in the ED ("onset-to-arrival") was also calculated and categorized as <2 hours (ie, optimally eligible for diagnostic workup and intravenous tissue plasminogen activator within the 3-hour window), 2 to <6 hours (potentially eligible for intravenous or intra-arterial tissue plasminogen activator), and 
6 hours/unknown onset-to-arrival interval. Differences in proportions of categorical variables were evaluated using 
2 tests.
Modeling Strategy
We used accelerated failure time models, a class of parametric time-to-event (survival) models that allow for interval-censored data.32,33 The accelerated failure time model assumes that the effect of a covariate is proportional with respect to survival time rather than proportional with respect to the hazard like in the more widely used proportional hazards model.32 Accelerated failure time models require assumptions about the distribution of time; we chose the distributions that provided the best fit for the data by visual examination of probability plots for exponential, Weibull, logistic, log-normal, and log-logistic distributions. We present model results as time ratios (TRs), which represent the ratio of average times between 2 contrasting groups.
Univariate TRs for door-to-doctor and door-to-image times were estimated for all exposure variables of interest, including individual symptoms, the 5 individual stroke warning signs, the presence of any warning sign, suspect stroke, sex, and other demographic and clinical characteristics. Adjusted models were developed using backward elimination techniques (P<0.3 to enter, P<0.1 to stay). Age, race, emergency medical services, and hospital site were included as a priori confounders regardless of significance. The fit of the final models was assessed by examining Cox-Snell residual plots.34 The final models were also rerun after restricting to patients who arrived within 6 hours of stroke onset and within 2 hours of stroke onset. To further understand the door-to-image delays, we performed an additional analysis of doctor-to-image time among all patients and among those who arrived within 6 hours or within 2 hours. We considered clustering within hospital by repeating the analyses using random effects terms for hospital site (Stata; StataCorp, College Station, Texas). Results were similar; thus, we only present the fixed-effect results. All other statistical analyses were performed using SAS Version 9.1.3 (Statistical Analysis Software, Cary, NC).
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Results |
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Females were older (mean age, 72 versus 68 years), more likely to be nursing home residents, and to be nonambulatory prior to their stroke, but less likely to have a history of heart disease or to smoke (Table 1). Overall, there was no statistically significant difference in prehospital delay (P=0.15), although slightly more males than females arrived within 6 hours of stroke onset (42.6% versus 39.0%). The crude median door-to-doctor times were 27 (interquartile range, 13 to 50) minutes for men and 29 (15 to 54) minutes for women. Median door-to-image times were 82 (49 to 133) minutes for men and 95 (59 to 152) minutes for women.
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Table 2 shows the prevalence of stroke warning signs, suspect stroke, and individual symptoms reported at presentation by sex. Males were significantly more likely than women to report trouble with walking, balance, or dizziness (warning sign 4; 13.7% versus 9.5%) and to present with any warning sign or suspected stroke (91.4% versus 87.5%). For individual symptoms, sex differences were subtle and none reached statistical significance.
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Table 3 shows unadjusted TRs for door-to-doctor and door-to-image times by stroke warning signs and individual symptoms. Admission with a label of suspect stroke was not associated with door-to-doctor time (TR, 1.04). Both warning signs 3 (vision) and 4 (walking, balance, or dizziness) were associated with slower door-to-doctor times (30% and 21% slower, respectively). Individual symptoms associated with faster door-to-doctor times (ie, TRs <1.0) included facial droop (20% faster), speech/language problems (15% faster), and loss of consciousness (46% faster). Slower door-to-doctor times were observed for numbness (23% slower) and dizziness (25% slower).
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In contrast to door-to-doctor times, suspect stroke was associated with a significantly faster door-to-image time (13% faster) as was warning Sign 2 (confusion/speech, 12% faster). However, warning signs 3 (vision), 4 (trouble with walking, balance, or dizziness), and 5 (headache) were all associated with slower door-to-image times. For individual symptoms, weakness was associated with 10% faster door-to-image times, whereas numbness was associated with 11% slower door-to-image times. Facial droop, any unilateral symptoms, speech/language problems, nonheadache pain, and loss of consciousness were also all associated with faster door-to-image times, whereas dizziness was associated with slower door-to-image time.
Adjusted model results for door-to-doctor time are shown in Table 4. Apart from the a priori confounders, ie, age, race, emergency medical services, and hospital site, only a medical history of stroke/TIA and 3 presenting symptoms entered the model. We observed a statistically significant sex disparity in door-to-doctor time; compared with male patients, females waited 11% longer before being seen by a doctor (adjusted TR, 1.11). As expected, patients with shorter onset-to-arrival times and those who arrived by emergency medical services had much shorter door-to-doctor times; however, unexpectedly, patients with a history of stroke had 14% slower door-to-doctor times. Patients who reported speech/language problems and those who had loss of consciousness had faster door-to-doctor times than those who did not report these problems, whereas subjects with difficulty walking had slower door-to-doctor times. The door-to-doctor sex disparity was smaller and nonsignificant among patients who arrived within 6 hours of symptom onset (TR, 1.05; 95% CI, 0.92 to 1.21) but was larger although nonsignificant within the 2-hour arrival group (TR, 1.18; 95% CI, 0.94 to 1.49).
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Analogous results for door-to-image time are presented in Table 5. After adjusting for demographics, individual symptoms, and warning signs, we observed a statistically significant sex difference in door-to-image times (TR, 1.15) indicating that time to imaging was 15% slower for women. Suspect stroke, weakness, facial droop, speech difficulty, and loss of consciousness were all associated with faster door-to-image times (ie, TRs <1), whereas vision problems (warning sign 3), trouble with walking, dizziness or loss of balance or coordination (warning sign 4), confusion, and pain were all associated with longer door-to-image times. Among patients who arrived within 6 hours after symptom onset, the slower door-to-image interval for women remained unchanged, and the delays associated with vision problems, confusion, and pain became stronger. Among patients who arrived within 2 hours, the sex difference in door-to-image time was even stronger (TR, 1.24; 95% CI, 1.07 to 1.44).
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Adjusted analyses of doctor-to-image time intervals found that women had longer delays both among all patients (TR, 1.13; 95% CI, 1.04 to 1.23) and among those who arrived within 6 hours of onset (TR, 1.12; 95% CI, 0.98 to 1.27) or 2 hours of onset (TR, 1.30; 95% CI, 1.09 to 1.54).
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Discussion |
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In this study from a representative statewide stroke registry, we found that women experienced longer delays in their ED workups than men, both in door-to-doctor and door-to-image intervals. Stroke symptoms reported at presentation were strongly associated with in-hospital delays and reported symptoms differed somewhat by sex, but the sex differences in symptoms did not explain the greater delays in door-to-image times experienced by women.
Our findings of sex differences in symptom presentation—with women more often presenting with pain but less often presenting with a recognized warning sign or suspect stroke—are in general agreement with the limited information published to date. A study conducted in 10 east Texas hospitals elicited presenting symptom data through structured interviews with 1124 patients with acute stroke or proxy respondents.28 Compared with men, women had significantly greater odds of reporting pain (OR, 1.78), change in level of consciousness (OR, 1.42), and nonspecific symptoms unlikely to have a neurological cause (OR, 1.36). Women also had lower odds of presenting with imbalance (OR, 0.70) or gait problems (OR, 0.67), which agrees with our findings. Other studies have found that women more often present with loss of consciousness,2,8 although our results did not confirm this. We also did not corroborate findings that women more often present with headaches.2,5,35 Overall, the sex differences in symptoms we identified were relatively minor, but did indicate that women were slightly less likely than men to present with an obvious stroke warning sign or label of suspect stroke.
We found that after adjustment for demographics, medical history, and presenting symptoms, women had 11% longer door-to-doctor times compared with men. This sex difference was halved after restricting the analysis to those who arrived within 6 hours of onset but paradoxically was increased in the group that arrived within 2 hours. Women also had a 15% longer delay in door-to-image times compared with men. This difference was similar among patients who arrived <6 hours of onset and was stronger among those who arrived within 2 hours. Examination of the doctor-to-image time intervals confirmed that women had significantly longer delay than men and that this delay was found even among the subgroups who arrived within 6 hours and 2 hours of onset.
Many of the studies that have reported on sex differences in in-hospital delays have limited power (ie, sample sizes <300 patients) and limited consideration of confounders,19,20,24–27 but a few larger studies have been published.21–23 A study conducted in 4 Berlin hospitals used proportional hazard models to evaluate door-to-image times among 558 patients with stroke hospitalized in 2000 to 2001.22 Women had significantly longer median door-to-image times in univariate analyses (120 versus 102 minutes; hazard ratio, 0.83). This result was attenuated slightly after adjusting for age, health insurance, National Institutes of Health Stroke Scale, prehospital delay, weekend admission, and hospital (adjusted hazard ratio, 0.87; 95% CI, 0.74 to 1.04). Among 3491 Paul Coverdell National Acute Stroke Registry patients from 4 states (2005 to 2006) who arrived within 2 hours of symptom onset, women had a longer door-to-image interval (0.78 hour versus 0.68 hour, P<0.001) and a lower percentage of women received imaging within 1 hour after arrival.21 However, this study did not adjust for potential confounders. In a report on 15 177 patients from the North Carolina Collaborative Stroke Registry, women had longer door-to-image times and lower odds of receiving imaging within 25 minutes of ED arrival compared with men after adjusting for race, prehospital delay, emergency medical services use, and other confounders.23 This study also found that among patients who arrived within 2 hours of symptom onset, women had a statistically significant 11% longer door-to-image time than men.23 This figure compares to the 24% longer delay we estimated in the equivalent subgroup.
Limitations of our data and analysis methods should be considered. It is possible that there remain differences in clinically apparent neurological deficits that result in delayed ED workup for women with acute stroke; however, we cannot evaluate this because the registry did not collect detailed neurological examination data. The chief complaint data were derived from patient charts and not from a standardized questionnaire; however, given the strong correlations between the presenting symptoms and hospital process times, we believe this information is valid. Indeed, the chief complaint drives the triage path for patients with acute stroke in the ED and so likely provides more relevant information in terms of understanding ED delays than detailed neurological symptom data.
Taken together, our results indicate that women who arrive in the ED with acute stroke take longer to be seen by a doctor and to get imaged. Our study corroborates the greater in-hospital delays for women and extends previous findings to rule out demographics, medical history, early arrival, and, most importantly, differences in symptom presentation as possible explanations. Our data indicate that decisions related to the stroke diagnostic workup are made less urgently for women, although the reasons for this are not clear. Despite the fact that we did not see major differences in symptom presentation and accounted for these in the analyses, these findings might be explained by a lower index of suspicion for stroke in women among the ED staff. Obviously, slower ED evaluation times could have implications for women’s eligibility to receive acute stroke treatments and may be explain, in part, why tissue plasminogen activator treatment rates are lower in women.10–15 More detailed studies of specific processes of care in the ED are necessary to understand the origins of these sex disparities in in-hospital delay. With further data it may become possible to make specific recommendations regarding the education of ED staff concerning the recognition and timely evaluation of acute stroke in women and possibly to create public health messages targeted toward women.
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Acknowledgments |
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We thank the participating institutions and their staff who provided data: Spectrum Health Systems, Grand Rapids; St Joseph Mercy Hospital, Ann Arbor; University of Michigan Hospital, Ann Arbor; Borgess Medical Center, Kalamazoo; Sparrow Health Systems, Lansing; Ingham Regional Medical Center, Lansing; Detroit Receiving Hospital; Henry Ford Wyandotte Hospital; St Joseph Mercy of Macomb; Northern Michigan Regional Health System, Petoskey; St Mary’s Hospital, Saginaw; Bronson Methodist Hospital, Kalamazoo; Harper University Hospital, Detroit; Alpena General Hospital; and St Joseph Health Systems, Tawas.
Source of Funding
This study was supported by US Centers for Disease Control and Prevention Cooperative Agreement No. U50/CCU520272-01.
Disclosures
None.
Received November 15, 2008; revision received January 9, 2009; accepted January 22, 2009.
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