Heterogeneity of obstructive sleep apnea phenotypes after ischemic stroke: Outcome variation by cluster analysis.

INTRODUCTION: Obstructive sleep apnea (OSA) is common but under-recognized after stroke. The aim of this study was to determine whether post-stroke phenotypic OSA subtypes are associated with stroke outcome in a population-based observational cohort. METHODS: Ischemic stroke patients (n = 804) diagnosed with OSA (respiratory event index ≥10) soon after ischemic stroke were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) project. Functional, cognitive, and quality of life outcomes were assessed at 90 days post-stroke and long-term stroke recurrence was ascertained. Latent profile analysis was performed based on demographic and clinical features, pre-stroke sleep characteristics, OSA severity, and vascular risk factors. Regression models were used to assess the association between phenotypic clusters and outcomes. RESULTS: Four distinct phenotypic clusters provided the best fit. Cluster 1 was characterized by more severe stroke; cluster 2 by severe OSA and higher prevalence of medical comorbidities; cluster 3 by mild stroke and mild OSA; and cluster 4 by moderate OSA and mild stroke. Compared to cluster 3 and after adjustment for baseline stroke severity, cluster 1 and cluster 2 had worse 90-day functional outcome and cluster 1 also had worse quality of life. No difference in cognitive outcome or stroke recurrence rate was noted by cluster. CONCLUSION: Post-stroke OSA is a heterogeneous disorder with different clinical phenotypes associated with stroke outcomes, including both daily function and quality of life. The unique presentations of OSA after stroke may have important implications for stroke prognosis and personalized treatment strategies.

Patterns of repeated diagnostic testing for COVID-19 in relation to patient characteristics and outcomes.

BACKGROUND: Whilst the COVID-19 diagnostic test has a high false-negative rate, not everyone initially negative is re-tested. Michigan Medicine, a primary regional centre, provided an ideal setting for studying testing patterns during the first wave of the pandemic. OBJECTIVES: To identify the characteristics of patients who underwent repeated testing for COVID-19 and determine if repeated testing was associated with downstream outcomes amongst positive cases. METHODS: Characteristics, test results, and health outcomes for patients presenting for a COVID-19 diagnostic test were collected. We examined whether patient characteristics differed with repeated testing and estimated a false-negative rate for the test. We then studied repeated testing patterns in patients with severe COVID-19-related outcomes. RESULTS: Patient age, sex, body mass index, neighbourhood poverty levels, pre-existing type 2 diabetes, circulatory, kidney, and liver diseases, and cough, fever/chills, and pain symptoms 14 days prior to a first test were associated with repeated testing. Amongst patients with a positive result, age (OR: 1.17; 95% CI: (1.05, 1.34)) and pre-existing kidney diseases (OR: 2.26; 95% CI: (1.41, 3.68)) remained significant. Hospitalization (OR: 7.88; 95% CI: (5.15, 12.26)) and ICU-level care (OR: 6.93; 95% CI: (4.44, 10.92)) were associated with repeated testing. The estimated false-negative rate was 23.8% (95% CI: (19.5%, 28.5%)). CONCLUSIONS: Whilst most patients were tested once and received a negative result, a meaningful subset underwent multiple rounds of testing. These results shed light on testing patterns and have important implications for understanding the variation of repeated testing results within and between patients.

Diabetes and ischaemic stroke outcome.

AIM: To compare all-cause mortality, stroke recurrence and functional outcomes in people who have experienced stroke, with and without diabetes. METHODS: We captured data on population-based ischaemic strokes (2006-2012) in Nueces County, Texas. Data were collected from participant interviews and medical records. Differences in cumulative mortality and stroke recurrence risk by diabetes status were estimated at 30 days and 1 year using Cox models. Differences in 90-day functional outcomes (activities of daily living/instrumental activities of daily living score: range 1-4; higher scores worse) by diabetes status were assessed using Tobit regression. Effect modification by ethnicity was examined. RESULTS: There were 1301 ischaemic strokes, 46% with history of known diabetes. The median (interquartile range) age was 70 (58-81) years and 61% were Mexican American. People with diabetes were younger and more likely to be Mexican American compared with those without diabetes. After adjustment, diabetes predicted mortality (30-day hazard ratio 1.44, 95% CI 0.97-2.12; 1-year hazard ratio 1.47, 95% CI 1.09-1.97) but not stroke recurrence (1-year hazard ratio 1.27, 95% CI 0.78-2.07). People with diabetes had a worse functional outcome score that was explained by cardiovascular risk factors and pre-stroke factors. Diabetes was not associated with functional outcome in the fully adjusted model (final adjusted activities of daily living/instrumental activities of daily living score difference 0.11, 95% CI -0.07 to 0.30). Effect modification by ethnicity was not significant (P>0.3 for all models). CONCLUSIONS: Diabetes was associated with higher mortality and worse functional outcome but not stroke recurrence. Interventions are needed to decrease the adverse outcomes associated with diabetes, particularly in Mexican-American people.

Bleeding patterns during the menopausal transition in the multi-ethnic Study of Women's Health Across the Nation (SWAN): a prospective cohort study.

OBJECTIVE: Previous studies describing menses duration and heaviness of flow during the menopausal transition (MT) have been short in duration and limited to white women. We estimated the frequency of and risk factors for prolonged bleeding, spotting and heavy bleeding during the MT in an ethnically diverse population. DESIGN: Prospective community-based cohort study. SETTING USA: southeastern Michigan, northern California and Los Angeles, California. POPULATION: A total of 1320 midlife women who participated in the Study of Women's Health Across the Nation (SWAN) Menstrual Calendar Substudy. Participants included African-American, white, Chinese, and Japanese women. METHODS: Women completed daily menstrual calendars from 1996 to 2006, and provided information on hormone therapy, smoking and physical activity. Annual measures included height and weight. Kaplan-Meier survival analysis and multivariable regression were used to analyse the data. MAIN OUTCOME MEASURES: Menses of 10+ days, spotting of 6+ days, heavy bleeding of 3+ days. RESULTS: At least three occurrences of menses 10+ days was reported by 77.7% (95% confidence interval [95% CI] 56.7-93.2), of 6+ days of spotting by 66.8% (95% CI 55.2-78.0) and of 3+ days of heavy bleeding by 34.5% (95% CI 30.2-39.2) of women. Menses of 10+ days, 6+ days of spotting, and 3+ days of heavy bleeding were associated with MT stage, uterine fibroids, hormone use and ethnicity. Body mass index was associated with 3+ days of heavy bleeding. CONCLUSIONS: These data provide clinicians and women with important information about the expected frequency of prolonged and heavy bleeding and spotting during the menopausal transition that may facilitate clinical decision making.

Effect of insurance status on postacute care among working age stroke survivors.

OBJECTIVE: Utilization of postacute care is associated with improved poststroke outcomes. However, more than 20% of American adults under age 65 are uninsured. We sought to determine whether insurance status is associated with utilization and intensity of institutional postacute care among working age stroke survivors. METHODS: A retrospective cross-sectional study of ischemic stroke survivors under age 65 from the 2004-2006 Nationwide Inpatient Sample was conducted. Hierarchical logistic regression models controlling for patient and hospital-level factors were used. The primary outcome was utilization of any institutional postacute care (inpatient rehabilitation or skilled nursing facilities) following hospital admission for ischemic stroke. Intensity of rehabilitation was explored by comparing utilization of inpatient rehabilitation facilities and skilled nursing facilities. RESULTS: Of the 33,917 working age stroke survivors, 19.3% were uninsured, 19.8% were Medicaid enrollees, and 22.8% were discharged to institutional postacute care. Compared to those privately insured, uninsured stroke survivors were less likely (adjusted odds ratio [AOR] 0.53, 95% confidence interval [CI] 0.47-0.59) while stroke survivors with Medicaid were more likely to utilize any institutional postacute care (AOR = 1.40, 95% CI 1.27-1.54). Among stroke survivors who utilized institutional postacute care, uninsured (AOR = 0.48, 95% CI 0.36-0.64) and Medicaid stroke survivors (AOR = 0.27, 95% CI 0.23-0.33) were less likely to utilize an inpatient rehabilitation facility than a skilled nursing facility compared to privately insured stroke survivors. CONCLUSIONS: Insurance status among working age acute stroke survivors is independently associated with utilization and intensity of institutional postacute care. This may explain differences in poststroke outcomes among uninsured and Medicaid stroke survivors compared to the privately insured.

Enrollment of women and minorities in NINDS trials.

OBJECTIVE: To determine policy-associated changes over time in 1) the enrollment of women and minorities in National Institute of Neurological Disorders and Stroke (NINDS)-funded clinical trials and 2) the trial publication reporting of race/ethnicity and gender. METHODS: All NINDS-funded phase III trials published between 1985 and 2008 were identified. Percent of African Americans, Hispanic Americans, and women enrolled in the trials was calculated for those trials with available data. Z tests were used to compare reporting and enrollment data from before (period 1) and after (period 2) 1995 when NIH enacted their policies regarding race, ethnicity, and gender. Percent of main trial publications reporting enrollment of African Americans, Hispanic Americans, and women was also calculated. RESULTS: Of the 56 trials identified, 100%, 48%, and 25% reported enrollment by gender, race, and ethnicity. Women constituted 42.1% of the trial population. Enrollment of women increased over time (36.9% period 1; 49.0% period 2, p < 0.001). African Americans constituted 19.8% of the enrollees in trials with available data and enrollment increased over time (11.6% period 1; 30.7% period 2, p < 0.001). Hispanic Americans constituted 5.8% of subjects in trials with available data and enrollment decreased over time (7.4% period 1; 5.0% period 2, p < 0.001). CONCLUSIONS: Improvements in reporting of race/ethnicity in publications and enrollment of Hispanics in NINDS trials are needed. While African American representation is above population levels, Hispanic Americans are underrepresented in NINDS trials and representation is declining despite Hispanics' increasing representation in the US population.

Predicting ischaemic stroke subtype from presenting systolic blood pressure: the BASIC Project.

OBJECTIVE: We hypothesized that low presenting systolic blood pressure (SBP) predicted cardioembolic stroke aetiology. DESIGN: Active and passive surveillance were used to identify all ischaemic strokes as part of the Brain Attack Surveillance in Corpus Christi (BASIC) population-based study. Multinomial logistic regression was used to examine the association between stroke subtype and first documented SBP in the medical record. SETTING: Nueces County, TX, USA (313,645 residents in 2000). The community is urban with the majority of the population residing in the city of Corpus Christi. The area is served by seven adult acute care hospitals. PATIENTS: Three hundred and eight cases with completed ischaemic stroke and determined subtype aetiology between January 2000 and December 2002. RESULTS: Lower presenting SBP was associated with stroke subtype (P = 0.001). This association remained significant in the final model adjusted for age and history of coronary artery disease. The odds of cardioembolic versus small vessel occlusion increased by 20% (OR = 1.20, 95% CI: 1.07-1.35) for every 10 mmHg decrease in presenting SBP. Other covariates including race/ethnicity, gender, history of hypertension, and diabetes were neither significant predictors of stroke subtype, nor did they confound the association of SBP and stroke subtype. A 5 year increase in age increased the odds of cardioembolic subtype by 25% (OR = 1.25, 95% CI: 1.07-1.47). CONCLUSIONS: Lower initial SBP and older age at ischaemic stroke presentation were associated with cardioembolic stroke. Suspicion of cardioembolic stroke should be increased in those presenting with low SBP.

Gender and ethnic differences in subarachnoid hemorrhage.

BACKGROUND: Mexican Americans (MAs) comprise the largest component of the largest minority group within the United States. The purpose of this study was to examine ethnic and gender differences in the epidemiology, presentation, and outcomes after subarachnoid hemorrhage (SAH) in a representative United States community. Targeted public health interventions are dependent on accurate assessments of groups at highest disease risk. METHODS: All patients with nontraumatic SAH older than 44 years were prospectively identified from January 1, 2000, to December 31, 2006, as part of the Brain Attack Surveillance In Corpus Christi project, an urban population-based study in southeast Texas. Risk ratios for cumulative SAH incidence comparing MAs with non Hispanic whites (NHWs) and women with men were calculated. Descriptive statistics for other clinical and demographic variables were computed overall, by gender, and by ethnicity. RESULTS: A total of 107 patients had a SAH during the time period (7-year cumulative incidence: 11/10,000); of these, 43 were NHW (40% of cases vs 53% of the population) and 64 were MA (60% of cases vs 48% of the population). The overall age-adjusted risk ratio for SAH in MAs compared with NHWs was 1.67 (95% CI: 1.13, 2.47), and in women compared to men was 1.74 (95% CI 1.16, 2.62). Overall in-hospital mortality was 32.2%. No ethnic difference was observed for discharge disability or in-hospital mortality. CONCLUSIONS: Subarachnoid hemorrhage disproportionately affects Mexican Americans and women. Public health interventions should target these groups to reduce the impact of this severe disease.

Early care limitations independently predict mortality after intracerebral hemorrhage.

OBJECTIVE: Intracerebral hemorrhage (ICH) is associated with a high early mortality rate. We examined the impact of early do not resuscitate (DNR) orders and other limitations in aggressive care on mortality after ICH in a community-based study. METHODS: Cases of spontaneous ICH from 2000 to 2003 were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) project, with deaths ascertained through 2005. Charts were reviewed for early (<24 hours from presentation) DNR orders, withdrawal of care, or deferral of other life sustaining interventions, analyzed together as combined DNR (C-DNR). Multivariable Cox-proportional hazards models were used to examine the association between short- and long-term all-cause mortality and early C-DNR, adjusted for demographics and established predictors of mortality after ICH. RESULTS: Of 18,393 subjects screened for cerebrovascular disease, 270 non-traumatic ICH cases were included. Cumulative mortality risk was 0.43 at 30 days and 0.55 over the study course. Early C-DNR was noted in 34% of cases and was associated with a doubling in the hazard of death both at 30 days (hazard ratio [HR] 2.17, 95% CI 1.38, 3.41) and at end of follow-up (HR 1.92, 95% CI 1.29, 2.87) despite adjustment for age, gender, ethnicity, Glasgow Coma Scale, ICH volume, intraventricular hemorrhage, and infratentorial hemorrhage. CONCLUSIONS: Early care limitations are independently associated with both short- and long-term all-cause mortality after intracerebral hemorrhage (ICH) despite adjustment for expected predictors of ICH mortality. Physicians should carefully consider the effect of early limitations in aggressive care to avoid limiting care for patients who may survive their acute illness.

Neighborhood environment and risk of ischemic stroke: the brain attack surveillance in Corpus Christi (BASIC) Project.

The authors explored whether neighborhood-level characteristics are associated with ischemic stroke and whether the association differs by ethnicity, age, and gender. Using data from the Brain Attack Surveillance in Corpus Christi Project (January 2000-June 2003), they identified cases of ischemic stroke (n = 1,247) from both hospital and out-of-hospital sources. Census tracts served as proxies for neighborhoods, and neighborhood socioeconomic status scores were constructed from census variables (higher scores represented less disadvantage). In Poisson regression analyses comparing the 90th percentile of neighborhood score with the 10th, the relative risk of stroke was 0.49 (95% confidence interval (CI): 0.41, 0.58). After adjustment for age, gender, and ethnicity, this association was attenuated (relative risk (RR) = 0.79, 95% CI: 0.63, 1.00). There was no ethnic difference in the association of score with stroke (p for interaction = 0.79). Significant effect modification was found for age (p for interaction < 0.001) and gender (p for interaction = 0.04), with increasing scores being protective against stroke in men and younger persons. Associations were attenuated after adjustment for education (men: RR = 0.77, 95% CI: 0.55, 1.07; persons aged <65 years: RR = 0.65, 95% CI: 0.41, 1.02). Neighborhood characteristics may influence stroke risk in certain gender and age groups. Mechanisms for these associations should be examined.

Projected costs of ischemic stroke in the United States.

BACKGROUND: There are barriers to acute stroke care in minority groups as well as a higher incidence of ischemic stroke when compared with non-Hispanic whites. OBJECTIVE: To estimate the future economic burden of stroke in non-Hispanic whites, Hispanics, and African Americans in the United States from 2005 to 2050. METHODS: We used U.S. Census estimates of the race-ethnic group populations age 45 years and older. We obtained stroke epidemiology and service utilization data from the Northern Manhattan Stroke Study and the Brain Attack Surveillance in Corpus Christi project and other published data. We estimated costs directly from Medicare reimbursement or from studies that used Medicare reimbursement. Direct and indirect costs considered included ambulance services, initial hospitalization, rehabilitation, nursing home costs, outpatient clinic visits, drugs, informal caregiving, and potential lost earnings. RESULTS: The total cost of stroke from 2005 to 2050, in 2005 dollars, is projected to be 1.52 trillion dollars for non-Hispanic whites, 313 billion dollars for Hispanics, and 379 billion dollars for African Americans. The per capita cost of stroke estimates are highest in African Americans (25,782 dollars), followed by Hispanics (17,201 dollars), and non-Hispanic whites (15,597 dollars). Loss of earnings is expected to be the highest cost contributor in each race-ethnic group. CONCLUSIONS: The economic burden of stroke in African Americans and Hispanics will be enormous over the next several decades. Further efforts to improve stroke prevention and treatment in these high stroke risk groups are necessary.

Presentation of intracerebral haemorrhage in a community.

BACKGROUND: Studies on intracerebral haemorrhage (ICH) from tertiary care centres may not be an accurate representation of the true spectrum of disease presentation. OBJECTIVE: To describe the clinical and imaging presentation of ICH in a community devoid of the referral bias of an academic medical centre; and to investigate factors associated with lower Glasgow coma scale (GCS) score at presentation, as GCS is crucial to early clinical decision making. METHODS: The study formed part of the BASIC project (Brain Attack Surveillance in Corpus Christi), a population based stroke surveillance study in a bi-ethnic Texas community. Cases of first non-traumatic ICH were identified from years 2000 to 2003, using active and passive surveillance. Clinical data were collected from medical records by trained abstractors, and all computed tomography (CT) scans were reviewed by a study physician. Multivariable linear regression was used to identify clinical and CT predictors of a lower GCS score. RESULTS: 260 cases of non-traumatic ICH were identified. Median ICH volume was 11 ml (interquartile range 3 to 36) with hydrocephalus noted in 45%. Median initial GCS score was 12.5 (7 to 15). Hydrocephalus score (p = 0.0014), ambient cistern effacement (p = 0.0002), ICH volume (p = 0.014), and female sex (p = 0.024) were independently associated with lower GCS score at presentation, adjusting for other variables. CONCLUSIONS: ICH has a wide range of severity at presentation. Hydrocephalus is a potentially reversible cause of a lower GCS score. Since early withdrawal of care decisions are often based on initial GCS, recognition of the important influence of hydrocephalus on GCS is warranted before withdrawal of care decisions are made.

Differences in intracerebral hemorrhage between Mexican Americans and non-Hispanic whites.

BACKGROUND: Mexican Americans (MAs) have higher incidence rates of intracerebral hemorrhage (ICH) than non-Hispanic whites (NHWs). The authors present clinical and imaging characteristics of ICH in MAs and NHWs in a population-based study. METHODS: This work is part of the Brain Attack Surveillance in Corpus Christi (BASIC) project. Cases of nontraumatic ICH were identified from 2000 to 2003. Multivariable logistic regression was used to assess the independent associations between ethnicity and ICH location (lobar vs nonlobar) and volume (> or = 30 vs < 30 mL), adjusting for demographics and baseline clinical characteristics. Logistic regression was also used to determine the association between ethnicity and in-hospital mortality, adjusting for confounders. RESULTS: A total of 149 MAs and 111 NHWs with ICH were identified. MAs were younger (70 vs 77, p < 0.001), more often male (55% vs 42%, p = 0.04), had a lower prevalence of atrial fibrillation (2.0% vs 13%, p < 0.001), and a higher prevalence of diabetes (39% vs 19%, p < 0.001). MA ethnicity was independently associated with nonlobar hemorrhage (OR 2.08, 95% CI: 1.15, 3.70). MAs had over two times the odds of having small (< 30 mL) hemorrhages compared with NHWs (OR = 2.41, 95% CI: 1.31, 4.46). NHWs had higher in-hospital mortality, though this association was no longer significant after adjustment for ICH volume, location, age, and sex. CONCLUSIONS: There are significant differences in the characteristics of ICH in MAs and NHWs, with MA patients more likely to have smaller, nonlobar hemorrhages. These differences may be used to examine the underlying pathophysiology of ICH.

Emergency department evaluation of ischemic stroke and TIA: the BASIC Project.

OBJECTIVE: To identify demographic and clinical variables of emergency department (ED) practices in a community-based acute stroke study. METHODS: By both active and passive surveillance, the authors identified cerebrovascular disease cases in Nueces County, TX, as part of the Brain Attack Surveillance in Corpus Christi (BASIC) Project, a population-based stroke surveillance study, between January 1, 2000, and December 31, 2002. With use of multivariable logistic regression, variables independently associated with three separate outcomes were sought: hospital admission, brain imaging in the ED, and neurologist consultation in the ED. Prespecified variables included age, sex, ethnicity, insurance status, NIH Stroke Scale score, type of stroke (ischemic stroke or TIA), vascular risk factors, and symptom presentation variables. Percentage use of recombinant tissue plasminogen activator (rt-PA) was calculated. RESULTS: A total of 941 Mexican Americans (MAs) and 855 non-Hispanic whites (NHWs) were seen for ischemic stroke (66%) or TIA (34%). Only 8% of patients received an in-person neurology consultation in the ED, and 12% did not receive any head imaging. TIA was negatively associated with neurology consultations compared with completed stroke (odds ratio [OR] 0.35 [95% CI 0.21 to 0.57]). TIA (OR 0.14 [0.10 to 0.19]) and sensory symptoms (OR 0.59 [0.44 to 0.81]) were also negatively associated with hospital admission. MAs (OR 0.58 [0.35 to 0.98]) were less likely to have neurology consultations in the ED than NHWs. Only 1.7% of patients were treated with rt-PA. CONCLUSIONS: Neurologists are seldom involved with acute cerebrovascular care in the emergency department (ED), especially in patients with TIA. Greater neurologist involvement may improve acute stroke diagnosis and treatment efforts in the ED.

A population-based study of acute stroke and TIA diagnosis.

BACKGROUND: Acute stroke therapy is heavily dependent on the diagnostic acumen of the physician in the emergency department (ED). OBJECTIVE: To determine this diagnostic accuracy in a population-based multiethnic stroke study. METHODS: The Brain Attack Surveillance in Corpus Christi (BASIC) Project prospectively ascertained all acute stroke or TIA cases in an urban Texas county of 313,645 residents without an academic medical center. Cases were validated by board-certified neurologists using source documentation. Case validation was used as the gold standard to compare the diagnosis given by the ED physician. RESULTS: From January 2000 to August 2002, a total of 13,015 patients were screened. Of these, 1,800 were validated as stroke/TIA. Overall sensitivity of the emergency physician for the BASIC-validated diagnosis was 92%, and positive predictive value was 89%. Of the cases that the emergency physician thought were stroke, 11% were validated as no stroke. In multivariable modeling, motor symptoms was an independent predictor of protection from false-negative ED diagnosis of stroke/TIA (odds ratio [OR] = 0.61; 95% CI 0.41 to 0.89). Protection from false-positive stroke/TIA diagnosis was predicted by sensory symptoms (OR = 0.43; 95% CI 0.28 to 0.66), motor symptoms (OR = 0.44; 95% CI 0.32 to 0.62), and severe neurologic deficit (OR = 0.33; 95% CI 0.14 to 0.78). History of stroke/TIA predicted false-positive stroke diagnosis (OR = 1.72; 95% CI 1.23 to 2.40). The majority of disagreements occurred in patients with generalized neurologic or acute medical, nonneurologic syndromes. CONCLUSIONS: Physicians practicing in the ED are sensitive for stroke/TIA diagnosis. The modest positive predictive value argues for a systems approach with neurology support so that proper decisions regarding acute stroke therapy can be made.