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Introduction The risk of intracerebral haemorrhage (ICH) associated with hypertension (HTN) is well documented. While the prevalence of HTN increases with age, the greatest odds ratio (OR) for HTN as a risk for ischemic stroke is at an early age. We sought to evaluate if the risk for ICH from HTN was higher in the youngest patients of each race. Patients and methods The Ethnic/Racial Variations of ICH (ERICH) study is a prospective multicenter case-control study of ICH among whites, blacks, and Hispanics. Participants were divided into age groups based on race-specific quartiles. Cases in each race/age group were compared to controls using logistic regression (i.e., cases and controls unmatched). The probability of ICH among cases and controls for each race were compared against independent variables of HTN, quartile of age and interaction of quartile and age also using logistic regression. Results Overall, 2033 non-lobar ICH cases and 2060 controls, and 913 lobar ICH cases with 927 controls were included. ORs were highest in the youngest age quartile for non-lobar haemorrhage for blacks and Hispanics and highest in the youngest quartile for lobar haemorrhage for all races. The formal test of interaction between age and HTN was significant in all races for all locations with the exception of lobar ICH in whites (p = 0.2935). Discussion Hypertension is a strong independent risk factor for ICH irrespective of location among persons of younger age, consistent with the hypothesis that first exposure to HTN is a particularly sensitive time for all locations of ICH.

ObjectiveTo test the hypothesis that thrombogenic atrial cardiopathy may be relevant to stroke-related racial disparities, we compared atrial cardiopathy phenotypes between Black vs White patients with ischemic stroke.MethodsWe assessed markers of atrial cardiopathy in the Greater Cincinnati/Northern Kentucky Stroke Study, a study of stroke incidence in a population of 1.3 million. We obtained ECGs and reports of echocardiograms performed during evaluation of stroke during the 2010/2015 study periods. Patients with atrial fibrillation (AF) or flutter (AFL) were excluded. Investigators blinded to patients' characteristics measured P-wave terminal force in ECG lead V1 (PTFV1), a marker of left atrial fibrosis and impaired interatrial conduction, and abstracted left atrial diameter from echocardiogram reports. Linear regression was used to examine the association between race and atrial cardiopathy markers after adjustment for demographics, body mass index, and vascular comorbidities.ResultsAmong 3,426 ischemic stroke cases in Black or White patients without AF/AFL, 2,391 had a left atrial diameter measurement (mean, 3.65 ± 0.70 cm). Black race was associated with smaller left atrial diameter in unadjusted (β coefficient, −0.11; 95% confidence interval [CI], −0.17 to −0.05) and adjusted (β, −0.15; 95% CI, −0.21 to −0.09) models. PTFV1 measurements were available in 3,209 patients (mean, 3,434 ± 2,525 μV*ms). Black race was associated with greater PTFV1 in unadjusted (β, 1.59; 95% CI, 1.21–1.97) and adjusted (β, 1.45; 95% CI, 1.00–1.80) models.ConclusionsWe found systematic Black–White racial differences in left atrial structure and pathophysiology in a population-based sample of patients with ischemic stroke.Classification of EvidenceThis study provides Class II evidence that atrial cardiopathy phenotypes differ in Black people with acute stroke compared to White people.

Key Points Question Does the prevalence and burden of risk factors for lobar and nonlobar intracerebral hemorrhage (ICH) differ among Black, Hispanic, and White populations? Findings In this case-control study of 3000 cases of ICH among Black, Hispanic, and White patients, the ɛ2 and ɛ4 alleles of APOE, the gene encoding apolipoprotein E, were associated with lobar ICH in White but not Black and Hispanic patients; hypertension was a risk factor for both lobar and nonlobar ICH in all groups; and the mean age for ICH among Black and Hispanic patients was more than 10 years younger than that of their White counterparts. Black and Hispanic patients had a higher attributable risk percentage for treated or untreated hypertension and lack of health insurance than White patients. Meaning These findings suggest that potentially modifiable risk factors and social determinants of health are important contributors to the disproportionate ICH burden experienced by Black and Hispanic populations., This case-control study examines the prevalence, odds, and population attributable risk for established and novel risk factors for intracerebral hemorrhage, stratified by intracerebral hemorrhage location and racial/ethnic group., Importance Black and Hispanic individuals have an increased risk of intracerebral hemorrhage (ICH) compared with their White counterparts, but no large studies of ICH have been conducted in these disproportionately affected populations. Objective To examine the prevalence, odds, and population attributable risk (PAR) percentage for established and novel risk factors for ICH, stratified by ICH location and racial/ethnic group. Design, Setting, and Participants The Ethnic/Racial Variations of Intracerebral Hemorrhage Study was a case-control study of ICH among 3000 Black, Hispanic, and White individuals who experienced spontaneous ICH (1000 cases in each group). Recruitment was conducted between September 2009 and July 2016 at 19 US sites comprising 42 hospitals. Control participants were identified through random digit dialing and were matched to case participants by age (±5 years), sex, race/ethnicity, and geographic area. Data analyses were conducted from January 2019 to May 2020. Main Outcomes and Measures Case and control participants underwent a standardized interview, physical measurement for body mass index, and genotyping for the ɛ2 and ɛ4 alleles of APOE, the gene encoding apolipoprotein E. Prevalence, multivariable adjusted odds ratio (OR), and PAR percentage were calculated for each risk factor in the entire ICH population and stratified by racial/ethnic group and by lobar or nonlobar location. Results There were 1000 Black patients (median [interquartile range (IQR)] age, 57 [50-65] years, 425 [42.5%] women), 1000 Hispanic patients (median [IQR] age, 58 [49-69] years; 373 [37.3%] women), and 1000 White patients (median [IQR] age, 71 [59-80] years; 437 [43.7%] women). The mean (SD) age of patients with ICH was significantly lower among Black and Hispanic patients compared with White patients (eg, lobar ICH: Black, 62.2 [15.2] years; Hispanic, 62.5 [15.7] years; White, 71.0 [13.3] years). More than half of all ICH in Black and Hispanic patients was associated with treated or untreated hypertension (PAR for treated hypertension, Black patients: 53.6%; 95% CI, 46.4%-59.8%; Hispanic patients: 46.5%; 95% CI, 40.6%-51.8%; untreated hypertension, Black patients: 45.5%; 95% CI, 39.%-51.1%; Hispanic patients: 42.7%; 95% CI, 37.6%-47.3%). Lack of health insurance also had a disproportionate association with the PAR percentage for ICH in Black and Hispanic patients (Black patients: 21.7%; 95% CI, 17.5%-25.7%; Hispanic patients: 30.2%; 95% CI, 26.1%-34.1%; White patients: 5.8%; 95% CI, 3.3%-8.2%). A high sleep apnea risk score was associated with both lobar (OR, 1.68; 95% CI, 1.36-2.06) and nonlobar (OR, 1.62; 95% CI, 1.37-1.91) ICH, and high cholesterol was inversely associated only with nonlobar ICH (OR, 0.60; 95% CI, 0.52-0.70); both had no interactions with race and ethnicity. In contrast to the association between the ɛ2 and ɛ4 alleles of APOE and ICH in White individuals (eg, presence of APOE ɛ2 allele: OR, 1.84; 95% CI, 1.34-2.52), APOE alleles were not associated with lobar ICH among Black or Hispanic individuals. Conclusions and Relevance This study found sleep apnea as a novel risk factor for ICH. The results suggest a strong contribution from inadequately treated hypertension and lack of health insurance to the disproportionate burden and earlier onset of ICH in Black and Hispanic populations. These findings emphasize the importance of addressing modifiable risk factors and the social determinants of health to reduce health disparities.

Objectives Population-level estimates of the median intracerebral hemorrhage (ICH) volume would allow for the evaluation of clinical trial external validity and determination of temporal trends. We previously reported the median ICH volume in 1988. However, differences in risk factor management, neuroimaging, and demographics may have affected ICH volumes. The goal of this study is to determine the median volume of ICH within a population-based cross-sectional study, including whether it has changed over time. Methods The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study was a population-based study of ICH among residents of the Greater Cincinnati/Northern Kentucky region from 2008 through 2012. This study utilizes those data and compares with ICH cases from the same region in 1988. Initial computed tomography images of the head were reviewed, and ICH volumes were calculated using consistent methodology. Results From 2008 through 2012, we identified 1117 cases of ICH. The median volume of ICH was 14.0 mL and was lower in black (11.6) than in white (15.5) patients. Median volumes of lobar and deep ICH were 28.8 mL and 9.8 mL, respectively. Median ICH volume changed significantly from 1988 to 2008–2012, with age-and-race-adjusted volume decreasing from 18.3 mL to 13.76 mL (p = 0.025). Conclusions Median volume of ICH was 13.76 mL, and this should be considered in clinical trial design. Median ICH volume has apparently decreased from 1988 to 2008–2012.

OBJECTIVES Intracerebral hemorrhage (ICH) has the highest morbidity and mortality rate of any stroke subtype and clinicians often administer prophylactic antiseizure medications (ASMs) as a means of preventing post-stroke seizures, particularly following lobar ICH. However, evidence for ASM efficacy in preventing seizures and reducing disability is lacking given limited randomized trials. Herein, we report analysis from a large prospective observational study that evaluates the effect of primary prophylactic ASM administration on seizure occurrence and disability following ICH. MATERIALS AND METHODS Primary analysis was performed on 1630 patients with ICH enrolled in the ERICH study. A propensity score for administration of prophylactic ASM was developed and patients were matched by the closest propensity score (difference

BackgroundA previous study suggested that intracranial aneurysms are more likely to occur in the same arterial territory within families. We aimed to replicate this analysis in independent families and in a sample limited to intracranial aneurysms that ruptured.MethodsAmong families with ≥2 first-degree relatives with intracranial aneurysms, we randomly matched index families to comparison families, and compared concordance in intracranial aneurysm territory between index and comparison families using a conditional logistic events/trials model. We analyzed three European cohorts separately, and pooled the results with those of the Familial Intracranial Aneurysm study by performing an inverse variance fixed effects meta-analysis. The main analysis included both unruptured and ruptured intracranial aneurysms, and a secondary analysis only ruptured intracranial aneurysms.ResultsAmong 70 Dutch, 142 Finnish, and 34 French families, concordance regarding intracranial aneurysm territory was higher within families than between families, although not statistically significant. Meta-analysis revealed higher concordance in territory within families overall (odds ratio [OR] 1.7, 95%CI 1.3-2.2) and for each separate territory except the anterior cerebral artery. In the analysis of ruptured intracranial aneurysms, overall territory concordance was higher within families than between families (OR 1.8; 95%CI 1.1-2.7) but the territory-specific analysis showed statistical significance only for the internal carotid artery territory.ConclusionsWe confirmed that familial intracranial aneurysms are more likely to occur in the same arterial territory within families. Moreover, we found that ruptured aneurysms were also more likely to occur in the same arterial territory within families.

Background and Purpose: For survivors of oral anticoagulation therapy (OAT)–associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the apolipoprotein E ( APOE ) gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and APOE genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest. Methods: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and APOE genotype predict ICH recurrence. We then developed and validated a combined APOE -MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis. Results: Cortical superficial siderosis, cerebral microbleed, and APOE ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all P APOE genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, P =0.033). In the MGH (training) data set, CSS, cerebral microbleed, and APOE ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH. Conclusions: Combining MRI and APOE genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined APOE -MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.

BACKGROUND Patients with spontaneous intracerebral hemorrhage (ICH) are predisposed to venous thromboembolic (VTE) complications, such as deep vein thrombosis and pulmonary embolism. OBJECTIVE To evaluate, in a multicenter, retrospective cohort study, the rate of VTE complications in ICH patients during acute hospitalization, identify potential risk factors, and assess their association with functional outcome. METHODS We retrospectively analyzed prospectively collected data from 19 centers and 41 sites that participated in the Ethnic/Racial Variations of Intracerebral Hemorrhage study, from August 2010 to February 2016. We compared ICH patients with VTE complications to those without VTE complications. Statistical analyses were performed to determine predictors of VTE complications and poor outcome (modified Rankin Scale ≥ 4) at discharge and 3-mo follow-up. RESULTS Of the 2902 ICH patients who were eligible for analysis, 87 (3.0%) had VTE complications: 57 (2.0%) had only deep vein thrombosis, 19 (0.7%) had only pulmonary embolism, and 11 (0.4%) had both. In the multivariable logistic regression analysis, a prior history of VTE (odds ratio [OR] = 6.8; P

ObjectiveTo clarify whether recurrence risk for intracerebral hemorrhage (ICH) is higher among black and Hispanic individuals and whether this disparity is attributable to differences in blood pressure (BP) measurements and their variability.MethodsWe analyzed data from survivors of primary ICH enrolled in 2 separate studies: (1) the longitudinal study conducted at Massachusetts General Hospital (n = 759), and (2) the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) study (n = 1,532). Participants underwent structured interview at enrollment (including self-report of race/ethnicity) and were followed longitudinally via phone calls and review of medical records. We captured systolic BP (SBP) and diastolic BP measurements, and quantified variability as SBP and diastolic BP variation coefficients. We used multivariable (Cox regression) survival analysis to identify risk factors for ICH recurrence.ResultsWe followed 2,291 ICH survivors (1,121 white, 529 black, 605 Hispanic, and 36 of other race/ethnicity). Both black and Hispanic patients displayed higher SBP during follow-up (p < 0.05). Black participants also displayed greater SBP variability during follow-up (p = 0.032). In univariable analyses, black and Hispanic patients were at higher ICH recurrence risk (p < 0.05). After adjusting for BP measurements and their variability, both Hispanic (hazard ratio = 1.51, 95% confidence interval 1.14–2.00, p = 0.004) and black (hazard ratio = 1.98, 95% confidence interval 1.36–2.86, p < 0.001) patients remained at higher risk of ICH recurrence.ConclusionBlack and Hispanic patients are at higher risk of ICH recurrence; hypertension severity (average BP and its variability) does not fully account for this finding. Additional studies will be required to further elucidate determinants for this health disparity.

We previously published rates of pediatric stroke using our population-based Greater Cincinnati Northern Kentucky Stroke Study (GCNK) for periods July 1993–June 1994 and 1999. We report population-based rates from 2 additional study periods: 2005 and 2010. We identified all pediatric strokes for residents of the GCNK region that occurred in July 1, 1993–June 30, 1994, and calendar years 1999, 2005, and 2010. Stroke cases were ascertained by screening discharge ICD-9 codes, and verified by a physician. Pediatric stroke was defined as stroke in those

Purpose We aimed to identify the effect of hyperosmolar therapy (mannitol and hypertonic saline) on outcomes after intracerebral hemorrhage (ICH) in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study. Methods Comparison of ICH cases treated with hyperosmolar therapy versus untreated cases was performed using a propensity score based on age, initial Glasgow Coma Scale, location of ICH (lobar, deep, brainstem, and cerebellar), log-transformed initial ICH volume, presence of intraventricular hemorrhage, and surgical interventions. ERICH subjects with a pre-ICH modified Rankin Scale (mRS) score of 3 or lower were included. Treated cases were matched 1:1 to untreated cases by the closest propensity score (difference ≤.15), gender, and race and ethnicity (non-Hispanic white, non-Hispanic black, or Hispanic). The McNemar and the Wilcoxon signed-rank tests were used to compare 3-month mRS outcomes between the 2 groups. Good outcome was defined as a 3-month mRS score of 3 or lower. Results As of December 31, 2013, the ERICH study enrolled 2279 cases, of which 304 hyperosmolar-treated cases were matched to 304 untreated cases. Treated cases had worse outcome at 3 months compared with untreated cases (McNemar, P = .0326), and the mean 3-month mRS score was lower in the untreated group (Wilcoxon, P = .0174). Post hoc analysis revealed more brain edema, herniation, and death at discharge for treated cases. Conclusions Hyperosmolar therapy was not associated with better 3-month mRS outcomes for ICH cases in the ERICH study. This finding likely resulted from greater hyperosmolar therapy use in patients with edema and herniation rather than those agents leading to worse outcomes. Further studies should be performed to determine if hyperosmolar agents are effective in preventing poor outcomes.

Background: We previously developed predictive models for 3-month mortality and modified Rankin Score (mRS) after ischemic stroke. Aim: The aim was to test model validity for 3-month mortality and mRS after ischemic stroke in two independent data sets. Methods: Our derivation models used data from 451 subjects with ischemic stroke in 1999 enrolled in the Greater Cincinnati/Northern Kentucky Stroke Study (GCKNSS). We utilized two separate cohorts of ischemic strokes through GCKNSS (460 in 2005 and 504 in 2010) to assess external validity by utilizing measures of agreement between predicted and observed values, calibration, and discrimination using Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis. Results: The 3-month mortality model performed well in the validation datasets with an average prediction error (Brier score) of 0.045 for 2005 and 0.053 for 2010 and excellent discrimination with an area under the curve of 0.86 (95% CI: 0.79, 0.93) for 2005 and 0.84 (0.76, 0.92) for 2010. Predicted 3-month mRS also performed well in the validation datasets with R2 of 0.57 for 2005 and 0.50 for 2010 and a root mean square error of 0.85 for 2005 and 1.05 for 2010. Predicted mRS tended to be higher than actual in both validation datasets. Re-estimation of the model parameters for age and severe white matter hyperintensity in both 2005 and 2010, and for diabetes in 2005, improved predictive accuracy. Conclusions: Our previously developed stroke models performed well in two study periods, suggesting validity of the model predictions.

Background We aimed to compare sex-specific associations between cardiovascular risk factors and diabetes mellitus (DM) among patients with acute ischemic stroke (AIS) in the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS). Methods The GCNKSS ascertained AIS cases in 2005 and 2010 among adult (age ≥20 years) residents of a biracial population of 1.3 million. Past and current stroke risk factors were compared between those with and without DM using chi-square and multiple logistic regression to examine sex-specific profiles. Results There were 3515 patients with incident AIS; 1919 (55%) were female, 697 (20%) were black, and 1146 (33%) had DM. Among both women and men with DM, significantly more were obese, and had hypertension, high cholesterol, and coronary artery disease (CAD) compared with those without DM. For women with AIS, in multivariable sex-specific adjusted analyses, older age was associated with a decreased odds of having DM (aOR=0.88, 95%CI 0.80-0.98). For women with CAD, the odds of DM were increased (aOR=1.76, 95%CI 1.33-2.32). Age and CAD were not significant factors in differentiating the profiles of men with and without DM. Conclusions Women with DM had strokes at a younger age, whereas no such age difference existed in men. As opposed to men, women with DM were also more likely to have CAD compared with those without DM, suggesting a sex difference in the association between DM and vascular disease. These findings may suggest a need for more aggressive risk factor management in diabetic women.

Background and Purpose— Statin use may be associated with improved outcome in intracerebral hemorrhage patients. However, the topic remains controversial. Our analysis examined the effect of prior, continued, or new statin use on intracerebral hemorrhage outcomes using the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) data set. Methods— We analyzed ERICH (a multicenter study designed to examine ethnic variations in the risk, presentation, and outcomes of intracerebral hemorrhage) to explore the association of statin use and hematoma growth, mortality, and 3-month disability. We computed subset analyses with respect to 3 statin categories (prior, continued, or new use). Results— Two thousand four hundred and fifty-seven enrolled cases (mean age, 62 years; 42% females) had complete data on mortality and 3-month disability (modified Rankin Scale). Among those, 1093 cases were on statins (prior, n=268; continued, n=423; new, n=402). Overall, statin use was associated with reduced mortality and disability without any effect on hematoma growth. This association was primarily driven by continued/new statin use. A multivariate analysis adjusted for age and major predictors for poor outcome showed that continued/new statins users had good outcomes compared with prior users. However, statins may have been continued/started more frequently among less severe patients. When a propensity score was developed based on factors that could influence a physician’s decision in prescribing statins and used as a covariate, continued/new statin use was no longer a significant predictor of good outcome. Conclusions— Although statin use, especially continued/new use, was associated with improved intracerebral hemorrhage outcomes, this effect may merely reflect the physician’s view of a patient’s prognosis rather than a predictor of survival.

Objective:To analyze the dose–risk relationship for alcohol consumption and intracerebral hemorrhage (ICH) in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study.Methods:ERICH is a multicenter, prospective, case-control study, designed to recruit 1,000 non-Hispanic white patients, 1,000 non-Hispanic black patients, and 1,000 Hispanic patients with ICH. Cases were matched 1:1 to ICH-free controls by age, sex, race/ethnicity, and geographic area. Comprehensive interviews included questions regarding alcohol consumption. Patterns of alcohol consumption were categorized as none, rare (2 drinks per day and Results:Multivariable analyses demonstrated an ordinal trend for alcohol consumption: rare (odds ratio [OR] 0.57, p < 0.0001), moderate (OR 0.65, p < 0.0001), intermediate (OR 0.82, p = 0.2666), and heavy alcohol consumption (OR 1.77, p = 0.0003). Subgroup analyses demonstrated an association of rare and moderate alcohol consumption with decreased risk of both lobar and nonlobar ICH. Heavy alcohol consumption demonstrated a strong association with increased nonlobar ICH risk (OR 2.04, p = 0.0003). Heavy alcohol consumption was associated with significant increase in nonlobar ICH risk in black (OR 2.34, p = 0.0140) and Hispanic participants (OR 12.32, p < 0.0001). A similar association was not found in white participants.Conclusions:This study demonstrated potential protective effects of rare and moderate alcohol consumption on ICH risk. Heavy alcohol consumption was associated with increased ICH risk. Race/ethnicity was a significant factor in alcohol-associated ICH risk; heavy alcohol consumption in black and Hispanic participants poses significant nonlobar ICH risk.

Background and Purpose— Computed tomographic angiography and conventional angiography provide timely vascular anatomic information in patients with stroke. However, iodinated contrast dye may cause acute kidney injury (AKI). Within a large, biracial population, we examined in-hospital incidence of new or worsening kidney disease in patients with stroke and its association with administration of intravenous dye. Methods— All adult residents of the Greater Cincinnati/Northern Kentucky region with acute ischemic stroke or intracerebral hemorrhage who presented to an emergency department in 2010 were included. Prevalence of unsuspected kidney disease at the time of emergency department presentation and the incidence of AKI after admission in 2 groups of patients—those who did and those who did not receive intravenous dye—were determined. Results— In 2010, 2299 patients met inclusion criteria (89% ischemic stroke and 11% intracerebral hemorrhage); mean age 69 years (SD 15), 22% black, and 54% women. Among these patients, 37% had kidney disease at baseline, including 22% (516/2299) in whom this was unsuspected. Two percent (2%; 15/853) of patients with baseline kidney disease developed AKI during the hospital stay. Of those with no baseline kidney disease, 1% (14/14 467) developed AKI. There was no association between dye administration and new or worsening kidney disease. Conclusions— Although 22% of patients in the Greater Cincinnati/Northern Kentucky stroke population had unsuspected kidney disease, the incidence of new or worsening kidney disease was low, and AKI was not associated with dye administration. These findings confirm single-center reports that the risk of severe renal complications after contrast dye is small.

Background and Purpose— Sex differences in stroke incidence over time were previously reported from the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study). We aimed to determine whether these differences continued through 2015 and whether they were driven by particular age groups. Methods— Within the GCNKSS population of 1.3 million, incident (first ever) strokes among residents ≥20 years of age were ascertained at all local hospitals during 5 periods: July 1993 to June 1994 and calendar years 1999, 2005, 2010, and 2015. Out-of-hospital cases were sampled. Sex-specific incidence rates per 100 000 were adjusted for age and race and standardized to the 2010 US Census. Trends over time by sex were compared (overall and age stratified). Sex-specific case fatality rates were also reported. Bonferroni corrections were applied for multiple comparisons. Results— Over the 5 study periods, there were 9733 incident strokes (56.3% women). For women, there were 229 (95% CI, 215–242) per 100 000 incident strokes in 1993/1994 and 174 (95% CI, 163–185) in 2015 ( P P Conclusions— Overall stroke incidence decreased from the early 1990s to 2015 for both sexes. Future studies should continue close surveillance of sex differences in the 20- to 44-year and ≥85-year age groups, and future stroke prevention strategies should target strokes in the young- and middle-age groups, as well as intracerebral hemorrhage.

OBJECTIVE: We aimed to identify risk factors for seizures after intracerebral hemorrhage, and to validate the prognostic value of the previously reported CAVE score (0–4 points: cortical involvement, age 10 mL, and early seizures within 7 days of hemorrhage). PATIENTS AND METHODS: Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) was a prospective study of spontaneous intracerebral hemorrhage. We included patients who did not have a prior history of seizure and survived to discharge. Univariate analysis and multiple logistic regression modeling were used to identify risk factors for seizure. RESULTS: From 2010 to 2015, 3,000 cases were recruited, and 2,507 patients were included in this study. Seizures after hospital discharge developed in 77 patients (3.1%). Patients with lobar (cortical) hemorrhage (OR 3.0, 95% CI 1.8–5.0), larger hematoma volume (OR 1.5 per cm(3), 95% CI 1.2–2.0), and surgical evacuation of hematoma (OR 2.6, 95% CI 1.4–4.8) had a higher risk of late seizure, and older patients had a lower risk (OR 0.88 per 5-year interval increase, 95% CI 0.81–0.95). The CAVE score was highly associated with seizure development (OR 2.5 per unit score increase, 95% CI 2.0–3.2, p

Background: The risk of intracerebral hemorrhage (ICH) with hypertension (HTN) is well documented, with prior studies showing that HTN is the most important risk factor associated with ICH. Prior studies have shown that while the prevalence of HTN increases with age, the odds ratio (OR) of HTN for non-lobar ICH is greater earlier in life. We have previously found a lack of Apolipoprotein E allele association with lobar ICH in minority populations. Here we seek to determine if, similar to non-lobar ICH, the odds ratio of HTN for lobar ICH is greater at an earlier age. Methods: The Ethnic/Racial Variations of ICH (ERICH) study is a prospective multicenter case-control study of ICH among whites, blacks, and Hispanics. Cases were enrolled from 42 sites. Controls matched to cases 1:1 by age (±5 years), sex, ethnicity/race, and metropolitan area were identified by random-digit dialing. Participants were interviewed to determine history of HTN. Participants were divided into age groups based on ethnicity-specific quartiles. Cases in each ethnic/age group were compared to controls using logistic regression (i.e., cases and controls unmatched). ORs were calculated to show the risk of lobar ICH associated with HTN by quartile. Results: Overall, 917 lobar ICH cases and 932 controls were included. The Table shows the multivariable OR. ORs were highest in the youngest age quartile across all races (6.47 for blacks, 5.72 for Hispanics and 2.74 for whites). HTN produced a significant increase in risk for the youngest two quartiles in blacks and Hispanics, but only the youngest quartile in whites. However, the age of the lowest quartile in whites was equivalent to the bottom two quartiles in minorities. Discussion: Similar to non-lobar ICH, HTN earlier in life bears a greater risk of lobar ICH than later in life and this risk is across a greater range in disproportionately affected minorities. Research into how new onset or early life HTN leads to disproportionate risk compared to late life is needed.

Background: We previously reported an increased incidence of stroke in the population with diabetes. This was particularly pronounced in those under 65 years of age. With guidelines now including glycemic monitoring during hospitalization, we examined incidence attributable to diabetes in 2010 and 2015. Methods: Ischemic strokes in the 5-county Greater Cincinnati/Northern Kentucky region were ascertained, then physician verified, at all 15 area hospitals using ICD-9 codes 430 to 436 or ICD10 codes I60 to I68. First ever ischemic strokes in patients aged 20 years and older were included in this analysis. Population age-specific rates of diabetes were estimated using the 2009-2010 and 2015-2016 NHANES databases, then applied to local population numbers, extracted from the US Census Bureau website, to estimate the denominator for calculation of incidence rates. Incidence rates were adjusted by age race and sex, as appropriate, to the 2010 US population. Diabetes was defined as reported in the electronic medical record or glycohemoglobin A1c &gt 6.4% during hospitalization. Results: There were a total of 4141 ischemic strokes; 55% female and 22% black. Stroke rates continue to be substantially higher in those with diagnosed diabetes, than those without diabetes overall and for those less than 65 years in both time periods, as well as those 65 years and older except for the black population in 2010. Racial disparities continue in both the less than 65 and 65 years and older age groups. Stroke rates were higher for Blacks in the less than 65 year age group for those both with and without diabetes; with risk ratios ranging from 1.3 to 2.7. Of note the stroke rate has decreased between 2010 and 2015 for those with diabetes Conclusions: The population with diabetes continues to be at increased risk of stroke, especially in those less than 65 years of age and those of black race.

Background and Purpose— Patients with intracerebral hemorrhage (ICH) and atrial fibrillation (AF) are at risk for ischemic events. While risk calculators (CHA 2 DS 2 -VASc and HAS-BLED) have been validated to assess risk for ischemic stroke and major bleeding in AF patients, decisions about anticoagulation must consider the net clinical benefit of anticoagulation. Furthermore, stroke and bleeding risk are highly correlated, making decisions more difficult. Methods— We examined patients in the GERFHS III study (Genetic and Environmental Risk Factors for Hemorrhagic Stroke)—a population-based retrospective study of spontaneous ICH patients without a structural or traumatic cause in the Greater Cincinnati/Northern Kentucky region between July 2008 and December 2012. CHA 2 DS 2 -VASc and HAS-B(L)ED (minus L because labile international normalized ratio was unavailable) scores were calculated for ICH patients with AF. Using a Markov state transition model, we estimated net clinical benefit of anticoagulation relative to no treatment in quality-adjusted life years (QALYs). We defined minimal clinically relevant benefit as 0.1 QALYs. Results— Among 1186 cases of spontaneous ICH, 95 cases had AF and met our survival criteria. Within 1 year, 8 of 95 (8%) would be expected to have a major bleeding event on anticoagulation, and 5 of 95 (5%) of patients would be expected to have an ischemic stroke off anticoagulation. Sixty-eight of 95 (71%) patients would have higher risk for major bleeding than for ischemic stroke. Anticoagulation with directly acting anticoagulants would result in no clinically significant gain or loss in 73%. Roughly 12% would gain >0.1 QALYs, and 15% would lose >0.1 QALYs. Among patients receiving aspirin, most have no significant net clinical benefit or loss. Overall, anticoagulation of the entire cohort would result in an aggregate loss of 0.92 QALYs. Conclusions— Our analysis suggests that universal anticoagulation after ICH would be associated with a net loss of QALY. Additional factors should be considered before anticoagulating patients with AF after ICH. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00930280.

Introduction: Data from the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) through 2010 showed that over time, stroke incidence rates decreased to a greater extent in men than in women. We aimed to determine whether this difference continued through 2015 and whether the differences are driven by particular age groups. Methods: Within the GCNKSS population of 1.3 million, all incident strokes among residents ≥20 years old were ascertained at all local hospitals during 7/93–6/94 and calendar years 1999, 2005, 2010, and 2015. Out-of-hospital cases were sampled. Sex-specific incidence rates per 100,000 were adjusted for age and race, standardized to the 2010 U.S. Census. Trends over time by sex were compared (overall and age-stratified); a Bonferroni correction was applied for multiple comparisons. Results: In total over the five study periods, there were 9721 incident strokes (ischemic, ICH, and SAH); 56.4% were women. Incidence of ischemic strokes decreased from 254 (95%CI 236,272) in 1993/4 to 177 (95%CI 164,189) in 2015 among men (p Conclusions: Stroke incidence decreased between the early 1990s and 2015 for both sexes, contrary to previous data on trends through 2010 which demonstrated a significant decrease in men but not women. Temporal changes are being driven by the 65–84 year age group in both men and women, as well as the ≥ 85 age group in men. Future prevention strategies should target young and middle age adults for both sexes as well as those over 85 for women.

Background: Cerebellar lesions reportedly account for 2-7% of acute infarct visits, but this may be an underestimate since prior studies were not population-based or from the modern imaging era. Cerebellar symptoms are also often nonspecific such that increased MRI use might lead to a higher proportion of stroke due to cerebellar lesions. Details about presenting features of cerebellar infarcts and baseline medication use are also not well known. Methods: We used the 2010 Greater Cincinnati/Northern Kentucky Stroke Study. Strokes were identified by screening ICD9 codes 430-436 and physician verification. Infarct location was categorized as isolated cerebellar, mixed cerebellar (cerebellar plus ≥1 other location), or non-cerebellar. Isolated dizziness was defined as dizziness/vertigo without other focal symptoms. Atherosclerotic cardiovascular disease (ASCVD) 10-year risk scores were calculated. Descriptive statistics and multivariable logistic regression were used to compare infarct categories. Results: Isolated cerebellar lesions occurred in 4.6% (90/1940; 95% CI, 3.7%-5.7%) of infarct events. An additional 4% (77/1940; 95%CI, 3.1%-4.9%) were mixed cerebellar infarcts. Mixed cerebellar infarcts had clinical characteristics more similar to non-cerebellar events than to cerebellar events. The multivariable model found an association of isolated cerebellar infarct with low NIHSS (odds ratio [OR] 2.3, 95% CI 1.1-4.8) and any dizziness/vertigo (OR 5.1, 95% CI, 2.4-10.6), but not with isolated dizziness/vertigo, age, or sex. Median ASCVD scores were high in all infarct categories (21, interquartile range [IQR] 9-35 for isolated cerebellar; 32, IQR 15-42 for mixed cerebellar; 31, IQR 16-52 for all others). Both cerebellar and non-cerebellar strokes had a high frequency of baseline antiplatelet or anticoagulant use (52.1% vs 56.2%), whereas baseline statin therapy was less common in isolated cerebellar infarcts (34.1% vs 43.8%). Conclusions: This population-based study during the modern imaging era found that about 5% of stroke cases have isolated cerebellar infarcts and nearly 9% have any cerebellar infarct. Both cerebellar and non-cerebellar presentations have high baseline vascular risk and antiplatelet/anticoagulant use.

Objective: We sought to assess whether the proportion of stroke patients who utilized Emergency Medical Services (EMS) has changed over time in a population-based epidemiological study. Methods: Stroke and transient ischemic attack (TIA) patients were identified in a population of 1.3 million in the Cincinnati area from data in 1999, 2005, 2010, and 2015. Patient charts and EMS records were analyzed by research nurses and reviewed by study physicians. This analysis excluded strokes/TIAs that occurred while in a hospital, out of town, during EMS transport, or at unknown location. Patients with unknown EMS utilization, stroke severity, baseline pre-stroke disability, race, stroke type, or under age 18 were excluded. Proportion of EMS utilization by stroke patients was calculated and Cochran-Armitage Trend Test was used to analyze trends in EMS utilization over time. Multivariable logistic regression was used to determine the association between age, race, sex, prior stroke, stroke type, where the stroke occurred, stroke severity, and pre-stroke disability with EMS use. Results: In 1999, 2005, 2010 and 2015, 2968 of 3860, 2900 of 3643, 3010 of 3503, and 3327 of 3767 stroke cases were included, respectively. EMS use by stroke patients did not change significantly over time (52%, 51%, 52%, 53%, p=0.12 for trend). In 1999 and 2015, age, pre-stroke disability, stroke severity, hemorrhagic stroke and stroke occurring at work were significantly associated with EMS use. Race, sex, and prior stroke were not. Slight variation in associations occurred in 2005 and 2010, with stroke at work not reaching significance in 2005 and 2010, and pre-stroke disability not reaching significance in 2005. Conclusion: EMS use by stroke patients in our population did not change from 1999 to 2015. With the recent advances in treatment options for stroke, novel and effective approaches to increase EMS use are warranted.

Background and Purpose Acute ischemic stroke (AIS) patients may benefit from endovascular thrombectomy (EVT) up to 24 h since last known normal (LKN). Advanced imaging is required for patient selection. Small or rural hospitals may not have sufficient CT technician and radiology support to rapidly acquire and interpret images. We estimated transfer rates using non-contrast head CT and stroke severity to select patients to be transferred to larger centers for evaluation. Methods We identified all AIS among residents of the study region in 2010. Only cases age ≥ 18 with baseline mRS 0–2 that presented to an ED were included. Among cases that presented between 6 and 24 h from LKN, those without evidence of acute infarct on head CT and with initial NIHSS ≥6 or ≥ 10 were identified. Results Of 1359 AIS cases, 448 (33.0%) presented between 6 and 24 h, of which 383 (85.5%) showed no evidence of acute infarct on CT. Of cases with no acute infarct on CT, 89/383 (23.2%) had NIHSS ≥6, of which 66 (74.2%) initially presented to a hospital without thrombectomy capabilities; and 51/383 (13.3%) had NIHSS ≥10, of which 40 (78.4%) presented to a non-thrombectomy hospital. Conclusions In our population, 40–66 AIS patients annually (0.8–1.3/week, or 3–5 patients/100,000 persons/year) may present to non-thrombectomy hospitals and need to be transferred using non-contrast CT and stroke severity as screening tools. Such an approach may sufficiently mitigate the impact of delays in treatment on outcomes, without overburdening the referring nor accepting hospitals.

Background and Purpose— In this study, we aim to investigate the association of computed tomography–based markers of cerebral small vessel disease with functional outcome and recovery after intracerebral hemorrhage. Methods— Computed tomographic scans of patients in the ERICH study (Ethnic and Racial Variations of Intracerebral Hemorrhage) were evaluated for the extent of leukoaraiosis and cerebral atrophy using visual rating scales. Poor functional outcome was defined as a modified Rankin Scale (mRS) of ≥3. Multivariable logistic and linear regression models were used to explore the associations of cerebral small vessel disease imaging markers with poor functional outcome at discharge and, as a measure of recovery, change in mRS from discharge to 90 days poststroke. Results— After excluding in-hospital deaths, data from 2344 patients, 583 (24.9%) with good functional outcome (mRS of 0–2) at discharge and 1761 (75.1%) with poor functional outcome (mRS of 3–5) at discharge, were included. Increasing extent of leukoaraiosis ( P for trend, 0.01) and only severe (grade 4) global atrophy (odds ratio, 2.02; 95% CI, 1.22–3.39, P =0.007) were independently associated with poor functional outcome at discharge. Mean (SD) mRS change from discharge to 90-day follow-up was 0.57 (1.18). Increasing extent of leukoaraiosis ( P for trend, 0.002) and severe global atrophy (β [SE], −0.23 [0.115]; P =0.045) were independently associated with less improvement in mRS from discharge to 90 days poststroke. Conclusions— In intracerebral hemorrhage survivors, the extent of cerebral small vessel disease at the time of intracerebral hemorrhage is associated with poor functional outcome at hospital discharge and impaired functional recovery from discharge to 90 days poststroke.

Background and Purpose— Clinical trials in spontaneous intracerebral hemorrhage (ICH) have used volume cutoffs as inclusion criteria to select populations in which the effects of interventions are likely to be the greatest. However, optimal volume cutoffs for predicting poor outcome in deep locations (thalamus versus basal ganglia) are unknown. Methods— We conducted a 2-phase study to determine ICH volume cutoffs for poor outcome (modified Rankin Scale score of 4–6) in the thalamus and basal ganglia. Cutoffs with optimal sensitivity and specificity for poor outcome were identified in the ERICH ([Ethnic/Racial Variations of ICH] study; derivation cohort) using receiver operating characteristic curves. The cutoffs were then validated in the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) by comparing the c-statistic of regression models for outcome (including dichotomized volume) in the validation cohort. Results— Of the 3000 patients enrolled in ERICH, 1564 (52%) had deep ICH, of whom 1305 (84%) had complete neuroimaging and outcome data (660 thalamic and 645 basal ganglia hemorrhages). Receiver operating characteristic curve analysis identified 8 mL in thalamic (area under the curve, 0.79; sensitivity, 73%; specificity, 78%) and 18 mL in basal ganglia ICH (area under the curve, 0.79; sensitivity, 70%; specificity, 83%) as optimal cutoffs for predicting poor outcome. The validation cohort included 834 (84%) patients with deep ICH and complete neuroimaging data enrolled in ATACH-2 (353 thalamic and 431 basal ganglia hemorrhages). In thalamic ICH, the c-statistic of the multivariable outcome model including dichotomized ICH volume was 0.80 (95% CI, 0.75–0.85) in the validation cohort. For basal ganglia ICH, the c-statistic was 0.81 (95% CI, 0.76–0.85) in the validation cohort. Conclusions— Optimal hematoma volume cutoffs for predicting poor outcome in deep ICH vary by the specific deep brain nucleus involved. Utilization of location-specific volume cutoffs may improve clinical trial design by targeting deep ICH patients that will obtain maximal benefit from candidate therapies.

OBJECTIVE: Previously we reported that ischemic stroke incidence is declining over time for men but not women. We sought to describe temporal trends of sex differences in incidence of transient ischemic attack (TIA) within the same large, biracial population. METHODS: Among the population of 1.3 million in the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS) region, TIAs among area residents (≥20 years old) were identified at all local hospitals. Out of hospital cases were ascertained using a sampling scheme. First-ever cases and first within each study period for a patient were included in incidence rates. All cases were physician-adjudicated. Incidence rates (during 7/93-6/94 and calendar years 1999, 2005, and 2010) were calculated using the age-, race-, and sex-specific number of TIAs divided by the GCNKSS population in that group; rates were standardized to the 2010 U.S. population. T-tests with Bonferroni correction were used to compare rates over time. RESULTS: There were a total of 4746 TIA events; 53% were female, and 12% were black. In males, incidence decreased from 153 (95%CI 139-167) per 100,000 in 1993/4 to 117 (95%CI 107-128) in 2010 (p0.05). CONCLUSIONS: Within the GCNKSS population, TIA incidence decreased significantly over time in males but not females, data which parallels trends in ischemic stroke in the GCNKSS over the same time period. Future research is needed to determine if these sex differences in incidence over time continue past 2010.

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.

Background Although statin therapy is associated with reduced stroke and mortality risk, some studies report that higher lipid levels are associated with improved outcomes following ischemic stroke. Aims We examined the association of hyperlipidemia (HLD) combined with statin therapy on all-cause mortality in stroke patients. Methods All stroke patients in the Greater Cincinnati Northern Kentucky region of ∼1.3 million were identified using ICD-9 discharge codes in 2005 and 2010. Stroke patients with and without HLD were categorized based on their reported statin use at baseline or discharge into three groups: no-HLD/no-statins, HLD/no-statins, and HLD/on-statins. Cox proportional hazards model was used to estimate the risk of mortality at 30 days, 1 year, and 3 years poststroke. Results Overall, 77% (2953) of the 3813 ischemic stroke patients were diagnosed with HLD and 72% ( n = 2123) of those patients were on statin medications. The mean age was 70.0 ± 14.6 years, 56% were women, and 21% were black. In adjusted analyses, the HLD/no-statins group showed 35% (adjusted hazard ratio (aHR) = 0.65, 95% CI: 0.46–0.92), 27% (aHR = 0.73, 95% CI: 0.59–0.90), and 17% (aHR = 0.83, 95% CI: 0.70–0.97) reduced risk of mortality at 30 days, 1 year, and 3 years, respectively, poststroke, compared with no-HLD/no-statins group. The HLD/on-statins group showed an additional 17% significant survival benefit at 3 years poststroke compared with HLD/no-statins group. Conclusions A diagnosis of HLD in ischemic stroke patients is associated with reduced short- and long-term mortality, irrespective of statin use. Statin therapy is associated with significant, additional long-term survival benefit.

Introduction: We previously reported that the incidence of stroke was decreasing for whites but stable for blacks from 1993/94 to 2005. We sought to describe recent temporal trends and racial disparities in stroke incidence within our large, bi-racial population, by including 2010 and preliminary data from 2015. Methods: The Greater Cincinnati/Northern Kentucky region includes two southern Ohio and three Northern Kentucky counties on the Ohio River, a population of 1.3 million representative of the US population in terms of sociodemographics and percent black race. Our study ascertained all hospitalized strokes that occurred in the population between 7/1/93 and 6/30/94 and in calendar years 1999, 2005, 2010 and 2015. For 2015, nursing review of medical records is complete but physician review is not; thus 2015 rates are preliminary. The denominator for the calculation of incidence rates (in those aged ≥20 years) was estimated from the U.S. Census Bureau website (www.census.gov). The 95% confidence intervals (CI) for the incidence rates were calculated assuming a Poisson distribution. Rates are age, sex, and race adjusted, as appropriate, and standardized to the 2010 U.S. population. Results: First-ever stroke incidence rates stratified by subtype, race, and study period are presented in the Table. We project that stroke incidence did not significantly change in 2015 vs. 2010 for either blacks or whites, regardless of stroke subtype. Blacks have a substantially higher incidence of stroke compared with whites in all study periods, without significant change in disparity over time. Discussion: In contrast to the significant decline in stroke incidence among whites from 1993-94 to 2005, we did not observe a statistically significant decrease in 2010 and 2015. This may be due to true stabilization of rates over time, or less statistical power to detect smaller declines. The substantial black/white racial disparity in stroke incidence has not changed over time.

Background: Both intraventricular hemorrhage (IVH) and white matter lesion (WML) severity are associated with higher rates of death and disability among cases of intracerebral hemorrhage (ICH). Prior reports suggest higher WML burden is associated with propensity of IVH. However, those analyses were not stratified by location. Our objective was to investigate the hypothesis that a higher degree of WML would be associated with a higher risk of IVH after controlling for ICH location. Methods: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) III study was a prospective study of hemorrhagic stroke in the Greater Cincinnati/Northern Kentucky region. We utilized the interviewed cohort from the study and systematically graded WML using the Van Swieten Scale (0-4) and presence or absence of IVH in baseline head CT scans. Additional variables included ICH volume, location of ICH and vascular risk factors. We used multiple logistic regression with backward elimination to adjust for relevant covariates. Results: Among the included 426 ICH patients (mean± SD age 71.2± 13.8; 49% females), 161 (38%) had presence of IVH. In patients with IVH, the proportion of severe WML (39.7%) was significantly higher compared with patients without IVH (27.2%) (p=0.0044). The median volume of ICH was 14.4 mL (IQR, 4.9-46.3) in patients with IVH as compared with 8.9 ml (IQR, 2.6-20.8) in patients without IVH (p Conclusion: Moderate to severe white matter lesions are a risk for intraventricular hemorrhage. Further studies are needed to determine if greater severity of IVH or subsequent rupture into IVH are associated with higher grades of WML.

Introduction: Blacks in the U.S. face twice the risk of ischemic stroke as whites, and this disparity is not fully explained by established stroke risk factors. Although atrial fibrillation (AF) is a major risk factor for stroke, blacks are less often diagnosed with AF than whites. It is unclear whether this paradox exists because AF is less thoroughly ascertained in blacks compared to whites or because blacks have less predisposing substrate and thus a truly lower risk of AF. Hypothesis: Based on our prior work, we hypothesized that black patients with ischemic stroke less often have left atrial enlargement, a major predisposing factor for AF. Methods: We compared left atrial size in black versus white patients in the Greater Cincinnati/Northern Kentucky Stroke Study, a study of racial disparities in stroke incidence in a nationally representative population of 1.3 million. We obtained reports of echocardiograms performed for stroke evaluation among patients in the 2010 and 2015 study periods. Patients with known AF or atrial flutter were excluded. Investigators blinded to patients’ characteristics abstracted left atrial diameter from echocardiogram reports. Linear regression was used to examine the association between race and left atrial diameter after adjustment for demographics, body mass index, and comorbidities. Results: Among 2,980 cases of ischemic stroke without AF, the median age was 66 years, 52% were female, and 30% were black. The overall mean left atrial diameter was 3.65 (±0.69) cm. Despite a higher burden of vascular risk factors and comorbidities, blacks had significantly smaller left atrial diameters (mean difference, -0.10 cm; 95% CI, -0.04 to -0.17 cm). This difference persisted after adjustment for demographics, comorbidities, and body mass index (adjusted mean difference, -0.15 cm; 95% CI, -0.09 to -0.21 cm). Conclusions: In a population-based sample, we found that black patients with ischemic stroke had smaller left atrial size than white patients. Our results suggest that the paradox of greater stroke risk but lower AF risk in blacks compared with whites at least partly stems from a lesser degree of AF substrate in blacks.

Introduction: Anticoagulant therapy after intracerebral hemorrhage (ICH) in patients with atrial fibrillation or deep vein thrombosis has been associated with a marked reduction of death. Prevention of ischemic stroke could explain this reduction. We sought to describe the causes of death after discharge and beyond 30 days in a longitudinal follow-up of a multi-racial/ethnic cohort of ICH. We hypothesized that recurrent ICH and ischemic stroke are the most common cause of death after ICH. Methods: The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study was a prospective, multi-center, case-control study of ICH among whites, blacks, and Hispanics. Subjects previously in the ERICH study were approached for enrollment in the Longitudinal Follow-up of ICH Survivors (ERICH-L) study. A standardized research interview was completed over the phone and 959 contacts were made with participants and surrogates to capture outcomes of interest at 6-month intervals, including information on ICH recurrence, ischemic stroke, cognitive performance, and cause of death. The median follow-up was 4.3 years with an IQR of 3.2-5.4. The cause of death categories were ICH, cardiac, ischemic CVA, other, cancer, pulmonary, renal, endocrine, accidents, infection, dementia and unknown. Results: There were 180 deaths (18.8%) reported by surrogates contacted in the ERICH-L study. Of those, 63 causes of death were unknown or considered unverifiable. The most common cause of death reported was decline from the index ICH (32.7%). The next most common cause of death was cardiac (14%), other (12.1%), infection (11.2%), cancer (10.3%) and ischemic stroke (1.9%). Some examples reported as other are liver failure, old age, myelodysplastic syndrome, suicide and Parkinson’s Disease. Recurrent ICH occurred in 4 out of 107 known causes of death. By year 5, cardiac causes surpassed ICH as the cause of death. Conclusion: Cardiac causes of death were more common than either recurrent ICH or ischemic stroke, surpassed only by decline from the index ICH. Future efforts to prevent causes of death after ICH should address cardiac disease and risk factors. This finding may explain the effect of restarting anticoagulant or antiplatelet therapy and improved mortality.

Introduction: The REGARDS study previously reported a lack of racial disparity in recurrent ischemic stroke (IS) events, despite large racial differences in incident IS. We sought to evaluate recurrent stroke rates at 1 year after an index ischemic (IS) or hemorrhagic (ICH and SAH) stroke or TIA within a large, biracial population representative of the US in terms of % blacks and sociodemographics with a large number of index events Methods: The Greater Cincinnati/Northern Kentucky Stroke Study ascertained all hospitalized strokes and TIAs among residents of a 5-county population of 1.3 million in 7/1/14-12/31/14 (blacks only) and 2015 (all residents), as well as recurrent strokes (but not TIAs) in 2016. One year risk of recurrent stroke was estimated by Kaplan-Meier analysis. Association between recurrent stroke and demographics/risk factors was assessed by proportional hazards analysis. Results: Among the 2014-15 cases, there were 3883 index events (2512 IS, 374 ICH, 92 SAH, 900 TIA, 5 unknown type). Median age was 70 (IQR 59, 81); 27% were black and 54% female. Recurrent events within 12 months of the index event occurred in 319 patients (276 IS, 38 ICH, 5 SAH). Those with recurrence were more likely black than those without (34% vs 27%, p Discussion: The risk of recurrent stroke was significantly associated with index event type and stroke risk factors (hypertension, diabetes, smoking, and prior stroke). Black race was not a significant independent predictor of recurrent stroke after adjusting for other known stroke risk factors.

Introduction: The NIH StrokeNet trial network aims to improve recruitment and retention into stroke clinical trials. In addition to StrokeNet infrastructure, a population-based feasibility assessment is performed prior to submission to NIH. We sought to describe the impact of this assessment on the design and recruitment efficiency of the DEFUSE 3 trial, the first trial to be proposed and completed entirely within NIH StrokeNet. Methods: We identified all ischemic stroke (IS) cases in the region in 2005 by screening all local hospital ICD-9 codes 430-436 among residents of the Greater Cincinnati/Northern Kentucky (GCNK) region, a biracial population of 1.3 million through chart abstraction and physician review. Initial proposed, and final revised DEFUSE 3 trial entry criteria were analyzed for population-based eligibility. Results: DEFUSE 3 is an acute reperfusion ischemic stroke (IS) trial conducted at 38 US centers between 5/16-5/17. Initial inclusion/exclusion criteria proposed by trial PIs predicted that 2.4% (46 of 1843 in 2005) of IS patients would be eligible for DEFUSE-3. After criteria revision, this increased to 4.0% (74/1843). Four exclusion criteria were changed by study PIs after receiving feedback: upper age limit, baseline disability, time since last seen normal, and NIHSS (Table). Overall, 57% (104/182) of enrolled patients qualified via the broadened study entry criteria. In subsequent implementation, the trial randomized 0.47 patients per site per month which was nearly twice the expected enrollment rate. Conclusion: Feedback from formal epidemiologic feasibility assessment to trial investigators during multicenter clinical trial design led to a broadening of entry criteria, and more than half of eventually enrolled patients were eligible only because of the expanded criteria. Iterative trialist-epidemiologist interaction is a promising approach to improve multicenter clinical trial planning and efficient study conduct.

Introduction: Previous data have shown worse post-stroke outcomes in women than men based on non-patient centered outcomes (modified rankin score (mRS)) obtained via patient contact. Our aim was to compare sex differences in post-stroke outcomes in a population-based cohort using patient-centered outcome measures obtained from the electronic medical record (EMR). Methods: Patients with ischemic stroke (IS) who presented to a single healthcare system (4 hospitals and outpatient facilities) in Northern Kentucky during 1/2015-12/2015, a subsample of the Greater Cincinnati Northern Kentucky Stroke Study, were included. Those who died prior to study time points were excluded. Cases of IS were ascertained by trained study nurses using ICD codes and EMR review. Outcomes (mRS and quality of life (EQ5D)) were estimated from EMR, a method previously shown to have good interrater agreement with telephone follow-up. EQ5D measures health-related quality of life across 5 dimensions. Utility weighted mRS (UW-mRS) were calculated by applying validated weights to mRS. Outcomes at 3- and 6-months were compared by sex using ordinal logistic regression for mRS and linear regression for UW-mRS and EQ5D, adjusted by demographics, pre-stroke mRS, stroke severity, and co-morbidities. Results: We included 382 cases; 51% were women, 94% were white. Women were older (median (IQR) 71 (61-81) vs. 66 (57-77)) than men, but pre-stroke mRS was similar (median (IQR) 1 (0-3) vs. 1 (0-2)). NIHSS was similar by sex (median 3 IQR (1-6) vs. 2 (1-5)). After adjustment, 3- and 6-month outcomes were similar by sex. Conclusions: In our cohort, sex differences in unadjusted outcomes may be related to age, pre-stroke functional status, co-morbidities, and depression, as differences were not present in adjusted models. Relatively minor strokes in our cohort may also explain similar outcomes by sex. Future studies should strive to identify intervenable targets to improve patient-centered outcomes post-stroke.

Introduction: Risk of lobar and non-lobar intracerebral hemorrhage (ICH) varies among blacks, whites and Hispanics. We sought to determine whether these differences could be due to variability in the effects of Apolipoprotein E (APOE) epsilon (ε) alleles, the most potent genetic risk factor for ICH. Methods: Primary ICH cases and controls were collected from US and European sites contributing to the International Stroke Genetic Consortium (ISGC). We meta-analyzed the effects of APOE allele status on ICH risk applying a two-stage clustering approach based on race/ethnicity and the contributing study. Models were adjusted for age, sex, history of hypertension, hypercholesterolemia, warfarin, statin and antiplatelet use, smoking and alcohol use. A propensity score analysis was used to model the influence of APOE against the burden of hypertension across races/ethnicities. Results: 13,124 subjects (54.5% male, median age 66 years) were included. In whites, APOE ε2 (odds ratio (OR)=1.85, 95% confidence interval (CI)=1.27-2.69, p Conclusion: APOE ε4 and ε2 alleles affect lobar ICH risk variably by race and ethnicity. Associations are confirmed in whites but can be shown in Hispanics only when the excess burden of hypertension is propensity score-matched. Further studies are needed to explore interactions between APOE alleles and environmental exposures that vary by race and ethnicity in representative populations at risk for ICH.

Introduction: Previously, we reported that stroke incidence in the young (age < 55) significantly increased in both blacks and whites over four study periods between 1993 and 2010. Here we further describe this temporal trend, adding data from 2015. Methods: The Greater Cincinnati/Northern Kentucky region includes 2 southern Ohio and 3 contiguous Northern Kentucky counties (estimated population, 1.3 M). Our study determined first-ever hospital-ascertained strokes that occurred in the population from 7/1/93 to 6/30/94 and in calendar years 1999, 2005, 2010, and 2015 by screening ICD9 (and ICD10, in 2015) codes of all inpatient and emergency department visits. Cases were abstracted by study nurses and verified by study physicians. Results for 2015 are preliminary. The denominator for the calculation of incidence rates (in those aged ≥20 years) was extracted from the U.S. Census Bureau website (www.census.gov). Age- and race -specific incidence rates with 95% confidence intervals (CI) were calculated assuming a Poisson distribution. We tested for differences in age trends using Student’s t-test, X 2 , and Poisson regression as appropriate. Results: The mean± SD age of stroke was 71.3±13.6 in 1993-94, 70.9±14.4 in 1999, 68.4±15.5 in 2005, 68.5±15.6 in 2010, and 68.7±15.4 in 2015 (p Discussion: The disturbing trend of increasing stroke in the young (age < 55) has leveled off slightly since 2010 but is still of great public health significance as younger strokes carry the potential for greater lifetime burden of disability. Further study is needed to determine the reasons for these results, including examination of race-specific trends.

Introduction: Previous studies have shown biases in screening for toxicologic substances among stroke patients but have limited generalizability. Our objective was to investigate predictors of the use of drug screens among stroke patients in a large population based study. Methods: The Greater Cincinnati Northern Kentucky Stroke Study is a population-based study of stroke cases ascertained from a biracial population of 1.3 million people in a 5-county region of southern Ohio/northern Kentucky. All hospital ascertained cases of stroke (ischemic (IS), transient ischemic attack (TIA), hemorrhagic (ICH), subarachnoid hemorrhage (SAH)), occurring during calendar year 2015 were included. Trained study nurses abstracted data on whether a drug screen was ordered (between emergency department (ED) presentation and hospital discharge). Screening tests for alcohol were not included. Multivariable logistic regression was used to identify predictors of use of a drug screen. Potential predictors were patient sex, age, race, select comorbidities, smoking status, stroke severity (NIHSS), treatment location and stroke type. Results: Of 3865 stroke cases (53.8% women, 20.8% black, mean age 69.7(14.8) years), 12.0% had a drug screen performed. Adjusted, black race (aOR 1.93 95%CI 1.52-2.44), current smoking (aOR 1.97 95%CI 1.58-2.47), higher NIHSS (aOR 1.22 95%CI 1.15-1.28 per 5 unit increase) and being treated in an academic ED (aOR 2.04, 95%CI 1.62-2.55) increased the likelihood of a drug screen, while female gender (aOR 0.75 95%CI 0.60-0.93) and older age (aOR 0.61 per 10 years, 95%CI 0.56-0.66) decreased the likelihood. Conclusions: In a large population based study of stroke patients, drug screens were more likely to be ordered in men, blacks, smokers, younger patients, and those seen in academic EDs. It is unknown whether these trends are similar among hospitalized patients with other diagnoses. Additionally, current evidence suggests that such differential testing may lead to missed counselling opportunities in those not tested as well as lower likelihood of thrombolytic treatment in those who are tested. Future research should investigate the yield of such drug screens and explore whether guidelines in ordering drug tests could help to avoid testing biases.

Objective: To update trends on documented substance abuse among young adults (18-54 years old) with stroke within the Greater Cincinnati/Northern Kentucky Stroke Study population, to include preliminary results from 2015. Background: Substance abuse is associated with stroke. In our population, we previously reported increases in overall substance abuse, smoking history, and use of alcohol or drugs >Design/Methods: Using ICD-9 discharge codes 430-436, potential acute stroke events are identified among 18- to 55-year-old residents of the 5 county study region. Five one-year study periods are included (7/93-6/94, 1999, 2005, 2010, 2015). Study nurses abstract all events which then undergo physician review. We searched for trends in smoking history, illicit drug use, heavy alcohol consumption, overall substance abuse (current smoking, alcohol, and illicit drug), and urine/blood test positive for alcohol or illicit drugs at presentation. Results: There were 2220 stroke events (75 % ischemic). Sex and age distribution remained stable; however, percent black increased from 35% to 46% between 1993/94 and 2015, as did the proportion of ischemic strokes (74% to 77%). Current smoking and alcohol use remained stable while illicit drug use increased significantly overall and within the age subgroups of 18-34 years and 35-54 years (see table). Conclusions: Illicit drug use continues to increase among young adults with stroke. Even though the possibility of testing bias needs to be explored further, our reported results are likely an under estimation of true rates as there are no readily available tests for new designer drugs which have become more available since the early 2000’s. Future analysis will also focus on the relationship between our findings and the U.S. opioid epidemic.

Introduction: Intracerebral hemorrhage (ICH) is the most severe subtype of stroke with a high mortality rate and majority of survivors suffering significant disability. The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study prospectively recruited 1000 white, 1000 black and 1000 Hispanic spontaneous ICH cases. Herein, we report the main results of the predictors of 3 month outcome after ICH. Hypothesis: We hypothesized that ICH Score variables of age, ICH volume, ICH location, presence of intraventricular hemorrhage (IVH), and presenting Glasgow Coma Scale would predict long-term disability in addition to prior validation of mortality. Methods: Between 2010-2015, cases were prospectively recruited with uniform phenotype definitions, centralized neuroimaging review and with telephone follow-up at 3 months. Apolipoprotein E genotyping was performed centrally. Individual characteristics were screened for association under a logistic regression model, 90-day mRS ≥ 4 versus 0-3, and those meeting P Results: The Table presents the prevalence/average of each variable entering the final multivariate model for association with poor (mRS 4-6) compared to good (mRS 0-3) outcome at 3 months. When analyses were repeated excluding withdrawal of care, overall Graeb (IVH) score fell out of the model (with presence of IVH replacing it) but the remaining variables were retained and in the same direction of effect. C-statistic for the multivariate model = 0.884 compared to 0.763 for ICH score alone (p=1.7E-22). Conclusion: ICH score elements were validated as predictive of 3 month outcome. Novel baseline characteristics such as white matter hyperintensity as well as subsequent clinical events that may affect outcomes were identified. Location specific results to be presented.

Introduction: Intracerebral hemorrhage (ICH) results in high mortality and high rate of disability among survivors. The effects of preexisting small vessel disease (SVD) on functional outcomes after ICH is uncertain and understanding manifestations of brain health such as white matter lesions (WML) and atrophy are a top priority for developing prognostic indicators. Our objective was to determine whether WML and brain atrophy is associated with functional outcomes in ICH patients. Hypothesis: We hypothesized that higher burden of WML and atrophy will have a poor outcome independent of age, ICH volume, ICH location, IVH, and presenting Glasgow Coma Scale (GCS) score. Methods: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) III study is a prospective study of hemorrhagic stroke in the Greater Cincinnati/Northern Kentucky region. We utilized the interviewed cohort from the study and systematically graded WML using the Van Swieten Scale (0-4) and measured brain atrophy (2 linear measurements) in baseline head CT scans. The outcome measures included modified Rankin Scale (mRS) at 3 months. Primary outcome was disability or death (mRS 3-6). Results: A total of 441 CT scans were graded; 48 patients were excluded due to missing mRS. Among the included 393 ICH patients (mean±SD age 71.5± 13.8; 48% females), old age, high ICH volume, low GCS score, severe WML (Van Swieten score 3-4), and atrophy were significantly associated with poor outcomes (mRS 3-6) in univariate analysis. In multivariate analysis, severe WML (p=0.039), atrophy (p= 0.0131), old age (p Conclusion: Poor brain health manifesting as cerebral SVD markers of WML and atrophy are simple and independent baseline predictors of poor outcome in acute ICH. Further study for inclusion into outcome measures such as ICH Score should be considered.

BACKGROUND: Intraventricular hemorrhage (IVH) and white matter lesion (WML) severity are associated with higher rates of death and disability in intracerebral hemorrhage (ICH). A prior report identified an increased risk of IVH with greater WML burden but did not control for location of ICH. We sought to determine whether a higher degree of WML is associated with a higher risk of IVH after controlling for ICH location. METHODS: Utilizing the patient population from two large ICH studies; the Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS III) Study and the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study, we graded WML using the Van Swieten Scale (0-1 for mild, 2 for moderate, and 3-4 for severe WML) and presence or absence of IVH in baseline CT scans. We used multivariable regression models to adjust for relevant covariates. RESULTS: Among 3023 ICH patients, 1260 (41.7%) had presence of IVH. In patients with IVH, the proportion of severe WML (28.6%) was higher compared with patients without IVH (21.8%) (p

Introduction: Intracerebral hemorrhage (ICH) is the most severe subtype of stroke. Its mortality rate is high, and the majority of survivors suffer significant disability. The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study prospectively recruited 1000 non-Hispanic white, 1000 non-Hispanic black, and 1000 Hispanic spontaneous ICH cases to study the epidemiology and genomics of ICH. Herein, we report the primary determinants of 3-month outcome after ICH in a large, multi-ethnic cohort. Methods: Between 2010 and 2015, cases were prospectively recruited with uniform data collection and phenotype definitions, centralized neuroimaging review, and telephone follow-up at 3 months. Individual characteristics were screened for association with 3-month outcome of modified Rankin Scale (mRS) ≥4 versus ≤3 under a logistic regression model, and those meeting P

ObjectiveAPOE ε2 and ε4 alleles have been associated with lobar intracerebral hemorrhage (ICH) in predominately white populations; we sought to evaluate whether this held true among black and Hispanic populations.MethodsThe Ethnic/Racial Variations of Intracerebral Hemorrhage study is a prospective, multicenter case-control study of ICH among white, black, and Hispanic participants. Controls were recruited to match cases based on age, ethnicity/race, sex, and geographic location. APOE genotyping and ICH location was determined blinded to clinical data.ResultsThere were 907 cases of lobar ICH and 2,660 controls with APOE results. Both APOE ε2 (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.1–2.0, p = 0.01) and APOE ε4 (OR 2.0, 95% CI 1.5–2.6, p < 1 × 10−4) were associated with lobar ICH among white participants. Among black participants, neither APOE ε2 (OR 1.0, 95% CI 0.7–1.5, p = 0.97) nor APOE ε4 (OR 1.0, 95% CI 0.7–1.4, p = 0.90) were independent risk factors for lobar ICH. Similarly, among Hispanic participants, neither APOE ε2 (OR 1.0, 95% CI 0.6–1.8, p = 0.89) nor APOE ε4 (OR 1.2, 95% CI 0.8–1.7, p = 0.36) were associated with lobar ICH. Hypertension was a significant risk factor for lobar ICH in all 3 racial/ethnic groups.ConclusionIn contrast to Caucasian patients, in which amyloid risk factors predominate in lobar ICH, we found that hypertension was the predominant risk factor for lobar ICH. While APOE alleles are a risk factor for lobar ICH in white patients, they appear to have a much lower effect in lobar ICH in African American and Hispanic American populations. This suggests APOE ε2 and APOE ε4 do not affect lobar ICH risk homogeneously across ethnic populations. In addition, hypertension has a prominent role in lobar ICH risk, particularly among minorities.

Background: We sought to determine whether a small pool of ancestry-informative DNA markers (AIMs) improves modeling of intracerebral hemorrhage (ICH) risk in heterogeneous populations, compared with self-identified race/ethnicity (SIRE) alone.Methods: We genotyped 15 preselected AIMs to perform principal component (PC) analysis in the ERICH study (a multi-center case-control study of ICH in whites, blacks, and Hispanics). We used multivariate logistic regression and tests for independent samples to compare associations for genetic ancestry and SIRE with ICH-associated vascular risk factors (VRFs). We then compared the performance of models for ICH risk that included AIMs and SIRE alone.Results: Among 4,935 subjects, 34.7% were non-Hispanic black, 35.1% non-Hispanic white, and 30.2% Hispanic by SIRE. In stratified analysis of these SIRE groups, AIM-defined ancestry was strongly associated with seven of the eight VRFs analyzed (p < 0.001). Within each SIRE group, regression of AIM-derived PCs against VRFs confirmed independent associations of AIMs across at least two race/ethnic groups for seven VRFs. Akaike information criterion (AIC) (6,294 vs. 6,286) and likelihood ratio test (p < 0.001) showed that genetic ancestry defined by AIMs achieved a better ICH risk modeling compared to SIRE alone.Conclusion: Genetically-defined ancestry provides valuable risk exposure information that is not captured by SIRE alone. Particularly among Hispanics and blacks, inclusion of AIMs adds value over self-reported ancestry in controlling for genetic and environmental exposures that influence risk of ICH. While differences are small, this modeling approach may be superior in highly heterogeneous clinical poulations. Additional studies across other ancestries and risk exposures are needed to confirm and extend these findings.

Objectives The objective of this study was to evaluate operational policies that may improve the proportion of eligible stroke patients within a population who would receive intravenous recombinant tissue plasminogen activator (rt-PA) and minimize time to treatment in eligible patients. Methods In the context of a regional stroke team, the authors examined the effects of staff location and telemedicine deployment policies on the timeliness of thrombolytic treatment, and estimated the efficacy and cost-effectiveness of six different policies. A process map comprising the steps from recognition of stroke symptoms to intravenous administration of rt-PA was constructed using data from published literature combined with expert opinion. Six scenarios were investigated: telemedicine deployment (none, all, or outer-ring hospitals only) and staff location (center of region or anywhere in region). Physician locations were randomly generated based on their zip codes of residence and work. The outcomes of interest were onset-to-treatment (OTT) time, door-to-needle (DTN) time, and the proportion of patients treated within 3 hours. A Monte Carlo simulation of the stroke team care-delivery system was constructed based on a primary data set of 121 ischemic stroke patients who were potentially eligible for treatment with rt-PA. Results With the physician located randomly in the region, deploying telemedicine at all hospitals in the region (compared with partial or no telemedicine) would result in the highest rates of treatment within 3 hours (80% vs. 75% vs. 70%) and the shortest OTT (148 vs. 164 vs. 176 minutes) and DTN (45 vs. 61 vs. 73 minutes) times. However, locating the on-call physician centrally coupled with partial telemedicine deployment (five of the 17 hospitals) would be most cost-effective with comparable eligibility and treatment times. Conclusions Given the potential societal benefits, continued efforts to deploy telemedicine appear warranted. Aligning the incentives between those who would have to fund the up-front technology investments and those who will benefit over time from reduced ongoing health care expenses will be necessary to fully realize the benefits of telemedicine for stroke care.

Objective 1) To develop a machine learning approach for detecting stroke cases and subtypes from hospitalization data, 2) to assess algorithm performance and predictors on real-world data collected by a large-scale epidemiology study in the US; and 3) to identify directions for future development of high-precision stroke phenotypic signatures. Materials and methods We utilized 8,131 hospitalization events (ICD-9 codes 430–438) collected from the Greater Cincinnati/Northern Kentucky Stroke Study in 2005 and 2010. Detailed information from patients’ medical records was abstracted for each event by trained research nurses. By analyzing the broad list of demographic and clinical variables, the machine learning algorithms predicted whether an event was a stroke case and, if so, the stroke subtype. The performance was validated on gold-standard labels adjudicated by stroke physicians, and results were compared with stroke classifications based on ICD-9 discharge codes, as well as labels determined by study nurses. Results The best performing machine learning algorithm achieved a performance of 88.57%/93.81%/92.80%/93.30%/89.84%/98.01% (accuracy/precision/recall/F-measure/area under ROC curve/area under precision-recall curve) on stroke case detection. For detecting stroke subtypes, the algorithm yielded an overall accuracy of 87.39% and greater than 85% precision on individual subtypes. The machine learning algorithms significantly outperformed the ICD-9 method on all measures (P value

Background Intracranial aneurysms more often occur in the same arterial territory within families. Several aneurysm locations are associated with specific circle of Willis variations. We investigated whether the same circle of Willis variations are more likely to occur in first-degree relatives than in unrelated individuals. Methods We assessed four circle of Willis variations (classical, A1-asymmetry, incomplete posterior communicating artery and fetal circulation) in two independent groups of families with familial aneurysms and ≥2 first-degree relatives with circle of Willis imaging on MRA/CTA. In each (index) family we determined the proportion of first-degree relatives with the same circle of Willis variation as the proband and compared it to the proportion of first-degree relatives of a randomly selected unrelated (comparison) family who had the same circle of Willis variation as the index family’s proband. Concordance in index families and comparison families was compared with a conditional logistic events/trials model. The analysis was simulated 1001 times; we report the median concordances, odds ratios (ORs), and 95% confidence intervals (95%CI). The groups were analysed separately and together by meta-analysis. Results We found a higher overall concordance in circle of Willis configuration in index families than in comparison families (meta-analysis, 244 families: OR 2.2, 95%CI 1.6–3.0) mostly attributable to a higher concordance in incomplete posterior communicating artery (meta-analysis: OR 2.8, 95%CI 1.8–4.3). No association was found for the other three circle of Willis variations. Conclusions In two independent groups of families with familial aneurysms, the incomplete PcomA variation occurred more often within than between families suggesting heritability of this circle of Willis variation. Further studies should investigate genetic variants associated with circle of Willis formation.