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Background: Smoking cessation rates after stroke and transient ischemic attack are suboptimal, and smoking cessation interventions are underutilized. We performed a cost-effectiveness analysis of smoking cessation interventions in this population. Methods: We constructed a decision tree and used Markov models that aimed to assess the cost-effectiveness of varenicline, any pharmacotherapy with intensive counseling, and monetary incentives, compared with brief counseling alone in the secondary stroke prevention setting. Payer and societal costs of interventions and outcomes were modeled. The outcomes were recurrent stroke, myocardial infarction, and death using a lifetime horizon. Estimates and variance for the base case (35% cessation), costs and effectiveness of interventions, and outcome rates were imputed from the stroke literature. We calculated incremental cost-effectiveness ratios and incremental net monetary benefits. An intervention was considered cost-effective if the incremental cost-effectiveness ratio was less than the willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY) or when the incremental net monetary benefit was positive. Probabilistic Monte Carlo simulations modeled the impact of parameter uncertainty. Results: From the payer perspective, varenicline and pharmacotherapy with intensive counseling were associated with more QALYs (0.67 and 1.00, respectively) at less total lifetime costs compared with brief counseling alone. Monetary incentives were associated with 0.71 more QALYs at an additional cost of $120 compared with brief counseling alone, yielding an incremental cost-effectiveness ratio of $168/QALY. From the societal perspective, all 3 interventions provided more QALYs at less total costs compared with brief counseling alone. In 10 000 Monte Carlo simulations, all 3 smoking cessation interventions were cost-effective in >89% of runs. Conclusions: For secondary stroke prevention, it is cost-effective and potentially cost-saving to deliver smoking cessation therapy beyond brief counseling alone.

Background: Posterior reversible encephalopathy syndrome (PRES) can cause short-term cerebrovascular complications, such as brain infarction and hemorrhage. We hypothesized that PRES is also associated with an increased long-term risk of stroke. Methods: We performed a retrospective cohort study in the United States using statewide all-payer claims data from 2016 to 2018 on all admissions to nonfederal hospitals in 11 states. Adults with PRES were compared with adults with renal colic (negative control) and transient ischemic attack (TIA; positive control). Any stroke and the secondary outcomes of ischemic and hemorrhagic stroke were ascertained using International Classification of Diseases, Tenth Revision, Clinical Modification codes . We excluded prevalent stroke. We used time-to-event statistics to calculate incidence rates and Cox proportional hazards analyses to evaluate the association between PRES and stroke, adjusting for demographics and stroke risk factors. In a sensitivity analysis, outcomes within 2 weeks of index admission were excluded. Results: We identified 1606 patients with PRES, 1192 with renal colic, and 38 216 with TIA. Patients with PRES had a mean age of 56±17 years; 72% were women. Over a median follow-up of 0.9 years, the stroke incidence per 100 person-years was 6.1 (95% CI, 5.0–7.4) after PRES, 1.0 (95% CI, 0.62–1.8) after renal colic, and 9.7 (95% CI, 9.4–10.0) after TIA. After statistical adjustment for patient characteristics and risk factors, patients with PRES had an elevated risk of stroke compared with renal colic (hazard ratio [HR], 2.3 [95% CI, 1.7–3.0]), but lower risk than patients with TIA (HR, 0.67 [95% CI, 0.54–0.82]). In secondary analyses, compared with TIA, PRES was associated with hemorrhagic stroke (HR, 2.0 [95% CI, 1.4–2.9]). PRES was associated with ischemic stroke when compared with renal colic (HR, 1.9 [95% CI, 1.4–2.7]) but not when compared with TIA (HR, 0.49 [95% CI, 0.38–0.63]). Results were similar with 2-week washout. Conclusions: Patients with PRES had an elevated risk of incident stroke.

Patients with cancer and acute ischemic stroke (AIS) face high rates of recurrent thromboembolism or death.To examine whether hematologic and embolic biomarkers soon after AIS are associated with subsequent adverse clinical outcomes.We prospectively enrolled 50 adults with active solid tumor cancer and AIS at two hospitals from 2016 to 2020. Blood was collected 72-120 h after stroke onset. A 30-min transcranial Doppler (TCD) microemboli detection study was performed. The exposure variables were hematologic markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of TCD microemboli. The primary outcome was a composite of recurrent arterial/venous thromboembolism or death. We used Cox regression to evaluate associations between biomarkers and subsequent outcomes.During an estimated median follow-up time of 48 days (IQR, 18-312), 43 (86%) participants developed recurrent thromboembolism or death, including 28 (56%) with recurrent thromboembolism, of which 13 were recurrent AIS (26%). In unadjusted analysis, D-dimer (HR 1.6; 95% CI 1.2-2.0), P-selectin (HR 1.9; 95% CI 1.4-2.7), sICAM-1 (HR 2.2; 95% CI 1.6-3.1), sVCAM-1 (HR 1.6; 95% CI 1.2-2.1), and microemboli (HR 2.2; 95% CI 1.1-4.5) were associated with the primary outcome, whereas thrombin-antithrombin and thrombomodulin were not. D-dimer was the only marker associated with recurrent AIS (HR 1.2; 95% CI 1.0-1.5). Results were generally consistent in analyses adjusted for important prognostic variables.Markers of hypercoagulability and embolic disease may be associated with adverse clinical outcomes in cancer-related stroke.

Stroke from basilar artery occlusion is associated with a poor natural history with high rates of death and disability. Intravenous thrombolysis administered within 4.5 hours of last known well time improves the odds of a good neurological outcome after ischemic stroke, including in patients with basilar artery occlusion. Thrombectomy for basilar artery occlusion has had mixed outcomes. The WAKE-UP randomized clinical trial demonstrated that administration of intravenous thrombolysis can benefit select patients with wake-up strokes whose brain MRI shows restricted diffusion but no accompanying T2 FLAIR change. We report a case of a wake-up acute ischemic stroke presenting with acute vertigo followed by progressive brainstem dysfunction from a basilar artery occlusion. The patient was successfully treated with intravenous thrombolysis beyond 4.5 hours of last known well and symptom discovery time according to an MRI tissue-based approach resulting in partial recanalization of her basilar artery and recovery to near normal. This case suggests that hyperacute MRI can serve as a tissue clock to select patients with wake-up stroke for acute reperfusion therapy even if they do not meet standard trial inclusion criteria, including patients with basilar artery occlusion.

Background: In patients with intracerebral hemorrhage (ICH), it is unclear whether early neurological deterioration, hematoma expansion (HE), and outcome vary by supratentorial ICH location (deep versus lobar). Herein, we assessed these relationships in a clinical trial cohort that underwent brain imaging early after symptom onset. We hypothesized that HE would occur more frequently, and outcome would be worse in patients with deep ICH. Methods: We performed a post hoc analysis of the FAST (Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment) trial including all patients with supratentorial hemorrhage. Enrolled patients underwent brain imaging within 3 hours of symptom onset and 24 hours after randomization. Multivariable regression was used to test the association between ICH location and 3 outcomes: HE (increase of ≥33% or 6mL), early neurological deterioration (decrease in Glasgow Coma Scale score ≥2 points or increase in National Institutes of Health Stroke Scale ≥4 points within 24 hours of admission), and 90-day outcome (modified Rankin Scale). Results: Of 841 FAST trial patients, we included 728 (mean age 64 years, 38% women) with supratentorial hemorrhages (deep n=623, lobar n=105). HE (44 versus 27%, P =0.001) and early neurological deterioration (31 versus 17%, P =0.001) were more common in lobar hemorrhages. Deep hemorrhages were smaller than lobar hemorrhages at baseline (12 versus 35mL, P P P =0.03). However, when adjusting for variables included in the ICH score including ICH volume, deep location was associated with worse and lobar location with better outcome (odds ratio lobar location, 0.58 [95% CI, 0.38–0.89]; P =0.01). Conclusions: In this secondary analysis of randomized trial patients, lobar ICH location was associated with larger ICH volume, more HE and early neurological deterioration, and worse outcome than deep ICH. After adjustment for prognostic variables, however, deep ICH was associated with worse outcome, likely due to their proximity to eloquent brain structures.

Mobile stroke units (MSUs) are specialized ambulances equipped with the personnel, equipment, and imaging capability to diagnose and treat acute stroke in the prehospital setting. Over the past decade, MSUs have proliferated throughout the world, particularly in European and US cities, culminating in the formation of an international consortium. Randomized trials have demonstrated that MSUs increase stroke thrombolysis rates and reduce onset-to-treatment times but until recently it was uncertain if these advantages would translate into better patient outcomes. In 2021, 2 pivotal, large, controlled clinical trials, B_PROUD and BEST-MSU, demonstrated that as compared with conventional emergency care, treatment aboard MSUs was safe and led to improved functional outcomes in patients with stroke. Further, the observed benefit of MSUs appeared to be primarily driven by the higher frequency of ultra-early thrombolysis within the golden hour. Nevertheless, questions remain regarding the cost-effectiveness of MSUs, their utility in nonurban settings, and optimal infrastructure. In addition, in much of the world, MSUs are currently not reimbursed by insurers nor accepted as standard care by regulatory bodies. As MSUs are now established as one of the few proven acute stroke interventions with an effect size that is comparable to that of intravenous thrombolysis and stroke units, stroke leaders and organizations should work with emergency medical services, governments, and community stakeholders to determine how MSUs might benefit individual communities, and their optimal organization and financing. Future research to explore the effect of MSUs on intracranial hemorrhage and thrombectomy outcomes, cost-effectiveness, and novel models including the use of rendezvous transports, helicopters, and advanced neuroimaging is ongoing. Recommended next steps for MSUs include reimbursement by insurers, integration with ambulance networks, recognition by program accreditors, and inclusion in registries that monitor care quality.

Background: Continued smoking after stroke is associated with a high risk of stroke recurrence and other cardiovascular disease. We sought to comprehensively understand the epidemiology of smoking cessation in stroke survivors in the United States. Furthermore, we compared smoking cessation in stroke and cancer survivors because cancer is another smoking-related condition in which smoking cessation is prioritized. Methods: We performed a cross-sectional analysis of data from the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System, an annual, nationally representative health survey. Using pooled data from 2013 to 2019, we identified stroke and cancer survivors with a history of smoking. We used survey procedures to estimate frequencies and summarize quit ratios with attention to demographic and geographic (state-wise and rural-urban) factors for stroke survivors. The quit ratio is conventionally defined as the proportion of ever smokers who have quit. Then, we used multivariable logistic regression to compare quit ratios in stroke and cancer survivors while adjusting for demographics and smoking-related comorbidities. Results: Among 4 434 604 Americans with a history of stroke and smoking, the median age was 68 years (interquartile range, 59–76), and 45.4% were women. The overall quit ratio was 60.8% (95% CI, 60.1%–61.6%). Quit ratios varied by age group, sex, race and ethnicity, and several geographic factors. There was marked geographic variation in quit ratios, ranging from 48.3% in Kentucky to 71.5% in California. Furthermore, compared with cancer survivors, stroke survivors were less likely to have quit smoking (odds ratio, 0.72 [95% CI, 0.67–0.79]) after accounting for differences in demographics and smoking-related comorbidities. Conclusions: There were considerable demographic and geographic disparities in smoking quit ratios in stroke survivors, who were less likely to have quit smoking than cancer survivors. A targeted initiative is needed to improve smoking cessation for stroke survivors.

Background: Administrative data can be useful for stroke research but have historically lacked data on stroke severity. Hospitals increasingly report the National Institutes of Health Stroke Scale (NIHSS) score using an International Classification of Diseases , Tenth Revision ( ICD-10 ) diagnosis code, but this code’s validity remains unclear. Methods: We examined the concordance of ICD-10 NIHSS scores versus NIHSS scores recorded in CAESAR (Cornell Acute Stroke Academic Registry). We included all patients with acute ischemic stroke from October 1, 2015, when US hospitals transitioned to ICD-10 , through 2018, the latest year in our registry. The NIHSS score (range, 0–42) recorded in our registry served as the reference gold standard. ICD-10 NIHSS scores were derived from hospital discharge diagnosis code R29.7xx, with the latter 2 digits representing the NIHSS score. Multiple logistic regression was used to explore factors associated with availability of ICD-10 NIHSS scores. We used ANOVA to examine the proportion of variation ( R 2 ) in the true (registry) NIHSS score that was explained by the ICD-10 NIHSS score. Results: Among 1357 patients, 395 (29.1%) had an ICD-10 NIHSS score recorded. This proportion increased from 0% in 2015 to 46.5% in 2018. In a logistic regression model, only higher registry NIHSS score (odds ratio per point, 1.05 [95% CI, 1.03–1.07]) and cardioembolic stroke (odds ratio, 1.4 [95% CI, 1.0–2.0]) were associated with availability of the ICD-10 NIHSS score. In an ANOVA model, the ICD-10 NIHSS score explained almost all the variation in the registry NIHSS score ( R 2 =0.88). Fewer than 10% of patients had a large discordance (≥4 points) between their ICD-10 and registry NIHSS scores. Conclusions: When present, ICD-10 codes representing NIHSS scores had excellent agreement with NIHSS scores recorded in our stroke registry. However, ICD-10 NIHSS scores were often missing, especially in less severe strokes, limiting the reliability of these codes for risk adjustment.

Background: An estimated 40% of Americans will develop cancer in their lifetime, and most will require one or multiple surgeries for diagnosis and treatment. We sought to determine whether cancer is an independent risk factor for perioperative arterial ischemic events. Methods: We performed a retrospective cohort study of patients who had major inpatient or outpatient surgery registered in the National Surgical Quality Improvement Program (NSQIP) between 2006-2016. The study exposure was disseminated cancer. The study outcome was a perioperative arterial ischemic event, defined as an ischemic stroke or myocardial infarction within 30 days of surgery. Multivariable Cox regression was used to evaluate the association between the study exposure and outcome while adjusting for potential confounders. Various sensitivity analyses were conducted. Results: Among 5,609,675 NSQIP cases, 122,221 (2.2%) surgeries involved patients with disseminated cancer. Patients’ mean age was 56 years (SD, 17); 57% were women. The Kaplan-Meier 30-day perioperative arterial ischemic event rate was 0.96% (95% CI, 0.91-1.02%) among patients with disseminated cancer vs 0.48% (95% CI, 0.47-0.49%) among patients without disseminated cancer (HR, 2.0; 95% CI, 1.9-2.1) (Figure). In Cox regression analyses adjusting for demographics, functional status, comorbidities, surgical setting, anesthesia type, and relevant clinical factors, disseminated cancer remained associated with a perioperative arterial ischemic event (HR, 1.3; 95% CI, 1.2-1.4). This association persisted across analyses excluding neurosurgical and cardiac surgeries, restricting to elective surgeries, and restricting to patients with functional independence before surgery. Conclusions: In a large, nationwide, surgical registry, comorbid cancer was associated with an estimated 20-40% increased risk of perioperative arterial ischemic events.

Background: Few data exists on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials. Methods: A pre-specified subgroup analysis of tPA-eligible patients with PD enrolled in a prospective multicenter trial of Mobile Stroke Units (MSUs) vs standard management by emergency medical services (EMS). All patients had baseline mRS scores. Co-primary outcomes were mean utility-weighted modified Rankin Scale score (uw-mRS) and return to baseline mRS at 90 days. Linear and logistic regression models compared outcomes in patients with vs without PD, and patients with PD treated by MSU vs EMS. Time metrics, safety, quality of life, and health-care utilization were also compared. Results: Of 1047 patients, 254 had baseline mRS >= 2 (159 MSU, 95 EMS; 31% mRS 2, 52% mRS 3, 17% mRS 4). Compared to patients without disability, patients with PD were older, had higher NIHSS, more comorbidities, less often lived at home, were treated slower, and had less thrombectomy. Patients with PD had worse 90-day uw-mRS (0.39 vs 0.80), higher mortality, more health-care utilization and worse quality of life than patients without PD. However, rates of symptomatic intracranial hemorrhage and final diagnoses of stroke mimics were similar between groups, and 52% of patients with PD returned to their baseline mRS. Patients with PD treated within the first hour had better 90-day uw-mRS than those treated later (0.48 vs 0.36, p=0.01). Comparing patients with PD treated by MSU vs EMS, time from last-known-well to tPA bolus was shorter (82 vs 111 min), and 24% vs 0% were treated in the first hour. Among patients with PD, MSU patients had non-significantly better 90-day uw-mRS (0.41 vs 0.35, p=0.09) and higher rate of returning to baseline mRS (56% vs 44%, p=0.09) than EMS patients. There was no interaction between either time to treatment (p=0.24) or MSU vs EMS group assignment (p= 0.42), 90-day uw-mRS, and PD vs no disability status. Conclusion: Although outcomes after stroke are less favorable in patients with vs without PD, in a large, controlled trial, we found no interaction between baseline disability and the benefit of MSU treatment. Our data support the earliest treatment of acute stroke patients regardless of premorbid functional status.

Introduction: Cirrhosis is associated with an increased risk of hemorrhagic stroke (HS). Liver fibrosis, typically a silent condition, is antecedent to cirrhosis. We hypothesized that liver fibrosis is associated with an increased risk of HS. Further, because apolipoprotein E2 (ApoE2) and E4 (ApoE4) are associated with HS, and because liver-derived peripheral ApoE4 may disrupt endothelial integrity, we evaluated for effect modification by these isoforms. Methods: We performed a cohort analysis using the UK Biobank Study, which prospectively enrolled adults in 2007, with continuous follow-up. We excluded participants with prevalent HS or thrombocytopenia. Liver fibrosis was defined using the validated Fibrosis-4 score. The primary outcome, incident HS (intracerebral or subarachnoid hemorrhage), was captured in UK Biobank based on hospitalization and death registry data. We used Cox proportional hazards models to evaluate the association of liver fibrosis with HS while adjusting for HS risk factors (demographics, systolic blood pressure, hemoglobin A1c, total cholesterol, BMI, tobacco and alcohol use, antithrombotic use). Effect modification by ApoE2 and ApoE4 were evaluated using interaction terms and stratified analyses. Results: Among 453,251 included participants, the mean age was 57 years and 54% were women. Approximately 2% had liver fibrosis, 16% used antithrombotic agents, 29% were ApoE4 carriers, and 15% were ApoE2 carriers. In adjusted Cox models, liver fibrosis was associated with an increased risk of HS (HR, 2.17; 95% CI, 1.51-3.12) (Figure). This relationship appeared stronger in ApoE4 homozygotes (HR, 8.27; 95% CI, 2.30-29.73) than in others (HR, 2.18; 95% CI, 1.47-3.24) (P=0.05, interaction). ApoE4 carrier status, ApoE2 carrier status, and ApoE2 homozygosity did not modify this relationship (P>0.20, interactions). Conclusions: Liver fibrosis was associated with an increased risk of HS, possibly more so in ApoE4 homozygous persons.

Introduction: While the goal of IV tissue plasminogen activator (TPA) is to prevent infarction, few data exist on averted stroke. Methods: Secondary analysis of a multicenter trial from 2014-2020 comparing outcomes between patients treated for stroke by mobile stroke unit (MSU) vs standard care (SC). The analytical cohort were patients with suspected stroke treated with IV TPA. The primary outcome was a time-defined averted stroke diagnosis, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours. The secondary outcome was a tissue-defined averted stroke diagnosis, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours and no acute infarction/hemorrhage on imaging. We used multivariable logistic regression to evaluate associations between study exposures (demographics, comorbidities, stroke characteristics) and outcomes. Results: Among 1009 patients with a median last known well-to-TPA time of 87 minutes, 276 patients (27%) had a time-defined averted stroke (31% MSU, 21% SC) and 159 patients (16%) had a tissue-defined averted stroke (18% MSU, 11% SC). Factors independently associated with time-defined averted stroke were younger age (OR, 0.98; 95% CI, 0.96-0.99), female sex (0R, 0.51; 95% CI, 0.36-0.74), hyperlipidemia (OR, 1.81, 95% CI, 1.24-2.64), normal premorbid function (0R, 2.22; 95% CI, 1.37-3.67), lower glucose (OR, 0.996; 95% CI, 0.993-0.999), lower MAP (OR, 0.991; 95% CI, 0.983-0.998), MSU care (OR, 1.77; 95% CI, 1.21-2.62), lower NIH stroke scale (OR, 0.89; 95% CI, 0.86-0.93), and no large vessel occlusion (LVO) (OR, 0.52; 95% CI, 0.32-0.83). For tissue-based averted stroke, younger age, female sex, hyperlipidemia, lower MAP, MSU treatment, lower NIH stroke scale, and no LVO were significantly associated. Conclusion: In a modern acute stroke trial, one-in-four patients treated with TPA for stroke recovered within 24 hours and one-in-six had no demonstrable brain injury on imaging. Younger age, female sex, hyperlipidemia, lower MAP, MSU care, lower stroke severity, and no LVO may increase the odds of averting stroke.

Background and Purpose: Coronavirus disease 2019 (COVID-19) may be associated with increased risk for ischemic stroke. We present prevalence and characteristics of strokes in patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection enrolled in the American Heart Association COVID-19 Cardiovascular Disease Registry. Methods: In this quality improvement registry study, we examined demographic, baseline clinical characteristics, and in-hospital outcomes among hospitalized COVID-19 patients. The primary outcomes were ischemic stroke or transient ischemic attack (TIA) and in-hospital death. Results: Among 21 073 patients with COVID-19 admitted at 107 hospitals between January 29, 2020, and November 23, 2020, 160 (0.75%) experienced acute ischemic stroke/TIA (55.3% of all acute strokes) and 129 (0.61%) had other types of stroke. Among nonischemic strokes, there were 44 (15.2%) intracerebral hemorrhages, 33 (11.4%) subarachnoid hemorrhages, 21 (7.3%) epidural/subdural hemorrhages, 2 (0.7%) cerebral venous sinus thromboses, and 24 (8.3%) strokes not otherwise classified. Asians and non-Hispanic Blacks were overrepresented among ischemic stroke/TIA patients compared with their overall representation in the registry, but adjusted odds of stroke did not vary by race. Median time from COVID-19 symptom onset to ischemic stroke was 11.5 days (interquartile range, 17.8); median National Institutes of Health Stroke Scale score was 11 (interquartile range, 17). COVID-19 patients with acute ischemic stroke/TIA had higher prevalence of hypertension, diabetes, and atrial fibrillation compared with those without stroke. Intensive care unit admission and mechanical ventilation were associated with higher odds of acute ischemic stroke/TIA, but older age was not a predictor. In adjusted models, acute ischemic stroke/TIA was not associated with in-hospital mortality. Conclusions: Ischemic stroke risk did not vary by race. In contrast to the association between older age and death from COVID-19, ischemic stroke risk was the highest among middle-aged adults after adjusting for comorbidities and illness severity, suggesting a potential mechanism for ischemic stroke in COVID-19 independent of age-related atherosclerotic pathways.

Background Access to mechanical thrombectomy (MT) in the United States remains limited. Given potential staffing challenges, we hypothesized that access to thrombectomy would be worse off hours. Methods We used 2016 to 2018 all‐payer claims data from all nonfederal emergency departments and acute care hospitals across 11 US states encompassing 80 million residents. Using recorded arrival times, hospital presentation was classified as on hours if it fell between 8:00 a.m. and 6:00 p.m. on weekdays and as off hours otherwise. We examined the association between off‐hours arrival and MT using multiple adjusted logistic regression models. In a subset of patients with available National Institutes of Health Stroke Scale data, we performed a sensitivity analysis limited to patients who presented to a thrombectomy hub with a probable large‐vessel occlusion, defined as a documented National Institutes of Health Stroke Scale score ≥12, and underwent intravenous thrombolysis. Similar analyses were performed to assess MT odds during extreme off hours, defined as midnight to 6:00 a.m., compared to 8:00 a.m. to 2:00 p.m. Results Among 169 199 patients with ischemic stroke, the 82 784 (48.9%) who presented during off hours more often presented to thrombectomy hubs and teaching hospitals and more often received intravenous thrombolysis. Among 31 148 patients with documented National Institutes of Health Stroke Scale scores, those presenting off hours had higher scores (4 [interquartile range, 2–10] versus 2 [interquartile range, 1–9]; P P =0.25). In adjusted models, off‐hours presentation was not significantly associated with lower odds of MT (odds ratio [OR], 0.94; [95% CI, 0.85–1.03]). Our findings were similar in a sensitivity analysis limited to patients with a probable large‐vessel occlusion who initially presented to a thrombectomy hub and underwent intravenous thrombolysis (OR, 0.87; [95% CI, 0.69–1.09]). Extreme off‐hours presentation was associated with a lower likelihood of MT (OR, 0.83; [95% CI, 0.75–0.93]). Conclusion In a large, population‐based sample of ischemic stroke patients across the United States, the odds of MT were similar during on and off hours. Extreme off hours seem to be associated with decreased access to treatment.

Background Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard m...

OBJECTIVE: To evaluate whether patients discharged to home after an emergency department (ED) visit for headache face a heightened short-term risk of stroke. BACKGROUND: Stroke hospitalizations that occur soon after ED visits for headache complaints may reflect diagnostic error. METHODS: We conducted a retrospective cohort study using statewide administrative claims data for all ED visits and admissions at nonfederal hospitals in Florida 2005–2018 and New York 2005–2016. Using standard International Classification of Diseases (ICD) codes, we identified adult patients discharged to home from the ED (treat-and-release visit) with a benign headache diagnosis (cohort of interest) as well as those with a diagnosis of renal colic or back pain (negative controls). The primary study outcome was hospitalization within 30 days for stroke (ischemic or hemorrhagic) defined using validated ICD codes. We assess the relationship between index ED visit discharge diagnosis and stroke hospitalization adjusting for patient demographics and vascular comorbidities. RESULTS: We identified 1,502,831 patients with an ED treat-and-release headache visit; mean age was 41 (standard deviation: 17) years and 1,044,520 (70%) were female. A total of 2150 (0.14%) patients with headache were hospitalized for stroke within 30 days. In adjusted analysis, stroke risk was higher after headache compared to renal colic (hazard ratio [HR]: 2.69; 95% confidence interval [CI]: 2.29–3.16) or back pain (HR: 4.0; 95% CI: 3.74–4.3). In the subgroup of 26,714 (1.78%) patients with headache who received brain magnetic resonance imaging at index ED visit, stroke risk was only slightly elevated compared to renal colic (HR: 1.47; 95% CI: 1.22–1.78) or back pain (HR: 1.49; 95% CI: 1.24–1.80). CONCLUSION: Approximately 1 in 700 patients discharged to home from the ED with a headache diagnosis had a stroke in the following month. Stroke risk was three to four times higher after an ED visit for headache compared to renal colic or back pain.

Severe hypertension can accompany neurological symptoms without obvious signs of target organ damage. However, acute cerebrovascular events can also be a cause and consequence of severe hypertension. We therefore use US population-level data to determine prevalence and clinical characteristics of patients with severe hypertension and neurological complaints.We used nationally representative data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) collected in 2016-2019 to identify adult ED patients with severely elevated blood pressure (BP) defined as systolic BP ≥ 180 mmHg and/or diastolic BP ≥120 mmHg. We used ED reason for visit data fields to define neurological complaints and used diagnosis data fields to define acute target organ damage. We applied survey visit weights to obtain national estimates.Based on 5083 observations, an estimated 40.4 million patients (95% CI: 37.5-43.0 million) in EDs nationwide from 2016 to 2019 had severe hypertension, equating to 6.1% (95% CI: 5.7-6.5%) of all ED visits. Only 2.8% (95% CI: 2.0-3.9%) of ED patients with severe hypertension were diagnosed with acute cerebrovascular disease; hypertensive urgency was diagnosed in 92.0% (95% CI: 90.3-93.4%). Neurological complaints were frequent in both patients with (75.6%) and without (19.9%) cerebrovascular diagnoses. Hypertensive urgency patients with neurological complaints were more often older, female, had prior stroke/TIA, and had neuroimaging than patients without these complaints. Non-migraine headache and vertigo were the most common neurological complaints recorded.In a nationally representative survey, one-in-sixteen ED patients had severely elevated BP and one-fifth of those patients had neurological complaints.

Objective The objective of this study was to examine the pathophysiology of ischemic stroke with cancer. Methods We conducted a prospective cross-sectional study from 2016 to 2020 at 2 hospitals. We enrolled 3 groups of 50 adult participants each. The main group included patients with active solid tumor cancer and acute ischemic stroke. The control groups included patients with acute ischemic stroke only or active cancer only. The patients with stroke-only and patients with cancer-only were matched to the patients with cancer-plus-stroke by age, sex, and cancer type, if applicable. The outcomes were prespecified hematological biomarkers and transcranial Doppler microemboli detection. Hematological biomarkers included markers of coagulation (D-dimer and thrombin-antithrombin), platelet function (P-selectin), and endothelial integrity (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], and soluble vascular cell adhesion molecule-1 [sVCAM-1]). Hematological biomarkers were compared between groups using the Kruskal-Wallis and Wilcoxon Rank-Sum tests. In multivariable linear regression models, we adjusted for race, number of stroke risk factors, smoking, stroke severity, and antithrombotic use. Transcranial Doppler microemboli presence was compared between groups using chi-square tests. Results Levels of all study biomarkers were different between groups. In univariate between-group comparisons, patients with cancer-plus-stroke had higher levels of D-dimer, sICAM-1, sVCAM-1, and thrombomodulin than both control groups; higher levels of thrombin-antithrombin than patients with cancer-only; and higher levels of P-selectin than patients with stroke-only. Findings were similar in multivariable analyses. Transcranial Doppler microemboli were detected in 32% of patients with cancer-plus-stroke, 16% of patients with stroke-only, and 6% of patients with cancer-only (p = 0.005). Interpretation Patients with cancer-related stroke have higher markers of coagulation, platelet, and endothelial dysfunction, and more circulating microemboli, than matched controls. ANN NEUROL 2021;90:159-169.

ObjectiveTo estimate the incidence of hospitalization for reversible cerebral vasoconstriction syndrome (RCVS), we identified RCVS-related hospital admissions across 11 US states in 2016.MethodsWe tested the validity of ICD-10 code I67.841 in 79 patients with hospital admissions for RCVS or other cerebrovascular diseases at 1 academic and 1 community hospital. After determining that this code had a sensitivity of 100% (95% confidence interval [CI], 82%–100%) and a specificity of 90% (95% CI, 79%–96%), we applied it to administrative data from the Healthcare Cost and Utilization Project on all hospital admissions across 11 states. Age- and sex-standardized RCVS incidence was calculated using census data. Descriptive statistics were used to analyze associated diagnoses.ResultsAcross 5,067,250 hospital admissions in our administrative data, we identified 222 patients with a discharge diagnosis of RCVS in 2016. The estimated annual age- and sex-standardized incidence of RCVS hospitalization was 2.7 (95% CI, 2.4–3.1) cases per million adults. Many patients had concomitant neurologic diagnoses, including subarachnoid hemorrhage (37%), ischemic stroke (16%), and intracerebral hemorrhage (10%). In the 90 days before the index admission, 97 patients had an emergency department (ED) visit and 34 patients a hospital admission, most commonly for neurologic, psychiatric, and pregnancy-related diagnoses. Following discharge from the RCVS hospital admission, 58 patients had an ED visit and 31 had a hospital admission, most commonly for neurologic diagnoses.ConclusionsUsing population-wide data, we estimated the age- and sex-standardized incidence of hospitalization for RCVS in US adults as approximately 3 per million per year.

The grim circumstances of the COVID-19 pandemic have highlighted the need to refine and adapt stroke systems of care. Patients’ care-seeking behaviors have changed due to perceived risks of in-hospital treatment during the pandemic. In response to these challenges, we optimized a recently implemented, novel outpatient approach for the evaluation and management of minor stroke and transient ischemic attack, entitled RESCUE-TIA. This modified approach incorporated telemedicine visits and remote testing, and proved valuable during the pandemic. In this review article, we provide the evidence-based rationale for our approach, describe its operationalization, and provide data from our initial experience.

Cerebrovascular complications among critically ill patients with COVID-19 have yet to be fully characterized. In this retrospective case series from a single academic tertiary care referral center in New York City, we present 12 patients with ischemic or hemorrhagic strokes that were found on imaging after a period of prolonged sedation in the setting of COVID-19 pneumonia. This series demonstrates a pattern of cerebrovascular events clinically masked by deep sedation required for management of COVID-19 related acute respiratory distress syndrome (ARDS). Of the 12 patients included, 10 had ischemic stroke, 4 of which had hemorrhagic conversion, and 2 had primary intracerebral hemorrhage. Ten patients were on therapeutic anticoagulation prior to discovery of their stroke, and the remainder received intermediate dose anticoagulation (in a range between prophylactic and therapeutic levels). Additional studies are needed to further characterize the counterbalancing risks of ischemic and hemorrhagic stroke, as well as the optimal management of this patient population.

To derive models that identify patients with COVID-19 at high risk for stroke.We used data from the AHA's Get With The Guidelines® COVID-19 Cardiovascular Disease Registry to generate models for predicting stroke risk among adults hospitalized with COVID-19 at 122 centers from March 2020-March 2021. To build our models, we used data on demographics, comorbidities, medications, and vital sign and laboratory values at admission. The outcome was a cerebrovascular event (stroke, TIA, or cerebral vein thrombosis). First, we used Cox regression with cross validation techniques to identify factors associated with the outcome in both univariable and multivariable analyses. Then, we assigned points for each variable based on corresponding coefficients to create a prediction score. Second, we used machine learning techniques to create risk estimators using all available covariates.Among 21,420 patients hospitalized with COVID-19, 312 (1.5%) had a cerebrovascular event. Using traditional Cox regression, we created/validated a COVID-19 stroke risk score with a C-statistic of 0.66 (95% CI, 0.60-0.72). The CANDLE score assigns 1 point each for prior cerebrovascular disease, afebrile temperature, no prior pulmonary disease, history of hypertension, leukocytosis, and elevated systolic blood pressure. CANDLE stratified risk of an acute cerebrovascular event according to low- (0-1: 0.2% risk), medium- (2-3: 1.1% risk), and high-risk (4-6: 2.1-3.0% risk) groups. Machine learning estimators had similar discriminatory performance as CANDLE: C-statistics, 0.63-0.69.We developed a practical clinical score, with similar performance to machine learning estimators, to help stratify stroke risk among patients hospitalized with COVID-19.

Introduction: We previously showed that patients with cancer and acute ischemic stroke (AIS) have higher markers of coagulation, platelet, and endothelial activation, and more circulating microemboli than patients with AIS and no cancer. Herein, we evaluate whether these markers are associated with clinical outcomes in patients with cancer and AIS. Methods: In the MOST-Cancer prospective study, we enrolled 50 adults with active solid-tumor cancer and AIS at 2 New York hospitals from 2016-2020. We collected blood from participants 72-120 hours after stroke onset. We performed a 30-minute transcranial Doppler (TCD) microemboli detection study a median of 4 days after stroke onset. The exposure variables were hematological markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of microemboli on TCD. The primary outcome was a composite of recurrent arterial or venous thromboembolism or death. The secondary outcome was recurrent AIS. We used Cox regression to evaluate individual associations between biomarkers and subsequent outcomes. Results: Median age was 69 years (IQR, 60-76) and 24 participants (48%) were women. The most common cancers were lung (28%) and pancreatic (22%); 86% of participants had distant metastases. During a mean follow-up of 278 days (SD, 367), 43 (86%) participants had the primary outcome of recurrent thromboembolism or death, including 28 (56%) who had recurrent thromboembolism, 13 who had recurrent AIS (26%), and 30 (60%) who died. D-dimer, P-selectin, sICAM-1, sVCAM-1, and microemboli were associated with the composite outcome (Table). Similar results were seen for recurrent AIS. Conclusion: Markers of hypercoagulability and embolic disease were associated with adverse clinical outcomes in cancer-related stroke.

Introduction: Posterior reversible encephalopathy syndrome (PRES) can cause brain infarction and hemorrhage in the acute phase. We hypothesized that PRES is also associated with an increased long-term risk of stroke. Methods: We performed a retrospective cohort study using statewide all-payer claims data from 2016-2018 for all admissions to nonfederal hospitals in 11 states. Adult patients with PRES were compared to patients with TIA (positive control) and renal colic (negative control), as done in prior studies. The primary outcome was any stroke, and secondary outcomes were ischemic and hemorrhagic stroke. Diagnoses were ascertained using ICD-10-CM codes. We excluded patients with stroke before and during index admissions for PRES and controls. We used Cox proportional hazards analyses to evaluate associations between PRES and stroke, adjusting for demographics, stroke risk factors, and factors associated with PRES (cancer, kidney disease, rheumatological disease). In a sensitivity analysis, stroke events within 4 weeks of index admissions were excluded. Results: We identified 3,086 patients with PRES, 85,189 with TIA, and 3,094 with renal colic. Patients with PRES (55±17 years) and renal colic (54±18 years) were younger than those with TIA (72±14 years). Median follow-up was 1.1 years and similar between groups. Stroke incidence was 3.2 per 100 person-years after PRES, 3.8 per 100 person-years after TIA, and 0.4 per 100 person-years after renal colic (Figure). After adjustment, patients with PRES had a similar stroke risk as patients with TIA (HR, 0.9; 95% CI, 0.8-1.2), and a higher stroke risk than patients with renal colic (HR, 2.6; 95% CI, 2.0-3.5). Compared to TIA, PRES had a higher risk of hemorrhagic stroke (HR, 2.9; 95% CI, 2.2-3.9) and a lower risk of ischemic stroke (HR, 0.7; 95% CI, 0.6-0.9). Results were similar with a 4-week washout period. Conclusions: PRES is associated with an increased risk of future stroke, specifically hemorrhagic stroke.

Introduction: The cost effectiveness of smoking-cessation interventions after ischemic stroke and TIA has not been evaluated. We performed a cost-effectiveness analysis of smoking-cessation interventions in this population. Methods: We constructed a decision tree model to compare brief counseling alone to 3 interventions: varenicline, any pharmacotherapy with intensive counseling, and monetary incentives. Direct health care costs of interventions and outcomes were modeled. The outcomes were recurrent stroke, myocardial infarction, and death using a 5-year horizon. Estimates and variance for the base case (42% cessation), costs and effectiveness of interventions, and outcome rates were imputed from the stroke literature. Using standard techniques, we calculated incremental cost-effectiveness ratios (ICER) and net-monetary benefits (NMB). An intervention was considered cost effective if the ICER was less than the standard willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) or when the NMB was maximized. Sensitivity analyses and a probabilistic Monte Carlo simulation modeled the impact of parameter uncertainty, including for the base case cessation rate and costs and effectiveness of interventions (TreeAge Pro). Results: All three interventions were cost effective based on the ICER: varenicline - $7,422/QALY, pharmacotherapy with counseling - $14,550/QALY, and monetary incentives - $23,280/QALY. In one-way sensitivity analyses, interventions costing up to $1,729 remained cost-effective. In a two-way sensitivity analysis varying the cost and effectiveness of smoking-cessation interventions, all three interventions were cost effective based on NMB (Figure). In 10,000 Monte Carlo simulations, smoking-cessation interventions were cost effective 90% of the time, as compared to brief counseling alone. Conclusion: Smoking-cessation strategies are cost effective in secondary prevention after stroke and TIA.

ObjectiveTo evaluate the relationship between prior antiplatelet therapy (APT) and outcomes after primary intracerebral haemorrhage (ICH), and assess if it varies by haematoma location.MethodsWe pooled individual patient data from the Virtual International Stroke Trials Archive-ICH trials dataset, Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase III trial. The exposure was APT preceding ICH diagnosis. The primary outcome was haematoma expansion at 72 hours. Secondary outcomes were admission haematoma volume, all-cause mortality, death or major disability (modified Rankin Scale (mRS) score ≥4) and shift in mRS distribution. Mixed-effects models were used to assess the relationship between APT and outcomes. Secondary analyses were stratified by ICH location and study cohort.ResultsAmong 1420 patients with ICH, there were 782 (55.1%) lobar and 596 (42.0%) deep haemorrhages. APT was reported in 284 (20.0%) patients. In adjusted regression models, prior APT was not associated with haematoma expansion (OR, 0.97; 95% CI 0.60 to 1.57), major disability or death (OR, 1.05; 95% CI 0.61 to 1.63), all-cause mortality (OR, 0.89; 95% CI 0.47 to 1.85), admission haematoma volume (beta, −0.17; SE, 0.09; p=0.07) and shift in mRS (p=0.43). In secondary analyses, APT was associated with admission haematoma volume in lobar ICH (beta, 0.25; SE, 0.12; p=0.03), but there was no relationship with other ICH outcomes when stratified by haematoma location or study cohort.ConclusionsIn a large heterogeneous cohort of patients with ICH, prior APT was not associated with haematoma expansion or functional outcomes after ICH, regardless of haematoma location. APT was associated with admission haematoma volumes in lobar ICH.

Objective We wanted to determine whether pregnancy is associated with cervical artery dissection. Methods We performed a case-control study using claims data from all nonfederal emergency departments and acute care hospitals in New York and Florida between 2005 and 2015. Cases were women 12-42 years of age hospitalized with cervical artery dissection, defined using validated diagnosis codes for carotid/vertebral artery dissection. Controls were women 12-42 years of age with a primary diagnosis of renal colic. Cases and controls were matched 1:1 on age, race, insurance, income, state, and visit year. The exposure variable was pregnancy, defined as labor and delivery within 90 days before or 6 months after the index visit. Logistic regression was used to compare the odds of pregnancy between cases and controls. We performed a secondary cohort-crossover study comparing the risk of cervical artery dissection during pregnancy versus the same time period 1 year later. Results Pregnancy was twice as common among 826 women with cervical artery dissection compared with the 826 matched controls with renal colic (odds ratio, 2.5; 95% confidence interval [CI], 1.3-4.7). In our secondary analysis, pregnancy was associated with a higher risk of cervical artery dissection (incidence rate ratio [IRR], 2.2; 95% CI, 1.3-3.5), with the heightened risk limited to the postpartum period (IRR, 5.5; 95% CI, 2.6-11.7). Interpretation Pregnancy, specifically the postpartum period, was associated with hospitalization for cervical artery dissection. Although these findings might in part reflect ascertainment bias, our results suggest that arterial dissection is one mechanism by which pregnancy can lead to stroke. ANN NEUROL 2020;88:596-602.

Background and Purpose— Patients who continue to smoke after a stroke face a higher risk of recurrent stroke. While several effective drugs for smoking cessation became available over the past 2 decades, whether active smoking has decreased among stroke survivors is unknown. We, therefore, evaluated trends in active smoking among stroke survivors during this period. Methods— We performed trends analyses using cross-sectional data collected every 1 to 2 years from 2 US health surveys spanning 1999 to 2018. In the National Health and Nutrition Examination Survey (NHANES) and the Behavioral Risk Factor Surveillance System (BRFSS) survey, participants were asked about prior stroke and active tobacco smoking. In NHANES, serum cotinine levels were available as a secondary measure of active smoking. We used multivariable logistic regression models for survey data to assess trends in active smoking among participants with and without prior stroke. Results— Among 49 375 participants in NHANES during 1999 to 2016 and 3 621 741 participants in BRFSS during 2011 to 2018, the prevalence of stroke was ≈3%. The overall prevalence of active smoking among stroke survivors was 24% in NHANES and 23% in BRFSS. Among individuals without prior stroke, the odds of smoking decreased over time in both NHANES (odds ratio, 0.95 per 2 years [95% CI, 0.93–0.96]) and BRFSS (odds ratio, 0.96 per year [95% CI, 0.96–0.96]). In contrast, there was no decrease in smoking among stroke survivors in NHANES (odds ratio, 1.00 [95% CI, 0.93–1.07]) or BRFSS (odds ratio, 0.99 [95% CI, 0.98–1.004]). Results were consistent in secondary analysis using biochemical ascertainment of active smoking in NHANES and in sensitivity analyses accounting for potential demographic changes in stroke epidemiology. Conclusions— In contrast to the general population, the prevalence of active smoking among stroke survivors has not decreased during the past 2 decades.

Background and Purpose— The risk of arterial ischemic events after subdural hemorrhage (SDH) is poorly understood. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction among patients with and without nontraumatic SDH. Methods— We performed a retrospective cohort study using claims data from 2008 through 2014 from a nationally representative sample of Medicare beneficiaries. The exposure was nontraumatic SDH. Our primary outcome was an arterial ischemic event, a composite of acute ischemic stroke and acute myocardial infarction. Secondary outcomes were ischemic stroke alone and myocardial infarction alone. We used validated International Classification of Diseases , Ninth Revision , Clinical Modification diagnosis codes to identify our predictor and outcomes. Using Cox regression and corresponding survival probabilities, adjusted for demographics and vascular comorbidities, we computed the hazard ratio in 4-week intervals after SDH discharge. We performed secondary analyses stratified by strong indications for antithrombotic therapy (composite of atrial fibrillation, peripheral vascular disease, valvular heart disease, and venous thromboembolism). Results— Among 1.7 million Medicare beneficiaries, 2939 were diagnosed with SDH. In the 4 weeks after SDH, patients’ risk of an arterial ischemic event was substantially increased (hazard ratio, 3.6 [95% CI, 1.9–5.5]). There was no association between SDH diagnosis and arterial ischemic events beyond 4 weeks. In secondary analysis, during the 4 weeks after SDH, patients’ risk of ischemic stroke was increased (hazard ratio, 4.2 [95% CI, 2.1–7.3]) but their risk of myocardial infarction was not (hazard ratio, 0.8 [95% CI, 0.2–1.7]). Patients with strong indications for antithrombotic therapy had increased risks for arterial ischemic events similar to patients in the primary analysis, but those without such indications did not demonstrate an increased risk for arterial ischemic events. Conclusions— Among Medicare beneficiaries, we found a heightened risk of arterial ischemic events driven by an increased risk of ischemic stroke, in the 4 weeks after nontraumatic SDH. This increased risk may be due to interruption of antithrombotic therapy after SDH diagnosis.

Background and Purpose— The risk of arterial ischemic events after intracerebral hemorrhage (ICH) is poorly understood given the lack of a control group in prior studies. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction (MI) among patients with and without ICH. Methods— We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008 to 2014. Our exposure was acute ICH, identified using validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Our primary outcome was a composite of acute ischemic stroke and MI, whereas secondary outcomes were ischemic stroke alone and MI alone. We used Cox regression analysis to compute hazard ratios during 1-month intervals after ICH. Sensitivity analyses entailed exclusion of patients with atrial fibrillation and valvular heart disease. Results— Among 1 760 439 Medicare beneficiaries, 5924 had ICH. The 1-year cumulative incidence of an arterial ischemic event was 5.7% (95% CI, 4.8–6.8) in patients with ICH and 1.8% (95% CI, 1.7–1.9) in patients without ICH. After adjusting for potential confounders, the risk of an arterial ischemic event remained significantly increased for the first 6 months after ICH and was especially high in the first month (hazard ratio, 6.7 [95% CI, 5.0–8.6]). In secondary analysis, the risk of ischemic stroke was increased in the first 6 months after ICH (hazard ratio, 6.1 [95% CI, 3.5–9.3]) but the risk of MI was not (hazard ratio, 1.6 [95% CI, 0.3–2.9]). In sensitivity analyses excluding patients with atrial fibrillation and valvular heart disease, the association between ICH and arterial ischemic events was similar to that of the primary analysis. Conclusions— In a large population-based cohort, we found that elderly patients with ICH had a substantially increased risk of ischemic stroke in the first 6 months after diagnosis. Further exploration of this risk is needed to determine optimal secondary prevention strategies for these patients.

OBJECTIVES: Cancer can present as stroke. Several cancer types have established screening guidelines. We investigated adherence to guideline-recommended cancer screening in stroke survivors versus the general population. MATERIALS AND METHODS: We performed a cross-sectional analysis using 2012–2018 data from the CDC’s Behavioral Risk Factor Surveillance System (BRFSS) survey. BRFSS is a nationally-representative telephone survey of non-institutionalized Americans that collects data about health conditions and behaviors, including cancer screening. We defined guideline-recommended colorectal, lung, and breast cancer screening based on the U.S. Preventive Services Task Force recommendations. We used survey-specific methods to estimate up-to-date screening rates for those with and without prior stroke. We used logistic regression to estimate the odds of up-to-date screening in stroke survivors compared to those without history of stroke after adjustment for potential confounders. RESULTS: Among 1,018,440 respondents eligible for colorectal cancer screening, 66% were up-to-date. Among 6,880 respondents eligible for lung cancer screening, 16% were up-to-date. Among 548,434 women eligible for breast cancer screening, 78% were up-to-date. After adjustment for demographics and confounders, stroke survivors were more likely to have up-to-date colorectal cancer screening (OR, 1.10; 95% CI, 1.05–1.16), equally likely to undergo lung cancer screening (OR, 0.99; 95% CI, 0.62–1.59), and less likely to undergo breast cancer screening (OR, 0.87; 95% CI, 0.80–0.94). CONCLUSIONS: In a nationwide analysis, stroke survivors had similar suboptimal adherence to guideline-recommended cancer screening as the general population.

Background and Purpose— Comorbid cancer is common in patients with acute ischemic stroke (AIS). As blood mRNA profiles can distinguish AIS mechanisms, we hypothesized that cancer-related AIS would have a distinctive gene expression profile. Methods— We evaluated 4 groups of 10 subjects prospectively enrolled at 3 centers from 2009 to 2018. This included the group of interest with active solid tumor cancer and AIS and 3 control groups with active cancer only, AIS only, or vascular risk factors only. Subjects in the AIS-only and cancer-only groups were matched to subjects in the cancer-stroke group by age, sex, and cancer type (if applicable). Subjects in the vascular risk factor group were matched to subjects in the cancer-stroke and stroke-only groups by age, sex, and vascular risk factors. Blood was drawn 72 to 120 hours after stroke. Total RNA was processed using 3′ mRNA sequencing. ANOVA and Fisher least significant difference contrast methods were used to estimate differential gene expression between groups. Results— In the cancer-stroke group, 50% of strokes were cryptogenic. All groups had differentially expressed genes that could distinguish among them. Comparing the cancer-stroke group to the stroke-only group and after accounting for cancer-only genes, 438 genes were differentially expressed, including upregulation of multiple genes/pathways implicated in autophagy signaling, immunity/inflammation, and gene regulation, including IL (interleukin)-1, interferon, relaxin, mammalian target of rapamycin signaling, SQSTMI1 (sequestosome-1), and CREB1 (cAMP response element binding protein-1). Conclusions— This study provides evidence for a distinctive molecular signature in blood mRNA expression profiles of patients with cancer-related AIS. Future studies should evaluate whether blood mRNA can predict detection of occult cancer in patients with AIS. Clinical Trial Registration— URL: https://clinicaltrials.gov . Unique identifier: NCT02604667.

ObjectiveTransesophageal echocardiography (TEE) is sometimes used to search for cardioembolic sources after ischemic stroke or transient ischemic attack (TIA). TEE visualizes some sources better than transthoracic echocardiography, but TEE is invasive and may cause aspiration. Few data exist on the risk of respiratory complications after TEE in patients who had stroke or TIA. Our objective was to determine whether TEE was associated with increased risk of respiratory failure in patients who had ischemic stroke or TIA.DesignThis is a retrospective cohort study using administrative data from inpatient and outpatient insurance claims collected by the US federal government’s Centers for Medicare and Medicaid Services.SettingHospitals and outpatient clinics throughout the USA.Participants99 081 patients ≥65 years old hospitalized for out-of-hospital ischemic stroke or TIA, defined by validated International Classification of Disease-9/10 diagnosis codes and present-on-admission codes, using claims data from 2008 to 2018 in a random 5% sample of Medicare beneficiaries.Main outcome measuresAcute respiratory failure, defined as endotracheal intubation and/or mechanical ventilation, starting on the first day after admission through 28 days afterward.ResultsOf 99 081 patients included in this analysis, 73 733 (74.4%) had an ischemic stroke and 25 348 (25.6%) a TIA. TEE was performed in 4677 (4.7%) patients and intubation and/or mechanical ventilation in 1403 (1.4%) patients. The 28-day cumulative risk of respiratory failure after TEE (1.4%; 95% CI 0.8% to 2.7%) was similar to that seen in those without TEE (1.4%; 95% CI 1.4% to 1.5%) (p=0.84). After adjustment for age, sex, race, Charlson comorbidities, diagnosis of stroke versus TIA, intravenous thrombolysis, and mechanical thrombectomy, TEE was not associated with an increased risk of respiratory failure (HR, 0.9; 95% CI 0.6 to 1.2).ConclusionsIn a cohort of older patients who had ischemic stroke or TIA, TEE was not associated with an increased risk of subsequent respiratory failure.

Background: It is important to understand the risk for in-hospital mortality of adults hospitalized with acute coronavirus disease 2019 (COVID-19) infection with a history of heart failure (HF). Methods: We examined patients hospitalized with COVID-19 infection from January 1, 2020 to July 22, 2020, from 88 centers across the US participating in the American Heart Association’s COVID-19 Cardiovascular Disease registry. The primary exposure was history of HF and the primary outcome was in-hospital mortality. To examine the association between history of HF and in-hospital mortality, we conducted multivariable modified Poisson regression models that included sociodemographics and comorbid conditions. We also examined HF subtypes based on left ventricular ejection fraction in the prior year, when available. Results: Among 8920 patients hospitalized with COVID-19, mean age was 61.4±17.5 years and 55.5% were men. History of HF was present in 979 (11%) patients. In-hospital mortality occurred in 31.6% of patients with history of HF, and 16.9% in patients without a history of HF. In a fully adjusted model, history of HF was associated with increased risk for in-hospital mortality (relative risk: 1.16 [95% CI, 1.03–1.30]). Among 335 patients with left ventricular ejection fraction, heart failure with reduced ejection fraction was significantly associated with in-hospital mortality in a fully adjusted model (heart failure with reduced ejection fraction relative risk: 1.40 [95% CI, 1.10–1.79]; heart failure with mid-range ejection fraction relative risk: 1.06 [95% CI, 0.65–1.73]; heart failure with preserved ejection fraction relative risk, 1.06 [95% CI, 0.84–1.33]). Conclusions: Risk for in-hospital mortality was substantial among adults with history of HF, in large part due to age and comorbid conditions. History of heart failure with reduced ejection fraction may confer especially elevated risk. This population thus merits prioritization for the COVID-19 vaccine.

Supplemental Digital Content is available in the text., Background and Purpose: We systematically evaluated the impact of the coronavirus 2019 (COVID-19) pandemic on stroke care across the world. Methods: Observational studies comparing characteristics, acute treatment delivery, or hospitalization outcomes between patients with stroke admitted during the COVID-19 pandemic and those admitted before the pandemic were identified by Medline, Scopus, and Embase databases search. Random-effects meta-analyses were conducted for all outcomes. Results: We identified 46 studies including 129 491 patients. Patients admitted with stroke during the COVID-19 pandemic were found to be younger (mean difference, −1.19 [95% CI, −2.05 to −0.32]; I2=70%) and more frequently male (odds ratio, 1.11 [95% CI, 1.01–1.22]; I2=54%) compared with patients admitted with stroke in the prepandemic era. Patients admitted with stroke during the COVID-19 pandemic, also, had higher baseline National Institutes of Health Stroke Scale scores (mean difference, 0.55 [95% CI, 0.12–0.98]; I2=90%), higher probability for large vessel occlusion presence (odds ratio, 1.63 [95% CI, 1.07–2.48]; I2=49%) and higher risk for in-hospital mortality (odds ratio, 1.26 [95% CI, 1.05–1.52]; I2=55%). Patients with acute ischemic stroke admitted during the COVID-19 pandemic had higher probability of receiving endovascular thrombectomy treatment (odds ratio, 1.24 [95% CI, 1.05–1.47]; I2=40%). No difference in the rates of intravenous thrombolysis administration or difference in time metrics regarding onset to treatment time for intravenous thrombolysis and onset to groin puncture time for endovascular thrombectomy were detected. Conclusions: The present systematic review and meta-analysis indicates an increased prevalence of younger patients, more severe strokes attributed to large vessel occlusion, and higher endovascular treatment rates during the COVID-19 pandemic. Patients admitted with stroke during the COVID-19 pandemic had higher in-hospital mortality. These findings need to be interpreted with caution in view of discrepant reports and heterogeneity being present across studies.

Introduction: Non-traumatic subarachnoid hemorrhage (SAH) is associated with poor long-term functional outcomes, but the risk of ischemic stroke among SAH survivors is poorly understood. Objectives: The aim of this study was to evaluate the risk of ischemic stroke among survivors of SAH. Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008 to 2015. The exposure was a diagnosis of SAH, while the outcome was an acute ischemic stroke, both identified using previously validated ICD-9-CM diagnosis codes. We used Cox regression analysis adjusting for demographics and stroke risk factors to evaluate the association between SAH and long-term risk of ischemic stroke. Results: Among 1.7 million Medicare beneficiaries, 912 were hospitalized with non-traumatic SAH. During a median follow-up of 5.2 years (IQR, 2.7–6.7), the cumulative incidence of ischemic stroke was 22 per 1,000 patients per year among patients with SAH, and 7 per 1,000 patients per year in those without SAH. In adjusted Cox models, SAH was associated with an increased risk of ischemic stroke (HR, 2.0; 95% confidence interval, 1.4–2.8) as compared to beneficiaries without SAH. Similar results were obtained in sensitivity analyses, when treating death as a competing risk (sub HR, 3.0; 95% CI, 2.8–3.3) and after excluding ischemic stroke within 30 days of SAH discharge (HR, 1.5; 95% CI, 1.1–2.3). Conclusions: In a large, heterogeneous national cohort of elderly patients, survivors of SAH had double the long-term risk of ischemic stroke. SAH survivors should be closely monitored and risk stratified for ischemic stroke.

Background and Purpose: The impact of arterial ischemic events after intracerebral hemorrhage (ICH) on outcomes is unclear. This study aimed to evaluate the risk of death among ICH survivors with and without an incident arterial ischemic event. Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries with a non-traumatic ICH from January 2008 to October 2015. Our exposure was an arterial ischemic event, a composite of acute ischemic stroke or myocardial infarction (MI), identified using validated ICD-9-CM diagnosis codes. The outcome was mortality. We used marginal structural models to analyze the risk of death among ICH patients with and without an arterial ischemic event, after adjusting for confounders as time-varying covariates. Results: Among 8,804 Medicare beneficiaries with ICH, 2,371 (26.9%) had an arterial ischemic event. During a median follow-up time of 1.9 years (interquartile range, 0.7-3.9), ICH patients with an arterial ischemic event had a mortality rate of 21.7 (95% confidence interval [CI], 20.4-23.0) per 100 person-years compared to a rate of 15.0 (95% CI, 14.4-15.6) per 100 person-years in those without. In the marginal structural model, an arterial ischemic event was associated with an increased risk of death (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.6-1.9). In secondary analyses, the mortality risk was elevated after an ischemic stroke (HR, 1.7; 95% CI, 1.5-1.8), and MI (HR, 3.0; 95% CI, 2.4-3.8). Conclusions: We found that elderly patients who survived an ICH had an increased risk of death after a subsequent ischemic stroke or MI.

Background and Purpose: Mechanical thrombectomy helps prevent disability in patients with acute ischemic stroke involving occlusion of a large cerebral vessel. Thrombectomy requires procedural expertise and not all hospitals have the staff to perform this intervention. Few population-wide data exist regarding access to mechanical thrombectomy. Methods: We examined access to thrombectomy for ischemic stroke using discharge data from calendar years 2016 to 2018 from all nonfederal emergency departments and acute care hospitals across 11 US states encompassing 80 million residents. Facilities were classified as hubs if they performed mechanical thrombectomy, gateways if they transferred patients who ultimately underwent mechanical thrombectomy, and gaps otherwise. We used standard descriptive statistics and unadjusted logistic regression models in our primary analyses. Results: Among 205 681 patients with ischemic stroke, 100 139 (48.7% [95% CI, 48.5%–48.9%]) initially received care at a thrombectomy hub, 72 534 (35.3% [95% CI, 35.1%–35.5%]) at a thrombectomy gateway, and 33 008 (16.0% [95% CI, 15.9%–16.2%]) at a thrombectomy gap. Patients who initially received care at thrombectomy gateways were substantially less likely to ultimately undergo thrombectomy than patients who initially received care at thrombectomy hubs (odds ratio, 0.27 [95% CI, 0.25–0.28]). Rural patients had particularly limited access: 27.7% (95% CI, 26.9%–28.6%) of such patients initially received care at hubs versus 69.5% (95% CI, 69.1%–69.9%) of urban patients. For 93.8% (95% CI, 93.6%–94.0%) of patients with stroke at gateways, their initial facility was capable of delivering intravenous thrombolysis, compared with 76.3% (95% CI, 75.8%–76.7%) of patients at gaps. Our findings were unchanged in models adjusted for demographics and comorbidities and persisted across multiple sensitivity analyses, including analyses adjusting for estimated stroke severity. Conclusions: We found that a substantial proportion of patients with ischemic stroke across the United States lacked access to thrombectomy even after accounting for interhospital transfers. US systems of stroke care require further development to optimize thrombectomy access.

Objective To determine whether cerebrovascular risk factors are associated with subsequent diagnoses of Parkinson disease, and whether these associations are similar in magnitude to those with subsequent diagnoses of Alzheimer disease. Methods This was a retrospective cohort study using claims data from a 5% random sample of Medicare beneficiaries from 2008 to 2015. The exposures were stroke, atrial fibrillation, coronary disease, hyperlipidemia, hypertension, sleep apnea, diabetes mellitus, heart failure, peripheral vascular disease, chronic kidney disease, chronic obstructive pulmonary disease, valvular heart disease, tobacco use, and alcohol abuse. The primary outcome was a new diagnosis of idiopathic Parkinson disease. The secondary outcome was a new diagnosis of Alzheimer disease. Marginal structural Cox models adjusting for time-dependent confounding were used to characterize the association between exposures and outcomes. We also evaluated the association between cerebrovascular risk factors and subsequent renal colic (negative control). Results Among 1,035,536 Medicare beneficiaries followed for a mean of 5.2 years, 15,531 (1.5%) participants were diagnosed with Parkinson disease and 81,974 (7.9%) were diagnosed with Alzheimer disease. Most evaluated cerebrovascular risk factors, including prior stroke (hazard ratio = 1.55; 95% confidence interval = 1.39-1.72), were associated with the subsequent diagnosis of Parkinson disease. The magnitudes of these associations were similar, but attenuated, to the associations between cerebrovascular risk factors and Alzheimer disease. Confirming the validity of our analytical model, most cerebrovascular risk factors were not associated with the subsequent diagnosis of renal colic. Interpretation Cerebrovascular risk factors are associated with Parkinson disease, an effect comparable to their association with Alzheimer disease. ANN NEUROL 2019;86:572-581.

Objective Atrial cardiopathy without atrial fibrillation (AF) may be a potential cardiac source of embolic strokes of undetermined source (ESUS). Atrial volume is a feature of atrial cardiopathy, but the relationship between atrial volume and ESUS remains unclear. Methods We compared left atrial volume among ischemic stroke subtypes in the Cornell Acute Stroke Academic Registry (CAESAR), which includes all patients with acute ischemic stroke at our hospital since 2011. Stroke subtype was determined by neurologists per the TOAST classification and consensus ESUS definition. Left atrial volume index (LAVI) was obtained directly from our echocardiography image system (Xcelera, Philips Healthcare). We used t‐tests and analysis of variance for unadjusted comparisons and targeted minimum loss‐based estimation for comparisons adjusted for demographics and comorbidities. Results Among 2116 patients in CAESAR from 2011 to 2016, 1293 had LAVI measurements. LAVI varied across subtypes (P