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Background: Utilization of oral anticoagulants for acute ischemic stroke (AIS) prevention in patients with atrial fibrillation (AF) increased in the United States over the last decade. Whether this increase has been accompanied by any change in AF prevalence in AIS at the population level remains unknown. The aim of this study is to evaluate trends in AF prevalence in AIS hospitalizations in various age, sex, and racial subgroups over the last decade. Methods: We used data contained in the 2010–2020 National Inpatient Sample to conduct a serial cross-sectional study. Primary AIS hospitalizations with and without comorbid AF were identified using International Classification of Diseases Codes. Joinpoint regression was used to compute annualized percentage change (APC) in prevalence and to identify points of change in prevalence over time. Results: Of 5,190,148 weighted primary AIS hospitalizations over the study period, 25.1% had comorbid AF. The age- and sex-standardized prevalence of AF in AIS hospitalizations increased across the entire study period 2010–2020 (average APC: 1.3%, 95% confidence interval (CI): 0.8–1.7%). Joinpoint regression showed that prevalence increased in the period 2010–2015 (APC: 2.8%, 95% CI: 1.9–3.9%) but remained stable in the period 2015–2020 (APC: –0.3%, 95% CI: –1.0 to 1.9%). Upon stratification by age and sex, prevalence increased in all age/sex groups from 2010 to 2015 and continued to increase throughout the entire study period in hospitalizations in men 18–39 years (APC: 4.0%, 95% CI: 0.2–7.9%), men 40–59 years (APC: 3.4%, 95% CI: 1.9–4.9%) and women 40–59 years (APC: 4.4%, 95% CI: 2.0–6.8%). In contrast, prevalence declined in hospitalizations in women 60–79 (APC: –1.0%, 95% CI: –0.5 to –1.5%) and women ⩾ 80 years over the period 2015–2020 but plateaued in hospitalizations in similar-aged men over the same period. Conclusion: AF prevalence in AIS hospitalizations in the United States increased over the period 2010–2015, then plateaued over the period 2015–2020 due to declining prevalence in hospitalizations in women ⩾ 60 years and plateauing prevalence in hospitalizations in men ⩾ 60 years. [ABSTRACT FROM AUTHOR]

Background: The prevalence, incidence and risk factors of atrial fibrillation (AF) in a large, geographically and ethnically diverse cohort in the United States have not been fully described. Methods: We analyzed data from 173,099 participants of the All of Us Research Program recruited in the period 2017–2019, with 92,318 of them having electronic health records (EHR) data available, and 35,483 having completed a medical history survey. Presence of AF at baseline was identified from self-report and EHR records. Incident AF was obtained from EHR. Demographic, anthropometric and clinical risk factors were obtained from questionnaires, baseline physical measurements and EHR. Results: At enrollment, mean age was 52 years old (range 18–89). Females and males accounted for 61% and 39% respectively. Non-Hispanic Whites accounted for 67% of participants, with non-Hispanic Blacks, non-Hispanic Asians and Hispanics accounting for 26%, 4% and 3% of participants, respectively. Among 92,318 participants with available EHR data, 3,885 (4.2%) had AF at the time of study enrollment, while the corresponding figure among 35,483 with medical history data was 2,084 (5.9%). During a median follow-up of 16 months, 354 new cases of AF were identified among 88,433 eligible participants. Individuals who were older, male, non-Hispanic white, had higher body mass index, or a prior history of heart failure or coronary heart disease had higher prevalence and incidence of AF. Conclusion: The epidemiology of AF in the All of Us Research Program is similar to that reported in smaller studies with careful phenotyping, highlighting the value of this new resource for the study of AF and, potentially, other cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: We sought to characterize the specialty classification of US physicians who provide critical care for neurological/neurosurgical disease.Methods: Using inpatient claims between 2009 and 2015 from a nationally representative 5% sample of Medicare beneficiaries, we selected hospitalizations for neurological/neurosurgical diseases with potential to result in life-threatening manifestations requiring critical care. Using Current Procedural Terminology® codes, we determined the medical specialty of providers submitting critical care claims, and, using National Provider Identifier numbers, we merged in data from the United Council for Neurologic Subspecialties (UCNS) to determine whether the provider was a UCNS diplomate in neurocritical care. We defined providers with a clinical neuroscience background as neurologists, neurosurgeons, and/or UCNS diplomates in neurocritical care. We defined neurocritical care service as a critical care claim with a qualifying neurological/neurosurgical diagnosis in patients with a relevant primary hospital discharge diagnosis and ≥ 3 total critical care claims, excluding claims from the first day of hospitalization since these were mostly emergency-department claims. Our findings were reported using descriptive statistics with exact confidence intervals (CI).Results: Among 1,952,305 Medicare beneficiaries, we identified 99,937 hospitalizations with at least one claim for neurocritical care. In our primary analysis, neurologists accounted for 28.0% (95% CI, 27.5-28.5%) of claims, neurosurgeons for 3.7% (95% CI, 3.5-3.9%), UCNS-certified neurointensivists for 25.8% (95% CI, 25.3-26.3%), and providers with any clinical neuroscience background for 42.8% (95% CI, 42.2-43.3%). The likelihood of management by physicians with a clinical neuroscience background increased proportionally with patients' county-level socioeconomic status and such providers were 3 times more likely to be based at an academic medical center than other physicians who billed for critical care in our sample (odds ratio, 2.9; 95% CI, 1.1-8.1).Conclusions: Physicians with a dedicated clinical neuroscience background accounted for less than half of neurocritical care service in US Medicare beneficiaries. [ABSTRACT FROM AUTHOR]

Objective: Oral anticoagulation treatment (OAT) resumption is a therapeutic dilemma in intracerebral hemorrhage (ICH) care, particularly for lobar hemorrhages related to amyloid angiopathy. We sought to determine whether OAT resumption after ICH is associated with long-term outcome, accounting for ICH location (ie, lobar vs nonlobar).Methods: We meta-analyzed individual patient data from: (1) the multicenter RETRACE study (n = 542), (2) a U.S.-based single-center ICH study (n = 261), and (3) the Ethnic/Racial Variations of Intracerebral Hemorrhage study (n = 209). We determined whether, within 1 year from ICH, OAT resumption was associated with: (1) mortality, (2) favorable functional outcome (modified Rankin Scale = 0-3), and (3) stroke incidence. We separately analyzed nonlobar and lobar ICH cases using propensity score matching and Cox regression models.Results: We included 1,012 OAT-related ICH survivors (633 nonlobar and 379 lobar). Among nonlobar ICH survivors, 178/633 (28%) resumed OAT, whereas 86/379 (23%) lobar ICH survivors did. In multivariate analyses, OAT resumption after nonlobar ICH was associated with decreased mortality (hazard ratio [HR] = 0.25, 95% confidence interval [CI] = 0.14-0.44, p < 0.0001) and improved functional outcome (HR = 4.22, 95% CI = 2.57-6.94, p < 0.0001). OAT resumption after lobar ICH was also associated with decreased mortality (HR = 0.29, 95% CI = 0.17-0.45, p < 0.0001) and favorable functional outcome (HR = 4.08, 95% CI = 2.48-6.72, p < 0.0001). Furthermore, OAT resumption was associated with decreased all-cause stroke incidence in both lobar and nonlobar ICH (both p < 0.01).Interpretation: These results suggest novel evidence of an association between OAT resumption and outcome following ICH, regardless of hematoma location. These findings support conducting randomized trials to explore risks and benefits of OAT resumption after ICH. Ann Neurol 2017;82:755-765. [ABSTRACT FROM AUTHOR]

The article discusses a study of the national trends in ambulance use (AU) by patients with stroke in the U.S. from 1997 to 2008, using the data collected by the National Hospital Ambulatory Medical Care Survey. The researchers examined trends within groups of patients with a primary diagnosis of ischemic stroke and those with subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack, defined by characteristics such as age, sex, race and stroke subtype. They found that the proportion of patients with stroke who arrived at the emergency department via ambulance did not change between 1997 and 2008.

This Viewpoint reviews evidence of the benefits of thrombectomy for patients with ischemic stroke due to large vessel occlusion, and details the systems of care that need to be developed to ensure that all patients who might benefit from the procedure can be rapidly identified, transported, imaged, and treated under the care of qualified specialists. [ABSTRACT FROM AUTHOR]

Background: The risk of arterial thromboembolism in patients with cancer is incompletely understood.Objectives: The authors aimed to better define this epidemiological relationship, including the effects of cancer stage.Methods: Using the Surveillance Epidemiology and End Results-Medicare linked database, the authors identified patients with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, pancreatic, or gastric cancer or non-Hodgkin lymphoma from 2002 to 2011. They were individually matched by demographics and comorbidities to a Medicare enrollee without cancer, and each pair was followed through 2012. Validated diagnosis codes were used to identify arterial thromboembolism, defined as myocardial infarction or ischemic stroke. Cumulative incidence rates were calculated using competing risk survival statistics. Cox hazards analysis was used to compare rates between groups at discrete time points.Results: The authors identified 279,719 pairs of patients with cancer and matched control patients. The 6-month cumulative incidence of arterial thromboembolism was 4.7% (95% confidence interval [CI]: 4.6% to 4.8%) in patients with cancer compared with 2.2% (95% CI: 2.1% to 2.2%) in control patients (hazard ratio [HR]: 2.2; 95% CI: 2.1 to 2.3). The 6-month cumulative incidence of myocardial infarction was 2.0% (95% CI: 1.9% to 2.0%) in patients with cancer compared with 0.7% (95% CI: 0.6% to 0.7%) in control patients (HR: 2.9; 95% CI: 2.8 to 3.1). The 6-month cumulative incidence of ischemic stroke was 3.0% (95% CI: 2.9% to 3.1%) in patients with cancer compared with 1.6% (95% CI: 1.6% to 1.7%) in control patients (HR: 1.9; 95% CI: 1.8 to 2.0). Excess risk varied by cancer type (greatest for lung), correlated with cancer stage, and generally had resolved by 1 year.Conclusions: Patients with incident cancer face a substantially increased short-term risk of arterial thromboembolism. [ABSTRACT FROM AUTHOR]

Clinically recognized atrial fibrillation (AF) is associated with higher risk of complications, including ischemic stroke, cognitive decline, heart failure, myocardial infarction, and death. It is increasingly recognized that AF frequently is undetected until complications such as stroke or heart failure occur. Hence, the public and clinicians have an intense interest in detecting AF earlier. However, the most appropriate strategies to detect undiagnosed AF (sometimes referred to as subclinical AF) and the prognostic and therapeutic implications of AF detected by screening are uncertain. Our report summarizes the National Heart, Lung, and Blood Institute's virtual workshop focused on identifying key research priorities related to AF screening. Global experts reviewed major knowledge gaps and identified critical research priorities in the following areas: (1) role of opportunistic screening; (2) AF as a risk factor, risk marker, or both; (3) relationship between AF burden detected with long-term monitoring and outcomes/treatments; (4) designs of potential randomized trials of systematic AF screening with clinically relevant outcomes; and (5) role of AF screening after ischemic stroke. Our report aims to inform and catalyze AF screening research that will advance innovative, resource-efficient, and clinically relevant studies in diverse populations to improve the diagnosis, management, and prognosis of patients with undiagnosed AF. [ABSTRACT FROM AUTHOR]

Background and purpose To assess the rate of neurological complications and mortality after tuberculous meningitis in the United States. Methods The authors performed a retrospective cohort study of all patients 18 years or older hospitalized for tuberculous meningitis in California between 2005 and 2010, New York between 2006 and 2012, and Florida between 2005 and 2012. Outcomes of interest were mortality and the following neurological complications: stroke, seizure, hydrocephalus requiring a ventriculoperitoneal shunt, vision impairment, and hearing impairment. Kaplan–Meier survival statistics were used to assess the cumulative rate of neurological complications and death. Cox proportional hazards regression was used to compare rates of complications in patients with and without human immunodeficiency virus (HIV) after adjustment for comorbidities. Results 806 patients with tuberculous meningitis were identified, among whom the cumulative rate of any complication or death was 55.4% (95% CI, 51.5–59.3%). More than two-thirds of complications occurred during the initial hospitalization for tuberculous meningitis. Individual neurological complications were not uncommon: the cumulative rate of stroke was 16.8% (95% CI, 14.0–20.0%), the rate of seizure was 18.8% (95% CI, 15.4–22.8%), and the rate of ventriculoperitoneal shunting was 8.4% (95% CI, 6.4–10.9%). Vision impairment occurred in 21.6% (95% CI, 18.5–25.1%) of patients and hearing impairment occurred in 6.8% (95% CI, 4.9–9.4%). The mortality rate was 21.5% (95% CI, 18.4–24.9%). Patients with HIV infection were not at increased risk of complications compared to patients without HIV (hazard ratio, 1.2; 95% CI, 0.9–1.6). Conclusions Tuberculous meningitis is associated with significant risk of neurological complications and death in the United States. [ABSTRACT FROM AUTHOR]

Background and Aims: Most cancer patients require surgery for diagnosis and treatment. This study evaluated whether cancer is a risk factor for perioperative arterial ischaemic events., Methods: The primary cohort included patients registered in the National Surgical Quality Improvement Program (NSQIP) between 2006 and 2016. The secondary cohort included Healthcare Cost and Utilization Project (HCUP) claims data from 11 US states between 2016 and 2018. Study populations comprised patients who underwent inpatient (NSQIP, HCUP) or outpatient (NSQIP) surgery. Study exposures were disseminated cancer (NSQIP) and all cancers (HCUP). The primary outcome was a perioperative arterial ischaemic event, defined as myocardial infarction or stroke diagnosed within 30 days after surgery., Results: Among 5 609 675 NSQIP surgeries, 2.2% involved patients with disseminated cancer. The perioperative arterial ischaemic event rate was 0.96% among patients with disseminated cancer vs. 0.48% among patients without (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.90-2.13). In Cox analyses adjusting for demographics, functional status, comorbidities, surgical specialty, anesthesia type, and clinical factors, disseminated cancer remained associated with higher risk of perioperative arterial ischaemic events (HR, 1.37; 95% CI, 1.28-1.46). Among 1 341 658 surgical patients in the HCUP cohort, 11.8% had a diagnosis of cancer. A perioperative arterial ischaemic event was diagnosed in 0.74% of patients with cancer vs. 0.54% of patients without cancer (HR, 1.35; 95% CI, 1.27-1.43). In Cox analyses adjusted for demographics, insurance, comorbidities, and surgery type, cancer remained associated with higher risk of perioperative arterial ischaemic events (HR, 1.31; 95% CI, 1.21-1.42)., Conclusion: Cancer is an independent risk factor for perioperative arterial ischaemic events., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Infertility treatment with assisted reproductive technologies (ARTs) has been associated with adverse vascular events in some but not all previous studies. Endothelial damage, prothrombotic factor release, and a higher prevalence of cardiovascular risk factors in those receiving ART have been invoked to explain this association. We sought to explore the relationship between ART and stroke risk using population-level data., Methods: We conducted a retrospective cohort study using data from the National Inpatient Sample registry from 2015 to 2020, including all delivery hospitalizations for patients aged 15 to 55 years. The study exposure was use of ART. The primary end point was any stroke defined as ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, or cerebral venous thrombosis during index delivery hospitalization. Individual stroke subtypes (ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral venous thrombosis) were evaluated as secondary end points. Standard International Classification of Diseases, Tenth Revision , Clinical Modification algorithms were used to define study exposure, comorbidities, and prespecified end points. In addition to reporting population-level estimates, propensity score adjustment by inverse probability weighting was used to mimic the effects of randomization by balancing baseline clinical characteristics associated with stroke between ART and non-ART users., Results: Among 19 123 125 delivery hospitalizations identified, patients with prior ART (n=202 815, 1.1%) experienced significantly higher rates of any stroke (27.1/100 000 versus 9.1/100 000), ischemic stroke (9.9/100 000 versus 3.3/100 000), subarachnoid hemorrhage (7.4/100 000 versus 1.6/100 000), intracerebral hemorrhage (7.4/100 000 versus 2.0/100 000), and cerebral venous thrombosis (7.4/100 000 versus 2.7/100 000) in comparison to non-ART users (all P <0.001 for all unadjusted comparisons). Following inverse probability weighting analysis, ART was associated with increased odds of any stroke (adjusted odds ratios, 2.14 (95% CI, 2.02-2.26); P <0.001)., Conclusions: Using population-level data among patients hospitalized for delivery in the United States, we found an association between ART and stroke after adjustment for measured confounders., Competing Interests: Disclosures Dr Liberman is supported by National Institute for Neurological Disorders and Stroke (NINDS) research grant K23NS10764. Dr Navi has received personal fees for serving as a neurology expert witness. Dr Kamel reports PI for the ARCADIA trial (NIH/NINDS U01NS095869), which receives in-kind study drug from the BMS-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics; other funding from NIH (R01HL144541, R01NS123576, U01NS106513); Deputy Editor for JAMA Neurology; clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; end point adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group. Dr Seitz has stock in Colgate-Palmolive Company and had stock (sold December 2022) in Baxter International, Inc, Bristol Myers Squibb Company, CVS Health Corporation, Johnson & Johnson, Eli Lilly, and Company, Proctor & Gamble Company, UnitedHealth Group Incorporated, Walgreen Boots Alliance, Inc, and White Mountains Insurance.

Importance: Ischemic stroke is a serious complication of cardiac intervention, including surgery and percutaneous procedures. Endovascular thrombectomy (EVT) is an effective treatment for ischemic stroke and may be particularly important for cardiac intervention patients who often cannot receive intravenous thrombolysis., Objective: To examine trends in EVT for ischemic stroke during hospitalization of patients with cardiac interventions vs those without in the United States., Design, Setting, and Participants: This cohort study involved a retrospective analysis using data for 4888 US hospitals from the 2016-2020 National Inpatient Sample database. Participants included adults (age ≥18 years) with ischemic stroke (per codes from the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification), who were organized into study groups of hospitalized patients with cardiac interventions vs without. Individuals were excluded from the study if they had either procedure prior to admission, EVT prior to cardiac intervention, EVT more than 3 days after admission or cardiac intervention, or endocarditis. Data were analyzed from April 2023 to October 2023., Exposures: Cardiac intervention during admission., Main Outcomes and Measures: The odds of undergoing EVT by cardiac intervention status were calculated using multivariable logistic regression. Adjustments were made for stroke severity in the subgroup of patients who had a National Institutes of Health Stroke Scale (NIHSS) score documented. As a secondary outcome, the odds of discharge home by EVT status after cardiac intervention were modeled., Results: Among 634 407 hospitalizations, the mean (SD) age of the patients was 69.8 (14.1) years, 318 363 patients (50.2%) were male, and 316 044 (49.8%) were female. A total of 12 093 had a cardiac intervention. An NIHSS score was reported in 218 576 admissions, 216 035 (34.7%) without cardiac intervention and 2541 (21.0%) with cardiac intervention (P < .001). EVT was performed in 23 660 patients (3.8%) without cardiac intervention vs 194 (1.6%) of those with cardiac intervention (P < .001). After adjustment for potential confounders, EVT was less likely to be performed in stroke patients with cardiac intervention vs those without (adjusted odds ratio [aOR], 0.27; 95% CI, 0.23-0.31), which remained consistent after adjusting for NIHSS score (aOR, 0.28; 95% CI, 0.22-0.35). Among individuals with a cardiac intervention, receiving EVT was associated with a 2-fold higher chance of discharge home (aOR, 2.21; 95% CI, 1.14-4.29)., Conclusions and Relevance: In this study, patients hospitalized with ischemic stroke and cardiac intervention may be less than half as likely to receive EVT as those without cardiac intervention. Given the known benefit of EVT, there is a need to better understand the reasons for lower rates of EVT in this patient population.

Background: The usage rates of mineralocorticoids (fludrocortisone) to treat hyponatremia and isotonic crystalloids (saline and balanced crystalloids) to maintain intravascular volume in patients with aneurysmal subarachnoid hemorrhage (aSAH) patients across the United States are unknown., Methods: We surveyed National Institute of Neurologic Disorders and Stroke (NINDS) StrokeNet sites in 2023, which are mostly large, tertiary, academic centers, and analyzed subarachnoid hemorrhage encounters from 2010 to 2020 in the Premier Healthcare Database that is representative of all types of hospitals and captures about 20 % of all acute inpatient care in the United States., Results: Although mineralocorticoids are used by 70 % of the NINDS StrokeNet sites, it is used in less than 20 % of the aSAH encounters in the Premier Database. Although saline is ubiquitously used, balanced crystalloids are increasingly used for fluid therapy in aSAH patients. Its use in the NINDS StrokeNet sites and the Premier Healthcare Database is 41 and 45 %, respectively., Conclusions: The use of mineralocorticoids remains low, and balanced crystalloids are increasingly used as fluid therapy in aSAH patients. The effectiveness of mineralocorticoids and balanced crystalloids in improving outcomes for aSAH patients must be rigorously tested in randomized clinical trials., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The Stroke Treatment Academic Industry Roundtable (STAIR) convened a session and workshop regarding enrollment in acute stroke trials during the STAIR XII meeting on March 22, 2023. This forum brought together stroke physicians and researchers, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss the current status and opportunities for improving enrollment in acute stroke trials. The workshop identified the most relevant issues impacting enrollment in acute stroke trials and addressed potential action items for each. Focus areas included emergency consent in the United States and other countries; careful consideration of eligibility criteria to maximize enrollment and representativeness; investigator, study coordinator, and pharmacist availability outside of business hours; trial enthusiasm/equipoise; site start-up including contractual issues; site champions; incorporation of study procedures into standard workflow as much as possible; centralized enrollment at remote sites by study teams using telemedicine; global trials; and coenrollment in trials when feasible. In conclusion, enrollment of participants is the lifeblood of acute stroke trials and is the rate-limiting step for testing an exciting array of new approaches to improve patient outcomes. In particular, efforts should be undertaken to broaden the medical community's understanding and implementation of emergency consent procedures and to adopt designs and processes that are easily incorporated into standard workflow and that improve trials' efficiencies and execution. Research and actions to improve enrollment in ongoing and future trials will improve stroke outcomes more broadly than any single therapy under consideration., Competing Interests: Disclosures Dr Broderick receives monies from National Institute of Neurological Disorders and Stroke (NINDS) for research grants, receives study medication and monies for temperature monitoring and after-business hour enrollments from Novo Nordisk for NINDS-funded FASTEST Trial (rFVIIa for Acute Hemorrhagic Stroke Administered at Earliest Time Trial). The Department of Neurology receives monies to an educational/research fund from Genentech for his role on Executive Committee of Timeless Trial; from Roche Pharmaceuticals for consulting, from BrainsGate Ltd for consulting; from Basking Biosciences, from Kroger Prescription Plans Inc’s Pharmacy &Therapeutics Committee as voting member of committee. Dr Silva reports funding from the Brazilian Ministry of Health for the Resilient and OPTIMAL trials; consulting and speaker fees from AstraZeneca, Biogen, Boehringer Ingelheim, and Pfizer; consulting fees from IschemaView and Bayer, and speaker fees from Abbott. Dr Selim receives grant funding from the NINDS and NIA (related to and outside of the current work), and royalties from Up to Date and Cambridge University Press and is on the Advisory Board of MedRhythms Inc. Dr Kasner has received grant funding (to institution) from Genentech, Diamedica, Bristol-Myers Squibb, Bayer, Stryker, and Medtronic; consulting fees from Shionogi, Abbvie, Artivion, AstraZeneca, and NeuExcell; and royalties from UpToDate and Elsevier. Dr Adeoye receives funding from NINDS and has equity in and is the Chief Medical Officer for Sense Diagnostics, Inc and receives compensation from NICO Corporation for data and safety monitoring services. Dr Hill reports grants from MicroVention Inc; employment by University of Calgary; grants from Medtronic; grants from Boehringer Ingelheim; grants from Medtronic; grants from Medtronic; grants from Canadian Institutes of Health Research; grants from Biogen Inc; compensation from Brainsgate Ltd for consultant services; and grants from NoNO Inc. Dr Mistry receives funding from National Institutes of Health/NINDS and Patient-Centered Outcomes Research Institute (PCORI) and receives monies for consulting for RAPID AI, Abbvie, and the American Heart Association. Dr Smith is an employee of AbbVie Inc, and holds AbbVie stock and stock options. All inputs to this article are based on personal experiences and opinions, and do not necessarily reflect AbbVie’s views. J. Sutherland is the Clinical Operations Manager for Revalesio. Dr Lyden receives royalty Income for “Thrombolytic Therapy for Acute Stroke” Third Edition Springer Press, is the PI for NINDS grants U24 NS13006000 and UG3 NS119199, and monies for consulting for Apex Innovations. Dr Jauch receives monies for consulting for RapidAI, and reports compensation from Schultz & Pogue, LLP, and McLeod Law Group for expert witness services. Dr Hernandez-Jimenez works for aptaTargets Dr Mocco receives grant funding from Stryker Neurovascular, Penumbra, and Microvention, as well as a research award from PCORI. Dr Mocco reports stock holdings in Endostream; stock holdings in Viz.ai; stock options in Neuroradial Technologies; stock options in Echovate; compensation from CVAid for consultant services; compensation from Penumbra Inc for other services; stock options in Whisper; compensation from RIST Neurovascular, Inc, for consultant services; stock options in Neurotechnology Investors, LLC, Managers; stock holdings in Q’Apel; grants from PCORI; compensation from Stryker for other services; compensation from MicroVention Inc for other services; stock holdings in Vastrax; stock holdings in Imperative Care Inc; compensation from Synchron for consultant services; stock holdings in Blinktbi; stock holdings in Cerebrotech; stock options in Sim&Cure; stock holdings in Spinaker; stock options in Spinaker; compensation from CVAid for consultant services; stock options in Songbird; stock options in E8; compensation from Perflow for consultant services; employment by Mount Sinai Health System; stock options in Tulavi; stock options in Borvo; stock holdings in Viseon Inc; stock options in Radical; and stock options in Neurolutions. E. Deljkich is Vice President, Clinical Affairs, Imperative Care. Dr Kamel is the PI for the ARCADIA trial (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke; NIH/NINDS U01NS095869), which received in-kind study drug from the BMS-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics; other funding from NIH (R01HL144541, R01NS123576, and U01NS106513); Deputy Editor for JAMA Neurology; clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; end point adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group.

Background The duration and magnitude of increased stroke risk after a hospitalization for acute systolic heart failure (HF) remains uncertain. Methods and Results The authors performed a retrospective cohort study using claims (2008-2018) from a nationally representative 5% sample of Medicare beneficiaries aged ≥66 years. Cox regression models were fitted separately for the groups with and without acute systolic HF to examine its association with the incidence of ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. Corresponding survival probabilities were used to compute the hazard ratio (HR) in each 30-day interval after discharge. The authors stratified patients by the presence of atrial fibrillation (AF) before or during the hospitalization for acute systolic HF. Among 2 077 501 eligible beneficiaries, 94 641 were hospitalized with acute systolic HF. After adjusting for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 30 days after discharge from an acute systolic HF hospitalization for patients with AF (HR, 2.4 [95% CI, 2.1-2.7]) and without AF (HR, 4.6 [95% CI, 4.0-5.3]). The risk of stroke remained elevated for 60 days in patients with AF (HR, 1.4 [95% CI, 1.2-1.6]) and was not significantly elevated afterward. The risk of stroke remained significantly elevated through 330 days in patients without AF (HR, 2.1 [95% CI, 1.7-2.7]) and was no longer significantly elevated afterward. Conclusions A hospitalization for acute systolic HF is associated with an increased risk of ischemic stroke up to 330 days in patients without concomitant AF.

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: 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.

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.

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., Competing Interests: Declaration of Competing Interest Hooman Kamel serves as co-PI for the NIH-funded ARCADIA trial which receives in-kind study drug from the BMS-Pfizer Alliance and in-kind study assays from Roche Diagnostics, serves as Deputy Editor for JAMA Neurology, serves as a steering committee member of Medtronic's Stroke AF trial (uncompensated), and serves on an endpoint adjudication committee for a trial of empagliflozin for Boehringer-Ingelheim. Neal Parikh has received personal fees for medicolegal consulting on stroke. Babak Navi has received personal fees for medicolegal consulting on stroke. The other authors have no disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Background: The detrimental impact of tobacco smoking on brain health is well recognized., Objective: To evaluate whether smoking acts synergistically with hypertension and diabetes to influence cognitive performance., Methods: We performed a cross-sectional analysis using the US National Health and Nutrition Examination Survey. Participants were tested for serum cotinine, a validated cigarette smoking/exposure biomarker, and had standardized blood pressure and hemoglobin A1c measurements. Participants were administered four cognitive tests: Digit Symbol Substitution (DSST), Animal Fluency, Immediate Recall, and Delayed Recall. Multivariable linear regression models adjusted for demographics and confounders evaluated the association of cotinine with cognition. Interaction testing evaluated effect modification by hypertension, diabetes, and their continuous measures (systolic blood pressure and hemoglobin A1c)., Results: For 3,007 participants, mean age was 69.4 years; 54% were women. Using cotinine levels, 14.9% of participants were categorized as active smokers. Higher cotinine levels were associated with worse DSST performance when modeling cotinine as a continuous variable (β, -0.70; 95% CI, -1.11, -0.29; p < 0.01) and when categorizing participants as active smokers (β, -5.63; 95% CI, -9.70, -1.56; p < 0.01). Cotinine was not associated with fluency or memory. Effect modification by hypertension and diabetes were absent, except that cotinine was associated with worse Immediate Recall at lower blood pressures., Conclusion: Higher levels of a smoking and secondhand exposure biomarker were associated with worse cognitive performance on a multidomain test. Overall, the relationship of cotinine with cognition was not contingent on or amplified by hypertension or diabetes; smoking is detrimental for brain health irrespective of these comorbidities.

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.

Background: Prior studies on rupture risk of brain arteriovenous malformations (AVMs) in women undergoing pregnancy and delivery have reported conflicting findings, but also have not accounted for AVM morphology and heterogeneity. Here, we assess the association between pregnancy and the risk of intracranial hemorrhage (ICH) in women with AVMs using a cohort-crossover design in which each woman serves as her own control., Methods: Women who underwent pregnancy and delivery were identified using DRG codes from the Healthcare Cost and Utilization Project State Inpatient Databases for California (2005-2011), Florida (2005-2014), and New York (2005-2014). The presence of AVM and ICH was determined using ICD 9 codes. Pregnancy was defined as the 40 weeks prior to delivery, and postpartum as 12 weeks after. We defined a non-exposure control period as a 52-week period prior to pregnancy. The relative risks of ICH during pregnancy were compared against the non-exposure period using conditional Poisson regression., Results: Among 4 022 811 women identified with an eligible delivery hospitalization (median age, 28 years; 7.3% with gestational diabetes; 4.5% with preeclampsia/eclampsia), 568 (0.014%) had an AVM. The rates of ICH during pregnancy and puerperium were 6355.4 (95% CI 4279.4 to 8431.5) and 14.4 (95% CI 13.3 to 15.6) per 100 000 person-years for women with and without AVM, respectively. In cohort-crossover analysis, in women with AVMs the risk of ICH increased 3.27-fold (RR, 95% CI 1.67 to 6.43) during pregnancy and puerperium compared with a non-pregnant period., Conclusions: Among women with AVM, pregnancy and puerperium were associated with a greater than 3-fold risk of ICH., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Intracerebral hemorrhage and arterial ischemic disease share risk factors, to our knowledge, but the association between the 2 conditions remains unknown., Objective: To evaluate whether intracerebral hemorrhage was associated with an increased risk of incident ischemic stroke and myocardial infarction., Design, Setting, and Participants: An analysis was conducted of pooled longitudinal participant-level data from 4 population-based cohort studies in the United States: the Atherosclerosis Risk in Communities (ARIC) study, the Cardiovascular Health Study (CHS), the Northern Manhattan Study (NOMAS), and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Patients were enrolled from 1987 to 2007, and the last available follow-up was December 31, 2018. Data were analyzed from September 1, 2019, to March 31, 2020., Exposure: Intracerebral hemorrhage, as assessed by an adjudication committee based on predefined clinical and radiologic criteria., Main Outcomes and Measures: The primary outcome was an arterial ischemic event, defined as a composite of ischemic stroke or myocardial infarction, centrally adjudicated within each study. Secondary outcomes were ischemic stroke and myocardial infarction. Participants with prevalent intracerebral hemorrhage, ischemic stroke, or myocardial infarction at their baseline study visit were excluded. Cox proportional hazards regression was used to examine the association between intracerebral hemorrhage and subsequent arterial ischemic events after adjustment for baseline age, sex, race/ethnicity, vascular comorbidities, and antithrombotic medications., Results: Of 55 131 participants, 47 866 (27 639 women [57.7%]; mean [SD] age, 62.2 [10.2] years) were eligible for analysis. During a median follow-up of 12.7 years (interquartile range, 7.7-19.5 years), there were 318 intracerebral hemorrhages and 7648 arterial ischemic events. The incidence of an arterial ischemic event was 3.6 events per 100 person-years (95% CI, 2.7-5.0 events per 100 person-years) after intracerebral hemorrhage vs 1.1 events per 100 person-years (95% CI, 1.1-1.2 events per 100 person-years) among those without intracerebral hemorrhage. In adjusted models, intracerebral hemorrhage was associated with arterial ischemic events (hazard ratio [HR], 2.3; 95% CI, 1.7-3.1), ischemic stroke (HR, 3.1; 95% CI, 2.1-4.5), and myocardial infarction (HR, 1.9; 95% CI, 1.2-2.9). In sensitivity analyses, intracerebral hemorrhage was associated with arterial ischemic events when updating covariates in a time-varying manner (HR, 2.2; 95% CI, 1.6-3.0); when using incidence density matching (odds ratio, 2.3; 95% CI, 1.3-4.2); when including participants with prevalent intracerebral hemorrhage, ischemic stroke, or myocardial infarction (HR, 2.2; 95% CI, 1.6-2.9); and when using death as a competing risk (subdistribution HR, 1.6; 95% CI, 1.1-2.1)., Conclusions and Relevance: This study found that intracerebral hemorrhage was associated with an increased risk of ischemic stroke and myocardial infarction. These findings suggest that intracerebral hemorrhage may be a novel risk marker for arterial ischemic events.

Background: Recent clinical trials have established the efficacy of endovascular stroke therapy and intravenous thrombolysis using advanced imaging, particularly computed tomography perfusion (CTP). The availability and utilization of CTP for patients and hospitals that treat acute ischemic stroke (AIS), however, is uncertain., Methods: We performed a retrospective cross-sectional analysis using 2 complementary Medicare datasets, full sample Texas and 5% national fee-for-service data from 2014 to 2017. AIS cases were identified using International Classification of Diseases , Ninth Revision and International Classification of Diseases , Tenth Revision coding criteria. Imaging utilization performed in the initial evaluation of patients with AIS was derived using Current Procedural Terminology codes from professional claims. Primary outcomes were utilization of imaging in AIS cases and the change in utilization over time. Hospitals were defined as imaging modality-performing if they submitted at least 1 claim for that modality per calendar year. The National Medicare dataset was used to validate state-level findings, and a local hospital-level cohort was used to validate the claims-based approach., Results: Among 50 797 AIS cases in the Texas Medicare fee-for-service cohort, 64% were evaluated with noncontrast head CT, 17% with CT angiography, 3% with CTP, and 33% with magnetic resonance imaging. CTP utilization was greater in patients treated with endovascular stroke therapy (17%) and intravenous thrombolysis (9%). CT angiography (4%/y) and CTP (1%/y) utilization increased over the study period. These findings were validated in the National dataset. Among hospitals in the Texas cohort, 100% were noncontrast head CT-performing, 77% CT angiography-performing, and 14% CTP-performing in 2017. Most AIS cases (69%) were evaluated at non-CTP-performing hospitals. CTP-performing hospitals were clustered in urban areas, whereas large regions of the state lacked immediate access., Conclusions: In state-wide and national Medicare fee-for-service cohorts, CTP utilization in patients with AIS was low, and most patients were evaluated at non-CTP-performing hospitals. These findings support the need for alternative means of screening for AIS recanalization therapies.

Background and Purpose: Recent studies suggest that alteration of the normal gut microbiome contributes to atherosclerotic burden and cardiovascular disease. While many gastrointestinal diseases are known to cause disruption of the normal gut microbiome in humans, the clinical impact of gastrointestinal diseases on subsequent cerebrovascular disease remains unknown. We conducted an exploratory analysis evaluating the relationship between gastrointestinal diseases and ischemic stroke., Methods: We performed a retrospective cohort study using claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included only beneficiaries ≥66 years of age. We used previously validated diagnosis codes to ascertain our primary outcome of ischemic stroke. In an exploratory manner, we categorized gastrointestinal disorders by anatomic location, disease chronicity, and disease mechanism. We used Cox proportional hazards models to examine associations of gastrointestinal disorder categories and ischemic stroke with adjustment for demographics and established vascular risk factors., Results: Among a mean of 1 725 246 beneficiaries in each analysis, several categories of gastrointestinal disorders were associated with an increased risk of ischemic stroke after adjustment for established stroke risk factors. The most notable positive associations included disorders of the stomach (hazard ratio, 1.17 [95% CI, 1.15-1.19]) and functional (1.16 [95% CI, 1.15-1.17]), inflammatory (1.13 [95% CI, 1.12-1.15]), and infectious gastrointestinal disorders (1.13 [95% CI, 1.12-1.15]). In contrast, we found no associations with stroke for diseases of the anus and rectum (0.97 [95% CI, 0.94-1.00]) or neoplastic gastrointestinal disorders (0.97 [95% CI, 0.94-1.00])., Conclusions: In exploratory analyses, several categories of gastrointestinal disorders were associated with an increased risk of future ischemic stroke after adjustment for demographics and established stroke risk factors.

Background and Purpose: We sought to understand practice patterns in management of patients who have ischemic stroke while adherent to oral anticoagulation for non-valvular atrial fibrillation (NVAF) in the United States (US)., Methods: We distributed an iteratively revised online survey to US neurologists in May-June 2019. Survey questions focused on clinicians' practices regarding diagnostic evaluation and secondary prevention after ischemic stroke in patients already on oral anticoagulation for NVAF. Standard descriptive statistics were used to summarize participants' characteristics and responses., Results: Of the 120 participating clinicians, 79% were attending physicians. Most respondents (66%) were trained in vascular neurology, and 79% were employed in hospital-based, academic settings. For patients with ischemic stroke despite anticoagulation, most respondents indicated that they obtain extracranial and intracranial vessel imaging (72% and 82%, respectively). Most respondents (83%) routinely change therapy to a direct oral anticoagulant (DOAC) for patients experiencing ischemic stroke while on warfarin. In cases of ischemic stroke while on a DOAC, 38% of respondents routinely switch agents, 42% do not routinely switch agents, and 20% routinely add an antiplatelet agent. In this scenario, 83% of respondents who switch agents indicated that the reason was a possible better response to a drug that acts through a different mechanism. The most common reason for not switching while on a DOAC was the lack of randomized trial data., Conclusions: There is a high degree of variability in practice patterns among US neurologists caring for patients with ischemic stroke while already on oral anticoagulation for NVAF., Competing Interests: Declaration of Competing Interest Dr. Salehi Omran has nothing to disclose. Dr. Parikh has nothing to disclose. Dr. Zambrano Espinoza has nothing to disclose. Dr. Lerario has nothing to disclose. Dr. Levine has nothing to disclose. Dr. Kamel serves as co-PI for the NIH-funded ARCADIA trial which receives in-kind study drug from the BMS-Pfizer Alliance and in-kind study assays from Roche Diagnostics, serves as Deputy Editor for JAMA Neurology, serves as a steering committee member of Medtronic's Stroke AF trial (uncompensated), serves on an endpoint adjudication committee for a trial of empagliflozin for Boehringer-Ingelheim, and has served on an advisory board for Roivant Sciences related to Factor XI inhibition. Dr. Marshall has nothing to disclose. Dr. Willey has nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Historic concerns about the cardiovascular and neuropsychiatric side effects of smoking-cessation pharmacotherapy have in part limited their use. We sought to evaluate whether depressive symptoms are associated with active smoking among survivors of stroke and myocardial infarction (MI). To do this, we performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (2005-2016). We included participants ≥20 years old with prior stroke or MI and any history of smoking. Symptoms of depression, at survey participation, were ascertained using the Patient Health Questionnaire-9. Active smoking was defined using self-report and, secondarily, with cotinine measures. We used logistic regression to evaluate the association between depression and active smoking after adjusting for demographics, smoking-related medical conditions, and health-related behaviors. We found that, among stroke and MI survivors with any history of smoking, 37.9% (95% CI, 34.5-41.3%) reported active smoking and 43.8% (95% CI, 40.3-47.3%) had biochemical evidence of smoking. Rates of active smoking were similar for stroke and MI survivors. Twenty-one percent screened positive for depression. In adjusted models, depression was associated with active smoking in the combined group of stroke and MI survivors (odds ratio, 2.28; 95% CI, 1.24-4.20) and in stroke survivors (odds ratio, 2.97; 95% CI, 1.20-7.38). Tests of heterogeneity by event type did not reveal an interaction. Findings were similar when using cotinine measures. We conclude that symptoms of depression were associated with active smoking among stroke and MI survivors. Stroke and MI survivors with symptoms of depression may require targeted smoking-cessation interventions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Healthcare payers in the United States are increasingly tying provider payments to quality and value using pay-for-performance policies. Cost-effectiveness analysis quantifies value in healthcare but is not currently used to design or prioritize pay-for-performance strategies or metrics. Acute ischemic stroke care provides a useful application to demonstrate how simulation modeling can be used to determine cost-effective levels of financial incentives used in pay-for-performance policies and associated challenges with this approach., Methods and Results: Our framework requires a simulation model that can estimate quality-adjusted life years and costs resulting from improvements in a quality metric. A monetary level of incentives can then be back-calculated using the lifetime discounted quality-adjusted life year (which includes effectiveness of quality improvement) and cost (which includes incentive payments and cost offsets from quality improvements) outputs from the model. We applied this framework to an acute ischemic stroke microsimulation model to calculate the difference in population-level net monetary benefit (willingness-to-pay of $50 000 to $150 000/quality-adjusted life year) accrued under current Medicare policy (stroke payment not adjusted for performance) compared with various hypothetical pay-for-performance policies. Performance measurement was based on time-to-thrombolytic treatment with tPA (tissue-type plasminogen activator). Compared with current payment, equivalent population-level net monetary benefit was achieved in pay-for-performance policies with 10-minute door-to-needle time reductions (5057 more acute ischemic stroke cases/y in the 0-3-hour window) incentivized by increasing tPA payment by as much as 18% to 44% depending on willingness-to-pay for health., Conclusions: Cost-effectiveness modeling can be used to determine the upper bound of financial incentives used in pay-for-performance policies, although currently, this approach is limited due to data requirements and modeling assumptions. For tPA payments in acute ischemic stroke, our model-based results suggest financial incentives leading to a 10-minute decrease in door-to-needle time should be implemented but not exceed 18% to 44% of current tPA payment. In general, the optimal level of financial incentives will depend on willingness-to-pay for health and other modeling assumptions around parameter uncertainty and the relationship between quality improvements and long-run quality-adjusted life expectancy and costs.

Background Atrial fibrillation (AF) is associated with a 5-fold increased stroke risk. While most patients with AF warrant anticoagulation, optimal treatment remains uncertain for patients with AF without cardiovascular comorbidities because the risk of stroke in this population has not been well-characterized. Methods and Results Participants (N=28 253; 55% women, mean age 64.6±9.4 years), from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study (2003-present) were classified into 1 of 4 groups based on the presence or absence of AF and the presence or absence of cardiovascular comorbidities. Cox proportional hazards analysis was used to compare the risk of stroke between groups. During 244 560 person-years of follow-up (median 8.7 years), 1206 strokes occurred. Compared with patients with neither AF nor cardiovascular comorbidities, we did not find an increased stroke risk (hazard ratio [HR], 1.23; 95% CI, 0.62-2.18 [ P =0.511]) among participants with AF alone. Participants without AF but with cardiovascular comorbidities had both an elevated stroke risk (HR, 1.77; 95% CI, 1.48-2.18 [ P <0.0001]) and an increased risk of cardioembolic stroke (HR, 2.34; 95% CI, 1.48-3.90 [ P =0.0002]). Conclusions In this large cohort of participants with AF without cardiovascular comorbidities, we found that AF itself, without cardiovascular comorbidities, did not confer increased risk of stroke. Cardiovascular comorbidities, however, were associated with an increased risk of both stroke of any type and cardioembolic stroke, even in the absence of AF.

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 Sex differences have been found in stroke risk factors, incidence, treatment, and outcomes. There are conflicting data on whether diagnostic evaluation for stroke may differ between men and women. Methods and Results We performed a retrospective cohort study using inpatient and outpatient claims between 2008 and 2016 from a nationally representative 5% sample of Medicare beneficiaries. We included patients ≥65 years old and hospitalized with ischemic stroke, defined by International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD-9-CM ) and ICD-10-CM diagnosis codes. Logistic regression was used to determine the association between female sex and the odds of diagnostic testing and specialist evaluation, adjusted for age, race, and number of Charlson comorbidities. Among 78 822 patients with acute ischemic stroke, 58.3% (95% CI, 57.9-58.6%) were women. Female sex was associated with decreased odds of intracranial vessel imaging (odds ratio [OR]: 0.94; 95% CI, 0.91-0.97), extracranial vessel imaging (OR: 0.89; 95% CI, 0.86-0.92), heart-rhythm monitoring (OR: 0.92; 95% CI, 0.87-0.98), echocardiography (OR: 0.92; 95% CI, 0.89-0.95), evaluation by a neurologist (OR: 0.94; 95% CI, 0.91-0.97), and evaluation by a vascular neurologist (OR: 0.94; 95% CI, 0.90-0.97), after adjustment for age, race, and comorbidities. These findings were unchanged in separate sensitivity analyses excluding patients who died during the index hospitalization or were discharged to hospice and excluding patients with atrial fibrillation diagnosed before their index stroke. Conclusions In a nationally representative cohort of Medicare beneficiaries, we found that women with acute ischemic stroke were less likely to be evaluated by stroke specialists and less likely to undergo standard diagnostic testing compared with men.

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.

Background and Purpose- Allergic reactions, including anaphylaxis, can sometimes occur after intravenous thrombolysis in patients with acute ischemic stroke. However, it remains unclear whether patients with stroke who receive thrombolytic agents face a higher risk of anaphylaxis than those who do not receive thrombolytics. Methods- We performed a retrospective cohort study using inpatient and outpatient claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included patients who were ≥65 years old and hospitalized with acute ischemic stroke, defined by validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Our exposure was treated with an intravenous thrombolytic agent during the index hospitalization ( International Classification of Diseases, Ninth Revision, Clinical Modification code 99.10). Our primary outcome was anaphylaxis, defined using an accepted International Classification of Diseases, Ninth Revision, Clinical Modification code algorithm (989.5, 995.0-4, 995.6x, E905, E905.3, E905.5, or E905.8-9). A secondary outcome was anaphylactic shock (995.0 or 995.6x). Multiple logistic regression was used to evaluate the association between intravenous thrombolysis and anaphylaxis after adjustment for demographics, vascular risk factors, the Charlson comorbidity index, exposure to intravenous contrast dye, treatment with mechanical thrombectomy, and history of allergic reactions. Results- Among 66 989 patients with stroke, the 3176 (4.7%) who underwent intravenous thrombolysis more often had atrial fibrillation (47.7% versus 37.4%) and more often received intravenous contrast dye (44.3% versus 21.9%) but were otherwise similar in terms of demographics and comorbidities. Anaphylaxis developed in 17 (0.54%; 95% CI, 0.31%-0.86%) patients who received intravenous thrombolysis versus 45 (0.07%; 95% CI, 0.05%-0.09%) who did not. After adjustment for demographics, comorbidities, contrast dye, mechanical thrombectomy, and history of allergies, there was a significant association between receipt of intravenous thrombolysis and anaphylaxis (odds ratio, 7.8; 95% CI, 4.3-13.9). We found a similar association for anaphylactic shock. Conclusions- Although a rare occurrence, the risk of anaphylaxis among patients with acute ischemic stroke was significantly higher among those who received intravenous thrombolysis.

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., (© 2019 American Neurological Association.)

Aims: Although catheter ablation has emerged as an important therapy for patients with symptomatic atrial fibrillation (AF), there are limited data on sex-based differences in outcomes. We sought to compare in-hospital outcomes and 30-day readmissions of women and men undergoing AF ablation., Methods and Results: Using the United States Nationwide Readmissions Database, we analysed patients undergoing AF ablation between 2010 and 2014. Based on ICD-9-CM codes, we identified co-morbidities and outcomes. Multivariable logistic regression and inverse probability-weighting analysis were performed to assess female sex as a predictor of endpoints. Of 54 597 study patients, 20 623 (37.7%) were female. After adjustment for age, co-morbidities, and hospital factors, women had higher rates of any complication [adjusted odds ratio (aOR) 1.39; P < 0.0001], cardiac perforation (aOR 1.39; P = 0.006), and bleeding/vascular complications (aOR 1.49; P < 0.0001). Thirty-day all-cause readmission rates were higher for women compared to men (13.4% vs. 9.4%; P < 0.0001). Female sex was independently associated with readmission for AF/atrial tachycardia (aOR 1.48; P < 0.0001), cardiac causes (aOR 1.40; P < 0.0001), and all causes (aOR 1.25; P < 0.0001). Similar findings were confirmed with inverse probability-weighting analysis. Despite increased complications and readmissions, total costs for AF ablation were lower for women than men due to decreased resource utilization., Conclusions: Independent of age, co-morbidities, and hospital factors, women have higher rates of complications and readmissions following AF ablation. Sex-based differences and disparities in the management of AF need to be explored to address these gaps in outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background It is uncertain whether aortic diseases, such as aneurysm and dissection, are associated with intracranial aneurysm formation and aneurysmal subarachnoid hemorrhage (SAH). Methods and Results We used data on claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. Our exposure variable was hospitalization with an unruptured or ruptured aortic aneurysm or aortic dissection. The outcome was nontraumatic SAH. Variables were ascertained by International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD-9-CM ), diagnosis codes. Survival statistics were used to calculate incidence rates. Cox proportional hazards analysis was used to examine the association between aortic aneurysm/dissection and SAH while adjusting for demographics, vascular risk factors, and Charlson comorbidities. Among 1 781 917 beneficiaries, 32 551 (1.8%) had a documented aortic aneurysm or dissection. During 4.6±2.2 years of follow-up, 2538 patients (0.14%) developed a nontraumatic SAH. The incidence of SAH was 9 (95% CI, 7-11) per 10 000 patients per year in those with aortic aneurysm/dissection compared with 3 (95% CI, 3-3) per 10 000 patients per year in those without aortic aneurysm/dissection. After adjustment for demographics, stroke risk factors, and Charlson comorbidities, patients with aortic aneurysm/dissection faced an increased risk of SAH (hazard ratio, 1.4; 95% CI, 1.02-1.9; P =0.04). Conclusions In a nationally representative sample of Medicare beneficiaries, aortic aneurysm/dissection was associated with an increased risk of nontraumatic SAH.

Objective: We sought to characterize the US nationwide temporal trends in recanalization therapy utilization for ischemic stroke among patients with and without cancer., Methods: We identified all acute ischemic stroke (AIS) hospitalizations in the National Inpatient Sample from January 1, 1998 to September 30, 2015. The primary exposure was solid or hematologic cancer. The primary outcome was use of intravenous thrombolysis. The secondary outcome was use of endovascular therapy (EVT)., Results: Among 9,508,804 AIS hospitalizations, 503,510 (5.3%) involved cancer patients. Intravenous thrombolysis use among ischemic stroke patients with cancer increased from .01% (95% confidence interval [CI], .00%-.02%) in 1998 to 4.91% (95% CI, 4.33%-5.48%) in 2015, whereas intravenous thrombolysis use among ischemic stroke patients without cancer increased from .02% (95% CI, .01%-.02%) in 1998 to 7.22% (95% CI, 6.98%-7.45%) in 2015. The demographic- and comorbidity-adjusted odds ratio/year of receiving intravenous thrombolysis was similar in patients with cancer (1.21; 95% CI, 1.20-1.23) versus those without (1.20; 95% CI, 1.19-1.21). EVT use among ischemic stroke patients with cancer increased from .05% (95% CI, .02%-.07%) in 2006 to 1.90% (95% CI, 1.49%-2.31%) in 2015, whereas EVT use among ischemic stroke patients without cancer increased from .09% (95% CI, .00%-.18%) in 2006 to 1.88% (95% CI, 1.68%-2.09%) in 2015., Conclusions: Among 9.5 million AIS hospitalizations, patients with cancer received intravenous thrombolysis about two thirds as often as patients without cancer. This difference persisted over time despite increased utilization in both groups. EVT utilization was similar between cancer and non-cancer AIS patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose- There has been a recent sharp rise in opioid-related deaths in the United States. Intravenous opioid use can lead to infective endocarditis (IE) which can result in stroke. There are scant data on recent trends in this neurological complication of opioid abuse. We hypothesized that increasing opioid abuse has led to a higher incidence of stroke associated with IE and opioid use. Methods- We used the 1993 to 2015 releases of the National Inpatient Sample and validated International Classification of Diseases, Ninth Revision, Clinical Modification codes ( ICD-9-CM) to identify hospitalizations with the combination of opioid abuse, IE, and stroke (defined as ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage). Survey weights provided by the National Inpatient Sample were used to calculate nationally representative estimates and population estimates from the United States. Census data were used to calculate annual hospitalization rates per 10 million person-years. Joinpoint regression was used to assess trends. Results- From 1993 through 2015, there were 5283 hospitalizations with stroke associated with IE and opioid use. Across this period, the rate of such hospitalizations increased from 2.4 (95% CI, 0.5-4.3) to 18.8 (95% CI, 14.4-23.3) per 10 million US residents. Joinpoint regression detected 2 segments: no significant change in the hospitalization rate was apparent from 1993 to 2008 (annual percentage change, 1.9%; 95% CI, -2.2% to 6.1%), and then rates significantly increased from 2008 to 2015 (annual percentage change, 20.3%; 95% CI, 10.5%-30.9%), most dramatically in non-Hispanic white patients in the Northeastern and Southern United States. Conclusions- US hospitalization rates for stroke associated with IE and opioid use were stable for ≈2 decades but then sharply increased starting in 2008, coinciding with the emergence of the opioid epidemic.

Background and Purpose- Recent landmark trials provided overwhelming evidence for effectiveness of endovascular stroke therapy (EST). Yet, the impact of these trials on clinical practice and effectiveness of EST among lower volume centers remains poorly characterized. Here, we determine population-level patterns in EST performance in US hospitals and compare EST outcomes from higher versus lower volume centers. Methods- Using validated diagnosis codes from data on all discharges from hospitals and Emergency Rooms in Florida (2006-2016) and the National Inpatient Sample (2012-2016) we identified patients with acute ischemic stroke treated with EST. The primary end point was good discharge outcome defined as discharge to home or acute rehabilitation facility. Multivariate regressions adjusted for medical comorbidities, intravenous tPA (tissue-type plasminogen activator) usage and annual hospital stroke volume were used to evaluate the likelihood of good outcome over time and by annual hospital EST volume. Results- A total of 3890 patients (median age, 73 [61-82] years, 51% female) with EST were identified in the Florida cohort and 42 505 (median age, 69 [58-79], 50% female) in the National Inpatient Sample. In both Florida and the National Inpatient Sample, the number of hospitals performing EST increased continuously. Increasing numbers of EST procedures were performed at lower annual EST volume hospitals over the studied time period. In adjusted multivariate regression, there was a continuous increase in the likelihood of good outcomes among patients treated in hospitals with increasing annual EST procedures per year (odds ratio, 1.1; 95% CI, 1.1-1.2 in Florida and odds ratio, 1.3; 95% CI, 1.2-1.4 in National Inpatient Sample). Conclusions- Analysis of population-level datasets of patients treated with EST from 2006 to 2016 demonstrated an increase in the number of centers performing EST, resulting in a greater number of procedures performed at lower volume centers. There was a positive association between EST volume and favorable discharge outcomes in EST-performing hospitals.

Cancer patients face an increased risk of arterial thromboembolism; however, it is uncertain when this excess risk begins. This study evaluated the risk of arterial thromboembolism before cancer diagnosis. Using the population-based Surveillance Epidemiology and End Results-Medicare linked dataset, we identified 374 331 patients ≥67 years of age with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, uterine, pancreatic, gastric cancer, or non-Hodgkin lymphoma from 2005 through 2013. Cancer patients were individually matched by demographics and comorbidities to Medicare beneficiaries without cancer, who served as controls. Validated diagnosis codes were used to identify arterial thromboembolic events, defined as a composite of myocardial infarction or ischemic stroke. The Mantel-Haenszel estimator was used to compare risks of arterial thromboembolic events between cancer and noncancer groups during 30-day periods in the 360 days before date of cancer diagnosis. From 360 to 151 days before cancer diagnosis, the 30-day interval risks of arterial thromboembolic events were similar between cancer patients and matched controls. From 150 to 1 day before cancer diagnosis, the interval 30-day risks of arterial thromboembolic events were higher in cancer patients vs matched controls, progressively increasing as the cancer diagnosis date approached and peaking during the 30 days immediately before cancer diagnosis, when 2313 (0.62%) cancer patients were diagnosed with an arterial thromboembolic event vs 413 (0.11%) controls (odds ratio, 5.63; 95% confidence interval, 5.07-6.25). In conclusion, the risk of arterial thromboembolic events begins to increase 150 days before the date of cancer diagnosis in older persons and peaks in the 30 days before., (© 2019 by The American Society of Hematology.)

Background Black individuals in the United States experience higher rates of ischemic stroke than other racial groups but have lower rates of clinically apparent atrial fibrillation ( AF ). It is unclear whether blacks truly have less AF or simply more undiagnosed AF . Methods and Results We performed a retrospective cohort study using inpatient and outpatient claims from 2009 to 2015 for a 5% nationally representative sample of Medicare beneficiaries. We included patients aged ≥66 years with at least 1 documented Current Procedural Terminology code for interrogation of an implantable pacemaker, cardioverter-defibrillator, or loop recorder and no documented history of AF , atrial flutter, or stroke before their first device interrogation. Kaplan-Meier statistics and Cox proportional hazards models were used to examine the association between black race and the composite outcome of AF or atrial flutter while adjusting for age, sex, and vascular risk factors. Among 47 417 eligible patients, the annual incidence of AF /atrial flutter was 12.2 (95% CI , 11.5-13.1) per 100 person-years among blacks and 17.6 (95% CI , 17.4-17.9) per 100 person-years among non-black beneficiaries. After adjustment for confounders, black beneficiaries faced a lower hazard of AF /atrial flutter than non-black beneficiaries (hazard ratio, 0.75; 95% CI , 0.70-0.80). Despite the lower risk of AF , black patients faced a higher hazard of ischemic stroke (hazard ratio, 1.37; 95% CI , 1.22-1.53). Conclusions Among Medicare beneficiaries with implanted cardiac devices capable of detecting atrial rhythm, black patients had a lower incidence of AF despite a higher burden of vascular risk factors and a higher risk of stroke.

Background: Case series have reported reversible left ventricular dysfunction, also known as stress cardiomyopathy or Takotsubo cardiomyopathy (TCM), in the setting of acute neurological diseases such as subarachnoid hemorrhage. The relative associations between various neurological diseases and Takotsubo remain incompletely understood., Methods: We performed a cross-sectional study of all adults in the National Inpatient Sample, a nationally representative sample of US hospitalizations, from 2006 to 2014. Our exposures of interest were primary diagnoses of acute neurological disease, defined by ICD-9-CM diagnosis codes. Our outcome was a diagnosis of TCM. Binary logistic regression models were used to examine the associations between our pre-specified neurological diagnoses and TCM after adjustment for demographics., Results: Among acute neurological diagnoses, the strongest associations were seen with subarachnoid hemorrhage (odds ratio [OR] 11.7; 95% confidence interval [CI] 10.2-13.4), status epilepticus (OR 4.9; 95% CI 3.7-6.3), and seizures (OR 1.3; 95% CI 1.1-1.5). In a sensitivity analysis including secondary diagnoses of acute neurological diagnoses, associations were also seen with transient global amnesia (OR 2.3; 95% CI 1.5-3.6), meningoencephalitis (OR 2.1; 95% CI 1.7-2.5), migraine (OR 1.7; 95% CI 1.5-1.8), intracerebral hemorrhage (OR 1.3; 95% CI 1.1-1.5), and ischemic stroke (OR 1.2; 95% CI 1.1-1.3). In addition, female sex was strongly associated with Takotsubo (OR 5.1; 95% CI 4.9-5.4)., Conclusion: TCM appears to be associated with varying degrees with several acute neurological diseases besides subarachnoid hemorrhage.

Rationale: Recent data suggest that a thrombogenic atrial substrate can cause stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may explain some proportion of cryptogenic strokes., Aims: The aim of the ARCADIA trial is to test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial cardiopathy., Sample Size Estimate: 1100 participants., Methods and Design: Biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial conducted at 120 U.S. centers participating in NIH StrokeNet., Population Studied: Patients ≥ 45 years of age with embolic stroke of undetermined source and evidence of atrial cardiopathy, defined as ≥ 1 of the following markers: P-wave terminal force >5000 µV × ms in ECG lead V 1 , serum NT-proBNP > 250 pg/mL, and left atrial diameter index ≥ 3 cm/m 2 on echocardiogram. Exclusion criteria include any atrial fibrillation, a definite indication or contraindication to antiplatelet or anticoagulant therapy, or a clinically significant bleeding diathesis. Intervention: Apixaban 5 mg twice daily versus aspirin 81 mg once daily. Analysis: Survival analysis and the log-rank test will be used to compare treatment groups according to the intention-to-treat principle, including participants who require open-label anticoagulation for newly detected atrial fibrillation., Study Outcomes: The primary efficacy outcome is recurrent stroke of any type. The primary safety outcomes are symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage., Discussion: ARCADIA is the first trial to test whether anticoagulant therapy reduces stroke recurrence in patients with atrial cardiopathy but no known atrial fibrillation.

Background: In 2013, investigators from A Randomized Trial of Unruptured Brain Arteriovenous Malformations (AVM; ARUBA) reported that interventions to obliterate unruptured AVMs caused more morbidity and mortality than medical management., Objective: We sought to determine whether interventions for unruptured AVM decreased after publication of ARUBA results., Methods: We used the Nationwide Readmissions Database to assess trends in interventional AVM management in patients ≥18 years of age from 2010 through 2015. Unruptured brain AVMs were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 747.81 and excluding any patient with a diagnosis of intracranial hemorrhage. Our primary outcome was interventional AVM treatment, identified using ICD-9-CM procedure codes for surgical resection, endovascular therapy, and stereotactic radiosurgery. Join-point regression was used to assess trends in the incidence of interventional AVM management among adults from 2010 through 2015., Results: There was no significant U.S. population level change in unruptured brain AVM intervention rates before versus after ARUBA (p = 0.59), with the incidence of AVM intervention ranging from 8.0 to 9.2 per 10 million U.S. residents before the trial publication to 7.7-8.3 per 10 million afterwards., Conclusions: In a nationally representative sample, we found no change in rates of interventional unruptured AVM management after publication of the ARUBA trial results., (© 2019 S. Karger AG, Basel.)