Objectives: We sought to understand the knowledge, attitudes, and beliefs of emergency medicine (EM) physicians towards non-specific neurological conditions and the use of clinical decision support (CDS) to improve diagnostic accuracy. Methods: We conducted semi-structured interviews of EM physicians at four emergency departments (EDs) affiliated with a single US healthcare system. Interviews were conducted until thematic saturation was achieved. Conventional content analysis was used to identify themes related to EM physicians' perspectives on acute diagnostic neurology; directed content analysis was used to explore views regarding CDS. Each interview transcript was independently coded by two researchers using an iteratively refined codebook with consensus-based resolution of coding differences. Results: We identified two domains regarding diagnostic safety: (1) challenges unique to neurological complaints and (2) challenges in EM more broadly. Themes relevant to neurology included: (1) knowledge gaps and uncertainty, (2) skepticism about neurology, (3) comfort with basic as opposed to detailed neurological examination, and (4) comfort with non-neurological diseases. Themes relevant to diagnostic decision making in the ED included: (1) cognitive biases, (2) ED system/environmental issues, (3) patient barriers, (4) comfort with diagnostic uncertainty, and (5) concerns regarding diagnostic error identification and measurement. Most participating EM physicians were enthusiastic about the potential for well-designed CDS to improve diagnostic accuracy for non-specific neurological complaints. Conclusions: Physicians identified diagnostic challenges unique to neurological diseases as well as issues related more generally to diagnostic accuracy in EM. These physician-reported issues should be accounted for when designing interventions to improve ED diagnostic accuracy.

BACKGROUND:A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. METHODS:This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. RESULTS:Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140-720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51-1.73]; P=0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; P=0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; P=0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; P=0.02). CONCLUSIONS:In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.

Background: Misdiagnosis of cerebrovascular disease among Emergency Department (ED) patients with headache has been reported. We hypothesized that markers of substandard diagnostic processes would be associated with subsequent ischemic cerebrovascular events among patients discharged from the ED with a headache diagnosis even after adjusting for demographic variables and medical history. Methods: We conducted a case-control study of adult ED patients diagnosed with a primary headache disorder at Montefiore Medical Center from 9/1/2013-9/1/2018. Cases were defined as patients hospitalized for an ischemic stroke or TIA within 365 days of their index ED visit. Control patients were defined as those who lacked a subsequent hospitalization for cerebrovascular disease. Pre-specified demographic, clinical, and diagnostic process factors were compared between groups; conditional logistic regression was used to assess the separate and joint influence of baseline features on risk of cerebral ischemia. Results: A total of 93 consecutive headache patients with a subsequent ischemic stroke/TIA hospitalization were matched to 93 controls (n = 186). Cases were older than controls and more likely to have traditional cerebrovascular risk factors. Neurological consultation was obtained more often for cases (13% vs. 4%; P = 0.03), cases were in the ED for longer (6 vs. 5 h, P = 0.03), and more frequently received neuroimaging (80% vs. 48%; P < 0.0001). Rates of neurological examination, documented differential diagnoses, and clear discharge follow up plans were similar between cases and controls. In our conditional logistic regression model, only history of prior stroke/TIA was associated with increased odds of subsequent cerebral ischemia. Conclusion: Factors associated with diagnostic process failures did not increase the odds of subsequent ischemic stroke/TIA hospitalization following ED headache visit in our study. (C) 2020 Published by Elsevier Inc.

Background: Emergent treatment with intravenous thrombolysis and mechanical thrombectomy improved outcomes in patients with acute ischemic stroke. We aim to identify differences in acute stroke treatment trends between strokes occurring in the anterior versus posterior circulation. Methods: The IAC (Initiation of Anticoagulation after Cardioembolic stroke) study represents pooled data registry of 8 comprehensive stroke centers across the United States and included patients with cardioembolic stroke in the setting of AFib. In a post hoc analysis, we identified and separated patients into posterior circulation stroke (PCS) and anterior circulation stroke (ACS) groups based on imaging. Patients without infarct locations or those with multi-circulation infarcts were excluded. We compared baseline characteristics, stroke severity and the treatment trends with alteplase (tPA) and mechanical thrombectomy (MT) in PCS vs ACS using Fisher exact test, t-test and non-parametric tests. We then performed multivariable logistic regression adjusted for baseline differences to determine the associations between PCS and tPA or MT. Results: Of the 2084 patients in IAC cohort, 1589 met inclusion criteria for this study, in which 294 (22.7%) had PCS. Mean age was 76.8 years, 29.3% received tPA and 26.9% had MT. When compared to ACS, patients with PCS were more likely to be men (55.4% vs 45.6%, p=0.003), have diabetes (42.8% vs 29.8, p< 0.001) and lower median NIHSS score on admission (4 vs 8, p<0.001). Patients with PCS were less likely to receive tPA (16.3% vs 32.3%, p<0.001) or MT (10.9% vs 30.6%, p<0.001). Other variables were not significantly different. When adjusted for baseline differences, patients with PCS remained less likely to be treated with tPA (adjusted OR 0.49, 95%CI 0.35-0.70, p<0.001) or MT (adjusted OR 0.38, 95%CI 0.25-0.58, p<0.001). Conclusion: Posterior circulation strokes are half as likely to receive thrombolytic therapy and almost a third as likely to have thrombectomy, even after adjusting for baseline stroke severity scores. This is possibly due to difficulty in timely identification and diagnostic delays. There is need for better tools incorporating posterior circulation stroke signs and symptoms to allow for early detection and treatment.

Background and purpose: A proportion of patients with ischemic stroke and atrial fibrillation (AF) have an ischemic stroke despite being prescribed anticoagulation therapy. In this study of patients with ischemic stroke in the setting of AF, we aim to determine the association between prior anticoagulant therapy and 90-day recurrent ischemic events and delayed symptomatic intracranial hemorrhage (sICH). Methods: We included consecutive patients with acute ischemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from 8 comprehensive stroke centers in the United States. We compared recurrent ischemic events and delayed sICH risk using unadjusted and adjusted cox-regression analyses between patients who were prescribed anticoagulation (AC p ) vs. were naïve to anticoagulation therapy prior to the ischemic stroke (AC n ). For ischemic events, we adjusted for CHA 2 DS 2 -Vasc, anticoagulation initiation, and switching anticoagulant (DOAC to Warfarin or Warfarin to DOAC). For delayed sICH, we adjusted for age, sex, NIHSS score, and early hemorrhagic transformation. Results: 2070 patients had home anticoagulation treatment status recorded. When compared to the AC n group, the AC p group were more likely to have higher median (IQR) CHA 2 DS 2 -Vasc score [5 (4-6) vs. 5 (3-6), p = 0.001], lower NIHSS score [8 (3 - 18) vs. 10 (4 - 18), p = 0.015], severe left atrial enlargement (43.5% vs. 34.5%, p < 0.001), and less likely to receive alteplase (14.4% vs. 36.2%, p < 0.001). In the adjusted cox hazard model, AC p was associated with increased risk of 90-day recurrent ischemic events (adjusted HR 1.52 95% CI 1.01 - 2.29, p = 0.047) but not increased risk of 90-day sICH (adjusted HR 1.10 95% CI 0.46 - 2.61, p = 0.838). In a sensitivity analysis, with severe left atrial enlargement added to the model, the association between AC p and recurrent ischemic event risk did not meaningfully change (adjusted HR 1.41 95% CI 0.87 - 2.28, p = 0.162). Conclusion: Patients with AF and ischemic stroke despite being prescribed anticoagulation therapy are at higher risk of recurrent events. Studies are needed to understand mechanisms of ischemic stroke in these patients to improve stroke prevention strategies.

Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p <0.001) but overall reduced risk of 90-day mortality (adjusted OR 0.58, 95% CI 0.39 - 0.87, p = 0.009). Among patients undergoing MT, alteplase use was associated with a trend towards a reduction in 90-day mortality (adjusted OR 0.68 95% CI 0.45 - 1.04, p = 0.077). In the subgroup of patients prescribed DOAC treatment (n = 327; 24 received alteplase), alteplase treatment was associated with a trend towards smaller infarct size (< 10 mL), (adjusted OR 0.40, 95% CI 0.15 - 1.12, p = 0.082) without a significant difference in the odds of 90-day mortality (adjusted OR 0.51, 95% CI 0.12 - 2.13, p = 0.357) or hemorrhagic transformation (adjusted OR 0.27, 95% CI 0.03 - 2.07, p = 0.206). Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.

Background Intravenous alteplase improves outcome after acute ischemic stroke without a benefit in 90‐day mortality. There are limited data on whether alteplase is associated with reduced mortality in patients with atrial fibrillation (AF)‐related ischemic stroke whose mortality rate is relatively high. We sought to determine the association of alteplase with hemorrhagic transformation and mortality in patients with AF. Methods and Results We retrospectively analyzed consecutive patients with acute ischemic stroke between 2015 and 2018 diagnosed with AF included in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study, which pooled data from stroke registries at 8 comprehensive stroke centers across the United States. For our primary analysis, we included patients who did not undergo mechanical thrombectomy (MT), and secondary analyses included patients who underwent MT. We used binary logistic regression to determine whether alteplase use was associated with risk of hemorrhagic transformation and 90‐day mortality. There were 1889 patients (90.6%) who had 90‐day follow‐up data available for analyses and were included; 1367 patients (72.4%) did not receive MT, and 522 patients (27.6%) received MT. In our primary analyses we found that alteplase use was independently associated with an increased risk for hemorrhagic transformation (odds ratio [OR], 2.23; 95% CI, 1.57–3.17) but reduced risk of 90‐day mortality (OR, 0.58; 95% CI, 0.39–0.87). Among patients undergoing MT, alteplase use was not associated with a significant reduction in 90‐day mortality (OR, 0.68; 95% CI, 0.45–1.04). Conclusions Alteplase reduced 90‐day mortality of patients with acute ischemic stroke with AF not undergoing MT. Further study is required to assess the efficacy of alteplase in patients with AF undergoing MT.

Thursday, April 30April 14, 2020Free AccessFactors Associated with Subsequent Cerebral Vascular Disease after Emergency Department Headache Visits: a nested case-control study (984)Jenny Lu, Richard Lipton, Khadean Moncrieffe, Daniel Labovitz, and Ava LibermanAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.984 Letters to the Editor

Background/Aims: Guidelines suggest initiating anticoagulation after cardioembolic stroke within 4-14 days from the index event. Data supporting this suggestion did not account for important factors such as infarct burden or early hemorrhagic transformation. Methods: We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with an acute cardioembolic stroke in the setting of atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days) and the primary outcome was the composite endpoint of recurrent stroke/TIA/systemic embolism, symptomatic intracerebral hemorrhage (sICH), or major extracranial hemorrhage (ECH) within 90 days. Results: We enrolled 2090 patients from 8 comprehensive centers in the United States, 1325 met the inclusion criteria (362 were excluded due to non-composite endpoint related death within 90 days, 145 lost to follow up, and 258 were not started on oral anticoagulation or the timing was not reported). Anticoagulation (875 DOAC, 404 Warfarin) was initiated in 0-3 days in 49.7%, 4-14 days in 40.4%, and >14 days in 9.9%. The combined endpoint occurred in 10.7% (142) (98 ischemic events, 21 sICH, and 30 ECH) and did not differ between the three groups: 0-3 days (11.9%), 4-14 days (9.9%), >14 days (9.9%), p=0.525. After adjusting for confounders (such as infarct volume, bridging, CHADS2-Vasc, cardiac thrombus, and hemorrhage on 24-hr imaging), oral anticoagulation timing in the 4-14 day period (vs. >14) was not associated with a reduction in ischemic events (adjusted OR 0.74, p=0.438) and oral anticoagulation timing 4-14 days (vs. 0-3) was not associated with a reduction in sICH (OR 1.28, p=0.638). Factors associated with sICH were bridging (OR 5.36, p=0.001) and hemorrhage on 24-hr imaging (OR 7.26, p<0.001) whereas for ischemic events were warfarin treatment (OR 1.66 95%, p = 0.030) and prior stroke (OR 1.81, p=0.013). Conclusion: In this multicenter real world cohort, the recommended (4-14 days) timeframe to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required determine the optimal timing of anticoagulation initiation.

Introduction Predictors of long-term ischaemic and haemorrhagic complications in atrial fibrillation (AF) have been studied, but there are limited data on predictors of early ischaemic and haemorrhagic complications after AF-associated ischaemic stroke. We sought to determine these predictors. Methods The Initiation of Anticoagulation after Cardioembolic stroke study is a multicentre retrospective study across that pooled data from consecutive patients with ischaemic stroke in the setting of AF from stroke registries across eight comprehensive stroke centres in the USA. The coprimary outcomes were recurrent ischaemic event (stroke/TIA/systemic arterial embolism) and delayed symptomatic intracranial haemorrhage (d-sICH) within 90 days. We performed univariate analyses and Cox regression analyses including important predictors on univariate analyses to determine independent predictors of early ischaemic events (stroke/TIA/systemic embolism) and d-sICH. Results Out of 2084 patients, 1520 patients qualified; 104 patients (6.8%) had recurrent ischaemic events and 23 patients (1.5%) had d-sICH within 90 days from the index event. In Cox regression models, factors associated with a trend for recurrent ischaemic events were prior stroke or transient ischemic attack (TIA) (HR 1.42, 95% CI 0.96 to 2.10) and ipsilateral arterial stenosis with 50%–99% narrowing (HR 1.54, 95% CI 0.98 to 2.43). Those associated with sICH were male sex (HR 2.68, 95% CI 1.06 to 6.83), history of hyperlipidaemia (HR 2.91, 95% CI 1.08 to 7.84) and early haemorrhagic transformation (HR 5.35, 95% CI 2.22 to 12.92). Conclusion In patients with ischaemic stroke and AF, predictors of d-sICH are different than those of recurrent ischaemic events; therefore, recognising these predictors may help inform early stroke versus d-sICH prevention strategies.

BACKGROUND AND PURPOSE:In patients with acute ischemic stroke and atrial fibrillation, treatment with low molecular weight heparin increases early hemorrhagic risk without reducing early recurrence, and there is limited data comparing warfarin to direct oral anticoagulant (DOAC) therapy. We aim to compare the effects of the treatments above on the risk of 90-day recurrent ischemic events and delayed symptomatic intracranial hemorrhage. METHODS:We included consecutive patients with acute ischemic stroke and atrial fibrillation from the IAC (Initiation of Anticoagulation after Cardioembolic) stroke study pooling data from stroke registries of 8 comprehensive stroke centers across the United States. We compared recurrent ischemic events and delayed symptomatic intracranial hemorrhage between each of the following groups in separate Cox-regression analyses: (1) DOAC versus warfarin and (2) bridging with heparin/low molecular weight heparin versus no bridging, adjusting for pertinent confounders to test these associations. RESULTS:We identified 1289 patients who met the bridging versus no bridging analysis inclusion criteria and 1251 patients who met the DOAC versus warfarin analysis inclusion criteria. In adjusted Cox-regression models, bridging (versus no bridging) treatment was associated with a high risk of delayed symptomatic intracranial hemorrhage (hazard ratio, 2.74 [95% CI, 1.01-7.42]) but a similar rate of recurrent ischemic events (hazard ratio, 1.23 [95% CI, 0.63-2.40]). Furthermore, DOAC (versus warfarin) treatment was associated with a lower risk of recurrent ischemic events (hazard ratio, 0.51 [95% CI, 0.29-0.87]) but not delayed symptomatic intracranial hemorrhage (hazard ratio, 0.57 [95% CI, 0.22-1.48]). CONCLUSIONS:Our study suggests that patients with ischemic stroke and atrial fibrillation would benefit from the initiation of a DOAC without bridging therapy. Due to our study limitations, these findings should be interpreted with caution pending confirmation from large prospective studies.

Objective Guidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation, such as infarct size, hemorrhagic transformation, or high‐risk features on echocardiography. Methods We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with ischemic stroke and atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0–3 days, 4–14 days, or >14 days), and outcomes were recurrent stroke/transient ischemic attack/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days. Results Among 2,084 patients, 1,289 met the inclusion criteria. The combined endpoint occurred in 10.1% (n = 130) subjects (87 ischemic events, 20 sICH, and 29 ECH). Overall, there was no significant difference in the composite endpoint between the 3 groups (0–3 days: 10.3%, 64/617; 4–14 days: 9.7%, 52/535; >14 days: 10.2%, 14/137; p = 0.933). In adjusted models, patients started on anticoagulation between 4 and 14 days did not have a lower rate of sICH (vs 0–3 days; odds ratio [OR] = 1.49, 95% confidence interval [CI] = 0.50–4.43), nor did they have a lower rate of recurrent ischemic events (vs >14 days; OR = 0.76, 95% CI = 0.36–1.62, p = 0.482). Interpretation In this multicenter real‐world cohort, the recommended (4–14 days) time frame to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required to determine the optimal timing of anticoagulation initiation. ANN NEUROL 2020;88:807–816

COVID-19 associated coagulopathy and mortality related to thrombotic complications have been suggested as biological mediators in racial disparities related to COVID-19. We studied the adjusted prevalence of acute ischemic stroke, pulmonary embolism, myocardial infarction, and deep venous thrombosis stratified by race in hospitalized patients in one New York City borough during the local COVID-19 surge. The multi-racial cohort included 4299 patients hospitalized with COVID-19, 9% of whom were white, 40% black, 41% Hispanic and 10% Asian or other. We found a 6.1% prevalence of composite thrombotic events. There were no significant race-specific differences in thrombotic events when adjusting for basic demographics, socioeconomic factors, medical comorbidities or biomarkers using a stepwise regression model. We therefore found no evidence that the racial disparities related to COVID-19, and specifically thrombotic complications, are caused by biological differences in race.

BACKGROUND AND PURPOSE:Understanding factors associated with ischemic stroke despite therapeutic anticoagulation is an important goal to improve stroke prevention strategies in patients with atrial fibrillation (AF). We aim to determine factors associated with therapeutic or supratherapeutic anticoagulation status at the time of ischemic stroke in patients with AF. METHODS:The Initiation of Anticoagulation after Cardioembolic stroke (IAC) study is a multicenter study pooling data from stroke registries of eight comprehensive stroke centers across the United States. Consecutive patients hospitalized with acute ischemic stroke in the setting of AF were included in the IAC cohort. For this study, we only included patients who reported taking warfarin at the time of the ischemic stroke. Patients not on anticoagulation and patients who reported use of a direct oral anticoagulant were excluded. Analyses were stratified based on therapeutic (INR ≥2) versus subtherapeutic (INR <2) anticoagulation status. We used binary logistic regression models to determine factors independently associated with anticoagulation status after adjustment for pertinent confounders. In particular, we sought to determine whether atherosclerosis with 50% or more luminal narrowing in an artery supplying the infarct (a marker for a competing atherosclerotic mechanism) and small stroke size (≤ 10 mL; implying a competing small vessel disease mechanism) related to anticoagulant status. RESULTS:Of the 2084 patients enrolled in the IAC study, 382 patients met the inclusion criteria. The mean age was 77.4 ± 10.9 years and 52.4% (200/382) were women. A total of 222 (58.1%) subjects presented with subtherapeutic INR. In adjusted models, small stroke size (OR 1.74 95% CI 1.10-2.76, p = 0.019) and atherosclerosis with 50% or more narrowing in an artery supplying the infarct (OR 1.96 95% CI 1.06-3.63, p = 0.031) were independently associated with INR ≥2 at the time of their index stroke. CONCLUSION:Small stroke size (≤ 10 ml) and ipsilateral atherosclerosis with 50% or more narrowing may indicate a competing stroke mechanism. There may be important opportunities to improve stroke prevention strategies for patients with AF by targeting additional ischemic stroke mechanisms to improve patient outcomes.