Biomarkers of Coagulation and Inflammation in COVID-19-Associated Ischemic Stroke.

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Anticoagulation Timing in Cardioembolic Stroke and Recurrent Event Risk.

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.

Ischaemic stroke on anticoagulation therapy and early recurrence in acute cardioembolic stroke: the IAC study.

BACKGROUND AND PURPOSE: A subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH). METHODS: We included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve). RESULTS: Among 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641). CONCLUSION: AF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary prevention strategies.

Factors associated with hospitalization for ischemic stroke and TIA following an emergency department headache visit.

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.

Under Treatment of High-Risk TIA Patients with Clopidogrel-Aspirin in the Emergency Setting.

BACKGROUND: Treating high-risk transient ischemic attack (TIA) with dual antiplatelet therapy (DAPT) reduces subsequent ischemic stroke risk yet current rates of clopidogrel-aspirin treatment are uncertain. MATERIALS AND METHODS: We conducted a retrospective cohort study of consecutive TIA patients who presented to any of the four emergency departments (ED) of a single urban health system from 1/1/2018-3/1/2020. Medical record review was used to describe the cohort and assess clopidogrel-aspirin treatment. Patient eligibility for clopidogrel-aspirin was determined using relevant criteria from the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial. Comparisons among eligible patients who received versus did not receive clopidogrel-aspirin were conducted using t-test, chi-squared, and Mann-Whitney as indicated. RESULTS: We identified 248 TIA patients of whom 95 met eligibility criteria for clopidogrel-aspirin treatment. Among these 95 patients, mean age was 69.5 (SD: 12), 68.4% were women, and median ABCD2 score was 5 (IQR: 4-6). A total of 26/95 (27.4%) eligible patients received clopidogrel-aspirin within 24 hours of symptom onset. Appropriate clopidogrel-aspirin use was associated with having a stroke code called upon ED arrival (88.5% vs. 34.8%; P<0.001), being evaluated by a vascular neurologist (88.5% vs. 21.1%; P<0.001), and not presenting to the community ED site wherein only a single patient received clopidogrel-aspirin. CONCLUSIONS: In a multisite, single health system study, nearly three-fourths of high-risk TIA patients eligible for clopidogrel-aspirin treatment did not receive it. Appropriate clopidogrel-aspirin use was highest among patients seen by vascular neurologists and lowest at the community ED, though under treatment was evident at all sites.

Misdiagnosis of Cervicocephalic Artery Dissection in the Emergency Department.

Background and Purpose- Cervicocephalic artery dissection is an important cause of stroke. The clinical presentation of dissection can resemble that of benign neurological conditions leading to delayed or missed diagnosis. Methods- We performed a retrospective cohort study using statewide administrative claims data from all Emergency Department visits and admissions at nonfederal hospitals in Florida from 2005 to 2015 and New York from 2006 to 2015. Using validated International Classification of Diseases, Ninth Revision, CM codes, we identified adult patients hospitalized for cervicocephalic artery dissection. We defined probable misdiagnosis of dissection as having an Emergency Department treat-and-release visit for symptoms or signs of dissection, including headache, neck pain, and focal neurological deficits in the 14 days before dissection diagnosis. Multivariable logistic regression was used to compare adverse clinical outcomes in patients with and without probable misdiagnosis. Results- Among 7090 patients diagnosed with a dissection (mean age 52.7 years, 44.9% women), 218 (3.1% [95% CI, 2.7%-3.5%]) had a preceding probable Emergency Department misdiagnosis. After adjustment for demographics and vascular risk factors, there were no differences in rates of stroke (odds ratio, 0.82 [95% CI, 0.62-1.09]) or in-hospital death (odds ratio, 0.26 [95% CI, 0.07-1.08]) between dissection patients with and without a probable misdiagnosis at index hospitalization. Conclusions- We found that ≈1 in 30 dissection patients was probably misdiagnosed in the 2 weeks before their diagnosis.

Anticoagulation Type and Early Recurrence in Cardioembolic Stroke: The IAC Study.

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.

Early ischaemic and haemorrhagic complications after atrial fibrillation-related ischaemic stroke: analysis of the IAC study.

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.

Factors associated with therapeutic anticoagulation status in patients with ischemic stroke and atrial fibrillation.

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.

Diagnostic yield of echocardiography in cancer patients with ischemic stroke.

The yield of echocardiography in cancer patients with acute ischemic stroke is unknown. We identified adult patients with active systemic cancer diagnosed with acute ischemic stroke at a tertiary-care cancer center from 2005 through 2009 who underwent transthoracic (TTE) or transesophageal echocardiography (TEE). Two neurologists independently reviewed all clinical data, including TTE and TEE reports, and adjudicated whether echocardiographic studies revealed a definite or possible source of stroke according to pre-defined criteria. Patients were classified as having suspected cardioembolic strokes if imaging showed embolic-appearing infarcts in more than one vascular territory. Among 220 patients with cancer and ischemic stroke who underwent echocardiography, 216 (98%) had TTE and 37 (17%) had TEE. TTE revealed a definite source in 15 (7%, 95% CI 4-10%) patients and a possible source in 42 (19%, 95% CI 14-25%), while TEE revealed a definite source in 10 (27%, 95% CI 12-42%) patients and a possible source in 14 (38%, 95% CI 21-54%). In 92 patients with suspected cardioembolic strokes who underwent TTE, 6 (7%, 95% CI 1-12%) had a definite source, including 4 with marantic endocarditis, and 20 (22%, 95% CI 13-30%) had a possible source. Twenty-one of these patients also underwent TEE, which demonstrated a definite or possible source in 16 (76%, 95% CI 56-96%) patients, including marantic endocarditis in 4 (19%). The yield of TTE for detecting marantic endocarditis and other cardiac sources of stroke in cancer patients is low, but TEE may provide a higher yield in targeted patients.

Cryptogenic subtype predicts reduced survival among cancer patients with ischemic stroke.

BACKGROUND AND PURPOSE: Cryptogenic stroke is common in patients with cancer. Autopsy studies suggest that many of these cases may be because of marantic endocarditis, which is closely linked to cancer activity. We, therefore, hypothesized that among patients with cancer and ischemic stroke, those with cryptogenic stroke would have shorter survival. METHODS: We retrospectively analyzed all adult patients with active systemic cancer diagnosed with acute ischemic stroke at a tertiary care cancer center from 2005 through 2009. Two neurologists determined stroke mechanisms by consensus. Patients were diagnosed with cryptogenic stroke if no specific mechanism could be determined. The diagnosis of marantic endocarditis was restricted to patients with cardiac vegetations on echocardiography or autopsy and negative blood cultures. Patients were followed until July 31, 2012, for the primary outcome of death. Kaplan-Meier statistics and the log-rank test were used to compare survival between patients with cryptogenic stroke and patients with known stroke mechanisms. Multivariate Cox proportional hazard analysis evaluated the association between cryptogenic stroke and death after adjusting for potential confounders. RESULTS: Among 263 patients with cancer and ischemic stroke, 133 (51%) were cryptogenic. Median survival in patients with cryptogenic stroke was 55 days (interquartile range, 21-240) versus 147 days (interquartile range, 33-735) in patients with known stroke mechanisms (P<0.01). Cryptogenic stroke was independently associated with death (hazard ratio, 1.64; 95% confidence interval, 1.25-2.14) after adjusting for age, systemic metastases, adenocarcinoma histology, and functional status. CONCLUSIONS: Cryptogenic stroke is independently associated with reduced survival in patients with active cancer and ischemic stroke.

Headache and acute stroke.

Disorders associated with prominent headaches, such as migraine with aura and cerebral arterial and venous diseases, increase the risk of ischemic and hemorrhagic stroke. Central nervous system vasculitis, posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome, and cerebral venous thrombosis are all disorders associated with severe or persistent headache in which the risk for ischemic and hemorrhagic stroke is increased. Hemorrhagic strokes, more frequently than ischemic strokes, present with distinct headaches, usually accompanied by focal neurological symptoms. Pregnancy, and especially the postpartum period, is a time of overlap between new-onset headache and stroke risk.

Factors Associated with Anticoagulation Initiation for New Atrial Fibrillation in an Urban Emergency Department.

Objective: To explore factors associated with anticoagulation (AC) initiation after atrial fibrillation (AF) diagnosis. Design: Retrospective cohort study. Setting: Urban medical center. Patients: Adults with emergency department (ED) diagnosis of new onset AF from 1/1/2017-1/1/2020 discharged home. Methods: We compared patients initiated on AC, our primary outcome, to those not initiated on AC. Stroke, major bleeding, and AC initiation within 1 year of visit were secondary outcomes. We hypothesized that minority race and non-English language preference are associated with failure to initiate AC. Results: Of 111 patients with AF, 88 met inclusion criteria. Mean age was 65 (SD 15); 47 (53%) were women. 49 (56%) patients were initiated on AC. Age (61 vs 68 years; P=.02), non-English language (28% vs 10%; P=.03), leaving ED against medical advice (AMA) (36% vs 14%; P=.04), and CHA2DS2-VASc score of 1 (41% vs 6%; P<=.001) were associated with no AC initiation. There were no associations between patient-reported race/ethnicity and AC. Cardiology consultation (83.67% vs 30.78%; P<.0001) and higher median CHA2DS2-VASc score (3[2-4]) vs. 2[1-4]; P=.047) were associated with AC. Of 73 patients with follow-up data at 1 year, 2 (8%) not initiated on AC had strokes, 2 (4%) initiated on AC had major bleeds, and 15 (62.5%) not initiated on AC in the ED subsequently were initiated on AC. Conclusion: More than half of ED patients with new AF eligible for AC were initiated on it. Work to improve AC utilization among patients with new AF who left AMA from ED and those who prefer to communicate in a non-English language may be warranted.

Treating High-Risk TIA and Minor Stroke Patients With Dual Antiplatelet Therapy: A National Survey of Emergency Medicine Physicians.

BACKGROUND: Treatment with aspirin plus clopidogrel, dual antiplatelet therapy (DAPT), within 24 hours of high-risk transient ischemic attack (TIA) or minor stroke symptoms to eligible patients is recommended by national guidelines. Whether or not this treatment has been adopted by emergency medicine (EM) physicians is uncertain. METHODS: We conducted an online survey of EM physicians in the United States. The survey consisted of 13 multiple choice questions regarding physician characteristics, practice settings, and usual approach to TIA and minor stroke treatment. We report participant characteristics and use chi-squared tests to compare between groups. RESULTS: We included 162 participants in the final study analysis. 103 participants (64%) were in practice for >5 years and 96 (59%) were at nonacademic centers; all were EM board-certified or board-eligible. Only 9 (6%) participants reported that they would start DAPT for minor stroke and 8 (5%) reported that they would start DAPT after high-risk TIA. Aspirin alone was the selected treatment by 81 (50%) participants for minor stroke patients who presented within 24 hours of symptom onset and were not candidates for thrombolysis. For minor stroke, 69 (43%) participants indicated that they would defer medical management to consultants or another team. Similarly, 75 (46%) of participants chose aspirin alone to treat high-risk TIA; 74 (46%) reported they would defer medical management after TIA to consultants or another team. CONCLUSION: In a survey of EM physicians, we found that the reported rate of DAPT treatment for eligible patients with high-risk TIA and minor stroke was low.

Associating cryptogenic ischemic stroke in the young with cardiovascular risk factor phenotypes.

Acute Ischemic Stroke (AIS) in the young is increasing in prevalence and the largest subtype within this cohort is cryptogenic. To curb this trend, new ways of defining cryptogenic stroke and associated risk factors are needed. We aimed to gain insights into the presence or absence of cardiovascular risk factors in cases of cryptogenic stroke. We conducted a retrospective cohort study of patients aged 18-49 who presented to an urban tertiary care center with AIS. We manually collected predefined demographic, clinical, laboratory and radiological variables. Clinical risk phenotypes were determined using these variables through multivariate analysis of patients with the small and large vessel disease subtypes (vascular phenotype) and cardioembolic subtype (cardiac phenotype). The resultant phenotype models were applied to cases deemed cryptogenic. Within the 449 patients who met criteria, patients with small and large vessel disease (vascular phenotype) had higher rates of hypertension, intracranial atherosclerosis, and diabetes mellitus, and higher admission glucose, HbA1c, admission blood pressure, and cholesterol compared to the patients with cardioembolic AIS. The cardioembolic subgroup (cardiac phenotype) had significantly higher rates of congestive heart failure (CHF), rheumatic heart disease, atrial fibrillation, clotting disorders, left ventricular hypertrophy, larger left atrial sizes, lower ejection fractions, and higher B-type natriuretic peptide and troponin levels. Adjusted multivariate analysis produced six variables independently associated with the vascular phenotype (age, male sex, hemoglobin A1c, ejection fraction (EF), low-density lipoprotein (LDL) cholesterol, and family history of AIS) and five independently associated with the cardiac phenotype (age, female sex, decreased EF, CHF, and absence of intracranial atherosclerosis). Applying these models to cryptogenic stroke cases yielded that 51.5% fit the vascular phenotype and 3.1% fit the cardiac phenotype. In our cohort, half of young patients with cryptogenic stroke fit the risk factor phenotype of small and large vessel strokes.

Emergency medicine physicians' perspectives on diagnostic accuracy in neurology: a qualitative study.

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.

Head Computed tomography during emergency department treat-and-release visit for headache is associated with increased risk of subsequent cerebrovascular disease hospitalization.

OBJECTIVES: The occurrence of head computed tomography (HCT) at emergency department (ED) visit for non-specific neurological symptoms has been associated with increased subsequent stroke risk and may be a marker of diagnostic error. We evaluate whether HCT occurrence among ED headache patients is associated with increased subsequent cerebrovascular disease risk. METHODS: We conducted a retrospective cohort study of consecutive adult patients with headache who were discharged home from the ED (ED treat-and-release visit) at one multicenter institution. Patients with headache were defined as those with primary ICD-9/10-CM discharge diagnoses codes for benign headache from 9/1/2013-9/1/2018. The primary outcome of cerebrovascular disease hospitalization was identified using ICD-9/10-CM codes and confirmed via chart review. We matched headache patients who had a HCT (exposed) to those who did not have a HCT (unexposed) in the ED in a one-to-one fashion using propensity score methods. RESULTS: Among the 28,121 adult patients with ED treat-and-release headache visit, 45.6% (n=12,811) underwent HCT. A total of 0.4% (n=111) had a cerebrovascular hospitalization within 365 days of index visit. Using propensity score matching, 80.4% (n=10,296) of exposed patients were matched to unexposed. Exposed patients had increased risk of cerebrovascular hospitalization at 365 days (RR: 1.65: 95% CI: 1.18-2.31) and 180 days (RR: 1.62; 95% CI: 1.06-2.49); risk of cerebrovascular hospitalization was not increased at 90 or 30 days. CONCLUSIONS: Having a HCT performed at ED treat-and-release headache visit is associated with increased risk of subsequent cerebrovascular disease. Future work to improve cerebrovascular disease prevention strategies in this subset of headache patients is warranted.

Cost-Effectiveness of Advanced Neuroimaging for Transient and Minor Neurological Events in the Emergency Department.

Background Accurate diagnosis of patients with transient or minor neurological events can be challenging. Recent studies suggest that advanced neuroimaging can improve diagnostic accuracy in low-risk patients with transient or minor neurological symptoms, but a cost-effective emergency department diagnostic evaluation strategy remains uncertain. Methods and Results We constructed a decision-analytic model to evaluate 2 diagnostic evaluation strategies for patients with low-risk transient or minor neurological symptoms: (1) obtain advanced neuroimaging (magnetic resonance imaging brain and magnetic resonance angiography head and neck) on every patient or (2) current emergency department standard-of-care clinical evaluation with basic neuroimaging. Main probability variables were: proportion of patients with true ischemic events, strategy specificity and sensitivity, and recurrent stroke rate. Direct healthcare costs were included. We calculated incremental cost-effectiveness ratios, conducted sensitivity analyses, and evaluated various diagnostic test parameters primarily using a 1-year time horizon. Cost-effectiveness standards would be met if the incremental cost-effectiveness ratio was less than willingness to pay. We defined willingness to pay as $100 000 US dollars per quality-adjusted life year. Our primary and sensitivity analyses found that the advanced neuroimaging strategy was more cost-effective than emergency department standard of care. The incremental effectiveness of the advanced neuroimaging strategy was slightly less than the standard-of-care strategy, but the standard-of-care strategy was more costly. Potentially superior diagnostic approaches to the modeled advanced neuroimaging strategy would have to be >92% specific, >70% sensitive, and cost less than or equal to standard-of-care strategy's cost. Conclusions Obtaining advanced neuroimaging on emergency department patient with low-risk transient or minor neurological symptoms was the more cost-effective strategy in our model.

Effect of Alteplase Use on Outcomes in Patients With Atrial Fibrillation: Analysis of the Initiation of Anticoagulation After Cardioembolic Stroke Study.

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.