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Individuals with stroke often experience significant impairment of the upper limb. Rehabilitation interventions targeting the upper limb are typically associated with only small to moderate gains. The knowledge that body schema can be altered in other upper limb conditions has contributed to the development of tailored rehabilitation approaches. This study investigated whether individuals with stroke experienced alterations in body schema of the upper limb. If so, this knowledge may have implications for rehabilitation approaches such as motor imagery.An observational study performed online consisting of left/right judgment tasks assessed by response time and accuracy of: (i) left/right direction recognition; (ii) left/right shoulder laterality recognition; (iii) left/right hand laterality recognition; (iv) mental rotation of nonembodied objects. Comparisons were made between individuals with and without stroke. Secondary comparisons were made in the stroke population according to side of stroke and side of pain if experienced.A total of 895 individuals (445 with stroke) participated. Individuals with stroke took longer for all tasks compared to those without stroke, and were less accurate in correctly identifying the laterality of shoulder (P0.001) and hand (P0.001) images, and the orientation of nonembodied objects (P0.001). Moreover, the differences observed in the hand and shoulder tasks were greater than what was observed for the control tasks of directional recognition and nonembodied mental rotation. No significant differences were found between left/right judgments of individuals with stroke according to stroke-affected side or side of pain.Left/right judgments of upper limb are frequently impaired after stroke, providing evidence of alterations in body schema. The knowledge that body schemas are altered in individuals with longstanding stroke may assist in the development of optimal, well-accepted motor imagery programs for the upper limb.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A394).

Refereed/Peer-reviewed Background: Chronic pain and somatosensory impairment are common following a stroke. It is possible that an interaction exists between pain and somatosensory impairment and that a change in one may influence the other. We therefore investigated the presence of chronic pain and self-reported altered somatosensory ability in individuals with stroke, aiming to determine if chronic pain is more common in stroke survivors with somatosensory impairment than in those without. Methods: Stroke survivors were invited to complete an online survey that included demographics, details of the stroke, presence of chronic pain, and any perceived changes in body sensations post-stroke. Results: Survivors of stroke (n = 489) completed the survey with 308 indicating that they experienced chronic pain and 368 reporting perceived changes in somatosensory function. Individuals with strokes who reported altered somatosensory ability were more likely to experience chronic pain than those who did not (OR = 1.697; 95% CI 1.585, 2.446). Further, this difference was observed for all categories of sensory function that were surveyed (detection of light touch, body position, discrimination of surfaces and temperature, and haptic object recognition). Conclusions: The results point to a new characteristic of chronic pain in strokes, regardless of nature or region of the pain experienced, and raises the potential of somatosensory impairment being a rehabilitation target to improve pain-related outcomes for stroke survivors.

Background: Chronic pain and body perception disturbance are common following stroke. It is possible that an interaction exists between pain and body perception disturbance, and that a change in one may influence the other. We therefore investigated the presence of body perception disturbance in individuals with stroke, aiming to determine if a perceived change in hand size contralateral to the stroke lesion is more common in those with chronic pain than in those without. Methods: Stroke survivors (N = 523) completed an online survey that included: stroke details, pain features, and any difference in perceived hand size post-stroke. Results: Individuals with stroke who experienced chronic pain were almost three times as likely as those without chronic pain to perceive their hand as now being a different size (OR = 2.895; 95%CI 1.844, 4.547). Further, those with chronic pain whose pain included the hand were almost twice as likely to perceive altered hand size than those whose pain did not include the hand (OR = 1.862; 95%CI 1.170, 2.962). This was not influenced by hemisphere of lesion (p = 0.190). Conclusions: The results point to a new characteristic of chronic pain in stroke, raising the possibility of body perception disturbance being a rehabilitation target to improve function and pain-related outcomes for stroke survivors.

BACKGROUND: The incidence of sudden cardiac death and sudden death caused by arrhythmia, as determined by autopsy, in persons with human immunodeficiency virus (HIV) infection has not been clearly established. METHODS: Between February 1, 2011, and September 16, 2016, we prospectively identified all new deaths due to out-of-hospital cardiac arrest among persons 18 to 90 years of age, with or without known HIV infection, for comprehensive autopsy and toxicologic and histologic testing. We compared the rates of sudden cardiac death and sudden death caused by arrhythmia between groups. RESULTS: Of 109 deaths from out-of-hospital cardiac arrest among 610 unexpected deaths in HIV-positive persons, 48 met World Health Organization criteria for presumed sudden cardiac death; of those, fewer than half (22) had an arrhythmic cause. A total of 505 presumed sudden cardiac deaths occurred between February 1, 2011, and March 1, 2014, in persons without known HIV infection. Observed incidence rates of presumed sudden cardiac death were 53.3 deaths per 100,000 person-years among persons with known HIV infection and 23.7 deaths per 100,000 person-years among persons without known HIV infection (incidence rate ratio, 2.25; 95% confidence interval [CI], 1.37 to 3.70). Observed incidence rates of sudden death caused by arrhythmia were 25.0 and 13.3 deaths per 100,000 person-years, respectively (incidence rate ratio, 1.87; 95% CI, 0.93 to 3.78). Among all presumed sudden cardiac deaths, death due to occult drug overdose was more common in persons with known HIV infection than in persons without known HIV infection (34% vs. 13%). Persons who were HIV-positive had higher histologic levels of interstitial myocardial fibrosis than persons without known HIV infection. CONCLUSIONS: In this postmortem study, the rates of presumed sudden cardiac death and myocardial fibrosis were higher among HIV-positive persons than among those without known HIV infection. One third of apparent sudden cardiac deaths in HIV-positive persons were due to occult drug overdose. (Supported by the National Heart, Lung, and Blood Institute.)

Background: San Francisco (California USA) is a relatively compact city with a population of 884,000 and nine stroke centers within a 47 square mile area. Emergency Medical Services (EMS) transport distances and times are short and there are currently no Mobile Stroke Units (MSUs). Methods: This study evaluated EMS activation to computed tomography (CT [EMS-CT]) and EMS activation to thrombolysis (EMS-TPA) times for acute stroke in the first two years after implementation of an emergency department (ED) focused, direct EMS-to-CT protocol entitled “Mission Protocol” (MP) at a safety net hospital in San Francisco and compared performance to published reports from MSUs. The EMS times were abstracted from ambulance records. Geometric means were calculated for MP data and pooled means were similarly calculated from published MSU data. Results: From July 2017 through June 2019, a total of 423 patients with suspected stroke were evaluated under the MP, and 166 of these patients were either ultimately diagnosed with ischemic stroke or were treated as a stroke but later diagnosed as a stroke mimic. The EMS and treatment time data were available for 134 of these patients with 61 patients (45.5%) receiving thrombolysis, with mean EMS-CT and EMS-TPA times of 41 minutes (95% CI, 39-43) and 63 minutes (95% CI, 57-70), respectively. The pooled estimates for MSUs suggested a mean EMS-CT time of 35 minutes (95% CI, 27-45) and a mean EMS-TPA time of 48 minutes (95% CI, 39-60). The MSUs achieved faster EMS-CT and EMS-TPA times (P Conclusions: In a moderate-sized, urban setting with high population density, MP was able to achieve EMS activation to treatment times for stroke thrombolysis that were approximately 15 minutes slower than the published performance of MSUs.

Background and Purpose: Findings from the Framingham Heart Study suggest that declines in dementia incidence rates over recent decades are partially due to decreases in stroke incidence and mortality; however, whether trends of declining dementia rates extend to survivors of incident stroke remains unclear. We investigated evidence for temporal trends in memory change related to incident stroke in a nationally representative cohort. Methods: Adults age 50+ in the HRS (Health and Retirement Study) were followed across three successive 6-year epochs (epoch 1: 1998–2004, n=16 781; epoch 2: 2004–2010, n=15 345; and epoch 3: 2010–2016; n=15 949). Participants were included in an epoch if they were stroke-free at the start of that epoch. Annual rates of change in a composite z-standardized memory score were compared using demographic-adjusted linear regression models for stroke-free participants, those who survived after stroke, and those who died after stroke, considering memory change before stroke, at the time of stroke, and for years following stroke. Results: Crude stroke incidence rates decreased from 8.5 per 1000 person-years in epoch 1 to 6.8 per 1000 person-years in epoch 3. Rates of memory change before and following stroke onset were similar across epochs. Memory decrement immediately after stroke onset attenuated from −0.37 points (95% CI, −0.44 to −0.29) in epoch 1 to −0.26 (95% CI, −0.33 to −0.18) points in epoch 2 and −0.25 (95% CI, −0.33 to −0.17) points in epoch 3 ( P value for linear trend=0.02). Conclusions: Decreases in stroke-related dementia in recent years may be partially attributable to smaller memory decrements immediately after stroke onset. Findings suggest reductions in stroke incidence and improvements in stroke care may also reduce population burden of dementia. Further investigations into whether temporal trends are attributable to improvements in stroke care are needed.

IMPORTANCE: Dual antiplatelet therapy (DAPT) with ticagrelor and aspirin has been found to be effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA) in individuals who carry CYP2C19 loss-of-function (LOF) alleles; however, uncertainties remain about the time course of benefit and risk with ticagrelor and aspirin in these patients. OBJECTIVE: To obtain time-course estimates of efficacy and risk with ticagrelor and aspirin after minor stroke or TIA in individuals with CYP2C19 LOF alleles. DESIGN, SETTING, AND PARTICIPANTS: The Ticagrelor or Clopidogrel With Aspirin in High-risk Patients With Acute Nondisabling Cerebrovascular Events II (CHANCE-2) randomized clinical trial enrolled patients 40 years and older from 202 hospitals in China with acute minor stroke or TIA who carried CYP2C19 LOF alleles between September 23, 2019, and March 22, 2021, and were followed up for 90 days. All 6412 patients enrolled in the CHANCE-2 trial were included in this secondary analysis. Data were analyzed in October 2021. INTERVENTIONS: Ticagrelor (180 mg on day 1 followed by 90 mg twice daily on days 2-90) or clopidogrel (300 mg on day 1 followed by 75 mg daily on days 2-90). All patients received aspirin (75-300 mg on day 1 followed by 75 mg daily for 21 days). MAIN OUTCOMES AND MEASURES: The efficacy outcome was major ischemic event, defined as the composite of ischemic stroke or nonhemorrhagic death. Safety outcomes included moderate to severe bleeding and any bleeding. RESULTS: A total of 6412 patients were included (3205 in the ticagrelor and aspirin group and 3207 in the clopidogrel and aspirin group). The median (IQR) age was 65 (57-71) years, and 4242 patients (66%) were men. The reduction of major ischemic events with ticagrelor and aspirin predominately occurred in the first week (absolute risk reduction, 1.34%; 95% CI, 0.29 to 2.39) and attenuated but remained in the next 3 weeks (absolute risk reduction in the second week, 0.11%; 95% CI, −0.24 to 0.45; absolute risk reduction in the third week, 0.14%; 95% CI, −0.11 to 0.38; absolute risk reduction in the fourth week, 0.04%; 95% CI, −0.18 to 0.25). The risk of moderate to severe bleeding was consistently low in the ticagrelor and aspirin group. The absolute increase in any bleeding seen in the first week (0.87%; 95% CI, 0.25 to 1.50) remained in the next 3 weeks (absolute increase in the second week, 1.21%; 95% CI, 0.75 to 1.68; absolute increase in the third week, 0.33%; 95% CI, −0.05 to 0.72; absolute increase in the fourth week, 0.23%; 95% CI, −0.03 to 0.49). CONCLUSION AND RELEVANCE: Among patients with minor stroke or TIA who carried CYP2C19 LOF alleles, benefit with ticagrelor and aspirin was present predominately in the first week, with additional small benefit accruing in the next 2 weeks.

Purpose of review This article reviews the evidence base and recommendations for medical management for secondary stroke prevention. Recent findings Recent developments for secondary stroke prevention include evidence to support the use of short-term dual antiplatelet therapy after minor stroke and transient ischemic attack, direct oral anticoagulants for nonvalvular atrial fibrillation, reversal agents for direct oral anticoagulant-associated hemorrhage, and aspirin rather than presumptive anticoagulation with a direct oral anticoagulant for embolic stroke of undetermined source. Summary Most strokes are preventable. The mainstays of medical management for secondary stroke prevention include antihypertensive therapy; antithrombotic therapy, with antiplatelet agents for most stroke subtypes or anticoagulants such as warfarin or a direct oral anticoagulant for cardioembolic stroke specifically; cholesterol-lowering therapy, principally with statins, but with potential roles for ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors in selected patients; and glycemic control to prevent microvascular complications from diabetes mellitus or pioglitazone in selected patients with insulin resistance but not diabetes mellitus.

Background: Recent data suggest that in patients with acute myocardial infarction (MI), the effect of clopidogrel on risk reduction of cardiovascular outcomes is more pronounced in smokers. The aim of this study was to determine the effect of smoking status on subsequent stroke risk in patients with minor ischemic stroke or TIA and determine whether smoking improves the effect of clopidogrel treatment on subsequent stroke risk reduction. Methods: This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. The POINT trial compared clopidogrel plus aspirin (DAPT) to aspirin alone for prevention of recurrent stroke, myocardial infarction, or vascular death within 3 months of a high-risk TIA or minor ischemic stroke. We used multivariable cox-regression models to determine the effect of smoking on the risk of subsequent ischemic stroke. We also performed interaction analyses to determine whether the effect of clopidogrel on subsequent ischemic stroke differed with respect to smoking status. Results: Data from 4,877 participants enrolled in the POINT trial were analyzed. Among these, 1,004 were current smokers and 3,873 were non-smokers. Smoking was associated with a non-significantly increased risk of recurrent ischemic stroke during follow up (hazard ratio, 1.31 [95% CI, 0.97 - 1.78], P=0.076). The effect of clopidogrel on ischemic stroke was not significantly different in non-smokers (hazard ratio, 0.74 [95% CI, 0.56 - 0.98], P=0.03) compared to smokers (adjusted hazard ratio, 0.63 [95% CI, 0.37 - 1.05], P=0.078), P for interaction = 0.572. In addition, the effect of clopidogrel on major hemorrhage was not significantly different in current smokers (hazard ratio, 2.59 [95% CI, 1.08 - 6.21], P=0.032) compared to non-smokers (hazard ratio, 1.67 [95% CI, 0.40 - 7.00], P=0.481), P for interaction = 0.613. Conclusions: Cigarette smoking was associated with a non-significantly higher risk of subsequent ischemic stroke and smoking did not modify the effect of clopidogrel-based dual antiplatelet therapy on subsequent ischemic stroke risk reduction. Every effort should be made to encourage tobacco dependence treatment and cessation in patients with minor ischemic stroke and TIA.

Background and Purpose: Dual antiplatelet therapy has been shown to reduce the risk of recurrent stroke in patients with minor stroke or transient ischemic attack. However, whether the effect of dual antiplatelet therapy is modified by pretreatment antiplatelet status is unclear. Methods: This is a post hoc analysis of the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke). Patients were divided into 2 groups based on pretreatment antiplatelet use. The primary outcome was ischemic stroke within 90 days of randomization. Results: We included 4881 patients of whom 41% belonged to the no pretreatment antiplatelet. Ischemic stroke occurred in 6% and 5% in the antiplatelet pretreatment and no antiplatelet pretreatment, respectively. Antiplatelet pretreatment was not associated with the risk of ischemic stroke (adjusted hazard ratio, 1.05 [95% CI, 0.81–137]) or risk of major hemorrhage (hazard ratio, 1.10 [95% CI, 0.55–2.21]; P =0.794). The effect of dual antiplatelet therapy on recurrent ischemic stroke risk was not different in patients who were on antiplatelet before randomization (adjusted hazard ratio, 0.69 [95% CI, 0.50–0.94]) as opposed to those who were not (adjusted hazard ratio, 0.75 [95% CI, 0.50–1.12]), P for interaction = 0.685. Conclusions: In patients with minor stroke and high-risk transient ischemic attack, dual antiplatelet therapy reduces the risk of ischemic stroke regardless of premorbid antiplatelet use.

Ischemic stroke is one of the most debilitating and deadliest conditions worldwide. Intravenous t-PA is the current standard treatment within 4 hours after onset of symptoms. Recent randomized controlled trials have demonstrated the efficacy of neurointerventional intra-arterial treatment in acute ischemic stroke. About 20% of acute ischemic stroke are classified as wake-up strokes, which falls out of the conventional treatment time window. New evidence suggests that some patients with longer time from symptom onset (up to 24 hours) may benefit from thrombectomy, probably in part due to variations in collateral circulation among individual patients. Advanced imaging can play a crucial role in identifying patients who could benefit from endovascular intervention presenting within extended treatment time windows. In this article, we review the advanced imaging algorithm for ischemic stroke workup in the multiple studies published to date and summarize the results of the clinical trials for late ischemic stroke that can be clinically useful.

Key Points Question Among patients with transient ischemic attack and stroke, what is the association between blood pressure and dual antiplatelet therapy and rates of secondary stroke within 90 days after the original ischemic event? Findings In a post hoc analysis of 4781 patients in the POINT trial, having a baseline systolic blood pressure less than 140 mm Hg was associated with dual antiplatelet therapy significantly reducing the risk of ischemic stroke recurrence by 64% compared with aspirin alone, whereas having a baseline systolic blood pressure greater than or equal to 140 mm Hg was not associated with benefit for dual antiplatelet therapy. Meaning Additional research is needed to replicate these findings and potentially test whether mild blood pressure reduction combined with dual antiplatelet therapy started within 12 hours of stroke onset lowers early risk of stroke recurrence., This cohort study investigates whether dual antiplatelet therapy is associated with stroke recurrence among patients with or without elevated baseline systolic blood pressure in the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial., Importance Elevated systolic blood pressure (SBP) after acute ischemic stroke and transient ischemic attack (TIA) is associated with future stroke risk. Objective To explore the association of dual antiplatelet therapy (DAPT) with stroke recurrence among patients with acute ischemic stroke and TIA with or without elevated baseline SBP. Design, Setting, and Participants This cohort study performed a post hoc subgroup analysis of the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which was a multicenter trial conducted from 2010 to 2018 at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand. Patients enrolled in POINT with available blood pressure and outcome data were included in this cohort. Statistical analysis was performed from November 2020 to January 2021. Exposures Baseline SBP less than 140 mm Hg vs greater than or equal to 140 mm Hg and the interaction term of SBP (

Background and Purpose: Randomized trials demonstrated the benefit of dual antiplatelet therapy in patients with minor ischemic stroke or high-risk transient ischemic attack. We sought to determine whether the presence of carotid stenosis was associated with increased risk of ischemic stroke and whether the addition of clopidogrel to aspirin was associated with more benefit in patients with versus without carotid stenosis. Methods: This is a post-hoc analysis of the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) that randomized patients with minor ischemic stroke or high-risk transient ischemic attack within 12 hours from last known normal to receive either clopidogrel plus aspirin or aspirin alone. The primary predictor was the presence of ≥50% stenosis in either cervical internal carotid artery. The primary outcome was ischemic stroke. We built Cox regression models to determine the association between carotid stenosis and ischemic stroke and whether the effect of clopidogrel was modified by ≥50% carotid stenosis. Results: Among 4881 patients enrolled POINT, 3941 patients met the inclusion criteria. In adjusted models, ≥50% carotid stenosis was associated with ischemic stroke risk (hazard ratio, 2.45 [95% CI, 1.68–3.57], P P =0.014) versus those with ≥50% carotid stenosis (adjusted hazard ratio, 0.88 [95% CI, 0.45–1.72], P =0.703), P value for interaction=0.573. Conclusions: The presence of carotid stenosis was associated with increased risk of ischemic stroke during follow-up. The effect of added clopidogrel was not significantly different in patients with versus without carotid stenosis. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03354429.

BackgroundDo-not-resuscitate (DNR) orders are commonly used after intracerebral hemorrhage (ICH) and have been shown to be a predictor of mortality independent of disease severity. We determined the frequency of early DNR orders in ICH patients and whether a previously reported association with increased mortality still exists.MethodsWe performed a retrospective analysis of patients discharged from non-federal California hospitals with a primary diagnosis of ICH from January 2013 through December 2014. Characteristics included hospital ICH volume and type and whether DNR order was placed within 24h of admission (early DNR order). The risk of in-hospital mortality was evaluated both on the individual and hospital level using multivariable analyses. A case mix-adjusted hospital DNR index was calculated for each hospital by comparing the actual number of DNR cases with the expected number of DNR cases from a multivariate model.ResultsA total of 9,958 patients were treated in 180 hospitals. Early DNR orders were placed in 20.1% of patients and 54.2% of these patients died during their hospitalization compared to 16.0% of patients without an early DNR order. For every 10% increase in a hospital's utilization of early DNR orders, there was a corresponding 26% increase in the likelihood of in-hospital mortality. Patients treated in hospitals within the highest quartile of adjusted DNR use had a higher relative risk of death compared to the lowest quartile (RR 3.9 vs 5.2) though the trend across quartiles was not statistically significant.ConclusionsThe use of early DNR orders for ICH continues to be a strong predictor of in-hospital mortality. However, patients treated at hospitals with an overall high or low use of early DNR had similar relative risks of death whether or not there was an early DNR order, suggesting that such orders may not be a proxy for less aggressive care as seen previously.

Background: The combination of aspirin and clopidogrel for 90 days after minor stroke or transient ischemic attack (TIA) reduced the risk of recurrent stroke in the POINT trial. The risk reduction was greater in patients with infarct on CT or MRI compared to those without infarct. Objective: To investigate the effect of DAPT on minor stroke and TIA in the POINT trial based on (1) the presence or absence of infarct attributed to the index event (“index infarct”) and (2) whether the index event was classified as stroke or TIA. Design/Methods: Patients were divided into two groups based on whether they had an “index infarct” or not. Baseline demographics and clinical variables were compared between groups using standard statistical tests. We used univariate and multivariable cox-regression models to determine associations between presence of infarct on imaging and primary and secondary outcomes, and interaction analyses to determine whether the presence of “index infarct” modifies the effect of DAPT on study outcomes. We also explored whether the association of “index-infarct” with primary and secondary outcomes varied by index diagnosis (TIA vs. minor stroke). Results: Amongst 4881 enrolled in POINT, 4876 patients had data on whether there was an “index-infarct”; 1793 (36.8%) had “index-infarct”. In adjusted cox-regression analyses, the presence of “index infarct” was associated with the primary efficacy outcome (HR 3.02 95% CI 2.34-3.89, p < 0.01) and subsequent ischemic stroke (HR 3.10 95% CI 2.39-4.02, p < 0.01). The effect of DAPT vs. aspirin on primary efficacy outcome was more pronounced in patients with “index infarct” (HR 0.58 95% CI 0.43-0.79, p Conclusions: In the POINT trial, efficacy of DAPT was greater in patients with infarct on imaging attributed to the index event. Future work should focus on determining clinical factors associated with this group to help identify patients most likely to benefit from acute DAPT.

Background We investigated the association between geographic proximity to hospitals and the administration rate of reperfusion therapy for acute ischemic stroke. Methods We identified patients with acute ischemic stroke who visited the hospital within 12 hours of symptom onset from a prospective nationwide multicenter stroke registry. Reperfusion therapy was classified as intravenous thrombolysis (IVT), endovascular therapy (EVT), or combined therapy. The association between the proportion of patients who were treated with reperfusion therapy and the ground transport time was evaluated using a spline regression analysis adjusted for patient-level characteristics. We also estimated the proportion of Korean population that lived within each 30-minute incremental service area from 67 stroke centers accredited by the Korean Stroke Society. Results Of 12,172 patients (mean age, 68 ± 13 years; men, 59.7%) who met the eligibility criteria, 96.5% lived within 90 minutes of ground transport time from the admitting hospital. The proportion of patients treated with IVT decreased significantly when stroke patients lived beyond 90 minutes of the transport time (P = 0.006). The proportion treated with EVT also showed a similar trend with the transport time. Based on the residential area, 98.4% of Korean population was accessible to 67 stroke centers within 90 minutes. Conclusion The use of reperfusion therapy for acute stroke decreased when patients lived beyond 90 minutes of the ground transport time from the hospital. More than 95% of the South Korean population was accessible to 67 stroke centers within 90 minutes of the ground transport time., Graphical Abstract

Do-not-resuscitate (DNR) orders are commonly used after intracerebral hemorrhage (ICH) and have been shown to be a predictor of mortality independent of disease severity. We determined the frequency of early DNR orders in ICH patients and whether a previously reported association with increased mortality still exists.We performed a retrospective analysis of patients discharged from non-federal California hospitals with a primary diagnosis of ICH from January 2013 through December 2014. Characteristics included hospital ICH volume and type and whether DNR order was placed within 24 h of admission (early DNR order). The risk of in-hospital mortality was evaluated both on the individual and hospital level using multivariable analyses. A case mix-adjusted hospital DNR index was calculated for each hospital by comparing the actual number of DNR cases with the expected number of DNR cases from a multivariate model.A total of 9,958 patients were treated in 180 hospitals. Early DNR orders were placed in 20.1% of patients and 54.2% of these patients died during their hospitalization compared to 16.0% of patients without an early DNR order. For every 10% increase in a hospital's utilization of early DNR orders, there was a corresponding 26% increase in the likelihood of in-hospital mortality. Patients treated in hospitals within the highest quartile of adjusted DNR use had a higher relative risk of death compared to the lowest quartile (RR 3.9 vs 5.2) though the trend across quartiles was not statistically significant.The use of early DNR orders for ICH continues to be a strong predictor of in-hospital mortality. However, patients treated at hospitals with an overall high or low use of early DNR had similar relative risks of death whether or not there was an early DNR order, suggesting that such orders may not be a proxy for less aggressive care as seen previously.

Background and Purpose: Clopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the CYP2C19 gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function CYP2C19 alleles and outcome by treatment group in POINT. Methods: Of the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for CYP2C19 *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death. Results: Nine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09–1.21]; P =0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32–1.34]; P =0.25) among noncarriers. There was no significant interaction by genotype for major ischemia ( P =0.36) or stroke ( P =0.33). Conclusions: This substudy of POINT found no significant interaction with CYP2C19 loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00991029.

Background Psoriasis is the most common chronic inflammatory condition involving the T helper cell system. Population studies have demonstrated that patients with psoriasis and/or psoriatic arthritis have an increased risk of developing vascular risk factors, including diabetes, hypertension, and obesity, and increased risk of adverse vascular events, including myocardial infarction and stroke. Population studies have generally investigated the individual contributions of psoriasis and psoriatic arthritis to development of vascular risk factors; fewer studies have investigated the additive contribution of comorbid inflammatory disorders. We present a case of a woman with psoriasis, psoriatic arthritis, and comorbid vascular risk factors. Case presentation A 49 year-old Caucasian woman with a history of severe psoriasis and psoriatic arthritis since adolescence presented with bilateral lower extremity weakness. She was found to have acute bilateral watershed infarcts and multifocal subacute infarcts. Her evaluation revealed vascular risk factors and elevated non-specific systemic inflammatory markers; serum and cerebral spinal fluid did not reveal underlying infection, hypercoagulable state, or vasculitis. Over the course of days, she exhibited precipitous clinical deterioration related to multiple large vessel occlusions, including the bilateral anterior cerebral arteries and the left middle cerebral artery. Autopsy revealed acute thrombi and diffuse, severe atherosclerosis. Conclusion Patients with early onset inflammatory disease activity or comorbid inflammatory disorders may have an even higher risk of developing metabolic syndrome and adverse vascular events compared to patients with late-onset disease activity or with a single inflammatory condition. The described case illustrates the complex relationship between inflammatory disorders and vascular risk factors. The degree of systemic inflammation, as measured by severity of disease activity, has been shown to have a dose-response relationship with comorbid vascular risk factors and vascular events. Dysregulation of the Th1 and Th17 system has been implicated in the development of atherosclerosis and may explain the severe atherosclerosis seen in such chronic inflammatory conditions. Further research will help refine screening and management guidelines to account for comorbid inflammatory disorders and related disease severity.

In the era of effective antiretroviral therapy (ART), HIV has become a manageable disease marked by an elevated risk of non-AIDS-related comorbidities, including stroke. Rates of stroke are higher in people living with HIV (PLWH) compared with the general population. Elevated stroke risk may be attributable to traditional risk factors, HIV-associated chronic inflammation and immune dysregulation, and possible adverse effects of long-standing ART use. Tailoring stroke prevention strategies for PLWH requires knowledge of how stroke pathogenesis may differ from non-HIV-associated stroke, knowledge of long-term stroke outcomes in HIV, and accurate stroke risk assessment tools. As a result, the approach to primary and secondary stroke prevention in PLWH relies heavily on guidelines developed for the general population, with an emphasis on optimization of traditional vascular risk factors and early initiation of ART. This review summarizes existing evidence on HIV-associated stroke mechanisms and considerations for stroke prevention for PLWH.

Stroke is one of the leading causes of death and disability worldwide. Standard treatment for stroke is intravenous (IV) injection of tissue plasminogen activator (t-PA) rapidly after symptom onset. However, there are limitations of IV t-PA treatment, such as a short time window for administration and risk for hemorrhage. Recent trials have demonstrated the benefit of endovascular treatment when added to standard treatment to improve outcomes for patients. Advanced imaging was utilized in some trials to identify patients with proximal intracranial occlusion to target for endovascular reperfusion therapy, and to exclude patients with large infarct cores or poor collateral circulation who would not be expected to benefit from intervention. This article summarizes the use of imaging in recent stroke trials in details, provides a stroke imaging protocol, and provides tips which radiologists should know to help their neurointerventionalists.

Background: Studies of out-of-hospital cardiac arrest and sudden cardiac death (SCD) use emergency medical services records, death certificates, or definitions that infer cause of death; thus, the true incidence of SCD is unknown. Over 90% of SCDs occur out-of-hospital; nonforensic autopsies are rarely performed, and therefore causes of death are presumed. We conducted a medical examiner–based investigation to determine the precise incidence and autopsy-defined causes of all SCDs in an entire metropolitan area. We hypothesized that postmortem investigation would identify actual sudden arrhythmic deaths among presumed SCDs. Methods: Between February 1, 2011, and March 1, 2014, we prospectively identified all incident deaths attributed to out-of-hospital cardiac arrest (emergency medical services primary impression, cardiac arrest) between 18 to 90 years of age in San Francisco County for autopsy, toxicology, and histology via medical examiner surveillance of consecutive out-of-hospital deaths, all reported by law. We obtained comprehensive records to determine whether out-of-hospital cardiac arrest deaths met World Health Organization (WHO) criteria for SCD. We reviewed death certificates filed quarterly for missed SCDs. Autopsy-defined sudden arrhythmic deaths had no extracardiac cause of death or acute heart failure. A multidisciplinary committee adjudicated final cause. Results: All 20 440 deaths were reviewed; 12 671 were unattended and reported to the medical examiner. From these, we identified 912 out-of-hospital cardiac arrest deaths; 541 (59%) met WHO SCD criteria (mean 62.8 years, 69% male) and 525 (97%) were autopsied. Eighty-nine additional WHO-defined SCDs occurred within 3 weeks of active medical care with the death certificate signed by the attending physician, ineligible for autopsy but included in the countywide WHO-defined SCD incidence of 29.6/100 000 person-years, highest in black men ( P P =0.024); 286 of 293 (98%) had structural cardiac disease. Conclusions: Forty percent of deaths attributed to stated cardiac arrest were not sudden or unexpected, and nearly half of presumed SCDs were not arrhythmic. These findings have implications for the accuracy of SCDs as defined by WHO criteria or emergency medical services records in aggregate mortality data, clinical trials, and cohort studies.

ObjectiveSince cardic fibrosis was previously found more frequently in patients with sudden unexpected death in epilepsy (SUDEP) than control cases, we compared blinded and quantitative reviews of cardiac pathology in SUDEP to multiple control groups.MethodsWe adjudicated causes of death in epilepsy patients as part of consecutive out-of-hospital sudden cardiac deaths (SCDs) from the Postmortem Systematic Investigation of Sudden Cardiac Death (POSTSCD) study. Blinded cardiac gross and microscopic examinations were performed by forensic and cardiac pathologists.ResultsOf 541 SCDs over 37 months (mean age 62.8 years, 69% male), 525 (97%) were autopsied; 25/525 (4.8%) had epilepsy (mean age 56.4 years ± 15.4, range 27–92; 67% male). The 25 epilepsy patients died of definite SUDEP/definite SUDEP-plus (n = 8), possible SUDEP (n = 10), or other causes (n = 7). Comparison groups included autopsy-defined sudden arrhythmic death (SAD; n = 285) and trauma (n = 104) and we adjusted for age, sex, HIV, coronary artery disease, congestive heart failure, and cardiomyopathy in the analyses. Compared to SAD cases, SUDEP cases had less gross and histologic evidence of cardiac pathology; significant for cardiac mass (p < 0.0011), coronary artery disease (p < 0.0024), total cardiac fibrosis (CF) (p = 0.022), and interstitial CF (p = 0.013). Compared to trauma cases, SUDEP cases had similar cardiac pathology including CF.ConclusionAmong SUDEP cases, cardiac pathology was less severe than in SAD cases but similar to trauma and epilepsy controls. Our data do not support prior studies finding elevated rates of CF among SUDEP cases compared to controls. Larger studies including molecular analyses would further our understanding of cardiac changes associated with SUDEP.

To determine whether neurologic consultation influences the use of therapeutic hypothermia.We identified adult patients treated for cardiac arrest from October 2009 through September 2015 at 149 academic medical centers and their affiliate hospitals using discharge diagnosis codes in Vizient database. Neurology consultation was defined as a neurologist participating in patient care at any point during the hospitalization. Use of therapeutic hypothermia was identified using procedure codes. We used multivariable models to evaluate the association between neurologic consultation and therapeutic hypothermia before and after adjustment for patient baseline characteristics and hospital factors including inpatient volume and relative volume of cardiac arrest cases.We identified 136,830 hospitalizations for cardiac arrest. The 9,336 (6.8%) encounters involving a neurologist had higher severity of illness, longer hospital stay, and longer intensive care unit stay. There were 5,034 (3.7%) encounters where patients underwent therapeutic hypothermia. Hypothermia use was significantly more common when neurologists were involved during hospitalization (7.9% vs. 3.4%; OR 2.44, 95% CI 2.2-2.6; p0.01). After adjustment, neurologic consultation continued to be associated with the use of therapeutic hypothermia (adjusted OR 2.5, 95% CI 2.3-2.8), particularly among hospitals in the highest quartile of total inpatient volume (OR 4.6, 95% CI 4.0-5.3). Lower in-hospital mortality was also associated with neurological consultation after adjusting for therapeutic hypothermia (59.2% vs. 61.3%, p0.01).The involvement of a neurologist in cardiac arrest patients is associated with increased use of therapeutic hypothermia, though therapeutic hypothermia for cardiac arrest likely remains underutilized.

Objective:To determine the definite and potential frequency of seizures and epilepsy as a cause of death (COD) and how often this goes unrecognized.Methods:Prospective determination of seizures or epilepsy and final COD for individuals aged 18–90 years with out-of-hospital sudden cardiac deaths (SCDs) from the population-based San Francisco POST SCD Study. We compared prospective seizure or epilepsy diagnosis and final COD as adjudicated by a multidisciplinary committee (pathologists, electrophysiologists, and a vascular neurologist) vs retrospective adjudication by 2 epileptologists with expertise in seizure-related mortality.Results:Of 541 SCDs identified during the 37-month study period (mean age 62.8 years, 69% men), 525 (97%) were autopsied; 39/525 (7.4%) had seizures or epilepsy (mean age: 58 years, range: 27–92; 67% men), comprising 17% of 231 nonarrhythmic sudden deaths. The multidisciplinary team identified 15 cases of epilepsy, 6 sudden unexpected deaths in epilepsy (SUDEPs), and no deaths related to acute symptomatic seizures. The epileptologists identified 25 cases of epilepsy and 8 definite SUDEPs, 10 possible SUDEPs, and 5 potential cases of acute symptomatic seizures as a COD.Conclusions:Among the 25 patients identified with epilepsy by the epileptologists, they found definite or possible SUDEP in 72% (18/25) vs 24% (6/25) by the multidisciplinary group (6/15 cases they identified with epilepsy). The epileptologists identified acute symptomatic seizures as a potential COD in 5/14 patients with alcohol-related seizures. Epilepsy is underdiagnosed among decedents. Among patients with seizures and epilepsy who die suddenly, seizures and SUDEP often go unrecognized as a potential or definite COD.

Background: Vitamin K antagonist (VKA)–associated intracerebral hemorrhages (ICHs) are more likely to expand and are associated with higher mortality than primary ICH. Prompt reversal of anticoagulant effect with prothrombin complex concentrate (PCC) may promote hemostasis and decrease hematoma expansion. The aim of this study was to evaluate the impact of an electronic order set designed to standardize and facilitate more timely reversal of coagulopathy in VKA-associated ICH. Methods: We identified all adults who received PCC for VKA-associated ICH from June 2012 to June 2015 at University of California San Francisco Medical Center, which included a period before and after an electronic order set became available in 2014. We abstracted baseline demographics and clinical data from electronic health records. The primary outcome was time from radiographic identification of ICH to administration of PCC. Results: Thirty-one patients received PCC for VKA-associated ICH, including 17 patients before and 14 patients after the order set became available. Baseline demographics and clinical features were similar. Order set use was associated with a significant decrease in the time from identification of ICH on imaging to the administration of PCC (median 83 vs 45 minutes; P = .02), more accurate dosing (29.4% vs 92.9%; P < .01), and a shorter time from the PCC order to follow-up international normalized ratio (INR) testing (median 164 vs 85 minutes, P = .001). Conclusion: An electronic order set for administering PCC for VKA-associated ICH was associated with significantly faster time to PCC administration and increased dosing accuracy.

Background Although ischemic stroke risk is increased among people living with HIV infection, little is known about the epidemiology of ischemic stroke subtypes in contemporary HIV-infected cohorts. We examined the distribution of ischemic stroke subtypes among predominantly treated HIV-infected individuals to determine if and how the distribution differs from that of the general population. Methods We studied 60 HIV-infected and 60 HIV-uninfected adults with a history of first-ever ischemic stroke between 2000 and 2012. Ischemic strokes were classified as 1 of 5 subtypes based on established criteria. We used multinomial logistic regression models to compare the relative frequency of ischemic stroke subtypes by HIV status. Results Large artery atherosclerosis (23%) and stroke of undetermined etiology (23%) were the most common stroke subtypes among HIV-infected individuals. The most recent plasma HIV viral load before the stroke event differed by subtype, with a median undetectable viral load for individuals with large artery stroke and stroke of undetermined etiology. Using cardioembolic stroke as the reference subtype, HIV-infected individuals were at higher proportional risk of stroke of undetermined etiology compared with uninfected individuals (relative risk ratio [RRR]: 8.6, 95% confidence interval [CI]: 1.2-63.7, P = .04). Among HIV-infected individuals with virologically suppressed infection, we observed a trend toward a greater proportion of strokes attributable to large artery atherosclerosis (RRR: 6.7, 95% CI: .8-57.9, P = .08). Conclusions HIV-infected individuals may be at greater proportional risk of stroke of undetermined etiology compared with uninfected individuals. Further investigation is warranted to confirm this finding and determine underlying reasons for this greater risk.

Dual antiplatelet therapy with clopidogrel and aspirin is effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA). Uncertainties remained about the optimal duration of dual antiplatelet therapy for minor stroke or TIA.To obtain precise estimates of efficacy and risk of dual antiplatelet therapy after minor ischemic stroke or TIA.This analysis pooled individual patient-level data from 2 large-scale randomized clinical trials that evaluated clopidogrel-aspirin as a treatment to prevent stroke after a minor stroke or high-risk TIA. The Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) trial enrolled patients at 114 sites in China from October 1, 2009, to July 30, 2012. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial enrolled patients at 269 international sites from May 28, 2010, to December 19, 2017. Both were followed up for 90 days. Data analysis occurred from November 2018 to May 2019.In the 2 trials, patients with minor stroke or high-risk TIA were randomized to clopidogrel-aspirin or aspirin alone within 12 hours (POINT) or 24 hours (CHANCE) of symptom onset.The primary efficacy outcome was a major ischemic event (ischemic stroke, myocardial infarction, or death from ischemic vascular causes). The primary safety outcome was major hemorrhage.The study enrolled 5170 patients (CHANCE) and 4881 patients (POINT). Analysis included individual data from 10 051 patients (5016 in the clopidogrel-aspirin treatment group and 5035 in the control group) with a median age of 63.2 (interquartile range, 55.0-72.9) years; 6106 patients (60.8%) were male. Clopidogrel-aspirin treatment reduced the risk of major ischemic events at 90 days compared with aspirin alone (328 of 5016 [6.5%] vs 458 of 5035 [9.1%]; hazard ratio [HR], 0.70 [95% CI, 0.61-0.81]; P .001), mainly within the first 21 days (263 of 5016 [5.2%] vs 391 of 5035 [7.8%]; HR, 0.66 [95% CI, 0.56-0.77]; P .001), but not from day 22 to day 90. No evidence of heterogeneity of treatment outcome across trials or prespecified subgroups was observed. Major hemorrhages were more frequent in the clopidogrel-aspirin group, but the difference was nonsignificant.In this analysis of the POINT and CHANCE trials, the benefit of dual antiplatelet therapy appeared to be confined to the first 21 days after minor ischemic stroke or high-risk TIA.

Background: Conventional definitions of sudden cardiac death (SCD) presume cardiac cause. We studied the World Health Organization–defined SCDs autopsied in the POST SCD study (Postmortem Systematic Investigation of SCD) to determine whether premortem characteristics could identify autopsy-defined sudden arrhythmic death (SAD) among presumed SCDs. Methods: Between January 2, 2011, and January 4, 2016, we prospectively identified all 615 World Health Organization–defined SCDs (144 witnessed) 18 to 90 years in San Francisco County for medical record review and autopsy via medical examiner surveillance. Autopsy-defined SADs had no extracardiac or acute heart failure cause of death. We used 2 nested sets of premortem predictors—an emergency medical system set and a comprehensive set adding medical record data—to develop Least Absolute Selection and Shrinkage Operator models of SAD among witnessed and unwitnessed cohorts. Results: Of 615 presumed SCDs, 348 (57%) were autopsy-defined SAD. For witnessed cases, the emergency medical system model (area under the receiver operator curve 0.75 [0.67–0.82]) included presenting rhythm of ventricular tachycardia/fibrillation and pulseless electrical activity, while the comprehensive (area under the receiver operator curve 0.78 [0.70–0.84]) added depression. If only ventricular tachycardia/fibrillation witnessed cases (n=48) were classified as SAD, sensitivity was 0.46 (0.36–0.57), and specificity was 0.90 (0.79–0.97). For unwitnessed cases, the emergency medical system model (area under the receiver operator curve 0.68 [0.64–0.73]) included black race, male sex, age, and time since last seen normal, while the comprehensive (area under the receiver operator curve 0.75 [0.71–0.79]) added use of β-blockers, antidepressants, QT-prolonging drugs, opiates, illicit drugs, and dyslipidemia. If only unwitnessed cases Conclusions: Our models identify premortem characteristics that can better specify autopsy-defined SAD among presumed SCDs and suggest the World Health Organization definition can be improved by restricting witnessed SCDs to ventricular tachycardia/fibrillation or nonpulseless electrical activity rhythms and unwitnessed cases to

In patients with acute minor ischemic stroke or high-risk transient ischemic attack enrolled in the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke [POINT] Trial), the combination of clopidogrel and aspirin for 90 days reduced major ischemic events but increased major hemorrhage in comparison to aspirin alone.In a secondary analysis of POINT (N=4881), we assessed the time course for benefit and risk from the combination of clopidogrel and aspirin. The primary efficacy outcome was a composite of ischemic stroke, myocardial infarction, or ischemic vascular death. The primary safety outcome was major hemorrhage. Risks and benefits were estimated for delayed times of treatment initiation using left-truncated models.Through 90 days, the rate of major ischemic events was initially high then decreased markedly, whereas the rate of major hemorrhage remained low but relatively constant throughout. With the use of a model-based approach, the optimal change point for major ischemic events was 21 days (0-21 days hazard ratio 0.65 for clopidogrel-aspirin versus aspirin; 95% CI, 0.50-0.85; P=0.0015, in comparison to 22-90 days hazard ratio, 1.38; 95% CI, 0.81-2.35; P=0.24). Models showed benefits of clopidogrel-aspirin for treatment delayed as long as 3 days after symptom onset.The benefit of clopidogrel-aspirin occurs predominantly within the first 21 days, and outweighs the low, but ongoing risk of major hemorrhage. When considered with the results of the CHANCE trial (Clopidogrel in High-Risk Patients With Non-disabling Cerebrovascular Events), a similar trial treating with clopidogrel-aspirin for 21 days and showing no increase in major hemorrhage, these results suggest that limiting clopidogrel-aspirin use to 21 days may maximize benefit and reduce risk after high-risk transient ischemic attack or minor ischemic stroke.URL: https://www.clinicaltrials.gov. Unique identifier: NCT00991029.

Stroke symptoms can be unsettling, even when symptoms resolve, but focusing on stroke prevention can be empowering provided that effective interventions for appropriate patient populations are available. Current options include interventions for symptomatic carotid artery stenosis, anticoagulation for atrial fibrillation, high-dose statins, new oral anticoagulants, new developments in atrial fibrillation detection, and new therapeutics are in development. For antiplatelet therapy, aspirin monotherapy is effective but dual antiplatelet therapy with the combination of aspirin and clopidogrel increases hemorrhage risks over the long term that outweigh potential benefits. In the short term though, both the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) and Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trials have shown a benefit of short-term dual-antiplatelet therapy, though the increased major hemorrhage risk seen in POINT could justify applying dual-antiplatelet therapy to just the first 21 days. Furthermore, since clopidogrel is a prodrug that must be metabolized to have antiplatelet activity, it is not surprising that the treatment effect in CHANCE was limited to patients who were not carriers of loss-of-function alleles for clopidogrel metabolism. Ticagrelor, an antiplatelet agent which failed to meet its primary endpoint as monotherapy compared to aspirin in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial, is currently being tested as combination therapy with aspirin compared to aspirin alone in Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES). These developments along with improvements to the infrastructure to perform rapid evaluations and to apply intensive secondary stroke prevention interventions hold continued promise for the future.

Introduction: In-hospital strokes have a different pattern of risk factors, etiologies, and mimics than strokes that are initially evaluated in the Emergency Department. In-hospital stroke patients often have multiple confounding comorbidities which may provide alternative explanations for suspected stroke symptoms. Objective: To characterize strokes vs. stroke mimics among in-hospital Code Stroke activations. Methods: We identified all adults with an in-hospital Code Stroke activation between September 2014 and February 2018 at a single academic medical center (660 beds) and abstracted the reason for Code Stroke activation, comorbidities, primary inpatient service, patient location, NIHSS, and final diagnosis from comprehensive electronic health records. Univariate and multivariate logistic regression were used to assess the association between clinical variables and stroke mimics. Results: Of 461 in-hospital Code Stroke activations, the final diagnoses were 110 (24%) ischemic stroke or TIA, 35 (7.5%) intracranial hemorrhage, and 316 (68.5%) stroke mimics. Of the 85 patients with a final diagnosis of ischemic stroke, 9 (8%) received tPA and 2 underwent embolectomy (1.8%). The most common reason for Code Stroke activation was altered mental status (48%). Altered mental status (OR 0.20, 95% CI 0.10-0.39) and previously-known CNS tumor (OR 0.18, CI 0.05-0.69) were least likely to be associated with a final diagnosis of stroke. The most common stroke mimics were toxic/metabolic encephalopathy, seizure, and delirium. Limb weakness (OR 6.93, CI 3.86-12.7), recent cardiac/vascular procedure (OR 5.03, CI 1.92-8.89) and NIHSS (OR 1.09 per point, CI 1.05-1.13) were predictive of stroke in multivariate analysis. Conclusions: A majority of in-hospital Code Stroke activations are for stroke mimics. Altered mental status was the most common reason for Code Stroke activation, yet was least likely to be associated with a final diagnosis of stroke. While rapid recognition of stroke symptoms and timely Code Stroke activations are critical to maximizing opportunities to apply acute interventions, variability in the reasons for Code Stroke activation particularly for undifferentiated altered mental status may be a target for future optimization.

Introduction: Misclassification of outcome events can potentially lead to biased treatment effect estimates. Efforts to avoid endpoint misclassification in large-scale multicenter randomized clinical trials such as POINT have included an independent adjudication committee blinded to study treatments to standardize assessment of outcomes and reduce risk of ascertainment bias of main study endpoints. Debate continues about the scientific value of such committees and whether independent assessments improve reliability of study results, particularly when compared to the considerable time and resources consumed by the process. Methods: An independent adjudication committee adjudicated 467 primary and secondary efficacy outcomes and major and minor bleeding events, including the primary efficacy endpoint, a composite of new ischemic vascular events: ischemic stroke, myocardial infarction or ischemic vascular death at 90 days. The impact of the adjudicated endpoint process was studied by comparing the primary results using site-assessed endpoints versus adjudicator-assessed endpoints. Time from randomization to first endpoint of interest was calculated using the log-rank test and the hazard ratio and 95% CI were computed using a Cox proportional hazards model. Rate of agreement between site-assessed and adjudicator-assessed outcomes was also calculated. All analyses were completed according to the intention-to-treat principle. Results: The primary results of POINT have been published. The hazard ratios (HRs) (95% confidence interval [CI]) for clopidogrel versus aspirin therapy for the primary composite endpoint were 0.75 (0.59-0.95) for adjudicator-assessed events and 0.76 (0.60-0.95) for investigator-assessed events. Agreement between the composite endpoint for adjudicated-assessed and investigator-assessed events was 90.7%. Conclusion: Independent endpoint adjudication did not significantly impact estimates of the primary efficacy treatment effect in POINT compared to site-assessed endpoints. If misclassification of outcome events is infrequent, and careful site selection, study design and outcome definitions are in place, independent adjudication may have no meaningful impact on estimates of treatment effect.

Introduction: An online process for eliciting and assessing information from stroke patients to prescreen for stroke recovery studies holds potential to accelerate enrollment, but the validity of using self-reported information for online pre-screening is uncertain. Methods: Among patients in the UCSF Stroke Recovery Initiative, a nationwide, online participant recruitment registry of stroke patients that have expressed an interest in stroke recovery studies (strokerecoveryinitiative.ucsf.edu; NCT03318432), we compared self-reported information on stroke subtype (ischemic vs. hemorrhagic), location (MCA, cerebellar, brainstem), and functional status (modified Rankin Scale) elicited online to final validated responses as determined by follow-up semi-structured telephone interviews. We used descriptive statistics and Cohen’s kappa to evaluate the concordance of self-reported information against validated responses. Results: A total of 1,283 of the 3,959 participants in the recruitment registry were selected for semi-structured telephone follow-up (mean age 56; 55% male; average of 2.6 years after the index stroke). There was moderate agreement between self-report and telephone-validated responses for stroke subtype (84.4% agreement, kappa=0.68 for ischemic stroke; 83.0% agreement, 0.70 for hemorrhagic stroke) and similar performance for stroke location (86.1% agreement, kappa=0.75 for MCA location; 81.1% agreement, 0.66 for cerebellar location; 86.9% agreement, 0.78 for brainstem location). Agreement for the modified Rankin Scale for functional status was somewhat lower overall (66.7% agreement, kappa=0.53) but self-reported scores were within 1 point of the validated score 94% of the time. Conclusion: Using self-reported information to prescreen patients for stroke recovery studies requires a permissive approach to basic eligibility criteria to flag potentially-eligible candidates for additional follow-up. The efficiency and high-throughput of an online prescreening process would benefit from having studies with eligibility criteria that are developed with an efficient prescreening process in mind as well as high-throughput pre-screening instruments that are optimized for self-report.

Introduction: Prior studies have documented disparities in key acute stroke care metrics, with women and minorities more likely to have treatment delays and less likely to receive IV tPA. Objective: To evaluate whether implementation of a direct ambulance-to-CT stroke protocol reduces race, sex, and primary language disparities in stroke treatment times. Methods: We identified patients with confirmed strokes that had been transported by ambulance to our emergency department before and after implementation of a direct ambulance-to-CT protocol for suspected stroke at our urban safety-net hospital. We used the Mann-Whitney U test to compare median door-to-CT (DTC) and door-to-needle (DTN) times by sex, race, and primary language during the pre- and post-intervention periods. Results: A total of 106 stroke patients in the pre-intervention group and 119 in the post-intervention group were included in this analysis. The pre-intervention group included 57 (53.8%) women, 20 (18.9%) whites, and 68 (64.2%) English-speaking patients. The post-intervention group included 58 (48.7%) women, 26 (21.9%) whites, and 77 (64.7%) English-speaking patients. A total of 48 pre-intervention patients and 47 post-intervention patients received tPA. Overall, median DTC and DTN times were significantly lower in the post-intervention group compared to the pre-intervention group (21 minutes vs. 10, p Conclusions: While no significant disparities in stroke treatment times by sex, race, or primary language were identified in the pre-intervention period, implementation of a direct ambulance-to-CT protocol was associated with greater improvements in DTN times for men than for women.

Introduction: Across 269 international sites, the POINT trial randomly assigned 4881 patients with minor ischemic stroke or high-risk transient ischemic attack to receive either clopidogrel at a loading dose of 600 mg on day 1 followed by 75 mg per day, plus aspirin at a dose of 50-325 mg per day or the same range of doses of aspirin alone. Dual antiplatelet therapy significantly reduced the incidence of major ischemic events, but also significantly increased the incidence of major hemorrhage. Clopidogrel is a prodrug that requires metabolism by the cytochrome P450 complex to act on the P2Y12 platelet receptor. CYP2C19 (cytochrome P450 family 2 subfamily C polypeptide 19) variants are associated with variable rates of metabolism of clopidogrel and thus pharmacogenomic effects may be clinically relevant. Methods: Genomic DNA was extracted from peripheral blood monocytes using the standard protocols. Genotyping for CYP2C19 *2, *3 and *17 alleles (rs4244285, rs4986893 and rs12248560) defines metabolizer/activator status and was performed using custom TaqMan Allelic Discrimination Assays on a QuantStudio™ 7 Flex Real-Time PCR System. Results: As of June 28, 2018, a total of 445 trial participants had DNA available for analysis. CYP2C19 allele genotyping demonstrated approximately one quarter of subjects (n=127; 28.6%) would be defined as poor or Intermediate metabolizers of clopidogrel. Conclusions: Based on targeted cytochrome P 450 genotyping, about one quarter of POINT patients have reduced clopidogrel activation. Additional genotyping is ongoing. We plan to present results assessing whether the treatment effect of clopidogrel is limited to those with CYP2C19 genotypes associated with normal drug metabolism.

Objectives To compare outcomes between two models of acute ischemic stroke care. Namely 1) “drip-and-stay”, i.e. IV tissue plasminogen activator (tPA) administered at a spoke hospital in a telestroke network, with the patient remaining at the spoke, versus 2) “drip-and-ship”, i.e. tPA administered at a spoke hospital with subsequent patient transfer to a hub hospital, and 3) “hub”, i.e. tPA and subsequent treatment at a hub hospital. Materials and Methods We performed a systematic review and meta-analysis according to PRISMA guidelines. Literature searches of MEDLINE, Embase, and Cochrane from inception-October 2019 included randomized control trials and observational cohort studies comparing the drip-and-stay model to hub and drip-and-ship models. Outcomes of interest were functional independence (modified Rankin Scale ≤ 1), symptomatic intracranial hemorrhage (sICH), mortality, and length of stay. Pooled effect estimates were calculated using a fixed-effects meta-analysis and random-effects Bayesian meta-analysis. Non-inferiority was calculated using a fixed-margin method. Results Of 2806 unique records identified, 10 studies, totaling 4,164 patients, fulfilled the eligibility criteria. Meta-analysis found no significant difference in functional outcomes (mRS0-1) (6 studies, RR=1.09, 95%CI 0.98–1.22, p=0.123), sICH (8 studies, RR=0.98, 95%CI 0.64–1.51, p=0.942), or 90-day mortality (5 studies, RR=0.98, 95%CI 0.73–1.32, p=0.911, respectively) between patients treated in a drip-and-stay model compared to patients treated in drip-and-ship or hub models. There was no significant heterogeneity in these outcomes. Drip-and-stay outcomes (mRS 0–1, sICH) were non-inferior when compared to the combined group. Conclusions Our findings indicate that drip-and-stay is non-inferior to current models of drip-and-ship or hub stroke care, and may be as safe and as effective as either.

Background: Chronic pain is common following stroke, however there is little known about the treatments for pain that are being accessed by stroke survivors, nor their perceived effectiveness. Objectives: The objectives were to: i) identify the number and type of treatments for pain currently used by stroke survivors with chronic pain; and ii) examine the self-perceived effectiveness of medication and non-medication treatments for pain. Methods: Cross-sectional survey. Participants with stroke and self-reported chronic pain completed an online survey that measured demographics, stroke related factors, intensity of pain, treatments for pain, and perceived effect of medication and non-medication treatments for pain. Results: Of 322 stroke survivors who completed the survey, the majority (90.1%) reported current use of pain treatment(s). Medications were accessed by 257 (79.8%), with the most common being anti-inflammatories (39.8%), anticonvulsants (29.5%) and antidepressants (24.8%). Paracetamol (12.1%) was the most common non-prescribed medication used. Polypharmacy was high, with 129 (40.1%) reporting taking 2 or more medications. Medication treatments were self-reported to be effective in 47.1% of those taking medication. Non-medication treatments were accessed by 208 (64.6%), with Physical Therapy/Physiotherapy being most common (48.1%), followed by Occupational Therapy (15.5%) and Psychology (11.8%). Use of multiple non-medication treatments was reported by 85 (26.4%). Non-medication treatments were reported to be effective by 52.4% of those receiving them. Conclusions: Survey findings indicate that stroke survivors with chronic pain demonstrate high utilization of pain treatments, despite the perception that treatment is often ineffective. This highlights the need to develop effective pain interventions for stroke survivors. Refereed/Peer-reviewed