Was COVID-19 Associated With Worsening Inequities in Stroke Treatment and Outcomes?

Background COVID-19 stressed hospitals and may have disproportionately affected the stroke outcomes and treatment of Black and Hispanic individuals. Methods and Results This retrospective study used 100% Medicare Provider Analysis and Review file data from between 2016 and 2020. We used interrupted time series analyses to examine whether the COVID-19 pandemic exacerbated disparities in stroke outcomes and reperfusion therapy. Among 1 142 560 hospitalizations for acute ischemic strokes, 90 912 (8.0%) were Hispanic individuals; 162 752 (14.2%) were non-Hispanic Black individuals; and 888 896 (77.8%) were non-Hispanic White individuals. The adjusted odds of mortality increased by 51% (adjusted odds ratio [aOR], 1.51 [95% CI, 1.34-1.69]; P<0.001), whereas the rates of nonhome discharges decreased by 11% (aOR, 0.89 [95% CI, 0.82-0.96]; P=0.003) for patients hospitalized during weeks when the hospital's proportion of patients with COVID-19 was >30%. The overall rates of motor deficits (P=0.25) did not increase, and the rates of reperfusion therapy did not decrease as the weekly COVID-19 burden increased. Black patients had lower 30-day mortality (aOR, 0.70 [95% CI, 0.69-0.72]; P<0.001) but higher rates of motor deficits (aOR, 1.14 [95% CI, 1.12-1.16]; P<0.001) than White individuals. Hispanic patients had lower 30-day mortality and similar rates of motor deficits compared with White individuals. There was no differential increase in adverse outcomes or reduction in reperfusion therapy among Black and Hispanic individuals compared with White individuals as the weekly COVID-19 burden increased. Conclusions This national study of Medicare patients found no evidence that the hospital COVID-19 burden exacerbated disparities in treatment and outcomes for Black and Hispanic individuals admitted with an acute ischemic stroke.

Recent Vitamin K Antagonist Use and Intracranial Hemorrhage After Endovascular Thrombectomy for Acute Ischemic Stroke.

Importance: Use of oral vitamin K antagonists (VKAs) may place patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke caused by large vessel occlusion at increased risk of complications. Objective: To determine the association between recent use of a VKA and outcomes among patients selected to undergo EVT in clinical practice. Design, Setting, and Participants: Retrospective, observational cohort study based on the American Heart Association's Get With the Guidelines-Stroke Program between October 2015 and March 2020. From 594 participating hospitals in the US, 32 715 patients with acute ischemic stroke selected to undergo EVT within 6 hours of time last known to be well were included. Exposure: VKA use within the 7 days prior to hospital arrival. Main Outcome and Measures: The primary end point was symptomatic intracranial hemorrhage (sICH). Secondary end points included life-threatening systemic hemorrhage, another serious complication, any complications of reperfusion therapy, in-hospital mortality, and in-hospital mortality or discharge to hospice. Results: Of 32 715 patients (median age, 72 years; 50.7% female), 3087 (9.4%) had used a VKA (median international normalized ratio [INR], 1.5 [IQR, 1.2-1.9]) and 29 628 had not used a VKA prior to hospital presentation. Overall, prior VKA use was not significantly associated with an increased risk of sICH (211/3087 patients [6.8%] taking a VKA compared with 1904/29 628 patients [6.4%] not taking a VKA; adjusted odds ratio [OR], 1.12 [95% CI, 0.94-1.35]; adjusted risk difference, 0.69% [95% CI, -0.39% to 1.77%]). Among 830 patients taking a VKA with an INR greater than 1.7, sICH risk was significantly higher than in those not taking a VKA (8.3% vs 6.4%; adjusted OR, 1.88 [95% CI, 1.33-2.65]; adjusted risk difference, 4.03% [95% CI, 1.53%-6.53%]), while those with an INR of 1.7 or lower (n = 1585) had no significant difference in the risk of sICH (6.7% vs 6.4%; adjusted OR, 1.24 [95% CI, 0.87-1.76]; adjusted risk difference, 1.13% [95% CI, -0.79% to 3.04%]). Of 5 prespecified secondary end points, none showed a significant difference across VKA-exposed vs VKA-unexposed groups. Conclusions and Relevance: Among patients with acute ischemic stroke selected to receive EVT, VKA use within the preceding 7 days was not associated with a significantly increased risk of sICH overall. However, recent VKA use with a presenting INR greater than 1.7 was associated with a significantly increased risk of sICH compared with no use of anticoagulants.

Carotid Intimal Sarcoma Presenting as Large Vessel Occlusion and Diagnosed by Embolus Histopathology: Case Report.

Objective: The objective of this study was to present the clinical, histopathologic, and radiographic findings of a unique case of intimal sarcoma (IS) embolus presenting as a large vessel occlusion causing an ischemic stroke without a detectable primary tumor site. Methods: Extensive examinations, multimodal imaging, laboratory testing, and histopathologic analysis were used in evaluation. Results: We report the case of a patient who presented with acute embolic ischemic stroke and was found to have IS based on a histopathologic evaluation of his embolectomy specimen. Subsequent comprehensive imaging studies failed to detect a primary tumor site. Multidisciplinary interventions including a course of radiotherapy were performed. The patient died of recurrent multifocal strokes 92 days after diagnosis. Discussion: Meticulous histopathologic analysis should be conducted on cerebral embolectomy specimens. Histopathology may be useful in diagnosing IS.

Nurse's Role in Perioperative Neurological Evaluation and Management to Lower the Risk of Acute Stroke in Patients Undergoing Noncardiac, Nonneurological Surgery.

Perioperative nurses have the opportunity to play a key role in prevention and recognition of stroke in patients undergoing noncardiac, nonneurological surgery and may impact this potentially devastating complication. Effective nursing care of the older adult requires a specialized knowledge base. Scientific Statements are a cornerstone of the knowledge base that informs this care. This article summarizes the recently released American Heart Association/American Stroke Association Scientific Statement entitled: Perioperative Neurological Evaluation and Management to Lower the Risk of Acute Stroke in Patients Undergoing Noncardiac, Nonneurological Surgery and discusses the nurse's role in the care of this vulnerable patient population.

Association of Time Elapsed Since Ischemic Stroke With Risk of Recurrent Stroke in Older Patients Undergoing Elective Nonneurologic, Noncardiac Surgery.

Importance: Perioperative strokes are a major cause of death and disability. There is limited information on which to base decisions for how long to delay elective nonneurologic, noncardiac surgery in patients with a history of stroke. Objective: To examine whether an association exists between the time elapsed since an ischemic stroke and the risk of recurrent stroke in older patients undergoing elective nonneurologic, noncardiac surgery. Design, Setting, and Participants: This cohort study used data from the 100% Medicare Provider Analysis and Review files, including the Master Beneficiary Summary File, between 2011 and 2018 and included elective nonneurologic, noncardiac surgeries in patients 66 years or older. Patients were excluded if they had more than 1 procedure during a 30-day period, were transferred from another hospital or facility, were missing information on race and ethnicity, were admitted in December 2018, or had tracheostomies or gastrostomies. Data were analyzed May 7 to October 23, 2021. Exposures: Time interval between a previous hospital admission for acute ischemic stroke and surgery. Main Outcomes and Measures: Acute ischemic stroke during the index surgical admission or rehospitalization for stroke within 30 days of surgery, 30-day all-cause mortality, composite of stroke and mortality, and discharge to a nursing home or skilled nursing facility. Multivariable logistic regression models were used to estimate adjusted odds ratios (AORs) to quantify the association between outcome and time since ischemic stroke. Results: The final cohort included 5 841 539 patients who underwent elective nonneurologic, noncardiac surgeries (mean [SD] age, 74.1 [6.1] years; 3 371 329 [57.7%] women), of which 54 033 (0.9%) had a previous stroke. Patients with a stroke within 30 days before surgery had higher adjusted odds of perioperative stroke (AOR, 8.02; 95% CI, 6.37-10.10; P < .001) compared with patients without a previous stroke. The adjusted odds of stroke were not significantly different at an interval of 61 to 90 days between previous stroke and surgery (AOR, 5.01; 95% CI, 4.00-6.29; P < .001) compared with 181 to 360 days (AOR, 4.76; 95% CI, 4.26-5.32; P < .001). The adjusted odds of 30-day all-cause mortality were higher in patients who underwent surgery within 30 days of a previous stroke (AOR, 2.51; 95% CI, 1.99-3.16; P < .001) compared with those without a history of stroke, and the AOR decreased to 1.49 (95% CI, 1.15-1.92; P < .001) at 61 to 90 days from previous stroke to surgery but did not decline significantly, even after an interval of 360 or more days. Conclusions and Relevance: The findings of this cohort study suggest that, among patients undergoing nonneurologic, noncardiac surgery, the risk of stroke and death leveled off when more than 90 days elapsed between a previous stroke and elective surgery. These findings suggest that the recent scientific statement by the American Heart Association to delay elective nonneurologic, noncardiac surgery for at least 6 months after a recent stroke may be too conservative.

Mobile Stroke Unit Operational Metrics: Institutional Experience, Systematic Review and Meta-Analysis.

Background: The available literature on mobile stroke units (MSU) has focused on clinical outcomes, rather than operational performance. Our objective was to establish normalized metrics and to conduct a meta-analysis of the current literature on MSU performance. Methods: Our MSU in upstate New York serves 741,000 people. We present prospectively collected, retrospectively analyzed data from the inception of our MSU in October of 2018, through March of 2021. Rates of transportation/dispatch and MSU utilization were reported. We also performed a meta-analysis using MEDLINE, SCOPUS, and Cochrane Library databases, calculating rates of tPA/dispatch, tPA-per-24-operational-hours ("per day"), mechanical thrombectomy (MT)/dispatch and MT/day. Results: Our MSU was dispatched 1,719 times in 606 days (8.5 dispatches/24-operational-hours) and transported 324 patients (18.8%) to the hospital. Intravenous tPA was administered in 64 patients (3.7% of dispatches) and the rate of tPA/day was 0.317 (95% CI 0.150-0.567). MT was performed in 24 patients (1.4% of dispatches) for a MT/day rate of 0.119 (95% CI 0.074-0.163). The MSU was in use for 38,742 minutes out of 290,760 total available minutes (13.3% utilization rate). Our meta-analysis included 14 articles. Eight studies were included in the analysis of tPA/dispatch (342/5,862) for a rate of 7.2% (95% CI 4.8-9.5%, I2 = 92%) and 11 were included in the analysis of tPA/day (1,858/4,961) for a rate of 0.358 (95% CI 0.215-0.502, I2 = 99%). Seven studies were included for MT/dispatch (102/5,335) for a rate of 2.0% (95% CI 1.2-2.8%, I2 = 67%) and MT/day (103/1,249) for a rate of 0.092 (95% CI 0.046-0.138, I2 = 91%). Conclusions: In this single institution retrospective study and meta-analysis, we outline the following operational metrics: tPA/dispatch, tPA/day, MT/dispatch, MT/day, and utilization rate. These metrics are useful for internal and external comparison for institutions with or considering developing mobile stroke programs.

Functional status at 30 and 90 days after mild ischaemic stroke.

BACKGROUND/OBJECTIVE: This study compares the global disability status of patients who had a mild ischaemic stroke at 30 and 90 days poststroke, as measured by the modified Rankin Scale (mRS), and identifies predictors of change in disability status between 30 and 90 days. METHODS: The study population included 1339 patients who had a ischaemic stroke enrolled in the Mild and Rapidly Improving Stroke Study with National Institutes of Health (NIH) stroke score 0-5 and mRS measurements at 30 and 90 days. Outcomes were (1) Improvement defined as having mRS >1 at 30 days and mRS 0-1 at 90 days OR mRS >2 at 30 days and mRS 0-2 at 90 days and (2) Worsening defined as an increase of ≥2 points or a worsening from mRS of 1 at 30 days to 2 at 90 days. Demographic and clinical characteristics at hospital arrival were abstracted from medical records, and regression models were used to identify predictors of functional improvement and decline from 30 to 90 days post-stroke. Significant predictors were mutually adjusted in multivariable models that also included age and stroke severity. RESULTS: Fifty-seven per cent of study participants had no change in mRS value from 30 to 90 days. Overall, there was moderate agreement in mRS between the two time points (weighted kappa=0.59 (95% CI 0.56 to 0.62)). However, worsening on the mRS was observed in 7.54% of the study population from 30 to 90 days, and 17.33% improved. Participants of older age (per year OR 1.02, 95% CI 1.00 to 1.03), greater stroke severity (per NIH Stroke Scale (NIHSS) point at admission OR 1.17, 95% CI 1.03 to 1.34), and those with no alteplase treatment (OR 1.72, 95% CI 1.11 to 2.69) were more likely to show functional decline after mutual adjustment. DISCUSSION: A quarter of all mild ischaemic stroke participants exhibited functional changes between 30 and 90 days, suggesting that the 30-day outcome may insufficiently represent long-term recovery in mild stroke and longer follow-up may be clinically necessary. TRIAL REGISTRATION NUMBER: NCT02072681.

Frequency and Prognostic Significance of Clinical Fluctuations Before Hospital Arrival in Stroke.

BACKGROUND AND PURPOSE: Clinical fluctuations in ischemic stroke symptoms are common, but fluctuations before hospital arrival have not been previously characterized. METHODS: A standardized qualitative assessment of fluctuations before hospital arrival was obtained in an observational study that enrolled patients with mild ischemic stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score of 0-5) present on arrival to hospital within 4.5 hours of onset, in a subset of 100 hospitals participating in the Get With The Guidelines-Stroke quality improvement program. The number of fluctuations, direction, and the overall improvement or worsening was recorded based on reports from the patient, family, or paramedics. Baseline NIHSS on arrival and at 72 hours (or discharge if before) and final diagnosis and stroke subtype were collected. Outcomes at 90 days included the modified Rankin Scale, Barthel Index, Stroke Impact Scale 16, and European Quality of Life. Prehospital fluctuations were examined in relation to hospital NIHSS change (admission to 72 hours or discharge) and 90-day outcomes. RESULTS: Among 1588 participants, prehospital fluctuations, consisting of improvement, worsening, or both were observed in 35.5%: 25.1% improved once, 5.3% worsened once, and 5.1% had more than 1 fluctuation. Those who improved were less likely and those who worsened were more likely to receive alteplase. Those who improved before hospital arrival had lower change in the hospital NIHSS than those who did not fluctuate. Better adjusted 90-day outcomes were noted in those with prehospital improvement compared to those without any fluctuations. CONCLUSIONS: Fluctuations in neurological symptoms and signs are common in the prehospital setting. Prehospital improvement was associated with better 90-day outcomes, controlling for admission NIHSS and alteplase treatment. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02072681.

Mobile stroke care expedites intravenous thrombolysis and endovascular thrombectomy.

BACKGROUND: The number of mobile stroke programmes has increased with evidence, showing they expedite intravenous thrombolysis. Outstanding questions include whether time savings extend to patients eligible for endovascular therapy and impact clinical outcomes. OBJECTIVE: Our mobile stroke unit (MSU), based at an academic medical centre in upstate New York, launched in October 2018. We reviewed prospective observational data sets over 26 months to identify MSU and non-MSU emergency medical service (EMS) patients who underwent intravenous thrombolysis or endovascular thrombectomy for comparison of angiographic and clinical outcomes. RESULTS: Over 568 days in service, the MSU was dispatched 1489 times (2.6/day) and transported 300 patients (20% of dispatches). Intravenous tissue plasminogen activator (tPA) was administered to 57 MSU patients and the average time from 911 call-to-tPA was 42.5 min (±9.2), while EMS transported 73 patients who received tPA at 99.4 min (±35.7) (p<0.001). Seven MSU patients (12%) received tPA from 3.5 hours to 4.5 hours since last known well and would likely have been outside the window with EMS care. Endovascular thrombectomy was performed on 21 MSU patients with an average 911 call-to-groin puncture time of 99.9 min (±18.1), while EMS transported 54 patients who underwent endovascular thrombectomy (ET) at 133.0 min (±37.0) (p=0.0002). There was no difference between MSU and traditional EMS in modified Rankin score at 90-day clinic follow-up for patients undergoing intravenous thrombolysis or endovascular thrombectomy, whether assessed as a dichotomous or ordinal variable. CONCLUSIONS: Mobile stroke care expedited both intravenous thrombolysis and endovascular thrombectomy. There is an ongoing need to show improved functional outcomes with MSU care.

Predictors of Outcomes in Patients With Mild Ischemic Stroke Symptoms: MaRISS.

Background and Purpose: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective of this study is to describe multidimensional outcomes, identify predictors of worse outcomes, and explore the effect of thrombolysis in this population. Methods: This prospective observational study included patients with ischemic stroke or transient ischemic attack, a baseline National Institutes of Health Stroke Scale (NIHSS) score 0 to 5, presenting within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale score of 0 to 1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16, and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. Results: A total of 1765 participants were included from 100 Get With The Guidelines-Stroke participating hospitals (age, 65±14; 42% women; final diagnosis of ischemic stroke, 90%; transient ischemic attack, 10%; 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid recipients, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, and extremity weakness. Similar outcomes were noted for the alteplase-treated and untreated groups. Alteplase-treated patients were younger (64±13 versus 67±1.4) with higher NIHSS (2.9±1.4 versus 1.7±1.4). After adjusting for age, sex, race/ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an association with Stroke Impact Scale-16 in the restricted sample of baseline NIHSS score 3­5. Few symptomatic intracerebral hemorrhages were recorded (<1%). Conclusions: A large proportion of stroke patients presenting with low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort, but a suggestion of efficacy was noted in the NIHSS 3­5 subgroup. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02072681.

Perioperative Neurological Evaluation and Management to Lower the Risk of Acute Stroke in Patients Undergoing Noncardiac, Nonneurological Surgery: A Scientific Statement From the American Heart Association/American Stroke Association.

Perioperative stroke is a potentially devastating complication in patients undergoing noncardiac, nonneurological surgery. This scientific statement summarizes established risk factors for perioperative stroke, preoperative and intraoperative strategies to mitigate the risk of stroke, suggestions for postoperative assessments, and treatment approaches for minimizing permanent neurological dysfunction in patients who experience a perioperative stroke. The first section focuses on preoperative optimization, including the role of preoperative carotid revascularization in patients with high-grade carotid stenosis and delaying surgery in patients with recent strokes. The second section reviews intraoperative strategies to reduce the risk of stroke, focusing on blood pressure control, perioperative goal-directed therapy, blood transfusion, and anesthetic technique. Finally, this statement presents strategies for the evaluation and treatment of patients with suspected postoperative strokes and, in particular, highlights the value of rapid recognition of strokes and the early use of intravenous thrombolysis and mechanical embolectomy in appropriate patients.

Retrospective analysis of the hemodynamic consequences of prehospital supplemental oxygen in acute stroke.

OBJECTIVE: Hyperoxia, the delivery of high levels of supplemental oxygen (sO2) despite normoxia, may increase cerebral oxygenation to penumbral tissue and improve stroke outcomes. However, it may also alter peripheral hemodynamic profiles with potential negative effects on cerebral blood flow (CBF). This study examines the hemodynamic consequences of prehospital sO2 in stroke. METHODS: A retrospective analysis of adult acute stroke patients (aged ≥18 years) presenting via EMS to an academic Comprehensive Stroke Center between January 1, 2013 and December 31, 2017 was conducted using demographic and clinical characteristics obtained from Get with the Guidelines-Stroke registry and subjects' medical records. Outcomes were compared across three groups based on prehospital oxygen saturation and sO2 administration. Chi-square, ANOVA, and multivariable linear regression were used to determine if sO2 was associated with differences in peripheral hemodynamic profiles. RESULTS: All subjects had similar initial EMS vitals except for oxygen saturation. However, both univariate and multivariable analysis revealed that hyperoxia subjects had slightly lower average ED mean arterial pressures (MAP) compared to normoxia (Cohen's d = 0.313). CONCLUSIONS: Prehospital-initiated hyperoxia for acute stroke is associated with a small, but significant decrease in average ED MAP, without changes in heart rate, compared to normoxia. While limited by the inability to link changes in peripheral hemodynamical profiles directly to changes in CBF, this study suggests that hyperoxia may result in a relative hypotension. Further studies are needed to determine if this small change in peripheral vascular resistance translates into a clinically significant reduced CBF.

Considerations for Reduction of Risk of Perioperative Stroke in Adult Patients Undergoing Cardiac and Thoracic Aortic Operations: A Scientific Statement From the American Heart Association.

Perioperative stroke is one of the most severe and feared complications of cardiac surgery. Based on the timing of onset and detection, perioperative stroke can be classified as intraoperative or postoperative. The pathogenesis of perioperative stroke is multifactorial, which makes prediction and prevention challenging. However, information on its incidence, mechanisms, diagnosis, and treatment can be helpful in minimizing the perioperative neurological risk for individual patients. We herein provide suggestions on preoperative, intraoperative, and postoperative strategies aimed at reducing the risk of perioperative stroke and at improving the outcomes of patients who experience a perioperative stroke.

Prehospital supplemental oxygen for acute stroke - A retrospective analysis.

OBJECTIVE: Brief early administration of supplemental oxygen (sO2) to create hyperoxia may increase oxygenation to penumbral tissue and improve stroke outcomes. Hyperoxia may also result in respiratory compromise and vasoconstriction leading to worse outcomes. This study examines the effects of prehospital sO2 in stroke. METHODS: This is a retrospective analysis of adult acute stroke patients (aged ≥18 years) presenting via EMS to an academic Comprehensive Stroke Center between January 1, 2013 and December 31, 2017. Demographic and clinical characteristics obtained from Get with the Guidelines-Stroke registry and subjects' medical records were compared across three groups based on prehospital oxygen saturation and sO2 administration. Chi-square, ANOVA, and multivariate logistic regression were used to determine if sO2 status was associated with neurological outcomes or respiratory complications. RESULTS: 1352 eligible patients were identified. 62.7% (n = 848) did not receive sO2 ("controls"), 10.7% (n = 144) received sO2 due to hypoxia ("hypoxia"), and 26.6% (n = 360) received sO2 despite normoxia ("hyperoxia"). The groups represented a continuum from more severe deficits (hypoxia) to less severe deficits (controls): mean prehospital GCS (hypoxia -12, hyperoxia - 2, controls - 14 p ≤ 0.001), mean initial NIHSS (hypoxia - 15, hyperoxia - 13, controls - 8 p < 0.001). After controlling for potential confounders, all groups had similar rates of respiratory complications and favorable neurological outcomes. CONCLUSIONS: Hyperoxic subjects had no significant increase in respiratory complications, nor did they differ in neurologic outcomes at discharge when controlling for confounders. While limited by the retrospective nature, this suggests brief, early sO2 for stroke may be safe to evaluate prospectively.

Final Results of the RHAPSODY Trial: A Multi-Center, Phase 2 Trial Using a Continual Reassessment Method to Determine the Safety and Tolerability of 3K3A-APC, A Recombinant Variant of Human Activated Protein C, in Combination with Tissue Plasminogen Activator, Mechanical Thrombectomy or both in Moderate to Severe Acute Ischemic Stroke.

OBJECTIVE: Agonism of protease-activated receptor (PAR) 1 by activated protein C (APC) provides neuro- and vasculoprotection in experimental neuroinjury models. The pleiotropic PAR1 agonist, 3K3A-APC, reduces neurological injury and promotes vascular integrity; 3K3A-APC proved safe in human volunteers. We performed a randomized, controlled, blinded trial to determine the maximally tolerated dose (MTD) of 3K3A-APC in ischemic stroke patients. METHODS: The NeuroNEXT trial, RHAPSODY, used a novel continual reassessment method to determine the MTD using tiers of 120, 240, 360, and 540 µg/kg of 3K3A-APC. After intravenous tissue plasminogen activator, intra-arterial mechanical thrombectomy, or both, patients were randomized to 1 of the 4 doses or placebo. Vasculoprotection was assessed as microbleed and intracranial hemorrhage (ICH) rates. RESULTS: Between January 2015 and July 2017, we treated 110 patients. Demographics resembled a typical stroke population. The MTD was the highest-dose 3K3A-APC tested, 540 µg/kg, with an estimated toxicity rate of 7%. There was no difference in prespecified ICH rates. In exploratory analyses, 3K3A-APC reduced ICH rates compared to placebo from 86.5% to 67.4% in the combined treatment arms (p = 0.046) and total hemorrhage volume from an average of 2.1 ± 5.8 ml in placebo to 0.8 ± 2.1 ml in the combined treatment arms (p = 0.066). INTERPRETATION: RHAPSODY is the first trial of a neuroprotectant for acute ischemic stroke in a trial design allowing thrombectomy, thrombolysis, or both. The MTD was 540 µg/kg for the PAR1 active cytoprotectant, 3K3A-APC. A trend toward lower hemorrhage rate in an exploratory analysis requires confirmation. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02222714. ANN NEUROL 2019;85:125-136.

Establishing Recommendations for Stroke Systems in the Thrombectomy Era: The Upstate New York Stakeholder Proceedings.

BACKGROUND AND PURPOSE: The American Heart Association/American Stroke Association and Department of Health Stroke Coverdell Program convened a stakeholder meeting in upstate NY to develop recommendations to enhance stroke systems for acute large vessel occlusion. METHODS: Prehospital, hospital, and Department of Health leadership were invited (n=157). Participants provided goals/concerns and developed recommendations for prehospital triage and interfacility transport, rating each using a 3-level impact (A [high], B, and C [low]) and implementation feasibility (1 [high], 2, and 3 [low]) scale. Six weeks later, participants finalized recommendations. RESULTS: Seventy-one stakeholders (45% of invitees) attended. Six themes around goals/concerns emerged: (1) emergency medical services capacity, (2) validated prehospital screening tools, (3) facility capability, (4) triage/transport guidelines, (5) data capture/feedback tools, and (6) facility competition. In response, high-impact (level A) prehospital recommendations, stratified by implementation feasibility, were (1) use of online medical control for triage (6%); (2) regional transportation strategy (31%), standardized emergency medical services checklists (18%), quality metrics (14%), standardized prehospital screening tools (13%), and feedback for performance improvement (7%); and (3) smartphone application algorithm for screening/decision-making (6%) and ambulance-based telemedicine (6%). Level A interfacility transfer recommendations were (1) standardized transfer process (32%)/timing goals (16%)/regionalized systems (11%), performance metrics (11%), image sharing capabilities (7%); (2) provider education (9%) and stroke toolbox (5%); and (3) interfacility telemedicine (7%) and feedback (2%). CONCLUSIONS: The methods used and recommendations generated provide models for stroke system enhancement. Implementation may vary based on geographic need/capacity and be contingent on establishing standard care practices. Further research is needed to establish optimal implementation strategies.

Immediate and Sustained Decrease in Smoking Urges After Acute Insular Cortex Damage.

INTRODUCTION: Smoking urges are fundamental aspects of nicotine dependence that contribute significantly to drug use and postquit relapse. Recent evidence has indicated that damage to the insular cortex disrupts smoking behaviors and claims to reduce urges associated with nicotine use, although tools that assess urge have yet to be used to validate these findings. We examined the effect of insular versus non-insular damage on urge using a well-accepted urge scale. METHODS: This 3-month observational prospective cohort study consisted of 156 current smokers hospitalized for acute ischemic stroke (38 with insular infarctions, 118 with non-insular infarctions). During hospitalization, the Questionnaire of Smoking Urges (QSU)-brief was assessed retrospectively based on experiences before the stroke (baseline, T0), prospectively immediately following the stroke (T1) and once more via telephone at 3-month follow-up (T2), with higher scores indicating greater urge. Bivariate statistics and multivariable linear regression were used to evaluate differences in QSU-brief scores, relative to baseline, between exposure groups, controlling for age, baseline dependence, stroke severity, use of nicotine replacement, and damage to other mesocorticolimbic regions. RESULTS: A greater reduction in QSU-brief score was seen in the insular group compared to the non-insular group from T0 to T1 (covariate-adjusted difference in means of -1.15, 95% CI: -1.85, -0.44) and similarly from T0 to T2 (covariate-adjusted difference in means of -0.93, 95% CI: -1.79, -0.07). CONCLUSIONS: These findings confirm the potential role of the insula in regulating nicotine-induced urges and support the growing evidence of its novelty as a key target for smoking cessation interventions. IMPLICATIONS: Human lesioning studies that evaluate the insula's involvement in maintaining nicotine addiction make inferences of the insula's role in decreasing urge, but do not use validated instruments that directly assess urges. This study corroborates prior findings using the continuous Questionnaire of Smoking Urges to quantify changes in urge from before lesion onset to immediate and 3-month follow-up time points.

Informed Consent for Intravenous Tissue Plasminogen Activator in New York State Designated Stroke Centers.

OBJECTIVE: Our objective was to assess informed consent procedures for intravenous tissue plasminogen activator in acute stroke among New York State (NYS) Department of Health (DOH) designated stroke centers. METHODS: A 13-question survey stratified by 0- to 3-hour and 3.0- to 4.5-hour treatment windows was used to determine the type of consent or if no consent was required. RESULTS: Of the 117 hospitals, 111 responded (95%). All 111 hospitals provided treatment within the 3-hour window, whereas 97 (87%) provided treatment beyond the 3-hour window (P < .001). For hospitals that did provide treatment, there was a difference between the percentages of hospitals requiring consent (verbal or written) within 3 hours (82%) and beyond 3 hours (92%) (P = .04). Of the hospitals requiring consent, there was a difference in the type of consent: 31 of 91 (34%) required written consent within the 3-hour window, whereas 57 of 89 (64%) required written consent beyond the 3-hour window (P < .001). Within both treatment windows, 98% accepted a health-care proxy or surrogate in lieu of the patient. Of the hospitals with less than 500 beds, 11 of 81 (14%) did not require consent within the 3-hour treatment window, compared to hospitals with 500 or more beds where 9 of 30 (30%) did not require consent within the 3-hour treatment window (P < .05). Beyond the 3-hour treatment window, hospitals with more than 500 beds required written consent-2-fold increase "compared to less than 3 hour window" (P < .05). Fifty-five percent of the hospitals were academic, whereas 45% were nonacademic. Academic status was not related to the type of consent in either window. CONCLUSIONS: Significant variability exists in the types of informed consent based on hospital bed size and treatment windows across NYS DOH designated stroke centers.

Damage to the insula leads to decreased nicotine withdrawal during abstinence.

BACKGROUND AND AIMS: Current pharmacotherapies for tobacco dependence are generally well tolerated, but have relatively high rates of relapse. They target primarily the brains' mesocorticolimbic 'reward' pathway. However, recent evidence suggests that the insular cortex, a central cerebral hemispheric region historically overlooked in addiction models, may also play an important role in cognitive and emotional processes that facilitate drug use. We examined whether insular versus non-insular damage from ischemic stroke attenuated acute withdrawal from cigarette smoking and reduced the likelihood of nicotine replacement therapy (NRT) use during hospitalization. DESIGN: Data were derived from a longitudinal study with 3 months' follow-up, beginning June 2013 and ending May 2014. SETTING: Three acute care hospitals in Rochester, NY, USA. PARTICIPANTS: One-hundred and fifty-six current smokers hospitalized for acute ischemic stroke (38 with insular infarctions and 118 with non-insular infarctions, assessed by three neuroradiologists). MEASUREMENTS: The Wisconsin Smoking Withdrawal Scale (WSWS) and Minnesota Nicotine Withdrawal Scale (MNWS) were administered during hospitalization (a period of forced abstinence) to assess the frequency and severity of withdrawal symptoms. NRT use was also assessed during hospitalization. FINDINGS: On average, smokers with insular damage had a lower WSWS score during admission [mean=5.89, standard deviation (SD)=4.72] compared with those with non-insular damage (mean=9.20, SD=4.71; P<0.001) [covariate-adjusted difference in means of -3.12, 95% confidence interval (CI)=-4.97, -1.27]. A similar difference was also noted when the MNWS was used (P=0.02). Furthermore, participants with insular lesions appeared to be less likely to use NRT during admission compared with those with non-insular lesions [odds ratio (OR)=0.72, 95% CI=0.32, 1.64]. CONCLUSIONS: Current smokers with damage to their insular cortex brain region appear to experience fewer and less severe tobacco withdrawal symptoms, and appear to be less likely to require nicotine replacement therapy during hospitalization, compared with smokers with non-insular damage. These findings support the potential role of the insular cortex in regulating withdrawal during abstinence, a motivator responsible for the maintenance of addictive behaviors.