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The last decade has seen significant advances in the accumulation of medical data, the computational techniques to analyze that data, and corresponding improvements in management. Interventions such as thrombolytics and mechanical thrombectomy improve patient outcomes after stroke in selected patients; however, significant gaps remain in our ability to select patients, predict complications, and understand outcomes. Big data and the computational methods needed to analyze it can address these gaps. For example, automated analysis of neuroimaging to estimate the volume of brain tissue that is ischemic and salvageable can help triage patients for acute interventions. Data-intensive computational techniques can perform complex risk calculations that are too cumbersome to be completed by humans, resulting in more accurate and timely prediction of which patients require increased vigilance for adverse events such as treatment complications. To handle the accumulation of complex medical data, a variety of advanced computational techniques referred to as machine learning and artificial intelligence now routinely complement traditional statistical inference. In this narrative review, we explore data-intensive techniques in stroke research, how it has informed the management of stroke patients, and how current work could shape clinical practice in the future., (© 2023. The American Society for Experimental Neurotherapeutics, Inc.)

Randomized clinical trials of acute stroke have led to major advances in acute stroke therapy over the past decade. Despite these successes, recruitment in acute trials is often difficult. We outline challenges in recruitment for acute stroke trials and present potential solutions, which can increase the speed and decrease the cost of identifying new treatments for acute stroke. One of the largest opportunities to increase the speed of enrollment and make trials more generalizable is expansion of inclusion criteria whose impact on expected recruitment can be assessed by epidemiologic and registry databases. Another barrier to recruitment besides the number of eligible patients is availability of study investigators limited to business hours, which may be helped by financial support for after-hours call. The wider use of telemedicine has accelerated quicker stroke treatment at many hospitals and has the potential to accelerate research enrollment but requires training of clinical investigators who are often inexperienced with this approach. Other potential solutions to enhance recruitment include rapid prehospital notification of clinical investigators of potential patients, use of mobile stroke units, advances in the process of emergency informed consent, storage of study medication in the emergency department, simplification of study treatments and data collection, education of physicians to improve equipoise and enthusiasm for randomization of patients within a trial, and clear recruitment plans, and even potentially coenrollment, when there are competing trials at sites. Without successful recruitment, scientific advances and clinical benefit for acute stroke patients will lag.

Introduction: Intracerebral hemorrhage is the deadliest form of stroke. Hematoma expansion, growth of the hematoma between the baseline computed tomography scan and a follow-up computed tomography scan at 24 ± 6 h, predicts long-term disability or death. Recombinant factor VIIa (rFVIIa) has reduced hematoma expansion in previous clinical trials with a variable effect on clinical outcomes, with the greatest impact on hematoma expansion and potential benefit when administered within 2 h of symptom onset., Methods: Factor VIIa for Hemorrhagic Stroke Treatment at Earliest Possible Time (FASTEST, NCT03496883) is a randomized controlled trial that will enroll 860 patients at ∼100 emergency departments and mobile stroke units in five countries. Patients are eligible for enrollment if they have acute intracerebral hemorrhage within 2 h of symptom onset confirmed by computed tomography, a hematoma volume of 2 to 60 mL, no or small volumes of intraventricular hemorrhage, do not take anticoagulant medications or concurrent heparin/heparinoids (antiplatelet medications are permissible), and are not deeply comatose. Enrolled patients will receive rFVIIa 80 µg/kg or placebo intravenously over 2 min. The primary outcome measure is the distribution of the ordinal modified Rankin Scale at 180 days. FASTEST is monitored by a Data Safety Monitoring Board. Safety endpoints include thrombotic events (e.g. myocardial infarction). Human subjects research is monitored by an external Institutional Review Board in participating countries., Discussion: In the US, FASTEST will be first NIH StrokeNet Trial with an Exception from Informed Consent which allows enrollment of non-communicative patients without an immediately identifiable proxy.

Background: Intracerebral hemorrhage (ICH) is the deadliest form of stroke. In observational studies, lower serum magnesium has been linked to more hematoma expansion (HE) and intracranial hemorrhage, implying that supplemental magnesium sulfate is a potential acute treatment for patients with ICH and could reduce HE. FAST-MAG (Field Administration of Stroke Therapy - Magnesium) was a clinical trial of magnesium sulfate started prehospital in patients with acute stroke within 2 hours of last known well enrolled. CT was not required prior to enrollment, and several hundred patients with acute ICH were enrolled. In this ancillary analysis, we assessed the effect of magnesium sulfate treatment upon HE in patients with acute ICH., Methods: We retrospectively analyzed data that were prospectively collected in the FAST-MAG study. Patients received intravenous magnesium sulfate or matched placebo within 2 hours of onset. We compared HE among patients allocated to intravenous magnesium sulfate or placebo with a Mann-Whitney U . We used the same method to compare neurological deficit severity (National Institutes of Health Stroke Scale) and global disability (modified Rankin Scale) at 3 months., Results: Among 268 patients with ICH meeting study entry criteria, mean 65.4±13/4 years, 33% were female, and 211 (79%) had a history of hypertension. Initial deficit severities were median (interquartile range) of 4 (3-5) on the Los Angeles Motor Scale in the field and National Institutes of Health Stroke Scale score of 16 (9.5-25.5) early after hospital arrival. Follow-up brain imaging was performed a median of 17.1 (11.3-22.7) hours after first scan. The magnesium and placebo groups did not statistically differ in hematoma volume on arrival, 10.1 (5.6-28.7) versus 12.4 (5.6-28.7) mL ( P =0.6), or HE, 2.0 (0.1-7.4) versus 1.5 (-0.2 to 8) mL ( P =0.5). There was no difference in functional outcomes (modified Rankin Scale score of 3-6), 59% versus 50% ( P =0.5)., Conclusions: Magnesium sulfate did not reduce HE or improve functional outcomes at 90 days. A benefit for patients with initial hypomagnesemia was not addressed., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT00059332.

Background and Purpose: Since the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis), aggressive medical management (AMM), which includes dual antiplatelet therapy (DAPT) and high-dose statin (HDS) therapy, is recommended for patients with symptomatic intracranial atherosclerotic disease. However, limited data on the real-world application of this regimen exist. We hypothesized that recurrent stroke risk among patients treated with AMM is similar to the medical arm of the SAMMPRIS cohort., Methods: Using a prospective registry, we identified all patients admitted between August 2012 and March 2015 with (1) confirmed ischemic stroke or transient ischemic attack; (2) independently adjudicated symptomatic intracranial atherosclerotic disease; and (3) follow-up at 30 days. We analyzed 30-day risk of recurrent ischemic stroke stratified by treatment: (1) AMM: DAPT plus HDS therapy, (2) HDS alone, and (3) DAPT alone. We also assessed 30-day risk among patients who met prespecified SAMMPRIS eligibility criteria., Results: Among 99 patients who met study criteria (51.5% male, 54.5% black, mean age 68.2±11.2 years), 49 (48.5%) patients were treated with AMM, 69 (69.7%) with DAPT, and 73 (73.7%) with HDS therapy. At 30 days, 20 (20.2%) patients had recurrent strokes in the territory of stenosis. Compared with the risk in the medical arm of SAMMPRIS (4.4%), the 30-day risk of recurrent stroke was 20.4% in AMM patients, 21.5% in HDS patients, 22.4% in DAPT patients, and 23.2% in SAMMPRIS-eligible patients (all P <0.001)., Conclusions: Recurrent stroke risk within 30 days in patients with symptomatic intracranial atherosclerotic disease was higher than that observed in the medical arm of SAMMPRIS even in the subgroup receiving AMM. Replication of the SAMMPRIS findings requires further prospective study., (© 2017 American Heart Association, Inc.)

Objective: We investigated health-related quality of life (HRQOL) in patients with TIA and minor ischemic stroke (MIS) using Neuro-QOL, a validated, patient-reported outcome measurement system., Methods: Consecutive patients with TIA or MIS who had (1) modified Rankin Scale (mRS) score of 0 or 1 at baseline, (2) initial NIH Stroke Scale score of ≤5, (3) no acute reperfusion treatment, and (4) 3-month follow-up, were recruited. Recurrent stroke, disability by mRS and Barthel Index, and Neuro-QOL scores in 5 prespecified domains were prospectively recorded. We assessed the proportion of patients with impaired HRQOL, defined as T scores more than 0.5 SD worse than the general population average, and identified predictors of impaired HRQOL using logistic regression., Results: Among 332 patients who met study criteria (mean age 65.7 years, 52.4% male), 47 (14.2%) had recurrent stroke within 90 days and 41 (12.3%) were disabled (mRS >1 or Barthel Index <95) at 3 months. Any HRQOL impairment was noted in 119 patients (35.8%). In multivariate analysis, age (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.04), initial NIH Stroke Scale score (adjusted OR 1.39, 95% CI 1.17-1.64), recurrent stroke (adjusted OR 2.10, 95% CI 1.06-4.13), and proxy reporting (adjusted OR 3.94, 95% CI 1.54-10.10) were independent predictors of impaired HRQOL at 3 months., Conclusions: Impairment in HRQOL is common at 3 months after MIS and TIA. Predictors of impaired HRQOL include age, index stroke severity, and recurrent stroke. Future studies should include HRQOL measures in outcome assessment, as these may be more sensitive to mild deficits than traditional disability scales., (© 2015 American Academy of Neurology.)

Background: Some previously identified predictors of 30-day stroke readmission, including age and stroke severity, are nonmodifiable. We assessed the hypothesis that in-hospital medical complications, which are potentially modifiable, after ischemic stroke (IS) and transient ischemic attack (TIA) predict 30-day readmission., Methods: In a single-center prospective cohort study of IS and TIA patients admitted from August 1, 2012, to July 31, 2013, we identified those who survived to 30-day follow-up or died during a readmission within 30 days. Patients readmitted within 30 days of discharge were identified by telephone assessment and review of hospital records. We evaluated the association between 12 prespecified and prospectively collected poststroke medical complications and 30-day readmission adjusting for baseline characteristics, in-hospital course and treatments, and discharge status using univariable and multivariable Cox proportional hazards models., Results: Among 505 patients, 107 (21.2%) patients had at least 1 medical complication during hospitalization. The most common complications were urinary tract infection (8.7%), venous thromboembolism (6.1%), and pneumonia (4.6%). Seventy-eight (15.4%) patients were readmitted within 30 days. On multivariable Cox proportional hazards analysis, cardioembolic or large-artery atherosclerotic subtype (adjusted hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.17-2.83) and any medical complication (adjusted HR, 1.68; 95% CI, 1.04-2.73) increased the risk of 30-day readmission. Among the 24 readmitted patients who experienced an initial medical complication, 10 (41.6%) were considered potentially preventable., Conclusions: The occurrence of medical complications after IS or TIA increased the risk of 30-day all-cause readmission. Stroke patients with medical complications may be suitable for targeted interventions to prevent readmissions., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Stroke is a treatable disease. Despite the therapeutic nihilism of the past, the advent of thrombolysis has changed the way stroke is approached. Acute ischemic stroke is a challenging and heterogeneous disease. Treatment needs to be based on an understanding of the underlying pathophysiology of ischemia. Interventions are designed to improve neuronal salvage and outcome. The underlying tenets of stroke therapy focus on the brain parenchyma, arterial flow (pipes), perfusion, the ischemic milieu or penumbra, and prevention of complications. This article focuses on the practical issues of ischemic stroke care, with a brief review of supporting literature.

Because current therapies for acute stroke are limited, attention must be paid to primary and secondary prevention of stroke. This article focuses on the treatment of chronic hypertension in particular. There is no "one-size-fits-all" treatment, although recent randomized trials have shown that certain agents may be more helpful. Although an exhaustive review would require a textbook, this article reviews some major recent trials and provides evidence-based guidelines for treatment of hypertension for both primary and secondary prevention of stroke.