Contemporary Trends in the Nationwide Incidence of Primary Intracerebral Hemorrhage.

BACKGROUND: We report contemporary trends in nationwide incidence of intracerebral hemorrhage (ICH) across demographic and regional strata over a 15-year period. METHODS: Utilizing the Nationwide Inpatient Sample (2004-2018) and US Census Bureau data, we calculated ICH incidence rates for age, race/ethnicity, sex, and hospital region sub-cohorts across 5 consecutive 3-year periods (2004-2006 to 2016-2018). We fit Poisson and log binomial regression models to evaluate demographic and regional differences in ICH incidence and trends in prevalence of hypertension and past/current anticoagulant use among hospitalized ICH patients. RESULTS: Overall, the annual incidence rate (95% CI) of ICH per 100 000 was 23.15 (23.10-23.20). The 3-year incidence of ICH (per 100 000) increased from 62.79 in 2004 to 2006 to 78.86 in 2016 to 2018 (adjusted incidence rate ratio, CI: 1.11 [1.02-1.20]), coinciding with increased 3-year prevalence of hypertension and anticoagulant use among hospitalized ICH patients (adjusted risk ratio, CI: hypertension-1.16 [1.15-1.17]; anticoagulant use-2.30 [2.14-2.47]). We found a significant age-time interaction, whereby ICH incidence increased significantly faster among those aged 18 to 44 years (adjusted incidence rate ratio, CI: 1.10 [1.05-1.14]) and 45 to 64 years (adjusted incidence rate ratio, CI: 1.08 [1.03-1.13]), relative to those aged ≥75 years. CONCLUSIONS: Rising ICH incidence among young and middle-aged Americans warrants ICH prevention strategies targeting these economically productive age groups.

A Contemporary Review of Epidemiology, Risk Factors, Etiology, and Outcomes of Premature Stroke.

PURPOSE OF REVIEW: Recent data identifies increases in young ischemic and hemorrhagic strokes. We provide a contemporary overview of current literature on stroke among young patients or premature stroke along with directions for future investigation. RECENT FINDINGS: Strokes in the young are highly heterogenous and often cryptogenic. Sex distribution and risk factors shift from women among the youngest age groups (< 35) to men over the age of 45, with a coinciding rise in traditional vascular risk factors. Incidence is higher in minority and socioeconomically disadvantaged populations, and the impact of stroke among these communities may be exaggerated by disparities in symptom recognition and access to care. Special diagnostic work-up may be needed, and a lower threshold for diagnosis is warranted as potential misdiagnosis is a concern and may preclude necessary triage and management. Although "premature strokes" form a relatively small proportion of total incidence, they vary greatly across subgroups and present an outsized impact on quality of life and productivity.

Social Determinants of Health and Cardiovascular Disease: Current State and Future Directions Towards Healthcare Equity.

PURPOSE OF REVIEW: We sought to examine the role of social and environmental conditions that determine an individual's behaviors and risk of disease-collectively known as social determinants of health (SDOH)-in shaping cardiovascular (CV) health of the population and giving rise to disparities in risk factors, outcomes, and clinical care for cardiovascular disease (CVD), the leading cause of death in the United States (US). RECENT FINDINGS: Traditional CV risk factors have been extensively targeted in existing CVD prevention and management paradigms, often with little attention to SDOH. Limited evidence suggests an association between individual SDOH (e.g., income, education) and CVD. However, inequities in CVD care, risk factors, and outcomes have not been studied using a broad SDOH framework. We examined existing evidence of the association between SDOH-organized into 6 domains, including economic stability, education, food, neighborhood and physical environment, healthcare system, and community and social context-and CVD. Greater social adversity, defined by adverse SDOH, was linked to higher burden of CVD risk factors and poor outcomes, such as stroke, myocardial infarction (MI), coronary heart disease, heart failure, and mortality. Conversely, favorable social conditions had protective effects on CVD. Upstream SDOH interact across domains to produce cumulative downstream effects on CV health, via multiple physiologic and behavioral pathways. SDOH are major drivers of sociodemographic disparities in CVD, with a disproportionate impact on socially disadvantaged populations. Efforts to achieve health equity should take into account the structural, institutional, and environmental barriers to optimum CV health in marginalized populations. In this review, we highlight major knowledge gaps for each SDOH domain and propose a set of actionable recommendations to inform CVD care, ensure equitable distribution of healthcare resources, and reduce observed disparities.

Disparities in COVID-19 hospitalizations and mortality among black and Hispanic patients: cross-sectional analysis from the greater Houston metropolitan area.

BACKGROUND: Disparate racial/ethnic burdens of the Coronavirus Disease 2019 (COVID-19) pandemic may be attributable to higher susceptibility to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or to factors such as differences in hospitalization and care provision. METHODS: In our cross-sectional analysis of lab-confirmed COVID-19 cases from a tertiary, eight-hospital healthcare system across greater Houston, multivariable logistic regression models were fitted to evaluate hospitalization and mortality odds for non-Hispanic Blacks (NHBs) vs. non-Hispanic Whites (NHWs) and Hispanics vs. non-Hispanics. RESULTS: Between March 3rd and July 18th, 2020, 70,496 individuals were tested for SARS-CoV-2; 12,084 (17.1%) tested positive, of whom 3536 (29.3%) were hospitalized. Among positive cases, NHBs and Hispanics were significantly younger than NHWs and Hispanics, respectively (mean age NHBs vs. NHWs: 46.0 vs. 51.7 years; p < 0.001 and Hispanic vs. non-Hispanic: 44.0 vs. 48.7 years; p < 0.001). Despite younger age, NHBs (vs. NHWs) had a higher prevalence of diabetes (25.2% vs. 17.6%; p < 0.001), hypertension (47.7% vs. 43.1%; p < 0.001), and chronic kidney disease (5.0% vs. 3.3%; p = 0.001). Both minority groups resided in lower median income (median income [USD]; NHBs vs. NHWs: 63,489 vs. 75,793; p < 0.001, Hispanic vs. non-Hispanic: 59,104 vs. 68,318; p < 0.001) and higher population density areas (median population density [per square mile]; NHBs vs. NHWs: 3257 vs. 2742; p < 0.001, Hispanic vs. non-Hispanic: 3381 vs. 2884; p < 0.001). In fully adjusted models, NHBs (vs. NHWs) and Hispanics (vs. non-Hispanic) had higher likelihoods of hospitalization, aOR (95% CI): 1.42 (1.24-1.63) and 1.61 (1.46-1.78), respectively. No differences were observed in intensive care unit (ICU) utilization or treatment parameters. Models adjusted for demographics, vital signs, laboratory parameters, hospital complications, and ICU admission vital signs demonstrated non-significantly lower likelihoods of in-hospital mortality among NHBs and Hispanic patients, aOR (95% CI): 0.65 (0.40-1.03) and 0.89 (0.59-1.31), respectively. CONCLUSIONS: Our data did not demonstrate racial and ethnic differences in care provision and hospital outcomes. Higher susceptibility of racial and ethnic minorities to SARS-CoV-2 and subsequent hospitalization may be driven primarily by social determinants.

Use of single versus multiple vasodilator agents in the treatment of cerebral vasospasm: is more better than less?

BACKGROUND: Patients with cerebral vasospasm caused by aneurysmal subarachnoid hemorrhage (aSAH) are often treated with intra-arterial (IA) vasodilator infusion. However, the optimal drug regimen is yet to be elucidated. METHODS: A retrospective review of patients with aSAH and cerebral vasospasm treated with IA vasodilator infusion was performed. Patients in group 1 (2008-2011) were treated with a single agent, either nicardipine or verapamil, and patients in group 2 (2010-2016) were treated with a regimen of nitroglycerin, verapamil, and nicardipine. The post-infusion improvement ratio (PIIR) was compared between groups. Adjusted multivariate logistic regression models were utilized to determine whether patients treated with multiple vasodilators had an improved functional outcome, defined by the modified Rankin Scale, at discharge and 90-day follow-up. RESULTS: Among 116 patients from group 1 (N = 47) and group 2 (N = 69), the median age was 54.5 years [IQR, 46-53 years] and 78% were female. Use of multiple-agent therapy resulted in a 24.36% improvement in vessel diameter over single-agent therapy (median PIIR: group 1, 10.5% [IQR, 5.3-21.1%] vs group 2, 34.9% [IQR, 21.4-66.0%]; p < 0.0001). In the adjusted multivariate logistic regression, the use of multiple-agent therapy was associated with a better functional outcome at discharge (OR 0.15, 95% CI [0.04-0.55]; p < 0.01) and at 90-day follow-up (OR 0.20, 95% CI [0.05-0.77]; p < 0.05) when compared to single-agent therapy. CONCLUSION: In this study, we found that patients treated for cerebral vasospasm with IA infusion of multiple vasodilators had an increased vessel response and better functional outcomes compared to those treated with a single agent.

National Trends in Transfer of Patients with Primary Intracerebral Hemorrhage: An Analysis of 12-Year Nationwide Data.

OBJECTIVES: The guidelines of the American Hospital Association encourage transferring intracerebral hemorrhage patients from community hospitals to centers with stroke expertise. However, research on the differences in outcomes between transferred intracerebral hemorrhage hospitalizations and directly admitted hospitalizations have been largely limited to small single-center studies. In this study, we explored the national trends in transferred intracerebral hemorrhage hospitalizations, as well as evaluated the differences, in terms of demographic characteristics, co-morbidity, resource utilization, and outcomes, between transferred intracerebral hemorrhage hospitalizations and directly admitted hospitalizations. MATERIALS AND METHODS: From the National Inpatient Sample (2004 - 2016), we assessed the linear trends in the proportion of interhospital transfers for intracerebral hemorrhage hospitalizations. We constructed a series of multivariate logistic regression models to explore the association of transfer status with inpatient mortality and discharge disposition, controlling for demographic, clinical, and hospital characteristics. We used survey design variables to report nationally weighted estimates. RESULTS: Among 786,999 hospitalizations, 137,340 (17.5%, 95% CI: 16.4-18.6) were transferred. Overall, interhospital transfers for intracerebral hemorrhage has been increasing over the 12-year period of this study. Patients in transferred hospitalizations were younger, more likely to be white, and more likely to have private insurance. Transferred hospitalizations were associated with significantly lower adjusted odds of inpatient mortality, compared to directly admitted hospitalizations. CONCLUSIONS: As the US healthcare system continues shifting towards value-based care, evidence on the short- and long-term outcomes of transfer of intracerebral hemorrhage patients will inform optimal management of intracerebral hemorrhage patients.

Association Between Sociodemographic Determinants and Disparities in Stroke Symptom Awareness Among US Young Adults.

BACKGROUND AND PURPOSE: Despite declining stroke rates in the general population, stroke incidence and hospitalizations are rising among younger individuals. Awareness of and prompt response to stroke symptoms are crucial components of a timely diagnosis and disease management. We assessed awareness of stroke symptoms and response to a perceived stroke among young adults in the United States. METHODS: Using data from the 2017 National Health Interview Survey, we assessed awareness of 5 common stroke symptoms and the knowledge of planned response (ie, calling emergency medical services) among young adults (<45 years) across diverse sociodemographic groups. Common stroke symptoms included: (1) numbness of face/arm/leg, (2) confusion/trouble speaking, (3) difficulty walking/dizziness/loss of balance, (4) trouble seeing in one/both eyes, and (5) severe headache. RESULTS: Our study population included 24 769 adults, of which 9844 (39.7%) were young adults who were included in our primary analysis, and represented 107.2 million US young adults (mean age 31.3 [±7.5] years, 50.6% women, and 62.2% non-Hispanic White). Overall, 2718 young adults (28.9%) were not aware of all 5 stroke symptoms, whereas 242 individuals (2.7%; representing 2.9 million young adults in the United States) were not aware of a single symptom. After adjusting for confounders, Hispanic ethnicity (odds ratio, 1.96 [95% CI, 1.17-3.28]), non-US born immigration status (odds ratio, 2.02 [95% CI, 1.31-3.11]), and lower education level (odds ratio, 2.77 [95% CI, 1.76-4.35]), were significantly associated with lack of symptom awareness. Individuals with 5 high-risk characteristics (non-White, non-US born, low income, uninsured, and high school educated or lower) had nearly a 4-fold higher odds of not being aware of all symptoms (odds ratio, 3.70 [95% CI, 2.43-5.62]). CONCLUSIONS: Based on data from the National Health Interview Survey, a large proportion of young adults may not be aware of stroke symptoms. Certain sociodemographic subgroups with decreased awareness may benefit from focused public health interventions.

National Institutes of Health StrokeNet Training Core.

Background and Purpose- The National Institutes of Health (NIH) StrokeNet provides a nationwide infrastructure to advance stroke research. Capitalizing on this unique opportunity, the NIH StrokeNet Training Core (NSTC) was established with the overarching goal of enhancing the professional development of a diverse spectrum of professionals who are embedded in the stroke clinical trials network of the NIH StrokeNet. Methods- This special report provides a descriptive account of the rationale, organization, and activities of the NSTC since its inception in 2013. Current processes and their evolution over time for facilitating training of NIH StrokeNet trainees have been highlighted. Data collected for monitoring training are summarized. Outcomes data (publications and grants) collected by NSTC was supplemented by publicly available resources. Results- The NSTC comprises of cross-network faculty, trainees, and education coordinators. It helps in the development and monitoring of training programs and organizes educational and career development activities. Trainees are provided directed guidance towards their mandated research projects, including opportunities to present at the International Stroke Conference. The committee has focused on developing sustainable models of peer-to-peer interaction and cross-institutional mentorships. A total of 124 professionals (43.7% female, 10.5% underrepresented minorities) have completed training between 2013 and 2018, of whom 55% were clinical vascular neurologists. Of the total, 85% transitioned to a formal academic position and 95% were involved in stroke research post-training. Altogether, 1659 indexed publications have been authored or co-authored by NIH StrokeNet Trainees, of which 58% were published during or after their training years. Based on data from 109 trainees, 33% had submitted 72 grant proposals as principal or co-principal investigators of which 22.2% proposals have been funded. Conclusions- NSTC has provided a foundation to foster nationwide training in stroke research. Our data demonstrate strong contribution of trainees towards academic scholarship. Continued innovation in educational methodologies is required to adapt to unique training opportunities such as the NIH StrokeNet.

Intravenous Bone Marrow Mononuclear Cells for Acute Ischemic Stroke: Safety, Feasibility, and Effect Size from a Phase I Clinical Trial.

Cellular therapy is a promising investigational modality to enhance poststroke recovery. We conducted a single-arm, phase I clinical trial to determine the safety and feasibility of intravenous (IV) administration of autologous bone marrow mononuclear cells (MNCs) after acute ischemic stroke (AIS). Patients with moderate severity of AIS underwent bone marrow harvest followed by IV reinfusion of MNCs within 24-72 hours of onset. A target dose of 10 million cells per kilogram was chosen based on preclinical data. Patients were followed up daily during hospitalization and at 1, 3, 6, 12, and 24 months for incidence of adverse events using laboratory, clinical (12 months), and radiological (24 months) parameters. The trial was powered to detect severe adverse events (SAEs) with incidences of at least 10% and planned to enroll 30 patients. Primary outcomes were study-related SAEs and the proportion of patients successfully completing study intervention. A propensity score-based matched control group was used for the estimation of effect size (ES) for day-90 modified Rankin score (mRS). There were no study-related SAEs and, based on a futility analysis, enrolment was stopped after 25 patients. All patients successfully completed study intervention and most received the target dose. Secondary analysis estimated the ES to be a reduction of 1 point (95% confidence interval: 0.33-1.67) in median day-90 mRS for treated patients as compared with the matched control group. Bone marrow harvest and infusion of MNCs is safe and feasible in patients with AIS. The estimated ES is helpful in designing future randomized controlled trials. Stem Cells 2019;37:1481-1491.

A Retrospective Study to Identify Novel Factors Associated with Post-stroke Anxiety.

BACKGROUND AND PURPOSE: Post-stroke anxiety (PSA) is common and disabling. PSA should be considered as an important outcome in stroke. However, there is a lack of understanding of factors that may be linked to PSA. The purpose of this study was to determine the frequency of PSA and sociodemographic and clinical factors associated with PSA in a cohort of racially and ethnically diverse stroke patients. METHODS: We conducted a retrospective study of ischemic and hemorrhagic stroke patients seen in a stroke outpatient clinic from August 1, 2017 to June 30, 2018. Patients were eligible if a Generalized Anxiety Disorder 7-Item (GAD-7) instrument was available. GAD-7 scores greater than or equal to 10 indicated the presence of moderate to severe PSA. Multivariable logistic regression was used to identify independent sociodemographic and clinical factors associated with PSA. RESULTS: Records from 289 stroke patients with a GAD-7 instrument were analyzed. PSA was common (21%; GAD-7 ≥ 10). Fifty-seven percent of females had a GAD-7 greater than or equal to 10 compared to 41% of females who had a GAD-7 less than 10 (P = .03). Multivariable analysis found that self-reported nonmarried status (odds ratio, 3.27; 95% confidence interval, 1.44-7.44), excessive fatigue (odds ratio, 4.46; 95% confidence interval, 1.87-10.63), and depression (odds ratio, 1.24; 95% confidence interval, 1.16-1.33) were independently associated with PSA. CONCLUSIONS: PSA may occur more frequently in those who report non-married, excessive fatigue, or depression. Trials of PSA interventions should consider the potential impact of social support, depression, and comorbid conditions contributing to post-stroke fatigue, including sleep apnea.

Real-World Treatment Trends in Endovascular Stroke Therapy.

Background and Purpose- Recent landmark trials provided overwhelming evidence for effectiveness of endovascular stroke therapy (EST). Yet, the impact of these trials on clinical practice and effectiveness of EST among lower volume centers remains poorly characterized. Here, we determine population-level patterns in EST performance in US hospitals and compare EST outcomes from higher versus lower volume centers. Methods- Using validated diagnosis codes from data on all discharges from hospitals and Emergency Rooms in Florida (2006-2016) and the National Inpatient Sample (2012-2016) we identified patients with acute ischemic stroke treated with EST. The primary end point was good discharge outcome defined as discharge to home or acute rehabilitation facility. Multivariate regressions adjusted for medical comorbidities, intravenous tPA (tissue-type plasminogen activator) usage and annual hospital stroke volume were used to evaluate the likelihood of good outcome over time and by annual hospital EST volume. Results- A total of 3890 patients (median age, 73 [61-82] years, 51% female) with EST were identified in the Florida cohort and 42 505 (median age, 69 [58-79], 50% female) in the National Inpatient Sample. In both Florida and the National Inpatient Sample, the number of hospitals performing EST increased continuously. Increasing numbers of EST procedures were performed at lower annual EST volume hospitals over the studied time period. In adjusted multivariate regression, there was a continuous increase in the likelihood of good outcomes among patients treated in hospitals with increasing annual EST procedures per year (odds ratio, 1.1; 95% CI, 1.1-1.2 in Florida and odds ratio, 1.3; 95% CI, 1.2-1.4 in National Inpatient Sample). Conclusions- Analysis of population-level datasets of patients treated with EST from 2006 to 2016 demonstrated an increase in the number of centers performing EST, resulting in a greater number of procedures performed at lower volume centers. There was a positive association between EST volume and favorable discharge outcomes in EST-performing hospitals.

No Weekend or After-Hours Effect in Acute Ischemic Stroke Patients Treated by Telemedicine.

BACKGROUND: Stroke outcomes have been shown to be worse for patients presenting overnight and on weekends (after-hours) to stroke centers compared with those presenting during business hours (on-hours). Telemedicine (TM) helps provide evaluation and safe management of stroke patients. We compared time metrics and outcomes of stroke patients who were assessed and received intravenous recombinant tissue plasminogen activator (IV-tPA) via TM during after-hours with those during on-hours. METHODS: Analysis of our TM registry from September 2015 to December 2016, identified 424 stroke patients who were assessed via TM and received IV-tPA. We compared baseline characteristics, clinical variables, time metrics, and outcomes between the after-hours (5 pm-7:59 am, weekends) and on-hours (weekdays 8 am-4:59 pm) patients. RESULTS: Of the 424 patients, 268 were managed via TM during after-hours, and 156 during on-hours. Baseline characteristics and clinical variables were similar between the groups. Importantly, there were no differences in all relevant time metrics including door to IV-tPA bolus time. IV-tPA complications (including all intracerebral hemorrhage (ICH), any systemic bleeding, and angioedema), discharge disposition, and 90-day modified Rankin Scale were also similar in the groups. CONCLUSIONS: There was no difference in IV-tPA treatment times, acute stroke evaluation times, or mortality between the patients treated after-hours versus on-hours. Unlike in-person neurology coverage at many centers, the coverage provided by TM does not differ depending on the hour or day. Access to stroke specialists 24/7 via TM can ensure dependable and timely clinical care for acute stroke patients regardless of the time of day or day of the week.

Rationale and Design of a Statewide Cohort to examine efficient resource utilization for patients with Intracerebral hemorrhage (EnRICH).

BACKGROUND: Intracerebral hemorrhage is a devastating disease with no specific treatment modalities. A significant proportion of patients with intracerebral hemorrhage are transferred to large stroke treatment centers, such as Comprehensive Stroke Centers, because of perceived need for higher level of care. However, evidence of improvement in patient-centered outcomes for these patients treated at larger stroke treatment centers as compared to community hospitals is lacking. METHODS / DESIGN: "Efficient Resource Utilization for Patients with Intracerebral Hemorrhage (EnRICH)" is a prospective, multisite, state-wide, cohort study designed to assess the impact of level of care on long-term patient-centered outcomes for patients with primary / non-traumatic intracerebral hemorrhage. The study is funded by the Texas state legislature via the Lone Star Stroke Research Consortium. It is being implemented via major hub hospitals in large metropolitan cities across the state of Texas. Each hub has an extensive network of "spoke" hospitals, which are connected to the hub via traditional clinical and administrative arrangements, or by telemedicine technologies. This infrastructure provides a unique opportunity to track outcomes for intracerebral hemorrhage patients managed across a health system at various levels of care. Eligible patients are enrolled during hospitalization and are followed for functional, quality of life, cognitive, resource utilization, and dependency outcomes at 30 and 90 days post discharge. As a secondary aim, an economic analysis of the incremental cost-effectiveness of treating intracerebral hemorrhage patients at higher levels of care will be conducted. DISCUSSION: Findings from EnRICH will provide much needed evidence of the effectiveness and efficiency of regionalized care for intracerebral hemorrhage patients. Such evidence is required to inform policy and streamline clinical decision-making.

Benchmarking Telestroke Proficiency: Page-to-Needle Time Among Neurovascular Fellows and Attendings.

BACKGROUND AND PURPOSE: Formal telestroke training for neurovascular fellows (NVFs) is necessary because of growing use of telestroke technologies in the management of acute ischemic stroke; yet, educational approaches and training benchmarks are not formalized. Time between telestroke consultant page and tissue-type plasminogen activator administration (page-to-needle time, PTNT) can provide an objective measure of proficiency. We compared PTNT between NVFs and neurovascular attendings (NVAs) and evaluated changes in PTNT with experience. METHODS: We identified suspected acute ischemic stroke patients in our telestroke registry from July 2013 to December 2015 who received tissue-type plasminogen activator. Using multivariable quantile regression, we estimated the difference and 95% confidence interval in median PTNT between NVFs and NVAs. We also report the coefficient of change in PTNT over increasing number of telestroke consults. RESULTS: NVFs evaluated 53.7% of 618 tissue-type plasminogen activator cases over telestroke. NVAs had significantly shorter PTNT compared with NVFs, with a difference in median PTNT of -9 minutes (95% confidence interval, -12.3 to -5.7). This difference persisted when adjusted for relative tissue-type plasminogen activator contraindications. For each additional telestroke consult, PTNT decreased by 0.07 minutes for NVFs or NVAs (P=0.02 and <0.01, respectively). CONCLUSIONS: PTNT improves by ≈1 minute for every 14 consults for both NVFs and NVAs. Our findings support the importance of integrating telestroke training into supervised neurovascular fellowships to increase proficiency prior to independent practice and suggest that PTNT can be a benchmark for tracking proficiency.

Nationwide Estimates of 30-Day Readmission in Patients With Ischemic Stroke.

BACKGROUND AND PURPOSE: Readmission within 30 days of hospital discharge for ischemic stroke is an important quality of care metric. We aimed to provide nationwide estimates of 30-day readmission in the United States, describe important reasons for readmission, and sought to explore factors associated with 30-day readmission, particularly the association with recanalization therapy. METHODS: We conducted a weighted analysis of the 2013 Nationwide Readmission Database to represent all US hospitalizations. Adult patients with acute ischemic stroke including those who received intravenous tissue-type plasminogen activator and intra-arterial therapy were identified using International Classification of Diseases-Ninth Revision codes. Readmissions were defined as any readmission during the 30-day post-index hospitalization discharge period for the eligible patient population. Proportions and 95% confidence intervals for overall 30-day readmissions and for unplanned and potentially preventable readmissions are reported. Survey design logistic regression models were fit for determining crude and adjusted odds ratios and 95% confidence interval for association between recanalization therapy and 30-day readmission. RESULTS: Of the 319 317 patients with acute ischemic stroke, 12.1% (95% confidence interval, 11.9-12.3) were readmitted. Of these, 89.6% were unplanned and 12.9% were potentially preventable. More than 20% of all readmissions were attributable to acute cerebrovascular disease. Readmitted patients were older and had a higher comorbidity burden. After controlling for age, sex, insurance status, and comorbidities, patients who underwent recanalization therapy had significantly lower odds of 30-day readmission (odds ratio, 0.82; 95% confidence interval, 0.77-0.89). CONCLUSIONS: Up to 12% of patients with ischemic stroke get readmitted within 30 days post-discharge period, and recanalization therapy is associated with 11% to 23% lower odds of 30-day readmission.

Prospective, open-label safety study of intravenous recombinant tissue plasminogen activator in wake-up stroke.

OBJECTIVE: It is estimated that one of four ischemic strokes are noticed upon awakening and are not candidates for intravenous recombinant tissue plasminogen activator (rtPA) because their symptoms are >3 hours from last seen normal (LSN). We tested the safety of rtPA in a multicenter, single-arm, prospective, open-label study (NCT01183533) in patients with wake-up stroke (WUS). METHODS: We aimed to enroll 40 WUS patients with disabling deficits. Patients were 18 to 80 years of age, National Institutes of Health Stroke Scale (NIHSS) ≤25, and selected only on the appearance of noncontrast computed tomography (ie, over one-third middle cerebral artery territory hypodensity). Standard-dose (0.9mg/kg) intravenous rtPA had to be started ≤3 hours of patient awakening. The primary safety outcome was symptomatic intracerebral hemorrhage (sICH) with preplanned stopping rules and data safety board oversight. Other endpoints included: asymptomatic intracerebral hemorrhage; clinical improvement in NIHSS; and 90-day modified Rankin Scale (mRS) score. RESULTS: Between October 2010 and October 2013, all 40 preplanned patients were enrolled (50% men) at five stroke centers. Four patients (10%) were subsequently determined to be mimics. Patients had a mean age of 60.8, median NIHSS of 6.5 (range, 2-24), and received thrombolysis at a mean time of 10.3 ± 2.6 LSN and 2.6 ± 0.6 hours from awakening with deficits. No sICH or parenchymal hematomas occurred. At 3 months, 20 of 38 (52.6%) patients achieved excellent recovery with mRS scores of 0 or 1 (2 patients were lost to follow-up). INTERPRETATION: Intravenous thrombolysis was safe in this prospective WUS study of patients selected by noncontrast CT. A randomized effectiveness trial appears feasible using a similar, pragmatic design. Ann Neurol 2016;80:211-218.

Systematic Review and Meta-Analysis of Bone Marrow-Derived Mononuclear Cells in Animal Models of Ischemic Stroke.

BACKGROUND AND PURPOSE: Bone marrow-derived mononuclear cells (BMMNCs) offer the promise of augmenting poststroke recovery. There is mounting evidence of safety and efficacy of BMMNCs from preclinical studies of ischemic stroke; however, their pooled effects have not been described. METHODS: Using Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, we conducted a systematic review of preclinical literature for intravenous use of BMMNCs followed by meta-analyses of histological and behavioral outcomes. Studies were selected based on predefined criteria. Data were abstracted by 2 independent investigators. After quality assessment, the pooled effects were generated using mixed-effect models. Impact of possible biases on estimated effect size was evaluated. RESULTS: Standardized mean difference and 95% confidence interval for reduction in lesion volume was significantly beneficial for BMMNC treatment (standardized mean difference: -3.3; 95% confidence interval, -4.3 to -2.3). n=113 each for BMMNC and controls. BMMNC-treated animals (n=161) also had improved function measured by cylinder test (standardized mean difference: -2.4; 95% confidence interval, -3.1 to -1.6), as compared with controls (n=205). A trend for benefit was observed for adhesive removal test and neurological deficit score. Study quality score (median: 6; Q1-Q3: 5-7) was correlated with year of publication. There was funnel plot asymmetry; however, the pooled effects were robust to the correction of this bias and remained significant in favor of BMMNC treatment. CONCLUSIONS: BMMNCs demonstrate beneficial effects across histological and behavioral outcomes in animal ischemic stroke models. Although study quality has improved over time, considerable degree of heterogeneity calls for standardization in the conduct and reporting of experimentation.

Clotting factors to treat thrombolysis-related symptomatic intracranial hemorrhage in acute ischemic stroke.

BACKGROUND: Symptomatic intracranial hemorrhage (sICH) occurs uncommonly after ischemic stroke therapy with tissue plasminogen activator (tPA). Clotting factor administration may be a treatment option. OBJECTIVE: To determine if treatment with clotting factors (fresh frozen plasma [FFP] or cryoprecipitate) was associated with improved outcomes in sICH. METHODS: We conducted a retrospective cohort study within University of Texas at Houston Stroke registry involving consecutive patients from February 1, 2007, to June 30, 2011, with tPA-related sICH, including cases with subsequent intra-arterial therapy. Outcomes were Modified Rankin Scale (mRS) score at discharge, death, and hematoma expansion. RESULTS: Of 921 patients treated with tPA, 48 (5.2%) had sICH and 45 met criteria for the study. Nineteen patients received clotting factors (42.2%; 18 received FFP and 7 received cryoprecipitate), whereas 26 (57.8%) patients received conservative management without clotting factors. None of the patients treated with clotting factors and only 2 of those who did not receive clotting factors had a good outcome, mRS score of 2 or less. All the patients treated with clotting factors and most of those not treated were left bedridden or dead (mRS score 4-6), 19 (100%) versus 22 (85%). Mortality was 9 (47.4%) versus 9 (34.6%), respectively. There was no difference in hematoma expansion between the 2 groups. CONCLUSIONS: We found no evidence that treatment for sICH with clotting factors has a favorable effect on clinical or radiological outcomes. However, the sample was small because of the low frequency of sICH. New treatments are urgently needed for this uncommon yet serious condition.