Glucose Control and Risk of Symptomatic Intracerebral Hemorrhage Following Thrombolysis for Acute Ischemic Stroke: A SHINE Trial Analysis.

BACKGROUND AND OBJECTIVES: Baseline hyperglycemia is associated with worse outcomes in acute ischemic stroke (AIS), including higher risk of symptomatic intracerebral hemorrhage (sICH) following treatment with thrombolysis. Prospective data are lacking to inform management of post-thrombolysis hyperglycemia. In a prespecified analysis from the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial of hyperglycemic stroke management, we hypothesized that post-thrombolysis hyperglycemia is associated with a higher risk of sICH. METHODS: Hyperglycemic AIS patients <12 hours onset were randomized to intensive insulin (target range 80-130 mg/dL) vs standard sliding scale (80-179 mg/dL) over a 72-hour period, stratified by treatment with thrombolysis. Three board-certified vascular neurologists independently reviewed all sICH events occurring within 7 days, defined by neurologic deterioration of ≥4 points on the NIH Stroke Scale (NIHSS). Associations between blood glucose control and sICH were analyzed using logistic regression accounting for NIHSS, age, systolic blood pressure, onset to thrombolysis time, and endovascular therapy (odds ratios [OR], 95% CI). Additional analysis compared patients in a high-risk group (age older than 60 years and NIHSS ≥8) vs all others. Categorical variables and outcomes were compared using the χ2 test (p < 0.05). RESULTS: Of 1151 SHINE participants, 725 (63%) received thrombolysis (median age 65 years, 46% women, 29% Black, 18% Hispanic). The median NIHSS was 7, baseline blood glucose was 187 (interquartile range 153-247) mg/dL, and 80% were diabetic. Onset to thrombolysis time was 2.2 hours (1.6-2.9). Post-thrombolysis sICH occurred in 3.6% (3.0% intensive vs 4.3% standard glucose control, OR 1.10, 0.60-2.01, p = 0.697). In the first 12 hours, every 10 mg/dL higher glucose increased the odds of sICH (OR 1.08, 1.03-1.14, p = 0.004), and a greater proportion of glucose measures in the normal range (80-130 mg/dL) decreased the odds of sICH (0.89, 0.80-0.99, p = 0.030). These associations were strongest in the high-risk group (age older than 60 years and NIHSS ≥8). DISCUSSION: In this prespecified analysis from the SHINE trial, intensive insulin therapy was not associated with a reduced risk of post-thrombolysis sICH compared with standard sliding scale. However, early post-thrombolysis hyperglycemia was associated with a higher risk of sICH overall, particularly in older patients with more severe strokes. Further prospective research is warranted to address the risk of sICH in hyperglycemic stroke patients undergoing endovascular therapy. TRIAL REGISTRATION INFORMATION: NCT01369069.

Trends in American Indian/Alaskan native self-reported stroke prevalence and associated modifiable risk factors in the United States from 2011-2021.

BACKGROUND: Stroke prevalence varies by race/ethnicity, as do the risk factors that elevate the risk of stroke. Prior analyses have suggested that American Indian/Alaskan Natives (AI/AN) have higher rates of stroke and vascular risk factors. METHODS: We included biyearly data from the 2011-2021 Behavioral Risk Factor Surveillance System (BRFSS) surveys of adults (age ≥18) in the United States. We describe survey-weighted prevalence of stroke per self-report by race and ethnicity. In patients with self-reported stroke (SRS), we also describe the prevalence of modifiable vascular risk factors. RESULTS: The weighted number of U.S. participants represented in BRFSS surveys increased from 237,486,646 in 2011 to 245,350,089 in 2021. SRS prevalence increased from 2.9% in 2011 to 3.3% in 2021 (p<0.001). Amongst all race/ethnicity groups, the prevalence of stroke was highest in AI/AN at 5.4% and 5.6% in 2011 and 2021, compared to 3.0% and 3.4% for White adults (p<0.001). AI/AN with SRS were also the most likely to have four or more vascular risk factors in both 2011 and 2021 at 23.9% and 26.4% compared to 18.2% and 19.6% in White adults (p<0.001). CONCLUSION: From 2011-2021 in the United States, AI/AN consistently had the highest prevalence of self-reported stroke and highest overall burden of modifiable vascular risk factors. This persistent health disparity leaves AI/AN more susceptible to both incident and recurrent stroke.

Inspiring diverse researchers in Virginia: Cultivating research excellence through a career-building program.

Historically underrepresented groups in biomedical research have continued to experience low representation despite shifting demographics. Diversity fosters inclusive, higher quality, and innovative team science. One avenue for diversifying research teams is integrating diversity-focused initiatives into Clinical and Translational Science Award (CTSA) Programs, such as the integrated Translational Health Research Institute of Virginia (iTHRIV). In 2020, iTHRIV participated in Building Up, developed by the University of Pittsburgh CTSA, and intended to increase representation and improve career support for underrepresented groups in the biomedical workforce. Drawing lessons from this study, iTHRIV implemented the "inspiring Diverse Researchers in Virginia" (iDRIV) program. This yearlong program provided education, coaching, mentoring, and sponsorship for underrepresented early career investigators in the biomedical workforce. To date, 24 participants have participated in the program across three cohorts. Participants have been predominantly female (92%), with 33% identifying as Hispanic/Latinx, 29% as Black, and 13% as Asian. Notably, 38% of scholars have subsequently achieved at least one accomplishment, such as receiving a local research honor or award and an extramural funding award from a foundation or federal agency. The iTHRIV iDRIV program serves as a model for providing career support to developing investigators from underrepresented backgrounds, with the overall goal of improving patient health.

Seven Strategies to Integrate Equity within Translational Research in Neurology.

The rapidly accelerating translation of biomedical advances is leading to revolutionary therapies that are often inaccessible to historically marginalized populations. We identified and synthesized recent guidelines and statements to propose 7 strategies to integrate equity within translational research in neurology: (1) learn history; (2) learn about upstream forces; (3) diversify and liberate; (4) change narratives and adopt best communication practices; (5) study social drivers of health and lived experiences; (6) leverage health technologies; and (7) build, sustain, and lead culturally humble teams. We propose that equity should be a major goal of translational research, equally important as safety and efficacy. ANN NEUROL 2024;95:432-441.

Disseminating for impact: creating curriculum activities for translational dissemination for the clinical and translational research workforce.

There has been an increased focus on the practices associated with dissemination for the translation of research to clinical practice and ultimately, policy. Simultaneously, there has been attention placed on the role of the clinical research workforce in supporting optimal dissemination efforts for impact and societal benefit. Curriculums focused on education opportunities for dissemination for translational scientists have been under-reported. The Translational Science Benefits Model (TSBM) is a framework that has been developed to support assessment of clinical and translational research outcomes that measure impact (both in the clinical and community setting) beyond traditional citations in academic journals/bibliometric activities. The TSBM framework outlines more than 30 different facets of impact and can provide a basis for operationalizing broad impacts of research for translational and clinical scientists. Engagement science offers methods and modalities to work with individual stakeholders, and collaborators in a team science model, and engagement with external scholars and society. This article will describe the use of the TSBM framework and engagement science strategies to develop a translational dissemination framework with novel components for evaluation of dissemination and implementation activities. We propose using the translational dissemination framework to guide the development of an educational curriculum for the clinical research workforce. We outline the educational domains and proposed evaluation criteria essential in implementing this innovative translational dissemination educational content for the clinical and translational research workforce.

Building our research administrator workforce as our clinical and translational research programs become increasingly complex.

Introduction: Research administrators (RA's) are critical members of the research workforce. For purposes of this article, research administrators are personnel who support the development, compliance, management, and financial oversight of sponsored research. There are currently very few institutional career development and mentoring programs available to research administrators. Recruitment and retention of quality research administrators has been especially challenging across the country in recent years. Methods: In an effort to address this gap in training and to increase recruitment and retention, the integrated Translational Health Research Institute of Virginia (iTHRIV), a collaborative NIH-NCATS funded Clinical Translational Science Award (CTSA) hub, has developed an innovative program of workforce development and mentoring for research administrators. This article provides an overview of one institutional training and development initiative, the Research Administration Program for Training and Resources (RAPTR). RAPTR provides training, resources and mentoring to develop a Community of Practice. Results: The program provides a forum where research administrators can share ideas, practices, and challenges. Discussion: This manuscript describes the benefits and lessons learned from our early experience in this program. We highlight selected components that may be generalizable to other institutions and describe individualized components, which require local policies and processes.

Inspiring Diverse Researchers in Virginia: Cultivating Research Excellence Through a Career Building Program.

Historically underrepresented groups in biomedical research have continued to experience low representation despite shifting demographics. Diversity fosters inclusive, higher quality, and innovative team science. One avenue for diversifying research teams is integrating diversity-focused initiatives into Clinical and Translational Science Award (CTSA) Programs, such as the integrated Translational Health Research Institute of Virginia (iTHRIV). In 2020, iTHRIV participated in Building Up, developed by the University of Pittsburgh CTSA, intended to increase representation and improve career support for underrepresented groups in the biomedical workforce. Drawing lessons from this study, iTHRIV implemented the "inspiring Diverse Researchers in Virginia" (iDRIV) program. This year-long program provided education, coaching, mentoring, and sponsorship for underrepresented early-career investigators in the biomedical workforce. To date, 24 participants have participated in the program across three cohorts. Participants have been predominantly female (92%), with 33% identifying as Hispanic/Latinx, 29% as Black, and 13% Asian. Notably, 38% of scholars have subsequently achieved at least one accomplishment, such as receiving a local research honor or award and an extramural funding award from a foundation or federal agency. The iTHRIV iDRIV program serves as a model for providing career support to developing investigators from underrepresented backgrounds, with the overall goal of improving patient health.

NINDS Health Equity Strategic Planning Process Overview, High-Level Recommendations, and Guide.

Neurologic mortality is increasing in the United States and is occurring in an inequitable manner. There is a major need for innovative research strategies to eliminate these inequities. In 2020, the National Institute of Neurological Disorders and Stroke (NINDS) embarked on a health equity strategic planning process, which culminated in a 3-day public workshop and research recommendations provided by a working group of its National Advisory Neurological Disorders and Stroke Council (NANDSC WG) to the NINDS. This Neurology® supplement is dedicated to the NINDS health equity strategic planning process. As cochairs of the NANDS WG, we developed this summary to provide an overview of the process and a guide for navigating this special issue. Detailed recommendations from the NANDS WG are distributed throughout various articles in this supplement and supported with extensive commentary on the state of the science in health equity. Consolidated high-level recommendations from this process are presented at the end of this article.

The Lives Lost to Inequities: Avertable Deaths From Neurologic Diseases in the Past Decade.

BACKGROUND AND OBJECTIVES: Mortality rates for neurologic diseases are increasing in the United States, with large disparities across geographical areas and populations. Racial and ethnic populations, notably the non-Hispanic (NH) Black population, experience higher mortality rates for many causes of death, but the magnitude of the disparities for neurologic diseases is unclear. The objectives of this study were to calculate mortality rates for neurologic diseases by race and ethnicity and-to place this disparity in perspective-to estimate how many US deaths would have been averted in the past decade if the NH Black population experienced the same mortality rates as other groups. METHODS: Mortality rates for deaths attributed to neurologic diseases, as defined by the International Classification of Diseases, were calculated for 2010 to 2019 using death and population data obtained from the Centers for Disease Control and Prevention and the US Census Bureau. Avertable deaths were calculated by indirect standardization: For each calendar year of the decade, age-specific death rates of NH White persons in 10 age groups were multiplied by the NH Black population in each age group. A secondary analysis used Hispanic and NH Asian populations as the reference groups. RESULTS: In 2013, overall age-adjusted mortality rates for neurologic diseases began increasing, with the NH Black population experiencing higher rates than NH White, NH American Indian and Alaska Native, Hispanic, and NH Asian populations (in decreasing order). Other populations with higher mortality rates for neurologic diseases included older adults, the male population, and adults older than 25 years without a high school diploma. The gap in mortality rates for neurologic diseases between the NH Black and NH White populations widened from 4.2 individuals per 100,000 in 2011 to 7.0 per 100,000 in 2019. Over 2010 to 2019, had the NH Black population experienced the neurologic mortality rates of NH White, Hispanic, or NH Asian populations, 29,986, 88,407, or 117,519 deaths, respectively, would have been averted. DISCUSSION: Death rates for neurologic diseases are increasing. Disproportionately higher neurologic mortality rates in the NH Black population are responsible for a large number of excess deaths, making research and policy efforts to address the systemic causes increasingly urgent.

Twenty-Year Disparity Trends in United States Stroke Death Rate by Age, Race/Ethnicity, Geography, and Socioeconomic Status.

BACKGROUND AND OBJECTIVES: In 2017, the Centers for Disease Control and Prevention (CDC) issued an alert that, after decades of consistent decline, the stroke death rate levelled off in 2013, particularly in younger individuals and without clear origin. The objective of this analysis was to understand whether social determinants of health have influenced trends in stroke mortality. METHODS: We performed a longitudinal analysis of county-level ischemic and hemorrhagic stroke death rate per 100,000 adults from 1999 to 2018 using a Bayesian spatiotemporally smoothed CDC dataset stratified by age (35-64 years [younger] and 65 years or older [older]) and then by county-level social determinants of health. We reported stroke death rate by county and the percentage change in stroke death rate during 2014-2018 compared with that during 2009-2013. RESULTS: We included data from 3,082 counties for younger individuals and 3,019 counties for older individuals. The stroke death rate began to increase for younger individuals in 2013 (p < 0.001), and the slope of the decrease in stroke death rate tapered for older individuals (p < 0.001). During the 20-year period of our study, counties with a high social deprivation index and ≥10% Black residents consistently had the highest rates of stroke death in both age groups. Comparing stroke death rate during 2014-2018 with that during 2009-2013, larger increases in younger individuals' stroke death rate were seen in counties with ≥90% (vs <90%) non-Hispanic White individuals (3.2% mean death rate change vs 1.7%, p < 0.001), rural (vs urban) populations (2.6% vs 2.0%, p = 0.019), low (vs high) proportion of medical insurance coverage (2.9% vs 1.9%, p = 0.002), and high (vs low) substance abuse and suicide mortality (2.8 vs 1.9%, p = 0.008; 3.3% vs 1.5%, p < 0.001). In contrast to the younger individuals, in older individuals, the associations with increased death rates were with more traditional social determinants of health such as the social deprivation index, urban location, unemployment rate, and proportion of Black race and Hispanic ethnicity residents. DISCUSSION: Improvements in the stroke death rate in the United States are slowing and even reversing in younger individuals and many US counties. County-level increases in stroke death rate were associated with distinct social determinants of health for younger vs older individuals. These findings may inform targeted public health strategies.

Increased stroke severity and mortality in patients with SARS-CoV-2 infection: An analysis from the N3C database.

BACKGROUND: Studies from early in the COVID-19 pandemic showed that patients with ischemic stroke and concurrent SARS-CoV-2 infection had increased stroke severity. We aimed to test the hypothesis that this association persisted throughout the first year of the pandemic and that a similar increase in stroke severity was present in patients with hemorrhagic stroke. METHODS: Using the National Institute of Health National COVID Cohort Collaborative (N3C) database, we identified a cohort of patients with stroke hospitalized in the United States between March 1, 2020 and February 28, 2021. We propensity score matched patients with concurrent stroke and SARS-COV-2 infection and available NIH Stroke Scale (NIHSS) scores to all other patients with stroke in a 1:3 ratio. Nearest neighbor matching with a caliper of 0.25 was used for most factors and exact matching was used for race/ethnicity and site. We modeled stroke severity as measured by admission NIHSS and the outcomes of death and length of stay. We also explored the temporal relationship between time of SARS-COV-2 diagnosis and incidence of stroke. RESULTS: Our query identified 43,295 patients hospitalized with ischemic stroke (5765 with SARS-COV-2, 37,530 without) and 18,107 patients hospitalized with hemorrhagic stroke (2114 with SARS-COV-2, 15,993 without). Analysis of our propensity matched cohort revealed that stroke patients with concurrent SARS-COV-2 had increased NIHSS (Ischemic stroke: IRR=1.43, 95% CI:1.33-1.52, p<0.001; hemorrhagic stroke: IRR=1.20, 95% CI:1.08-1.33, p<0.001), length of stay (Ischemic stroke: estimate = 1.48, 95% CI: 1.37, 1.61, p<0.001; hemorrhagic stroke: estimate = 1.25, 95% CI: 1.06, 1.47, p=0.007) and higher odds of death (Ischemic stroke: OR 2.19, 95% CI: 1.79-2.68, p<0.001; hemorrhagic stroke: OR 2.19, 95% CI: 1.79-2.68, p<0.001). We observed the highest incidence of stroke diagnosis on the same day as SARS-COV-2 diagnosis with a logarithmic decline in counts. CONCLUSION: This retrospective observational analysis suggests that stroke severity in patients with concurrent SARS-COV-2 was increased throughout the first year of the pandemic.

Collateral status, hyperglycemia, and functional outcome after acute ischemic stroke.

BACKGROUND: Mixed data exist regarding the association between hyperglycemia and functional outcome after acute ischemic stroke when accounting for the impact of leptomeningeal collateral flow. We sought to determine whether collateral status modifies the association between treatment group and functional outcome in a subset of patients with large vessel occlusion enrolled in the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial. METHODS: In this post-hoc analysis, we analyzed patients enrolled into the SHINE trial with anterior circulation large vessel occlusion who underwent imaging with CT angiography prior to glucose control treatment group assignment. The primary analysis assessed the degree to which collateral status modified the effect between treatment group and functional outcome as defined by the 90-day modified Rankin Scale score. Logistic regression was used to model the data, with adjustments made for thrombectomy status, age, post-perfusion thrombolysis in cerebral infarction (TICI) score, tissue plasminogen activator (tPA) use, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Five SHINE trial centers contributed data for this analysis. Statistical significance was defined as a p-value < 0.05. RESULTS: Among the 1151 patients in the SHINE trial, 57 with angiographic data were included in this sub-analysis, of whom 19 had poor collaterals and 38 had good collaterals. While collateral status had no effect (p = 0.855) on the association between glucose control treatment group and functional outcome, patients with good collaterals were more likely to have a favorable functional outcome (p = 0.001, OR 5.02; 95% CI 1.37-16.0). CONCLUSIONS: In a post-hoc analysis using a subset of patients with angiographic data enrolled in the SHINE trial, collateral status did not modify the association between glucose control treatment group and functional outcome. However, consistent with prior studies, there was a significant association between good collateral status and favorable outcome in patients with large vessel occlusion stroke. TRIAL REGISTRATION: ClinicalTrials.gov Identifier is NCT01369069. Registration date is June 8, 2011.

Quantification of hematoma and perihematomal edema volumes in intracerebral hemorrhage study: Design considerations in an artificial intelligence validation (QUANTUM) study.

BACKGROUND: Hematoma and perihematomal edema volumes are important radiographic markers in spontaneous intracerebral hemorrhage. Accurate, reliable, and efficient quantification of these volumes will be paramount to their utility as measures of treatment effect in future clinical studies. Both manual and semi-automated quantification methods of hematoma and perihematomal edema volumetry are time-consuming and susceptible to inter-rater variability. Efforts are now underway to develop a fully automated algorithm that can replace them. A (QUANTUM) study to establish inter-quantification method measurement equivalency, which deviates from the traditional use of measures of agreement and a comparison hypothesis testing paradigm to indirectly infer quantification method measurement equivalence, is described in this article. The Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study aims to determine whether a fully automated quantification method and a semi-automated quantification method for quantification of hematoma and perihematomal edema volumes are equivalent to the hematoma and perihematomal edema volumes of the manual quantification method. METHODS/DESIGN: Hematoma and perihematomal edema volumes of supratentorial intracerebral hemorrhage on 252 computed tomography scans will be prospectively quantified in random order by six raters using the fully automated, semi-automated, and manual quantification methods. Primary outcome measures for hematoma and perihematomal edema volumes will be quantified via computed tomography scan on admission (<24 h from symptom onset) and on day 3 (72 ± 12 h from symptom onset), respectively. Equivalence hypothesis testing will be conducted to determine if the hematoma and perihematomal edema volume measurements of the fully automated and semi-automated quantification methods are within 7.5% of the hematoma and perihematomal edema volume measurements of the manual quantification reference method. DISCUSSION: By allowing direct equivalence hypothesis testing, the Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study offers advantages over radiology validation studies which utilize measures of agreement to indirectly infer measurement equivalence and studies which mistakenly try to infer measurement equivalence based on the failure of a comparison two-sided null hypothesis test to reach the significance level for rejection. The equivalence hypothesis testing paradigm applied to artificial intelligence application validation is relatively uncharted and warrants further investigation. The challenges encountered in the design of this study may influence future studies seeking to translate artificial intelligence medical technology into clinical practice.

Comparison of Bayesian vs Frequentist Adaptive Trial Design in the Stroke Hyperglycemia Insulin Network Effort Trial.

Importance: Bayesian adaptive trial design has the potential to create more efficient clinical trials. However, a barrier to the uptake of bayesian adaptive designs for confirmatory trials is limited experience with how they may perform compared with a frequentist design. Objective: To compare the performance of a bayesian and a frequentist adaptive clinical trial design. Design, Setting, and Participants: This prospective cohort study compared 2 trial designs for a completed multicenter acute stroke trial conducted within a National Institutes of Health neurologic emergencies clinical trials network, with individual patient-level data, including the timing and order of enrollments and outcome ascertainment, from 1151 patients with acute stroke and hyperglycemia randomized to receive intensive or standard insulin therapy. The implemented frequentist design had group sequential boundaries for efficacy and futility interim analyses at 90 days after randomization for 500, 700, 900, and 1100 patients. The bayesian alternative used predictive probability of trial success to govern early termination for efficacy and futility with a first interim analysis at 500 randomized patients and subsequent interims after every 100 randomizations. Main Outcomes and Measures: The main outcome was the sample size at end of study, which was defined as the sample size at which each of the studies stopped accrual of patients. Results: Data were collected from 1151 patients. As conducted, the frequentist design passed the futility boundary after 936 participants were randomized. Using the same sequence and timing of randomization and outcome data, the bayesian alternative crossed the futility boundary approximately 3 months earlier after 800 participants were randomized. Conclusions and Relevance: Both trial designs stopped for futility before reaching the planned maximum sample size. In both cases, the clinical community and patients would benefit from learning the answer to the trial's primary question earlier. The common feature across the 2 designs was frequent interim analyses to stop early for efficacy or for futility. Differences between how these analyses were implemented between the 2 trials resulted in the differences in early stopping.

Self-Reported Race as a Social Determinant of Stroke Risk in Observational Versus Clinical Trial Datasets.

OBJECTIVES: Self-reported Black (SRB) Americans are approximately twice as likely to have a stroke as self-reported White (SRW) Americans. While social determinants of health and vascular risk factors account for some of the disparity, half the increased risk remains unexplained and may be related to unmeasured real-world factors of the racialized experience. MATERIALS: and Methods In this cohort study, we compared SRB and SRW participants in the Systolic Blood Pressure Intervention Trial (SPRINT) to the same groups in the observational Atherosclerosis Risk in Communities (ARIC) study to evaluate if clinical trial participation mitigates disparities in stroke risk. We set the ARIC baseline at visit 4 and excluded participants with prior stroke to create an ARIC cohort similar in age to SPRINT participants. The study outcome was incident primary stroke. We report hazard ratios from Cox models and inverse-probability weighted Cox models with propensity score matching on participant age, sex, diabetes, atrial fibrillation, and smoking. RESULTS: We included 10,094 patients from ARIC and 8,869 from SPRINT, of which 26.1% were SRB. The risk of stroke between SRW participants in SPRINT versus ARIC was not significantly different (IPW-Weighted HR 0.78 [0.52-1.19]). SRB ARIC participants were twice as likely to have a stroke as SRW ARIC participants (IPW-Weighted HR = 1.96 [1.41-2.71]). However, SRB SPRINT participants did not have higher stroke risk compared to SRW SPRINT or ARIC participants (IPW-Weighted HR 0.99 [0.68--1.77] and 0.95 [.57-1.59], respectively). SRB SPRINT participants in the intensive BP control group had a lower risk of stroke compared to SRB ARIC participants (IPW-Weighted HR = 0.39 [0.20-0.75]). CONCLUSIONS: SRB race, compared to SRW race, is associated with an increase in primary stroke risk in the ARIC study but not in the SPRINT trial. The absence of the racial disparity in stroke incidence in SPRINT indicates that aspects of the disparity are modifiable. Population-based interventions that test this hypothesis deserve further attention.

The iTHRIV Commons: a cross-institution information and health research data sharing architecture and web application.

OBJECTIVE: The integrated Translational Health Research Institute of Virginia (iTHRIV) aims to develop an information architecture to support data workflows throughout the research lifecycle for cross-state teams of translational researchers. MATERIALS AND METHODS: The iTHRIV Commons is a cross-state harmonized infrastructure supporting resource discovery, targeted consultations, and research data workflows. As the front end to the iTHRIV Commons, the iTHRIV Research Concierge Portal supports federated login, personalized views, and secure interactions with objects in the ITHRIV Commons federation. The canonical use-case for the iTHRIV Commons involves an authenticated user connected to their respective high-security institutional network, accessing the iTHRIV Research Concierge Portal web application on their browser, and interfacing with multi-component iTHRIV Commons Landing Services installed behind the firewall at each participating institution. RESULTS: The iTHRIV Commons provides a technical framework, including both hardware and software resources located in the cloud and across partner institutions, that establishes standard representation of research objects, and applies local data governance rules to enable access to resources from a variety of stakeholders, both contributing and consuming. DISCUSSION: The launch of the Commons API service at partner sites and the addition of a public view of nonrestricted objects will remove barriers to data access for cross-state research teams while supporting compliance and the secure use of data. CONCLUSIONS: The secure architecture, distributed APIs, and harmonized metadata of the iTHRIV Commons provide a methodology for compliant information and data sharing that can advance research productivity at Hub sites across the CTSA network.

Acute Ischemic Stroke Interventions in the United States and Racial, Socioeconomic, and Geographic Disparities.

BACKGROUND AND OBJECTIVES: In patients with ischemic stroke (IS), IV alteplase (tissue plasminogen activator [tPA]) and endovascular thrombectomy (EVT) reduce long-term disability, but their utilization has not been fully optimized. Prior research has also demonstrated disparities in the use of tPA and EVT specific to sex, race/ethnicity, socioeconomic status, and geographic location. We sought to determine the utilization of tPA and EVT in the United States from 2016-2018 and if disparities in utilization persist. METHODS: This is a retrospective, longitudinal analysis of the 2016-2018 National Inpatient Sample. We included adult patients who had a primary discharge diagnosis of IS. The primary study outcomes were the proportions who received tPA or EVT. We fit a multivariate logistic regression model to our outcomes in the full cohort and also in the subset of patients who had an available baseline National Institutes of Health Stroke Scale (NIHSS) score. RESULTS: The full cohort after weighting included 1,439,295 patients with IS. The proportion who received tPA increased from 8.8% in 2016 to 10.2% in 2018 (p < 0.001) and who had EVT from 2.8% in 2016 to 4.9% in 2018 (p < 0.001). Comparing Black to White patients, the odds ratio (OR) of receiving tPA was 0.82 (95% confidence interval [CI] 0.79-0.86) and for having EVT was 0.75 (95% CI 0.70-0.81). Comparing patients with a median income in their zip code of ≤$37,999 to >$64,000, the OR of receiving tPA was 0.81 (95% CI 0.78-0.85) and for having EVT was 0.84 (95% CI 0.77-0.91). Comparing patients living in a rural area to a large metro area, the OR of receiving tPA was 0.48 (95% CI 0.44-0.52) and for having EVT was 0.92 (95% CI 0.81-1.05). These associations were largely maintained after adjustment for NIHSS, although the effect size changed for many of them. Contrary to prior reports with older datasets, sex was not consistently associated with tPA or EVT. DISCUSSION: Utilization of tPA and EVT for IS in the United States increased from 2016 to 2018. There are racial, socioeconomic, and geographic disparities in the accessibility of tPA and EVT for patients with IS, with important public health implications that require further study.

Cilostazol for Secondary Stroke Prevention: History, Evidence, Limitations, and Possibilities.

Cilostazol is a PDE3 (phosphodiesterase III) inhibitor with a long track record of safety that is Food and Drug Administration and European Medicines Agency approved for the treatment of claudication in patients with peripheral arterial disease. In addition, cilostazol has been approved for secondary stroke prevention in several Asian countries based on trials that have demonstrated a reduction in stroke recurrence among patients with noncardioembolic stroke. The onset of benefit appears after 60 to 90 days of treatment, which is consistent with cilostazol's pleiotropic effects on platelet aggregation, vascular remodeling, blood flow, and plasma lipids. Cilostazol appears safe and does not increase the risk of major bleeding when given alone or in combination with aspirin or clopidogrel. Adverse effects such as headache, gastrointestinal symptoms, and palpitations, however, contributed to a 6% increase in drug discontinuation among patients randomized to cilostazol in a large secondary stroke prevention trial (CSPS.com [Cilostazol Stroke Prevention Study for Antiplatelet Combination]). Due to limitations of prior trials, such as open-label design, premature trial termination, large loss to follow-up, lack of functional or cognitive outcome data, and exclusive enrollment in Asia, the existing trials have not led to a change in clinical practice or guidelines in Western countries. These limitations could be addressed by a double-blind placebo-controlled randomized trial conducted in a broader population. If positive, it would increase the evidence in support of long-term treatment with cilostazol for secondary prevention in the millions of patients worldwide who have experienced a noncardioembolic ischemic stroke.