Stop Stroke Research Articles

Successful Implementation Trial to Improve Stroke Risk (TCD) Screening in Children with Sickle Cell Anemia: A Roadmap to Care Enhancement

Stroke remains a devastating complication of sickle cell anemia (SCA). The STOP (Stroke Prevention Trial in Sickle Cell Anemia) protocol adopted in 2014 by the National Heart Lung and Blood Institute (NHLBI) guidelines includes stroke-risk screening using transcranial Doppler ultrasound (TCD) and prevention with chronic red cell transfusion therapy (CRCT). Theserecommendations were reinforced by the American Society of Hematology guidelines.However, despite the evidence supporting TCD screening in stroke prevention, the DISPLACE study (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) showed that real-world implementation was insufficient. To evaluate and improve sickle stroke screening, we conducted the NHLBI-funded multi-center DISPLACE study to identify barriers to TCD implementation and test novel methods for improving outcomes. DISPLACE is a 4-part study: 1) Retrospective calculation of TCD screening rates; 2) Assessment of barriers and facilitators; 3) Implementation trial to improve TCD screening and 4) Comparison of implementation sites to controls. Importantly, DISPLACE is the largest prospective study of children with SCA. This study employed a multi-level, multi-faceted cluster-randomized study of interventions to improve implementation rates of TCD. Methods: DISPLACE is a 28-center US consortium representing a range of: regions (urban vs rural), size (patient number), and institution type (academic vs community). In Part 1, sites performed a rigorous retrospective review of TCD screening from 2012-2016 to collect baseline rates. Part 2 included a barriers and facilitators assessment to TCD screening to inform the trial interventions: 1) Re-branding TCD as Sickle Stroke Screen, a meaningful name for SCD stakeholders; 2) Using a Single Coordinator (SC) for each site's TCD scheduling, and follow-up; 3) A custom designed provider-focused application, ProviderMinder TM (PM) created to remind providers to track TCD appointments and follow-up on results. When a TCD was due, PM alerted the provider to enter scan results or reason(s) missed. Once the TCD results (normal/conditional/abnormal) were entered in PM, providers were prompted to enter the next TCD date and/or intervention plan (if not normal). If a result was not entered, PM alerted the provider q3 days until the TCD was recorded as completed or rescheduled. The implementation trial (parts 3 and 4 of DISPLACE) included 16 sites that had the lowest TCD rates in part 1. The implementation trial included children with SCA aged 2-7 years (the group at highest risk for an abnormal TCD). Cluster randomization was used to allocate sites to PM alone (8 sites) or PM + SC (8 sites). The primary outcome was comparison of TCD rates between PM and PM+SC sites. Secondary outcomes included comparisons between 1) Part 3 sites' TCD rates and Part 1 baseline rates 2) Part 3 sites and control sites (to assess the impact of the educational rebranding of TCD). Results: Part 1 included 28 centers with 5246 children with SCA. Of the 16 intervention sites, 3 sites could not implement the interventions due to administrative issues but remained in the study and were re-designated as “control sites” and a 4th control site was added (they were not informed prospectively to avoid bias). Thus, there were 13 evaluable sites for the primary endpoint including 776 patients; 484 in sites using PM and 292 in sites using PM+SC. Control sites included 185 patients. The trial demonstrated superiority of the PM arm compared to the PM + SC arm (P<.0001 year 1 and p=0.002 year 2) in both years of implementation and in comparison, to the control sites (P<.0001 year 1, p=.009 year 2) with an overall improvement in mean TCD screening from part 1 by 25% (table 1). Conclusions: This was a highly successful implementation study in SCA. This study emphasizes the importance of performing barrier and facilitator assessments when introducing new guideline-recommended screenings into clinical practice. These findings also highlight the importance of ongoing quality assurance in SCA to ensure prevention practices are maintained. Despite the benefit of TCD (sickle stroke screening) in children with SCA, implementation was poor prior to these interventions. Results from this study will guide ongoing optimization of TCD screening and demonstrate the importance of adopting these interventions in the real world.

Demographics, Risk Factors, and Etiology of Posterior Cerebral Artery Stroke Causing Homonymous Hemianopia.

Posterior cerebral artery (PCA) strokes account for up to 10% of all ischemic strokes, often presenting with homonymous hemianopia. The proportion of these strokes attributed to various etiologies varies widely in previously published studies, owing largely to differing patient populations, definitions of stroke pathogenesis, and vascular territories involved. The Causative Classification System (CCS), an automated version of the Stop Stroke Study (SSS) Trial of Org 10,172 in Acute Stroke Treatment (TOAST) system, allows for a more rigorous assignment of stroke etiology. We excerpted clinical and imaging data on 85 patients who had PCA stroke with homonymous hemianopia examined at the University of Michigan. We compared the stroke risk factor profile of our PCA cohort with that of 135 patients with stroke in the distribution of the internal carotid artery (ICA) and middle cerebral artery (MCA) in an unpublished University of Michigan registry. We applied the CCS web-based calculator to our PCA cohort to determine stroke etiology. In our PCA cohort, 80.0% had at least 2 conventional stroke risk factors and 30.6% had 4 risk factors, most commonly systemic hypertension. The risk factor profile of our PCA cohort resembled that of our ICA/MCA cohort except that the mean age of our PCA cohort was more than a decade younger and had a significantly lower frequency of atrial fibrillation (AF) than our ICA/MCA cohort. In nearly half of the patients with AF in our PCA cohort, AF was diagnosed after the stroke. Among stroke etiologies in our PCA cohort, 40.0% were of undetermined cause, 30.6% were from cardioaortic embolism, 17.6% were from other determined causes, and only 11.8% were from supra-aortic large artery atherosclerosis. Strokes after endovascular or surgical interventions were prominent among other determined causes. Most patients in our PCA cohort had multiple conventional stroke risk factors, a finding not previously documented. Mean age at stroke onset and AF frequency were lower than in our ICA/MCA cohort, in agreement with previous studies. As some other studies have found, nearly 1/3 of strokes were attributed to cardioaortic embolism. Within that group, AF was often a poststroke diagnosis, a finding not previously highlighted. Compared with earlier studies, a relatively high portion of strokes were of undetermined etiology and of other determined etiologies, including stroke after endovascular or surgical interventions. Supra-aortic large artery atherosclerosis was a relatively uncommon explanation for stroke.

A novel etiological classification in patients with intracranial large vessel occlusion and endovascular treatment: discordance with the classic and SSS TOAST systems: A retrospective cohort study

Purpose: Among patients with acute ischemic stroke (AIS), those with intracranial large vessel occlusion (LVO) should undertake endovascular treatment (EVT) based on mechanical thrombectomy. Although the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system has been used in overall population of patients with AIS, especially for secondary prevention. In the current study, a new classification system for the LVO population is proposed.Methods: The classic TOAST and Stop Stroke Study TOAST (SSS TOAST) were applied to the LVO population. Based on discordance with those systems, a new LVO classification system was developed and applied to the LVO population. The new system comprised extracranial atherosclerosis (ECAS), intracranial atherosclerosis (ICAS), cardioembolism (CE), cryptogenic embolism, stroke of undetermined etiology (SUE; two or more etiologies), and stroke of other determined etiology (SOE) where small artery occlusion was removed.Results: The LVO classification system comprised 43 ECAS (6.52%), 141 ICAS (21.36%), 303 CE (45.91%), 75 cryptogenic embolism (11.36%), 75 SUE (11.36%; cardioembolic source in 98.67%), and 23 SOE (3.48%) patients. The ICAS group had a significantly longer median onset-to-puncture time than the other groups. In the ICAS group, 102 of 141 (72.34%) remained partial recanalization after EVT.Conclusion: The LVO classification system differentiating ECAS and ICAS in patients with large artery atherosclerosis and classifying cryptogenic embolism is more suitable for patients with EVT for intracranial LVO. Further studies for predicting underlying ICAS and planning treatment strategy should be performed.

Abstract P474: Sex-Specific Prevention of Stroke Through Reproductive Risk Factors and Sex Hormone Effects (STOP STROKE): Preliminary Findings

Background: There are known associations between sex-specific reproductive health factors such as reproductive lifespan and stroke risk. The relation of endogenous sex hormones, specifically sex hormone binding globulin (SHBG), to stroke risk remains uncertain, however, despite some data showing an inverse association between SHBG and stroke. We conducted a pilot case-control study to evaluate SHBG as a stroke risk factor, to report SHBG levels in the period immediately after acute ischemic stroke (AIS), and to demonstrate the feasibility of collecting data on sex hormones and reproductive history in this study population. Methods: In STOP STROKE, postmenopausal women were enrolled from a single large healthcare system in the northeast between July 2020 and May 2022. Case participants were postmenopausal women ≥50 years old newly admitted with AIS to a large stroke center; controls were postmenopausal women without a history of stroke recruited from an outpatient clinic in the same healthcare system. Among others, exclusion criteria included use of menopausal hormone therapy within 10 years, prior stroke, surgical menopause, and history of hormone-related cancers. We ascertained data on stroke risk factors and collected blood samples between 24 and 72 hours after stroke onset or at the time of enrollment for controls. Serum SHBG was measured using enzyme-linked immunosorbent assays. Following descriptive analyses, age- and BMI-adjusted SHBG levels were compared between cases and controls using multiple linear regression. Multiple logistic regression was then performed to assess associations between SHBG, clinical risk factors, and the outcome of AIS, with covariates chosen a priori based on prior literature. Results: In total, 32 cases and 30 controls were enrolled; median age was 69.0 years (IQR 64.5-82.0) for cases vs. 62.0 (IQR (59.0-68.0) for controls. The mean SHBG of AIS cases was 68.8 (SD 36.1) nmol/L compared to 56.6 (SD 30.0) nmol/L among controls (p=0.16). In models adjusted for age and body mass index (BMI), SHBG was similar between cases and controls (beta = 3.0, 95%CI -15.0 - 21.1, p=0.74). Adjusted for age, BMI, history of hypertension, history of diabetes, and age at menarche and menopause, there was a positive association between SHBG and AIS (OR 1.04, 95%CI 1.004-1.071, p=0.03). Conclusions: Our pilot study demonstrates the feasibility of enrolling newly admitted AIS patients and controls among postmenopausal women in the catchment area of our comprehensive stroke center. To understand initial findings of a positive association between SHBG and AIS, work is ongoing to measure estrogens and androgens at study baseline and all hormones in follow-up specimens (3-6 months post stroke).

Dissemination and Implementation Looking at the Care Environment (DISPLACE) Study Evaluates Novel Interventions to Improve TCD (Sickle Stroke Screening) Implementation

Background: Stroke is a devastating complication of sickle cell anemia (SCA). The STOP (Stroke Prevention Trial in Sickle Cell Anemia) protocol was adopted in 2014 by the National Heart Lung and Blood Institute (NHLBI) guidelines for stroke-risk screening using transcranial Doppler ultrasound (TCD) and prevention with chronic red cell transfusion therapy (CRCT). These guidelines were upheld in the recent American Society of Hematology guidelines. Despite strong evidence supporting TCD screening (and CRCT initiation) in stroke prevention, wide scale implementation has not been achieved 4. DISPLACE (Dissemination and Implementation Looking at the Care Environment) is a multicenter, NHLBI-funded study conducted to identify barriers to TCD implementation and test novel methods for improving outcomes. DISPLACE is a 3-part study: 1) Retrospective assessment of current practice; 2) Assessment of barriers and facilitators; and 3) Implementation trial to improve TCD screening. This report focuses on Part 3. Methods: DISPLACE is a 28-center consortium across the US representing a range of: region (urban vs rural), size, and institution type (academic vs community). During Part 1, sites performed a rigorous retrospective chart review of children with SCA aged 2-16 years from 2012-2016 to collect baseline TCD rates. Part 2 included a rigorous mixed methods of the barriers and facilitators assessment to TCD screening was performed that resulted in 3 main interventions: 1.Re-branding TCD as Sickle Stroke Screen, a meaningful name selected by patients/families with SCD; 2. A Single Coordinator (SC) for each site's TCD screening, scheduling, and follow-up; 3. A newly designed application, Provider Minder (trademarked; PM). PMwas created to remind providers of patient appointments (versus reminders only sent to patients/families). Data entry in PM included birth date (to calculate age), city/state of residence, distance from SCD clinic and insurance. Date of last TCD was recorded to calculate date of next screen. When the TCD was due, the system alerted the provider to enter appointment completion or reason(s) why it was missed. TCD results were entered for PM to prompt for the next TCD date in a 10-14 month window (normal screens), 2-6 weeks (conditional screens), and intervention plan (abnormal screens): repeat scan in <2 weeks or other. If the provider failed to enter a patient's result, PM alerted the provider q3 days until the TCD was recorded as completed/rescheduled. Part 3 included 16 sites who successfully completed data entry in Part 1 and had the lowest TCD implementation rates. Part 3 inclusion criteria were the same as Part 1 except to specifically select children with SCA now aged 2-7 (the highest risk group to have an abnormal TCD in Part 1). All 28 sites received re-branding educational material (also disseminated to non-study sites). Cluster randomization was used to allocate sites to PM (8 sites) or PM + SC (8 sites). The primary outcome is which intervention results in the best TCD rates. Secondary outcomes include Part 3 sites’ improvement in TCD rates (compared to historical rates) and impact of the educational/rebranding of TCD to "Sickle Stroke Screen” in sites (4) that did not participate in Part 3. Stroke status, presence of CRCT after an abnormal TCD, missed TCD appointments, and medical decisions following TCD were also recorded. Results: Part 1 included 28 centers with 5223 individuals with SCA in the database. Of the 16 Part 3 sites, three could not implement the interventions due to a simultaneous change in hospital administration and site PI (1), inability to use PM due to institutional firewall (1) and inability to implement due to site specific issues (1). These 3 sites remained in the study as "control sites” and a fourth control site was added. Thus, 13 sites implemented the interventions with 877 patients; 520 were in sites using PM and 357 were in sites using PM+SC. Demographic data for the 877 children with SCA are in Table 1. The study ended on May 31, 2022. Calculations of TCD rates at all sites are in process and will be presented. Conclusions: Despite the benefit of TCD screening in children with SCA, guideline-based implementation remains poor. The range of barriers to screening has been previously reported by the DISPLACE study team and were used to design the study interventions. Results from this study will guide optimization of the intervention protocol proven to enhance TCD implementation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The role of hypertension and diabetes mellitus on the etiology of middle cerebral artery disease.

BackgroundIschemic stroke (IS) caused by middle cerebral artery (MCA) disease is the most common type of IS caused by intracranial artery disease in the Chinese population. Hypertension and diabetes mellitus are the common risk factors of cerebral small vessel disease and large artery atherosclerosis (LAA). However, little is known about whether hypertension and diabetes mellitus had different correlations with the small artery occlusion (SAO) and LAA etiology of MCA disease. Therefore, our aim was to identify the predictors of the etiology of MCA disease.MethodsWe consecutively enrolled 967 patients with noncardiogenic IS in unilateral MCA territory. Vascular risk factors and the clinical–radiologic features of IS were analyzed. The etiology of IS were classified as SAO or LAA according to the Stop Stroke Study Trial of Org 10172 in Acute Stroke Treatment classification criteria. Multivariable logistic regression was used to identify the differences in the predictors between SAO and LAA etiology of MCA disease.ResultsMultivariable logistic regression identified male and hypertension as the predictors of the SAO etiology of MCA disease, however diabetes mellitus, repeated transient ischemic attack before the stroke, gaze palsy, aphasia, headache at admission, and disability at discharge as the predictors of the LAA etiology of MCA disease.ConclusionHypertension and diabetes mellitus are related with the different etiology of MCA disease.

Transcranial Doppler Screening In Children with Sickle Cell Disease of South Gujarat Population

Background: TCD (Transcranial Doppler) is a well-established study to predict Cerebrovascular stroke in SCD (Sickle cell disease). We aim to establish baseline TCD findings in Indian children with SCD and compare the results with the available STOP (Stroke prevention trial in Sickle Cell Anemia) protocol. We would also compare TCD findings in homozygous sickle cell disease and heterozygous sickle cell trait.&#x0D; Material and Methods: Seventy nine children with SCD were included in this study for one year period. TCD was performed and TAMMV (time-averaged maximum mean) velocity in the middle cerebral, anterior cerebral, posterior cerebral and internal carotid arteries was measured. Children were divided into two groups. Group I (56 homozygos–70.88%) and group II (23 heterozygos–29.11%).&#x0D; Results: In group I, 50 children fall in normal range with average TAMM velocity of 127.59 ± 17.48 cm/s. There was 1 (1.78%) abnormal result and 5 (8.9%) conditional results in group I. All results were normal in group II with average TAMM velocity of 116.33 ± 12.412 cm/sec. Middle cerebral artery was the only affected vessels amongst all.&#x0D; Conclusions: In our study, there was low prevalence of abnormal TCD results as compared to STOP protocol. The difference was significant in TAMM velocity between two groups, with all children being within normal range in group II. Result of this study differs from previous studies, done in western countries probably due to difference in haplotype.

Etiological Classification of Cerebral Ischemic Stroke by the TOAST, SSS-TOAST, and ASCOD Systems: The Impact of Observer's Experience on Reliability.

To assess the impact of observer's experience on reliability of etiological classification systems in patients with ischemic stroke. We retrospectively reviewed medical records of 80 patients with ischemic stroke in hospitals from August 2016 to March 2017 consecutively. Patients were classified by 4 observers with different clinical experiences and backgrounds (A, B, C, and D) according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST), Stop Stroke Study TOAST (SSS-TOAST), and ASCOD (A-atherosclerosis, S-small vessel disease, C-cardiac pathology, O-other cause, and D-dissection). The intraobserver reliability was assessed based on the initial and a second delayed assessment after 3 months, and the interobserver reliability of different pairs (A-B and C-D) and overall (A, B, C, and D) were compared based on the initial classification. The reliability values of the 3 classification systems were improved with observer's experience increasing, particularly in the TOAST system, in which the intraobserver reliability values of observers A, B, C, and D were 0.62, 0.73, 0.80, and 0.88, respectively, and slight differences were observed between the SSS-TOAST and ASCOD systems. The A-B pair had lower interobserver reliability value than the C-D pair, particularly in TOAST system with reliability values of 0.36 and 0.74, respectively, and a slight variation of interobserver reliability values were noted in the SSS-TOAST and ASCOD system. Observer's experience may affect the reliability of etiological classification systems in patients with ischemic stroke.

S855 TCD IMPLEMENTATION RATES AND RESULTS IN THE MODERN ERA OF SICKLE CELL ANEMIA: RESULTS FROM THE DISPLACE STUDY

Background:Stroke is one of the most devastating complications of sickle cell anemia (SCA). The STOP (Stroke Prevention Trial in Sickle Cell Anemia) protocol was adopted in 2014 by the National Heart Lung and Blood Institute (NHLBI) guidelines for stroke‐risk screening using transcranial Doppler ultrasound (TCD) and prevention with chronic red cell transfusion therapy (CRCT) 1. Despite high‐level evidence supporting the use of TCD screening (and CRCT initiation) in stroke prevention2,3, wide scale implementation has not been achieved 4.Aims:The DISPLACE (Dissemination and Implementation Looking at the Care Environment) project is a multicenter, NHLBI‐funded study whose primary aim is to identify barriers to implementation of the STOP protocol and test novel methods for improving outcomes. DISPLACE is a 3‐part study: retrospective assessment of current practice, qualitative review of barriers and facilitators to screening and a cluster‐randomized intervention project using implementation science to improve TCD screening and CRCT implementation. We are reporting on part 1 of this project evaluating implementation rates of TCD screening and TCD outcomes (abnormal and conditional) in a large contemporary cohort.Methods:DISPLACE is a large multi‐site study consortium of 28 centers across the United States representing a range of characteristics: region (urban vs rural), size, and institution type (academic vs community). Each site performed a rigorous retrospective chart review of children with SCA aged 2–16 years from 2012–2016. To be eligible for inclusion, children had to have been seen at their institution at least 2x/calendar year (for 1 year) and have confirmation of SCA. A custom electronic data capture (EDC) system facilitated entry of de‐identified data including demographics, TCD and MRI results, medications, transfusions, and laboratory values. The primary study outcome is to assess implementation of TCD screening (per center). TCD screening rates were calculated per center (TCD/child/year/center). TCD results were recorded in the EDC as normal, conditional or abnormal. Stroke status was also recorded as well as presence or absence of CRCT. Data included missed TCD appointments and medical decisions based on TCD results.Results:The study included 28 centers. In total, 5223 individuals with SCA (50.2% male, 93.7% HbSS) are included in the database (5187 of those eligible in the study period). This is the largest cohort of children with SCA ever studied. TCD screening rates varied widely among institutions ranging from 30–75.2% (mean 48.4%, median 47%). Of the total in the database, 3718 patients had a TCD during the study period (71.7%). Of those patients who had a TCD, 138 (3.7%) had an ABNORMAL TCD per STOP guidelines which is notably lower than the STOP study with a rate of abnormal TCD of 9.7% at study entry. Characteristics of patients with abnormal TCD (vs. those without) are forthcoming.Summary/Conclusion:Despite the benefit of TCD screening in children with SCA, guideline‐based implementation remains poor. The range of barriers to screening will help investigators optimize the intervention protocol to enhance TCD implementation. Notably, there are fewer children with abnormal screening rates in the modern era which may represent partial penetration of the STOP Protocol from prior screening and/or effect of disease‐modifying therapy. Data analysis is in process to further qualify these findings.

S856 ALTERATION OF IRON HOMEOSTASIS IN A MOUSE MODEL OF LIVER-STAGE PLASMODIUM INFECTION

Background: Stroke is one of the most devastating complications of sickle cell anemia (SCA). The STOP (Stroke Prevention Trial in Sickle Cell Anemia) protocol was adopted in 2014 by the National Heart Lung and Blood Institute (NHLBI) guidelines for stroke-risk screening using transcranial Doppler ultrasound (TCD) and prevention with chronic red cell transfusion therapy (CRCT) 1. Despite high-level evidence supporting the use of TCD screening (and CRCT initiation) in stroke prevention2,3, wide scale implementation has not been achieved 4. Aims: The DISPLACE (Dissemination and Implementation Looking at the Care Environment) project is a multicenter, NHLBI-funded study whose primary aim is to identify barriers to implementation of the STOP protocol and test novel methods for improving outcomes. DISPLACE is a 3-part study: retrospective assessment of current practice, qualitative review of barriers and facilitators to screening and a cluster-randomized intervention project using implementation science to improve TCD screening and CRCT implementation. We are reporting on part 1 of this project evaluating implementation rates of TCD screening and TCD outcomes (abnormal and conditional) in a large contemporary cohort. Methods: DISPLACE is a large multi-site study consortium of 28 centers across the United States representing a range of characteristics: region (urban vs rural), size, and institution type (academic vs community). Each site performed a rigorous retrospective chart review of children with SCA aged 2–16 years from 2012–2016. To be eligible for inclusion, children had to have been seen at their institution at least 2x/calendar year (for 1 year) and have confirmation of SCA. A custom electronic data capture (EDC) system facilitated entry of de-identified data including demographics, TCD and MRI results, medications, transfusions, and laboratory values. The primary study outcome is to assess implementation of TCD screening (per center). TCD screening rates were calculated per center (TCD/child/year/center). TCD results were recorded in the EDC as normal, conditional or abnormal. Stroke status was also recorded as well as presence or absence of CRCT. Data included missed TCD appointments and medical decisions based on TCD results. Results: The study included 28 centers. In total, 5223 individuals with SCA (50.2% male, 93.7% HbSS) are included in the database (5187 of those eligible in the study period). This is the largest cohort of children with SCA ever studied. TCD screening rates varied widely among institutions ranging from 30–75.2% (mean 48.4%, median 47%). Of the total in the database, 3718 patients had a TCD during the study period (71.7%). Of those patients who had a TCD, 138 (3.7%) had an ABNORMAL TCD per STOP guidelines which is notably lower than the STOP study with a rate of abnormal TCD of 9.7% at study entry. Characteristics of patients with abnormal TCD (vs. those without) are forthcoming. Summary/Conclusion: Despite the benefit of TCD screening in children with SCA, guideline-based implementation remains poor. The range of barriers to screening will help investigators optimize the intervention protocol to enhance TCD implementation. Notably, there are fewer children with abnormal screening rates in the modern era which may represent partial penetration of the STOP Protocol from prior screening and/or effect of disease-modifying therapy. Data analysis is in process to further qualify these findings.

Results from the Displace Consortium: Practice Patterns on the Use of Transcranial Doppler Screening for Risk of Stroke in Children with Sickle Cell Anemia

Abstract Introduction: Stroke is one of the most devastating complications of sickle cell anemia (SCA). The STOP (Stroke Prevention Trial in Sickle Cell Anemia) protocol has been adopted by National Heart Lung and Blood Institute (NHLBI) as the guideline for stroke screening using transcranial Doppler ultrasound (TCD) and prevention with chronic red cell transfusion therapy (CRCT). Evidence from the STOP I/II studies indicates the protocol is highly effective, yet wide scale implementation has not been achieved. The DISPLACE (Dissemination and Implementation Looking at the Care Environment) project is a multicenter, NHLBI funded consortium of 28 sites across the United States whose purpose is to identify barriers to the implementation of the STOP protocol and test novel methods for overcoming barriers. The purpose of this study was to use data on practice patterns to evaluate current measurement and practice standards at DISPLACE consortia sites. This abstract presents reported TCD screening and CRCT practices. Methods: A practice patterns survey was sent to the principal investigator (PI) for each DISPLACE site via RedCap ©. PIs were hematology/oncology specialty care providers for children with SCA. Sites represent urban and rural regions, large and small academic institutions, and community-based institutions. The survey was developed by the study investigators; questions were predominantly in a multiple-choice format. Items pertaining to TCD screening included: screening technique (including type of TCD); screening frequency; follow-up for abnormal, conditional, and inadequate results; standard value ranges. Results: All 28 PIs completed the survey. About half of the respondents were female (53.5%). Most identified as White (77.8%), followed by Asian (11.1%) and Black or African American (7.4%). Two identified as Hispanic or Latino (7.4%). Slightly more sites reported using standard TCD (57.1%) versus imaging TCD (TCDi) (42.9%). To calculate the time-averaged mean of the maximum (TAMM) velocities and characterize TCD results, nearly all sites use the middle cerebral artery (96.4%); a majority also use the anterior cerebral artery and/or the terminal internal cerebral artery or distal internal cerebral artery (71.4%). Fewer sites use the posterior cerebral artery (35.7%) or the basilar artery (14.3%). In 7.1% of sites, the radiologist determines which vessels to use during the exam. TCD screening is ordered for children with SCA annually in 92.9% of sites and every 6 months in 7.1% of sites. When TCD screening indicates abnormal TAMM velocities, 85.7% of sites initiate CRCT, 7.1% initiate hydroxyurea (HU) therapy, and 3.6% initiate both HU and CRCT. For additional evaluation, an MRI/MRA is obtained at 64.3% of sites. For high conditional results, the most common action is to initiate HU (67.9%). Other responses include obtaining an MRI/MRA (46.4%) and/or repeating the TCD in 2-4 weeks (25.0%), 6-8 weeks (35.7%), or 12-16 weeks (7.1%). Results deemed inadequate led to repeating the TCD in 2-12 weeks (57.1%) or in one year (3.6%), obtaining an MRI/MRA (57.1%), beginning HU therapy (7.1%), or no repeat TCD or change in management (3.6%). Actions for low conditional results include repeating the TCD (71.4%), obtaining an MRI/MRA (32.3%), and/or initiating HU therapy (57.1%). Surprisingly, sites use different TAMM ranges to characterize the normal/abnormal findings (Table 1). Conclusions: Nearly all DISPLACE sites order TCD screening annually, as recommended in the guidelines, with some ordering screening more frequently. A few sites did not report initiation of CRCT per STOP protocol for abnormal TCD results; however, over half of the sites reported following up with an MRI/MRA, which may suggest evaluating for vasculopathy prior to CRCT. Some sites reported beginning HU therapy for abnormal results; this may reflect consideration of patients for whom CRCT is not possible, but data were not collected for confirmation. Interestingly, results suggest a reliance on MRI/MRA since sites commonly reported ordering neuroradiology studies for abnormal, conditional, and inadequate TCD results. This may suggest an unclear pathway for children with borderline TCD results, and an area for future study. While reported value ranges closely approximated those in the STOP protocol, results indicate sites conducting screening with TCDi may use more conservative values than the validated protocol. Disclosures Phillips: NHLBI: Research Funding. Mueller:NHLBI: Research Funding. Schlenz:NHLBI: Research Funding. Melvin:NHLBI: Research Funding. Adams:NHLBI: Research Funding. Kanter:AstraZeneca: Membership on an entity's Board of Directors or advisory committees; bluebird bio: Membership on an entity's Board of Directors or advisory committees, Research Funding; Global Blood Therapeutics: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sancilio: Research Funding; NHLBI: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Apopharma: Research Funding; ASH: Membership on an entity's Board of Directors or advisory committees.

MStroke: “Mobile Stroke”—Improving Acute Stroke Care with Smartphone Technology

This study aimed to evaluate the effect of method and time of system activation on clinical metrics in cases utilizing the Stop Stroke (Pulsara, Inc.) mobile acute stroke care coordination application. A retrospective cohort analysis of stroke codes at 12 medical centers using Stop Stroke from March 2013 to May 2016 was performed. Comparison of metrics (door-to-needle time [DTN] and door-to-CT time [DTC], and rate of DTN ≤ 60 minutes [goal DTN]) was performed between subgroups based on method (emergency medical service [EMS] versus emergency department [ED]) and time of activation. Effects were adjusted for confounders (age, sex, National Institutes of Health Stroke Scale [NIHSS] score) using multiple linear and logistic regression. The final dataset included 2589 cases. Cases activated by EMS were more severe (median NIHSS score 8 versus 4, P < .0001) and more likely to receive recombinant tissue plasminogen activator (20% versus 12%, P < .0001) than those with ED activation. After adjustment, cases with EMS activation had shorter DTC (6.1 minutes shorter, 95% CI [-10.3, -2]) and DTN (12.8 minutes shorter, 95% CI [-21, -4.6]) and were more likely to meet goal DTN (OR 1.83, 95% CI [1.1, 3]). Cases between 1200 and 1800 had longer DTC (7.7 minutes longer, 95% CI [2.4, 13]) and DTN (21.1 minutes longer, 95% CI [9.3, 33]), and reduced rate of goal DTN (OR .3, 95% CI [.15, .61]) compared to those between 0000 and 0600. Incorporating real-time prehospital data obtained via smartphone technology provides unique insight into acute stroke codes. Activation of mobile electronic stroke coordination in the field appears to promote a more expedited and successful care process.

Stop Stroke: A Brief Report on Door-to-Needle Times and Performance After Implementing an Acute Care Coordination Medical Application and Implications to Emergency Medical Services.

The objective of this study was to evaluate the effect of the Stop Stroke (Pulsara; Bozeman, Montana USA) medical application on door-to-needle (DTN) time in patients presenting to the emergency department (ED) with an acute ischemic stroke (AIS). This was a retrospective cohort study of the Good Shepherd Health System (Longview, Texas USA) stroke quality improvement dashboard for a 25-month period from February 2012 through February 2014. Data analysis includes all data from Center for Medicare and Medicaid Services (CMS; Baltimore, Maryland USA) reportable cases receiving Tissue Plasminogen Activator (TPA) for AIS during the study period. The primary outcome was mean DTN times before and after initiating Stop Stroke. Secondary outcome was the effect on the DTN≤60-minute benchmark. During the study period, there were 533 stroke activations (200 before Stop Stroke implementation and 333 after). A total of 68 patients meeting inclusion criteria were analyzed (34 pre-app and 34 post- app). The observed mean DTN times post-app decreased 21 minutes (77 to 56 minutes), a 28% improvement (P=.001). Further, the patients meeting DTN≤60 minutes improved from 32% (11 of 34) to 82% (28 of 34) after the app's implementation. In this cohort of patients with AIS, Stop Stroke improved mean DTN times and number of patients treated within 60 minutes of arrival. These results demonstrate the app's effect of increasing awareness of suspected AIS and improving coordination of care, evidenced by the magnitude of its effect on treatment times. Dickson R , Nedelcut A , McPeek Nedelcut M . Stop Stroke: a brief report on door-to-needle times and performance after implementing an acute care coordination medical application and implications to Emergency Medical Services. Prehosp Disaster Med. 2017;32(3):343-347.

Ischemic stroke classification and risk of embolism in patients with Chagas disease.

Ischemic stroke (IS) and Chagas disease are strongly related. Nevertheless, little attention has been paid to this association and its natural history. The current guidelines concerning the management and secondary prevention of IS are largely based on the incomplete information or extrapolation of knowledge from other stroke etiologies. We performed a retrospective study which compared stroke etiologies among a cohort of hospitalized patients with IS and Chagas disease. The Instituto de Pesquisa Evandro Chagas/Fundação Oswaldo Cruz (IPEC/FIOCRUZ) embolic score was also used to identify and evaluate the risk of embolism in this population. A total of 86 patients were included in the analysis. The mean age of the study population was 58years, and 60% were men. According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) Classification, 45% of the strokes were of undetermined etiology and 45% of cardioembolic origin, while the Stop Stroke Study/Causative Classification System (SSS/CCS) TOAST indicated that 34% were undetermined and 50% cardioembolic (p<0.01); 44% of these patients were classified as having a high embolic risk according to the IPEC/FIOCRUZ score. Among the undetermined causes, 83.3% fulfilled the criteria for embolic stroke of undetermined source (ESUS). The SSS/CCS TOAST etiological classification system was superior to the classical TOAST criteria in identifying a cardioembolic etiology in patients with ischemic stroke and Chagas disease. The IPEC/FIOCRUZ score did not correlate with the number of patients who were determined to have cardioembolic stroke etiologies. The current guidelines for stroke prevention should be reviewed in this population.

Stop Stroke© Acute Care Coordination Medical Application; a Brief Report on Post Implementation Performance at a Primary Stroke Center (P2.307)

Stop Stroke© Acute Care Coordination Medical Application; a Brief Report on Post Implementation Performance at a Primary Stroke Center (P2.307)

Stop Stroke© Acute Care Coordination Medical Application: A Brief Report on Postimplementation Performance at a Primary Stroke Center

The objective of our study was to evaluate the effect of the Pulsara Stop Stroke© medical application on door-to-needle (DTN) time in patients presenting to our emergency department with acute ischemic stroke (AIS). The secondary objective was to evaluate the DTN performance of dedicated neurohospitalists versus private practice neurologists covering emergency department stroke call. We conducted a retrospective cohort study of the Good Shepherd Health System stroke quality improvement dashboard for an 18-month period. The primary outcome was mean DTN time performance in cases with and without Stop Stroke© usage. Secondary outcome was mean DTN time between neurohospitalist and private neurologists with and without use of Stop Stroke©. During the study period, there were 85 stroke activations receiving tissue plasminogen activator (63 with Stop Stroke©, 22 without Stop Stroke©). In cases where the app was used, we observed a reduction in mean DTN time of 40 minutes (87-47 minutes), a 46% reduction. There was no significant difference in DTN time observed between the neurohospitalist and private neurologist performance independent of app usage. Mean DTN less than 60 minutes improved with app use from 18% to 85% with Stop Stroke©. In patients arriving to our primary stroke center with AIS, use of Pulsara Stop Stroke© acute care coordination app decreased mean DTN time by 40 minutes, a significant 46% improvement in this metric and is consistent with other studies of the app. We further observed a 3.7× improvement in DTN less than 60 minutes with use of the app.

Abstract W P207: STOP STROKE©-A Novel Medical Application to Improve Coordination of Stroke Care: A Brief Report on Door to Thrombolysis Times After Initiating the Application

Hypothesis: We hypothesized that introduction of a care coordination application to our emergency stroke care would improve time to thrombolysis in acute ischemic stroke (AIS). Introduction: The objective of our study was to evaluate the effect of the STOP STROKE© medical application on patient arrival to thrombolytic times for patients arriving at our emergency department with AIS. STOP STROKE© is a novel medical application developed by physicians to improve the coordination and communication tasks essential to rapid assessment and care of patients suffering from AIS. Methods: We conducted a retrospective review of the Good Shepherd Health System stroke dashboard between February 2012 and February 2014 (13 months prior to STOP STROKE© and 12 months after). The stroke dashboard is a quality improvement database for acute stroke activations in patients arriving to our level II emergency department with annual volumes of 90,000. We analyzed all data from CMS reportable cases receiving TPA for AIS during the study period. The primary outcome was mean Door-to- Needle (DTN) times before and after initiating STOP STROKE©. Secondary outcome was the effect on the DTN &lt;60 min benchmark. Results: During the study period we had 533 stroke activations (200 pre-application and 333 post-application), representing an 80% increase in activations after the app. A total of 85 patients received TPA therapy for AIS (41 pre-application and 44 post-application). Of these, 17 cases were excluded that did not meet CMS criteria for reporting. We observed the mean D2N times post STOP STROKE© decreased 21 min (77 - 56min), a 28% improvement (p=0.001). Further, the patients meeting D2N &lt; 60 min improved from 32% (11/34) to 82% (28/34) after the app. Conclusions: In this cohort of patients with AIS, STOP STROKE© improved mean D2N times and number of patients treated within 60 min of arrival. Further we saw an increase in total stroke activations. We conclude our results demonstrate the app’s effect of increasing awareness of suspected AIS and improved coordination of care, evidenced by the magnitude of its effect on treatment times.

Abstract T MP106: Nursing Acceptance of a Novel Care Coordination Application to Reduce Time to Thrombolysis in Patients with Acute Ischemic Stroke: A Pilot Study

Background: STOP STROKE© is a novel medical application (app) developed to improve care coordination in acute ischemic stroke and was previously demonstrated to improve door to thrombolytic times. The app captures stroke benchmarking data in real time for quality assurance/improvement. Current literature reports that successful adoption of new health care technologies is not decided by hospital administration, but determined on the work floor. Purpose: We seek to determine the feasibility of an instrument used to measure end users’ intent to use, perceived usefulness, and perceived ease of use of STOP STROKE© and to capture the determinants of these constructs. Methods: We administered a 74-question, on-line survey to a convenience sample of 16 end users involved in acute stroke care after STOP STROKE© was instituted at our level II trauma center with annual emergency department volumes of 90,000. The Technology Acceptance Model (TAM) employs constructs including: perceived usefulness, ease of use, self-efficacy, external control, enjoyment, subjective norm, computer anxiety, voluntariness, image, job relevance, output quality, result demonstrability, and intent to use. Participants included emergency department charge nurses, cardiac catheterization lab nurses, house supervisors, and stroke coordinator. Data analysis included descriptive statistics and crosstabs. Results: Our sample consisted of 62% women, mean age 41 with an average of 10 years in their current role. Respondents had an average 4.8 years experience using smart phone technology. Overwhelmingly, nurses indicated they intended to use the app (93%), that it had usefulness (81.3%) and was easy to use (87.5%). Additionally, when comparing the app to the traditional stroke activation system, nurses felt that the app improved patient outcomes (86.7%), fit with current protocols and practice (93.3%), and that positive results were demonstrable (100%). Determinants were congruent with TAM theory. Conclusions: The use of TAM can measure acceptance and intent to use the app. Our findings will allow a fully-developed instrument to identify pre-implementation concerns and then measure intervention success in post-implementation surveys.

Cardiac MRI Improves Identification of Etiology of Acute Ischemic Stroke

Background: An accurate subtype classification of acute ischemic stroke is important in clinical practice as it can greatly influence patient care in terms of acute management and devising secondary stroke prevention strategies. Approximately, one third of ischemic strokes are cryptogenic despite a comprehensive workup. Diagnostic workup for detecting cardioaortic sources of cerebral embolism commonly includes transthoracic echocardiography (TTE). However, TTE has a limited diagnostic power to detect some of the cardioaortic abnormalities and additional imaging modalities are often needed to accurately assess such abnormalities. Purpose: We evaluated the feasibility of cardiovascular magnetic resonance (CMR) imaging to detect the cardioaortic sources of ischemic stroke. Methods: A total of 106 patients were included, of which 85 had an ischemic stroke and 21 had a transient ischemic attack (TIA). Routine diagnostic workup (RDW) included brain diffusion-weighted image MRI, telemetry, magnetic resonance angiography/CT angiography of head and neck, carotid duplex ultrasonography, laboratory studies and TTE. Patients additionally underwent CMR. Subtype assignment was performed in accordance with the Stop Stroke Study of the Trial of Org 10172 in Acute Stroke Treatment classification system by a stroke neurologist after reviewing the admission notes and diagnostic test results. A second subtype classification was assigned with an additional criterion defined based on delayed enhancement (DE)-CMR findings. Additionally, the presence of non-coronary artery disease (CAD) scarring was assessed in ischemic stroke patients and compared with the TIA patients as the control group. Results: RDW detected cardioaortic embolism (CAE) stroke in 32 (37.6%) patients and cryptogenic stroke in 23 patients (27.1%). Addition of CMR resulted in a 26.1% reduction in the rate of cryptogenic strokes (6 patients). Furthermore, DE-CMR findings allowed for reclassification of three additional cryptogenic subtypes, resulting in a 39.1% reduction of cryptogenic stroke rate. Non-CAD scarring was detected in 13 (15.3%) stroke patients as opposed to only 1 (4.8%) TIA patient. Conclusions: CMR is a valuable tool for the detection of CAE sources in patients with cryptogenic ischemic stroke and provides clinicians with a unique set of information that may substantially change the long-term management of these patients. DE-CMR also detects non-CAD scarring, which may indicate a predisposition to ischemic stroke. Further studies with larger samples and long-term follow-up are needed to further evaluate the clinical significance of our findings.

Can STOP Trial Velocity Criteria Be Applied to Iranian Children with Sickle Cell Disease?

Background and PurposeSickle cell disease (SCD) is strongly linked to stroke across all haplotypes in the pediatric population. Transcranial Doppler (TCD) ultrasound is known to identify the highest risk group in African-Americans who need to receive and stay on blood transfusions, but it is unclear if the same flow velocity cut-offs can be applied to the Iranian population. We aimed to evaluate baseline TCD findings in Iranian children with SCD and no prior strokes.MethodsChildren with genetically confirmed SCD (Arabian haplotype, homozygote) and without SCD (controls) were prospectively recruited from pediatric outpatient clinic over a period of 9 months. We performed TCD in both groups to determine flow velocities in the middle cerebral (MCA) and terminal internal carotid arteries (TICA).ResultsOf 74 screened children, 60 met the inclusion/exclusion criteria (62% female; mean age 10±4 years). Baseline characteristics did not differ between the cases and controls, except hemoglobin (Hb) which was significantly lower in the SCD group (P<0.001). The right MCA TAMM (Time Averaged Maximum Mean) was significantly higher than in controls (125+5.52 cm/s vs. 92.5+1.63 cm/s, P<0.001). Left MCA did not show differences. The TICA TAMM was also different between cases and controls (P<0.05).ConclusionsAmong Iranian children with asymptomatic SCD and without receiving recent transfusion TCD velocities are higher as compared to healthy controls but appear much lower than those observed in STOP (Stroke Prevention Trial in Sickle Cell Anemia) studies. We hypothesize that some children at high risk may be present with velocities lower than 170-200 cm/s thresholds. A prospective validation of ethnicity-specific prognostic criteria is warranted.