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Stroke prevention guidelines for sickle cell anemia (SCA) recommend transcranial Doppler (TCD) screening to identify children at stroke risk; however, TCD screening implementation remains poor. This report describes results from Part 1 of the 28-site DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study, a baseline assessment of TCD implementation rates. This report describes TCD implementation by consortium site characteristics; characteristics of TCDs completed; and TCD results based on age. The cohort included 5247 children with SCA, of whom 5116 were eligible for TCD implementation assessment for at least one study year. The majority of children were African American or Black, non-Hispanic and received Medicaid. Mean age at first recorded TCD was 5.9 years and 10.5 years at study end. Observed TCD screening rates were unsatisfactory across geographic regions (mean 49.9%; range 30.9–74.7%) independent of size, institution type, or previous stroke prevention trial participation. The abnormal TCD rate was 2.9%, with a median age of 6.3 years for first abnormal TCD result. Findings highlight real-world TCD screening practices and results from the largest SCA cohort to date. Data informed the Part 3 implementation study for improving stroke screening and findings may inform clinical practice improvements.

Introduction: Without intervention, children with sickle cell anemia (SCA) have an 11% chance of overt ischemic stroke. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) proved that children with SCA at increased risk of stroke can be identified using transcranial Doppler ultrasound (TCD) and, for those at risk, chronic red cell transfusion (CRCT) therapy is effective at preventing stroke. The 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines include annual TCD screening for children with SCA ages 2 - 16, and CRCT for primary and secondary ischemic stroke prevention. The NHLBI-funded Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) project was designed to 1.) evaluate current stroke screening and prevention practices in a 28-site consortium through intensive medical record review and an electronic data capture system, 2.) determine barriers and facilitators to stroke prevention practices through qualitative methods, and 3.) design and deliver interventions to increase rates of 'sickle stroke screening' using implementation strategies. The purpose of this abstract is to describe initial (pre-study) consortium actions following abnormal TCD results including whether all children had a repeat TCD within the next 4 weeks, whether they initiated CRCT, characteristics of which children received CRCT, and what alternate treatments were used. Methods: DISPLACE data collection years were 2012 - 2016. 5247 children with SCA who met criteria for annual TCD screening were entered into the electronic data capture system with clinical and demographic information. 163 children with abnormal TCD results were identified from the cohort database. Additional data were collected and subsequently adjudicated including timing of follow-up testing (repeat TCD or MRI) after abnormal TCD, implementation of CRCT following abnormal TCD, alternate treatment following abnormal TCD, and whether the STOP protocol was implemented. Data were analyzed using descriptive statistics. Results: In response to abnormal TCD, 75% of children had a repeat TCD ordered (Table 1). Of these, most repeat TCDs were completed within 3 months, with Conclusions: In this nationally representative sample of children with SCA at risk for stroke, nearly ¾ of children had a repeat TCDs, suggesting confirmation of abnormal results was common prior to beginning CRCT. Notably, there were a large number of ischemic strokes in children when CRCT was delayed futher confirming the utility of the screening and stroke prevention protocol. An additional key concern identified in this study were the barriers to STOP protocol implementation. Common reasons for lack of implementation included the parent's decision for HU instead of CRCT, delays in CRCT initiation, and delays in obtaining repeat TCDs. Difficulties implementing the STOP protocol suggest the need for interventions for more rapid initiation of CRCT and stroke prevention. Disclosures Kanter: AGIOS: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Sanofi: Consultancy; bluebird bio, inc: Consultancy, Honoraria; Medscape: Honoraria; Guidepoint Global: Honoraria; GLG: Honoraria; Jeffries: Honoraria; Cowen: Honoraria; Wells Fargo: Honoraria; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees.

Background: Stroke is one of the most devastating complications of sickle cell anemia (SCA). In 1998, the Stroke Prevention Trial in Sickle Cell Anemia (STOP), demonstrated that a high-risk group of children with SCA could be identified using Transcranial Doppler ultrasound(TCD) and that chronic red cell transfusion therapy (CRCT) could reduce the risk of first ischemic stroke in this group by over 90% (Adams, et al NEJM 1998).At STOP studyenrollment, 9.7% of children with SCA were identified as having an abnormal TCD. Baby HUG, (NCT00006400), an NHLBI supported phase III trial showed that severe anemia in SCA was associated with elevated white blood cell (WBC) and higher TCD velocities (Lebensburger, et al Blood 2010 ). It is unclear if lower hemoglobin (Hb) and/or higher WBC are causative of elevated TCD velocities or correlative biomarkers. As new disease therapies become available, it is important to know the current rate of abnormal TCD and characteristics of those patients. The DISPLACE (Dissemination and Implementation Looking at the Care Environment) project is a multicenter, NHLBI-funded study whose primary purpose is to identify barriers to implementation of stroke screening in SCA 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 implementation project to improve stroke screening. Part 1 of the study showedthat TCD screening rates varied widely among institutions ranging from 30-75.2% (mean 48.4%, median 47%). We are now reporting on the rate of abnormal TCD and the characteristics and outcomes of patients with abnormal TCD. Methods: DISPLACE is a consortium of 28 US centers. 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 must have been seen at their institution at least 2x during the study period 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. For children with SCA who had TCD or central nervous system imaging prior to 2012, these results were also entered into the EDC. TCD results were recorded in the EDC as normal, conditional or abnormal based on their institutional interpretation. Labs and vitals were entered for each patient in closest proximity to each TCD. Confirmation and adjudication of each abnormal TCD and associated outcomes were performed. Stroke status was also recorded as well as presence or absence of CRCT. Results: In total, 5247 children with SCA are included in the database of whom 5225 should have received a TCD. Of this cohort, 4210 children (80.6%) had at least one TCD recorded in the database. Within this group, 207 (4.9%) of children had an abnormal TCD and 816 (19.4%) had a conditional TCD. For those children who underwent TCD during the study (2012-2016) period, there were 105 (2.9%) abnormal TCD and 501 (13.6%) conditional TCD (Table 1). The mean age of children at the time of abnormal TCD was 6.6 years (range 2-16 yr). The majority of children were Of the total 5247 patients in the database, 3093 (59%) had been prescribed hydroxyurea (HU) and 999 (19%) were prescribed CRCT. CRCT was prescribed most often for abnormal TCD (37%) or secondary stroke prevention (31%). Discussion: DISPLACE is the largest contemporary cohort of children with SCA. The incidence of abnormal TCD in the DISPLACE cohort is significantly lower than at randomization in the STOP study. The number of children receiving CRCT is higher than expected which may partly account for the decrease in frequency of abnormal TCD. Many patients with abnormal TCD were receiving HU when their TCD was abnormal and were started on CRCT. Additionally, while the outcomes of children with conditional TCD are still being evaluated, many of those children reverted to normal TCD without intervention. These data may also help us redefine the use and interventions needed for abnormal TCD. Disclosures Kanter: NHLBI: Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc.: Consultancy; SCDAA: Membership on an entity's Board of Directors or advisory committees; Guidepoint Global: Consultancy; GLG: Consultancy; Sangamo: Consultancy, Honoraria; Modus: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Imara: Consultancy; Cowen: Consultancy; Jeffries: Consultancy; Medscape: Honoraria; Rockpointe: Honoraria; Peerview: Honoraria. Adams:GBT: Consultancy, Other: consultancy to companies GBT and Blueburd Bio; Bluebird: Consultancy.