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

Abstract

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.