Prevention of Stroke after STOP, A Retrospective Chart Review

描述（由申请人提供）：STOP和STOP II研究提供了第一个由I类证据支持的镰状细胞病综合性卒中预防策略。虽然TCD筛查和预防性输血策略在镰状细胞性贫血的卒中预防中非常有效（STOP试验），并且如果在输血30个月或更长时间后取消该治疗，则观察到高风险或卒中的逆转（STOP II），但尚不清楚该方法在试验完成后的真实的世界实践中的有效性。该项目利用了大量的财力和人力资源，获得STOP和STOP II数据，以及由此产生的数据库（研究者可用），其中包含超过3400名儿童的信息，通过深入分析研究参与者在试验后期间关于卒中预防行为（TCD和输血重新筛查）和卒中以及其他重要结局的医疗记录。两个结果是最重要的：1）中风-在这方面，中风发生后，试验的结果筛选失败（无TCD或时间安排不当或对筛查计划的依从性不足）或治疗失败（不推荐或不接受输血或尽管遵守了充分输血但仍发生突发性卒中）以及如何最好地利用这些信息来改善卒中预防实践;（2）转为高危中药治疗。数据库包含超过3000名儿童的初步（异常前）TCD数据，并根据试验期间的重新筛选，从STOP发布了转换概率。假设试验后在临床实践中进行了不同程度的重新筛选，并在试验后发现了新的异常;预测TCD异常发生率的试验后模型是否证实了STOP或与STOP中观察到的结果存在实质性差异？在任何一种情况下，试验后经验将与STOP数据相结合，以制定更强有力的TCD重新筛选循证临床指南（如果首次TCD未表明需要治疗），以确保对卒中风险进行充分监测。STOP和STOP II在专门的儿科SCD中心进行，将研究向成人提供者系统过渡对卒中预防的影响，评估态度，并将这些数据用于为进一步研究和教育提供建议。总体而言，该项目提供了大量新信息，将确保STOP和STOP II的主要投资在真实的世界应用中发挥最大优势，以预防SCD儿童的卒中。公共卫生相关性：这项调查的目的是获得和分析可以提高镰状细胞病儿童和年轻人护理质量的信息，特别是在预防中风方面。信息的分析将直接影响TCD筛查的指南。这些定性数据还将深入了解竞争疗法的价值以及治疗方案和中风事件的影响，并最终提供信息，以帮助预防镰状细胞病年轻人的毁灭性中风。

DESCRIPTION (provided by applicant): The STOP and STOP II studies provided the first comprehensive stroke prevention strategy in Sickle Cell Disease supported by Class I evidence. While the strategy of TCD screening and prophylactic transfusion was very efficacious in the Stroke Prevention in Sickle Cell Anemia (STOP trial), and reversion to high risk or stroke was observed if this therapy is removed even after 30 or more months of transfusion (STOP II) it is unclear how effective this approach is in real world practice after the trials were completed. This project leverages the enormous financial and human resources expended to obtain STOP and STOP II data, and their resulting data bases (available to the investigators) with information on over 3400 children, by making an in-depth analysis of the medical records of study participants in the post trial period regarding stroke prevention behaviors (re-screening with TCD and transfusion) and stroke as well as other important outcomes. Two outcomes are of paramount interest: 1) stroke - in this respect were the strokes that took place after the trial the result of screening failures (no TCD or inadequate timing or compliance with screening programs) or treatment failures (transfusion not recommended or accepted or breakthrough stroke despite compliance with adequate transfusion) and how can this information be best used to improve stroke prevention practices; 2) conversion to high risk TCD. The data bases contain preliminary (pre abnormal) TCD data on over 3000 children, and probabilities for conversion have been published from STOP based on rescreening during the trail. Assuming varying degrees of rescreening in clinical practice post trial, and new abnormals identified post trial; does the post trial model predicting the incidence of abnormal TCD confirm STOP or vary substantially from what was observed in STOP? In either case post trial experience will be combined with STOP data to formulate stronger evidence based clinical guidelines for re screening with TCD (if the first TCD does not indicate need for treatment) to insure adequate surveillance for stroke risk. STOP and STOP II were carried out in specialized pediatric SCD centers, the impact of transition to adult provider systems on stroke prevention will be studied, attitudes assessed and these data used to inform recommendations for further research and education. Overall the project provides substantial new information that will insure the major investment made in STOP and STOP II is used to best advantage in real world applications to prevent stroke in children with SCD. PUBLIC HEALTH RELEVANCE: The goal of this investigation is to obtain and analyze information that can improve the quality of care for children and young adults with sickle cell disease especially in the area of preventing stroke. The analysis of information will directly influence guidelines for TCD screening. These qualitative data will also provide insight into the value of competing therapies as well as the impact of treatment options and stroke events, and ultimately provide information to help prevent devastating stroke in young persons with Sickle Cell Disease.