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卒中综合预防策略。虽然TCD筛查和预防性输血策略在镰状细胞性贫血卒中预防（STOP试验）中非常有效，并且即使在输血30个月或更长时间（STOP II）后停止这种治疗，也会观察到高风险或卒中的逆转，但尚不清楚该方法在试验完成后在现实世界中的有效性。通过深入分析研究参与者在试验后期关于卒中预防行为（重新筛查TCD和输血）和卒中以及其他重要结果的医疗记录，该项目利用了巨大的财力和人力资源，获得了超过3400名儿童的STOP和STOP II数据及其结果数据库（可供调查者使用）。两个结果是最重要的：1)中风——在这方面是在试验失败后发生的中风（没有TCD或不适当的时机或不遵守筛查计划）或治疗失败（不推荐或接受输血或突破性中风，尽管遵守了适当的输血），以及如何最好地利用这些信息来改善中风预防措施；2)向高风险TCD转化。数据库包含3000多个儿童的初步（异常前）TCD数据，并根据在试验期间的重新筛选从STOP发布了转换概率。在临床实践中对试验后进行不同程度的再筛查，并在试验后发现新的异常；预测异常TCD发生率的试验后模型是否证实了STOP，还是与STOP中观察到的结果有很大差异？在这两种情况下，试验后的经验将与STOP数据相结合，以制定更强有力的基于证据的临床指南，用于TCD再筛查（如果第一次TCD不表明需要治疗），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，将研究过渡到成人提供者系统对卒中预防的影响，评估态度，并将这些数据用于为进一步的研究和教育提供建议。总的来说，该项目提供了大量的新信息，将确保STOP和STOP II的主要投资在预防SCD儿童中风的实际应用中发挥最大的优势。公共卫生相关性：本研究的目的是获取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。对信息的分析将直接影响TCD筛查的指导方针。这些定性数据还将深入了解竞争性疗法的价值，以及治疗方案和卒中事件的影响，并最终提供信息，帮助预防镰状细胞病年轻人的毁灭性卒中。

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.