Improving Pain in Sickle Cell Patients With Targeted Antithrombotic Therapy

 描述(申请人提供)：镰状细胞病(SCD)是一种慢性溶血性疾病，以反复发生血管闭塞发作(VOC)和进行性器官损害为特征。它在很小的时候就发作了，临床过程中不时会出现痛苦的致残危机，但治疗选择很少。一旦患者出现VOC，干预仅限于缓解疼痛；目前还没有治疗方法可以改变VOC的进程。因此，需要努力评估潜在的治疗干预措施并确定潜在的影响。我的研究工作集中在儿童和成人SCD患者身上，有一个明确的目标，即通过创新技术测量凝血状态，并确定潜在的治疗方案。我最近完成了一项小型先导性研究，评估了因VOC而入院的SCD患者的预防性抗凝剂量。我发现疼痛评分的绝对降幅更大，患者自控止痛的时间更短，这两项都需要进一步研究。现在，我已经准备好检查每天服用一种口服Xa因子抑制剂的效果，以减轻慢性日常疼痛和高凝状态。结果将包括每日疼痛评分、患者报告的结果和高凝标志物。为了全面评估SCD患者疼痛的影响，我将使用患者报告结果测量信息系统(PROIS)，这是一份计算机化的适应性问卷，以评估疲劳、身体功能和疼痛影响。疼痛评分将通过Sickle cell移动应用程序记录，并通过科技(智能)应用程序记录症状。这款智能应用程序是由我的研究小组开发的，用于跟踪症状并提高服药依从性。为了顺利完成这项研究，我与凝血和SCD领域的领导者建立了坚实的导师关系，此外还组建了一个科学顾问委员会，以促进进一步的专业知识和洞察力。我还将继续完成获得临床研究硕士学位所需的课程，以加强我在临床研究方法学方面的背景。这个奖项的支持将为我提供机会，让我获得必要的经验、教学培训和指导，成为一名成功的、独立的血液学研究人员。重要的是，它还将为我在学术医学的长期职业生涯建立一个框架；进行创新研究，评估SCD患者的新型治疗药物。

 DESCRIPTION (provided by applicant): Sickle cell disease (SCD) is a chronic hemolytic disorder characterized by recurrent vaso-occlusive episodes (VOC) and progressive organ damage. It strikes at a young age, with a clinical course punctuated by painful disabling crises, yet treatment options are few. Once patients develop VOC, intervention is limited to pain alleviation; no therapy is currently available to alter the course of VOC. Therefore, efforts are needed to evaluate potential therapeutic interventions and determine the potential impact. My research efforts have focused on pediatric and adult patients with SCD, with a specific goal of measuring coagulation by innovative technologies and determining potential therapeutic options. I recently completed a small pilot study evaluating prophylactic dose anticoagulation for patients with SCD admitted for VOC. I found a greater absolute decrease in pain scores and shorter time on patient controlled analgesia, both arguing for further investigations. I now have positioned myself to examine the effect of an oral factor Xa inhibitor administered daily to decrease chronic daily pain and hypercoagulability. Outcomes will include daily pain scores, patient reported outcomes and hypercoagulable markers. To provide a comprehensive evaluation of the impact of pain in patients with SCD, I will use Patient Reported Outcome Measurement Information System (PROMIS), a computerized adaptive questionnaire, to evaluate fatigue, physical function and pain impact. Pain scores will be recorded through the Sickle cell Mobile Application to Record symptoms via Technology (SMART) app. The SMART app was developed by my research group to track symptoms and improve medication adherence. To allow successful completion of the study, I have established solid mentorship with the leaders in coagulation and SCD, in addition to assembling a scientific advisory board to promote further expertise and insight. I will also pursue completion of coursework required to obtain a Masters in Clinical Research, to strengthen my background in clinical research methodology. Support from this award will provide the opportunity for me to gain the necessary experience, didactic training, and mentorship to become a successful and independent researcher in hematology. Importantly, it will also build a framework for my long-term career in academic medicine; performing innovative research evaluating novel therapeutic agents in patients with SCD.