High-Impact Chronic Pain in Sickle Cell Disease

项目摘要/摘要 慢性疼痛(CP)是镰状细胞病(SCD)发病率和生活质量下降的主要原因。CP， 定义为在过去6个月中的大部分时间内出现疼痛，是发病和不良的主要原因 精神分裂症患者的健康相关生活质量CP的影响是可变的，有些人 经历严重的、致残的疼痛和日常活动中的疼痛干扰，而其他人则经历CP 没有活动限制。高冲击性慢性疼痛(HICP)，定义为慢性残疾疼痛，代表 受严重影响的子组，其CP尚未在SCD中表现出特征，这代表着一种关键的 知识鸿沟。在候选人的K23奖项中，她发现了令人信服的证据，证明存在严重的- 最大的自然史上最大的镰刀细胞流行病学研究(PISCES)中CP的影响亚群 SCD的疼痛研究。为了在临床环境中更好地研究慢性阻塞性肺疾病中的HICP，寻求咨询的患者 治疗性造血细胞移植(HCT)被正式筛查为HICP，因为HICP已被添加为 2019年SCD中HCT临床试验纳入标准。通过确定HICP在本组的临床相关性 现有队列(目标1)，候选人将开发电子健康记录(EHR)的原型草案- 派生的“计算表型”，它是一组定义的、可重复使用的数据元素 以便在未来的研究中从EHR中自动识别HICP。这一独特的与SCD和HICP的队列将 结合现有的纵向EHR数据进行研究，允许候选人探索纵向 HICP数年间疼痛发作频率的变化轨迹。对儿童HICP研究的赞誉 对于SCD，应聘者还将对双鱼座的数据进行二次分析，以确定结果 在患有类似HICP的CP的成人中，即那些有严重或频繁疼痛干扰的人，并确定 严重或频繁疼痛干扰的预测因素(目标2)。这些目标的完成将成为 SCD中HICP的表型及其对预后的影响，并开发了一个计算原型的草案 从EHR中识别HICP患者的表型。候选人的初步调查结果和访问权限 独特的现有队列提供了前所未有的机会来研究SCD的HICP，解决了一个主要的 知识鸿沟。这项提议是候选人K23奖励的新的但相关的扩展，这些关键 初步数据将直接通知候选人的R01提案，让她成为一名成功的， SCD慢性疼痛的独立调查者。

PROJECT SUMMARY/ABSTRACT Chronic pain (CP) is a major cause of morbidity and poor quality of life in sickle cell disease (SCD). CP, defined as the presence of ‘pain on most days of the past 6 months’, is a major cause of morbidity and poor Health Related Quality of Life (HRQoL) in SCD. The impact of CP is variable, with some individuals experiencing severe, disabling pain and pain interference with daily activities, while others experience CP without activity limitations. High-Impact Chronic Pain (HICP), defined as chronic pain with disability, represents a severely-impacted sub-group with CP that has not been characterized in SCD, which represents a critical knowledge gap. In the candidate’s K23 award, she found compelling evidence for the presence of a severely- affected subgroup of CP in the Pain in Sickle Cell Epidemiology Study (PiSCES), the largest natural history study of pain in SCD. To better study HICP in SCD in the clinical setting, patients seeking consultation for curative hematopoietic cell transplant (HCT) were formally screened for HICP, as HICP had been added as an inclusion criteria for clinical trials of HCT in SCD in 2019. By identifying the clinical correlates of HICP in this existing cohort (Aim 1), the candidate will develop a draft prototype for an electronic health record (EHR)- derived “computational phenotype”, which is a defined and reproducible set of data elements that can be used for automated identification of HICP from the EHR in future studies. This unique cohort with SCD and HICP will be studied in conjunction with existing longitudinal EHR data allowing the candidate to explore longitudinal trajectories of pain episode frequency in HICP over several years. To compliment the study of HICP in children with SCD, the candidate will also perform a secondary analyses of the PiSCES data to characterize outcomes in adults with CP analogous to HICP, i.e. those with severe or frequent pain interference, and identify predictors of severe or frequent pain interference (Aim 2). The completion of these aims will characterize the phenotype of HICP in SCD, its impact on outcomes, and develop a draft prototype of a computational phenotype to identify individuals with HICP from the EHR. The candidate’s preliminary findings and access to unique existing cohorts provide unprecedented opportunities to investigate HICP in SCD, addressing a major knowledge gap. This proposal is a new but related extension of the candidate’s K23 award, and these key preliminary data will directly inform the candidate’s R01 proposal, allowing her to becoming a successful, independent investigator in chronic pain in SCD.