High-Impact Chronic Pain in Sickle Cell Disease

镰状细胞病中的高影响慢性疼痛

• 批准号: 10993987
• 负责人: Nitya Bakshi
• 金额: $ 7.23万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2024-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10993987
• 关键词: Impact; Chronic; Pain; Sickle; Cell

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.

项目总结/摘要 慢性疼痛（CP）是镰状细胞病（SCD）发病和生活质量差的主要原因。CP， 定义为“过去6个月大部分时间疼痛”，是发病和不良反应的主要原因。 SCD患者的健康相关生活质量（HRQoL）。CP的影响是可变的，有些人 经历严重的，致残性疼痛和疼痛干扰日常活动，而其他人则经历CP 没有活动限制。高冲击性慢性疼痛（HICP），定义为慢性疼痛伴残疾，代表 患有CP的严重影响的亚组，尚未在SCD中表征，这代表了一个关键的 知识差距。在候选人的K23奖，她发现了令人信服的证据，存在严重的- 镰状细胞性贫血疼痛流行病学研究（PiSCES）中受影响的CP亚组， SCD疼痛研究。为了在临床环境中更好地研究SCD中的HICP， 治疗性造血细胞移植（HCT）被正式筛查HICP，因为HICP已被添加为 2019年HCT治疗SCD临床试验入选标准。通过确定HICP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”，这是一组定义的和可复制的数据元素，可以使用 用于在未来的研究中自动识别EHR中的HICP。这一独特的SCD和HICP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 几年来HICP疼痛发作频率的轨迹。对儿童HICP的研究表示赞赏 通过SCD，候选人还将对PiSCES数据进行二次分析，以描述结果 在患有类似于HICP的CP的成人中，即患有严重或频繁疼痛干扰的患者，并确定 严重或频繁疼痛干扰的预测因子（目标2）。这些目标的完成将是 SCD中HICP的表型，其对结果的影响，并制定一个计算原型草案 表型来从EHR中识别具有HICP的个体。候选人的初步调查结果和获得 独特的现有队列为研究SCD中的HICP提供了前所未有的机会， 知识差距。该提案是候选人K23奖的一个新的但相关的扩展，这些关键 初步数据将直接告知候选人的R 01提案，使她成为一个成功的， SCD慢性疼痛的独立研究者。