Investigating Pathways to Medication (Non)Adherence in Adolescent Solid Organ Transplant Patients

项目总结/摘要 免疫抑制（IS）药物不依从性是一个健康管理问题， 实体器官移植（SOT）受者的后果，使他们住院的风险增加 （1，2）、排斥反应（2-4）、移植物丢失和死亡率（1，4 -6）。不依从的风险在青春期达到峰值（7-10）， 使这一发展阶段成为干预的关键时期。已经进行了大量的研究工作， 改善依从性;然而，已发表的干预措施通常未显示出改善的临床结局 （十一）、为了解决这一差距，本申请提出了一个通过多个收集的数据的二次分析， 儿童器官移植临床试验联合会第11号协议（CTOT-C-11）：“患病率和 青少年实体器官移植受者创伤后应激症状（PTSS）的相关性。 CTOT-C-11是目前最大的青少年SOT接受者队列。的主要目的 一项拟议的研究是比较依从性（A）、轻度非依从性（B）和轻度非依从性（C）患者的人口统计学和社会心理特征。 (MA)和严重不依从（SA）的青少年SOT接受者，并确定风险模式， 有针对性的依从性干预和治疗手册。将使用药物测量依从性 水平变异性指数（MLVI），IS依从性的稳健生物标志物。假设患者/移植物 特征（PTSS、抑郁症状、性别、年龄、移植类型、保险状况）和父母因素 (PTSS、教育、婚姻状况）与坚持的联系和相互联系存在差异 水平（A、MA、SA）。也有人假设，症状严重程度或特征水平将预测 患者的依从性分类（例如，MA患者的PTSS高于A患者，但PTSS较低 与患者相比）。探索性分析将研究A、MA和SA患者的特征如何 与移植结局相关（即CTOT-C-11定义的排斥/移植失败）。这个项目将达到高潮 在制定干预和治疗手册，旨在提高坚持。的分析 主要目标中所述的方法将用于将干预成分针对特定的依从性水平 （A、MA和SA）-尚未在该人群中尝试的方法。本拟议项目旨在 提高对不依从行为的理解，以加强可用于 因此，我们可以帮助临床医生，从而更广泛地促进SOT接受者和慢性病人群的健康。 拟议的研究金培训计划将为申请人提供深入的函授培训 分析[分类数据的高级统计方法（12）]，干预开发和治疗 手工书写。培训将在纽约市的研究机构福德姆大学进行， 西奈山伊坎医学院，也是纽约市的一个学术医学教学机构。两者都将提供 为拟议的培训活动和专业发展机会提供实质性支持， 准备申请人成为一个成功的贡献者干预科学和行为健康。

PROJECT SUMMARY/ABSTRACT Immunosuppressive (IS) medication nonadherence is a health management problem with dire consequences for solid organ transplant (SOT) recipients, placing them at increased risk for hospitalization (1,2), rejection (2–4), graft loss, and mortality (1,4–6). The risk for nonadherence peaks in adolescence (7–10), making this developmental stage a critical time for intervention. Significant research efforts have been made to improve adherence; yet, published interventions have generally not demonstrated improved clinical outcomes (11). To address this gap, this application proposes a secondary analysis of data collected through the multi- site Clinical Trials in Organ Transplantation in Children consortium’s Protocol 11 (CTOT-C-11): “Prevalence & Correlates of Post-Traumatic Stress Symptoms (PTSS) in Adolescent Solid Organ Transplant Recipients.” CTOT-C-11 is the largest currently established cohort of adolescent SOT recipients. The primary aim of the proposed study is to compare demographic and psychosocial profiles of adherent (A), mildly nonadherent (MA), and severely nonadherent (SA) adolescent SOT recipients and identify patterns of risk to create a targeted adherence intervention and treatment manual. Adherence will be measured using the Medication Level Variability Index (MLVI), a robust biomarker of IS adherence. It is hypothesized that patient/transplant characteristics (PTSS, depressive symptoms, sex, age, transplant type, insurance status) and parental factors (PTSS, education, marital status) will have differential associations and interconnections with the adherence levels (A, MA, SA). It is also hypothesized that degree of symptom severity or characteristic level will predict patients’ adherence class (e.g. MA patients will have higher PTSS compared to A patients, but lower PTSS compared to SA patients). Exploratory analyses will investigate how the profiles of A, MA, and SA patients are related to transplant outcomes (i.e. rejection/graft failure as defined by CTOT-C-11). This project will culminate in the development of an intervention and treatment manual designed to improve IS adherence. The analyses described in the primary aim will be used to target the intervention components to specific levels of adherence (A, MA, and SA) – an approach that has not been tried in this population. This proposed project seeks to advance the understanding of nonadherence behavior in order to strengthen the interventions available to clinicians and thereby promote the health of SOT recipients and chronically ill populations more broadly. The proposed fellowship training plan would provide the applicant in-depth training in correspondence analysis [an advanced statistical method for categorical data (12)], intervention development, and treatment manual writing. This training will take place at Fordham University, a research institution in New York City, and Icahn School of Medicine at Mount Sinai, an academic medical teaching facility also in NYC. Both will provide substantial support for the proposed training activities as well as professional development opportunities to prepare the applicant to become a successful contributor to intervention science and behavioral health.