Biologic Mechanisms and Dosing of Active Music Engagement to Manage Acute Treatment Distress and Improve Health Outcomes in Young Children with Acute Lymphoblastic Leukemia and Parents

项目摘要 音乐疗法已成为许多儿科和成人医院的标准姑息治疗服务。但 大多数音乐治疗研究都集中在使用音乐来改善心理社会方面， 健康，不考虑生物因素。此外，很少有研究检查剂量反应 关系。癌症治疗是一种内在的压力体验，许多年轻人 儿童和父母（照顾者）经历持续的、相互关联的情绪困扰和生活质量差。 许多父母也会因为孩子的癌症诊断而经历创伤性应激症状， 治疗我们之前测试的主动音乐参与（AME）干预使用主动音乐播放， 减少癌症治疗的压力属性，以帮助管理患者经历的情绪/创伤性痛苦。 幼儿（3-8岁）和父母，提高生活质量。最近的一项AME试验正在研究心理社会学 负责改变儿童/父母结果的行动机制。目前的研究扩展了这一点 通过检查AME对几种生物标志物的影响， 积极的音乐干预有助于缓解癌症相关的压力，并有可能改善免疫功能。 这两组随机对照试验的目的是检查作用的生物学机制， 急性期巩固期AME对儿童/父母应激的剂量-反应关系 淋巴细胞白血病（ALL）治疗。具体目标是：（1）确定AME是否降低儿童和 父母皮质醇，2）检查皮质醇作为AME对儿童和父母结果影响的中介，以及3） 检查AME对儿童和父母皮质醇的剂量反应关系。儿童/父母二人组（n=228）将 分层（按年龄、部位、ALL风险水平），并随机分为4个区组，分别接受AME或注意力控制。每个 在ALL巩固期间，一组患者将在每周门诊访视期间接受一次45分钟的治疗（4 8周标准风险; 8周高风险）。父母将在基线和最后一次测量后完成测量 学习会。前4个AME将在治疗前后采集儿童和父母唾液皮质醇样本 或注意力控制会议。在第1阶段之前，将从常规抽血中保留儿童血样 和4（所有参与者）和会议8（高风险参与者）。线性混合模型将用于估计 AME对儿童和父母皮质醇的影响。检查儿童和父母皮质醇作为AME影响的介质， 将在ANCOVA设置中执行儿童和父母结局，以拟合适当的中介模型 使用MPlus，然后使用百分位数自助法测试间接效应，以估计间接效应。 效果将使用图形图和非线性重复测量模型检查剂量-效应 AME与儿童和父母皮质醇的关系。研究结果将增加对 积极的音乐干预对多种生物标志物的影响以及对剂量反应效应的理解， 直接影响基于证据的音乐使用，以改善健康。

PROJECT SUMMARY Music therapy has become a standard palliative care service in many pediatric and adult hospitals. However, a majority of music therapy research has focused on the use of music to improve psychosocial dimensions of health, without considering biological dimensions. In addition, few studies have examined dose-response relationships. Cancer treatment is an inherently stressful experience, and a significant number of young children and parents (caregivers) experience persistent, interrelated emotional distress and poor quality of life. Many parents also experience traumatic stress symptoms because of their child's cancer diagnosis and treatment. Our previously tested Active Music Engagement (AME) intervention uses active music play to diminish stressful attributes of cancer treatment to help manage emotional/traumatic distress experienced by young children (ages 3-8) and parents and improve quality of life. A recent AME trial is examining psychosocial mechanisms of action responsible for change in child/parent outcomes. The current study expands on this work by examining AME's effects on several biomarkers to povide a more holistic understanding about how active music interventions work to mitigate cancer-related stress and its potential to improve immune function. The purposes of this two group, randomized controlled trial are to examine biological mechanisms of effect and dose-response relationships of AME on child/parent stress during the consolidation phase of Acute Lymphoblastic Leukemia (ALL) treatment. Specific aims are to: 1) establish whether AME lowers child and parent cortisol, 2) examine cortisol as a mediator of AME effects on child and parent outcomes, and 3) examine the dose-response relationship of AME on child and parent cortisol. Child/parent dyads (n=228) will be stratified (by age, site, ALL risk level) and randomized in blocks of four to AME or attention control. Each group will receive one 45-minute session during weekly clinic visits for the duration of ALL consolidation (4 weeks standard risk; 8 weeks high risk). Parents will complete measures at baseline and following the last study session. Child and parent salivary cortisol samples will be taken pre and post-session for the first 4 AME or attention control sessions. Child blood samples will be reserved from routine blood draws prior to sessions 1 and 4 (all participants) and session 8 (high risk participants). Linear mixed models will be used to estimate AME's effect on child and parent cortisol. Examining child and parent cortisol as mediators of AME effects on child and parent outcomes will be performed in an ANCOVA setting, fitting the appropriate mediation models using MPlus and then testing indirect effects using the percentile bootstrap approach to estimate the indirect effect. Graphical plots and non-linear repeated measures models will be used to examine the dose-response relationship of AME on child and parent cortisol. Findings will increase mechanistic understanding of the effects of active music interventions on multiple biomarkers and understanding of dose-response effects, with direct implications for the evidence-based use of music to improve health.