Pediatric TBI Treatments: Optimal Timing, Targets, and Patient Characteristics.

摘要 儿童创伤后行为问题的社会心理治疗的证据基础 脑损伤（TBI）受到控制不良的设计和小且异质的样品的限制。 然而，我们小组进行的一系列试点随机临床试验（RCT）和四项更大的多中心RCT， 强调了以家庭为中心的治疗（在线家庭问题解决（OFPS）和 在线父母技能培训（OPST）），以减少行为问题，执行功能障碍和照顾者 小儿创伤性脑损伤后的痛苦对这些研究的综合数据进行创新性的联合分析， 开发和测试治疗效果模型的统计功效，包括个体、损伤和 社会环境特征以及治疗依从性。我们建议进行第二次 对2001年至2015年期间进行的8项RCT的数据分析，涉及767名3岁以下儿童 和19岁，因复杂的轻度至重度TBI住院过夜。成果进行了评估 所有研究均为治疗前和6个月后，其中几项研究评估了治疗的维持 治疗完成后3 - 6个月随访时间点的效果。父母完成了对孩子的测量 行为问题和执行功能行为。年龄较大的儿童完成自我报告的措施， 抑郁、行为和执行功能。父母也完成了照顾者痛苦的评级， 抑郁症和家庭功能还收集了关于治疗依从性、接受其他 为所有参与者提供治疗和学校服务。我们将采用现代纵向多重插补 在联合跨研究分析之前协调跨研究测量的模型，以解决以下问题 目的：1）检查损伤后时间与治疗反应的关系; 2）检查 患者特征和发病前状况（例如，ADHD，LD）治疗反应; 3）确定哪些 儿童行为的各个方面（内化、外化、执行功能技能）对这种影响最为敏感 OFPS和OPST;以及4）开发随时间推移的行为恢复预测因子的综合模型 将治疗效果与其他康复疗法沿着。分析模型， 综合所有八项研究将采用混合效应来捕获跨研究变异性，并将包括 纵向相关性、非线性平均值和特征总结（如适用），以确定治疗效果 和治疗效果异质性。调查结果将提供有关如何优化和 为创伤后行为问题量身定制以家庭为中心的治疗。这也将加强我们对 儿童TBI后行为恢复的轨迹，并使我们能够确定 对复苏最为敏感。鉴于儿童TBI随机对照试验的固有困难和频繁失败， 拟议的项目有可能为儿童TBI的个性化管理提供信息， 把场地向前推。

Abstract The evidence base regarding psychosocial treatment for behavior problems that arise after pediatric traumatic brain injury (TBI) has been limited by poorly controlled designs and small and heterogeneous samples. However, a series of pilot randomized clinical trials (RCT) and four larger, multi-site RCTs by our group have underscored the potential promise of family-centered treatments (Online Family Problem Solving (OFPS) and Online Parent Skills Training (OPST)) in reducing behavior problems, executive dysfunction, and caregiver distress following pediatric TBI. Innovative joint analyses of combined data from these studies would provide the statistical power to develop and test models of treatment effects that incorporate individual, injury, and social environmental characteristics together with treatment adherence. We propose to conduct secondary data analyses of eight RCT conducted between 2001 and 2015 involving 767 children between the ages of 3 and 19 years who were hospitalized overnight for complicated mild to severe TBI. Outcomes were assessed pre-treatment and 6 months later in all studies, with several of the studies assessing maintenance of treatment effects at follow-up time points 3-6 months after treatment completion. Parents completed measures of child behavior problems and executive function behaviors. Older children completed self-report measures of depression, behavior, and executive functioning. Parents also completed ratings of caregiver distress, depression, and family functioning. Data were also collected on adherence to treatment, receipt of other treatments, and school services for all participants. We will employ modern longitudinal multiple imputation models to harmonize measurements across studies prior to joint cross-study analysis to address the following aims: 1) examine the association of time since injury with treatment response; 2) examine the relationship of patient characteristics and premorbid conditions (e.g., ADHD, LD) to treatment response; 3) Identify which aspects of child behavior (internalizing, externalizing, executive function skills) are most sensitive to the effects of OFPS and OPST; and 4) Develop a comprehensive model of predictors of behavioral recovery over time that incorporates the effects of treatment along with other rehabilitative therapies. Analysis models that synthesize all eight studies will employ mixed effects to capture cross-study variability, and will include longitudinal correlations, nonlinear means, and profile summaries as appropriate to identify treatment effects and treatment effect heterogeneity. Findings will provide important new information about how to optimize and tailor family-centered treatments for post-TBI behavior problems. It will also enhance our understanding of trajectories of behavioral recovery following pediatric TBI and allow us to identify measures/subscales that are most sensitive to recovery. Given the inherent difficulty and frequent failure of RCTs for pediatric TBI, the proposed project has the potential to inform individualized management of pediatric TBI and substantively move the field forward.