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

摘要 儿童创伤后行为问题的心理社会治疗的证据基础 脑损伤(TBI)一直受到控制不佳的设计和小样本和异质样本的限制。 然而，我们小组进行的一系列先导性随机临床试验(RCT)和四个更大的多部位RCT已经 强调以家庭为中心的治疗(在线家庭问题解决(OFP)和 在线家长技能培训(OPST))减少行为问题、执行功能障碍和照顾者 儿科颅脑损伤后的痛苦。对这些研究的综合数据进行创新性的联合分析将提供 开发和测试治疗效果模型的统计能力，包括个人、伤害和 社会环境特征与治疗依从性。我们建议进行第二次 2001年至2015年间进行的8项随机对照试验的数据分析，涉及767名3岁以下儿童 因复杂的轻重型颅脑损伤入院过夜19年。对结果进行评估 所有研究在治疗前和6个月后进行，其中几项研究评估了治疗的维持情况 治疗结束后3~6个月随访时点疗效。父母完成对孩子的测量 行为问题和执行功能行为。年龄较大的儿童完成了自我报告测量 抑郁、行为和执行功能。父母还完成了对照顾者痛苦的评估， 抑郁和家庭功能。还收集了坚持治疗、接受其他治疗的数据 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归因法 在联合交叉研究分析之前协调研究之间的测量的模型，以解决以下问题 目的：1)检查自受伤以来的时间与治疗反应的关系；2)检查 患者特征和发病前状况(如ADHD、LD)对治疗的反应；3)确定哪些 儿童行为的各个方面(内化、外化、执行功能技能)对这些影响最为敏感 OFP和OPST；以及4)开发随时间推移的行为恢复预测因素的综合模型 这将治疗的效果与其他康复疗法结合在一起。分析模型 综合所有八项研究将使用混合效应来捕捉跨研究的可变性，并将包括 识别治疗效果的纵向相关性、非线性方法和概况摘要 和治疗效果的异质性。调查结果将提供关于如何优化和 为脑外伤后的行为问题量身定做以家庭为中心的治疗方法。它还将增进我们对 儿童脑外伤后行为恢复的轨迹，并使我们能够确定以下测量/分量表 对恢复最为敏感。鉴于儿童颅脑损伤RCT的固有困难和经常失败， 拟议的项目有可能为儿童脑外伤的个性化管理提供信息，并具有实质性的意义 将该字段向前移动。

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.