Characterizing Disease Trajectory for Improving Treatment in Pediatric Crohn's Disease

项目摘要/摘要 克罗恩病(CD)，一种严重的慢性炎症性肠病(IBD)，曾 被认为在儿科人群中罕见，最近被认为是最重要的 影响儿童和青少年的慢性病，青少年发病率增加 年龄参差不齐。由于童年是身体、情感和社交成熟的时期，CD的发病 童年时期会严重延缓生长发育，危害心理健康，其负面影响可能 会持续一生。在目前的儿科CD研究中，疾病活动性通常是在 治疗后特定时间点的治疗比较和长期预测 结果。这些研究的结果是基于患者反应的快照， 关于疾病进展的时间性质的信息有限。此外，离散分析 未能对治疗和治疗之间的功能关系提供洞察力 生长，这是选择治疗方案所必需的，以诱导和维持缓解，同时 优化患者的成长和福祉。 为了填补这一重大空白，我们建议1)开发一系列统计工具来表征和 确定儿童CD(PCD)的疾病轨迹模式，以及2)结合时间 疾病轨迹中包含的信息，用于评估治疗和预测长期 期限结果。该项目的成果将有助于全面了解 PCD病因学，改善PCD患者的循证治疗策略，并可能 导致关于PCD优化护理标准的更好的临床实践的变化 病人。我们将利用来自PEDSnet的大量儿科人口，国家儿科 学习卫生系统，以增强研究成果和影响。这些数据来自 全国最大的八个儿科医疗系统(包括波士顿儿童医院， 费城儿童医院和辛辛那提儿童医院医疗中心)， 从2009年到2017年，总共有600多万儿童和1.5万名确诊为IBD的儿童。 此外，我们的研究产生的新知识和开源软件将是 与医疗保健提供系统实时集成，以改善医疗保健。成功 这项拟议的研究的发展有望直接影响到 PEDS网和全国范围内。

Project Summary/Abstract Crohn's disease (CD), a serious chronic inflammatory bowel disease (IBD) that was once considered rare in the pediatric population, is recently recognized as one of the most important chronic diseases that affect children and adolescents, with increasing incidence in youths of varying ages. As childhood is a time of physical, emotional, and social maturation, onset of CD in childhood can seriously delay growth, jeopardize mental health, and the negative impact may last a lifetime. In current pediatric CD research, disease activity is commonly evaluated at pre- specified time points post treatment for comparison of treatments and prediction of long-term outcomes. Findings from these studies are based on snapshots of patients' responses, with limited information on the temporal nature of disease progression. In addition, discrete analyses of disease activity fail to provide insights on functional relationship between treatment and growth, which is essential for selection of treatment to induce and maintain remission while optimizing the patient's growth and well-being. To fill this vital gap, we propose to 1) develop a series of statistical tools to characterize and identify patterns of disease trajectory of pediatric CD (PCD), and 2) incorporate the temporal information contained in disease trajectory for evaluation of treatments and prediction of long- term outcomes. The deliverables of this project will contribute to comprehensive understanding of PCD etiology, improvement of evidence-based treatment strategy for PCD patients, and may lead to changes toward better clinical practice regarding the criteria for optimized care for PCD patients. We will harness the large pediatric population from PEDSnet, a national pediatric learning health system, to empower the research findings and impacts. The data come from eight of the nation's largest pediatric health systems (including the Boston Children's Hospital, Children's hospital of Philadelphia and Cincinnati Children's Hospital Medical Center), covering more than 6 million children in total and 15 thousand with IBD diagnosis from 2009 to 2017. Furthermore, new knowledge and open-source software generated from our research will be integrated in real time with healthcare delivery systems to improve health care. Successful development of this proposed research has a promise of direct impacting the PCD patients in the PEDSnet and nationwide.