A Multi-Center Group to Study Acute Liver Failure in Children

研究儿童急性肝衰竭的多中心小组

基本信息

批准号：
8328975
负责人：
ROBERT H SQUIRES
金额：
$ 373.12万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-15 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8328975
关键词：
Acute Liver Failure Adrenal Cortex Hormones Benefits and Risks Biochemical Biological Markers Cessation of life Characteristics Child Childhood Classification Clinical Clinical Trials Clinical Trials Design Collaborations Complex Computer Simulation Computers Conduct Clinical Trials Coupled Data Decision Making Diagnosis Diagnostic Disease Disease Progression Enrollment Ensure Etiology Event Foundations Functional disorder Genomics Goals Heterogeneity Immune Immunologic Markers Immunologics Infant Inflammatory Informatics Intervention Knowledge Liver Regeneration Medical Mental Depression Methodology Modeling Monitor National Institute of Diabetes and Digestive and Kidney Diseases Natural Killer Cells Nature Nervous System Trauma Neurocognitive Organ Organ Donations Outcome Patients Phase II Clinical Trials Phenotype Physiological Policies Post-Traumatic Stress Disorders Process Proteomics Randomized Controlled Trials Recovery Registries Research Research Infrastructure Resources Risk Severity of illness Simulate Site Statistical Models Structure Systems Biology Techniques Testing Therapeutic Uncertainty United States National Institutes of Health Universities Variant Work analog base cohort complex biological systems cytokine data modeling design experience health related quality of life immunoregulation improved liver transplantation metabolomics novel organ allocation outcome forecast patient oriented phase 2 study prospective treatment strategy

项目摘要

Our goal is to improve short- and long-term outcomes for pediatric acute liver failure (PALF) through a better understanding of patient phenotypes, reassessment of risk classifications, and associating early events to outcome at one year. We will integrate two research efforts (Vodovotz-3U01 DK- 072146-05S1 and Roberts-1R21DK084201-01) currently collaborating with the PALF Study Group (NIH/NIDDK U01 DK072146-05) which are (1) modeling PALF as a complex biological system using physiological and inflammatory biomarkers and (2) developing models to represent the liver transplant (LT) decisions In PALF. To examine our hypotheses that clinical, biochemical, genomic, proteomic, metabolomic, immunologic, and cytokine analyses in PALF can be used to accurately define phenotypes that respond favorably to directed therapy (e.g., immunomodulation) as well as predict disease progression, including potential for spontaneous recovery or risk of death, all of which will provide a platform on which computer/informatics-based (e.g., in silico) studies can inform the design and conduct of clinical trials, and evaluate the impact of therapeutic decisions, including LT; we propose these Aims: Aim 1: To comprehensively characterize PALF phenotypes utilizing traditional clinical, biochemical, diagnostic, and management profiles supplemented by immune. Inflammatory and liver regeneration markers to identify factors that explain variations in outcomes for PALF phenotypes. Outcomes Include survival, LT, neurocognitive function, health-related quality of life (HRQOL), depression and post-traumatic stress disorder (PTSD) 6 months and 1 year after enrollment. Aim 2: To model the dynamics of PALF within and between distinct phenotypes using serially collected clinical, physiological, and biomarker data. Statistical modeling techniques will be augmented with models used to represent complex biological systems to more accurately reflect the dynamic nature of PALF. The data and models will be utilized to create a computer-based or "in silico" analog of PALF to simulate interventional studies and to assess treatment, including LT decision processes and to estimate the impact of improved decision-making on organ allocation.

我们的目标是通过更好地了解患者表型、重新评估风险分类以及将早期事件与一年的结果相关联，改善儿科急性肝衰竭 (PALF) 的短期和长期结果。我们将整合目前与 PALF 研究组 (NIH/NIDDK U01 DK072146-05) 合作的两项研究工作 (Vodovotz-3U01 DK-072146-05S1 和 Roberts-1R21DK084201-01)，它们 (1) 将 PALF 建模为一个复杂的生物系统使用生理和炎症生物标志物以及（2）开发代表肝移植的模型(LT) PALF 中的决定。为了检验我们的假设，即 PALF 中的临床、生化、基因组、蛋白质组学、代谢组学、免疫学和细胞因子分析可用于准确定义对定向治疗（例如免疫调节）有利的表型，并预测疾病进展，包括潜在的疾病进展。自然恢复或死亡风险，所有这些都将提供一个平台，在该平台上基于计算机/信息学（例如计算机）的研究可以为临床试验的设计和实施提供信息，以及评估治疗决策的影响，包括 LT；我们提出以下目标：目标 1：利用传统的临床、生化、诊断和管理特征并辅以免疫来全面表征 PALF 表型。炎症和肝再生标记物可识别解释 PALF 表型结果变化的因素。结果包括入组后 6 个月和 1 年内的生存率、LT、神经认知功能、健康相关生活质量 (HRQOL)、抑郁症和创伤后应激障碍 (PTSD)。目标 2：使用连续收集的临床、生理和生物标志物数据来模拟不同表型内和不同表型之间 PALF 的动态。统计建模技术将通过用于表示复杂生物系统的模型得到增强，以更准确地反映 PALF 的动态性质。这些数据和模型将用于创建基于计算机或“计算机模拟”的 PALF 模拟，以模拟介入研究并评估治疗，包括 LT 决策过程，并估计改进决策对器官分配的影响。