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联系起来，以改善小儿急性肝衰竭（PALF）的短期和长期结果。我们将整合两项研究工作（Vodovotz-3U01 DK-072146-05S1和Roberts-1R21DK084201-01），目前与PALF研究小组（NIH/NIDDK U01 DK072146-05）合作（使用Pallf unigogication and Pallf pallf pallf and（1），（1）使用Pallf Pallf pallf，（1）与Pallf Indorgication and Pallf and（1），（1）具有复杂的生物学模型（1）代表PALF中的肝移植（LT）决定。为了研究我们的假设，即PALF中的临床，生化，基因组，蛋白质组学，蛋白质组学，代谢组学和免疫学和细胞因子分析可用于准确定义对有方向的治疗响应的表型，这些表型对有方向的治疗响应（例如，用于疾病的潜在疾病，包括疾病的可能性，都可以在适用于疾病的可能性上，这些疾病的可能性（例如，对自发性恢复的可能性），该疾病的潜在均可响应。（例如，在计算机中）研究可以为临床试验的设计和行为提供信息，并评估包括LT在内的治疗决定的影响；我们提出了这些目的：目标1：使用传统的临床，生化，诊断和管理概况，以全面表征PALF表型，并补充了免疫。炎症和肝脏再生标记以识别解释PALF表型结果变化的因素。结果包括生存，LT，神经认知功能，与健康相关的生活质量（HRQOL），抑郁症和创伤后应激障碍（PTSD）6个月零1年。目标2：使用串行收集的临床，生理和生物标志物数据对PALF内部和不同表型之间的动力学进行建模。统计建模技术将通过用于代表复杂生物系统的模型来增强，以更准确地反映PALF的动态性质。数据和模型将用于创建基于计算机的PALF中的计算机或“中”类似物，以模拟介入研究并评估治疗，包括LT决策过程，并估算改进决策对器官分配的影响。