Multiple Medical Therapies for Pediatric TBI; Comparative Effectiveness Approach

儿童创伤性脑损伤的多种药物治疗；

基本信息

批准号：
8689194
负责人：
MICHAEL J BELL
金额：
$ 348.18万
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：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8689194
关键词：
Acute Adult Affect Age Carbon Dioxide Caring Cause of Death Centers for Disease Control and Prevention (U.S.)Cerebrospinal Fluid Cessation of life Child Child Care Child Welfare Child health care Clinical Cohort Studies Confounding Factors (Epidemiology)Data Data Collection Databases Detection Diet Drainage procedure Effectiveness Energy Intake Failure Future Geographic state Glasgow Coma Scale Glucose Guidelines Healed Health Hyperventilation Hypoxia Immune Injury International Intervention Intracranial Hypertension Intracranial Pressure Investigation Lead Life Literature Mannitol Measures Medical Metabolic Metabolism Monitor Nutritional Support Outcome Oxygen Patient Self-Report Patients Pharmacologic Substance Prevention Protocols documentation Publishing Randomized Controlled Trials Recommendation Regression Analysis Reporting Research Research Design Risk Saline Site Solutions Statistical Models Steroid therapy Steroids Testing Therapeutic Therapeutic Agents Time Translating Traumatic Brain Injury Uncertainty Variant administrative database base blood glucose regulation brain tissue burden of illness clinical care clinical practice clinical research site comparative effectiveness compare effectiveness cost design effectiveness research evidence based guidelines experience healing hypertension control hypertension treatment improved mortality natural hypothermia novel novel strategies novel therapeutics pediatric traumatic brain injury prophylactic prospective public health relevance standard of care treatment effect treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is the leading killer of children with over 7000 deaths reported in the US in 2005. In addition to this loss of life, the yearly costs of TBI on the health and welfare of children in the US is over $2 billion for acute care along and more than a million life-years are potentially at risk. Advances in care for children with severe TBI have been disappointingly slow. Randomized controlled trials (RCTs) of novel therapeutic agents and approaches have universally failed when applied in multiple centers. Evidenced-based guidelines are not sufficiently robust to generate meaningful recommendations because the literature has failed to demonstrate best practices for most aspects of TBI care. Variations in practices such as intracranial hypertension control, mitigation of secondary insults and metabolic support are substantial in contemporary clinical practice, leading to wide variations in patient outcomes and may ultimately overwhelm treatment effects that might be observed in a well-designed RCT. We propose an observational cohort study of 1000 children with severe TBI to compare the effectiveness of pediatric TBI therapies within an international consortium from the US, UK and EU. We will test 3 specific aims that encompass a total of 6 TBI therapies - (i) intracranial hypertension strategies - cerebrospinal fluid diversion and hyperosmolar therapies; (ii) secondary insult detection - prophylactic hyperventilation and brain tissue oxygen monitoring (PbO2); (iii) metabolic support - nutritional support and glucose management. Several statistical approaches, often used in comparative effectiveness research (CER) to control for confounders, will be employed including propensity score adjustments, regression analyses and novel statistical modeling. Successful completion of this proposal would provide compelling evidence to change clinical practices, provide evidence for several new recommendations for future guidelines and lead to improved research protocols that would be limit variability in TBI treatments - helping children immediately through better clinical practices and ultimately through more effective investigation.

描述（由申请人提供）：创伤性脑损伤 (TBI) 是儿童的头号杀手，2005 年美国报告有超过 7000 人死亡。除了生命损失之外，每年 TBI 还给儿童的健康和福利造成损失在美国，用于急性护理的资金超过 20 亿美元，超过 100 万生命年可能面临风险。严重创伤性脑损伤儿童的护理进展缓慢得令人失望。新型治疗药物和方法的随机对照试验（RCT）在多个中心应用时普遍失败。循证指南不足以产生有意义的建议，因为文献未能证明 TBI 护理大多数方面的最佳实践。在当代临床实践中，诸如颅内高压控制、减轻继发性损伤和代谢支持等实践的差异很大，导致患者结果存在很大差异，并可能最终压倒在精心设计的随机对照试验中可能观察到的治疗效果。我们提议对 1000 名患有严重 TBI 的儿童进行一项观察性队列研究，以比较来自美国、英国和欧盟的国际联盟内儿童 TBI 治疗的有效性。我们将测试 3 个具体目标，总共包含 6 种 TBI 疗法 - (i) 颅内高压策略 - 脑脊液改道和高渗疗法； (ii) 二次损伤检测——预防性过度换气和脑组织氧监测（PbO2）； (iii) 代谢支持——营养支持和血糖管理。将采用几种统计方法，通常用于比较有效性研究（CER）中以控制混杂因素，包括倾向评分调整、回归分析和新颖的统计模型。该提案的成功完成将为改变临床实践提供令人信服的证据，为未来指南的几项新建议提供证据，并改进研究方案，限制 TBI 治疗的变异性——立即通过更好的临床实践并最终通过更有效的方法帮助儿童调查。