Effectiveness of ICP Monitoring in Pediatric Traumatic Brain Injury

描述（由申请人提供）：这个以病人为导向的指导职业发展奖的建议，旨在支持博士的过渡。班尼特成为一个独立的临床科学家和国家领导人在定量比较有效性研究。班尼特博士是犹他州大学儿科重症监护助理教授。他曾接受过流行病学和比较有效性研究方法的培训，他的研究重点是改善创伤性脑损伤（TBI）儿童的预后。该提案将使班尼特博士能够发展概率数据库关联、前瞻性队列研究、倾向性方法、多重插补和混合模型方面的技能。班尼特博士的共同导师Mike Dean博士和石楠基南博士在临床试验、损伤研究、流行病学和大型数据库方面拥有丰富的专业知识。他的多学科咨询委员会由儿科创伤和创伤性脑损伤，神经外科，儿科健康信息系统（PHIS）和国家创伤数据库（NTDB）数据库，概率联系和比较有效性研究方法统计的国家领导人组成。班尼特博士的职业目标是使用比较有效的研究方法来改善患有严重TBI和其他伤害的儿童的结果。他的短期职业目标是成为儿科TBI研究和定量比较有效性方法的国家专家。班尼特博士的长期职业目标是成为一名独立的临床科学家，他将：1）通过分析干预措施的效果，改善TBI儿童的结局（颅内压（ICP）监测、渗透压治疗等），2）与创伤外科医生和其他人合作，扩大PHIS-NTDB的联系，对患有其他损伤的儿童进行干预措施的比较有效性分析，和3）参与多中心队列研究，通过儿科研究网络进行试验。犹他州大学的儿科重症监护部和儿科系有一种合作研究的文化，这种文化可以消除障碍，使医生科学家能够与当地机构（如Intermountain Healthcare（IHC））和国家组织（如美国外科医生学会（ACS）和儿童医院协会（CHA，前身为CHCA））合作。犹他州大学和儿科系为初级研究者的早期发展和指导提供了出色的资源，包括NIH资助的临床和转化科学中心（CCTS）和NIH资助的转化和比较有效性研究培训计划（TCER，班尼特博士是受资助的导师学者，目前有75%的受保护时间）。儿科重症监护部门拥有强大的计算基础设施以及统计和信息技术人员，以便为几个大型儿科研究网络提供数据管理，后勤支持和分析。所有这些资源都有助于研究环境，并可确保班尼特博士的持续成功。研究：TBI导致儿童大量死亡和残疾。支持对重度TBI儿童（格拉斯哥昏迷评分d 8）进行急性干预的现有证据有限。该提案旨在链接和验证两个具有互补临床信息的国家数据库，然后对严重TBI儿童的颅内压监测进行比较有效性分析。颅内压升高通常由严重的TBI引起，并通过引起额外的脑损伤而影响患者的预后。ICP监测用于检测ICP升高并指导严重TBI的治疗。已知治疗ICP升高可改善成人的结局;然而，儿童ICP监测的风险/获益比尚不清楚。尽管如此，专家意见建议对患有 严重的TBI，使得ICP监测的临床试验不太可能。因此，观察方法是评估儿童ICP监测有效性的最佳可用技术。目的1是使用概率链接技术连接PHIS和NTDB数据库，并使用一家医院的回顾性数据验证该链接的准确性。目的2是通过在一个单一的、高容量的儿科创伤中心进行一项为期三年的前瞻性队列研究，验证链接数据集中数据库代码的准确性和替代不良功能结局（气管造口术和胃造口术的生存率）。目的3是检验颅内压（ICP）监测与严重TBI儿童住院死亡率或功能结局不良可能性较低相关的假设。PI将在四年后通过重复数据集关联和比较有效性分析来验证目标3的结果。完成这些研究和他的培训目标将使班尼特博士产生宝贵的信息，以指导急性创伤性脑损伤儿童的护理，并成为一个独立的研究者和国家领导人在儿科创伤性脑损伤研究和比较有效性的研究方法。

DESCRIPTION (provided by applicant): This patient-oriented mentored career development award proposal is designed to support the transition of Dr. Tellen D. Bennett into an independent clinician-scientist and national leader in quantitative comparative effectiveness research. Dr. Bennett is an Assistant Professor of Pediatric Critical Care at the University of Utah. He has prior training in epidemiology and comparative effectiveness research methods, and his research is focused on improving outcomes in children with traumatic brain injury (TBI). This proposal will allow Dr. Bennett to develop skills in probabilistic database linkage, prospective cohort studies, propensity methods, multiple imputations, and mixed models. Drs. Mike Dean and Heather Keenan, Dr. Bennett's co- mentors, have extensive expertise in clinical trials, injury research, epidemiology, and large databases. His multidisciplinary advisory committee is made up of national leaders in pediatric trauma and traumatic brain injury, neurosurgery, the Pediatric Health Information System (PHIS) and National Trauma Data Bank (NTDB) databases, probabilistic linkage, and the statistics of comparative effectiveness research methods. Dr. Bennett's over-arching career goal is to improve the outcomes of children with severe TBI and other injuries using comparative effectiveness research methods. His short-term career goal is to become a national expert in pediatric TBI research and quantitative comparative effectiveness methods. Dr. Bennett's long-term career goal is to be an independent clinician-scientist who will: 1) Improve outcomes in children with TBI by analyzing the effect of interventions (intracranial pressure (ICP) monitoring, osmolar therapy, and others) in the linked dataset developed and validated in this proposal, 2) Collaborate with trauma surgeons and others to expand the PHIS-NTDB linkage to perform comparative effectiveness analyses of interventions in children with other injuries, and 3) Participate in multi-center cohort studies an trials conducted through pediatric research networks. The Division of Pediatric Critical Care and the Department of Pediatrics at the University of Utah have a culture of collaborative research that bridges barriers and enables physician scientists to work with local institutions such as Intermountain Healthcare (IHC) and national organizations such as the American College of Surgeons (ACS) and the Children's Hospital Association (CHA, formerly CHCA). The University of Utah and the Department of Pediatrics have outstanding resources for the early development and mentorship of junior investigators, including the NIH-funded Center for Clinical and Translational Science (CCTS) and the NIH- funded training program in Translational and Comparative Effectiveness Research (TCER, Dr. Bennett is a funded Mentored Scholar and currently has 75% protected time). The Division of Pediatric Critical Care maintains a robust computing infrastructure and statistical and information technology staff in order to provide data management, logistical support, and analyses for several large pediatric research networks. All of these resources contribute to the research environment and are available to ensure Dr. Bennett's continued success. Research: TBI causes substantial death and disability in children. The available evidence to support acute interventions in children with severe TBI (Glasgow Coma Scale d 8) is limited. This proposal aims to link and validate two national databases with complementary clinical information, and then conduct a comparative effectiveness analysis of intracranial pressure monitoring in children with severe TBI. Elevated ICP frequently results from severe TBI and worsens patient outcome by causing additional brain injury. ICP monitoring is used to detect elevated ICP and to guide treatment of severe TBI. Treatment of elevated ICP is known to improve outcomes in adults; however, the risk/benefit ratio of ICP monitoring in children is less clear. In spite of this, expert opinion recommends ICP monitoring in children with severe TBI, making a clinical trial of ICP monitoring unlikely. Therefore, observational methods are the best available techniques to assess the effectiveness of ICP monitoring in children. Aim 1 is to use probabilistic linkage techniques to link the PHIS and the NTDB databases and to validate the accuracy of that linkage using retrospective data from one hospital. Aim 2 is to validate the accuracy of database codes in the linked dataset and a proxy poor functional outcome, survival with tracheostomy and gastrostomy, by conducting a three-year prospective cohort study at a single, high volume, pediatric trauma center. Aim 3 is to test the hypothesis that intracranial pressure (ICP) monitoring is associated with a lower likelihood of hospital mortality or poor functional outcome in children with severe TBI. The PIs will validate the result of Aim 3 by repeating the dataset linkage and the comparative effectiveness analysis four years later. Completion of these studies and his training aims will allow Dr. Bennett to generate invaluable information to guide the acute care of children with TBI and to become an independent investigator and national leader in pediatric TBI research and comparative effectiveness research methods.