This mentored patient-oriented research 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 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 imputation 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. TBI causes substantial death and disability in children. The available evidence to support acute interventions in children with severe TBI (Glasgow Coma Scale <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, expet 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 database and the NTDB 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.

Public Health Relevance

This research is relevant to public health because traumatic brain injury is a frequent cause of morbidity and mortality in children. The overall goal of this research is to improve outcomes in children with severe traumatic brain injury by rigorously studying the effectiveness of intracranial pressure monitoring and other interventions recommended by experts but with limited supporting evidence.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Mentored Patient-Oriented Research Career Development Award (K23)
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Developmental Biology Subcommittee (CHHD)
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Tamburro, Robert F
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University of Colorado Denver
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Carlisle, Michael A; Bennett, Tellen D (2018) Phenotyping in Pediatric Traumatic Brain Injury. Pediatr Crit Care Med 19:998-999
Maddux, Aline B; Cox-Martin, Matthew; Dichiaro, Michael et al. (2018) The Association Between the Functional Status Scale and the Pediatric Functional Independence Measure in Children Who Survive Traumatic Brain Injury. Pediatr Crit Care Med 19:1046-1053
Feinstein, James A; Russell, Seth; DeWitt, Peter E et al. (2018) R Package for Pediatric Complex Chronic Condition Classification. JAMA Pediatr 172:596-598
Maddux, Aline B; Bennett, Tellen D (2018) Mortality After Pediatric Critical Illness: Made It Home, Still Vulnerable. Pediatr Crit Care Med 19:272-273
Maddux, Aline B; DeWitt, Peter E; Mourani, Peter M et al. (2018) Hospital Readmissions After Pediatric Trauma. Pediatr Crit Care Med 19:e31-e40
Bennett, Tellen D; Greene, Tom H; Keenan, Heather T (2018) Functional Outcome After Intracranial Presuure Monitoring-Reply. JAMA Pediatr 172:393
Bennett, Tellen D; DeWitt, Peter E; Dixon, Rebecca R et al. (2017) Development and Prospective Validation of Tools to Accurately Identify Neurosurgical and Critical Care Events in Children With Traumatic Brain Injury. Pediatr Crit Care Med 18:442-451
Bennett, Tellen D; DeWitt, Peter E; Greene, Tom H et al. (2017) Functional Outcome After Intracranial Pressure Monitoring for Children With Severe Traumatic Brain Injury. JAMA Pediatr 171:965-971
Ruzas, Christopher M; DeWitt, Peter E; Bennett, Kimberly S et al. (2017) EEG Monitoring and Antiepileptic Drugs in Children with Severe TBI. Neurocrit Care 26:256-266
Bennett, Kimberly Statler; DeWitt, Peter E; Harlaar, Nicole et al. (2017) Seizures in Children With Severe Traumatic Brain Injury. Pediatr Crit Care Med 18:54-63

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