A study protocol for risk stratification in children with concussion (RSiCC): Theoretical framework, design, and methods.
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2024-01
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Abstract
Research shows that one in five children will experience a concussion by age 16. Compared to adults, children experience longer and more severe postconcussive symptoms (PCS), with severity and duration varying considerably among children and complicating management of these patients. Persistent PCS can result in increased school absenteeism, social isolation, and psychological distress. Although early PCS diagnosis and access to evidence-based interventions are strongly linked to positive health and academic outcomes, symptom severity and duration are not fully explained by acute post-injury symptoms. Prior research has focused on the role of neuroinflammation in mediating PCS and associated fatigue; however relationship between inflammatory biomarkers and PCS severity, has not examined longitudinally. To identify which children are at high risk for persistent PCS and poor health, academic, and social outcomes, research tracking PCS trajectories and describing school-based impacts across the entire first year postinjury is critically needed. This study will 1) define novel PCS trajectory typologies in a racially/ethnically diverse population of 500 children with concussion (11-17 years, near equal distribution by sex), 2) identify associations between these typologies and patterns of inflammatory biomarkers and genetic variants, 3) develop a risk stratification model to identify children at risk for persistent PCS; and 4) gain unique insights and describe PCS impact, including fatigue, on longer-term academic and social outcomes. We will be the first to use NIH's symptom science model and patient-reported outcomes to explore the patterns of fatigue and other physical, cognitive, psychological, emotional and academic responses to concussion in children over a full year. Our model will enable clinicians and educators to identify children most at risk for poor long-term health, social, and academic outcomes after concussion. This work is critical to meeting our long-term goal of developing personalized concussion symptom-management strategies to improve outcomes and reduce disparities in the health and quality of life of children.
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Reuter-Rice, Karin, Amanda N Fitterer, Peter Duquette, Qing Yang, Anushka K Palipana, Daniel Laskowitz, Melanie E Garrett, Margaret Fletcher, et al. (2024). A study protocol for risk stratification in children with concussion (RSiCC): Theoretical framework, design, and methods. PloS one, 19(7). p. e0306399. 10.1371/journal.pone.0306399 Retrieved from https://hdl.handle.net/10161/33607.
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Scholars@Duke
Peter Joseph Duquette
Pete Duquette joined the Division of Child and Family Mental Health & Community Psychiatry and will be the Director of the Pediatric Neuropsychology Clinic. He earned a PhD in School Psychology from UNC-Chapel Hill in 2007 and completed a postdoctoral fellowship in Pediatric Neuropsychology at Children’s National Hospital in 2009. Dr. Duquette is board certified in Clinical Neuropsychology through the American Board of Professional Psychology. He specializes in assessment, consultation, and brief intervention with children, adolescents, and young adults with epilepsy, traumatic brain injury, spina bifida, cerebral palsy, and hematology-oncology conditions. Dr. Duquette also serves as the team neuropsychologist for concussion management to several sports teams in the area, including the Carolina Hurricanes (NHL) and NC Courage (NWSL).
Qing Yang
Dr. Qing Yang is Associate Professor and Biostatistician at Duke School of Nursing. She received her PhD in Biostatistics from University of California, Los Angeles. Dr. Yang’s statistical expertise is longitudinal data analysis and time-to-event data analysis. As a biostatistician, she has extensive experience collaborating with researchers in different therapeutic areas, including diabetes, cancer, cardiovascular disease and mental health. Her current research interests are advanced latent variable models that are widely used in symptom cluster research and intensive longitudinal data analysis that arise from mobile health research.
See my personal Github website.
Daniel Todd Laskowitz
Our laboratory uses molecular biology, cell culture, and animal modeling techniques to examine the CNS response to acute injury. In particular, our laboratory examines the role of microglial activation and the endogenous CNS inflammatory response in exacerbating secondary injury following acute brain insult. Much of the in vitro work in this laboratory is dedicated to elucidating cellular responses to injury with the ultimate goal of exploring new therapeutic interventions in the clinical setting of stroke, intracranial hemorrhage, and closed head injury.
In conjunction with the Multidisciplinary Neuroprotection Laboratories, we also focus on clinically relevant small animal models of acute CNS injury. For example, we have recently characterized murine models of closed head injury, subarachnoid hemorrhage, intracranial hemorrhage and perinatal hypoxia-ischemia, in addition to the standard rodent models of focal stroke and transient forebrain ischemia. Recently we have adapted several of these models from the rat to the mouse to take advantage of murine transgenic technology. The objective of these studies are two-fold: to gain better insight into the cellular responses and pathophysiology of acute brain injury, and to test novel therapeutic strategies for clinical translation. In both cell culture systems and animal models, our primary focus is on examining the role of oxidative stress and inflammatory mechanism in mediating brain injury following acute brain insult, and examining the neuroprotective effects of endogenous apolipoprotein E in the injured mammalian central nervous system.
Our laboratory is committed to translational research, and has several active clinical research protocols, which are designed to bring the research performed in the Multidisciplinary Research Laboratories to the clinical arena. These protocols are centered around patients following stroke and acute brain injury, and are primarily based out of the Emergency Room and Neurocritical Care Unit. For example, we are currently examining the role of inflammatory mediators for use as a point-of-care diagnostic marker following stroke, intracranial hemorrhage, and closed head injury. We have recently translated a novel apoE mimetic from the preclinical setting to a multi center Phase 2 trial evaluating efficacy in intracranial hemorrhage. We are also examining the functional role of different polymorphisms of of inflammatory cytokines in the setting of acute brain injury and neurological dysfunction following cardiopulmonary bypass.
Gerald Arthur Grant
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