US Estimates of Hospitalized Children With Severe Traumatic Brain Injury: Implications for Clinical Trials

Department of Emergency Medicine, University of Michigan, Ann Arbor MI 48105, USA.
PEDIATRICS (Impact Factor: 5.47). 12/2011; 129(1):e24-30. DOI: 10.1542/peds.2011-2074
Source: PubMed


To estimate sample sizes available for clinical trials of severe traumatic brain injury (TBI) in children, we described the patient demographics and hospital characteristics associated with children hospitalized with severe TBI in the United States.
We analyzed the 2006 Kids' Inpatient Database. Severe TBI hospitalizations were defined as children discharged with TBI who required mechanical ventilation or intubation. Types of high-volume severe TBI hospitals were categorized based on the numbers of discharged patients with severe TBI in 2006. National estimates of demographics and hospital characteristics were calculated for pediatric severe TBI. Simulation analyses were performed to assess the potential number of severe TBI cases from randomly selected hospitals for inclusion in future clinical trials.
The majority of children with severe TBI were discharged from either a children's unit in general hospitals (41%) or a nonchildren's hospital (34%). Less than 5% of all hospitals were high-volume TBI hospitals, which discharged >78% of severe TBI cases and were more likely to be a children's unit in a general hospital or a children's hospital. Simulation analyses indicate that there is a saturation point after which the benefit of adding additional recruitment sites decreases significantly.
Children with severe TBI are infrequent at any one hospital in the United States, and few hospitals treat large numbers of children with severe TBI. To effectively plan trials of therapies for severe TBI, much attention has to be paid to selecting the right types of centers to maximize enrollment efficiency.

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Available from: Huiyun Xiang, Mar 23, 2015
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    • "Traumatic Brain Injury (TBI) in children can cause more severe cognitive and behavioral deficits than comparable injuries in mature brains, and is one of the most common reasons for the development of significant lifelong disability in a child (Anderson et al., 2005; Rivara et al., 2012; Stanley et al., 2012; Roozenbeek et al., 2013). This is particularly important if we consider that children under the age of 4 years more frequently undergo TBI than any other age group (Koepsell et al., 2011) and that injured infants under the age of 12 months are at high risk of requiring intensive care support (Keenan et al., 2003). "
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    ABSTRACT: Disorders of the developing brain represent a major health problem. The neurological manifestations of brain lesions can range from severe clinical deficits to more subtle neurological signs or behavioral problems and learning disabilities, which often become evident many years after the initial damage. These long-term sequelae are due at least in part to central nervous system immaturity at the time of the insult. The blood-brain barrier (BBB) protects the brain and maintains homeostasis. BBB alterations are observed during both acute and chronic brain insults. After an insult, excitatory amino acid neurotransmitters are released, causing reactive oxygen species (ROS)-dependent changes in BBB permeability that allow immune cells to enter and stimulate an inflammatory response. The cytokines, chemokines and other molecules released as well as peripheral and local immune cells can activate an inflammatory cascade in the brain, leading to secondary neurodegeneration that can continue for months or even years and finally contribute to post-insult neuronal deficits. The role of the BBB in perinatal disorders is poorly understood. The inflammatory response, which can be either acute (e.g., perinatal stroke, traumatic brain injury) or chronic (e.g., perinatal infectious diseases) actively modulates the pathophysiological processes underlying brain injury. We present an overview of current knowledge about BBB dysfunction in the developing brain during acute and chronic insults, along with clinical and experimental data.
    Frontiers in Neuroscience 02/2015; 9:40. DOI:10.3389/fnins.2015.00040 · 3.66 Impact Factor
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    • "There is now a substantial literature showing that treatment with progesterone is beneficial in adult rodents after CCI, and the hormone shows promise as a treatment for acute TBI in adult patients [14]–[18]. The multicenter national ProTECT III (NCT00822900) and BHR Pharma's international SyNAPSe® (NCT01143064) Phase III clinical trials are independently evaluating the effects of progesterone treatment on acute TBI in adults, and the Pediatric Emergency Care Research Network (PECARN) is considering a progesterone trial in pediatric patients with moderate to severe TBI [19]. "
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    PLoS ONE 01/2014; 9(1):e87252. DOI:10.1371/journal.pone.0087252 · 3.23 Impact Factor
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    ABSTRACT: Despite decades of laboratory research and clinical trials, a safe and effective treatment for traumatic brain injury (TBI) has yet to be put into successful clinical use. I suggest that much of the problem can be attributed to a reductionist perspective and attendant research strategy directed to finding or designing drugs that target a single receptor mechanism, gene, or brain locus. This approach fails to address the complexity of TBI, which leads to a cascade of systemic toxic events in the brain and throughout the body that may persist over long periods of time. Attention is now turning to pleiotropic drugs: drugs that act on multiple genomic, proteomic and metabolic pathways to enhance morphological and functional outcomes after brain injury. Of the various agents now in clinical trials, the neurosteroid progesterone (PROG) is gaining attention despite the widespread assumption that it is "just a female hormone" with limited, if any, neuroprotective properties. This perspective should change. PROG is also a powerful developmental hormone that plays a critical role in protecting the fetus during gestation. I argue here that development, neuroprotection and cellular repair have a number of properties in common. I discuss evidence that PROG is pleiotropically neuroprotective and may be a useful therapeutic and neuroprotective agent for central nervous system injury and some neurodegenerative diseases. This article is part of a Special Issue entitled Hormones & Neurotrauma.
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