Journal of neurotrauma
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Journal of neurotrauma · Aug 2016
A Qualitative Study Exploring Factors Associated with Provider Adherence to Severe Pediatric Traumatic Brain Injury Guidelines.
Despite demonstrated improvement in patient outcomes with use of the Pediatric Traumatic Brain Injury (TBI) Guidelines (Guidelines), there are differential rates of adherence. Provider perspectives on barriers and facilitators to adherence have not been elucidated. This study aimed to identify and explore in depth the provider perspective on factors associated with adherence to the Guidelines using 19 focus groups with nurses and physicians who provided acute management for pediatric patients with TBI at five university-affiliated Level 1 trauma centers. ⋯ Provider training and experience, as well as attitudes towards other standardized care protocols, mirror the use and attitudes towards the Guidelines. Adherence was determined by the interaction of each of these guideline, institutional, and provider factors acting in concert. Incorporating provider perspectives on barriers and facilitators to adherence into hospital and team protocols is an important step toward improving adherence and ultimately patient outcomes.
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Journal of neurotrauma · Aug 2016
Autophagy modulation by lanthionine ketimine ethyl ester improves long-term outcome following central fluid percussion injury in the mouse.
Diffuse axonal injury is recognized as a progressive and long-term consequence of traumatic brain injury. Axonal injury can have sustained negative consequences on neuronal functions such as anterograde and retrograde transport and cellular processes such as autophagy that depend on cytoarchitecture and axon integrity. These changes can lead to somatic atrophy and an inability to repair and promote plasticity. ⋯ Lanthionine ketimine ethyl ester, a bioavailable derivative of a natural sulfur amino acid metabolite, has demonstrated effects on autophagy both in vitro and in vivo. Thirty minutes after a moderate central fluid percussion injury and throughout the survival period, lanthionine ketimine ethyl ester was administered, and mice were subsequently evaluated for learning and memory impairments and biochemical and histological changes over a 5-week period. Lanthionine ketimine ethyl ester, which we have shown previously to modulate autophagy markers and alleviate pathology and slow cognitive decline in the 3 × TgAD mouse model, spared cognition and pathology after central fluid percussion injury through a mechanism involving autophagy modulation.
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Journal of neurotrauma · Aug 2016
LIF Haplodeficiency Desynchronizes Glial Reactivity and Exacerbates Damage and Functional Deficits After a Concussive Brain Injury.
Reactions of both astrocytes and microglia to central nervous system injury can be beneficial or detrimental to recovery. To gain insights into the functional importance of gliosis, we developed a new model of adolescent closed-head injury (CHI) and interrogated the behavioral, physiological, and cellular outcomes after a concussive CHI in leukemia inhibitory factor (LIF) haplodeficient mice. ⋯ The prolonged accumulation of neurological impairment was accompanied by desynchronization of the gliotic response, increased cell death, axonal degeneration, diminished callosal compound action potential, and hypomyelination. Our results clearly show that LIF is an essential injury-induced cytokine that is required to prevent the propagation of secondary neurodegeneration.
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Journal of neurotrauma · Aug 2016
Randomized Controlled Trial Multicenter StudyExternal validation of the IMPACT prognostic models for traumatic brain injury on the SyNAPSe trial.
Prediction models for patients with traumatic brain injury (TBI) are important for multiple reasons, including case-mix adjustment, trial design, and benchmarking for quality-of-care evaluation. Models should be generalizable and therefore require regular external validation. We aimed to validate the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic models for moderate and severe TBI in a recent randomized controlled trial. ⋯ This pattern of miscalibration was consistent across all three models. In a contemporary trial setting, the IMPACT models have reasonable discrimination if enrollment restrictions apply. Observed changes in outcome distribution necessitate updating of previously developed prognostic models.
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Journal of neurotrauma · Aug 2016
ReviewA State of the Science Overview of Randomised Controlled Trials evaluating Acute Management of Moderate to Severe Traumatic Brain Injury.
Moderate-to-severe traumatic brain injury (TBI) remains a major global challenge, with rising incidence, unchanging mortality and lifelong impairments. State-of-the-science reviews are important for research planning and clinical decision support. This review aimed to identify randomized controlled trials (RCTs) evaluating interventions for acute management of moderate/severe TBI, synthesize key RCT characteristics and findings, and determine their implications on clinical practice and future research. ⋯ Considerable investment of resources in producing 191 completed RCTs for acute TBI management has resulted in very little translatable evidence. This may result from broad distribution of research effort, small samples, preponderance of single-center RCTs, and methodological shortcomings. More sophisticated RCT design, large multi-center RCTs in priority areas, increased focus on pre-clinical research, and alternatives to RCTs, such as comparative effectiveness research and precision medicine, are needed to fully realize the potential of acute TBI research to benefit patients.