Journal of neurotrauma
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Journal of neurotrauma · Jun 2017
ReviewTargeting translational successes through CANSORT-SCI: using pet dogs to identify effective treatments for spinal cord injury.
Translation of therapeutic interventions for spinal cord injury (SCI) from laboratory to clinic has been historically challenging, highlighting the need for robust models of injury that more closely mirror the human condition. The high prevalence of acute, naturally occurring SCI in pet dogs provides a unique opportunity to evaluate expeditiously promising interventions in a population of animals that receive diagnoses and treatment clinically in a manner similar to persons with SCI, while adhering to National Institutes of Health guidelines for scientific rigor and transparent reporting. In addition, pet dogs with chronic paralysis are often maintained long-term by their owners, offering a similarly unique population for study of chronic SCI. ⋯ The CANSORT-SCI group held an inaugural meeting November 20 and 21, 2015 to evaluate opportunities and challenges to the use of pet dogs in SCI research. Key challenges identified included lack of familiarity with the model among nonveterinary scientists and questions about how and where in the translational process the canine clinical model would be most valuable. In light of these, we review the natural history, outcome, and available assessment tools associated with canine clinical SCI with emphasis on their relevance to human SCI and the translational process.
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Over the past 10 years, our team has attended numerous Paralympic games and International Paralympic Committee (IPC)-sanctioned events where we have accumulated the largest data set to date from elite athletes with spinal cord injury (SCI). This empirical evidence has allowed us to address critical questions related to health and athletic performance in these incredibly medically complex individuals. Namely, does autonomic function influence performance? Can we account for this with the present sport classification? How can we prevent the doping practice of self-inducing life-threatening episodes of hypertension to improve performance (termed "boosting")? How does extremely high participation in routine upper-body wheelchair exercise impact cardiovascular and cerebrovascular disease risk? Is it possible to improve the sport classification to level the playing field between athletes with and without autonomic dysfunction? Herein, we will narratively address these questions, and provide our perspective on future directions and recommendations moving forward. ⋯ We will explore how an easy-to-execute test may be able to predict which individuals are most likely to develop autonomic dysfunctions that may negatively affect their health and performance. We also will evaluate the possibility that a level playing field may be even more difficult to establish than once thought, considering the importance of not only voluntary movement to performance, but also autonomic function. Finally, we also will discuss new changes in screening guidelines at Rio to assess the occurrence of boosting, which is a banned practice by the IPC.
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Journal of neurotrauma · Jun 2017
ReviewSuboptimal dosing parameters as possible factors in the negative Phase III clinical trials of progesterone in TBI.
To date, outcomes for all Phase III clinical trials for traumatic brain injury (TBI) have been negative. The recent disappointing results of the Progesterone for the Treatment of Traumatic Brain Injury (ProTECT) and Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury (SyNAPSe) Phase III trials for progesterone in TBI have triggered considerable speculation about the reasons for the negative outcomes of these two studies in particular and for those of all previous Phase III TBI clinical trials in general. ⋯ Given these circumstances and the exceptional pleiotropic potential of progesterone as a TBI (and stroke) therapeutic, we are advocating a return to Phase IIB testing. We advocate the incorporation of dose and schedule optimization focused on lower doses and a longer duration of treatment, combined with the addressing of other potential trial design problems raised by the authors in the recently published trial results.