A Multi-Modal Assessment of Clinical Predictors for Traumatic Brain Injury End-Points.

Traumatic brain injury (TBI) is a complex injury that has a multi-faceted recovery process. The current "gold standard" for classifying severity of TBI symptoms is the Glasgow Outcome Scale (GOSE), a crude measure of overall dysfunction after TBI. Exploratory factor analysis performed on TRACK-TBI Pilot (N = 297) identified candidate multi-variate outcome measures of neuropsychological impairment and cognitive speed and flexibility at 6 months post-TBI that were confirmed in data from the COBRIT study (N = 645) using confirmatory factor analysis. These new outcome measures were used as the dependent variables in an ordinal logistic regression model, using common data elements (CDE) collected in the emergency department as independent variables, including basic demographics, socioeconomic status, medical history, and measures of blood alcohol and blood pressure. We directly compared these prediction models with the GOSE as the 6-month outcome variable and found that in both the TRACK-TBI pilot and COBRIT studies, both neuropsychiatric complications (approx. 36.0% and 22.3% variance explained) and cognitive speed and flexibility (approx. 33.9% and 24.5% variance explained) were better explained by the prediction model, compared with GOSE (approx. 19.9% and 14.4% variance explained), respectively. While differences in overall distributions of impairment between TRACK-TBI pilot and COBRIT exist and should be explored further for applications of these prediction models, we think these multi-variate end-points more accurately characterize patients' functioning at six-months post-TBI. A multi-variate assessment of end-points seems especially important for characterizing TBI outcomes in cases where gross impairment, such as those measured by the GOSE, may be less evident.

The Irvine, Beatties, and Bresnahan (IBB) Forelimb Recovery Scale: An Assessment of Reliability and Validity.

The IBB scale is a recently developed forelimb scale for the assessment of fine control of the forelimb and digits after cervical spinal cord injury [SCI; (1)]. The present paper describes the assessment of inter-rater reliability and face, concurrent and construct validity of this scale following SCI. It demonstrates that the IBB is a reliable and valid scale that is sensitive to severity of SCI and to recovery over time. In addition, the IBB correlates with other outcome measures and is highly predictive of biological measures of tissue pathology. Multivariate analysis using principal component analysis (PCA) demonstrates that the IBB is highly predictive of the syndromic outcome after SCI (2), and is among the best predictors of bio-behavioral function, based on strong construct validity. Altogether, the data suggest that the IBB, especially in concert with other measures, is a reliable and valid tool for assessing neurological deficits in fine motor control of the distal forelimb, and represents a powerful addition to multivariate outcome batteries aimed at documenting recovery of function after cervical SCI in rats.

Methods for functional assessment after C7 spinal cord hemisection in the rhesus monkey.

BACKGROUND: Reliable outcome measures are essential for preclinical modeling of spinal cord injury (SCI) in primates. MEASURES: need to be sensitive to both increases and decreases in function in order to demonstrate potential positive or negative effects of therapeutics. OBJECTIVES: To develop behavioral tests and analyses to assess recovery of function after SCI in the nonhuman primate. METHODS: In all, 24 male rhesus macaques were subjected to complete C7 lateral hemisection. The authors scored recovery of function in an open field and during hand tasks in a restraining chair. In addition, EMG analyses were performed in the open field, during hand tasks, and while animals walked on a treadmill. Both control and treated monkeys that received candidate therapeutics were included in this report to determine whether the behavioral assays were capable of detecting changes in function over a wide range of outcomes. RESULTS: The behavioral assays are shown to be sensitive to detecting a wide range of motor functional outcomes after cervical hemisection in the nonhuman primate. Population curves on recovery of function were similar across the different tasks; in general, the population recovers to about 50% of baseline performance on measures of forelimb function. CONCLUSIONS: The behavioral outcome measures that the authors developed in this preclinical nonhuman primate model of SCI can detect a broad range of motor recovery. A set of behavioral assays is an essential component of a model that will be used to test efficacies of translational candidate therapies for SCI.

Patient-centered culturally sensitive health care: model testing and refinement.

OBJECTIVES: This article presents the results of an empirical test of a literature-based Patient-Centered Culturally Sensitive Health Care Model. The model was developed to explain and improve health care for ethnically diverse patients seen in community-based primary care clinics. DESIGN: Samples of predominantly low-income African American (n = 110) and non-Hispanic White American (n = 119) patients were recruited to complete questionnaires about their perceived health care provider cultural sensitivity and adherence to their provider's treatment regimen recommendations. MAIN OUTCOME MEASURES: Patients completed written measures of their perceived provider cultural sensitivity, trust in provider, interpersonal control, satisfaction with their health care provider, physical stress, and adherence to provider-recommended treatment regimen variables (i.e., engagement in a health promoting lifestyle, and dietary and medication adherence). RESULTS: Two-group path analyses revealed significant links between patient-perceived provider cultural sensitivity and adherence to provider treatment regimen recommendations, with some differences in associations emerging by race/ethnicity. CONCLUSION: The findings provide empirical support for the potential usefulness of the Patient-Centered Culturally Sensitive Health Care Model for explaining the linkage between the provision of patient-centered, culturally sensitive health care, and the health behaviors and outcomes of patients who experience such care.

Assessment of the role of MAP kinase in mediating activity-dependent transcriptional activation of the immediate early gene Arc/Arg3.1 in the dentate gyrus in vivo.

Different physiological and behavioral events activate transcription of Arc/Arg3.1 in neurons in vivo, but the signal transduction pathways that mediate induction in particular situations remain to be defined. Here, we explore the relationships between induction of Arc/Arg3.1 transcription in dentate granule cells in vivo and activation of mitogen-activated protein (MAP) kinase as measured by extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation. We show that ERK1/2 phosphorylation is strongly induced in dentate granule cells within minutes after induction of perforant path long-term potentiation (LTP). Phospho-ERK staining appears in nuclei within minutes after stimulation commences, and ERK phosphorylation returns to control levels within 60 min. Electroconvulsive seizures, which strongly induce prolonged Arc/Arg3.1 transcription in dentate granule cells, induced ERK1/2 phosphorylation in granule cells that returned to control levels within 30 min. Following 30, 60, and 120 min of exploration in a novel complex environment, Arc/Arg3.1 transcription was activated in many more granule cells than stained positively for p-ERK at all time points. Although Arc/Arg3.1 transcription was induced in most pyramidal neurons in CA1 following exploration, very few pyramidal neurons exhibited nuclear p-ERK1/2 staining. Local delivery of U0126 during the induction of perforant path LTP blocked transcriptional activation of Arc/Arg3.1 in a small region near the injection site and blocked Arc/Arg3.1 protein expression over a wider region. Our results indicate that activation of Arc/Arg3.1 transcription in dentate granule cells in vivo is mediated in part by MAP kinase activation, but other signaling pathways also contribute, especially in the case of Arc/Arg3.1 induction in response to experience.