Effect of clinical characteristics on cognitive performance in service members and veterans with histories of blast-related mild traumatic brain injury.

OBJECTIVE: To examine the relationship between clinical characteristics and cognitive performance in service members and veterans with histories of blast-related mild traumatic brain injury (mTBI). DESIGN: This study consisted of 40 Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) service members and veterans; 20 participants reported blast exposure and alteration of mental status consistent with mTBI and 20 participants denied blast exposure and had no history of traumatic brain injury (TBI), but could have experienced extra-cranial injuries. Measures of simple reaction time, processing speed, visual attention, working memory and mathematical processing were used to assess long-term effects of mTBI. Measures of post-traumatic stress symptom severity, pain intensity, sleep difficulty and subjective appraisal of cognition at time of testing were also obtained. Multivariate analyses were conducted with clinical characteristics and mTBI history as predictors of cognitive performance. RESULTS: There was no evidence of an effect of mTBI history on cognitive performance in this sample. However, post-traumatic stress symptom severity was significantly related to two measures of cognitive performance. CONCLUSIONS: This study demonstrated the importance of considering the effects of current clinical symptoms (e.g. post-traumatic stress) as possibly having greater influence on current cognitive functioning than the effects of a remote history of mTBI.

Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial.

IMPORTANCE: There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury. OBJECTIVE: To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24- and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL. INTERVENTIONS: Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells. MAIN OUTCOMES AND MEASURES: Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury. RESULTS: There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P < .001). Favorable outcome rates were 37/87 (42.5%) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 (33.0%) for 10 g/dL (95% CI for the difference, -0.06 to 0.25, P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009). CONCLUSIONS AND RELEVANCE: In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00313716.