BACKGROUND Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI. METHODS We conducted a double-blind, multicenter clinical trial in which patients with severe, moderate-to-severe, or moderate acute TBI (Glasgow Coma Scale score of 4 to 12, on a scale from 3 to 15, with lower scores indicating a lower level of consciousness) were randomly assigned to intravenous progesterone or placebo, with the study treatment initiated within 4 hours after injury and administered for a total of 96 hours. Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome, as determined with the use of the stratified dichotomy of the Extended Glasgow Outcome Scale score at 6 months after injury. Secondary outcomes included mortality and the Disability Rating Scale score. RESULTS A total of 882 of the planned sample of 1140 patients underwent randomization before the trial was stopped for futility with respect to the primary outcome. The study groups were similar with regard to baseline characteristics; the median age of the patients was 35 years, 73.7% were men, 15.2% were black, and the mean Injury Severity Score was 24.4 (on a scale from 0 to 75, with higher scores indicating greater severity). The most frequent mechanism of injury was a motor vehicle accident. There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome (relative benefit of progesterone, 0.95; 95% confidence interval [CI], 0.85 to 1.06; P = 0.35). Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group (relative risk, 3.03; CI, 1.96 to 4.66). There were no significant differences in the other prespecified safety outcomes. CONCLUSIONS This clinical trial did not show a benefit of progesterone over placebo in the improvement of outcomes in patients with acute TBI. (Funded by the National Institute of Neurological Disorders and Stroke and others; PROTECT III ClinicalTrials.gov number, NCT00822900.)

While there is no doubt that benzodiazepine administration leads to transient cognitive impairment in healthy adults, the nature and magnitude of such impairment has not been well described. The cognitive effects of a single dose of alprazolam 0.5 and 1 mg were therefore assessed in 36 healthy adults on measures of psychomotor function, visual attention, working memory, planning and learning in a double-blind parallel-groups study. Measures of these different cognitive functions were selected on the basis of their brevity and because they yielded distributions of performance data that were without skew, floor or ceiling effects of range restriction (i.e. normal distributions). With data satisfying the assumptions for parametric analysis, measures of effect size could be computed in addition to significance testing, thus allowing for direct and meaningful comparison between the different performance measures used. Alprazolam 0.5 mg reduced only the speed of attentional performance although the magnitude of this reduction was large (d = 0.8). At 1.0 mg, impairments in psychomotor function, equivalent to that seen for attentional function at the lower dose, were observed. In addition, moderate (d approx = 0.5) impairments in working memory, and learning also became obvious. When considered together, these results suggest that low-dose alprazolam primarily alters visual attentional function. At the higher dose psychomotor functions also become impaired, and it is likely that the combination of these led to the observed moderate impairments in higher level executive and memory processes. The current study also illustrates a method for directly comparing the magnitude of change in cognitive function between measures with different performance metrics.

At present, there is poor accuracy in assessing cognitive and vegetative symptoms in depression using clinician or self-rated measures, suggesting the need for development of standardized tasks to assess these functions. The current study assessed the psychometric properties and diagnostic specificity of a brief neuropsychological screening battery designed to assess core signs of depression; psychomotor retardation, attention and NOT THE PUBLISHED VERSION; this is the author's final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation at the bottom of the page.Psychiatry Research, Vol 152, No. 2-3 (August, 2007): pg. 143-154. DOI. This article is © Elsevier and permission has been granted for this version to appear in e-Publications@Marquette. Elsevier does not grant permission for this article to be further copied/distributed or hosted elsewhere without the express permission from Elsevier.3 executive functioning difficulties, and impaired emotion perception within an outpatient psychiatry setting. Three hundred eighty-four patients with mood disorders and 77 healthy volunteers participated. A large percentage of patients met diagnostic criteria for Major Depressive Disorder alone (49%) or with another comorbid psychiatric disorder (24%). A brief, 25-min battery of computer-based tests was administered to control participants and patients measuring the constructs of inhibitory control, attention, visual perception, and both executive and visual processing speed. The patient groups performed significantly worse than the control group regardless of diagnosis on visual perception and attention accuracy and processing speed factors. Surprisingly, the anxiety disorder group performed better than several other psychiatric disorder groups in inhibitory control accuracy. Developing valid and reliable measures of cognitive signs in mood disorders creates excellent opportunities for tracking cognitive status prior to initiation of treatment, and allows for reliable retest following treatment.

No abstract

Background and Purpose-Abnormalities in neurocognitive function are common after surgery for aneurysmal subarachnoid hemorrhage, even among patients with good functional outcomes. The time course of neurocognitive recovery, along with the long-term effects of mild intraoperative hypothermia (33°C) and aneurysm location, is unknown. We determined these in a subset of subarachnoid hemorrhage patients enrolled in the Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST). Methods-We performed a longitudinal, multicenter, prospective, blinded study of adult IHAST patients with a Glasgow Outcome Scoreϭ1 or 2 (independent function), 3 months postsurgery and a matched control group (nϭ45). Subjects were tested with a 5-test cognitive function battery and standard neurological evaluations at 3, 9 and 15 months postsurgery. The primary outcome measure was a composite score on cognitive test performance. Results-There were 303 IHAST patients available for inclusion: 218 eligible, 185 enrolled (89 hypothermic, 96 normothermic). Significant cognitive improvement was noted from 3 to 9 (PϽ0.001) and 3 to 15 (PϽ0.001) months in both hypothermic and normothermic groups, even after adjusting for practice effects observed in the control group. No significant change was identified between 9 and 15 months. Neither mild hypothermia nor aneurysm location (anterior communicating artery versus others) had a significant effect on recovery over time or frequency of cognitive impairment. Compared with control group, the frequency of cognitive impairment (Z score ϽϪ1.96) in all patients at 3, 9 and 15 months was 36%, 26% and 23%, respectively. Conclusions-In this population, cognitive improvement continued beyond 3 months, with a plateau between 9 and 15 months. This was not affected by the use of intraoperative hypothermia or anatomical location of aneurysm. (Stroke.