ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury.

STUDY OBJECTIVE: Laboratory evidence indicates that progesterone has potent neuroprotective effects. We conducted a pilot clinical trial to assess the safety and potential benefit of administering progesterone to patients with acute traumatic brain injury. METHODS: This phase II, randomized, double-blind, placebo-controlled trial was conducted at an urban Level I trauma center. One hundred adult trauma patients who arrived within 11 hours of injury with a postresuscitation Glasgow Coma Scale score of 4 to 12 were enrolled with proxy consent. Subjects were randomized on a 4:1 basis to receive either intravenous progesterone or placebo. Blinded observers assessed patients daily for the occurrence of adverse events and signs of recovery. Neurologic outcome was assessed 30 days postinjury. The primary safety measures were differences in adverse event rates and 30-day mortality. The primary measure of benefit was the dichotomized Glasgow Outcome Scale-Extended 30 days postinjury. RESULTS: Seventy-seven patients received progesterone; 23 received placebo. The groups had similar demographic and clinical characteristics. Laboratory and physiologic characteristics were similar at enrollment and throughout treatment. No serious adverse events were attributed to progesterone. Adverse and serious adverse event rates were similar in both groups, except that patients randomized to progesterone had a lower 30-day mortality rate than controls (rate ratio 0.43; 95% confidence interval 0.18 to 0.99). Thirty days postinjury, the majority of severe traumatic brain injury survivors in both groups had relatively poor Glasgow Outcome Scale-Extended and Disability Rating Scale scores. However, moderate traumatic brain injury survivors who received progesterone were more likely to have a moderate to good outcome than those randomized to placebo. CONCLUSION: In this small study, progesterone caused no discernible harm and showed possible signs of benefit.

The neural correlates of social anxiety disorder and response to pharmacotherapy.

This study attempted to define further the neural processing events underlying social anxiety in patients with social anxiety disorder (SAD) and their response to pharmacotherapy. Social anxiety-related changes in regional cerebral blood flow were defined by [15O]H2 positron emission tomography (PET) in medication-free individuals with generalized SAD (gSAD), and age- and sex-matched comparison subjects, and analyzed using a linear mixed effects model. PET studies were again acquired in the gSAD individuals following an 8-week, flexible dose treatment trial of nefazodone. Both script-guided mental imagery of an anxiogenic social situation and a confrontational mental arithmetic task were associated with marked increases in self-rated anxiety in both subject groups. For gSAD subjects, social anxiety induced by guided mental imagery was associated with increased activity in the left postcentral gyrus and lenticulate, and the right inferior frontal and middle temporal gyri. Social anxiety induced by the mental arithmetic task was associated with activation of the medial and left dorsolateral prefrontal cortex, cerebellum, thalamus, insula, and ventral striatum. Both tasks were associated with relative decreases in activity in the right amygdala and the hippocampus. A direct group comparison indicated that comparison subjects exhibited a differing pattern of social anxiety-related neural activations. Nefazodone treatment was associated with marked clinical improvement. Comparison of social anxiety-related neural activations prior to and after nefazodone administration indicated greater activity in the precentral gyrus, insula, midbrain/hypothalamus, and middle frontal and anterior cingulate gyrus prior to treatment, and greater activity in the left middle occipital and bilateral lingual gyri, postcentral gyrus, gyrus rectus, and hippocampus after treatment. The results of an analysis relating neural activity and treatment-related changes in symptom severity indicated differential neural responses associated with states of symptom remission vs partial response. The observed social anxiety-related changes in distributed neural activity are consistent with cognitive models of SAD and adaptive decreases in amygdala activity in response to social anxiogenics, and support the association of altered frontal cortical responses with treatment response.

Efficacy of an HIV prevention intervention for African American adolescent girls: a randomized controlled trial.

CONTEXT: African American adolescent girls are at high risk for human immunodeficiency virus (HIV) infection, but interventions specifically designed for this population have not reduced HIV risk behaviors. OBJECTIVE: To evaluate the efficacy of an intervention to reduce sexual risk behaviors, sexually transmitted diseases (STDs), and pregnancy and enhance mediators of HIV-preventive behaviors. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of 522 sexually experienced African American girls aged 14 to 18 years screened from December 1996 through April 1999 at 4 community health agencies. Participants completed a self-administered questionnaire and an interview, demonstrated condom application skills, and provided specimens for STD testing. Outcome assessments were made at 6- and 12-month follow-up. INTERVENTION: All participants received four 4-hour group sessions. The intervention emphasized ethnic and gender pride, HIV knowledge, communication, condom use skills, and healthy relationships. The comparison condition emphasized exercise and nutrition. MAIN OUTCOME MEASURES: The primary outcome measure was consistent condom use, defined as condom use during every episode of vaginal intercourse; other outcome measures were sexual behaviors, observed condom application skills, incident STD infection, self-reported pregnancy, and mediators of HIV-preventive behaviors. RESULTS: Relative to the comparison condition, participants in the intervention reported using condoms more consistently in the 30 days preceding the 6-month assessment (unadjusted analysis, intervention, 75.3% vs comparison, 58.2%) and the 12-month assessment (unadjusted analysis, intervention, 73.3% vs comparison, 56.5%) and over the entire 12-month period (adjusted odds ratio, 2.01; 95% confidence interval [CI], 1.28-3.17; P =.003). Participants in the intervention reported using condoms more consistently in the 6 months preceding the 6-month assessment (unadjusted analysis, intervention, 61.3% vs comparison, 42.6%), at the 12-month assessment (unadjusted analysis, intervention, 58.1% vs comparison, 45.3%), and over the entire 12-month period (adjusted odds ratio, 2.30; 95% CI, 1.51-3.50; P<.001). Using generalized estimating equation analyses over the 12-month follow-up, adolescents in the intervention were more likely to use a condom at last intercourse, less likely to have a new vaginal sex partner in the past 30 days, and more likely to apply condoms to sex partners and had better condom application skills, a higher percentage of condom-protected sex acts, fewer unprotected vaginal sex acts, and higher scores on measures of mediators. Promising effects were also observed for chlamydia infections and self-reported pregnancy. CONCLUSION: Interventions for African American adolescent girls that are gender-tailored and culturally congruent can enhance HIV-preventive behaviors, skills, and mediators and may reduce pregnancy and chlamydia infection.