Effect of propranolol and clonidine after severe traumatic brain injury: a pilot randomized clinical trial

Abstract Objective To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). Background Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit. Methods This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16–64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study. Results Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (− 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes. Conclusion Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048

Mental Health Screening of Female Juvenile Offenders: Replication of a Subtyping Strategy

Recent research indicates that adjudicated female youth have higher rates of mental health problems and histories of trauma exposure and abuse relative to adjudicated male youth. These differences are important for gender-specific assessment, intervention, and management strategies. We replicated a subtyping strategy for adjudicated female youth based on mental health screening data from the Massachusetts Youth Screening Instrument - 2 (MAYSI-2) by investigating subtype differences on trauma symptoms, abuse history, and other background variables. Cluster analysis of the standard MAYSI-2 scales revealed a three cluster solution replicating results from a prior study. Additionally, results indicated expected differences between female youth with mental health problems compared to those without mental health problems with co-occurring female youth (i.e., self-reported mental health and substance abuse problems) having have greater mental health problems and more extensive abuse histories compared to other subtypes