No abstract

An orally administered, fixed-dose coformulation of sodium phenylbutyratetaurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo. Participants completing the 6-month (24-week) randomized phase were eligible to receive PB-TURSO in the open-label extension. An all-cause mortality analysis (35-month maximum follow-up post-randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of followup of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB-TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34-0.92; P = .023). Initiation of PB-TURSO treatment at baseline resulted in a 6.5-month longer median survival as compared with placebo. Combined with results from CEN-TAUR, these results suggest that PB-TURSO has both functional and survival benefits in ALS.

BACKGROUND: Although emergence from the minimally conscious state (eMCS) is associated with symptoms including disorientation, memory and attention impairment, restlessness, and significant functional disability, the neurobehavioral profile of eMCS has not been empirically characterized. OBJECTIVE: Determine degree of cognitive impairment, presence of clinical symptoms and functional disability at time eMCS in patients with traumatic and non-traumatic brain injury (TBI, nTBI). METHODS: Retrospective observational study of 169 adults (median [interquartile range] age: 51 [29, 62] years; male: 116; TBI: 103) who emerged from MCS based on the Coma Recovery Scale-Revised while in an inpatient Disorders of Consciousness program. Outcome measures include the Confusion Assessment Protocol (CAP) and Disability Rating Scale (DRS). RESULTS: CAP administration was attempted in 54 subjects. Twenty-eight subjects had valid scores on all CAP items, with a median [interquartile range] of 4 [3-5] symptoms of confusion. Scores in 93% of this subsample were consistent with an acute confusional state. The most common symptoms were cognitive impairment (98% of subjects), disorientation (93%), and agitation (69%). The median DRS score upon emergence from MCS was 14.5 [13, 16], indicating severe disability (n = 140). CONCLUSIONS: eMCS is associated with an acute confusional state and severe disability. This finding may inform the lower boundary of confusion as well as approach to treatment and caregiver education.