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BackgroundGlutamate excitotoxicity might contribute to the pathophysiology of amyotrophic lateral sclerosis. In animal models, decreased excitatory aminoacid transporter 2 (EAAT2) overexpression delays disease onset and prolongs survival, and ceftriaxone increases EAAT2 activity. We aimed to assess the safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis in a combined phase 1, 2, and 3 clinical trial.MethodsThis three-stage randomised, double-blind, placebo-controlled study was done at 59 clinical sites in the USA and Canada between Sept 4, 2006, and July 30, 2012. Eligible adult patients had amyotrophic lateral sclerosis, a vital capacity of more than 60% of that predicted for age and height, and symptom duration of less than 3 years. In stages 1 (pharmacokinetics) and 2 (safety), participants were randomly allocated (2:1) to ceftriaxone (2 g or 4 g per day) or placebo. In stage 3 (efficacy), participants assigned to ceftriaxone in stage 2 received 4 g ceftriaxone, participants assigned to placebo in stage 2 received placebo, and new participants were randomly assigned (2:1) to 4 g ceftriaxone or placebo. Participants, family members, and site staff were masked to treatment assignment. Randomisation was done by a computerised randomisation sequence with permuted blocks of 3. Participants received 2 g ceftriaxone or placebo twice daily through a central venous catheter administered at home by a trained caregiver. To minimise biliary side-effects, participants assigned to ceftriaxone also received 300 mg ursodeoxycholic acid twice daily and those assigned to placebo received matched placebo capsules. The coprimary efficacy outcomes were survival and functional decline, measured as the slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00349622.FindingsStage 3 included 66 participants from stages 1 and 2 and 448 new participants. In total, 340 participants were randomly allocated to ceftriaxone and 173 to placebo. During stages 1 and 2, mean ALSFRS-R declined more slowly in participants who received 4 g ceftriaxone than in those on placebo (difference 0·51 units per month, 95% CI 0·02 to 1·00; p=0·0416), but in stage 3 functional decline between the treatment groups did not differ (0·09, -0·06 to 0·24; p=0·2370). No significant differences in survival between the groups were recorded in stage 3 (HR 0·90, 95% CI 0·71 to 1·15; p=0·4146). Gastrointestinal adverse events and hepatobiliary adverse events were more common in the ceftriaxone group than in the placebo group (gastrointestinal, 245 of 340 [72%] ceftriaxone vs 97 of 173 [56%] placebo, p=0·0004; hepatobiliary, 211 [62%] vs 19 [11%], p

BackgroundAdrenalectomy is a complex procedure performed in many settings, with and without residents and fellows. Patients often ask, "Will trainees be participating in my operation?" and seek reassurance that their care will not be adversely affected. The purpose of this study was to determine the association between trainee participation and adrenalectomy perioperative outcomes.Study designWe performed a cohort study of patients who underwent adrenalectomy from the 2005 to 2011 American College of Surgeons NSQIP database. Trainee participation was classified as none, resident, or fellow, based on postgraduate year of the assisting surgeon. Associations between trainee participation and outcomes were determined via multivariate linear and logistic regression.ResultsOf 3,694 adrenalectomies, 732 (19.8%) were performed by an attending surgeon with no trainee, 2,315 (62.7%) involved a resident, and 647 (17.5%) involved a fellow. The participation of fellows was associated with fewer serious complications (7.9% with no trainee, 6.0% with residents, and 2.8% with fellows; p < 0.001). In a multivariate model, the odds of serious 30-day morbidity were lower when attending surgeons operated with residents (odds ratio = 0.63; 95% CI, 0.45-0.89). Fellow participation was associated with significantly lower odds of overall (odds ratio = 0.51; 95% CI, 0.32-0.82) and serious (odds ratio = 0.31; 95% CI, 0.17-0.57) morbidity. There was no significant association between trainee participation and 30-day mortality.ConclusionsIn this analysis of multi-institutional data, the participation of residents and fellows was associated with decreased odds of perioperative adrenalectomy complications. Attending surgeons performing adrenalectomies with trainee assistance should reassure patients of the equivalent or superior care they are receiving.