BACKGROUND AND OBJECTIVES: There are no US Food and Drug Administration-approved therapies for neonatal seizures. Phenobarbital and phenytoin frequently fail to control seizures. There are concerns about the safety of seizure medications in the developing brain. Levetiracetam has proven efficacy and an excellent safety profile in older patients; therefore, there is great interest in its use in neonates. However, randomized studies have not been performed. Our objectives were to study the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment of neonatal seizures. METHODS:The study was a multicenter, randomized, blinded, controlled, phase IIb trial investigating the efficacy and safety of levetiracetam compared with phenobarbital as a firstline treatment for neonatal seizures of any cause. The primary outcome measure was complete seizure freedom for 24 hours, assessed by independent review of the EEGs by 2 neurophysiologists.RESULTS: Eighty percent of patients (24 of 30) randomly assigned to phenobarbital remained seizure free for 24 hours, compared with 28% of patients (15 of 53) randomly assigned to levetiracetam (P , .001; relative risk 0.35 [95% confidence interval: 0.22-0.56]; modified intention-to-treat population). A 7.5% improvement in efficacy was achieved with a dose escalation of levetiracetam from 40 to 60 mg/kg. More adverse effects were seen in subjects randomly assigned to phenobarbital (not statistically significant). CONCLUSIONS:In this phase IIb study, phenobarbital was more effective than levetiracetam for the treatment of neonatal seizures. Higher rates of adverse effects were seen with phenobarbital treatment. Higher-dose studies of levetiracetam are warranted, and definitive studies with long-term outcome measures are needed.WHAT'S KNOWN ON THIS SUBJECT: In 1999, a randomized controlled trial comparing phenobarbital and phenytoin in neonates revealed that each drug had 45% efficacy. These treatments remain the standard of care for neonatal seizures. Levetiracetam has a better safety profile; however, its efficacy is unproven in neonates.WHAT THIS STUDY ADDS: In this study conducted in the hypothermia era and with near real-time response to continuous video EEG monitoring, phenobarbital was more effective than levetiracetam in achieving seizure cessation. Dose-finding studies and phase III trials with long-term outcomes are needed.

Background: Prior epidemiological work has shown higher mortality in ischemic stroke patients admitted on weekends, which has been termed the ‘weekend effect’. Our aim was to assess stroke patient outcomes in order to determine the significance of the ‘weekend effect’ at 2 comprehensive stroke centers. Methods: Consecutive stroke patients were identified using prospective databases. Patients were categorized into 4 groups: intracerebral hemorrhage (ICH group), ischemic strokes not treated with IV t-PA (intravenous tissue plasminogen activator; IS group), acute ischemic strokes treated with IV t-PA (AIS-TPA group), and transient ischemic attack (TIA group). Weekend admission was defined as the period from Friday, 17:01, to Monday, 08:59. Patients treated beyond the 3-hour window, receiving intra-arterial therapy, or enrolled in nonobservational clinical trials were excluded. Patient demographics, NIHSS scores, and admission glucose levels were examined. Adverse events, poor functional outcome (modified Rankin scale, mRS, 3–6), and mortality were compared. Results: A total of 2,211 patients were included (1,407 site 1, 804 site 2). Thirty-six percent (800/2,211) arrived on a weekend. No significant differences were found in the ICH, IS, AIS-TPA, or TIA groups with respect to the rate of symptomatic ICH, mRS on discharge, discharge disposition, 90-day mRS, or 90-day mortality when comparing weekend and weekday groups. Using multivariate logistic regression to adjust for site, age, admission NIHSS, and blood glucose, weekend admission was not a significant independent predictive factor for in-hospital mortality in all strokes (OR = 1.10, 95% CI 0.74–1.63, p = 0.631). Conclusions: Our results suggest that comprehensive stroke centers (CSC) may ameliorate the ‘weekend effect’ in stroke patients. These results may be due to 24/7 availability of stroke specialists, advanced neuroimaging, or ongoing training and surveillance of specialized nursing care available at CSC. While encouraging, these results require confirmation in prospective studies.

The goal of preclinical Alzheimer disease (AD) clinical trials is to move diagnosis and treatment to presymptomatic stages, which will require biomarker testing and disclosure.OBJECTIVE To assess the short-term psychological outcomes of disclosing amyloid positron emission tomography results to older adults who did not have cognitive impairment. DESIGN, SETTING, AND PARTICIPANTSThis observational study included participants who were screening for a multisite randomized clinical trial that began on February 28, 2014, and is anticipated to be completed in 2022. Participants aged 65 to 85 years who had no known cognitive impairments underwent an amyloid positron emission tomography scan and learned their result from an investigator who used a protocol-specified process that included prescan education and psychological assessments. This report compares participants with elevated amyloid levels with at least 1 available outcome measure with participants who did not have elevated amyloid levels who enrolled in an observational cohort study and

Background and Purpose Therapeutic hypothermia (TH) is a potent neuroprotectant approved for cerebral protection after neonatal hypoxia-ischemia and cardiac arrest. TH for acute ischemic stroke is safe and feasible in pilot trials. We designed a study protocol to provide safer, faster TH in stroke patients. Methods Safety procedures and 4°C saline infusions for faster cooling were added to the Intravascular Cooling Treatment in Acute Stroke (ICTuS) trial protocol. A femoral venous intravascular cooling catheter following intravenous rt-PA in eligible patients provided 24 hours cooling followed by a 12 hour re-warm. Serial safety assessments and imaging were performed. The primary endpoint was 3-month modified Rankin score 0,1. Results Of the intended 1600 subjects, 120 were enrolled before the study was stopped. Randomly, 63 were to receive hypothermia (HY) plus anti-shivering treatment and 57 normothermia (NT). Compared to prior studies, cooling rates were improved with a cold saline bolus, without fluid overload. The intention-to-treat primary outcome of 90-day mRS 0,1 occurred in 33% HY and 38% NT subjects, OR (95% CL) of 0.81 (0.36, 1.85). Serious adverse events occurred equally. Mortality was 15.9% HY and 8.8% NT subjects, OR (95% CL) of 1.95 (0.56, 7.79). Pneumonia occurred in 19% HY vs. 10.5% in NT subjects, OR (95% CL) of 1.99 (0.63, 6.98). Conclusion Intravascular TH was confirmed to be safe and feasible in rt-PA treated acute ischemic stroke patients. Protocol changes designed to reduce pneumonia risk appeared to fail, although the sample is small. Clinical trial registration clinicaltrials.gov NCT 01123161.