Virtual coordinator and site training and reorganization of a multisite consortium upon grant renewal: Challenges of the NeuroNEXT network.

The COVID-19 pandemic abruptly forced changes in how to conduct multicenter clinical research. Gone were the days of face-to-face meetings and working together in person. Virtual teams became the norm rather than exception. The Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT: NN) was created with a vision to conduct studies in neurological diseases through partnership with academia, private foundations and industry. 1 A fundamental aspect of the establishment and maintenance of this network was and is the NeuroNEXT virtual coordinator network. We found ourselves well-prepared for methods required of the pandemic because of our prior experience.

Synergistic effect of sleep depth and seizures correlates with postictal heart rate.

Our objective was to determine the effect of sleep on heart rate following a recorded seizure. We prospectively acquired heart rate data in hospitalized epilepsy monitoring unit patients. We analyzed heart rate trends for multiple seizures (n = 101) in patients (n = 42) with electroencephalographically confirmed events. The patient's sleep state was scored for the 5 min preceding each seizure and correlated with the postictal nadir heart rate (PINHR). The depth of sleep during the 5 min before a seizure correlated (correlation coefficient [CC] = -.229, p < .05) with PINHR. This result was more significant and strengthened (CC = -.272, 95% confidence interval = -.392 to -.152, p < .001) when adjusted for covariates of age, generalized tonic-clonic seizures, and baseline heart rate. Sleep depth is an independent predictor of the change in heart rate following a seizure. Diminished heart rate following a seizure in the setting of sleep is likely secondary to non-rapid eye movement sleep's synergistic effect on parasympathetic tone.

Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington's Disease Patients-A Randomized Phase 2 Clinical Trial.

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington's disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington's Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression.

Population pharmacokinetics of oral baclofen in pediatric patients with cerebral palsy.

OBJECTIVE: To characterize the population pharmacokinetics (PK) of oral baclofen and assess impact of patient-specific covariates in children with cerebral palsy (CP) in order to support its clinical use. SUBJECTS DESIGN: Children (2-17 years of age) with CP received a dose of titrated oral baclofen from 2.5 mg 3 times a day to a maximum tolerated dose of up to 20 mg 4 times a day. PK sampling followed titration of 10-12 weeks. Serial R- and S-baclofen plasma concentrations were measured for up to 16 hours in 49 subjects. Population PK modeling was performed using NONMEM 7.1 (ICON PLC; Ellicott City, Maryland). RESULTS: R- and S-baclofen showed identical concentration-time profiles. Both baclofen enantiomers exhibited linear and dose/kg-proportional PK, and no sex differences were observed. Average baclofen terminal half-life was 4.5 hours. A 2-compartment PK model with linear elimination and transit absorption steps adequately described concentration-time profiles of both baclofen enantiomers. The mean population estimate of apparent clearance/F was 0.273 L/h/kg with 33.4% inter-individual variability (IIV), and the apparent volume of distribution (Vss/F) was 1.16 L/kg with 43.9% IIV. Delayed absorption was expressed by a mean transit time of 0.389 hours with 83.7% IIV. Body weight, a possible genetic factor, and age were determinants of apparent clearance in these children. CONCLUSION: The PK of oral baclofen exhibited dose-proportionality and were adequately described by a 2-compartment model. Our population PK findings suggest that baclofen dosage can be based on body weight (2 mg/kg per day) and the current baclofen dose escalation strategy is appropriate in the treatment of children with CP older than 2 years of age.

Prevalence of baby bottle versus breastfeeding graphics on products in national chain stores.

OBJECTIVE: This study surveyed the prevalence of bottle versus breastfeeding graphic images on products marketed for pregnant mothers and young children available for purchase in national chain stores. STUDY DESIGN AND METHODS: This was a product survey/content analysis. Eighteen national chain stores located in a 10-mile radius of Charlottesville, VA were visited. In total, 2,670 individual items in 11 categories of baby shower and baby gift merchandise (shower invitations, greeting cards, gift wrap, shower decorations, baby dolls, baby books, infant clothing, bibs, nursery decorations, baby blankets, and disposable diapers) were assessed. The main outcome measures were prevalences of baby bottle and breastfeeding graphic images. RESULTS: Baby bottle images were found on products in eight of the 11 categories of items surveyed. Thirty-five percent of baby dolls were marketed with a baby bottle. The prevalence of bottle images on items in all other categories, however, was low. Of the 2,670 items surveyed, none contained a breastfeeding image. CONCLUSIONS: The low prevalence of baby bottle images on commonly purchased baby gift and baby shower items is encouraging. However, the absence of breastfeeding images and the relatively high prevalence of baby dolls marketed with a baby bottle demonstrate that breastfeeding is not portrayed as the physiologic norm on these products. Product designers should explore ways to promote breastfeeding, consumers should make informed choices in product selection, and advocacy groups should promote guidelines for these products.