An open-label pilot study of pregabalin pharmacotherapy for alcohol use disorder.

Background: There is a need for alcohol use disorder (AUD) pharmacotherapy that can be administered to actively drinking outpatients. Pregabalin, a gabapentoid anticonvulsant, has preliminary evidence supporting effects on alcohol withdrawal and AUD.Objectives: To evaluate the safety, tolerability, and optimal dosing of pregabalin for treating AUD.Methods: In an open-label, 8-week, outpatient trial of eighteen adults (nine women) with AUD, participants were titrated to 600 mg/day (or the maximum tolerated dose) over 3 weeks and then maintained for 5 weeks.Results: The majority (11/14, 78.6%) of participants with at least one-week of medication exposure achieved a maximum dose of 600 mg/day. Mean retention was 6.8 weeks (SD = 2.6). Eighty percent (12/15) of participants with post-enrollment data reported any adverse effects during the trial; and for those reporting adverse effects the most common were drowsiness (33.3%, 4/12), and fogginess (25%, 3/12), dizziness (25%, 3/12), and insomnia (25%, 3/12). Two participants discontinued study medication due to adverse effects and one had a dose reduction. Mean Heavy Drinking Days (HDD)/week decreased significantly by 3.43 days (SD = 2.47; median (IQR) = 4.00 (1.00 to 5.50)); Wilcoxon signed rank test statistic ((S) = 49.5, p = .0006). Mean proportion of HDD significantly decreased on average by 48.7% (SD = 35.1%; median (IQR) = 57.1% (14.3% to 78.6%)). The proportion of abstinent days increased significantly on average by 36.1% (SD = 35.0%; median (IQR) = 17.9% (14.3% to 75.0%); S = 49.5, p = .0005).Conclusions: Pregabalin treatment of AUD appears to be safe and well tolerated in doses up to 600 mg per day.Trial Registration: clinicaltrials.gov identifier: NCT03256253.

3D airway model to assess airway dead space.

High flow therapy works partly by washout of airway dead space, the volume of which has not been quantified in newborns. This observational study aimed to quantify airway dead space in infants and to compare efficacy of washout between high flow devices in three-dimensional (3D) printed airway models of infants weighing 2.5-3.8 kg. Nasopharyngeal airway dead space volume was 1.5-2.0 mL/kg in newborns. A single cannula device produced lower carbon dioxide (CO2) levels than a dual cannula device (33.7, 31.2, 23.1, 15.9, 10.9 and 6.3 mm Hg vs 36.8, 35.5, 32.1, 26.8, 23.1 and 18.8 mm Hg at flow rates of 1, 2, 3, 4, 6 and 8 L/min, respectively; p<0.0001 at all flow rates). Airway pressure was 1 mm Hg at all flow rates with the single cannula but increased at higher flow rates with the dual cannula.Relative nasopharyngeal airway dead space volume is increased in newborns. In 3D-printed airway models, a single cannula high flow device produces improved CO2 washout with lower airway pressure.