ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

Objective To evaluate the effect of video laryngoscopy on the rate of endotracheal intubation on first laryngoscopy attempt among critically ill adults. Design A randomized, parallel-group, pragmatic trial of video compared with direct laryngoscopy for 150 adults undergoing endotracheal intubation by Pulmonary and Critical Care Medicine fellows. Setting Medical intensive care unit in a tertiary, academic medical center. Patients Critically ill patients ≥ 18 years old. Interventions Patients were randomized 1:1 to video or direct laryngoscopy for the first attempt at endotracheal intubation. Measurements and Main Results Patients assigned to video (n = 74) and direct (n = 76) laryngoscopy were similar at baseline. Despite better glottic visualization with video laryngoscopy, there was no difference in the primary outcome of intubation on the first laryngoscopy attempt (video 68.9% versus direct 65.8%, p = 0.68) in unadjusted analyses or after adjustment for the operator’s previous experience with the assigned device (odds ratio for video laryngoscopy on intubation on first attempt 2.02, 95% CI 0.82 – 5.02, p = 0.12). Secondary outcomes of time to intubation, lowest arterial oxygen saturation, complications, and in-hospital mortality were not different between video and direct laryngoscopy. Conclusions In critically ill adults undergoing endotracheal intubation, video laryngoscopy improves glottic visualization but does not appear to increase procedural success or decrease complications. Trial Registration clinicaltrials.gov Identifier: NCT02051816

Nicotine is the major addictive agent in tobacco smoke, and it is metabolized extensively by oxidation and glucuronide conjugation. The contributions of ethnicity and UGT2B10 haplotype on variation in nicotine metabolism were investigated. Nicotine metabolism was evaluated in two populations of smokers. In one population of African American and European American smokers (n ϭ 93), nicotine and its metabolites were analyzed in plasma and 24-h urine over 3 days while participants were abstinent and at steady state on the nicotine patch. In a second study of smokers (n ϭ 84), the relationship of a UGT2B10 haplotype linked with D67Y to nicotine and cotinine glucuronidation levels was determined. We observed that both African American ethnicity and the UGT2B10 D67Y allele were associated with a low glucuronidation phenotype. African Americans excreted less nicotine and cotinine as their glucuronide conjugates compared with European Americans; percentage of nicotine glucuronidation, 18.1 versus 29.3 (p Ͻ 0.002) and percentage of cotinine glucuronidation, 41.4 versus 61.7 (p Ͻ 0.0001). In smokers with a UGT2B10 Tyr67 allele, glucuronide conjugation of nicotine and cotinine was decreased by 20% compared with smokers without this allele. Two key outcomes are reported here. First, the observation that African Americans have lower nicotine and cotinine glucuronidation was confirmed in a population of abstinent smokers on the nicotine patch. Second, we provide the first convincing evidence that UGT2B10 is a key catalyst of these glucuronidation pathways in vivo.

Background: Tobacco exposure is routinely assessed by quantifying nicotine metabolites in plasma or urine. On average, 80% of nicotine undergoes C-oxidation to cotinine. However, interindividual variation in nicotine glucuronidation is substantial, and glucuronidation accounts for from 0% to 40% of total nicotine metabolism. We report here the effect of a polymorphism in a UDP-glucuronsyltransferase, UGT2B10, on nicotine metabolism and consumption.Methods: Nicotine, cotinine, their N-glucuronide conjugates, and total trans-3′-hydroxycotinine were quantified in the urine (n = 327) and plasma (n = 115) of smokers. Urinary nicotine N-oxide was quantified in 105 smokers. Nicotine equivalents, the sum of nicotine and all major metabolites, were calculated for each smoker. The relationship of the UGT2B10 Asp67Tyr allele to nicotine equivalents, N-glucuronidation, and C-oxidation was determined.Results: Individuals heterozygous for the Asp67Tyr allele excreted less nicotine or cotinine as their glucuronide conjugates than did wild-type, resulting in a 60% lower ratio of cotinine glucuronide to cotinine, a 50% lower ratio of nicotine glucuronide to nicotine, and increased cotinine and trans-3′-hydroxycotinine. Nicotine equivalents, a robust biomarker of nicotine intake, were lower among Asp67Tyr heterozygotes compared with individuals without this allele: 58.2 (95% confidence interval, 48.9-68.2) versus 69.2 nmol/mL (95% confidence interval, 64.3-74.5).Conclusions: Individuals heterozygous for UGT2B10 Asp67Tyr consume less nicotine than do wild-type smokers. This striking observation suggests that variations in nicotine N-glucuronidation, as reported for nicotine C-oxidation, may influence smoking behavior.Impact: UGT2B10 genotype influences nicotine metabolism and should be taken into account when characterizing the role of nicotine metabolism on smoking. Cancer Epidemiol Biomarkers Prev; 19(6); 1423-31.