Mitchell Nides

BACKGROUND AND METHODS: Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8. RESULTS: The abstinence rates at 12 months were 15.6 percent in the placebo group, as compared with 16.4 percent in the nicotine-patch group, 30.3 percent in the bupropion group (P<0.001), and 35.5 percent in the group given bupropion and the nicotine patch (P<0.001). By week 7, subjects in the placebo group had gained an average of 2.1 kg, as compared with a gain of 1.6 kg in the nicotine-patch group, a gain of 1.7 kg in the bupropion group, and a gain of 1.1 kg in the combined-treatment group (P<0.05). Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group (P<0.05 for both comparisons). A total of 311 subjects (34.8 percent) discontinued one or both medications. Seventy-nine subjects stopped treatment because of adverse events: 6 in the placebo group (3.8 percent), 16 in the nicotine-patch group (6.6 percent), 29 in the bupropion group (11.9 percent), and 28 in the combined-treatment group (11.4 percent). The most common adverse events were insomnia and headache. CONCLUSIONS: Treatment with sustained-release bupropion alone or in combination with a nicotine patch resulted in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo. Abstinence rates were higher with combination therapy than with bupropion alone, but the difference was not statistically significant.

BACKGROUND: Currently available smoking cessation therapies have limited success rates. Varenicline tartrate is a novel, selective nicotinic receptor partial agonist developed specifically for smoking cessation. This study evaluated the efficacy, tolerability, and safety of 3 varenicline doses for smoking cessation. Bupropion hydrochloride was included as an active control. METHODS: A phase 2, multicenter, randomized, double-blind, placebo-controlled study of healthy smokers (18-65 years old). Subjects were randomized to varenicline tartrate, 0.3 mg once daily (n = 128), 1.0 mg once daily (n = 128), or 1.0 mg twice daily (n = 127), for 6 weeks plus placebo for 1 week; to 150-mg sustained-release bupropion hydrochloride twice daily (n = 128) for 7 weeks; or to placebo (n = 127) for 7 weeks. RESULTS: During the treatment phase, the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate, 1.0 mg twice daily (48.0%; P<.001) and 1.0 mg once daily (37.3%; P<.001), than for placebo (17.1%). The bupropion rate was 33.3% (P = .002 vs placebo). The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate, 1.0 mg twice daily, group compared with the placebo group (14.4% vs 4.9%; P = .002). The bupropion rate was 6.3% (P = .60 vs placebo). Discontinuation owing to treatment-emergent adverse events was 15.9% for bupropion, 11.2% to 14.3% for varenicline, and 9.8% for placebo. No dose-related increases occurred in adverse events for varenicline. CONCLUSIONS: Varenicline tartrate demonstrated both short-term (1 mg twice daily and 1 mg once daily) and long-term efficacy (1 mg twice daily) vs placebo. Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation.

In a case-control study we assessed whether exposure to high job strain during the first 20 weeks of pregnancy increases the risk of preeclampsia and gestational hypertension. Cases (128 with preeclampsia and 201 with gestational hypertension) and controls (N = 401) were primiparous women who had a paid occupation for at least 1 week during the first 20 weeks of their pregnancy and who delivered between 1984 and 1986 in 10 hospitals of Quebec, Canada. Based on their job title, we assigned women scores of psychological demand and decision latitude derived from the National Population Health Survey and classified these women as exposed to high (high demand, low latitude) versus low (low demand, high latitude) job strain. Women exposed to high job strain were more likely to develop preeclampsia [adjusted odds ratio (aOR) = 2.1; 95% confidence interval (CI) = 1.1-4.1] than women exposed to low job strain. The risk was quite similar for women exposed to a full-time, high strain job (> or =35 hours per week) (aOR = 2.0) than in a part-time, high strain job (aOR = 1.8). High job strain increased the risk of gestational hypertension slightly (aOR = 1.3; 95% CI = 0.8-2.2). These results indicate that women exposed to high job strain are at higher risk of developing preeclampsia and, to a lesser extent, gestational hypertension.

Waters adjacent to the County of Los Angeles (CA) receive untreated runoff from a series of storm drains year round. Many other coastal areas face a similar situation. To our knowledge, there has not been a large-scale epidemiologic study of persons who swim in marine waters subject to such runoff. We report here results of a cohort study conducted to investigate this issue. Measures of exposure included distance from the storm drain, selected bacterial indicators (total and fecal coliforms, enterococci, and Escherichia coli), and a direct measure of enteric viruses. We found higher risks of a broad range of symptoms, including both upper respiratory and gastrointestinal, for subjects swimming (a) closer to storm drains, (b) in water with high levels of single bacterial indicators and a low ratio of total to fecal coliforms, and (c) in water where enteric viruses were detected. The strength and consistency of the associations we observed across various measures of exposure imply that there may be an increased risk of adverse health outcomes associated with swimming in ocean water that is contaminated with untreated urban runoff.

We studied patterns of inhaler usage in a sample of participants from two centers in the Lung Health Study clinical trial. The inhaler, containing either ipratropium bromide or a placebo, was prescribed to be taken as two inhalations three times daily. For 4 months we recorded adherence by both self-report (n = 95) and canister weight change (n = 70). We compared these results with data obtained from a microprocessor monitoring device, the Nebulizer Chronolog (NC), which records the date and time of each inhaler actuation. Seventy-three percent of the participants reported using the inhaler an average of three times daily; however, NC data showed that only 15% of the participants actually used the inhaler an average of 2.5 or more times per day. Canister weight overestimated adherence because only 62% of the NC sets contained the prescribed two actuations. Fourteen percent showed a pattern of actuation of their inhalers more than 100 times in a 3-h interval. We interpret this usage pattern to reflect deliberate emptying of inhalers to appear to be in good compliance with the prescribed program. We conclude that self-report and weighing of inhaler canisters overestimate adherence to the prescribed regimens. Furthermore, a substantial number of monitored inhaler users appear to deliberately dump their medication prior to follow-up visits.