David P.L. Sachs

The influence of gender, race, and menthol content on tobacco exposure measures.

Research has suggested that race, gender, and menthol cigarette use influence tobacco-smoke exposure measures and smoking-related disease risk. For example, a high proportion of Black smokers prefer menthol cigarettes and, despite smoking fewer cigarettes per day (CPD) than do Whites, tend to have higher cotinine levels. Additionally, Black males are more at risk for smoking-related lung cancer. High cotinine levels and smoking menthol cigarettes may lead to higher toxin intake, which contributes to increased disease risk. We explored the relationship between tobacco exposure variables (i.e., cotinine, CPD, carbon monoxide [CO], nicotine content, and nicotine dependence) with respect to race, gender, and menthol content in a sample of 307 smokers recruited from the greater Boston area to participate in a smoking cessation treatment trial. The pattern of correlations between tobacco exposure measures and cotinine showed a consistently positive correlation between cotinine and CO in all smokers and a correlation between cotinine and CPD in those who smoked nonmenthol cigarettes. Cotinine and CPD correlations varied by gender and race among menthol cigarette smokers. Consistently, we found a significant gender x race x menthol interaction on salivary cotinine level as well as cotinine/CPD ratio. These findings suggest that the relationship between number of cigarettes consumed and salivary cotinine is more complex than previously believed. It is not sufficient to look at race alone; researchers and clinicians need to look at race and gender concurrently, as well as type of cigarette consumed.

Efficacy of Bupropion for Relapse Prevention in Smokers With and Without a Past History of Major Depression

AbstractBACKGROUND: This study evaluated the efficacy of bupropion for relapse prevention in smokers with and without a past history of major depressive disorder. Changes in depressive symptoms were also examined. DESIGN: Data were gathered prospectively from a randomized, double-blind relapse prevention trial of bupropion conducted at five study sites. A total of 784 smokers (54% female, 97% white) were enrolled. Using the Structured Clinical Interview for Depression, 17% of the subjects reported a past history of major depressive disorder at baseline. All subjects received open-label bupropion SR (300 mg/d) for 7 weeks. Subjects abstinent from smoking at the end of 7 weeks (N=429) were randomized to bupropion SR (300 mg/d) or placebo for the remainder of the year and followed for 1 year off medication. The primary outcome measures were median time to relapse to smoking and the 7-day point-prevalence smoking abstinence rate. Self-reported abstinence from smoking was verified by expired air carbon monoxide. The Beck Depression Inventory was used to assess depressive symptoms at baseline and at weeks 8 and 12. RESULTS: Median time to relapse did not differ by past history of major depressive disorder. Bupropion was associated with higher point-prevalence smoking abstinence at the end of medication compared to placebo (P=.007), independent of a past history of major depressive disorder. Moreover, change in depressive symptoms during the double-blind phase did not differ for those with and without a past history of major depressive disorder. CONCLUSIONS: Extended use of bupropion for relapse prevention is effective for smokers with and without a history of major depression.

Effects of gender on relapse prevention in smokers treated with bupropion SR

BACKGROUND Recent data suggest that women smokers respond differently than men to cessation pharmacotherapies, particularly nicotine replacement therapy (NRT). Lower abstinence and higher relapse rates are often reported for women treated with NRT. Gender effects for those treated with non-nicotinic, bupropion-hydrochloride sustained release for relapse prevention have not been studied. METHODS Data from a multicenter relapse-prevention (RP) trial of bupropion (November 1995-June 1998) were analyzed for gender differences. Men and women smokers (N=784) were treated with open-label bupropion for 7 weeks. Those abstinent at Week 7 (n=432) were enrolled in the double-blind relapse-prevention phase and randomized to placebo or continued bupropion for 45 additional weeks. RESULTS Differences in point-prevalence abstinence rates between men (61.8%) and women (55.6%) in open-label bupropion (Week 7) were not significant. In the RP-phase Week 52, continuous abstinence rates for men and women were 37.8% and 36.4% (bupropion) and 36.6% and 29.9% (placebo), respectively; point-prevalence abstinence rates for men and women were 54.1% and 55.9% (bupropion) and 42.9% and 41.3% (placebo), respectively. Abstinence rates and time to relapse were superior for both men and women who received longer treatment. Gender differences within treatment groups were not significant. Median time to relapse was equal for men and women within each treatment group: Week 32 for bupropion and Week 20 for placebo. CONCLUSIONS Our data suggest that bupropion is a promising pharmacotherapy for preventing relapse, particularly for women.

Relationship between drug exposure and the efficacy and safety of bupropion sustained release for smoking cessation

A population pharmacokinetic and pharmacodynamic analysis evaluated the relationships of dose, plasma concentrations of bupropion and metabolites, and patient covariates with the safety and efficacy of bupropion sustained release (SR) for smoking cessation. A total of 519 outpatient chronic cigarette smokers were randomized to one of three bupropion SR doses: 100, 150, or 300 mg/day or placebo. The bupropion plasma concentration time data were fit and subject-specific bayesian estimates of clearance were obtained. Logistic regression analyses evaluated the role of dose, concentrations, and covariates in predicting efficacy and safety endpoints. For the evaluation of efficacy, patients were classified as quitters or non-quitters on the basis of a 4-week quit variable (defined as complete abstinence for weeks 4-7 of the study). For the evaluation of safety, patients were classified into two categories for each adverse event evaluated, corresponding to whether the patient ever experienced the adverse event during the course of the study or never experienced the event, regardless of whether the event was treatment-emergent. The efficacy of bupropion SR in facilitating smoking cessation was found to be related to dose and a mean metabolite concentration, and quitting in general was found to be related to the number of cigarettes smoked per day at baseline. Smoking cessation was 1.42, 1.69, and 2.84 times more likely in patients receiving 100, 150, and 300 mg/day of bupropion SR, respectively, as compared to placebo (p = 0.0001). As the baseline number of cigarettes smoked per day increased, the likelihood of quitting decreased regardless of the treatment condition. Insomnia and dry mouth were positively associated with mean metabolite concentrations, and dry mouth was inversely related to patient weight. Anxiety was inversely related to predicted steady-state concentration (Cpss), suggesting a positive effect on this withdrawal symptom. Bupropion SR exhibits a statistically significant dose/plasma level-response relationship for smoking cessation. Dry mouth and insomnia, related to concentrations, may be managed with dose reduction, with the realization that smoking cessation may be impaired.

Bupropion for pharmacologic relapse prevention to smoking: predictors of outcome.

The aim of this study was to identify predictors of successful relapse prevention in smokers receiving long-term sustained-release bupropion. Smokers (N= 784) who were interested in stopping smoking were enrolled in a 7-week, open-label bupropion phase. Abstinent subjects at the end of treatment and eligible to proceed (N= 429) were randomized to active bupropion or placebo through Week 52 and then followed for an additional year. The best overall predictor of less relapse to smoking was assignment to active bupropion. In aggregate, the results indicate that bupropion can be prescribed to diverse populations of smokers with expected comparable results. There was a medication effect that was independent of any predictor except older age and those who gained no or minimal weight during the open-label phase. Predictors of successful relapse prevention included lower baseline smoking rates, a Fagerström Tolerance Questionnaire score of < 6, and initiation of smoking at an older age. These data should encourage others to perform similar pharmacologic relapse prevention studies with this or other pharmacotherapies.

Medical risk and therapeutic effectiveness of rapid smoking

To assess the potential medical risks of rapid smoking, 24 healthy, male cigarette smokers were examined under the following conditions: baseline (after 12-hr tobacco abstinence), normal smoking, and rapid smoking. After normal and rapid smoking standard 12-lead EKG, arterial blood gases, and vital signs were evaluated, and during rapid smoking each subject was monitored electrocardiographically throughout the session. During or after rapid smoking there were no EKG abnormalities. Heart rate, respiratory rate, and systolic blood pressure rose after normal and rapid smoking. Many subjects developed elevated arterial pH with lowered serum potassium after rapid smoking, and two-thirds of the subjects developed relative hypoxemia. Among those who completed treatment, 61% were still abstaining from cigarettes after 6 months. Rapid smoking was found to be safe for healthy subjects. However, the safety of the technique among persons with cardiopulmonary disease cannot be predicted from the results of this study.

Effects of rapid smoking. Physiologic evaluation of a smoking-cessation therapy.

We studied 24 healthy young male smokers to ascertain the medical safety of a highly effective smoking-abatement technique called rapid smoking. In comparison with results obtained after a 12-h cigarette fast or after normal smoking, statistically significant increases occurred after rapid smoking in heart and respiratory rates, systolic blood pressure, carboxyhemoglobin, and pH (p less than 0.05), while arterial PCO2, HCO3-, and serum [K+] fell (p less than 0.05). Rapid smoking produced alveolar hyperventilation in all subjects. In eight, arterial PO2 increased appropriately, but in 16, fell paradoxically (p less than 0.01); seven had arterial PO2 below 80 torr. Because this fall could represent ventilation/perfusion mismatch due to early bronchoconstrictive disease, in subjects with normal flow/volume loops and spirometry rapid smoking may be a simple, provocative screening test for early airway disease. Despite the changes produced there were no arrhythmias. Rapid smoking is safe for healthy subjects but should not now be used for higher-risk patients.

Impact of a clinical preventive medicine curriculum for primary care faculty: Results of a dissemination model

BACKGROUND This study was designed to test a dissemination model for providing clinical preventive medicine (CPM) training to general internal medicine faculty across the United States. METHODS The model incorporated direct instruction of a few faculty as seminar facilitators who, in turn, taught a CPM curriculum to their faculty colleagues, who then could teach it to housestaff and students. The CPM curriculum consisted of six seminars that focused primarily on the risk factors for chronic diseases and on behavior change methods for modifying smoking, diet, and exercise. RESULTS Faculty who participated in the seminars had significant pre- to post-test increase in knowledge and reported self-efficacy to implement CPM strategies with patients, as well as changes in CPM clinical practices. These faculty, in turn, successfully disseminated CPM information to their housestaff, who also had increases in self-efficacy and changed clinical practices regarding CPM topics. CONCLUSIONS The successful implementation of the dissemination model attests to its viability as a mechanism for disseminating CPM curricula and increasing the emphasis on CMP issues in both clinical teaching and clinical encounters with patients.

Smoking cessation. Techniques and benefits.

Tobacco dependency syndrome is an organic disease caused by chronic use of inhaled tobacco smoke. It is occasionally controlled by willpower alone, but often requires pharmacotherapy in conjunction with various techniques to manage the psychological manifestations. The two effective drugs are bupropion, which is an oral antidepressant, and nicotine, which can be administered by several modalities, including a skin patch, an oral inhalant, a nasal spray, and a chewable oral preparation. Successful therapy may require both drugs, and multiple simultaneous nicotine modalities. High-dose nicotine therapy may achieve an abstinence rate of 80% during therapy, but maintaining drug-free abstinence at such high levels over long periods is less successful, possibly because the tobacco smoke-induced changes in brain structure and function are not easily reversed.

Environmental tobacco smoke and lung cancer incidence.

Tobacco smoking has been irrefutably linked to lung cancer risk. Exposure to environmental tobacco smoke and lung cancer risk has been more controversial. Various sources have claimed confounding factors such as diet and classification bias could account for the reported link. We review the available evidence and some recent papers on this topic and conclude that the evidence linking environmental tobacco smoke and lung cancer is unequivocal and cannot be explained by confounding factors.