Experience and expectations of patients on weight loss: The Learning Health System Network Experience.

OBJECTIVE: Weight perception and degree of confidence in achieving healthy lifestyle can be determinants of engagement in obesity interventions. This study explored patients' perceived need for weight loss and the degree of self-confidence in ability to lose weight and sought to identify factors associated with patients' self-confidence in ability to lose weight. METHODS: The authors analysed data from a survey mailed to primary care patients within five sites of the Learning Health Systems Network that explored participants' prior experience with weight management. RESULTS: Among the 2,263 participants who completed the survey section on 'Patients' Experience with Weight Management', perceived need to lose 51 lb or more was statistically significant among those with class III obesity compared with other body mass index (BMI) groups (p value < 0.001). Reported desire to lose weight was also significantly higher among those with the highest BMI than those who were overweight (p value < 0.001). However, this same group had the lowest belief in ability to lose weight (p value < 0.001). In a multiple regression analysis, female gender, higher BMI and need to lose >10 lb were each independently associated with less belief in being able to lose weight. CONCLUSIONS: Patients had varying perceptions on weight loss; those with category III obesity had the highest desire to lose weight but had the least confidence in ability to lose weight. Higher BMI, female gender and need to lose >10 lb were associated with decreased self-confidence in ability to lose weight.

Lessons learned on the road to a smoke-free Italy.

In the face of strong and protracted opposition by the Tobacco Industry (TI) and its allies, Italy's national smoke-free legislation came into force in 2005 prohibiting smoking in all indoor public places and workplaces including offices, bars, and restaurants. Using internal TI documents made public through US litigation, we reveal the industry's nearly 40-year effort to influence health policy related to secondhand smoke, including attempts to block Italy's national smoke-free legislation. Strategies included manipulating hospitality groups and establishing front organizations, manipulating journalists and media, and manipulating the science and direct lobbying against smoking restrictions. The TI's extensive plan to thwart smoke-free efforts in Italy can be used to inform other countries about the industry's tactics and Italy's experience in overcoming them by ultimately implementing a comprehensive workplace smoke-free law.

Nicotine patch use in pregnant smokers: smoking abstinence and delivery outcomes.

OBJECTIVE: To describe smoking abstinence and fetal effects of pregnant smokers who received 8 weeks of nicotine patch therapy. METHODS: One-sample study of 21 pregnant women smoking > or = 15 cigarettes/day during their third trimester of pregnancy despite physician advice to stop. Nicotine patch therapy (22 mg/24 h) was initiated during the first day of a 4-day in-hospital study and continued for a total of 8 weeks. Subjects returned weekly until delivery, at 4 weeks after delivery, and at 6 and 12 months after patch therapy. Fetal growth and well-being were assessed using ultrasound examinations and non-stress tests. RESULTS: Eight of 21 subjects completed all 8 weeks of patch therapy according to the protocol. Five subjects (24%) discontinued using the nicotine patch, owing to adverse skin reactions. There were eight subjects (38%) who were biochemically confirmed abstinent from smoking at the time of delivery; of these, seven were continuously abstinent from the start of patch therapy. Centile weight for gestational age did not change significantly over time for 12 subjects with serial ultrasound measurements available at baseline, 4 weeks and 8 weeks following initiation of patch therapy. In all cases, non-stress tests remained reactive or became reassuring with observation. No significant preterm deliveries occurred (gestational ages of 36.3-41.1 weeks). Three infants suffered severe neonatal morbidity; however, these problems were unrelated to nicotine patch therapy. CONCLUSION: Nicotine patch therapy has potential benefit for pregnant smokers who continue to smoke despite physician advice to stop.

A community-wide smoking cessation program: Quit and Win 1998 in Olmsted county.

BACKGROUND: Quit and Win is a community-wide stop smoking contest to help cigarette smokers stop smoking and educate the general public concerning smoking hazards. METHODS: All community residents, 15 years of age or older, were eligible to participate in either the stop smoking contest or the supporter contest. A random telephone survey to local households was conducted before and after the Quit and Win contest to assess the level of knowledge and attitude changes about smoking. RESULTS: Of the 304 smokers enrolled in the contest, 42% self-reported continuous tobacco abstinence for the 4-week contest period and 11% were abstinent at 1 year postcontest. Significant predictors for tobacco abstinence during the contest were formal education beyond high school, absence of other smokers in the household, having a support person enrolled in the support person contest, and the type of relationship that the support person had with their smoker. Survey results showed that this contest changed some local attitudes and increased general knowledge of smoking hazards. CONCLUSIONS: Community-wide stop smoking contests can be used to engage smokers and their support in the community and can be successful in reducing tobacco use.

Bupropion for smoking cessation : predictors of successful outcome.

OBJECTIVES: To identify predictors of smoking abstinence at the end of medication use that could assist in the optimal use of a sustained-release (SR) form of bupropion for treating cigarette smokers. DESIGN: A double-blind, placebo-controlled, dose-response trial. SETTING: Multicenter (three sites) study conducted in the United States. PARTICIPANTS: Six hundred fifteen healthy men and women (> or = 18 years of age) who were smoking > or = 15 cigarettes per day and who were motivated to stop smoking. INTERVENTION: Random assignment of patients to placebo or SR bupropion treatment, 100, 150, or 300 mg/d, for 7 weeks (total duration of study was 52 weeks: 7 weeks of treatment and 45 weeks of follow-up). MEASUREMENTS AND RESULTS: Logistic regression was used to identify predictors of abstinence at the end of the medication phase. Univariate predictors included the following: bupropion dose (p < 0.001); older age (p = 0.024); lower number of cigarettes smoked per day (cpd) (p < 0.001); lower Fagerström Tolerance Questionnaire score (p = 0.011); longest time previously abstinent that was < 24 h or > 4 weeks (p < 0.001); absence of other smokers in the household (p = 0.021); greater number of previous stop attempts (p = 0.019); and study site (p = 0.004). Multivariate predictors of abstinence at the end of the medication phase were the following: higher bupropion dose (p < 0.001); lower number of cpd (p < 0.001); longest time previously abstinent from smoking (p = 0.002); male gender (p = 0.014); and study site (p = 0.021). CONCLUSION: Bupropion SR therapy was effective in treating cigarette smokers independently of all other characteristics studied. Lower smoking rate, brief periods (ie, < 24 h) or long periods (ie, > 4 weeks) of abstinence with previous attempts to stop smoking, and male gender were predictive of better outcomes, independent of the dose of bupropion that was used.

Residential (inpatient) treatment compared with outpatient treatment for nicotine dependence.

OBJECTIVE: To compare smoking abstinence outcomes between smokers treated in a residential (inpatient) program and those treated in an outpatient program to determine if residential treatment was superior to outpatient treatment in smokers with moderate to severe nicotine dependence. PATIENTS AND METHODS: Patients treated in the residential nicotine dependence program at the Mayo Clinic, Rochester, Minn., between May 1, 1992, and January 31, 1996, were selected for this study. Each patient in the residential treatment group (n=146) was matched to 2 patients who received an outpatient nicotine dependence consultation by a trained counselor (n=292). Each patient was matched on age, sex, year seen, number of cigarettes smoked per day, longest previous abstinence, education, and marital status. Abstinence at 6 and 12 months was determined by self-report. For the purposes of analysis, each patient with missing outcome data was considered to be smoking. RESULTS: The 6-month abstinence rates for the residential group compared with the outpatient group were 45% and 26%, respectively (P<.001), and the 12-month abstinence rates were 45% and 23%, respectively (P<.001). After adjusting for matching variables that were not exactly matched (age, baseline number of cigarettes smoked per day, and longest previous abstinence) and the baseline variables, including education, age when started smoking, and degree of nicotine dependence, there was a significant effect of residential treatment on 6- and 12-month abstinence rates (P<.001). Odds ratio of 6-month abstinence in the residential group was 2.74 (95% confidence interval, 1.60-4.71; P<.001) and at 12 months was 3.03 (95% confidence interval, 1.74-5.27; P<.001). CONCLUSION: Residential treatment for tobacco dependence is superior to outpatient treatment in some smokers who are moderately to severely nicotine dependent.

Carbidopa/levodopa for smoking cessation: a pilot study with negative results.

The mesolimbic dopamine system is thought to be a critical substrate for drugs of addiction including nicotine. Since dopamine may play a critical role in mediating the reinforcing effects of nicotine, we hypothesized that administering levodopa in its therapeutic form (carbidopa/levodopa) might be effective for smoking cessation by replacing the effects of dopamine that smokers may seek during smoking. A pilot open-label study using carbidopa/levodopa for smokers wanting to stop smoking was carried out at the Mayo Clinic Nicotine Research Center, Rochester, MN. The dosing schedule was one tablet TID for 1 week, 1 1/2 tablets TID for 1 week, then two tablets TID for 6 weeks. Each tablet contained 25 mg of carbidopa and 100 mg of levodopa. The subjects were 40 adult smokers smoking > or = 20 cigarettes per day for 3 or more years. Self-reported abstinence from smoking was confirmed by expired air CO level of < or = 8 ppm. Nicotine withdrawal symptoms were assessed at baseline and daily during the medication phase. Smoking abstinence rates and withdrawal symptom relief were compared to the placebo (n = 153) arm of a previously reported bupropion smoking cessation trial. The biochemically confirmed, 7-day point-prevalence smoking abstinence rate at the end of carbidopa/levodopa treatment was 20.0% versus 19.0% for the placebo group (p > 0.10), and 12.5% of the carbidopa/levodopa group were abstinent versus 15.7% for the placebo group (p > 0.10) at 6 months. Subjects from both studies had significant increases in withdrawal scores from baseline, but there were no significant differences between the two groups at any time period. We found no differences in smoking abstinence rates or nicotine withdrawal symptom relief in smokers receiving carbidopa/levodopa compared to placebo. Despite the theoretical reasons why carbidopa/levodopa might be effective as a pharmacological adjunct in treating smokers, it was not observed in this group of smokers at this dose.

Nicotine patch therapy in 101 adolescent smokers: efficacy, withdrawal symptom relief, and carbon monoxide and plasma cotinine levels.

OBJECTIVES: To determine the efficacy of nicotine patch therapy in adolescents who want to stop smoking and to assess biochemical markers of smoking and nicotine intake. DESIGN: Nonrandomized, open-label trial using a 15 mg/16 h patch. SETTING: Two midwestern cities. SUBJECTS: One hundred one adolescents aged 13 through 17 years smoking at least 10 cigarettes per day (cpd). INTERVENTION: Six weeks of nicotine patch therapy and follow-up visits at 12 weeks and 6 months. MAIN OUTCOME MEASURES: Self-reported smoking abstinence verified by expired-air carbon monoxide (CO) level of no more than 8 ppm, nicotine withdrawal symptoms, and plasma cotinine level. RESULTS: Forty-one participants were female (mean [+/- SD] age, 16.5 [+/- 1.1] years). Median baseline smoking rate was 20.0 cpd (range, 10-40 cpd). Biochemically confirmed point prevalence smoking abstinence was 10.9% (11/101) at 6 weeks and 5.0% (5/101) at 6 months. The mean (+/- SD) plasma cotinine level at baseline was 1510.9 +/- 732.7 nmol/L; for nonsmoking subjects at weeks 3 and 6, 607.8 +/- 386.2 and 710.0 +/- 772.5 nmol/L, respectively. Plasma cotinine levels were correlated with CO levels at baseline (r = 0.27; P = .006), week 3 (r = 0.34; P = .004), and week 6 (r = 0.26; P = .03) and with mean cigarettes smoked per day during weeks 3 (r = 0.24; P = .04) and 6 (r = 0.30; P = .02). Mean smoking rates decreased significantly during the study, an effect that lessened at 12 weeks and 6 months. CONCLUSIONS: Nicotine patch therapy plus minimal behavioral intervention does not appear to be effective for treatment of adolescent smokers. Plasma cotinine and CO levels appear to be valid measures of smoking rates during the cessation process, but not at baseline. Smoking rates were reduced throughout the study. Additional pharmacological and behavioral treatments should be considered in adolescent smokers.

Does smoking reduction result in reduction of biomarkers associated with harm? A pilot study using a nicotine inhaler.

The aim of the study was to determine if smoking reduction using a nicotine inhaler in heavy cigarette smokers who wanted to reduce but not stop smoking results in decreased levels of known biomarkers of harm. The study design was a one-sample within-subject comparative open-label study of 23 (10 male and 13 female) subjects using a nicotine inhaler to reduce smoking, with follow-up at 24 weeks. A structured protocol was used with a smoking-reduction schedule from 40 or more cigarettes per day to 10 cigarettes per day by week 9. Behavioral counseling was provided by a research assistant and ad lib use of the nicotine inhaler for 12 weeks was permitted. Blood thiocyanate, cotinine, 4-aminobiphenyl hemoglobin adducts; urine NNAL and NNAL-glucuronide; and expired air carbon monoxide were measured. On average, the subjects were able to reduce their smoking by over 50% at week 12, but only two were able to reduce to 10 cigarettes per day. The reported reduction in smoking was not associated with a consistent reduction in the biomarkers. There was no reduction in the NNAL, 4-aminobiphenyl hemoglobin adducts nor carbon monoxide levels of expired air. There was a significant reduction of NNAL-glucuronide and the sum of NNAL and NNAL-glucuronide but only at week 24. Thiocyanate levels increased. Before widely promoting harm reduction as a treatment strategy for heavy smokers, more research needs to be performed to prove conclusively that such smokers who want to reduce but not stop can actually reduce and maintain their smoking rate at a level which is likely to reduce harm. It also needs to be determined whether a reduction in the smoking rate translates into reduction of harm. At the present, for heavy smokers, an abstinence approach seems to be more scientifically sound.

Cholesterol-lowering effect of stanol ester in a US population of mildly hypercholesterolemic men and women: a randomized controlled trial.

OBJECTIVE: To determine the efficacy of stanol esters in lowering cholesterol in a US population. SUBJECTS AND METHODS: After a run-in phase, 318 subjects were randomized to receive one of the following margarine-like spreads containing stanol ester or placebo for 8 weeks: EU 3 G: 1 g of stanol (ester form) per 8-g serving of a European formula 3 times a day; US 3 G: 1 g of stanol (ester form) per 8-g serving of a US reformulation 3 times a day; US 2 G: 0.67 g of stanol (ester form) per 8-g serving of a US reformulation 3 times a day; or placebo spread. RESULTS: Mean +/- SD baseline total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were 233+/-20 and 153+21 mg+/-dL, respectively. In the US 3 G group, 3 g daily of stanol esters lowered TC and LDL-C levels by 6.4% and 10.1%, respectively. There was a dose-dependent response compared with 2 g daily (US 2 G). Triglyceride and high-density lipoprotein cholesterol levels were unchanged. The incidence of adverse effects was not different from placebo. Serum vitamin A and 25-hydroxyvitamin D levels were not affected. CONCLUSIONS: Stanol esters lowered TC and LDL-C levels in a mildly hypercholesterolemic US population without evidence of adverse effects. It may be a useful dietary adjunct to lower cholesterol.

Over-the-counter nicotine patch therapy for smoking cessation: results from randomized, double-blind, placebo-controlled, and open label trials.

OBJECTIVES: The purpose of this study was to determine the efficacy and safety of the nicotine patch for smoking cessation in an over-the-counter environment. The years of study were 1994 to 1995. METHODS: Parallel 6-week trials were conducted: a placebo-controlled trial of no-cost 22-mg, 24-hour nicotine patch therapy and an open label trial of the same therapy with patches purchased by subjects. Participants (n = 958) were 18 years or older, had smoked at least 15 cigarettes daily for at least 6 months, and were enrolled at 3 study sites. The main outcome measure was self-reported smoking abstinence confirmed by expired carbon monoxide measurements. RESULTS: Smoking cessation rates in the placebo-controlled trial were 16.8% and 9.6% at week 6 and 8.7% and 4.3% at week 24 for the active patch and placebo groups, respectively. Smoking cessation rates in the open label-pay trial were 19.0% and 10.8% at weeks 6 and 24, respectively. A slight increase in adverse cardiovascular events was noted only in the open label-pay group in comparison with the placebo group. CONCLUSIONS: In an over-the-counter environment, the 22-mg, 24-hour nicotine patch is effective and safe for smoking cessation treatment.

Nicotine patch use in pregnant smokers: nicotine and cotinine levels and fetal effects.

OBJECTIVE: The aims of this study were (1) to determine whether nicotine patch therapy for pregnant women smokers acutely compromises fetal well-being and (2) to determine the serum and urine nicotine and cotinine levels in pregnant women while smoking, while abstinent from smoking, and while receiving nicotine patch therapy compared with levels in a historical control group of nonpregnant women smokers who abstained from smoking while receiving comparable doses of nicotine patch therapy. STUDY DESIGN: Pregnant cigarette smokers (n = 21) aged >/=18 years whose fetuses were beyond 24 weeks' gestational age were recruited for this 1-sample, repeated-measures study. Serial measurements of the mother and fetus were made at baseline while the mother was smoking, while abstaining from smoking, and while using nicotine patch therapy for 4 days in a special care hospital unit. Nonpregnant women smokers of similar age were used for comparison. Morning and afternoon serum and 24-hour urine levels of nicotine and cotinine were obtained during hospitalization. Indicators of fetal well-being assessed were fetal heart rate and reactivity, systolic/diastolic ratio of blood flow in the umbilical artery, and fetal activity seen on ultrasonography and quantitated as biophysical profiles. RESULTS: No evidence of fetal compromise was seen during the inpatient phase while nicotine patch therapy was administered. Steady state (inpatient day 4) serum levels of nicotine were similar to smoking levels and to those seen in historical control subjects (ie, nonpregnant women of child-bearing age who were abstinent from smoking and who used the same nicotine patch). Morning serum cotinine levels were significantly higher (P =.038) in the nonpregnant subjects than in the pregnant subjects, whereas afternoon levels were not significantly different. Steady state urinary levels of nicotine and cotinine were also not significantly different in pregnant versus nonpregnant patients. On inpatient days 2, 3, and 4, when the women were not smoking and were wearing the nicotine patch, the morning fetal heart rates were significantly reduced relative to baseline when the subjects were smoking. CONCLUSIONS: Nicotine patch therapy was not found to be associated with indications of fetal compromise during the in-hospital phase of nicotine patch therapy in pregnant smokers who were abstaining. Although not conclusive because of the small sample sizes, serum nicotine levels (morning and afternoon) appear similar in pregnant and nonpregnant subjects and similar for both groups when smoking (baseline) as compared to the steady state of nicotine patch use.

Development of depression during placebo-controlled trials of bupropion for smoking cessation: case reports.

BACKGROUND: Recent attention has focused on the relationship between depression and smoking cessation. This article describes 5 cases of severe depression that occurred during 2 multicenter trials using bupropion for smoking cessation. METHOD: Subjects were participants in 2 randomized, double-blind, placebo-controlled studies investigating the efficacy of bupropion for smoking cessation. Data from both trials were restricted to subjects at the Rochester, Minn., site in order to have access to the medical records for information on depression diagnosis, treatment, and follow-up. The first trial involved 205 smokers who received active bupropion or placebo for 7 weeks. In the second trial, 252 smokers received open-label bupropion therapy for 7 weeks. Those abstinent from smoking at the end of week 7 (N = 148) were randomly assigned to a 45-week, double-blind, relapse-prevention phase. RESULTS: In the first trial, 1 of the 205 participants (0.49%) experienced major depression during the 7-week treatment phase. In the second trial, none of the 252 subjects developed major depression during the 7-week, open-label phase. When results of both trials across the 7-week treatment phase (study 1, N = 205; study 2, N = 252) are combined, the rate of developing major depression was 0.22% (1 of 457). Of the 457 subjects, none of the 51 who received placebo and 1 (0.25%) of the 406 who received active bupropion developed major depression. In the second trial, 4 (2.7%) of the 148 subjects randomly assigned to the 45-week, relapse-prevention phase developed depression. Overall, 4 of the 5 cases from the 2 trials had a past history of major depression prior to study entry, but none had current major depression. CONCLUSION: Major depression may occur in some individuals during smoking cessation treatment with bupropion.

Efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism.

BACKGROUND: A past history of major depression or alcoholism has been associated with poorer smoking treatment outcomes. AIM: To evaluate the efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism, and changes in depressive symptoms during smoking abstinence. METHOD: Data were drawn from a multicentre trial of bupropion for smoking cessation. Smokers (n = 615) received placebo or bupropion sustained-release at 100, 150, or 300 mg/day for six weeks after target quit date (TQD). The primary outcome was the point prevalence smoking abstinence at the end of treatment and at one year. The Beck Depression Inventory (BDI) was used to assess depressive symptoms. RESULTS: A significant dose-response effect of bupropion for smoking cessation was found. This was independent of history of major depression or alcoholism. Among those continuously abstinent from smoking for two weeks following TQD, an increase in BDI score was associated with a return to smoking at end of treatment. CONCLUSIONS: Bupropion is efficacious for smoking cessation independently of a former history of major depression or alcoholism. Increases in depressive symptoms during an initial period of abstinence are associated with a return to smoking.

A new gas chromatography-mass spectrometry method for simultaneous determination of total and free trans-3'-hydroxycotinine and cotinine in the urine of subjects receiving transdermal nicotine.

trans-3'-Hydroxycotinine (THOC) has been recognized as the most abundant metabolite of nicotine. In an attempt to assess THOC and cotinine (COT) concentrations during nicotine transdermal therapy, we developed a new quantitative gas chromatography-mass spectrometry (GC-MS) method for simultaneous determination of total and free THOC and COT in human urine. The method utilizes the following: (a) hydrolysis of conjugated THOC and COT by beta-glucuronidase; (b) basic extraction of THOC and COT with mixed dichloromethane and n-butyl acetate; (c) derivatization of THOC with bis(trimethylflurosilyl)acetamide; and (d) separation and identification by GC-MS with selective ion monitoring. Lower limits of quantification for the assay were 50 and 20 microg/L for THOC and COT, respectively. The intra- and interassay CVs were 4.4% and 11% for THOC, and 3.9% and 10% for COT at 1000 microg/L. The results from six consecutive 24-h urine collections in 71 subjects administered daily transdermal nicotine doses of 11, 22, and 44 mg showed that, on average, free THOC was 76% of total THOC and free COT was 48% of total COT in all subjects. THOC is the major metabolite of nicotine and constitutes 20% of total nicotine intake at steady state, whereas urinary nicotine and COT excretion were 8% and 17%, respectively. The method is useful for simultaneous determination of free and total THOCand COT and can be used to assess the urinary excretion of these metabolites during transdermal nicotine therapy.

Response to nicotine dependence treatment in smokers with current and past alcohol problems.

Smoking prevalence among alcoholics is high, and evidence indicates that smokers with a history of alcohol abuse may have more difficulty quitting cigarette smoking. This study is a post hoc analysis comparing the smoking cessation rates of smokers with active or past alcohol problems to the rates in smokers with no history of alcohol problems who were participants in a randomized, controlled trial of smoking cessation therapy. Subjects received either 44 mg/24 hour or 22 mg/24 hour nicotine patch for 4 or 6 weeks, respectively, followed by a tapering schedule to complete 8 weeks of therapy and a randomly assigned behavioral intervention (minimal, brief individual counseling, group therapy). The Self-Administered Alcoholism Screening Test (SAAST) score was used to determine alcohol group assignment (no alcohol problems < 7; active alcohol problems > or = 7 and still drinking; past alcohol problems if not drinking due to a past history of alcohol problems). Among 382 subjects (171 men and 211 women), 281 had no alcohol problems (74%), 53 had past alcohol problems (14%), and 48 had active alcohol problems (13%). Smoking cessation rates assessed at both weeks 4 and 8 were significantly different across groups (p = 0.026 and 0.002 at weeks 4 and 8, respectively) with lower rates in the groups with past and active alcohol problems when compared to the "no problem" group. At week 26, subjects with past alcohol problems were less likely to be abstinent from smoking than no problem group subjects, but this was not statistically significant (odds ratio = 0.49, 95% confidence interval 0.22-->1.08). In the short term, smokers with past or active alcohol problems are less likely to quit smoking compared to those with no alcohol problems when treated with nicotine patch therapy for smoking cessation.

A randomized trial of naltrexone for smoking cessation.

AIMS: To evaluate the efficacy and safety of orally administered naltrexone, alone or in combination with nicotine patches, as a treatment for cigarette smoking. DESIGN: Randomized, partially-blinded, 2 x 2 factorial trial using naltrexone (active vs. placebo) and nicotine patches (active vs. none). PARTICIPANTS: One hundred cigarette smokers. INTERVENTION: Twelve weeks of either placebo-only, naltrexone-only, placebo with nicotine patches or naltrexone with nicotine patches. The naltrexone dose was 50 mg taken once daily, and the nicotine patch dose was 21 mg/24-hour for the first 8 weeks and 14 mg/24-hour for the remaining 4 weeks. Brief behavioral intervention was provided at each visit. MEASUREMENTS: One-week point-prevalence smoking abstinence rates confirmed by an expired air carbon monoxide level of 8 parts per million (ppm) or less, daily cigarette smoking and cigarette craving. FINDINGS: At the end of treatment, there was no effect of naltrexone on smoking abstinence. The smoking abstinence rates were 19% and 22% for the placebo only and naltrexone only treatment groups, respectively, and 48% and 46% for the placebo with nicotine patch and naltrexone with nicotine patch groups, respectively. However, the effect of the nicotine patch at this time was significant (p = 0.006), but not at the 6-month follow-up. No significant effect of naltrexone was observed on daily cigarette smoking on cigarette craving during the study. CONCLUSIONS: The opioid antagonist naltrexone was not found to be effective for smoking cessation and had no significant effect on daily cigarette consumption or craving. The results of the present study provide no support for the use of naltrexone, alone or in combination with nicotine patches, as a therapeutic treatment for smoking cessation.

Trends in smoking-related diseases. Why smoking cessation is still the best medicine.

Although millions of Americans have kicked the habit, the effects of cigarette smoking likely will be around for a long time. What was once regarded as a glamorous habit is now recognized as a health threat and an economic burden. But what headway has been made in the reduction of related morbidity and mortality? The authors of this article review the current epidemiologic data on smoking-related diseases and make an indisputable case for smoking cessation.

Temporal effects of nicotine nasal spray and gum on nicotine withdrawal symptoms.

Nicotine nasal spray and nicotine gum have been found to be effective in relieving nicotine withdrawal symptoms. In this randomized single-blind study, 91 cigarette smokers were randomly assigned to a single 1 mg dose of active nicotine nasal spray (n=29), active 4 mg nicotine gum (n=31), saline placebo nasal spray (n=16) or placebo gum (n=15). Following overnight abstinence, subjects repeatedly completed visual analog scales for assessing nicotine withdrawal symptoms over 30 min preceding (time -30 min to time 0) and 120 min following a single dose of study medication. This sequence was performed 3 times during the day. Nicotine withdrawal symptoms were assessed on a 41-point visual analog scale (1=no withdrawal, 41=extreme withdrawal). At the initial session only, blood samples for serum nicotine levels were taken at baseline, then at 5, 10, 30 and 120 min following study drug administration. The mean (+/-SD) age of the subjects was 38.6 (+/-10.1) years, 48% were females, smoking rate was 24.5 (+/-7.8) cigarettes per day, and years of smoking was 19.9 (+/-10.0). A single 1 mg dose of nicotine nasal spray provided more immediate relief for craving for a cigarette compared to a single 4 mg dose of nicotine gum. Serum venous nicotine levels for the active nicotine nasal spray and nicotine gum were comparable at 5 and 10 min while the levels were higher for nicotine gum at 30 and 120 min. Changes in withdrawal symptoms were not found to be related to serum venous nicotine levels. Our findings provide a rationale for the as needed use of nicotine nasal spray to control withdrawal symptoms, possibly in combination with other medications with longer acting effects.

Application of serum nicotine and plasma cotinine concentrations to assessment of nicotine replacement in light, moderate, and heavy smokers undergoing transdermal therapy.

As part of a clinical trial investigating the level of nicotine replacement with different doses of transdermal therapy for smoking cessation, peak and trough serum nicotine and plasma cotinine concentrations were measured in 70 subjects while they were actively smoking (baseline) and daily for 6 consecutive inpatient days while they were receiving transdermal nicotine. Subjects were randomly assigned to a daily 24-hour patch delivering a transdermal nicotine dose of 0, 11, 22, or 44 mg and stratified by self-reported smoking rate as either light (10-15 cigarettes per day), moderate (16-30 cigarettes per day), or heavy (>30 cigarettes per day). Steady-state concentrations of nicotine and cotinine were attained in 1 and 3 days, respectively, at all doses and were independent of baseline smoking rate. Mean percentage replacement of nicotine was calculated by dividing steady-state peak nicotine or cotinine concentrations by their respective baseline concentrations. Significant underreplacement occurred in subjects receiving the 11 mg/day patch regardless of baseline smoking rate. Underreplacement also occurred in moderate and heavy smokers receiving 22 mg/day and in light smokers at this same dose. Complete replacement occurred only in subjects receiving the 44 mg/day patch. These results have several implications for transdermal nicotine therapy. First, with the higher nicotine and cotinine levels observed with heavier smoking, it is inherent that one size does not fit all, and there is a need to consider more individualization of dosage for nicotine patch therapy. Second, there is substantial underreplacement with the 22 mg/day dose in moderate to heavy smokers and in some light smokers. Third, even with twice the usual dose (i.e., 44 mg/day), there was no accumulation of either nicotine or cotinine. Plasma cotinine levels after achievement of steady state (i.e., after 3 days of patch therapy) can be collected at any time and used to calculate percent replacement using baseline levels.