Smoking status as the new vital sign: effect on assessment and intervention in patients who smoke.

OBJECTIVE: To assess the effect of expanding the vital signs to include smoking status. DESIGN: We prospectively conducted exit interviews with patients at a general internal medicine clinic in Madison, Wisconsin, during a 16-month period from 1991 to 1993. METHODS: Patients were surveyed briefly before (N = 870) and after (N = 994) the implementation of a simple institutional change in clinical practice. This change involved training the staff in how to use progress notepaper with a vital sign stamp that included smoking status (current, former, or never) along with the traditional vital signs. Included in the survey were questions about whether the patient smoked, whether the patient was asked that day about smoking status (by a clinician or other staff), and, for smokers, whether they were urged to quit smoking and given specific advice on how to do so. RESULTS: After expansion of the vital signs, patients were much more likely to report inquiries about their smoking status on the day of a clinic visit (an increase from approximately 58% at baseline to 81% at intervention; P < 0.0001). The vital sign intervention was associated with significant increases in the percentage of smokers who reported that their clinician advised them that day to quit smoking (from approximately 49% at baseline to 70% during the intervention; P < 0.01) and in the percentage who reported that their clinician gave them specific advice that day on how to stop smoking (from approximately 24% at baseline to 43% during the intervention; P < 0.01). CONCLUSION: Expanding the vital signs to include smoking status was associated with a dramatic increase in the rate of identifying patients who smoke and of intervening to encourage and assist with smoking cessation. This simple, low-cost intervention may effectively prompt clinicians to inquire about use of tobacco and offer recommendations to smokers.

Two studies of the clinical effectiveness of the nicotine patch with different counseling treatments.

OBJECTIVE: To assess the effectiveness of transdermal nicotine therapy for smoking cessation and suppression of withdrawal severity in conjunction with two different adjuvant counseling treatments. DESIGN: Two independent randomized placebo-controlled double-blind trials. SETTING: Smoking cessation clinic. SUBJECTS: Eighty-eight (study 1) and 112 (study 2) adult volunteers motivated to quit smoking. INTERVENTIONS: Eight weeks of 22-mg transdermal nicotine therapy with group counseling (study 1); 4 weeks of 22 mg followed by 2 weeks of 11-mg transdermal nicotine therapy with brief individual counseling (study 2). MAIN OUTCOME MEASURES: Modified point prevalence (7 consecutive days of nonsmoking) at the end of patch treatment and 6 months after treatment initiation was assessed by self-report and biochemically confirmed; survival analyses were also conducted for both studies to compare treatment efficacy. Also, we examined the impact of the nicotine patch on specific withdrawal symptoms (anger, anxiety, awakening, difficulty concentrating, depression, hunger, impatience, and craving). RESULTS: Transdermal nicotine treatment produced higher cessation rates at the end of treatment than did placebo with both adjuvant counseling interventions: 59 percent vs 40 percent (p < 0.05 in study 1) and 37 percent vs 20 percent (p < 0.05 in study 2), respectively. Smoking cessation efficacy was maintained 6 months after initiation of treatment: 34 percent vs 21 percent (p = 0.08 in study 1) and 18 percent vs 7 percent (p = 0.05 in study 2). Survival analyses also revealed significant group differences in efficacy in both studies. Nicotine patches also suppressed a variety of withdrawal symptoms, including craving in the first weeks after patients quit smoking. CONCLUSION: Transdermal nicotine effectively augments smoking cessation rates with two different types of counseling treatment. Overall, the nicotine patch approximately doubles the sustained rate of smoking cessation. Additionally, the nicotine patch provides relief from some tobacco withdrawal symptoms.

Characterization of morphine's excitatory effects.

Although the excitatory effects of opiates have assumed greater importance in theories of compulsive drug use, the nature and time course of these effects remains unclear. The authors attempted to characterize the excitatory effects of morphine by administering doses of 5 mg/kg and 20 mg/kg in both warm and cold environments and by undertaking simultaneous assessments of core temperature, locomotor activity, and oxygen consumption. The results argue for a two receptor model to account for morphine's thermic effects: a high-affinity receptor that activates thermogenic systems, and a low-affinity receptor that mediates a poikilothermic response.

Effects of dose on effector mechanisms in morphine-induced hyperthermia and poikilothermia.

The effect of a variety of morphine doses on thermoregulatory effector systems was examined in ambient temperatures of 27.0 degrees C and 4.0 degrees C. Rats were given saline or morphine sulfate (5, 15, or 25 mg/kg); their core temperature, oxygen consumption, and activity were monitored for 4 or 6 h post-injection. The results suggest two distinct actions of morphine, possibly mediated by two opiate receptors. Low doses of morphine produce hyperthermia that is the result of a direct activation of activity and whole body heat production. High doses produce effects dependent on ambient temperature: hypermetabolism and hyperthermia in the 27.0 degrees C environment; hypometabolism, vasodilation, and hypothermia in the 4.0 degrees C environment. The findings suggest limitations in current set-point theories of morphine's thermic actions.

Aversion instead of preference learning indicated by nicotine place conditioning in rats.

Although nicotine is a drug of abuse for millions of smokers, it has been difficult to demonstrate clearly the motivational properties of nicotine with rats using the conditioned place preference (CPP) paradigm. The first experiment attempted to replicate CPPs reported by other researchers using nicotine doses of 0.4, 0.8, and 1.2 mg/kg. There was a trend for all three doses to produce aversions, but it was significant only for the 0.8 mg/kg dose. Exposures to the CS alone extinguished aversions, but a "priming" dose (0.2 mg/kg) of nicotine given after extinction produced aversions only in animals exposed to 1.2 mg/kg. Experiment 2 tested whether preexposure to morphine or nicotine would sensitize animals to nicotine's reinforcing effects. In this experiment, rats were exposed to either six nicotine (0.6 mg/kg) or morphine (1.0 mg/kg) dosings prior to preference conditioning. Neither preferences nor aversions were observed in any group following subsequent conditioning with 0.6 mg/kg nicotine. The results suggest that previous observations of preference effects may have been due to specific procedural factors or may have depended on negative reinforcement due to stress reduction.

Characterization of tobacco withdrawal symptoms: transdermal nicotine reduces hunger and weight gain.

The accurate assessment of both tobacco withdrawal and the impact of the nicotine patch on withdrawal may be compromised by attrition of subjects, or by subjects smoking during withdrawal. To reduce these occurrences, 211 participants were provided with intensive cessation counseling while trying to quit smoking with either nicotine (21 mg) or placebo transdermal patches. Subject attrition was low, with 80.5% of participants continuing through the 5-week study period. Abstinence rates were also high over this period (75% and 61% in active and placebo groups, respectively). In this multisite, double-blind trial, withdrawal severity was assessed using a nine-item daily self-report questionnaire, and abstinence was confirmed via CO monitoring. Abrupt smoking cessation increased multiple tobacco withdrawal symptoms/signs including craving for cigarettes, irritability, anxiety, appetite, sleep disruption, difficulty concentrating, restlessness, depression, and impatience. Treatment with transdermal nicotine reduced craving for cigarettes, anxiety, irritability, and appetite, as well as weight gain (1.85 versus 2.88 kg mean gain over 4 weeks in active and placebo groups, respectively).

Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of long-term use of bupropion sustained release (SR), the nicotine patch, and the combination of these 2 treatments in patients who initially failed treatment. METHODS: This was a post hoc analysis of a multicenter, double-blind, randomized, placebo-controlled clinical trial in 893 smokers. Patients were randomly assigned to 9 weeks of treatment with placebo (n = 160), bupropion SR (n = 244), nicotine patch (n = 244), or a combination of nicotine patch and bupropion SR (n = 245). The study was originally designed with a follow-up period of 52 weeks. In this analysis, short-term success was defined as smoking cessation after 14 or 21 days of therapy and long-term success was defined as smoking cessation after >21 days of therapy. Patients who did not achieve short-term success were evaluated for long-term success at week 9 (end of treatment), 6 months, and 1 year after the start of the study. RESULTS: The mean age of the smokers was 44 years. The majority (93%) of patients were white, and 52% were female. The study subjects smoked an average of 27 cigarettes per day. Among the 467 patients who initially failed treatment in the first 3 weeks, treatment with bupropion SR alone and in combination with the nicotine patch produced significant increases in successful smoking cessation rates from weeks 4 to 9 (19% bupropion SR or combination, 7% nicotine patch, 7% placebo), at month 6 (11% bupropion SR, 13% combination, 2% nicotine patch, 3% placebo), and at month 12 (10% bupropion SR, 7% combination, 2% nicotine patch, 1% placebo) (P < 0.05 for bupropion SR and combination vs nicotine patch or placebo). CONCLUSION: Among patients who initially failed treatment, continued therapy with bupropion SR, either alone or in combination with the nicotine patch, resulted in significantly higher short- and long-term smoking cessation rates than treatment with the nicotine patch alone or placebo.

Measures of affect and nicotine dependence predict differential response to smoking cessation treatments.

Smokers (N = 126) were randomly assigned to 6-session smoking cessation treatments consisting of 1 of 2 counseling strategies (skills training or support) and 1 of 2 nicotine exposure strategies (nicotine gum or rapid smoking). Counseling and nicotine strategies were completely crossed; all four combinations resulted in equivalent 1-year abstinence rates. Skills training produced higher initial cessation and more coping responses posttreatment than did support. Rapid smoking, but not nicotine gum, produced tachycardia to the taste of cigarettes posttreatment, consistent with cigarette aversion. The treatments were differentially effective among subpopulations of smokers: Subjects high in pretreatment negative affect responded best to support counseling; those low in pretreatment negative affect responded best to skills training. Self-reports of pretreatment craving predicted response to the nicotine exposure treatments.

Gender differences in smoking cessation.

Gender differences in smoking quit rates are frequently reported and are the subject of much speculation. This study examined the generalizability of gender differences in abstinence across study sites, treatments, and time of relapse, as well as potential mediators and moderators of gender effects. Participants were smokers who participated in 3 randomized clinical trials of the nicotine patch (N = 632). Men had higher cessation rates than women at all follow-ups. The impact of gender on abstinence was unaffected by controlling for study site, treatment, or time of relapse. There was little evidence for mediation or moderation of this relation by any of a host of predictor variables. The magnitude and consistency of the gender differential, coupled with an inability to account for it, highlights a compelling need for additional research specifically aimed at elucidating the relation between gender and abstinence.

Strike while the iron is hot: can stepped-care treatments resurrect relapsing smokers?

The efficacies of 2 group counseling step-up treatments for smoking cessation, cognitive-behavioral/skill training therapy (CBT) and motivational interviewing/supportive (MIS) therapy, were compared with brief intervention (BI) treatment in a sample of 677 smokers. Differential efficacy of the 2 step-up treatments was also tested in smokers at low and high risk for relapse (no smoking vs. any smoking during the first postquit week. respectively). All participants received 8 weeks of nicotine patch therapy. BI consisted of 3 brief individual cessation counseling sessions; CBT and MIS participants received BI treatment and 6 group counseling sessions. Neither CBT nor MIS treatment improved long-term abstinence rates relative to BI. Limited support was found for the hypothesis that high-risk smokers would benefit more from MIS than CBT. Other hypotheses were not supported.

Smoking outcome expectancies: factor structure, predictive validity, and discriminant validity.

Recent models of addiction posit that drug outcome expectancies are influential determinants of drug use. The current research examines the dimensional structure, predictive validity, and discriminant validity of expectancies for cigarette smoking in a prospective study. There was a good fit between the factor structure of the Smoking Consequences Questionnaire and the observed data. In addition, the internal consistency of each scale was satisfactory. Moreover, there was considerable evidence for the predictive and discriminant validity of expectancies. Expectancies of positive outcomes (positive reinforcement, negative reinforcement, and appetite-weight control) predicted withdrawal severity. Negative reinforcement expectancies and expectancies of negative consequences predicted cessation success. Predictive relations remained significant after controlling for related constructs: negative affect, stress, and dependence measures.

Development and validation of the Wisconsin Smoking Withdrawal Scale.

The accurate assessment of nicotine withdrawal is important theoretically and clinically. A 28-item scale, the Wisconsin Smoking Withdrawal Scale, was developed that contains 7 reliable subscales tapping the major symptom elements of the nicotine withdrawal syndrome. Coefficients alpha for the subscales range from .75 to .93. This scale is sensitive to smoking withdrawal, is predictive of smoking cessation outcomes, and yields data that conform to a 7-factor structure. The 7 scales predicted intratreatment smoking, chi2(7, N = 163) = 15.19, p = .034. Moreover, the questionnaire is sufficiently brief so that it can be used in both clinical and research contexts.

The Agency for Health Care Policy and Research smoking cessation clinical practice guideline: basics and beyond.

The 1996 Agency for Health Care Policy and Research's Smoking Cessation Clinical Practice Guideline provides a strong empirical foundation for effective smoking cessation interventions in primary care. Screening all patients for tobacco use status at each clinic visit and providing at least brief cessation advice to all smokers can have a significant system-wide effect. Adding additional treatment components, such as pharmacotherapy, problem solving, and social support, can increase quit rates by twofold or more. Information on effective and ineffective treatment components is provided, along with new information published after the release of the Guideline.

Immunogenicity and smoking-cessation outcomes for a novel nicotine immunotherapeutic.

NicVAX, a nicotine vaccine (3'AmNic-rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N = 301 smokers) tested the results of 200- and 400-µg doses administered four or five times over a period of 6 months, as compared with placebo. 3'AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five-injection, 400-µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3'AmNic-rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified.

New developments in approaches to smoking cessation.

Tobacco use is the leading cause of unnecessary illness and death in the United States consuming billions of dollars in scarce health care resources. In the period under review, several new treatments for tobacco addiction were introduced. New nicotine delivery systems, a nasal spray and an inhaler, reduced craving and withdrawal compared with placebo and improved medium- to long-term cessation rates. Nicotine patches and gum became available without a prescription in the United States, offering the potential for increased use and synergy between public health efforts and commercial advertising. Important new safety data were obtained on the use of nicotine replacement therapies in potentially high risk groups, such as adolescents, pregnant women, and persons with serious cardiovascular disease, indicating that these therapies pose little or no additional risk.

Tobacco smoking and new developments in public health and clinical interventions.

The public policy environment regarding tobacco use in the United States has experienced a dramatic change during the past year. Along with calls for regulatory review of cigarettes, important new scientific information has become available regarding the health effects of environmental tobacco smoke and the efficacy of nicotine replacement therapy, which is used to support smoking cessation efforts. Specifically, recent studies have suggested that environmental tobacco smoke exposure increases risk for coronary heart disease in nonsmoking adults in addition to causing lung cancer and other respiratory diseases. Children are exposed to environmental tobacco smoke at home and in public, resulting in increased risk of bronchitis, pneumonia, bronchial hyperresponsivity, and sudden infant death syndrome. In a climate of increasing concern about the direct and indirect effects of tobacco smoke, three independent meta-analyses concluded that nicotine replacement therapy increased smoking cessation efficacy two- to threefold. In addition, research is beginning to identify factors associated with successful and unsuccessful cessation attempts using nicotine replacement therapy, resulting in the possibility of individualized treatments and clinical interventions designed for maximum efficacy.