Anne M. Joseph

The Safety of Transdermal Nicotine as an Aid to Smoking Cessation in Patients with Cardiac Disease

BACKGROUND Transdermal nicotine therapy is widely used to aid smoking cessation, but there is uncertainty about its safety in patients with cardiac disease. METHODS In a randomized, double-blind, placebo-controlled trial at 10 Veterans Affairs medical centers, we randomly assigned 584 outpatients (of whom 576 were men) with at least one diagnosis of cardiovascular disease to a 10-week course of transdermal nicotine or placebo as an aid to smoking cessation. The subjects were monitored for a total of 14 weeks for the primary end points of the study (death, myocardial infarction, cardiac arrest, and admission to the hospital due to increased severity of angina, arrhythmia, or congestive heart failure); the secondary end points (admission to the hospital for other reasons and outpatient visits necessitated by increased severity of heart disease); any side effects of therapy; and abstinence from smoking. RESULTS There were 48 primary and 78 secondary end points noted in a total of 95 subjects. At least one of the primary end points was reached by 5.4 percent of the subjects in the nicotine group and 7.9 percent of the subjects in the placebo group (difference, 2.5 percent; 95 percent confidence interval, -1.6 to 6.5 percent; P=0.23). In the nicotine group, 11.9 percent of the subjects had at least one of the secondary end points, as compared with 9.7 percent in the placebo group (difference, 2.2 percent; 95 percent confidence interval, -2.2 to 7.4 percent; P= 0.37). After 14 weeks the rate of abstinence from smoking was 21 percent in the nicotine group, as compared with 9 percent in the placebo group (P=0.001), but after 24 weeks the abstinence rates were not significantly different (14 percent vs. 11 percent, P= 0.67). CONCLUSIONS Transdermal nicotine does not cause a significant increase in cardiovascular events in high-risk outpatients with cardiac disease. However, the efficacy of transdermal nicotine as an aid to smoking cessation in such patients is limited and may not be sustained over time.

Post-traumatic stress disorder and smoking: a systematic review.

We conducted a systematic review of what is known about the relationship between post-traumatic stress disorder (PTSD) and smoking to guide research on underlying mechanisms and to facilitate the development of evidence-based tobacco treatments for this population of smokers. We searched Medline, PsychINFO, and the Cochrane Central Register of Controlled Trials and identified 45 studies for review that presented primary data on PTSD and smoking. Smoking rates were high among clinical samples with PTSD (40%-86%) as well as nonclinical populations with PTSD (34%-61%). Most studies showed a positive relationship between PTSD and smoking and nicotine dependence, with odds ratios ranging between 2.04 and 4.52. Findings also suggest that PTSD, rather than trauma exposure itself, is more influential for increasing risk of smoking. A small but growing literature has examined psychological factors related to smoking initiation and maintenance and the overlapping neurobiology of PTSD and nicotine dependence. Observational studies indicate that smokers with PTSD have lower quit rates than do smokers without PTSD. Yet a few tobacco cessation treatment trials in smokers with PTSD have achieved quit rates comparable with controlled trials of smokers without mental disorders. In conclusion, the evidence points to a causal relationship between PTSD and smoking that may be bidirectional. Specific PTSD symptoms may contribute to smoking and disrupt cessation attempts. Intervention studies that test behavioral and pharmacological interventions designed specifically for use in patients with PTSD are needed to reduce morbidity and mortality in this population.

Smokers’ relative risk for aortic aneurysm compared with other smoking-related diseases: a systematic review

OBJECTIVE Aortic aneurysm has traditionally been considered a manifestation of atherosclerosis, but recent evidence suggests an independent pathogenesis, possibly similar to that of chronic obstructive pulmonary disease (COPD). Further insight into the pathogenesis of aortic aneurysm might be obtained by comparing its association with smoking with that of other smoking-related diseases. STUDY DESIGN We conducted a systematic review of studies providing relative risk associated with smoking for both aortic aneurysm and other smoking-related diseases. RESULTS We identified 10 eligible studies, which included more than 3 million subjects. The events reported in 9 studies were death from target diseases; the tenth study reported new diagnoses. Relative risk for aortic aneurysm-related events in current smokers was generally 3 to 6, compared with 1 to 2 for coronary artery disease or cerebrovascular disease and 5 to 12 for COPD. For each category of smoking in each study, relative risk associated with smoking was substantially greater for aortic aneurysm than for coronary artery disease or cerebrovascular disease. Our pooled estimates indicate that, in men, the association of ever smoking with aortic aneurysm is 2.5 times greater than the association of ever smoking with coronary artery disease (95% confidence interval [CI], 2.2, 2.8) and 3.5 times greater than the association of ever smoking with cerebrovascular disease (95% CI, 2.4, 5.3), but only 0.56 as great as the association of ever smoking with COPD (95% CI, 0.36, 0.86). CONCLUSIONS The difference in magnitude of these associations with smoking is consistent with a non-atherosclerotic cause for aortic aneurysm and/or a stronger effect of smoking on vascular disease in the peripheral arteries.

Integrating Tobacco Cessation Into Mental Health Care for Posttraumatic Stress Disorder: A Randomized Controlled Trial

CONTEXT Most smokers with mental illness do not receive tobacco cessation treatment. OBJECTIVE To determine whether integrating smoking cessation treatment into mental health care for veterans with posttraumatic stress disorder (PTSD) improves long-term smoking abstinence rates. DESIGN, SETTING, AND PATIENTS A randomized controlled trial of 943 smokers with military-related PTSD who were recruited from outpatient PTSD clinics at 10 Veterans Affairs medical centers and followed up for 18 to 48 months between November 2004 and July 2009. INTERVENTION Smoking cessation treatment integrated within mental health care for PTSD delivered by mental health clinicians (integrated care [IC]) vs referral to Veterans Affairs smoking cessation clinics (SCC). Patients received smoking cessation treatment within 3 months of study enrollment. MAIN OUTCOME MEASURES Smoking outcomes included 12-month bioverified prolonged abstinence (primary outcome) and 7- and 30-day point prevalence abstinence assessed at 3-month intervals. Amount of smoking cessation medications and counseling sessions delivered were tested as mediators of outcome. Posttraumatic stress disorder and depression were repeatedly assessed using the PTSD Checklist and Patient Health Questionnaire 9, respectively, to determine if IC participation or quitting smoking worsened psychiatric status. RESULTS Integrated care was better than SCC on prolonged abstinence (8.9% vs 4.5%; adjusted odds ratio, 2.26; 95% confidence interval [CI], 1.30-3.91; P = .004). Differences between IC vs SCC were largest at 6 months for 7-day point prevalence abstinence (78/472 [16.5%] vs 34/471 [7.2%], P < .001) and remained significant at 18 months (86/472 [18.2%] vs 51/471 [10.8%], P < .001). Number of counseling sessions received and days of cessation medication used explained 39.1% of the treatment effect. Between baseline and 18 months, psychiatric status did not differ between treatment conditions. Posttraumatic stress disorder symptoms for quitters and nonquitters improved. Nonquitters worsened slightly on the Patient Health Questionnaire 9 relative to quitters (differences ranged between 0.4 and 2.1, P = .03), whose scores did not change over time. CONCLUSION Among smokers with military-related PTSD, integrating smoking cessation treatment into mental health care compared with referral to specialized cessation treatment resulted in greater prolonged abstinence. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00118534.

Similar uptake of lung carcinogens by smokers of regular, light, and ultralight cigarettes

Cigarette design has changed markedly over the past 60 years and sales-weighed levels of tar and nicotine have decreased. Currently, cigarettes are classified as regular (>14.5 mg tar), light (>6.5-14.5 mg tar), and ultralight (≤6.5 mg tar), based on a Federal Trade Commission–specified machine-smoking protocol. Epidemiologic studies suggest that there is no difference in lung cancer risk among people who smoke light or ultralight cigarettes compared with regular cigarettes, but the uptake of lung carcinogens in smokers of these types of cigarettes has never been reported. We recruited 175 smokers, who filled out a tobacco use questionnaire in which their current brand was identified as regular, light, or ultralight. Urine samples were collected and analyzed for 1-hydroxypyrene (1-HOP), total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL plus its glucuronides) and total cotinine (cotinine plus its glucuronides). 1-HOP and total NNAL are biomarkers of uptake of polycyclic aromatic hydrocarbons and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, lung carcinogens in cigarette smoke. Total cotinine is a biomarker of nicotine uptake. There were no statistically significant differences in urinary levels of 1-HOP, total NNAL, and total cotinine in smokers of regular, light, and ultralight cigarettes, whether the results were expressed per mg urinary creatinine, per mL of urine, or per mg creatinine divided by cigarettes per day. Levels of machine measured tar were available for the cigarettes smoked by 149 of the subjects. There was no correlation between levels of tar and any of the biomarkers. These results indicate that lung carcinogen and nicotine uptake, as measured by urinary 1-HOP, total NNAL, and total cotinine is the same in smokers of regular, light, and ultralight cigarettes. The results are consistent with epidemiologic studies that show no difference in lung cancer risk in smokers of these cigarettes.

Relationships between Cigarette Consumption and Biomarkers of Tobacco Toxin Exposure

Epidemiologic studies show a dose-response relationship between cigarettes per day and health outcomes such as heart and lung disease, and health outcomes are related to some biomarkers of tobacco exposure. The objective of this study was to examine the relationships between cigarettes per day and levels of selected biomarkers of tobacco toxin exposure: carbon monoxide (CO), metabolites of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and polycyclic aromatic hydrocarbons [total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and 1-hydroxypyrene (1-HOP), respectively], and total cotinine (cotinine plus cotinine-N-glucuronide). We did a cross-sectional analysis of merged data from (a) two clinical trials and (b) two cohorts of light smokers (total n = 400). The mean age of participants was 50.4 years and the range of cigarette consumption was 1 to 100/d; however, few subjects smoked >45 cigarettes/d (n = 12). Results show that levels of the biomarkers CO, total NNAL, and total cotinine increase with an increase in the number of cigarettes smoked per day, but not in a linear fashion. 1-HOP is a less discriminating biomarker as levels are relatively stable regardless of the number of cigarettes smoked per day. There is considerable variability in toxin measurement, especially at high levels of smoking. There was a significant correlation between cigarettes per day and total NNAL, 1-HOP, total cotinine, and CO. Total NNAL was highly significantly correlated with total cotinine and CO and also significantly correlated with 1-HOP. These findings suggest that the number of cigarettes smoked per day is not necessarily a reliable measure of toxin exposure and may underestimate tobacco toxin exposure at low levels of smoking or overestimate exposure at high levels of smoking. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2963-8)

Racial/Ethnic Disparities in the Use of Nicotine Replacement Therapy and Quit Ratios in Lifetime Smokers Ages 25 to 44 Years

We examined racial/ethnic variations in the use of nicotine replacement therapy (NRT) and quit ratios among Caucasian, African American, Asian, and Latino lifetime smokers ages 25 to 44 years. We conducted cross-sectional analyses using data from individuals (n = 27,031) screened for enrollment in the Collaborative Study of the Genetics of Nicotine Dependence. Participants were randomly sampled from three Midwestern metropolitan areas using Health Maintenance Organization membership lists in Detroit, MI and Minneapolis, MN and a driver’s license registry in St. Louis, MO from March 2003 to August 2005. A telephone survey collected information on smoking history, previous quit attempts, and sociodemographic characteristics. Among lifetime smokers (n = 9,216), univariate analysis indicated that African Americans (22%) and Latinos (22%) were significantly less likely to report having ever used NRT for smoking cessation than Caucasians (31%). Asians (22%) also reported lower rates of using NRT than Caucasians, but this difference was marginally significant (P = 0.06). These disparities persisted in multivariate analysis for African Americans [adjusted odds ratio (OR), 0.76; 95% confidence interval (95% CI), 0.63-0.91; P < 0.01] but not for Latinos (adjusted OR, 0.76; 95% CI, 0.54-1.06; P = 0.11) or Asians (adjusted OR, 0.98; 95% CI, 0.60-1.60; P = 0.95). As measured by the quit ratio, African Americans (35%) were less likely to have quit smoking than Caucasians (52%). This disparity persisted in multivariate logistic regression (adjusted OR, 0.66; 95% CI, 0.56-0.78; P < 0.001). Asian and Latino smokers were as likely as Caucasians to report smoking cessation. Future prospective studies are needed to assess whether lower utilization of cessation treatments such as NRT contribute to the observed disparity in quit ratios for African Americans. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1640–7)

Ethnic Disparities in the Use of Nicotine Replacement Therapy for Smoking Cessation in an Equal Access Health Care System

Purpose. To examine ethnic variations in the use of nicotine replacement therapy (NRT) in an equal access health care system. Design. Cross-sectional survey. Setting. Eighteen Veterans Affairs medical and ambulatory care centers. Subjects. A cohort of male current smokers (n = 1606). Measures. Use of NRT (nicotine patch or nicotine gum), ethnicity, sociodemographics, health status, smoking-related history, and facility prescribing policy. Results. Overall, only 34% of African-American and 26% of Hispanic smokers have ever used NRT as a cessation aid compared with 50% of white smokers. In the past year, African-American smokers were most likely to have attempted quitting. During a serious past-year quit attempt, however, African-American and Hispanic smokers reported lower rates of NRT use than white smokers (20% vs. 22% vs. 34%, respectively, p = .001). In multivariate analyses, ethnicity was independently associated with NRT use during a past-year quit attempt. Compared with white smokers, African-American (adjusted odds ratio, .53; 95% confidence interval, .34–.83) and Hispanic (adjusted odds ratio, .55; 95% confidence interval, .28–1.08) smokers were less likely to use NRT. Conclusions. Assessment of variations in use of NRT demonstrates that African-American and Hispanic smokers are less likely to use NRT during quit attempts. Future research is needed on the relative contributions of patient, physician, and system features to gaps in guideline implementation to provide treatment for ethnic minority smokers.

Racial/ethnic differences in menthol cigarette smoking, population quit ratios and utilization of evidence‐based tobacco cessation treatments

AIMS This study examines the relationship between menthol cigarette smoking and the population quit ratio and whether menthol smokers differ in utilization of evidence-based smoking cessation aids among a nationally representative sample of US adult smokers. DESIGN, SETTING AND PARTICIPANTS Secondary data analysis of cross-sectional data from the 2005 National Health Interview Survey (NHIS) Cancer Control Supplement. The NHIS is a nationally representative survey of US households conducted annually. MEASUREMENTS The main outcome variables of interest were (1) the population quit ratio and (2) use of smoking quit aids. All analyses were conducted using SAS version 9.2 with SUDAAN, which corrects for the complex sampling design of the study. Univariate analyses were used to determine variables that differed significantly by menthol status and utilization of types of quit aids. Multiple logistic regression analysis modeled the relationship between menthol smoking status, demographic characteristics and smoking-related characteristics on the population quit ratio and utilization of quit aids. FINDINGS We observed significant differences in the population quit ratio for menthol versus non-menthol among African American smokers (34% versus 49%, P < 0.001), but not among whites (52% versus 50%). In multiple logistic regression analysis, there was a significant interaction between race and menthol smoking status. African American menthol smokers were significantly less likely than white non-menthol smokers to have quit smoking (adjusted odds ratio: 0.72, 95% confidence interval: 0.53, 0.97) after controlling for age group, sex, marital status, region and average number of cigarettes smoked per day. Menthol smoking status was not associated with differences in utilization of quit aids. CONCLUSIONS African Americans have the highest rates of menthol cigarette smoking of all racial and ethnic groups in the United States. Menthol cigarette smoking is associated negatively with successful smoking cessation among African Americans.

Chronic Disease Management for Tobacco Dependence: A Randomized, Controlled Trial

BACKGROUND Tobacco dependence disorder is a chronic relapsing condition, yet treatment is delivered in discrete episodes of care that yield disappointing long-term quit rates. METHODS We conducted a randomized controlled trial from June 1, 2004, through May 31, 2009, to compare telephone-based chronic disease management (1 year; longitudinal care [LC]) with evidence-based treatment (8 weeks; usual care [UC]) for tobacco dependence. A total of 443 smokers each received 5 telephone counseling calls and nicotine replacement therapy by mail for 4 weeks. They were then randomized to UC (2 additional calls) or LC (continued counseling and nicotine replacement therapy for an additional 48 weeks). Longitudinal care targeted repeat quit attempts and interim smoking reduction for relapsers. The primary outcome was 6 months of prolonged abstinence measured at 18 months of follow-up. RESULTS At 18 months, 30.2% of LC participants reported 6 months of abstinence from smoking, compared with 23.5% in UC (unadjusted, P = .13). Multivariate analysis showed that LC (adjusted odds ratio, 1.74; 95% CI, 1.08-2.80), quit attempts in past year (1.75; 1.06-2.89), baseline cigarettes per day (0.95; 0.92-0.99), and smoking in the 14- to 21-day interval post-quit (0.23; 0.14-0.38) predicted prolonged abstinence at 18 months. The LC participants who did not quit reduced smoking more than UC participants (significant only at 12 months). The LC participants received more counseling calls than UC participants (mean, 16.5 vs 5.8 calls; P < .001), longer total duration of counseling (283 vs 117 minutes; P < .001), and more nicotine replacement therapy (4.7 vs 2.4 boxes of patches; P < .001). CONCLUSION A chronic disease management approach increases both short- and long-term abstinence from smoking. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00309296.