Nancy A. Rigotti

Initial symptoms of nicotine dependence in adolescents

OBJECTIVES It has been assumed that nicotine dependence has a slow onset and occurs only after prolonged daily use of tobacco. A cohort of young adolescents was followed to determine when the first symptoms of nicotine dependence occur with respect to the duration and frequency of tobacco use. DESIGN A cohort of 681 seventh grade students (age 12–13 years) from seven schools in two small cities in central Massachusetts was followed over one year. Detailed information regarding tobacco use was obtained in individual confidential interviews conducted in school three times over the year. The latency time to the onset of symptoms of nicotine dependence was measured from the time a subject first smoked at a frequency of at least once per month. RESULTS 22% of the 95 subjects who had initiated occasional smoking reported a symptom of nicotine dependence within four weeks of initiating monthly smoking. One or more symptoms were reported by 60 (63%) of these 95 subjects. Of the 60 symptomatic subjects, 62% had reported experiencing their first symptom before smoking daily or began smoking daily only upon experiencing their first symptom. DISCUSSION The first symptoms of nicotine dependence can appear within days to weeks of the onset of occasional use, often before the onset of daily smoking. The existence of three groups of individuals—rapid onset, slower onset, and resistant—distinguishable from one another by their susceptibility to nicotine dependence, is postulated.

Osteoporosis in women with anorexia nervosa.

Because estrogen deficiency predisposes to osteoporosis, we assessed the skeletal mass of women with anorexia nervosa, using direct photon absorptiometry to measure radial bone density in 18 anorectic women and 28 normal controls. The patients with anorexia had significantly reduced mean bone density as compared with the controls (0.64 +/- 0.06 vs. 0.72 +/- 0.04 g per square centimeter, P less than 0.001). Vertebral compression fractures developed in two patients, and bone biopsy in one of them demonstrated osteoporosis. Bone density in the patients was not related to the estradiol level (r = 0.02). Levels of parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal despite low calcium intakes. The patients with anorexia who reported a high physical activity level had a greater bone density than the patients who were less active (P less than 0.001); this difference could not be accounted for by differences in age, relative weight, duration of illness, or serum estradiol levels. The bone density of physically active patients did not differ from that of active or sedentary controls. We conclude that women with anorexia nervosa have a reduced bone mass due to osteoporosis, but that a high level of physical activity may protect their skeletons.

Development of symptoms of tobacco dependence in youths: 30 month follow up data from the DANDY study

Objective: To determine if there is a minimum duration, frequency or quantity of tobacco use required to develop symptoms of dependence. Design and setting: A retrospective/prospective longitudinal study of the natural history of tobacco dependence employing individual interviews conducted three times annually in two urban school systems over 30 months. Detailed histories of tobacco use were obtained including dates, duration, frequency, quantity, patterns of use, types of tobacco, and symptoms of dependence. Participants: A cohort of 679 seventh grade students (age 12–13 years). Main outcome measures: The report of any of 11 symptoms of dependence. Results: Among 332 subjects who had used tobacco, 40% reported symptoms, with a median latency from the onset of monthly smoking of 21 days for girls and 183 days for boys. The median frequency of use at the onset of symptoms was two cigarettes, one day per week. The report of one or more symptoms predicted continued smoking through the end of follow up (odds ratio (OR) 44, 95% confidence interval (CI) 17 to 114, p < 0.001). Conclusions: Symptoms of tobacco dependence commonly develop rapidly after the onset of intermittent smoking, although individuals differ widely in this regard. Girls tend to develop symptoms faster. There does not appear to be a minimum nicotine dose or duration of use as a prerequisite for symptoms to appear. The development of a single symptom strongly predicted continued use, supporting the theory that the loss of autonomy over tobacco use begins with the first symptom of dependence.

Sustained-Release Bupropion for Pharmacologic Relapse Prevention after Smoking Cessation: A Randomized, Controlled Trial

Many effective behavioral and pharmacologic therapies are now available for treatment of smoking. The most effective strategy for treatment is combined behavioral intervention and pharmacologic therapy (1). Effective pharmacologic interventions for smoking cessation include several types of nicotine replacement and use of the non-nicotine medication bupropion (2, 3). Despite treatment advances, smoking relapse after successful intervention for smoking cessation occurs in 70% to 80% of patients within 6 to 12 months (4). Studies of relapse prevention strategies suggest that teaching coping skills may reduce the risk for relapse, but other behavioral therapies have shown little benefit (5, 6). Because pharmacologic therapy for smoking cessation has been proven effective and behavioral relapse prevention strategies alone have shown no great benefit, pharmacologic therapy for relapse prevention should be evaluated. Bupropion has been proven an effective intervention for smoking cessation, both as a single therapy and in combination with nicotine-patch therapy (2, 3). Because bupropion is effective for initiating abstinence from smoking and is safe for long-term therapy, we hypothesized that prolonged bupropion treatment in recently abstinent smokers would decrease the relapse rate. We compared sustained-release bupropion treatment with placebo for 1 year in participants who achieved initial abstinence after 7 weeks of therapy with open-label, sustained-release bupropion. Methods Participants This randomized, double-blind, placebo-controlled study of relapse prevention was performed at five sites (Mayo Clinic, Rochester, Minnesota; the Palo Alto Center for Pulmonary Disease Prevention, Palo Alto, California; Brown University, Providence, Rhode Island; Oregon Health Sciences University, Portland, Oregon; and Massachusetts General Hospital, Boston, Massachusetts) and was approved by the institutional review board at each site. We recruited participants through advertisements and press releases. After passing an initial screening interview by telephone, participants attended an informational meeting. At this meeting, the study was explained and the participants completed questionnaires and gave written, informed consent. The volunteers were eligible for study inclusion if they were 18 years of age or older, had smoked an average of at least 15 cigarettes or more per day for the past year, were motivated to stop smoking, and were in generally good health. Only one smoker per household was allowed in the study. Exclusion criteria included a personal or family history of a seizure disorder; history of severe head trauma; predisposition to seizures (such as history of brain tumor or stroke); history or current diagnosis of anorexia nervosa or bulimia; presence of an unstable medical or psychiatric condition; pregnancy; lactation; dependence on alcohol or other nonnicotine substance in the past year; current use of psychotropic medications; previous use of bupropion; current use of tobacco products other than cigarettes; or current use of any therapy for smoking cessation [such as nicotine replacement therapy; fluoxetine, clonidine, buspirone, or doxepin therapy; or behavioral therapy]. Persons with current major depression were also excluded. Potential participants were deemed to have current major depression if: 1) they met the criteria for this condition on the basis of their responses in a structured clinical interview [conducted by a trained study assistant], or 2) they were judged to have major depression by the physician performing the entrance history and physical examination (7). Treatment Beginning at the baseline visit and continuing through study week 7, all participants received open-label, sustained-release bupropion (bupropion SR), 300 mg/d (150 mg/d for 3 days, followed by 150 mg twice daily). At the baseline visit, participants were instructed to set a target quitting date after 1 week of medication use [usually day 8 of therapy]. Each participant attended weekly follow-up visits during the 7-week open-label phase. Participants were eligible for random assignment to receive bupropion or placebo in the double-blind phase if they 1) reported not smoking [not even a puff] during week 7 of the open-label phase and 2) had their self-report confirmed by an expired carbon monoxide level of 10 parts per million (ppm) or less. The randomly assigned participants returned for 14 visits during the double-blind phase (at weeks 8, 9, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) and 5 visits during the follow-up year (at weeks 53, 56, 64, 78, and 104). Participants also received a telephone follow-up at 21 months after study enrollment. At the baseline physical examination, each participant received a brief personalized message from the examining physician to stop smoking, set a target quitting date, and received self-help material that was based on a smoking cessation program designed by the U.S. National Cancer Institute (8). At each visit during the open-label and double-blind study phases, study assistants counseled participants for approximately 10 to 15 minutes. Randomization to the placebo or bupropion groups was computer generated at a central location; the investigators did not know the patient assignments. All bupropion and placebo pills were identical in shape, size, and color. Assessments At baseline, participants had a physical examination; underwent chest radiography, laboratory testing, and electrocardiography; and completed a Fagerstrm Tolerance Questionnaire and a Beck Depression Inventory. The Fagerstrm Tolerance Questionnaire is a widely used measure of nicotine dependence with scores that range from 0 to 11; scores of 6 or greater indicate higher levels of dependence (9, 10). At each visit through week 53, study assistants recorded adverse experiences, as well as use of study and concomitant medications. Participants maintained a daily diary of withdrawal symptoms (11) and daily cigarette use that was reviewed at each visit through week 12. The Beck Depression Inventory (administered at baseline and weeks 7, 8, 12, 52, 53, 56, 78, and 104) is a 21-item, self-administered questionnaire that assesses severity of depressive symptoms (12). Smoking status was self-reported at each visit; reports of abstinence were considered validated with a measurement of carbon monoxide level in expired air of no higher than 10 ppm. Outcome Measures The main outcomes of interest were 1) weekly point-prevalence abstinence during medication treatment, 2) continuous abstinence during medication treatment, and 3) time to first relapse. Secondary outcomes included weight change over time and point prevalence and continuous-abstinence rates after completion of drug therapy. The weekly point-prevalence smoking status was defined as 1) self-report of not smoking during the previous 7 days that was confirmed by an expired air carbon monoxide level of 10 ppm or lower and 2) two or fewer consecutive missed visits. Smoking relapse was defined as a self report of smoking or an expired air carbon monoxide level greater than 10 ppm. Participants were also considered to have smoking relapse if they missed more than two consecutive visits. All participants meeting the abstinence criteria at every visit were considered continuously abstinent. Self-report determined the date of smoking relapse. For participants who self-reported not smoking but who were classified as smoking because of an elevated carbon monoxide level or because of consecutive missed visits, the date of relapse was defined as the day after the most recent previous study visit at which smoking abstinence was biochemically confirmed. Statistical Analysis We determined that we needed a sample size of 170 participants in each randomly assigned treatment group to detect a significant between-group difference in end-of-treatment abstinence rates of 0.15 at a significance level of 0.05 and a power of 0.80. Assuming an abstinence rate of 35% for week 7 of the open-label phase, we determined that up to 1000 enrollees were needed to ensure a minimum sample of 340 nonsmoking participants (170 per group) for randomization. The 1-week point prevalence for smoking status during week 7 of the open-label bupropion phase was used to determine eligibility for random assignment to receive placebo or active sustained-release bupropion, 300 mg/d. To compare the baseline characteristics of the bupropion and placebo recipients, we used the two-sample t-test and the chi-square test for analysis of continuous and categorical variables, respectively. The efficacy of bupropion for preventing smoking relapse during the double-blind medication phase and follow-up phase was assessed by analyzing time to first smoking relapse. We used KaplanMeier survival estimates and a proportional hazards regression model (13, 14) to analyze time to first smoking relapse. For this analysis, time to first relapse was defined as the date of first relapse minus the date of randomization. For participants without relapse, time to first relapse was censored by using the date of their final (week 104) study visit. For the proportional hazards regression analysis, the response variable was time to first smoking relapse, and the independent variable was treatment. Randomization was stratified according to study site to ensure that similar numbers of participants were assigned to the treatment groups at each site. We verified that the treatment effect was not dependent on study site by performing an initial analysis that included the interaction of treatment by study site. Subsequently, we used a proportional hazards regression analysis with study site as a stratification factor to assess differences between treatment groups. Rates of point prevalence and continuous smoking abstinence were compared between treatment groups by using a logistic regression analysis with smoking status as the dependent variable and treat

Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Cardiovascular Disease A Randomized Trial

Background— Smoking cessation is a key component of secondary cardiovascular disease prevention. Varenicline, a partial &agr;4&bgr;2 nicotinic acetylcholine receptor agonist, is effective for smoking cessation in healthy smokers, but its efficacy and safety in smokers with cardiovascular disease are unknown. Methods and Results— A multicenter, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of varenicline with placebo for smoking cessation in 714 smokers with stable cardiovascular disease. Participants received varenicline (1 mg twice daily) or placebo, along with smoking-cessation counseling, for 12 weeks. Follow-up lasted 52 weeks. The primary end point was carbon monoxide–confirmed continuous abstinence rate for weeks 9 through 12 (last 4 weeks of treatment). The continuous abstinence rate was higher for varenicline than placebo during weeks 9 through 12 (47.0% versus 13.9%; odds ratio, 6.11; 95% confidence interval [CI], 4.18 to 8.93) and weeks 9 through 52 (19.2% versus 7.2%; odds ratio, 3.14; 95% CI, 1.93 to 5.11). The varenicline and placebo groups did not differ significantly in cardiovascular mortality (0.3% versus 0.6%; difference, −0.3%; 95% CI, −1.3 to 0.7), all-cause mortality (0.6% versus 1.4%; difference, −0.8%; 95% CI, −2.3 to 0.6), cardiovascular events (7.1% versus 5.7%; difference, 1.4%; 95% CI, −2.3 to 5.0), or serious adverse events (6.5% and 6.0%; difference, 0.5%; 95% CI, −3.1 to 4.1). As a result of adverse events, 9.6% of varenicline and 4.3% of placebo participants discontinued study drug. Conclusions— Varenicline is effective for smoking cessation in smokers with cardiovascular disease. It was well tolerated and did not increase cardiovascular events or mortality; however, trial size and duration limit definitive conclusions about safety. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov/ct2/show/NCT00282984. Unique identifier: NCT00282984.

Smoking Cessation Interventions for Hospitalized Smokers: A Systematic Review

BACKGROUND A hospital admission provides an opportunity to help people stop smoking. Providing smoking cessation advice, counseling, or medication is now a quality-of-care measure for US hospitals. We assessed the effectiveness of smoking cessation interventions initiated during a hospital stay. METHODS We searched the Cochrane Tobacco Addiction Review Groups register for randomized and quasirandomized controlled trials of smoking cessation interventions (behavioral counseling and/or pharmacotherapy) that began during hospitalization and had a minimum of 6 months of follow-up. Two authors independently extracted data from each article, with disagreements resolved by consensus. RESULTS Thirty-three trials met inclusion criteria. Smoking counseling that began during hospitalization and included supportive contacts for more than 1 month after discharge increased smoking cessation rates at 6 to 12 months (pooled odds ratio [OR], 1.65; 95% confidence interval [CI], 1.44-1.90). No benefit was found for interventions with less postdischarge contact. Counseling was effective when offered to all hospitalized smokers and to the subset admitted for cardiovascular disease. Adding nicotine replacement therapy to counseling produced a trend toward efficacy over counseling alone (OR, 1.47; 95% CI, 0.92-2.35). One study added bupropion hydrochloride to counseling, which had a nonsignificant result (OR, 1.56; 95% CI, 0.79-3.06). CONCLUSIONS Offering smoking cessation counseling to all hospitalized smokers is effective as long as supportive contacts continue for more than 1 month after discharge. Adding nicotine replacement therapy to counseling may further increase smoking cessation rates and should be offered when clinically indicated, especially to hospitalized smokers with nicotine withdrawal symptoms.

The Unmet Health Care Needs of Homeless Adults: A National Study

OBJECTIVES We assessed the prevalence and predictors of past-year unmet needs for 5 types of health care services in a national sample of homeless adults. METHODS We analyzed data from 966 adult respondents to the 2003 Health Care for the Homeless User Survey, a sample representing more than 436,000 individuals nationally. Using multivariable logistic regression, we determined the independent predictors of each type of unmet need. RESULTS Seventy-three percent of the respondents reported at least one unmet health need, including an inability to obtain needed medical or surgical care (32%), prescription medications (36%), mental health care (21%), eyeglasses (41%), and dental care (41%). In multivariable analyses, significant predictors of unmet needs included food insufficiency, out-of-home placement as a minor, vision impairment, and lack of health insurance. Individuals who had been employed in the past year were more likely than those who had not to be uninsured and to have unmet needs for medical care and prescription medications. CONCLUSIONS This national sample of homeless adults reported substantial unmet needs for multiple types of health care. Expansion of health insurance may improve health care access for homeless adults, but addressing the unique challenges inherent to homelessness will also be required.

Social Smoking Among US College Students

Objective. Young smokers commonly identify themselves as “social smokers,” a pattern of smoking behavior that is poorly understood. We assessed the prevalence and correlates of social smoking among US college students. Methods. Cross-sectional survey of a random sample of 10 904 students enrolled at 119 nationally representative US colleges in 2001. Results. A total of 51% of 2401 current (past 30-day) smokers were social smokers. (To assess social smoking, students were asked, “In the past 30 days, do you smoke mainly when you are with people, mainly when you are alone, or do you smoke as often by yourself as with others?” Students who stated that they smoked mainly with others rather than alone or equally by themselves and others were defined as social smokers for this analysis.) Social smoking was independently associated with a lower frequency and intensity of tobacco use, less nicotine dependence, less intention to quit, and fewer recent quit attempts. Conclusions. Social smoking is a distinct pattern of tobacco use that is common among college students and may represent a stage in the uptake of smoking.

Mortality Among Homeless Adults in Boston Shifts in Causes of Death Over a 15-Year Period

BACKGROUND Homeless persons experience excess mortality, but US-based studies on this topic are outdated or lack information about causes of death. To our knowledge, no studies have examined shifts in causes of death for this population over time. METHODS We assessed all-cause and cause-specific mortality rates in a cohort of 28 033 adults 18 years or older who were seen at Boston Health Care for the Homeless Program from January 1, 2003, through December 31, 2008. Deaths were identified through probabilistic linkage to the Massachusetts death occurrence files. We compared mortality rates in this cohort with rates in the 2003-2008 Massachusetts population and a 1988-1993 cohort of homeless adults in Boston using standardized rate ratios with 95% confidence intervals. RESULTS A total of 1302 deaths occurred during 90 450 person-years of observation. Drug overdose (n = 219), cancer (n = 206), and heart disease (n = 203) were the major causes of death. Drug overdose accounted for one-third of deaths among adults younger than 45 years. Opioids were implicated in 81% of overdose deaths. Mortality rates were higher among whites than nonwhites. Compared with Massachusetts adults, mortality disparities were most pronounced among younger individuals, with rates about 9-fold higher in 25- to 44-year-olds and 4.5-fold higher in 45- to 64-year-olds. In comparison with 1988-1993 rates, reductions in deaths from human immunodeficiency virus (HIV) were offset by 3- and 2-fold increases in deaths owing to drug overdose and psychoactive substance use disorders, resulting in no significant difference in overall mortality. CONCLUSIONS The all-cause mortality rate among homeless adults in Boston remains high and unchanged since 1988 to 1993 despite a major interim expansion in clinical services. Drug overdose has replaced HIV as the emerging epidemic. Interventions to reduce mortality in this population should include behavioral health integration into primary medical care, public health initiatives to prevent and reverse drug overdose, and social policy measures to end homelessness.

A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia.

The purpose of this study was to investigate the effect of adding sustained-release (SR) bupropion to cognitive behavioral therapy (CBT) on smoking behavior and stability of psychiatric symptoms in patients with schizophrenia. We conducted a 3-month, double-blind, placebo-controlled trial of bupropion SR, 150 mg/day, added to a concurrent CBT program with 3-month follow-up in 19 stable outpatients with schizophrenia who wanted to quit smoking. Eighteen subjects completed the trial. Bupropion treatment was associated with significantly greater reduction in smoking, as measured by self-report verified by expired-air carbon monoxide (6/9 subjects, 66%), than placebo (1/9 subjects, 11%) during the 3-month active treatment period and the 3-month follow-up period. One subject in the bupropion group (11%) and no subjects in the placebo group achieved sustained tobacco abstinence for the 6-month trial. Bupropion treatment was associated with improvement in negative symptoms and greater stability of psychotic and depressive symptoms, compared with placebo, during the quit attempt. Subjects in the bupropion group experienced significant weight loss, compared with those on placebo during the smoking cessation attempt. These data suggest that bupropion SR, 150 mg/day, combined with CBT, may facilitate smoking reduction in patients with schizophrenia while stabilizing psychiatric symptoms during a quit attempt.