Outcomes after chimeric antigen receptor T-cell therapy across large B-cell lymphoma subtypes.

Not available.

Blunted opioid regulation of the HPA stress response during nicotine withdrawal: therapeutic implications.

Endogenous opioids regulate pain, drug reward, and stress responses. We have previously shown reduced hypothalamic-pituitary-adrenal (HPA) responses to psychological stress and to opioid blockade among dependent smokers. In this study, we examined the extent to which biologically confirmed nicotine withdrawal alters endogenous opioid regulation of HPA axis functioning during rest and in response to acute stress. Smokers were randomly assigned to one of two conditions; 24 h withdrawal from all nicotine-containing products (n = 62) or smoking ad libitum (n = 44). A nonsmoking comparison group (n = 43) was also included. Participants (85 males and 64 females) completed two acute stress sessions during which a placebo or 50 mg of naltrexone (opioid antagonist) were administered using a double-blind design. Blood and saliva samples (assayed for cortisol and adrenocorticotropic hormone, i.e. ACTH) and mood measures were obtained during a resting absorption period, after acute stress (public speaking, mental arithmetic, and cold pressor tasks), and during an extended recovery period. Results indicated that opioid blockade (naltrexone) was associated with increased ACTH and cortisol responses to stress, and tobacco withdrawal was associated with blunted hormonal responses. A pattern of sex differences also emerged, with women exhibiting reduced ACTH responses to stress and higher ACTH and plasma cortisol responses to opioid blockade. These results indicated that compared to ad libitum smoking, nicotine withdrawal is associated with blunted opioid modulation of the HPA axis. Sex may modulate these effects. Blunted endogenous opioid regulation may underlie an incentive process that reinforces smoking behavior and may warrant therapeutic attention.

Exercise for Smoking Cessation in Postmenopausal Women: A Randomized, Controlled Trial.

BACKGROUND: Postmenopausal smokers have difficulty quitting smoking and experience considerable weight gain with smoking cessation. We examined whether adjunctive smoking treatment with exercise, compared to a relaxation control condition, could improve cigarette abstinence, decrease cigarettes smoked per day (CPD), and ameliorate changes in body mass index (BMI) in postmenopausal smokers. METHODS: Women (N = 301) signed informed consent and were randomized to treatment at two sites (Universities of Connecticut and Minnesota). We randomized groups of participants to a comprehensive group treatment program that included 12 weeks of varenicline and either a moderate exercise or relaxation component for 6 months. Participants were followed for a year after medication treatment. RESULTS: Overall, 17.3% of patients reported carbon monoxide-verified continuous abstinence for the 9- to 12-week period, and 11.6% reported prolonged abstinence at 1 year, with no significant differences between treatment conditions. CPD reported at study visits showed significant main effects for time in weeks, for site, and for treatment. The Exercise condition reported smoking fewer CPD over time, and that advantage widened over time. In terms of BMI, significant effects for time in weeks, and for the interaction of Week × Treatment condition, reflected gradually increasing BMI in these women over time, but with the increase in BMI slower in the Exercise condition. CONCLUSIONS: Exercise, compared to relaxation, was associated with a reduced BMI and CPD in postmenopausal women, but did not increase end of treatment or prolonged abstinence. Further research is needed to devise exercise programs that increase smoking cessation rates in postmenopausal women. IMPLICATIONS: This study adds to the literature on the effectiveness of a moderate exercise intervention compared to a relaxation control condition as an adjunctive treatment for smoking cessation in postmenopausal women. Our exercise program did not increase end of treatment or prolonged abstinence rates in postmenopausal women; however, there was a beneficial effect on smoking reduction and reduced body mass index. Additional research is needed to devise exercise programs that increase smoking cessation rates in postmenopausal women.

Improving Self-Care Management in Low-Income Latinos With Type 2 Diabetes Using Peer-Led U.S. Conversation Maps: A Quality Improvement Project in a Free Clinic.

A culturally sensitive Healthy Interactions Conversations Maps program was implemented for teaching diabetes self-management education (DSME) to Latinos with type 2 diabetes using peer-led educators in a community health center. Patients were invited to participate in a group care setting to improve access to providers and DSME. Goals were to improve diabetes distress, self-efficacy, and glycemic control as measured by A1C. Significant improvements were found for mean diabetes self-efficacy scores from before (2.53 ± 0.59) to after (2.91 ± 0.50) DSME (P <0.001). Mean A1C decreased significantly from before (9.51 ± 1.72%) to after (8.79 ± 1.68%) DSME (P = 0.043) at the end of the 6-month intervention. Thus, this program was found to be a useful tool for providing DSME in community health clinics serving low-income Latinos.

Stressful life events are associated with perinatal cigarette smoking.

Perinatal smoking, including smoking during pregnancy and postpartum smoking relapse, is a persistent public health problem. While childhood trauma has been linked to perinatal smoking, less is known about the association with more proximal stressful life events (SLEs). The objective of this study was to examine the association between SLEs that occurred during the year prior to childbirth with perinatal smoking. Using the Pregnancy Risk Assessment Monitoring System 2009-2011, perinatal smoking was assessed at three time points: (1) three months prior to pregnancy, (2) the last three months of pregnancy, and (3) two to six months postpartum. Survey respondents endorsed up to 13 SLEs (i.e., death of someone close). SLEs were analyzed individually, as well as using a cumulative score (range 0-13). Weighted analyses included unadjusted and adjusted logistic regression. Among those who smoked prior to pregnancy (n = 15,316), 48% (n = 7308) reported quitting smoking during pregnancy. Of those, 44% (n = 3126) reported postpartum smoking relapse. A total of 11 SLEs were associated with smoking during pregnancy and 2 SLEs were associated with postpartum smoking relapse. The odds of continued smoking during pregnancy was 12% higher for each SLE endorsed (adjusted odds ratio [aOR] = 1.12, 95% confidence interval [CI]: 1.09, 1.15) and this association was attenuated in relation to the odds of postpartum smoking relapse (aOR = 1.03, 95% CI: 0.99, 1.08). SLEs are associated with perinatal smoking. Additional research is needed to elucidate the mechanisms of action and to develop interventions specific to the needs of women who experience SLEs.

Influences of the Menstrual Phase on Cortisol Response to Stress in Nicotine Dependent Women: A Preliminary Examination.

INTRODUCTION: Evidence indicates that menstrual cycle phase plays a role in smoking withdrawal symptoms and craving. Stress increases these symptoms. Whether the stress regulatory mechanism is associated with menstrual phase and withdrawal symptoms is not well understood. METHODS: Thirty-seven female smokers and 16 female nonsmokers were asked to complete a laboratory session. In each group, approximately half of the participants were tested when they were in the follicular phase and the other half was tested in the luteal phase. The session included resting baseline, stress, and recovery periods. Saliva samples for the measurement of cortisol and subjective measures of craving and withdrawal symptoms were collected at the end of each period. RESULTS: A series of repeated measures analysis of covariance found a significant smoking group × menstrual phase × sampling time interaction in cortisol levels (p < .05). Follow-up analyses indicated a reduced cortisol stress response in the luteal group relative to the follicular group in smokers (p < .02). This difference was not found in nonsmokers. CONCLUSIONS: Menstrual cycle phase is related to hormonal stress response and smoking withdrawal symptomatology. IMPLICATIONS: We show influences of the menstrual cycle phase on stress response among smokers. This is demonstrated by a reduced cortisol response to stress in the luteal group relative to the follicular group among smokers. This menstrual phase difference was not found in nonsmokers.

Circulating orexin changes during withdrawal are associated with nicotine craving and risk for smoking relapse.

We examined the extent to which orexin measured during smoking and the early phase of abstinence was related to craving, withdrawal, stress hormones, and risk for smoking relapse in men and women. Considering its role in modulating nicotine-related reward, we predicted that a reduction in circulating orexin during withdrawal would be associated with increased craving and risk for smoking relapse. Two hundred and eighty five participants provided biological samples and self-report information to identify predictors of smoking relapse. All participants attended two laboratory sessions, which were before and after a period of required abstinence from smoking. After quitting, participants also attended four weekly sessions to track smoking relapse. Only smokers who relapsed within the follow-up period exhibited reduced orexin levels during the initial withdrawal period; ACTH, but not craving nor cortisol, increased across the abstinence period for successful abstainers but not for relapsers. Sex differences in orexin and craving or withdrawal associations also emerged. Adding sex, HPA hormones, and self-reported measures of craving and withdrawal as potential mediators had minimal effects on the above abstinence and orexin effects. These results provide the first evidence that circulating orexin may be a useful marker of risk for relapse; and sex, adrenal hormones, and self-reported craving and withdrawal were not mediators of this effect. The results point to a promising pathway to investigate objective biological markers for craving and smoking relapse and highlight the complexity of the neurobiology of relapse.

Postpartum Changes in Mood and Smoking-Related Symptomatology: An Ecological Momentary Assessment Investigation.

Introduction: Postpartum smoking relapse is a highly prevalent public health problem. Mood and breast feeding are significantly associated with smoking relapse, although less is known about the temporality of these relationships. Therefore, this study utilized ecological momentary assessments (EMA) to prospectively examine changes in mood and smoking-related symptomatology in relationship to three events-childbirth, termination of breast feeding, and smoking relapse. We expected all three events to significantly alter mood and smoking-related symptomatology. Methods: We enrolled a sample of pregnant women who had recently quit smoking and intended to remain quit during the postpartum. Participants were randomized to active/placebo progesterone to prevent postpartum relapse. Participants also completed daily EMA to collect data mood and smoking-related symptomatology as well as our three events of interest. Results: Participants (n = 46) were, on average, 26.5 ± 0.8 years old and, prior to pregnancy, smoked 10.1 ± 0.7 cigarettes/day. We noted a number of significant within- and between-subject relationships. For example, participants reported a 24% decline in negative affect after childbirth (p = .0016). Among those who relapsed to smoking (n = 23), participants randomized to placebo had a significant increase in cigarette craving after relapse (ß = 1.06, 95% confidence interval [CI] = 0.62 to 1.49, p value = .0003), whereas participants randomized to active progesterone did not (ß = 0.63, 95% CI = -0.35 to 1.62, p value = .1824). Conclusions: These observations suggest that mood and smoking-related symptomatology are influenced by childbirth, breast feeding, smoking relapse, and use of exogenous progesterone. Future research should explore how these observations may inform novel postpartum smoking relapse-prevention interventions. Implications: Postpartum smoking relapse has been a persistent public health problem for more than 40 years. Although a number of significant predictors of postpartum smoking relapse have been identified (eg, depression and breast feeding), much of these analyses have relied on cross-sectional and/or self-reported retrospective data. Therefore, for the first time, we utilized ecological momentary assessment to explore the effect of childbirth, termination of breast feeding, and smoking relapse on mood and smoking-related symptomatology (eg, craving). Numerous significant relationships were observed, including a 96% increase in craving after smoking relapse. These novel observations can inform new and effective postpartum smoking relapse-prevention programs.

Hospital Leadership Diversity and Strategies to Advance Health Equity.

BACKGROUND: Diversity in hospital leadership is often valued as important for achieving clinical excellence. The American Hospital Association surveyed hospitals about their actions to identify and address health disparities. The survey asked about the degree of representation of racial and ethnic minorities and women among executives and board members. METHODS: The survey contained 78 items in four domains: Leadership and Strategic Planning, Workforce, Data Collection, and Reducing Disparities. All items were standardized and pooled within each domain to construct four variables. Logistic regression models were used to assess the difference in domain scores, for each domain, between hospitals with (a) high and low representation of people of color in the C-suite, (b) high and low representation of women in the corporate (C-) suite, (c) high and low representation of people of color on the board, and (d) high and low representation of women on the board. RESULTS: Hospitals with more diverse boards with respect to race and ethnicity had significantly higher scores for all domains, indicating that these hospitals were pursuing substantially more strategies in all domains. In contrast, more racially and ethnically diverse executive suites were associated only with the Data Collection domain, while hospitals with a higher percentage of women in executive positions had lower scores for all domains except Data Collection. CONCLUSION: Hospitals with greater representation of racial and ethnic minorities in leadership positions had greater commitments to diversity initiatives. However, hospitals with women-particularly white women-in leadership positions reported fewer diversity initiatives. Future research is needed to examine the mechanisms and causality behind these associations.

What do medical students know about e-cigarettes? A cross-sectional survey from one U.S. medical school.

BACKGROUND: Although electronic cigarette (e-cigarette) use has rapidly increased, there is little data about what United States medical students know or are taught about them. This study examined medical students' experiences, knowledge, and attitudes regarding e-cigarettes, as well as their evaluation of their education on e-cigarettes. METHODS: A cross-sectional online survey of medical students currently enrolled at the University of Minnesota Medical School (n = 984) was conducted over a three-week period in August and September 2015. Primary outcomes included students' personal experiences with e-cigarettes, knowledge and attitudes about e-cigarettes, and students' assessment of their education on e-cigarettes. RESULTS: 66.9% medical students completed the survey. 58% (n = 382) of participants identified as female. 35.8% (n = 235) were "not sure" whether e-cigarettes were approved by the FDA for smoking cessation, while 4.1% (n = 27) falsely believed they were. While 82.9% (n = 543) agreed or strongly agreed that they felt confident in their ability to discuss traditional cigarette use with patients, only 12.4% (n = 81) agreed or strongly agreed that they felt confident in their ability to discuss e-cigarettes with patients. 94.8% (n = 619) of participants believed that they had not received adequate education about e-cigarettes in medical school. A higher proportion of males reported ever using an e-cigarette. CONCLUSIONS: The gaps in medical student knowledge and wide variances in attitudes about e-cigarettes at one medical school together with their report of inadequate education in an environment of increasing use of e-cigarette use in the U.S. speaks to a need for the development of medical school curriculum on e-cigarettes.

Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure: A Randomized Clinical Trial.

Importance: The optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined. Objectives: To determine the effects of immediate vs gradual reduction in nicotine content to very low levels and as compared with usual nicotine level cigarettes on biomarkers of toxicant exposure. Design, Setting, and Participants: A double-blind, randomized, parallel-design study with 2 weeks of baseline smoking and 20 weeks of intervention was conducted at 10 US sites. A volunteer sample of daily smokers with no intention to quit within 30 days was recruited between July 2014 and September 2016, with the last follow-up completed in March 2017. Interventions: (1) Immediate reduction to 0.4 mg of nicotine per gram of tobacco cigarettes; (2) gradual reduction from 15.5 mg to 0.4 mg of nicotine per gram of tobacco cigarettes with 5 monthly dose changes; or (3) maintenance on 15.5 mg of nicotine per gram of tobacco cigarettes. Main Outcomes and Measures: Between-group differences in 3 co-primary biomarkers of smoke toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT, indicator of polycyclic aromatic hydrocarbons) calculated as area under the concentration-time curve over the 20 weeks of intervention. Results: Among 1250 randomized participants (mean age, 45 years; 549 women [44%]; 958 [77%] completed the trial), significantly lower levels of exposure were observed in the immediate vs gradual reduction group for CO (mean difference, -4.06 parts per million [ppm] [95% CI, -4.89 to -3.23]; P < .0055), 3-HPMA (ratio of geometric means, 0.83 [95% CI, 0.77 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.88 [95% CI, 0.83 to 0.93]; P < .0055). Significantly lower levels of exposure were observed in the immediate reduction vs control group for CO (mean difference, -3.38 [95% CI, -4.40 to -2.36]; P < .0055), 3-HPMA (ratio of geometric means, 0.81 [95% CI, 0.75 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.86 [95% CI, 0.81 to 0.92]; P < .0055). No significant differences were observed between the gradual reduction vs control groups for CO (mean difference, 0.68 [95% CI, -0.31 to 1.67]; P = .18), 3-HPMA (ratio of geometric means, 0.98 [95% CI, 0.91 to 1.06]; P = .64), and PheT (ratio of geometric means, 0.98 [95% CI, 0.92 to 1.04]; P = .52). Conclusions and Relevance: Among smokers, immediate reduction of nicotine in cigarettes led to significantly greater decreases in biomarkers of smoke exposure across time compared with gradual reduction or a control group, with no significant differences between gradual reduction and control. Trial Registration: clinicaltrials.gov Identifier: NCT02139930.

Progesterone and Postpartum Smoking Relapse: A Pilot Double-Blind Placebo-Controlled Randomized Trial.

INTRODUCTION: Pregnancy is a strong motivator to quit smoking, yet postpartum relapse rates are high. Growing evidence suggests a role of sex hormones in drug abuse behavior and given the precipitous drop in sex hormones at delivery, they may play a role in postpartum relapse. This pilot study evaluates the feasibility and potential role of exogenous progesterone in postpartum smoking relapse. METHODS: This 12-week double-blind placebo-controlled randomized pilot trial randomized 46 abstinent postpartum women to active progesterone (PRO; 200mg twice a day) versus placebo (PBO) for 4 weeks. Participants were followed for relapse for 12 weeks. Main study outcomes include abstinence (point prevalence), feasibility (compliance per number of clinic visits attended, pill counts and Electronic Data Capture [EDC] completed) and self-reported acceptability. Safety was also measured by depressive symptom scores, adverse events, and breastfeeding. RESULTS: Overall retention rate was 87% at week 12. At week 4, abstinence rates were 75% in the PRO group and 68.2% in the PBO group (p = .75). Medication adherence was 68% and clinic visit attendance was 80%, with no differences by randomization. Depressive symptom scores, adverse events, and breastfeeding did not vary by randomization. CONCLUSIONS: Although the study was not powered to evaluate abstinence rates, we did observe a higher prevalence of abstinence at week 4 in the PRO group. Further, exogenous progesterone was well tolerated and did not adversely affect depressive symptoms or breastfeeding. Thus, the results of this pilot study indicate further investigation into progesterone as a postpartum relapse prevention strategy is warranted. IMPLICATIONS: This innovative pilot trial determined the feasibility of delivering exogenous progesterone as a potential prevention of postpartum smoking relapse. We observed high retention and moderate adherence rates, as well as high acceptability among participants. Further, though not statistically significant, more women in the treatment group remained abstinent from smoking during follow-up. This project adds to the growing body of literature on the role of sex hormones in smoking relapse and also provides support for a fully powered clinical trial.

Two colliding epidemics - obesity is independently associated with chronic pain interfering with activities of daily living in adults 18 years and over; a cross-sectional, population-based study.

BACKGROUND: Chronic pain interfering with activities of daily living is highly prevalent in the community. More than 600 million people worldwide are obese. The aim of this paper is to assess if such chronic pain is associated independently with obesity across the adult population, having controlled for other key factors. METHODS: The South Australian Health Omnibus is an annual, population-based, cross-sectional study. Data on 2616 participants were analysed for episodes of daily pain for three of the preceding six months. Obesity was derived from self-reported height and weight. Multivariable logistic regression analysed the associations between chronic pain interfering with activities of daily living, body mass index (BMI) and key socio-demographic factors. RESULTS: Chronic pain interfering with activities of daily living peaks in people ≥75 years of age while obesity peaks in the 45-54 age group. Pain and obesity together peak in the 55-74 year age group. In the adjusted multinominal logistic regression model, compared to those with no pain, there was a strong association between obesity and pain that interfered moderately or extremely with day-to-day activities (OR 2.25; 95 % CI 1.57-3.23; p < 0.001) having controlled for respondents' age, gender, rurality, country of birth and highest educational attainment. People over 65 years of age and those with lower educational levels were more likely to experience such chronic pain related to obesity. CONCLUSION: This study demonstrates a strong association between chronic pain and obesity/morbid obesity in the South Australian population. Prospective, longitudinal data are needed to understand the dynamic interaction between these two prevalent conditions.

Medical school curriculum characteristics associated with intentions and frequency of tobacco dependence treatment among 3rd year U.S. medical students.

OBJECTIVE: Physicians play a critical role in addressing tobacco dependence, yet report limited training. Tobacco dependence treatment curricula for medical students could improve performance in this area. This study identified student and medical school tobacco treatment curricula characteristics associated with intentions and use of the 5As for tobacco treatment among 3rd year U.S. medical students. METHODS: Third year medical students (N=1065, 49.3% male) from 10 U.S. medical schools completed a survey in 2009-2010 assessing student characteristics, including demographics, tobacco treatment knowledge, and self-efficacy. Tobacco curricula characteristics assessed included amount and type of classroom instruction, frequency of tobacco treatment observation, instruction, and perception of preceptors as role models. RESULTS: Greater tobacco treatment knowledge, self-efficacy, and curriculum-specific variables were associated with 5A intentions, while younger age, tobacco treatment self-efficacy, intentions, and each curriculum-specific variable were associated with greater 5A behaviors. When controlling for important student variables, greater frequency of receiving 5A instruction (OR=1.07; 95%CI 1.01-1.12) and perception of preceptors as excellent role models in tobacco treatment (OR=1.35; 95%CI 1.04-1.75) were significant curriculum predictors of 5A intentions. Greater 5A instruction (B=.06 (.03); p<.05) and observation of tobacco treatment (B=.35 (.02); p<.001) were significant curriculum predictors of greater 5A behaviors. CONCLUSIONS: Greater exposure to tobacco treatment teaching during medical school is associated with both greater intentions to use and practice tobacco 5As. Clerkship preceptors, or those physicians who provide training to medical students, may be particularly influential when they personally model and instruct students in tobacco dependence treatment.

Sex differences in hormonal responses to stress and smoking relapse: a prospective examination.

INTRODUCTION: Dysregulation in the hypothalamic-pituitary-adrenal axis has been shown to be associated with smoking relapse. No study has directly examined the role of sex differences in this relationship. METHODS: Nicotine dependent men (n = 52) and women (n = 46) interested in cessation completed 2 laboratory stress sessions during ad libitum smoking and after 48 hr of abstinence. The laboratory session included baseline, stress, and recovery periods. Blood and saliva samples were collected at the end of each period for the measurement of cortisol and adrenocorticotropic hormone. Self-report measures of craving and withdrawal symptoms were also collected. Participants attended 4 weekly follow-up sessions for counseling where they provided biological samples and self-report measures including smoking status. Relapse was defined by smoking cigarettes for 7 consecutive days post-cessation. RESULTS: Results showed that 60 participants relapsed during the 4-week period. Cox regression models from the abstinence session showed that cortisol levels regardless of source were predictive of relapse but the direction of prediction was sex dependent (Sex × Hormone, all ps < .05). Follow-up analyses further revealed that lower cortisol levels predicted relapse in men whereas greater cortisol levels predicted relapse in women (ps < .05). Enhanced craving predicted early smoking relapse in men but not in women (ps < .05). Data from the ad libitum session showed no differences in predicting relapse. CONCLUSION: These findings highlight that sex differences in the hormonal response to stress and subjective craving during nicotine withdrawal are critical predictors of risk for understanding early relapse.

Systematic and meta-analytic review of research examining the impact of menstrual cycle phase and ovarian hormones on smoking and cessation.

INTRODUCTION: To determine the effect of ovarian hormones on smoking, we conducted a systematic review of menstrual cycle effects on smoking (i.e., ad lib smoking, smoking topography, and subjective effects) and cessation-related behaviors (i.e., cessation, withdrawal, tonic craving, and cue-induced craving). METHODS: Thirty-six papers were identified on MEDLINE that included a menstrual-related search term (e.g., menstrual cycle, ovarian hormones), a smoking-related search term (e.g., smoking, nicotine), and met all inclusion criteria. Thirty-two studies examined menstrual phase, 1 study measured hormone levels, and 3 studies administered progesterone. RESULTS: Sufficient data were available to conduct meta-analyses for only 2 of the 7 variables: withdrawal and tonic craving. Women reported greater withdrawal during the luteal phase than during the follicular phase, and there was a nonsignificant trend for greater tonic craving in the luteal phase. Progesterone administration was associated with decreased positive and increased negative subjective effects of nicotine. Studies of menstrual phase effects on the other outcome variables were either small in number or yielded mixed outcomes. CONCLUSIONS: The impact of menstrual cycle phase on smoking behavior and cessation is complicated, and insufficient research is available upon which to conduct meta-analyses on most smoking outcomes. Future progress will require collecting ovarian hormone levels to more precisely quantify the impact of dynamic changes in hormone levels through the cycle on smoking behavior. Clarifying the relationship between hormones and smoking-particularly related to quitting, relapse, and medication response-could determine the best type and timing of interventions to improve quit rates for women.

Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial.

IMPORTANCE: Combining pharmacotherapies for tobacco-dependence treatment may increase smoking abstinence. OBJECTIVE: To determine efficacy and safety of varenicline and bupropion sustained-release (SR; combination therapy) compared with varenicline (monotherapy) in cigarette smokers. DESIGN, SETTING, AND PARTICIPANTS: Randomized, blinded, placebo-controlled multicenter clinical trial with a 12-week treatment period and follow-up through week 52 conducted between October 2009 and April 2013 at 3 midwestern clinical research sites. Five hundred six adult (≥18 years) cigarette smokers were randomly assigned and 315 (62%) completed the study. INTERVENTIONS: Twelve weeks of varenicline and bupropion SR or varenicline and placebo. MAIN OUTCOMES AND MEASURES: Primary outcome was abstinence rates at week 12, defined as prolonged (no smoking from 2 weeks after the target quit date) abstinence and 7-day point-prevalence (no smoking past 7 days) abstinence. Secondary outcomes were prolonged and point-prevalence smoking abstinence rates at weeks 26 and 52. Outcomes were biochemically confirmed. RESULTS: At 12 weeks, 53.0% of the combination therapy group achieved prolonged smoking abstinence and 56.2% achieved 7-day point-prevalence smoking abstinence compared with 43.2% and 48.6% in varenicline monotherapy (odds ratio [OR], 1.49; 95% CI, 1.05-2.12; P = .03 and OR, 1.36; 95% CI, 0.95-1.93; P = .09, respectively). At 26 weeks, 36.6% of the combination therapy group achieved prolonged and 38.2% achieved 7-day point-prevalence smoking abstinence compared with 27.6% and 31.9% in varenicline monotherapy (OR, 1.52; 95% CI, 1.04-2.22; P = .03 and OR, 1.32; 95% CI, 0.91-1.91; P = .14, respectively). At 52 weeks, 30.9% of the combination therapy group achieved prolonged and 36.6% achieved 7-day point-prevalence smoking abstinence compared with 24.5% and 29.2% in varenicline monotherapy (OR, 1.39; 95% CI, 0.93-2.07; P = .11 and OR, 1.40; 95% CI, 0.96-2.05; P = .08, respectively). Participants receiving combination therapy reported more anxiety (7.2% vs 3.1%; P = .04) and depressive symptoms (3.6% vs 0.8%; P = .03). CONCLUSIONS AND RELEVANCE: Among cigarette smokers, combined use of varenicline and bupropion, compared with varenicline alone, increased prolonged abstinence but not 7-day point prevalence at 12 and 26 weeks. Neither outcome was significantly different at 52 weeks. Further research is required to determine the role of combination therapy in smoking cessation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: http://clinicaltrials.gov/show/NCT00935818.

Cigarette smoking among women: how can we help?

Cigarette smoking remains a concern in the United States. Although more men than women in this country smoke, the gap appears to be narrowing. The risk for disease among women who smoke has risen sharply over the last 50 years and is now equal to that of men for lung cancer, chronic obstructive pulmonary disease and cardiovascular diseases. Female smokers also face health risks associated with pregnancy and use of oral contraceptives, menstrual irregularities, early menopause, osteoporosis and cervical cancer. In addition, they are less likely to have success quitting smoking. This article discusses some of the reasons why women have difficulty quitting, which can help guide physicians in assisting them with smoking cessation.

Delay discounting demonstrates lower impulsivity linked to a higher likelihood of succeeding at smoking cessation.

Sixty-eight percent of smokers want to quit, but only one in 10 are successful at smoking cessation. Recently, impulsivity has been studied in relation to smoking cessation with measures like the delay discounting task (DDT). We aimed to build on the robust literature that has already revealed the association between impulsivity and smoking cessation, as well as look at the differences between sexes for which there is conflicting evidence. We hypothesized that lower impulsivity would be positively associated with cessation success. In the parent cessation trial, participants were randomized to 12 weeks of progesterone or placebo. Participants were asked to quit smoking, and their smoking status was monitored via expired carbon monoxide throughout the study. Participants completed a DDT at screening, week 4, and week 8 using the 27-item Monetary Choice Questionnaire, where participants decided between a small immediate reward or a larger delayed reward (LDR). The effective delay 50 (ED50), which is the delay at which the LDR loses half its value, was analyzed. To estimate the association between ED50 and cessation, a logistic mixed model with a participant random intercept was fit, controlling for study week, randomization, sex, and age. For the 181 participants, a doubling of the ED50 was associated with an 18% increase in the odds of tobacco cessation (95% confidence interval: 0.2-38% increase; p=0.05). In agreement with our hypothesis, lower impulsivity correlated to greater tobacco cessation success. Our study also showed no evidence of sex differences in the association between ED50 and smoking cessation.