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.

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.

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.

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.

Menstrual phase and depressive symptoms differences in physiological response to nicotine following acute smoking abstinence.

INTRODUCTION: Accumulating evidence has linked depressive symptoms and sex hormones to risk for relapse; however, the specific mechanisms involved in these associations remain unknown. This randomized crossover study assessed physiological response to nicotine by menstrual phase in female smokers with and without depressive symptoms following acute smoking abstinence. METHODS: Females, ages 18-40 years with regular menstrual cycles, not on exogenous hormones or psychotropic medications, who reported smoking ≥ 5 cigarettes/day were enrolled. Participants were stratified into 2 groups: no depressive symptoms (NDS; n = 23) and depressive symptoms (DS; n = 24). After 4 days of biochemically verified smoking abstinence, participants completed 2 laboratory sessions in the follicular (F) and luteal (L) phases. Participants used nicotine nasal spray at Time 0, and blood pressure, heart rate, and serum nicotine were measured at Time -1, 5, 10, 20, 30, 45, 60, and 90 min. RESULTS: Participants (n = 47) were 29.1 ± 6.8 years old and smoked an average of 12.5 ± 5.1 cigarettes/day. The NDS group had more pronounced menstrual phase differences (F > L) in diastolic blood pressure, heart rate, and maximum concentrations of nicotine compared with the DS group (p < .05). CONCLUSIONS: This study observed an interaction between sex hormones and depressive symptoms such that those without depressive symptoms had a greater menstrual phase difference in the physiological response to nicotine. These data offer additional support for the role of sex hormones in the physiological response to nicotine, which may play a role in menstrual phase effects on smoking cessation.

Comparing an immediate cessation versus reduction approach to smokeless tobacco cessation.

INTRODUCTION: Relatively few studies have investigated pharmacological or behavioral treatment of smokeless tobacco (ST) users who do not have immediate quit plans. In this study, we compared a reduction treatment approach with an immediate cessation approach in a population of ST users who reported no immediate plans to quit. METHODS: Subjects randomly assigned to the immediate cessation condition set a quit date soon after enrollment and were offered 2 weeks of nicotine patch therapy to help in their cessation efforts. Subjects assigned to the ST reduction group were provided with their choice of either 4 mg nicotine lozenge or ST brand switching to help them reduce their ST use or levels of nicotine exposure, respectively. Quit date was 6 weeks after the onset of treatment. Follow-up was at 12 weeks and 26 weeks postenrollment and 26 weeks postquit. RESULTS: Both 7-day point prevalence abstinence and prolonged abstinence rates following the quit date were significantly higher in the immediate cessation group versus the reduction group at 12 and 26 weeks (all p values ≤ .04) and for prolonged abstinence at 6 months postquit (p = .002). Significant reductions in ST use among nonquitters were observed for both groups (p < .0001) with no differences between groups. CONCLUSION: Our study demonstrated that immediate cessation with an established quit date resulted in greater cessation success than a gradual reduction approach among ST users who do not have an immediate quit plan but are motivated to quit.

The educational and financial impact of using patient educators to teach introductory physical exam skills.

PURPOSE: Physical exam skills are essential to core competencies for physicians in training. It is increasingly difficult to secure time and funding for physician faculty to teach these critical skills. This study was designed to determine whether Patient Educators (PE) (non-physician instructors) in an introductory clinical medicine (ICM) course (1) were as effective as physician faculty in teaching the physical exam, (2) impacted consistency of student performance on a final practical exam, and (3) whether this model was cost effective. METHOD: PE were introduced into an ICM course at the University of Minnesota from 2006 to 2008. Each year, students' physical exam competencies were evaluated by a performance-based head-to-toe examination and 6 months later by an objective structured clinical examination (OSCE). Differences in test scores between years and variability (i.e., consistency) among yearly scores were assessed. The cost per student was calculated by considering a stable compensation cost per hour for the required number of physician faculty, standardized patients, and PE in each year. RESULTS: Mean student performance was statistically lower with PE, but only by two percentage points. The amount of variation within the medical student classes' physical exam skills remained stable as the use of PE expanded. Total educator salary costs per student declined from $449 in 2006 to $196 in 2008. CONCLUSIONS: In terms of sustainability and student performance, the use of trained lay educators has equivalent outcomes and is less costly for physical exam instruction in the pre-clinical years.

Cannabis use and stressful life events during the perinatal period: cross-sectional results from Pregnancy Risk Assessment Monitoring System (PRAMS) data, 2016.

AIMS: We aimed to determine the association between stressful life events (SLEs) in the year prior to childbirth with (1) pre-pregnancy cannabis use, (2) cessation of cannabis use during pregnancy and (3) postpartum relapse to cannabis use. DESIGN: We used data from the Pregnancy Risk Assessment Monitoring System (PRAMS) 2016, a cross-sectional, population-based surveillance system. SETTING: Mailed and telephone surveys conducted in five states-Alaska, Colorado, Maine, Michigan and Washington-in the United States. PARTICIPANTS: Women (n = 6061) who delivered a live infant within the last 6 months and had data on cannabis use. MEASUREMENTS: Self-reported data included SLEs (yes/no response for 14 individual events in the 12 months prior to childbirth) and cannabis use [yes/no prior to pregnancy, during pregnancy, and at the time of the survey (approximately 2-6 months postpartum)]. The associations between SLEs and cannabis use (primary outcomes) were examined in logistic regression models adjusted for maternal demographics (e.g. age, race, education), geography (i.e. state of residence) and cigarette smoking. FINDINGS: Pre-pregnancy, 16.4% (997/6061) of respondents endorsed using cannabis, with 36.4% (363/997) continuing cannabis use during pregnancy. Among the 63.6% (634/997) who did not report use during pregnancy, 23.2% (147/634) relapsed to cannabis use during the postpartum. Nine of the 14 possible SLEs were associated with increased odds of pre-pregnancy cannabis use [e.g. husband/partner or mother went to jail, adjusted odds ratio (aOR) = 2.16, 95% confidence interval (CI) = 1.30-3.62] and four were associated with increased odds of continued cannabis use during pregnancy (e.g. husband/partner lost job, aOR = 2.19, 95% CI = 1.21-3.96). The odds of postpartum relapse to cannabis were significantly associated with two SLEs (husband/partner said they did not want pregnancy, aOR = 2.86, CI = 1.10-7.72; husband/partner or mother went to jail, aOR = 0.37, 95% CI = 0.13-1.00). CONCLUSIONS: Stressful life events during the year prior to childbirth appear to be linked to greater odds of women's cannabis use during the perinatal period, especially during pre-pregnancy.

Circadian patterns of ad libitum smoking by menstrual phase.

OBJECTIVE: Recent research suggests nicotine metabolism may be influenced by sex hormones. Thus, we hypothesized that circadian smoking patterns would vary by menstrual phase. METHODS: Healthy female smokers (n = 31) between the ages of 18 and 40 with regular menstrual cycles, and not using hormones or psychotropic medications, were recruited for a randomized clinical study. Subjects recorded the time of each cigarette smoked and their menstrual phase with daily diaries prospectively for one complete menstrual cycle of ad libitum smoking. Analyses included Poisson regression to assess variations in the rate of smoking during waking hours (i.e., 6:00 a.m. and 12:00 midnight) and circadian smoking patterns by menstrual phase. RESULTS: Participants were 29.61 +/- 5.44 years of age and smoked 16.93 +/- 5.37 cigarettes per day. Participants had a lower rate of smoking during waking hours in the follicular phase as compared to the menses phase. There were no significant menstrual phase differences in the circadian smoking patterns. CONCLUSIONS: These results offer further support for the influence of sex hormones on smoking behavior, but not on circadian patterns of smoking. Additional research is needed to study the direct relationship between nicotine metabolism, sex hormones, menstrual phase, and smoking behavior.

Subjective response to intranasal nicotine administration in oral contraceptive users and naturally-cycling women.

INTRODUCTION: Approximately half of premenopausal women who smoke cigarettes also use hormonal contraceptives, with most using oral contraceptives (OCs). While research on the effects of endogenous hormones on smoking-related outcomes continues to expand, little is known about the influence of OCs on similar outcomes. We sought to explore differences in the subjective response to nicotine by OC use after stratifying by testing condition (e.g., smoking status). METHODS: Participants were regular (≥5 cigarettes/day) smokers, classified into OC and naturally cycling (NC) groups. All participants completed four total lab sessions by smoking status (ad libitum smoking, acute smoking abstinence) and anticipated progesterone level (low progesterone week (LPW), high progesterone week (HPW)). Each lab session included self-administration of intranasal nicotine (Time 0 min), assessment of subjective response via the Subjective State Scale (-30 and + 5 min). RESULTS: Compared to the NC group (n = 28), the OC group (n = 14) was younger (26.2 ±â€¯1.1 versus 24.2 ±â€¯1.1; p < 0.001) and had a lower Fagerström Test for Nicotine Dependence score (3.4 ±â€¯0.5 versus 2.6 ±â€¯0.5; p = 0.011). Progesterone-to-estradiol ratios varied significantly by group at three of the four time points (p < 0.05). During ad libitum smoking, the OC group had significantly lower craving after nicotine administration than the NC group (1.93 ±â€¯0.33 versus 2.89 ±â€¯0.23; p = 0.024). No other significant differences in subjective response were identified. CONCLUSIONS: Despite significantly different hormone levels, group differences in subjective response to nicotine were relatively few. Additional research is needed to elucidate the mechanisms involved in these observations, as well as explore how they may influence cessation in women.

Exogenous progesterone for smoking cessation in men and women: a pilot double-blind, placebo-controlled randomized clinical trial.

BACKGROUND AND AIMS: In some clinical studies men and women have been found to differ in their ability to quit smoking, perhaps as a result of progesterone. The primary aim of this study was to provide a preliminary test of whether progesterone (PRO), compared with placebo (PBO), was more effective for smoking cessation in men and women. DESIGN: Pilot double-blind, placebo-controlled randomized clinical trial. SETTING: Minneapolis/St Paul metro area, Minnesota, USA. PARTICIPANTS: A total of 216 participants were randomized, including 113 men (18-60 years; PRO = 56, PBO = 57) and 103 women (18-50 years, pre-menopausal with self-reported regular menstrual cycles; PRO = 51, PBO = 52). INTERVENTION: Participants were randomized (1 : 1 within sex group) to either PRO (200 mg twice daily) or PBO. Participants were assigned a quit date approximately 7 days after starting medication (luteal phase for women) and were followed for 12 weeks to assess relapse. MEASUREMENTS: The primary outcome was self-reported 7-day point prevalence abstinence (PPA) at week 4. Secondary outcomes included 7-day PPA at weeks 8 and 12, prolonged abstinence, continuous abstinence, urine cotinine < 50 ng/ml, expired carbon monoxide ≤ 5 parts per million (p.p.m.) and days to relapse. FINDINGS: There was a significant difference in 7-day PPA at week 4 among women [PRO: 18 (35.3%) versus PBO: 9 (17.3%), odds ratio (OR) = 2.61, 95% confidence interval (CI) = 1.04, 6.54, P = 0.041], but not among men [PRO: 13 (23.2%) versus PBO: 12 (21.1%), 1.13 (0.47, 2.76), P = 0.782]. There was some evidence that PRO delayed relapse in women (days to relapse; PRO: 20.5 ± 29.6 versus PBO: 14.3 ± 26.8, P = 0.03) but not in men (PRO: 13.4 ± 25.9 versus PBO: 13.3 ± 23.8, P = 0.69). CONCLUSIONS: Oral micronized progesterone may aid smoking cessation in women.

Longitudinal stability in cigarette smokers of urinary eicosanoid biomarkers of oxidative damage and inflammation.

The urinary metabolites (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α), an F2-isoprostane and biomarker of oxidative damage, and "prostaglandin E2 metabolite" (PGE-M), a biomarker of inflammation, are elevated in cigarette smokers. However, there is little information in the literature on the longitudinal stability of these widely used biomarkers. In a large clinical trial involving 10 institutional sites, smokers were given, free of charge over a period of 20 weeks, Spectrum NRC600/601 research cigarettes containing 15.5 mg nicotine/g tobacco. All participants were instructed to smoke these cigarettes for the duration of the study. At weeks 4, 8, 12, 16, and 20, first morning urine voids were collected and analyzed for 8-iso-PGF2α and PGE-M using validated liquid chromatography-electrospray ionization-tandem mass spectrometry methods. The mean level of 8-iso-PGF2α at Week 4 was 1.34 ± 1.08 (S.D.) pmol/mg creatinine (N = 226) while that of PGE-M was 73.7 ± 113 (S.D.) pmol/mg creatinine (N = 232). The corresponding levels at Week 20 were 1.35 ± 0.93 (S.D.) pmol/mg creatinine (N = 209) for 8-iso-PGF2α and 74.2 ± 142 (S.D.) pmol/mg creatinine (N = 210) for PGE-M. There was variation in these values in the intervening weeks. The intra-class correlation coefficients (ICC) were 0.51 (95% CI, 0.45, 0.57) and 0.36 (0.30, 0.43), for 8-iso-PGF2α and PGE-M, respectively, indicating fair longitudinal stability for 8-iso-PGF2α and poorer longitudinal stability for PGE-M in cigarette smokers. Males had higher ICC values than females for both 8-iso-PGF2α and PGE-M. These results indicate that, in addition to cigarette smoking, endogenous processes of oxidative damage and inflammation influence the levels of these biomarkers over time among current smokers.

Longitudinal stability in cigarette smokers of urinary biomarkers of exposure to the toxicants acrylonitrile and acrolein.

The urinary metabolites cyanoethyl mercapturic acid (CEMA) and 3-hydroxypropyl mercapturic acid (3-HPMA) have been widely used as biomarkers of exposure to acrylonitrile and acrolein, respectively, but there are no published data on their consistency over time in the urine of cigarette smokers. We provided, free of charge over a 20 week period, Spectrum NRC600/601 research cigarettes to cigarette smokers in the control arm of a randomized clinical trial of the reduced nicotine cigarette. Urine samples were collected at weeks 4, 8, 12, 16, and 20 and analyzed for CEMA and 3-HPMA, and total nicotine equivalents (TNE) using validated methods. Creatinine-corrected intra-class correlation coefficients for CEMA, 3-HPMA, and TNE were 0.67, 0.46, and 0.68, respectively, indicating good longitudinal consistency for CEMA, while that of 3-HPMA was fair. A strong correlation between CEMA and TNE values was observed. These data support the use of CEMA as a reliable biomarker of tobacco smoke exposure. This is the first report of the longitudinal stability of the biomarkers of acrylonitrile and acrolein exposure in smokers. The data indicate that CEMA, the biomarker of acrylonitrile exposure, is consistent over time in cigarette smokers, supporting its use. While 3-HPMA levels were less stable over time, this biomarker is nevertheless a useful monitor of human acrolein exposure because of its specificity to this toxicant.

Menstrual phase effects on smoking relapse.

AIMS: To examine if menstrual phase affects relapse in women attempting to quit smoking. DESIGN: An intent-to-treat randomized smoking cessation trial where women were assigned to quit smoking in either the follicular (F) or luteal (L) menstrual phase and were followed for up to 26 weeks. They were assessed for relapse by days to relapse and relapse phase to determine if those who begin a quit attempt during the F phase were more successful than those who begin during the L phase. SETTING: Tobacco Use Research Center, University of Minnesota, Minneapolis, Minnesota. PARTICIPANTS: A total of 202 women. MEASUREMENTS: Latency to relapse from continuous and prolonged abstinence, point prevalence, phase of relapse, first slip within the first 3 and 5 days post-quit date, subject completion rates and symptomatology (i.e. withdrawal and craving). FINDINGS: The mean days to relapse from continuous abstinence and relapse from prolonged abstinence for the F group were 13.9 and 20.6 days, respectively, and 21.5 and 39.2 days, respectively, for the L group. Using point prevalence analysis at 14 days, 84% of the F group had relapsed compared with 65% of the L group [chi(2)=10.024, P=0.002; odds ratio (OR) = 2.871, 95% confidence interval (CI), 1.474-5.590]. At 30 days, 86% of the F group relapsed, compared with 66% of the L group (chi(2)=11.076, P=0.001; OR=3.178, 95% CI, 1.594-6.334). CONCLUSION: Women attempting to quit smoking in the F phase had less favorable outcomes than those attempting to quit in the L phase. This could relate to ovarian hormones, which may play a role in smoking cessation for women.

Hormonal contraceptive use in smokers: Prevalence of use and associations with smoking motives.

INTRODUCTION: While endogenous sex hormones influence smoking-related outcomes, little is known about the role of hormonal contraceptives (HCs). This is despite dated estimates suggesting that HC use is prevalent among female smokers. Therefore, we sought to update estimates of the prevalence of HC use among female smokers and explore the association of HC use with various smoking motives (SMs). METHODS: This online cross-sectional survey recruited female smokers between the ages of 18-35. Survey questions assessed smoking behavior, SMs, use of HCs, and menstrual cycle regularity. RESULTS: Participants (n=734) were, on average (±standard deviation), 20.7±2.7 years old and smoked 7.3±6.7 cigarettes/day. The majority of females reported a history of HC use (85%) and half reported current use (48%). Cyclical HC users (n=227) scored significantly lower on three SMs compared to naturally-cycling women in the follicular phase (n=62) and significantly higher on 15 SMs compared to naturally-cycling women in the luteal phase (n=29). Women on cyclical HCs differed from women on long-acting HCs (n=128) on two SMs. Further, the naturally-cycling women in the follicular phase scoring significantly higher on 15 SMs compared to those in the luteal phase. DISCUSSION: These observations indicate that HC use remains prevalent in female smokers and may influence SMs. Additional research should replicate these observations and explore the implications on smoking cessation outcomes.

Association of exercise with smoking-related symptomatology, smoking behavior and impulsivity in men and women.

INTRODUCTION: Despite extensive efforts to develop effective smoking cessation interventions, 70-85% of American cigarette smokers who quit relapse within one year. Exercise has shown promise as an intervention; however, many results have been equivocal. This study explored how exercise is associated with smoking-related symptomatology, smoking behavior and impulsivity in male and female smokers. METHODS: Participants were recruited throughout the United States using the on-line crowdsourcing platform, Amazon's Mechanical Turk. They completed a survey with self-report measures assessing exercise, smoking-related symptomatology, smoking behavior and impulsivity. Differences between men and women were tested using t- and chi-square tests. Regression analyses tested for associations between exercise and smoking-related symptomatology, smoking behavior and impulsivity. RESULTS: Participants (N = 604) were, on average, 32 (SD = 6.2) years old, mostly Caucasian, with at least some college education and approximately half were women. Women exercised slightly less than men and had more negative affect, craving, physical symptoms and withdrawal. Women smoked more cigarettes per day, had greater nicotine dependency and more years of smoking. Positive affect was positively associated with exercise for both men and women; however, this association was significantly stronger in women. Negative affect and withdrawal were inversely associated with exercise for women only. Impulsivity was inversely associated with exercise for both men and women. CONCLUSION: Exercise was significantly associated with several smoking-related symptomatology, smoking behavior and impulsivity variables for both men and women, suggesting that exercise may be a useful intervention for smoking cessation. Future prospective research should determine how exercise directly impacts smoking cessation.

Differences in mood and cortisol by menstrual phase during acute smoking abstinence: A within-subject comparison.

There is evidence that smoking-cessation success differs by menstrual phase and sex hormone levels; however, the biological mechanisms underlying these differences are not clear. One possibility is that variation in cortisol throughout the menstrual cycle and early smoking abstinence may be partly responsible. The goal of this secondary-data analysis was to conduct a within-subject examination of the effects of menstrual phase and smoking abstinence on salivary cortisol and mood. Data are from a controlled crossover trial, in which participants completed 2 testing weeks during their follicular and luteal phases. During each testing week, they smoked ad libitum during the first 2 days and then abstained from smoking during the next 4 days. Salivary cortisol and self-reported mood were collected 5 times on the day before abstinence (D0) and the first (D1) and third (D3) days of abstinence. Participants (n = 125) were, on average (mean ± SE), 29.4 ± 0.6 years old and smoked 12.6 ± 0.5 cigarettes/day. Whereas salivary cortisol varied significantly by time of day (p < .0001) and smoking abstinence (D0 to D1: ß = -0.06 ± 0.02 log[ng/ml], p = .0074 and D3: ß = -0.05 ± 0.02 log[ng/ml], p = .0117). no significant differences by menstrual phase were observed. Craving increased from D0 to D1 during the follicular phase but decreased in the luteal phase (+0.31 vs. -0.15, ß = 0.46 ± 0.19, p = .0162). This work builds on prior observations in demonstrating a decrease in cortisol in acute smoking abstinence and menstrual phase differences in craving. The results provide further evidence that cortisol levels do not vary by menstrual phase in the first few days of abstinence. (PsycINFO Database Record