Examining Demand and Substitutability of Usual Brand Little Cigars/Cigarillos and Cigarettes in Young Adults Who Dual Use.

INTRODUCTION: Cigarette and little cigar/cigarillo (LCC) dual use is popular among young people and poses a substantial health risk. What remains unclear is the abuse liability of LCCs vs. cigarettes, LCCs' substitutability for cigarettes, and the influence of flavors on the abuse liability and substitutability of LCCs. METHODS: Sixty-five young adults (18-34 years) who dual use completed hypothetical purchase tasks to measure consumption of usual brand cigarettes and LCCs in 24 hours at increasing prices (demand), and LCC consumption at increasing cigarette prices (substitution). Three demand indices were calculated from raw data: breakpoint (price after which consumption reaches 0), Omax (maximum daily expenditure), and Pmax (price at maximum expenditure). Two indices were estimated using nonlinear mixed-effects modeling: intensity (consumption when free) and price-sensitivity (rate of decline in consumption as price increases). Substitution, and associations of flavored use with demand and substitution, were estimated using linear mixed models. RESULTS: Results indicated similar abuse liability for LCCs and cigarettes. Intensity was greater for cigarettes, but price-sensitivity was similar. Flavored LCC use was associated with lower price-sensitivity and greater intensity than unflavored. LCCs were significant substitutes for cigarettes, but the effect was small. Flavored use was not associated with substitution. CONCLUSIONS: Among young adults who dual use, LCCs and cigarettes had similar abuse liability, and those who used flavored had higher demand for their LCCs. A flavored cigar ban, as well as targeted prevention and cessation services for those who smoke flavored LCCs, may be important for reducing dual use in young adults. IMPLICATIONS: Cigarette and LCC dual use remains high among young adults. Using hypothetical purchase tasks with young adults who dual use, LCCs had abuse liability similar to cigarettes, but were only modest substitutes for cigarettes. Participants who used flavored LCCs reported greater abuse liability than those who used unflavored, but not greater substitution for cigarettes. Prevention and cessation services are needed to target LCCs in young people, particularly those smoking flavored products. A flavored cigar ban may help to reduce their demand.

Prevalence and factors associated with second hand smoke exposure among a sample of pregnant women in Cairo, Egypt.

PURPOSE: This study estimated the prevalence of and factors associated with secondhand smoke (SHS) exposure, and assessed attitudes and knowledge about SHS among pregnant women in Cairo, Egypt. METHODS: Pregnant women in the third trimester were recruited to participate in a survey assessing tobacco smoking and SHS exposure during their current pregnancy. Participants were recruited from three antenatal clinics in Cairo, Egypt, from June 2015 to May 2016. We examined differences in sociodemographic characteristics and SHS exposure, attitudes, and knowledge by smoking/SHS status. We used multivariable ordinary least squares regression to examine the association between husbands' smoking and pregnant women's mean daily hours of SHS exposure, adjusting for women's smoking status, age group, education, and urban (vs. suburban/rural) residence. RESULTS: Of two hundred pregnant women aged 16-37 years, about two-thirds (69%) had a husband who smoked tobacco. During their current pregnancy, most women reported being non-smokers (71%), and 38% of non-smokers reported being SHS-exposed. Non-smokers exposed to SHS tended to live in more rural areas and have husbands who smoked in the home. In adjusted analyses, having a husband who smoked was significantly associated with a greater mean number of hours of SHS exposure per day exposed, and this difference was driven by husbands who smoked in the home (p < 0.001). Women in the SHS-exposed group were less likely than other groups to agree that SHS exposure was harmful to their own or their future child's health; however, all groups agreed that SHS was harmful to newborn health. CONCLUSION: Among our sample of pregnant women in Cairo, Egypt, there was a high rate of SHS exposure as well as misconceptions about the safety of SHS exposure to a developing fetus. Our findings suggest a need for targeted education and gender-sensitive messaging about SHS exposure, along with improved enforcement of existing tobacco control policies.

Exposure to secondhand smoke (SHS) remains a major contributor to health problems in pregnant women and their children. Using a survey, this study sought to estimate how many pregnant women in Cairo Metropolitan Area, Egypt, were exposed to SHS and the factors contributing to that exposure, and to assess attitudes towards SHS. During their current pregnancy, 38% of non-smokers reported being exposed to SHS. Non-smokers exposed to SHS tended to live in more rural areas and have husbands who smoked in the home. Having a husband who smoked as well as a husband who smoked in the home was significantly associated with a greater average number of SHS exposure hours per day. Women in the SHS-exposed group were less likely than other groups to agree that SHS exposure was harmful to their own or their future child's health; however, all groups agreed that SHS was harmful to newborn health. Among pregnant women in Cairo, Egypt, there is a high rate of SHS exposure­often driven by SHS exposure in the home­as well as misconceptions about the safety of SHS exposure to a developing fetus. There is a need for targeted education and gender-sensitive messaging about SHS exposure along, with improved enforcement of existing tobacco control policies.

Manipulation of Menthol and Nicotine Content in Cigarettes: Effects on Smoking Behavior and Toxicant Exposure in Women Menthol Smokers.

BACKGROUND: The purpose of this study was to determine the effects of smoking and other outcomes of assigning cigarettes with reduced nicotine and/or no menthol to female menthol smokers. AIMS AND METHODS: Nontreatment-seeking female menthol smokers (N = 263) participated in a randomized controlled trial in which levels of menthol and nicotine in cigarettes were manipulated using experimental cigarettes. After a baseline period, participants were assigned to the following conditions for 6 weeks: (1) their own brand of cigarette (conventional nicotine with menthol), (2) a conventional nicotine cigarette with no menthol, (3) a cigarette with reduced nicotine (RNC) with menthol, or (4) a RNC cigarette and no menthol. Participants then returned to using their own brand and were followed for another 6 weeks. Outcomes included cigarettes smoked, biomarkers of exposure, and dependence measures. RESULTS: Results indicated that, after an initial increase, rates of smoking of all three experimental cigarettes were at or below baseline rates of smoking of one's own brand. Levels of biomarkers also decreased during the experimental phase but rebounded somewhat after participants resumed smoking their own brand. There was evidence that the overall amount of smoking decreased similarly among women who switched to non-menthol and/or RNC cigarettes. CONCLUSIONS: These results suggest that no detrimental effect will occur in nicotine or toxicant exposure levels with a ban on characterizing menthol and/or a product standard on nicotine content in cigarettes. IMPLICATIONS: The implication of this work is that there would be no risk to women menthol smokers associated with regulations restricting nicotine and eliminating menthol in cigarettes.

The inflammatory biomarker YKL-40 is elevated in the serum, but not the sputum, of E-cigarette users.

METHODS: We conducted a cross-sectional study of adults between 18 and 55 years old. Inclusion criteria were: exclusive e-cigarette use or cigarette smoking for ≥ 1 year or no history of tobacco use. Participants with a history of pulmonary illness, atopy, medications (except birth control pills), marijuana, and illegal substance use were excluded. Custom Multiplex ELISA was used to measure YKL-40 and other biomarker levels in the serum and induced sputum of the participants. Multivariable linear regression was used to compare the levels of YLK-40 in healthy participants, e-cigarette, and cigarette users after adjusting for age, sex, and BMI. RESULTS: We recruited 20 healthy controls, 23 cigarette smokers, and 22 exclusive e-cigarette users. Serum YKL-40 (ng/ml) was significantly higher in e-cigarette users (Median 21.2 [IQR 12.1-24.0] ng/ml) when compared to controls (12.2 [IQR 8.7-18.1] ng/ml, p = 0.016) but comparable to cigarette smokers (21.6 [IQR 11.62-51.7] ng/ml, p = 0.31). No significant differences were found in the serum or sputum of the other biomarkers tested. CONCLUSION: The inflammatory biomarker, YKL-40 is elevated in the serum but not the sputum of e-cigarette users with no reported pulmonary disease. Further research is necessary to characterize this association.

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.

Pregnant Smokers Receiving Opioid Agonist Therapy Have an Elevated Nicotine Metabolite Ratio: A Replication Study.

INTRODUCTION: Pregnant women exposed chronically to opioids smoked more cigarettes per day (CPD) and had a higher nicotine metabolite ratio (NMR), 3-hydroxycotinine/cotinine, a biomarker of nicotine metabolism and clearance, than those not receiving opioids. We examined CPD and NMR in a group of pregnant smokers, a quarter of whom were receiving opioid agonist therapy (OAT). AIMS AND METHODS: Pregnant smokers recruited to participate in a placebo-controlled trial of bupropion for smoking cessation provided a blood sample for measurement of NMR. RESULTS: Half (52.4%) of the 124 women with NMR data were African American. OAT-treated women (n = 34, 27.4%; 27 receiving methadone and 7 buprenorphine) were more likely to be white (79% vs. 30%, p < .001) and to have a lower mean PHQ-9 total score (2.91 [SD = 2.83] vs. 4.83 [SD = 3.82], p = .007). OAT-treated women reported smoking more CPD (9.50 [SD = 5.26] vs. 7.20 [SD = 3.65], p = .005) and had higher NMR (0.78 [SD = 0.36] vs. 0.56 [SD = 0.25], p = .001) than the non-OAT-treated group. In a linear regression analysis adjusting for race, depression severity, and CPD, NMR was greater in the OAT group (p = .025), among whom the daily methadone-equivalent dosage correlated with NMR (Spearman's ρ = 0.49, p = .003). CONCLUSIONS: Consistent with the findings of Oncken et al. (2019), we found that OAT smokers smoked more and had higher NMR than non-OAT smokers. As higher NMR is associated with a reduced likelihood of smoking cessation, the effects on NMR of both pregnancy and OAT could contribute to a lower smoking cessation rate in pregnant smokers receiving chronic opioid therapy. IMPLICATIONS: We replicated the finding that the NMR is significantly greater among pregnant smokers receiving OAT than those not receiving this treatment for opioid use disorder. Furthermore, we found that the dosage of the OAT was significantly associated with the NMR level. These findings may contribute to a poorer response to smoking cessation treatment in pregnant women treated with OAT, particularly those receiving high-dose therapy, and raise the question of whether novel approaches are needed to treat smoking in this subgroup of pregnant smokers.

Opioid Use and Rate of Nicotine Metabolism Among Pregnant Smokers.

INTRODUCTION: Smokers who use opioids smoke more cigarettes per day (CPD) than non-opioid users, which could be due to the effects of opioids on nicotine metabolism. Moreover, nicotine metabolism increases during pregnancy, potentially making quitting more difficult for pregnant smokers. We examined nicotine metabolism and its association with opioid use (OU) and CPD in pregnant smokers. METHODS: We recruited pregnant women who smoked at least 5 CPD for a clinical trial of smoking cessation. Plasma nicotine metabolite ratio (NMR; trans-3'-hydroxycotinine (3HC)/cotinine)-a biomarker of nicotine metabolism-OU (involving methadone, buprenorphine, fentanyl, oxycodone, or tramadol), and CPD were assessed at baseline. We used linear regression to examine the associations between log-transformed NMR, OU, and CPD, adjusting for race/ethnicity and menthol smoking. RESULTS: Among 129 pregnant smokers, 25 (19%) were opioid users; most were maintained on methadone (n = 14). Compared to non-OU smokers, OU smokers had higher median CPD (10.0 vs. 7.0, p = .0007), serum 3HC (81.0 vs. 42.0 ng/mL, p = .0001), and NMR (0.63 vs. 0.43, p < .0001). In addition, methadone-maintained smokers had a higher median NMR than non-OU smokers (0.66 vs. 0.43, p = .0004). Adjusting for covariates, log-transformed NMR was greater in OU smokers (p = .012), specifically methadone-maintained smokers (p = .024), than non-OU smokers. CONCLUSIONS: Our preliminary results show that OU is associated with a higher NMR in pregnant smokers. A larger study sample is needed to replicate this finding, examine potential mechanisms, and determine its clinical significance. IMPLICATIONS: Among pregnant smokers, we observed that nicotine metabolism was significantly faster among opioid users-the majority of whom were on methadone maintenance-compared to nonusers, which could have implications for smoking cessation. Further studies are needed to replicate this finding, evaluate potential mechanisms, and determine its clinical significance.

Biochemical Verification of Tobacco Use and Abstinence: 2019 Update.

BACKGROUND: The changing prevalence and patterns of tobacco use, the advent of novel nicotine delivery devices, and the development of new biomarkers prompted an update of the 2002 Society for Research on Nicotine and Tobacco (SRNT) report on whether and how to apply biomarker verification for tobacco use and abstinence. METHODS: The SRNT Treatment Research Network convened a group of investigators with expertise in tobacco biomarkers to update the recommendations of the 2002 SNRT Biochemical Verification Report. RESULTS: Biochemical verification of tobacco use and abstinence increases scientific rigor and is recommended in clinical trials of smoking cessation, when feasible. Sources, appropriate biospecimens, cutpoints, time of detection windows and analytic methods for carbon monoxide, cotinine (including over the counter tests), total nicotine equivalents, minor tobacco alkaloids, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol are reviewed, as well as biochemical approaches to distinguishing cigarette smoking from use of electronic nicotine delivery devices (ENDS). CONCLUSIONS: Recommendations are provided for whether and how to use biochemical verification of tobacco use and abstinence. Guidelines are provided on which biomarkers to use, which biospecimens to use, optimal cutpoints, time windows to detection, and methodology for biochemical verifications. Use of combinations of biomarkers is recommended for assessment of ENDS use. IMPLICATIONS: Biochemical verification increases scientific rigor, but there are drawbacks that need to be assessed to determine whether the benefits of biochemical verification outweigh the costs, including the cost of the assays, the feasibility of sample collection, the ability to draw clear conclusions based on the duration of abstinence, and the variability of the assay within the study population. This paper provides updated recommendations from the 2002 SRNT report on whether and how to use biochemical markers in determining tobacco use and abstinence.

Bupropion sustained release for pregnant smokers: a randomized, placebo-controlled trial.

BACKGROUND: Bupropion is used to treat depression during pregnancy. However, its usefulness as a smoking cessation aid for pregnant women is not fully known. OBJECTIVE: The objective of the study was to evaluate the preliminary efficacy of bupropion sustained release for smoking cessation during pregnancy. STUDY DESIGN: We conducted a randomized, prospective, double-blind, placebo-controlled, pilot trial. Pregnant women who smoked daily received individualized behavior counseling and were randomly assigned to a 12 week, twice-a-day treatment with 150 mg bupropion sustained release or placebo. The primary study objectives were to determine whether bupropion sustained release reduces nicotine withdrawal symptoms on the quit date and during the treatment period compared with placebo and whether it increases 7 day point prevalence abstinence at the end of the treatment period and at the end of pregnancy. RESULTS: Subjects in the bupropion (n = 30) and placebo (n = 35) groups were comparable in age, smoking history, number of daily smoked cigarettes, and nicotine dependence. After controlling for maternal age and race, bupropion sustained release reduced cigarette cravings (1.5 ± 1.1 vs 2.1 ± 1.2, P = .02) and total nicotine withdrawal symptoms (3.8 ± 4.3 vs 5.4 ± 5.1, P = .028) during the treatment period. Administration of bupropion sustained release reduced tobacco exposure, as determined by levels of carbon monoxide in exhaled air (7.4 ± 6.4 vs 9.1 ± 5.8, P = .053) and concentrations of cotinine in urine (348 ± 384 ng/mL vs 831 ± 727 ng/mL, P = .007) and increased overall abstinence rates during treatment (19% vs 2%, P = .003). However, there was no significant difference in 7 day point prevalence abstinence rates between the 2 groups at the end of medication treatment (17% vs 3%, P = .087) and at the end of pregnancy (10% vs 3%, P = .328). CONCLUSION: Individual smoking cessation counseling along with the twice-daily use of 150 mg bupropion sustained release increased smoking cessation rates and reduced cravings and total nicotine withdrawal symptoms during the treatment period. However, there was no significant difference in abstinence rates between groups at the end of medication treatment and at the end of pregnancy, likely because of the small sample size. A larger study is needed to confirm these findings and to examine the potential benefit/ risk ratio of bupropion sustained release for smoking cessation during pregnancy.

Correlates of Electronic Cigarettes Use Before and During Pregnancy.

INTRODUCTION: Electronic cigarette use is rapidly gaining in popularity. However, little is known about correlates and reasons for electronic cigarette use by women of reproductive age, a group for which the safety and efficacy of electronic cigarette use is of particular interest. METHODS: As part of a clinical trial for smoking cessation, we surveyed pregnant smokers about their lifetime use of electronic cigarettes, previous use of any adjunctive treatments for smoking cessation, and use of electronic cigarettes during pregnancy. We examined associations between electronic cigarette use and participant characteristics. RESULTS: Fifty-three percent (55/103) of participants had previously tried electronic cigarettes. Ever users smoked more cigarettes per day before pregnancy (p = .049), had a greater number of previous quit attempts (p = .033), and were more likely to identify as being Hispanic or non-Hispanic white than never users (p = .027). Fifteen percent of participants (15/103) reported previous use of electronic cigarettes for smoking cessation, which was more common than the use of any specific FDA-approved smoking cessation medication. Fourteen percent of participants (14/103) reported electronic cigarette use during pregnancy, most commonly to quit smoking. A history of substance abuse (p = .043) and more previous quit attempts (p = .018) were associated with electronic cigarette use during pregnancy. CONCLUSIONS: Use of electronic cigarettes to quit smoking may be common in women of reproductive age, including those who are pregnant. More research is needed to determine the risks and benefits of electronic cigarette use in this population of smokers. IMPLICATIONS: This study shows that electronic cigarettes are used by women of reproductive age, including pregnant smokers. The implications of this finding are that there is an urgent need to examine the risks and benefits of electronic cigarette use, especially by pregnant women. The study also shows that electronic cigarettes are commonly used as a smoking cessation aid in women of reproductive age. The greater likelihood of electronic cigarette use compared to proven adjunctive smoking treatments suggests that electronic cigarettes should be examined as a potential aid to cessation in this population.

Pharmacokinetics of Bupropion and Its Pharmacologically Active Metabolites in Pregnancy.

Bupropion sustained release is used to promote smoking cessation in males and nonpregnant females. However, its efficacy as a smoking cessation aid during pregnancy is not reported. The pregnancy-associated changes in maternal physiology may alter the pharmacokinetics and pharmacodynamics of bupropion and consequently its efficacy in pregnant smokers. Therefore, the aims of this study were to determine the steady-state pharmacokinetics of bupropion during pregnancy and the effect of functional genetic variants of CYP2B6 and CYP2C19 on bupropion pharmacokinetics in pregnant women. Plasma and urine concentrations of bupropion and its metabolites hydroxybupropion (OHBUP), threohydrobupropion, and erythrohydrobupropion were determined by liquid chromatography-mass spectrometry. Subjects were genotyped for five nonsynonymous single-nucleotide polymorphisms that result in seven CYP2B6 alleles, namely *2, *3, *4, *5, *6, *7, and *9, and for CYP2C19 variants *2, *3, and *17 The present study reports that the isoform-specific effect of pregnancy on bupropion-metabolizing enzymes along with the increase of renal elimination of the drug could collectively result in a slight decrease in exposure to bupropion in pregnancy. In contrast, pregnancy-induced increase in CYP2B6-catalyzed bupropion hydroxylation did not impact the plasma levels of OHBUP, probably due to a higher rate of OHBUP glucuronidation, and renal elimination associated with pregnancy. Therefore, exposure to OHBUP, a pharmacologically active metabolite of the bupropion, appears to be similar to that of the nonpregnant state. The predicted metabolic phenotypes of CYP2B6*6 and variant alleles of CYP2C19 in pregnancy are similar to those in the nonpregnant state.

Bupropion therapy during pregnancy: the drug and its major metabolites in umbilical cord plasma and amniotic fluid.

BACKGROUND: Bupropion is used for treatment of depression during pregnancy. However, its use as a smoking cessation aid for pregnant women is currently under evaluation. OBJECTIVE: The aim of this opportunistic study was to investigate the transfer of bupropion and its major pharmacologically active metabolites, hydroxybupropion and threohydrobupropion, across the placenta in vivo. In addition, the concentrations of the drug and its metabolites were determined in the amniotic fluid. STUDY DESIGN: The following samples were collected at deliveries from 22 women taking bupropion: maternal blood (n = 22), umbilical cord venous blood (n = 22), and amniotic fluid (n = 9). The concentrations of the drug and its metabolites in blood plasma and amniotic fluid were determined by means of liquid chromatography-mass spectrometry. Placental passage was calculated as a ratio of umbilical cord venous plasma to maternal plasma concentrations. RESULTS: The levels of hydroxybupropion and threohydrobupropion in umbilical cord venous plasma were invariably lower than their corresponding concentrations in maternal plasma. The concentrations of bupropion in umbilical cord plasma were lower than in maternal plasma in the majority of the maternal-cord blood pairs. The median values of the umbilical cord venous plasma to maternal plasma ratios were: bupropion, 0.53 (interquartile range 0.35, n = 18), hydroxybupropion, 0.21 (interquartile range 0.12, n = 18), and threohydrobupropion, 0.61 (interquartile range 0.11, n = 21). In umbilical cord venous plasma, the median concentration of bupropion was 5.3 ng/mL; hydroxybupropion, 103.6 ng/mL; and threohydrobupropion, 59.6 ng/mL. Bupropion and its metabolites were detectable in the amniotic fluid but the concentrations of threohydrobupropion were higher than those in the corresponding umbilical cord venous plasma. CONCLUSION: Bupropion and its active metabolites cross the placenta to the fetal circulation. The concentrations of hydroxybupropion and threohydrobupropion in umbilical cord venous plasma were higher than bupropion concentrations suggesting a higher fetal exposure to the metabolites than the parent drug. The higher levels of threohydrobupropion in the amniotic fluid than those in umbilical cord venous plasma suggest that enzymes involved in the metabolism of bupropion to threohydrobupropion are most likely active in the fetus. The biological consequences of fetal exposure to maternally administered bupropion and/or its active metabolites via placental transfer and recirculation of the amniotic fluid are yet to be determined.

Cigarette smoking and electronic cigarette vaping patterns as a function of e-cigarette flavourings.

INTRODUCTION: The present study examined the influence of flavouring on the smoking and vaping behaviour of cigarette smokers asked to adopt e-cigarettes for a period of 6 weeks. METHODS: Participants were 88 current male and female smokers with no intention to stop smoking, but who agreed to substitute e-cigarettes for their current cigarettes. On intake, participants were administered tests of taste and smell for e-cigarettes flavoured with tobacco, menthol, cherry and chocolate, and were given a refillable e-cigarette of their preferred flavour or a control flavour. Participants completed daily logs of cigarette and e-cigarette use and were followed each week. RESULTS: Analyses over days indicated that, during the 6-week e-cigarette period, cigarette smoking rates dropped from an average of about 16 to about 7 cigarettes/day. e-Cigarette flavour had a significant effect such that the largest drop in cigarette smoking occurred among those assigned menthol e-cigarettes, and the smallest drop in smoking occurred among those assigned chocolate and cherry flavours. e-Cigarette vaping rates also differed significantly by flavour assigned, with the highest vaping rates for tobacco- and cherry-flavoured e-cigarettes, and the lowest rates for those assigned to chocolate. CONCLUSIONS: The findings suggest that adoption of e-cigarettes in smokers may influence smoking rates and that e-cigarette flavourings can moderate this effect. e-Cigarette vaping rates are also influenced by flavourings. These findings may have implications for the utility of e-cigarettes as a nicotine replacement device and for the regulation of flavourings in e-cigarettes for harm reduction.

Effectiveness and Safety of a Clinical Decision Rule to Reduce Repeat Ionized Calcium Testing: A Pre/Post Test Intervention.

The American Recovery and Reinvestment Act authorizes the Centers for Medicare and Medicaid Services to reimburse hospitals that demonstrate meaningful use of certified electronic health record technology. We sought to demonstrate meaningful use by developing and implementing one clinical decision support rule in the computerized physician order entry system that targets clinician-ordered repeat ionized calcium measurement at the University of Connecticut Health Center. The rule consists of a pop-up computer reminder that is triggered by ordering a second ionized calcium test within 72 hours after an initial normal test, with no clear indication for repeat testing. We implemented the rule on December 14, 2010, and have reviewed all data collected through December 2014. We found that the number of repeat tests decreased from 46% to 14% with no significant increase in the number of serious adverse events. We conclude that computerized reminders can decrease unnecessary repeat testing in the inpatient setting.

Nicotine concentrations with electronic cigarette use: effects of sex and flavor.

INTRODUCTION: This study examined overall changes in nicotine concentrations when using a popular e-cigarette and 18 mg/mL nicotine e-Juice, and it further explored effects of sex and flavorings on these concentrations. METHODS: We recruited nontreatment-seeking smokers who were willing to try e-cigarettes for 2 weeks and abstain from cigarette smoking. Subjects were randomized to either menthol tobacco or non-menthol tobacco-flavored e-cigarette use for 7-10 days, and the next week they were crossed over to the other condition. On the last day of e-cigarette use of each flavor, subjects completed a laboratory session in which they used the e-cigarette for 5 min ad libitum. Nicotine concentrations were obtained 5 min before and 5, 10, 15, 20, and 30 min after the onset of e-cigarette use. RESULTS: Twenty subjects completed at least 1 monitoring session. Nicotine concentrations significantly increased from baseline to 5 min by 4 ng/mL at the first laboratory session (p < .01) and by 5.1 ng/mL at the second laboratory session (p < .01). Combining sessions, there were no main effects of sex or preferred flavor (based on smoking history) on changes in nicotine concentrations. After adding preferred flavor, sex, and visit order to the model, there was a significant preferred flavor by sex interaction (p < .01), such that women who received nonpreferred flavors had lower nicotine concentrations and rated their e-cigarette as less likeable (p < .01). CONCLUSION: We found nicotine concentrations significantly increase after e-cigarette use for 5 min, and flavor may impact nicotine concentrations with e-cigarette use in women.

Genetic Vulnerability to Menthol Cigarette Preference in Women.

BACKGROUND: Smokers may prefer menthol cigarettes to mask the bitter taste of nicotine. Variation in the taste receptor gene, TAS2R38, may contribute to preference for menthol cigarettes. AIMS: To determine whether two common haplotypes of TAS2R38 (proline-alanine-valine [PAV] and alanine-valine-isoleucine [AVI]), which have been associated, respectively, with bitter taste or a lack of bitter taste produced by propylthiouracil, are associated with preference for menthol cigarettes. METHODS: Data on smoking and blood for DNA extraction and genotyping were obtained from 323 pregnant non-Hispanic or Hispanic Caucasian smokers. We genotyped three TAS2R38 single nucleotide polymorphisms (rs713598, rs1726866, and rs10246939) and constructed haplotypes. We examined associations between menthol preference and the frequency and distribution of the AVI and PAV haplotypes among study participants. RESULTS: Participants smoked an average of 16 cigarettes per day before pregnancy. The PAV and AVI haplotype frequencies were 48% and 45%, respectively. Non-Hispanic women were less likely than Hispanic women to smoke menthol cigarettes. As hypothesized, the frequency of the PAV haplotype was greater in menthol than non-menthol smokers in both non-Hispanics (54% vs. 30%; χ(2) = 13.04, P < .001) and Hispanics (53% vs. 25%; χ(2) = 5.77, P = .016). This effect persisted after controlling for potential confounders in multivariate logistic regression. Menthol smokers had a greater number of PAV haplotypes/individual than non-menthol smokers [non-Hispanics odds ratio (OR) = 3.02 (1.56-5.85); P = .001; Hispanics OR = 3.60 (1.23-10.56); P = .020]. CONCLUSIONS: These preliminary data support the hypothesis that a genetic propensity to experience heightened bitter taste perception increases the preference for menthol cigarettes.

NIH electronic cigarette workshop: developing a research agenda.

BACKGROUND: Electronic cigarettes (e-cigarettes) represent an emerging public health issue. These devices deliver nicotine along with other constituents, including flavorants, via an inhalable aerosol. Their uptake is rapidly increasing in both adults and youths, primarily among current smokers. Public debate is increasing on how these devices should be regulated and used, yet only limited peer-reviewed research exists. To develop a informed policy for e-cigarettes, their effects on human behavior, physiology, and health need to be understood. PURPOSE: This paper describes proceedings from a National Institutes of Health-sponsored workshop, which was held in November 2013, to identify research needs related to the effects of e-cigarettes. Discussion topics included e-cigarette risks and abuse potential; the potential role for e-cigarettes in harm reduction and smoking cessation; unintended consequences of e-cigarette use, such as becoming a gateway to conventional cigarettes; and dual use of both e-cigarettes and conventional cigarettes. RESULTS AND CONCLUSIONS: The research needs identified by the workshop participants included the following: standards to measure the contents and emissions of e-cigarettes; biomarkers of exposure; physiological effects of e-cigarettes on tissues and organ systems, including pulmonary and cardiovascular; information on e-cigarette users, how the devices are used, and identification of the best tools to assess these measures; factors that drive use and influence patterns of use; and appropriate methods for evaluating a potential role for e-cigarettes in smoking or nicotine cessation. To understand fully the challenges and the opportunities that e-cigarettes represent, expertise will be needed in basic, behavioral, translational, and clinical sciences.

Topiramate for smoking cessation: a randomized, placebo-controlled pilot study.

INTRODUCTION: Topiramate (TOP) blocks glutamate receptors and facilitates GABA (γ-aminobutyric acid) neurotransmission, effects that may facilitate smoking cessation. We compared the effects of behavioral counseling combined with (a) TOP, (b) TOP/nicotine patch (TOP/NIC), or (c) placebo (PLC) for smoking cessation. METHODS: We conducted a 10-week randomized trial in which subjects and research personnel were blinded to TOP versus PLC but not to the TOP/NIC patch condition. In groups receiving TOP, the medication dosage was titrated gradually up to 200 mg/day. The smoking quit date (QD) was scheduled after 2 weeks of medication treatment. NIC (21 mg) was started on the QD in subjects randomized to the TOP/NIC condition. The main outcome measure was the end-of-treatment, 4-week continuous abstinence rate (CAR; biochemically confirmed). RESULTS: Fifty-seven subjects were randomized to treatment. The 4-week CAR was 1 of 19 (5%) in the PLC group, 5 of 19 (26%) in the TOP group, and 7 of 19 (37%) in the TOP/NIC group (p = .056). Pairwise comparisons showed a difference between TOP/NIC and PLC (p = .042) and a nonsignificant difference between TOP and PLC (p = .18). The PLC group gained 0.37 lb/week, the TOP group lost 0.41 lb/week, and the TOP/NIC group lost 0.07 lb/week (p = .004). Pairwise comparisons showed a difference between TOP and PLC (p < .001) and between TOP/NIC and PLC groups (p = .035). Paresthesia was more frequent in subjects on TOP than PLC (p = .011). CONCLUSIONS: TOP, alone or in combination with the NIC, resulted in a numerically higher quit rate than PLC and decreased weight. A larger, PLC-controlled trial is needed to confirm these findings.

A GABRA2 variant is associated with increased stimulation and 'high' following alcohol administration.

AIMS: Variation in genes encoding GABAA receptor subunits has been implicated in the risk of alcohol dependence (AD). We sought to replicate and extend previous findings of a moderating effect of single nucleotide polymorphisms (SNPs) in GABRA2 (which encodes the GABAA α-2 subunit) on the subjective effects of alcohol by examining SNPs in this and the adjacent GABRG1 gene on chromosome 4. METHODS: Fifty-two European-Americans (22 males, 28 light drinkers and 24 heavy drinkers) completed 3 laboratory sessions, during which they drank low-dose, high-dose, or placebo alcohol prior to undergoing periodic assessments of stimulation, sedation and drug enjoyment. We genotyped subjects for three SNPs previously associated with AD: rs279858 in GABRA2, and rs7654165 and rs6447493 in GABRG1. RESULTS: Two SNPs were associated with altered stimulatory effects of alcohol as measured on the Biphasic Alcohol Effects Scale, (rs279858: P = 0.0046; rs6447493: P = 0.0023); both effects were in the opposite direction of previous findings. Carriers of the rs279858 C allele experienced greater stimulation from alcohol. Further inspection of the rs6447493 interaction did not support a pharmacogenetic effect. The effects of rs279858 (but not the other two SNPs) on items from a secondary outcome measure, the Drug Effects Questionnaire (DEQ), were significant. Higher ratings by individuals with the C allele were observed on the DEQ items 'feel the alcohol effect' (P < 0.001), 'like the alcohol effect' (P < 0.001) and feel 'high' (P < 0.001). CONCLUSION: We did not find that the GABRG1 SNPs rs7654165 and rs6447493 moderated the effects of alcohol. Greater stimulatory and euphoric effects of alcohol in carriers of the rs279858 C allele may, in part, explain the previously reported association of this allele with AD.