RETRACTED: Changes in Tobacco Dependence and Association With Onset and Progression of Use by Product Type From Wave 1 to Wave 3 of the Population Assessment of Tobacco and Health (PATH) Study.

INTRODUCTION: This study examined trajectories of tobacco dependence (TD) in relation to changes in tobacco product use and explored the effects of product-specific adding, switching, or discontinued use on dependence over time. AIMS AND METHODS: Data were analyzed from the first three waves of the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative, longitudinal study of adults and youth in the United States. Data included 9556 Wave 1 (2013/2014) adult current established tobacco users who completed all three interviews and had established use at ≥2 assessments. Groups included cigarettes-only users, e-cigarettes-only users, cigars-only users, hookah-only users, any smokeless-only users, cigarette + e-cigarette dual users, and multiple product users. A validated 16-item scale assessed TD across product users. RESULTS: Wave 1 e-cigarette-only users' who maintained exclusive e-cigarette use increased levels of TD through Wave 3 as did those who added or switched to another product. Wave 1 multiple product users' TD decreased across waves. TD for all other Wave 1 user groups remained about the same. For Wave 1 cigarette-only smokers, switching to another product or moving to a pattern of no established use was associated with lower levels of TD than smokers whose use stayed the same. Movement to no established use of any tobacco product was consistently associated with lower TD for all other product users. CONCLUSIONS: Except for Wave 1 e-cigarette-only users, TD among US tobacco product users was stable over time, with daily users less likely to vary from baseline. IMPLICATIONS: The level of TD among most US tobacco users was stable over the first three waves of the PATH Study and trends in levels of TD were predominantly unrelated to changes in patterns of continued product use. Stable levels of TD suggest a population at persistent risk of health impacts from tobacco. Wave 1 e-cigarette users, including those maintaining exclusive e-cigarette use, experienced increasing levels of TD over time, perhaps because of increases in quantity or frequency of their e-cigarette product use or increasing efficiency of nicotine delivery over time.

Dopamine Release in Nucleus Accumbens Is under Tonic Inhibition by Adenosine A1 Receptors Regulated by Astrocytic ENT1 and Dysregulated by Ethanol.

Striatal adenosine A1 receptor (A1R) activation can inhibit dopamine release. A1Rs on other striatal neurons are activated by an adenosine tone that is limited by equilibrative nucleoside transporter 1 (ENT1) that is enriched on astrocytes and is ethanol sensitive. We explored whether dopamine release in nucleus accumbens core is under tonic inhibition by A1Rs, and is regulated by astrocytic ENT1 and ethanol. In ex vivo striatal slices from male and female mice, A1R agonists inhibited dopamine release evoked electrically or optogenetically and detected using fast-scan cyclic voltammetry, most strongly for lower stimulation frequencies and pulse numbers, thereby enhancing the activity-dependent contrast of dopamine release. Conversely, A1R antagonists reduced activity-dependent contrast but enhanced evoked dopamine release levels, even for single optogenetic pulses indicating an underlying tonic inhibition. The ENT1 inhibitor nitrobenzylthioinosine reduced dopamine release and promoted A1R-mediated inhibition, and, conversely, virally mediated astrocytic overexpression of ENT1 enhanced dopamine release and relieved A1R-mediated inhibition. By imaging the genetically encoded fluorescent adenosine sensor [GPCR-activation based (GRAB)-Ado], we identified a striatal extracellular adenosine tone that was elevated by the ENT1 inhibitor and sensitive to gliotoxin fluorocitrate. Finally, we identified that ethanol (50 mm) promoted A1R-mediated inhibition of dopamine release, through diminishing adenosine uptake via ENT1. Together, these data reveal that dopamine output dynamics are gated by a striatal adenosine tone, limiting amplitude but promoting contrast, regulated by ENT1, and promoted by ethanol. These data add to the diverse mechanisms through which ethanol modulates striatal dopamine, and to emerging datasets supporting astrocytic transporters as important regulators of striatal function.SIGNIFICANCE STATEMENT Dopamine axons in the mammalian striatum are emerging as strategic sites where neuromodulators can powerfully influence dopamine output in health and disease. We found that ambient levels of the neuromodulator adenosine tonically inhibit dopamine release in nucleus accumbens core via adenosine A1 receptors (A1Rs), to a variable level that promotes the contrast in dopamine signals released by different frequencies of activity. We reveal that the equilibrative nucleoside transporter 1 (ENT1) on astrocytes limits this tonic inhibition, and that ethanol promotes it by diminishing adenosine uptake via ENT1. These findings support the hypotheses that A1Rs on dopamine axons inhibit dopamine release and, furthermore, that astrocytes perform important roles in setting the level of striatal dopamine output, in health and disease.

Validation of the Wave 1 and Wave 2 Population Assessment of Tobacco and Health (PATH) Study Indicators of Tobacco Dependence Using Biomarkers of Nicotine Exposure Across Tobacco Products.

INTRODUCTION: This study examined the predictive relationships between biomarkers of nicotine exposure and 16-item self-reported level of tobacco dependence (TD) and subsequent tobacco use outcomes. AIMS AND METHODS: The Population Assessment of Tobacco and Health (PATH) Study surveyed adult current established tobacco users who provided urine biospecimens at Wave 1 (September 2013-December 2014) and completed the Wave 2 (October 2014-October 2015) interview (n = 6872). Mutually exclusive user groups at Wave 1 included: Cigarette Only, E-cigarette Only, Cigar Only, Hookah Only, Smokeless Tobacco Only, Cigarette Plus E-cigarette, multiple tobacco product users who smoked cigarettes, and multiple tobacco product users who did not smoke cigarettes. Total Nicotine Equivalents (TNE-2) and TD were measured at Wave 1. Approximate one-year outcomes included frequency/quantity used, quitting, and adding/switching to different tobacco products. RESULTS: For Cigarette Only smokers and multiple tobacco product users who smoked cigarettes, higher TD and TNE-2 were associated with: a tendency to smoke more, smoking more frequently over time, decreased likelihood of switching away from cigarettes, and decreased probability of quitting after one year. For other product user groups, Wave 1 TD and/or TNE-2 were less consistently related to changes in quantity and frequency of product use, or for adding or switching products, but higher TNE-2 was more consistently predictive of decreased probability of quitting. CONCLUSIONS: Self-reported TD and nicotine exposure assess common and independent aspects of dependence in relation to tobacco use behaviors for cigarette smokers. For other product user groups, nicotine exposure is a more consistent predictor of quitting than self-reported TD. IMPLICATIONS: This study suggests that smoking cigarettes leads to the most coherent pattern of associations consistent with a syndrome of TD. Because cigarettes continue to be prevalent and harmful, efforts to decrease their use may be accelerated via conventional means (eg, smoking cessation interventions and treatments), but also perhaps by decreasing their dependence potential. The implications for noncombustible tobacco products are less clear as the stability of tobacco use patterns that include products such as e-cigarettes continue to evolve. TD, nicotine exposure measures, and consumption could be used in studies that attempt to understand and predict product-specific tobacco use behavioral outcomes.

Biomarkers of Inflammation and Oxidative Stress among Adult Former Smoker, Current E-Cigarette Users-Results from Wave 1 PATH Study.

BACKGROUND: Former smokers who currently use e-cigarettes have lower concentrations of biomarkers of tobacco toxicant exposure than current smokers. It is unclear whether tobacco toxicant exposure reductions may lead to health risk reductions. METHODS: We compared inflammatory biomarkers (high-sensitivity C-reactive protein, IL6, fibrinogen, soluble intercellular adhesion molecule-1) and an oxidative stress marker (F2-isoprostane) among 3,712 adult participants in Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health Study by tobacco user groups: dual users of cigarettes and e-cigarettes; former smokers who currently use e-cigarettes-only; current cigarette-only smokers; former smokers who do not currently use any tobacco; and never tobacco users. We calculated geometric means (GM) and estimated adjusted GM ratios (GMR). RESULTS: Dual users experienced greater concentration of F2-isoprostane than current cigarette-only smokers [GMR 1.09 (95% confidence interval, CI, 1.03-1.15)]. Biomarkers were similar between former smokers who currently use e-cigarettes and both former smokers who do not use any tobacco and never tobacco users, but among these groups most biomarkers were lower than those of current cigarette-only smokers. The concentration of F2-isoprostane decreased by time since smoking cessation among both exclusive e-cigarette users (P trend = 0.03) and former smokers who do not currently use any tobacco (P trend = 0.0001). CONCLUSIONS: Dual users have greater concentration of F2-isoprostane than smokers. Exclusive e-cigarette users have biomarker concentrations that are similar to those of former smokers who do not currently use tobacco, and lower than those of exclusive cigarette smokers. IMPACT: This study contributes to an understanding of the health effects of e-cigarettes.

Transitions in frequency of hookah smoking among youth and adults: findings from waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) study, 2013-15.

BACKGROUND AND AIMS: The prevalence of hookah smoking has increased in the United States since at least 2010, especially among youth and young adults. This study assessed self-reported reasons for hookah smoking cessation and transition to or maintenance of high-frequency hookah smoking among current hookah smokers. DESIGN: Separately analyzed data from the Population Assessment of Tobacco and Health (PATH) study, a longitudinal cohort study. Frequency of and reasons for hookah smoking were ascertained at wave 1 (2013-14); frequency of hookah smoking and past-year cessation were ascertained at wave 2 (2014-15). Weighted multivariable logistic and ordinal logistic regression models were fitted to predict hookah smoking cessation and frequency of hookah smoking at wave 2, respectively, accounting for demographic and behavioral risk factors, reasons for hookah smoking and frequency of hookah smoking at wave 1. SETTING: United States. PARTICIPANTS: A total of 693 youth and 4400 adult past-year hookah smokers. MEASUREMENTS: Self-reported tobacco-use patterns and associated health behaviors were measured via audio computer-assisted self-interviews (ACASI). FINDINGS: At wave 1, 5.9% of youth and 7.5% of adults were past-year hookah smokers. Among all age groups, the leading reasons for hookah smoking were enjoyment of socializing while smoking, the availability of appealing flavors and believing that it was less harmful than cigarette smoking. The odds of cessation were lower for adults who liked hookah flavors [adjusted odds ratio (aOR) = 0.40; 95% confidence interval (CI) = 0.26-0.62] compared with adults who did not like hookah flavors. The odds of transitioning to, or maintaining, monthly or more frequent hookah smoking at wave 2, compared with cessation or less than monthly smoking, were higher for adults who liked hookah flavors [adjusted proportional odds ratio (aPOR) = 2.10; 95% CI = 1.48-2.99 and enjoyed socializing while smoking hookah (aPOR = 1.82; 95% CI =1.13-2.94) compared with adults who did not like hookah flavors or socializing. CONCLUSION: The availability of appealing flavors, affordability and socialization while smoking hookah in the United States are associated with reduced likelihood of cessation and increased likelihood of high-frequency hookah smoking.

Predictive validity of the adult tobacco dependence index: Findings from waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) study.

BACKGROUND AND AIMS: Building on published work1 establishing concurrent validity of a self-report tobacco dependence (TD) index among users of different tobacco products in Wave 1 (W1) of the Population Assessment of Tobacco and Health (PATH) Study, the current study examines prospective relationships with tobacco use behaviors to establish predictive validity of the TD index. Hypotheses suggested high levels of W1 TD would be associated with persistent tobacco use at Wave 2 (W2). PARTICIPANTS: A U.S. nationally representative sample of 32,320 adult W1 and W2 interviews focused on 11,615 W1 adults who were current established tobacco users and completed the W2 interview. FINDINGS: Higher TD scores and greater changes in TD scores were associated with greater quantity and frequency of tobacco use at the W2 interview for Cigarette Only (n = 7068), Smokeless (smokeless or snus pouches) Only (n = 772), Cigarette plus E-Cigarette (n = 592), and Multiple Products (n = 1866) users, although not significantly so for E-Cigarette Only (n = 367), Cigar Only (traditional, cigarillo, or filtered) (n = 584), or Hookah Only (n = 366) users. Higher TD was associated with decreased odds of successful quitting for Cigarette and Multiple Product users. Higher TD was associated with increased odds of a quit attempt for those in the Hookah and Multiple Products user groups and was not associated with quit attempts or deceased odds of quit success among exclusive E-Cigarette, Cigar, Smokeless and Cigarette plus E-Cigarette users. CONCLUSION: Support for the predictive validity of the PATH Study measures of adult TD will enable regulatory investigations of TD across several tobacco products.

Mental Health Problems and Onset of Tobacco Use Among 12- to 24-Year-Olds in the PATH Study.

OBJECTIVE: To examine whether mental health problems predict incident use of 12 different tobacco products in a nationally representative sample of youth and young adults. METHOD: This study analyzed Wave (W) 1 and W2 data from 10,533 12- to 24-year-old W1 never tobacco users in the Population Assessment of Tobacco and Health (PATH) Study. Self-reported lifetime internalizing and externalizing symptoms were assessed at W1. Past 12-month use of cigarettes, electronic nicotine delivery systems (ENDS), traditional cigars, cigarillos, filtered cigars, pipe, hookah, snus pouches, other smokeless tobacco, bidis and kreteks (youth only), and dissolvable tobacco was assessed at W2. RESULTS: In multivariable regression analyses, high-severity W1 internalizing (adjusted odds ratio [AOR] = 1.5, 95% CI = 1.3-1.8) and externalizing (AOR = 1.3, 95% CI = 1.1-1.5) problems predicted W2 onset of any tobacco use compared to no/low/moderate severity. High-severity W1 internalizing problems predicted W2 use onset across most tobacco products. High-severity W1 externalizing problems predicted onset of any tobacco (AOR = 1.6, 95% CI = 1.3-1.8), cigarettes (AOR = 1.4, 95% CI = 1.0-2.0), ENDS (AOR = 1.8, 95% CI = 1.5-2.1), and cigarillos (AOR = 1.5, 95% CI = 1.0-2.1) among youth only. CONCLUSION: Internalizing and externalizing problems predicted onset of any tobacco use. However, findings differed for internalizing and externalizing problems across tobacco products, and by age, gender, and race/ethnicity. In addition to screening for tobacco product use, health care providers should screen for a range of mental health problems as a predictor of tobacco use. Interventions addressing mental health problems may prevent youth from initiating tobacco use.

Correlates of Transitions in Tobacco Product Use by U.S. Adult Tobacco Users between 2013⁻2014 and 2014⁻2015: Findings from the PATH Study Wave 1 and Wave 2.

More than half of adult tobacco users in the United States (U.S.) transitioned in tobacco product use between 2013⁻2014 and 2014⁻2015. We examine how characteristics of adult tobacco users in the U.S. relate to transitions in tobacco product use. Population Assessment of Tobacco and Health (PATH) Study data were analyzed from 12,862 adult current tobacco users who participated in Wave 1 (W1, 2013⁻2014) and Wave 2 (W2, 2014⁻2015). Three types of transitions were examined-(1) adding tobacco product(s); (2) switching to non-cigarette tobacco product(s); and (3) discontinuing all tobacco use-among those currently using: (1) any tobacco product; (2) cigarettes only (i.e., exclusive cigarette); and (3) cigarettes plus another tobacco product(s) (i.e., poly-cigarette). Multinomial logistic regression analyses determined relative risk of type of transition versus no transition as a function of demographic and tobacco use characteristics. Transitions in tobacco product use among adult tobacco users were common overall, but varied among different demographic groups, including by age, sex, sexual orientation, race/ethnicity, educational attainment, and poverty level. Further, cigarette smokers with higher dependence scores were more likely to add product(s) and less likely to discontinue tobacco use compared to those with low dependence scores. That high nicotine dependence is a barrier to discontinuing tobacco use adds evidence to support policy to lower nicotine content of cigarettes and to evaluate new products for their potential to reduce cigarette use.

Transitions in Tobacco Product Use by U.S. Adults between 2013⁻2014 and 2014⁻2015: Findings from the PATH Study Wave 1 and Wave 2.

In 2013⁻2014, nearly 28% of adults in the United States (U.S.) were current tobacco users with cigarettes the most common product used and with nearly 40% of tobacco users using two or more tobacco products. We describe overall change in prevalence of tobacco product use and within-person transitions in tobacco product use in the U.S. between 2013⁻2014 and 2014⁻2015 for young adults (18⁻24 years) and older adults (25+ years). Data from Wave 1 (W1, 2013⁻2014) and Wave 2 (W2, 2014⁻2015) of the Population Assessment of Tobacco and Health (PATH) Study were analyzed (N = 34,235). Tobacco product types were categorized into: (1) combustible (cigarettes, cigars, pipe tobacco, hookah), (2) noncombustible (smokeless tobacco, snus pouches, dissolvable tobacco), and (3) electronic nicotine delivery systems (ENDS). Transitions for individual combustible-product types, and for single- and multiple-product use, were also considered. Overall prevalence of current tobacco use decreased from 27.6% to 26.3%. Among W1 non-tobacco users, 88.7% of young adults and 95.8% of older adults were non-tobacco users at W2. Among W1 tobacco users, 71.7% of young adults transitioned, with 20.7% discontinuing use completely, and 45.9% of older adults transitioned, with 12.5% discontinuing use completely. Continuing with/transitioning toward combustible product(s), particularly cigarettes, was more common than continuing with/transitioning toward ENDS. Tobacco use behaviors were less stable among young adults than older adults, likely reflecting greater product experimentation among young adults. Relative stability of cigarette use compared to other tobacco products (except older adult noncombustible use) demonstrates high abuse liability for cigarettes.

Longitudinal associations between youth tobacco and substance use in waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) Study.

BACKGROUND: While evidence suggests bidirectional associations between cigarette use and substance (alcohol or drug) use, how these associations are reflected across the range of currently available tobacco products is unknown. This study examined whether ever tobacco use predicted subsequent substance use, and ever substance use predicted subsequent tobacco use among 11,996 U.S. youth (12-17 years) from Waves 1 (2013-2014) and 2 (2014-2015) of the Population Assessment of Tobacco and Health (PATH) Study. METHODS: Ever use of cigarettes, e-cigarettes, traditional cigars, cigarillos, filtered cigars, pipe, hookah, snus pouches, smokeless tobacco excluding snus pouches, dissolvable tobacco, bidis, kreteks, alcohol, marijuana, prescription drugs, and other drugs (cocaine and other stimulants, heroin, inhalants, solvents, and hallucinogens) was assessed at Wave 1 followed by past 12-month use assessments at Wave 2. The analyses included covariates (demographics, mental health, sensation seeking, prior use) to mitigate confounding. RESULTS: Ever tobacco use predicted subsequent substance use. The magnitude of the associations was lowest for alcohol, higher for marijuana, and highest for other drugs. Ever substance use also predicted subsequent tobacco use. Specifically, ever alcohol, marijuana, and non-prescribed Ritalin/Adderall use predicted tobacco-product use. Ever e-cigarette and cigarette use exclusively and concurrently predicted subsequent any drug (including and excluding alcohol) use. E-cigarette and cigarette use associations in the opposite direction were also significant; the strongest associations were observed for exclusive cigarette use. CONCLUSION: Tobacco and substance use prevention efforts may benefit from comprehensive screening and interventions across tobacco products, alcohol, and drugs, and targeting risk factors shared across substances.

Co-occurrence of tobacco product use, substance use, and mental health problems among youth: Findings from wave 1 (2013-2014) of the population assessment of tobacco and health (PATH) study.

INTRODUCTION: Cigarette use is associated with substance use and mental health problems among youth, but associations are unknown for non-cigarette tobacco product use, as well as the increasingly common poly-tobacco use. METHODS: The current study examined co-occurrence of substance use and mental health problems across tobacco products among 13,617 youth aged 12-17years from Wave 1 (2013-2014) of the nationally representative Population Assessment of Tobacco and Health (PATH) Study. Participants self-reported ever cigarette, e-cigarette, smokeless tobacco, traditional cigar, cigarillo, filtered cigar, hookah, and other tobacco product use; alcohol, marijuana, and other drugs; and lifetime substance use, internalizing and externalizing problems. RESULTS: In multivariable regression analyses, use of each tobacco product was associated with substance use, particularly cigarillos and marijuana (AOR=18.9, 95% CI: 15.3-23.4). Cigarette (AOR=14.7, 95% CI: 11.8-18.2) and cigarillo (AOR=8.1, 95% CI: 6.3-10.3) use were strongly associated with substance use problems and tobacco users were more likely to report internalizing (AOR=1.6, 95% CI: 1.4-1.8) and externalizing (AOR=1.4, 95% CI: 1.3-1.6) problems. Female tobacco users were more likely to have internalizing problems than male tobacco users. Poly-tobacco users were more likely than exclusive users to use substances (AOR=3.4, 95% CI: 2.7-4.3) and have mental health (AOR=1.2, 95% CI: 1.0-1.5) and substance use (AOR=4.7, 95% CI: 3.4-6.6) problems. CONCLUSIONS: Regardless of the tobacco product used, findings reveal high co-occurrence of substance use and mental health problems among youth tobacco users, especially poly-tobacco users. These findings suggest the need to address comorbidities among high risk youth in prevention and treatment settings.

Comparison of Nicotine and Toxicant Exposure in Users of Electronic Cigarettes and Combustible Cigarettes.

Importance: Use of electronic cigarettes (e-cigarettes) is increasing. Measures of exposure to known tobacco-related toxicants among e-cigarette users will inform potential health risks to individual product users. Objectives: To estimate concentrations of tobacco-related toxicants among e-cigarette users and compare these biomarker concentrations with those observed in combustible cigarette users, dual users, and never tobacco users. Design, Setting, and Participants: A population-based, longitudinal cohort study was conducted in the United States in 2013-2014. Cross-sectional analysis was performed between November 4, 2016, and October 5, 2017, of biomarkers of exposure to tobacco-related toxicants collected by the Population Assessment of Tobacco and Health Study. Participants included adults who provided a urine sample and data on tobacco use (N = 5105). Exposures: The primary exposure was tobacco use, including current exclusive e-cigarette users (n = 247), current exclusive cigarette smokers (n = 2411), and users of both products (dual users) (n = 792) compared with never tobacco users (n = 1655). Main Outcomes and Measures: Geometric mean concentrations of 50 individual biomarkers from 5 major classes of tobacco product constituents were measured: nicotine, tobacco-specific nitrosamines (TSNAs), metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). Results: Of the 5105 participants, most were aged 35 to 54 years (weighted percentage, 38%; 95% CI, 35%-40%), women (60%; 95% CI, 59%-62%), and non-Hispanic white (61%; 95% CI, 58%-64%). Compared with exclusive e-cigarette users, never users had 19% to 81% significantly lower concentrations of biomarkers of exposure to nicotine, TSNAs, some metals (eg, cadmium and lead), and some VOCs (including acrylonitrile). Exclusive e-cigarette users showed 10% to 98% significantly lower concentrations of biomarkers of exposure, including TSNAs, PAHs, most VOCs, and nicotine, compared with exclusive cigarette smokers; concentrations were comparable for metals and 3 VOCs. Exclusive cigarette users showed 10% to 36% lower concentrations of several biomarkers than dual users. Frequency of cigarette use among dual users was positively correlated with nicotine and toxicant exposure. Conclusions and Relevance: Exclusive use of e-cigarettes appears to result in measurable exposure to known tobacco-related toxicants, generally at lower levels than cigarette smoking. Toxicant exposure is greatest among dual users, and frequency of combustible cigarette use is positively correlated with tobacco toxicant concentration. These findings provide evidence that using combusted tobacco cigarettes alone or in combination with e-cigarettes is associated with higher concentrations of potentially harmful tobacco constituents in comparison with using e-cigarettes alone.

US Adult Cigar Smoking Patterns, Purchasing Behaviors, and Reasons for Use According to Cigar Type: Findings From the Population Assessment of Tobacco and Health (PATH) Study, 2013-2014.

Introduction: The US cigar market is diverse, yet until recently most research studies and tobacco surveillance systems have not reported behavioral and related outcomes by cigar type. Methods: The 2013-2014 Population Assessment of Tobacco and Health Study collected data separately for filtered cigars (FCs), cigarillos, and traditional cigars, which were further distinguished as premium or nonpremium. Descriptive statistics for adult established current smokers of each cigar type and cigarettes were calculated for demographic characteristics, tobacco use patterns, purchasing behaviors and reasons for use. Adjusted prevalence ratios (APRs) using a marginal predictions approach with logistic regression assessed correlates of dual cigar and cigarette smoking. Results: Age, sex, race/ethnicity, education level, and poverty status of smokers varied according to cigar type. Daily cigar smoking prevalence and number of cigars smoked per day were higher for FCs (37.3%; median: 1.6 cigars/day, respectively), than all other cigar types (6.7%-25.3%, all p < .01; 0.1-0.4 cigars/day, all p < .01, respectively); daily smoking and cigars per day were similar for nonpremium cigars and cigarillos (p = .11; p = .33, respectively). Cigarette smoking was twice as common among smokers of nonpremium cigars, cigarillos, and FCs (58.0%-66.0%) than among premium cigars (29.9%). Among current cigar smokers, FC smokers (APR = 1.23, 95% confidence interval [CI] = 1.09-1.39), other tobacco product users (APR = 1.27, 95% CI = 1.15-1.41), and those with a GED/high school diploma or less (APR = 1.20, 95% CI = 1.09-1.33) were more likely to also smoke cigarettes. Conclusion: User characteristics, cigar smoking patterns, and dual smoking with cigarettes varied by cigar type highlighting the importance of adequately describing the cigar type studied and, where appropriate, differentiating results by cigar type. Implications: Despite the diversity of the cigar market place, historically many research studies and tobacco surveillance systems have treated cigars as a single product type. This study describes similarities and differences in the user characteristics, tobacco use patterns, and purchasing behaviors of premium, nonpremium, cigarillo, and filtered cigar smokers. To enhance tobacco regulatory science, sufficient descriptions of the cigar type(s) studied and, where appropriate, differentiation of the particular cigar type(s) studied should be undertaken to improve the interpretation of study findings, understanding of cigar use patterns and related behaviors and future approaches to reducing cigar-attributable morbidity and mortality.

Indicators of dependence for different types of tobacco product users: Descriptive findings from Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) study.

BACKGROUND AND AIMS: With no established standard for assessing tobacco dependence (TD) across tobacco products in surveys, the Population Assessment of Tobacco and Health (PATH) Study provides a unique platform for examining the psychometric properties and validity of multiple indicators of tobacco dependence across a range of tobacco products. PARTICIPANTS: A U.S. nationally representative sample from the 32,320 adult Wave 1 interviews with analyses focused on 14,287 respondents who were current established users of tobacco products. FINDINGS: This analysis confirms a single primary latent construct underlying responses to TD indicators for cigarettes, e-cigarettes, cigars, hookah, and smokeless tobacco products. Mutually exclusive past year tobacco-user groups included: cigarette only (n=8689), e-cigarette only (n=437), cigar only (traditional, cigarillo, or filtered) (n=706), hookah only (n=461), smokeless tobacco only (n=971), cigarette plus e-cigarette (n=709), and multiple tobacco product users (n=2314). Differential Item Functioning (DIF) analyses supported use of 16 of the 24 examined TD indicators for comparisons across tobacco users. With cigarette users as a reference (mean=0.0, SD=1.0), we observed a range of TD with hookah (mean=-1.71) and cigar (mean=-1.92) only users being the lowest, and cigarette plus e-cigarette product users being the highest (mean=0.35). Regression models including sociodemographic factors supported concurrent validity with increased product use frequency and TD among cigarette-only (p<0.001), e-cigarette only (p<0.002), cigar (p<0.001), hookah only (p<0.001), and smokeless tobacco users (p<0.001). CONCLUSION: The PATH Study Adult Wave 1 Questionnaire provided psychometrically valid measures of TD that enables future regulatory investigations of nicotine dependence across tobacco products.

Co-occurrence of tobacco product use, substance use, and mental health problems among adults: Findings from Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) Study.

BACKGROUND: Although non-cigarette tobacco product use is increasing among U.S. adults, their associations with substance use and mental health problems are unclear. This study examined co-occurrence of tobacco use, substance use, and mental health problems, and its moderation by gender, among 32,202U.S. adults from Wave 1 (2013-2014) of the nationally representative longitudinal Population Assessment of Tobacco and Health (PATH) Study. METHODS: Participants self-reported current cigarette, e-cigarette, traditional cigar, cigarillo, filtered cigar, hookah, smokeless tobacco and other tobacco product use; past year alcohol, marijuana, and other drug use; and past year substance use, internalizing and externalizing problems. RESULTS: Compared to non-current tobacco users, current users were more likely to report alcohol or drug use (adjusted odds ratio (AOR)=2.6; 95% confidence interval (CI): 2.3, 2.9), with the strongest associations observed for cigarillo and hookah users. Across all tobacco product groups, users were more likely to report internalizing (AOR=1.9; 95% CI: 1.7, 2.1), externalizing (AOR=1.6; 95% CI: 1.5, 1.8), and substance use (AOR=3.4; 95% CI: 2.9, 4.1) problems than non-users. Gender moderated many of these associations and, of these, all non-cigarette tobacco product associations were stronger among females. CONCLUSIONS: This nationally representative study of U.S. adults is the first to comprehensively document tobacco use, substance use, and mental health comorbidities across the range of currently available tobacco products, while also demonstrating that female tobacco users are at increased risk for substance use and mental health problems. These findings may point to gender differences in vulnerability and suggest that interventions incorporate gender-specific approaches.

Design and methods of the Population Assessment of Tobacco and Health (PATH) Study.

BACKGROUND: This paper describes the methods and conceptual framework for Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study data collection. The National Institutes of Health, through the National Institute on Drug Abuse, is partnering with the Food and Drug Administration's (FDA) Center for Tobacco Products to conduct the PATH Study under a contract with Westat. METHODS: The PATH Study is a nationally representative, longitudinal cohort study of 45 971 adults and youth in the USA, aged 12 years and older. Wave 1 was conducted from 12 September 2013 to 15 December 2014 using Audio Computer-Assisted Self-Interviewing to collect information on tobacco-use patterns, risk perceptions and attitudes towards current and newly emerging tobacco products, tobacco initiation, cessation, relapse behaviours and health outcomes. The PATH Study's design allows for the longitudinal assessment of patterns of use of a spectrum of tobacco products, including initiation, cessation, relapse and transitions between products, as well as factors associated with use patterns. Additionally, the PATH Study collects biospecimens from consenting adults aged 18 years and older and measures biomarkers of exposure and potential harm related to tobacco use. CONCLUSIONS: The cumulative, population-based data generated over time by the PATH Study will contribute to the evidence base to inform FDA's regulatory mission under the Family Smoking Prevention and Tobacco Control Act and efforts to reduce the Nation's burden of tobacco-related death and disease.

Fabrication of polypyrrole nano-arrays in lysozyme single crystals.

A template-directed method for the synthesis and organization of partially oxidized polypyrrole (PPy) nanoscale arrays within the solvent channels of glutaraldehyde-cross-linked lysozyme single crystals is presented. Macroscopic single crystals of the periodically arranged protein-polymer superstructure are electrically conductive, insoluble in water and organic solvents, and display increased levels of mechanical plasticity compared with native cross-linked lysozyme crystals.

Dosimetric effects of setup uncertainties on breast treatment delivery.

This study aimed to assess the dosimetric impact of setup errors during the delivery of radiotherapy to the breast, and use this information to make recommendations on intervention tolerances for portal imaging of breast treatments. Translational and rotational setup errors were simulated for 10 recent breast patients using an Oncentra MasterPlan treatment planning system. The effect of these errors on the breast and tumor bed target volumes receiving 95% and 107% of the prescribed dose were assessed. For the majority of patients, shifts of up to 10 mm or a 4 degrees patient rotation about the cranio-caudal axis had no significant effect on the dose distribution. Changes in dosimetry were more likely if the reference plan contained large hot or cold spots. For a typical patient, it is estimated that a shift of 5 mm in any one direction, or a 2 degrees patient rotation would not cause more than a 5% change in the target volume receiving between 95% and 107% of the prescribed dose. If combinations of errors occur, greater dosimetric changes would be expected. It is concluded that individual patient shifts of up to 5 mm or rotations about the cranio-caudal axis of 2 degrees or less are unlikely to affect dose-volume histogram parameters by an amount judged as clinically significant. Setup errors exceeding these values may cause large dosimetric changes for some patients, particularly those with larger hot or cold regions in the dose distribution, and intervention is therefore recommended.