A Comparison of Use Topography and Nicotine Pharmacokinetics Among Loose and Portioned Smokeless Tobacco Users.

INTRODUCTION: Moist snuff smokeless tobacco (ST) products are available in the United States in both "loose" and "portioned" (ie, pouched) formats, but no published study to date has clinically evaluated the associations between ST format, use behavior, and nicotine exposure. AIMS AND METHODS: Participants used their usual brand of ST (loose ST [n = 30] or portioned ST [n = 20]) during an experimental visit wherein use behavior and plasma nicotine pharmacokinetic parameters were measured following single use (first hour of the session) and ad libitum use (remaining 7 h of the session). Participants' ST products were chemically characterized prior to use for pH and nicotine content. RESULTS: The average amount per use (2.99 vs. 1.52 g; p = .005) and total amount used (11.45 vs. 5.4 g; p = .002) were significantly higher among the loose ST group. Maximum plasma nicotine concentration (Cmax; 33.4 vs. 19.1 ng/ml) and area under the nicotine concentration versus time curve (AUC) were significantly higher for the loose ST group for the first hour (1474.8 vs. 807.2 min* ng/ml; p = .003) and throughout the 8-hour session (15827.9 vs. 8155.3 min* ng/ml; p < .001). Significant associations were observed between free nicotine content and first use Cmax (rs = .488, loose ST group) and AUC0-1 h (rs = 0.448, loose ST group; rs = .441, portioned ST group). CONCLUSIONS: The loose ST group used more product and had a greater average deposition time per use than the portioned ST group. Nicotine exposure was more strongly associated with free nicotine content than total nicotine content. IMPLICATIONS: To our knowledge, the current investigation was the first study to date to clinically evaluate the associations between usual-brand smokeless format, use behavior, and nicotine exposure. We observed meaningful differences in use behavior and subsequent nicotine exposure between loose and portioned ST users. Further, we observed that nicotine exposure was more strongly associated with free nicotine content than total nicotine content.

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

INTRODUCTION: This study examined trajectories of tobacco dependence (TD) in relationship 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 from 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 aged 18 or older who completed all three interviews and had established use at ≥2 assessments. Mutually exclusive groups included: users of cigarettes only, e-cigarettes only, cigars only, hookah only, any smokeless only, cigarette + e-cigarette dual users, and other multiple product users. A validated 16-item scale assessed TD across product users. RESULTS: People who used e-cigarettes exclusively at wave 1 had small increases in TD through wave 3. 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 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 product users. CONCLUSIONS: Except for wave 1 e-cigarette only users (who experienced small increases in TD), TD among U.S. tobacco product users was stable over time, with daily users less likely to vary from baseline. IMPLICATIONS: The level of TD among most U.S. 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 experienced small increases in levels of TD over time, perhaps due to increases in quantity or frequency of their e-cigarette use or increasing efficiency of nicotine delivery over time.

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.

Systemic biomarkers of exposure associated with ENDS use: a scoping review.

OBJECTIVE: This scoping review provides an overview of the existing literature on biomarkers of exposure from electronic nicotine delivery systems (ENDS) use and identifies gaps in existing knowledge. DATA SOURCES: We searched two international databases (PubMed and Web of Science) to identify relevant studies published from August 2013 to February 2021. DATA SELECTION: Studies were included if they assessed and compared biomarkers of exposure between exclusive ENDS users, non-users, exclusive cigarette smokers, dual users of ENDS and cigarettes or cigarette smokers who switch to ENDS. DATA EXTRACTION AND SYNTHESIS: Of the 5074 studies identified, 188 studies met criteria and were selected for full-text screening. Of these, 27 studies were selected for inclusion and data extraction. CONCLUSIONS: Consistent, although limited, evidence shows that exclusive ENDS users have elevated levels of biomarkers of certain volatile organic compounds (VOCs; eg, acrylamide and acrylonitrile), metals (eg, cadmium and selenium) and propylene glycol compared with non-users; however, evidence for biomarkers of other toxicants (eg, acrolein, benzene and chromium) is mixed. Biomarkers of most VOCs are lower in ENDS users compared with cigarette smokers, and cigarette smokers who switch to ENDS consistently show reductions in VOC biomarkers. Evidence comparing metal exposures from exclusive ENDS use, cigarette smoking and dual use is mixed and depends on the metal. ENDS and e-liquid characteristics as well as use patterns may be associated with elevated exposure to VOCs and metals. Additional rigorous, controlled studies can assess biomarker exposures from ENDS use and inform the overall risk-benefit of ENDS use for different user populations.

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.

Longitudinal pathways of exclusive and polytobacco cigarette use among youth, young adults and adults in the USA: findings from the PATH Study Waves 1-3 (2013-2016).

OBJECTIVE: Cigarettes are the most harmful and most prevalent tobacco product in the USA. This study examines cross-sectional prevalence and longitudinal pathways of cigarette use among US youth (12-17 years), young adults (18-24 years) and adults 25+ (25 years and older). DESIGN: Data were drawn from the first three waves (2013-2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US adults and youth. Respondents with data at all three waves (youth, N=11 046; young adults, N=6478; adults 25+, N=17 188) were included in longitudinal analyses. RESULTS: Among Wave 1 (W1) any past 30-day (P30D) cigarette users, more than 60%, persistently used cigarettes across three waves in all age groups. Exclusive cigarette use was more common among adult 25+ W1 P30D cigarette users (62.6%), while cigarette polytobacco use was more common among youth (57.1%) and young adults (65.2%). Persistent exclusive cigarette use was the most common pathway among adults 25+ and young adults; transitioning from exclusive cigarette use to cigarette polytobacco use was most common among youth W1 exclusive cigarette users. For W1 youth and young adult cigarette polytobacco users, the most common pattern of use was persistent cigarette polytobacco use. CONCLUSIONS: Cigarette use remains persistent across time, regardless of age, with most W1 P30D smokers continuing to smoke at all three waves. Policy efforts need to continue focusing on cigarettes, in addition to products such as electronic nicotine delivery systems that are becoming more prevalent.

Initiation of any tobacco and five tobacco products across 3 years among youth, young adults and adults in the USA: findings from the PATH Study Waves 1-3 (2013-2016).

OBJECTIVE: This study reports weighted cross-sectional prevalence of never use of tobacco, and longitudinal past 12-month (P12M), past 30-day (P30D) and frequent P30D any tobacco or specific tobacco product initiation across three 1-year waves. Longitudinal three-wave pathways are examined to outline pathways of exclusive and polytobacco initiation, as well as pathways of new initiators of electronic nicotine delivery systems (ENDS) or cigarettes. DESIGN: Data were drawn from the first three waves (2013-2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth and adults. Respondents with data at all three waves (youth, N = 11 046; young adults, N = 6478; adults 25+, N = 17 188) were included in longitudinal analyses. RESULTS: Across the three age groups, weighted cross-sectional analyses revealed never any tobacco use decreased each year from 2013 to 2016, reflecting overall increases in tobacco initiation in the population during this time. Compared with cigarettes, cigars, hookah and smokeless tobacco, ENDS had the highest proportion of P12M initiation from Wave 1 to Wave 3 (W3) for each age group. Among youth Wave 2 P30D initiators of exclusive ENDS or cigarettes, the most common W3 outcome was not using any tobacco (ENDS: 59.0% (95% CI 48.4 to 68.8); cigarettes: 40.3% (95% CI 28.7 to 53.1)). CONCLUSIONS: Initiation rates of ENDS among youth and young adults have increased the number of ever tobacco users in the US prevention strategies across the spectrum of tobacco products which can address youth initiation of tobacco products.

Correlates of tobacco product cessation among youth and adults in the USA: findings from the PATH Study Waves 1-3 (2013-2016).

OBJECTIVE: To report on demographic and tobacco use correlates of cessation behaviours across tobacco products (cigarettes, electronic nicotine delivery systems (ENDS), cigars, hookah and smokeless tobacco) among the US population. DESIGN: Data were drawn from the first three waves (2013-2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth (ages 12-17) and adults (ages 18+) . Past 30-day (P30D) tobacco users at Wave 1 (W1) or Wave 2 (W2) were included (n=1374 youth; n=14 389 adults). Generalised estimating equations were used to evaluate the association between demographic and tobacco use characteristics at baseline, with cessation behaviours at follow-up (discontinuing use, attempting to quit, quitting), over two 1-year periods (W1-W2, W2-Wave 3). RESULTS: Among adult users of each type of tobacco product, frequency of use was negatively associated with discontinuing use. Among adult cigarette smokers, non-Hispanic white smokers, those with lower educational attainment and those with lower household income were less likely to discontinue cigarette use; ENDS use was positively associated with making quit attempts but was not associated with cigarette quitting among attempters; smokeless tobacco use was positively associated with quitting among attempters; tobacco dependence was negatively associated with quitting among attempters. Among youth cigarette smokers, tobacco dependence was negatively associated with making quit attempts. DISCUSSION: Demographic correlates of tobacco cessation behaviours underscore tobacco use disparities in the USA. Use of ENDS and use of smokeless tobacco products are positively associated with some adult cigarette cessation behaviours.

Correlates of tobacco product initiation among youth and adults in the USA: findings from the PATH Study Waves 1-3 (2013-2016).

OBJECTIVE: To report on demographic and tobacco product use correlates of tobacco product initiation (cigarettes, electronic nicotine delivery systems (ENDS), cigars, hookah and smokeless tobacco) among the US population. DESIGN: Data were from the first three waves (2013-2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth (aged 12-17 years) and adults (aged 18+ years). Never users of at least one type of tobacco product at Wave 1 (W1, 2013/14) or Wave 2 (W2, 2014/15) were included (n=12 987 youth; n=25 116 adults). Generalised estimating equations were used to evaluate the association between demographic and tobacco product use characteristics at baseline, and tobacco product initiation at follow-up (ever, past 30 day (P30D), frequent (use on 20 or more of thepast 30 days)) over two 1-year periods (W1-W2 and W2-Wave 3). RESULTS: Youth aged 15-17 years were more likely than youth aged 12-14 years and adults aged 18-24 years were more likely than older adults to initiate P30D tobacco use across products; non-heterosexuals were more likely than heterosexuals to initiate P30D cigarette and ENDS use. Older adults were more likely than young adults, and males were more likely than females, to be frequent users of ENDS on initiation. Ever use of another tobacco product predicted P30D initiation of each tobacco product. DISCUSSION: Other tobacco product use and age predict P30D tobacco initiation across products whereas associations with other demographic characteristics vary by product. Continued contemporary evaluation of initiation rates within the changing tobacco product marketplace is important.

Correlates of tobacco product reuptake and relapse among youth and adults in the USA: findings from the PATH Study Waves 1-3 (2013-2016).

OBJECTIVE: This study examines sociodemographic and tobacco use correlates of reuptake and relapse to tobacco use across a variety of tobacco products (cigarettes, electronic nicotine delivery systems, cigars, hookah and smokeless tobacco) among the US population. DESIGN: Data were drawn from the first three waves (2013-2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth (ages 12-17) and adults (ages 18+). Reuptake (past 30-day use among previous tobacco users) and relapse (current use among former established users; adults only) were examined among previous users of at least one type of tobacco product at Wave 1 (W1) or Wave 2 (W2) (n=19 120 adults, n=3039 youth). Generalised estimating equations were used to evaluate the association between demographic and tobacco use characteristics at baseline, with reuptake/relapse at follow-up, over two 1-year periods (W1-W2 and W2-Wave 3). RESULTS: Any tobacco product reuptake occurred in 7.8% of adult previous users and 30.3% of youth previous users. Correlates of any tobacco reuptake included being male, non-Hispanic black and bisexual in adults, but race and sexual orientation were not consistent findings in youth. Among recent former users, relapse rates were greater (32.9%). Shorter time since last use and greater levels of tobacco dependence showed the strongest association with any tobacco relapse. DISCUSSION: Continued clinical and public health efforts to provide adults with tools to cope with tobacco dependence symptoms, especially within the first year or two after quitting, could help prevent relapse.

Overview of tobacco use transitions for population health.

The Family Smoking Prevention and Tobacco Control Act provided the US Food and Drug Administration authority to regulate tobacco products using a population health standard. Models have been developed to estimate the population health impacts of tobacco initiation, cessation and relapse transitions. Models should be informed by high-quality, longitudinal data to estimate these constructs. Simulation studies have generated data to predict the impact of various tobacco control interventions, including the influence of regulations on tobacco use behaviours and health. The purpose of this paper is to provide a high-level conceptual overview for understanding tobacco transition behaviours and correlates of these behaviours using data from the Population Assessment of Tobacco and Health (PATH) Study, a US nationally representative longitudinal tobacco study of about 46 000 persons aged 12+ years. The papers that follow in this journal issue build and expand on this conceptual overview using data from the first three waves of the PATH Study. These papers describe use patterns of different tobacco products and their correlates, and can serve as foundations for more in-depth papers that will help the research community better understand the population health impacts and drivers of different tobacco use patterns.

Nicotine Content and Physical Properties of Large Cigars and Cigarillos in the United States.

Introduction: Cigars are combusted tobacco products consisting of filler, binder, and wrapper, which are derived from tobacco. Despite the abundance of literature on the composition of traditional combusted cigarettes, research is limited on the physical and chemical properties of cigars. Therefore, research on cigar properties may be useful to better understand their health impact. Methods: In this study, twenty large cigar and cigarillo products were characterized for physical properties (ie, weight, length, and diameter), filler nicotine content, and tobacco pH. Tobacco pH was used to calculate free nicotine content, free nicotine concentration, and percent free nicotine for all cigars using the Henderson-Hasselbach equation. An additional analysis was performed on a second batch of two large cigar and two cigarillo brands to determine within-brand consistency. All analyses were performed in triplicate. Results: The initial analysis of the twenty cigars showed that cigars exhibited wide variation in product size and nicotine content, although tobacco pH was similar across cigars. Furthermore, in the two large cigar and cigarillo brands analyzed a second time, there was considerable within-brand variance in nicotine content and concentration between the first and second analyses. Conclusions: While only a small sample of commercially-available cigars was analyzed, our data suggest there is wide variability in nicotine content and some physical properties in the domestic cigar market. The data may help to inform potential future regulatory decisions related to these products. Implications: This study reveals some of the challenges to experimental cigar research and illustrates the need to characterize cigar products (eg, nicotine and tobacco content) before use in clinical studies. Additional studies and characterization of the physical and chemical properties of cigars may be useful to further understand these products' toxicity, abuse potential, and public health impact.

Alcohol Use and Problems in Daily and Non-Daily Coffee Drinking College Females.

BACKGROUND: For more than a decade, a large proportion of research on caffeine use in college students has focused on energy drinks (ED), demonstrating an association between ED consumption and heavy/problem alcohol use. The present study examined the relationship between daily coffee consumption and varied measures of alcohol use and problems in a sample of college women. METHODS: Participants were undergraduate females (N=360) attending an urban university in 2001-02 and prior to the rise in ED popularity on college campuses. Analyses compared women who reported drinking coffee daily (DC; 16.9%), to women who did not (NDC; 83.1%) on standardized measures of alcohol use and problems. RESULTS: For both past month and year of drinking, DC women generally reported consuming more alcohol and were 2.1-2.6 times more likely to screen at risk for alcohol problems than their NDC counterparts. DC women were also more likely than NDC women to report problems related to drinking (e.g., experiencing blackouts, inability to stop drinking after they had started). CONCLUSIONS: Findings support potential benefits of health education and screening that goes beyond EDs, focusing on varied forms of caffeine consumption.

Patterns of Use of Smokeless Tobacco in US Adults, 2013-2014.

OBJECTIVES: To examine patterns of smokeless tobacco (SLT) use, by type, in wave 1 (2013-2014) of the Population Assessment of Tobacco and Health Study in the United States. METHODS: We analyzed data from 32 320 adults (aged ≥ 18 years) to assess the use of pouched snus and other SLT products (loose snus, moist snuff, dip, spit, and chewing tobacco). RESULTS: Overall, SLT use was most common among men, younger adults, non-Hispanic Whites, and nonurban respondents. Pouched snus users were more likely to report nondaily and polytobacco use than users of other SLT products. Respondents who used SLT some days were more likely to be current established cigarette smokers than those who used SLT every day (57.9% vs 20.2%). Furthermore, current established smokers who used SLT some days were more likely to smoke every day and had a higher median number of cigarettes smoked per day than smokers who used SLT every day. CONCLUSIONS: Polytobacco use, especially cigarette smoking, is common among SLT users. Pouched snus users are more likely to report nondaily snus use and polytobacco use than users of other SLT products.

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.

Correlates of tobacco product initiation among youth and young adults between waves 1-4 of the population assessment of tobacco and Health (PATH) study (2013-2018).

INTRODUCTION: While risk factors for cigarette smoking among youth and young adults are well-documented, less is known about the correlates of initiation of other tobacco products. This study aims to provide estimates and correlates of initiation among U.S. youth and young adults. METHODS: Data on youth aged 12-17 (n = 10,072) and young adults aged 18-24 (N = 5,727) who provided information on cigarettes, electronic nicotine delivery systems (ENDS), cigars, pipe, hookah and smokeless tobacco use in Wave 1 (W1: 2013-2014)-Wave 4 (W4: 2016-2018) of the nationally-representative PATH Study were used to calculate ever use initiation and correlates of initiation by W4. RESULTS: Nearly 6 million youth and 2.5 million young adults used tobacco for the first time between W1-W4. Approximately one quarter of youth and young adult ENDS never users initiated ENDS between W1-W4 of the PATH Study. Among youth, use of other tobacco products, ever substance use, and high externalizing problems were associated with initiation of most products. Among young adults, use of other tobacco products and ever substance use were associated with initiation of most products. In both youth and young adults, Hispanics were more likely to initiate hookah use than their non-Hispanic White counterparts. While male sex was a risk factor for most tobacco product initiation across both age groups, it was not associated with hookah initiation. CONCLUSIONS: Cigarette and non-cigarette products shared many correlates of initiation, although there are noteworthy demographic differences. Findings can help tailor product specific interventions to reach populations at risk during preliminary stages of use.

Role of CD38, a cyclic ADP-ribosylcyclase, in morphine antinociception and tolerance.

Our previous studies have demonstrated that an increase in intracellular levels of Ca(2+) in neurons is an important component of both the antinociception produced by morphine and morphine's tolerance. The present study tested the hypothesis that the Ca(2+) signaling second messenger, cyclic ADP-ribose (cADPR), derived from CD38 activation participates in morphine antinociception and tolerance. We first showed that morphine's antinociceptive potency was increased by the intracerebroventricular injection of CD38 substrate beta-NAD(+) in mice. Furthermore, morphine tolerance was reversed by intracerebroventricular administration of each of three different inhibitors of the CD38-cADPR-ryanodine receptor Ca(2+) signaling pathway. These inhibitors were the ADP-ribosylcyclase inhibitor nicotinamide, cADPR analog 8-bromo-cADPR, and a large dose of ryanodine (>50 muM) that blocks the ryanodine receptor. In CD38 gene knockout [CD38(-/-)] mice, the antinociceptive action of morphine was found to be less potent compared with wild-type (WT) mice, as measured by tail-flick response, hypothermia assay, and observations of straub tail. However, there was no difference in locomotor activation between CD38(-/-) and WT animals. It was also found that less tolerance to morphine developed in CD38(-/-) mice compared with WT animals. These results indicate that cADRP-ryanodine receptor Ca(2+) signaling associated with CD38 plays an important role in morphine tolerance.

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.

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.

The C. elegans gene dig-1 encodes a giant member of the immunoglobulin superfamily that promotes fasciculation of neuronal processes.

The adhesion of growing neurites into appropriate bundles or fascicles is important for the development of correct synaptic connectivity in the nervous system. We describe fasciculation defects of animals with mutations in the C. elegans gene dig-1 and show that dig-1 encodes a giant molecule (13,100 amino acids) of the immunoglobulin superfamily. Five new alleles of dig-1 were isolated in a screen for mutations affecting the morphology or function of several classes of head sensory neurons. Mutants showed process defasciculation of several classes of neurons. Analysis of a temperature-sensitive allele revealed that dig-1 is required during embryogenesis for normal process fasciculation of one class of head sensory neuron. Partial sequencing of two alleles, RNA interference (RNAi) and rescuing experiments showed that dig-1 encodes a giant molecule of the immunoglobulin superfamily. DIG-1 protein contains many domains associated with adhesion, is likely secreted, and has some features of proteoglycans. dig-1 mutants were originally isolated due to their displaced gonads [Thomas, J.H., Stern, M.J., Horvitz, H.R., 1990. Cell interactions coordinate the development of the C. elegans egg-laying system. Cell 62, 1041-52]; thus, dig-1 alleles were also characterized for their effects on gonad placement. Mutant phenotypes suggest that DIG-1 may mediate cell movement as well as process fasciculation and that different regions of the protein may mediate these functions.