Furan Metabolites Are Elevated in Users of Various Tobacco Products and Cannabis.

Humans are exposed to furan, a toxicant and possible human carcinogen, through multiple sources including diet and tobacco smoke. The urinary metabolites of furan are derived from the reaction of its toxic metabolite with protein nucleophiles and are biomarkers of exposure and potential harm. An established isotopic dilution liquid-chromatography mass spectrometry method was used to measure these biomarkers in urine from users of e-cigarettes, cannabis, and/or combustible tobacco with/without reduced nicotine levels. Amounts of furan mercapturic acid metabolites were higher in these individuals relative to nonsmokers, indicating that they may be at risk for potential furan-derived toxicities.

Exploring Potential for a Personalized Medicine Approach to Smoking Cessation With an American Indian Tribe.

INTRODUCTION: A potential precision medicine approach to smoking cessation is tailoring pharmacotherapy to a biomarker known as the nicotine metabolite ratio (NMR). Little is known about the potential impact and acceptability of this approach for American Indian (AI) persons. AIMS AND METHODS: Tribal-academic collaboration was formed and during 2019-2020 AI adults who smoke(N = 54) were recruited to (1) examine correlations between NMR, dependence, and smoking exposure; (2) assess the extent to which pharmacotherapy preference aligned with NMR-informed recommendations; (3) explore acceptability of NMR-informed pharmacotherapy selection. Participants provided samples for assessment of salivary NMR and urinary total nicotine equivalents (TNE) and completed a questionnaire that assessed cigarettes per day (CPD), Fagerstrom Test for Cigarette Dependence (FTCD), pharmacotherapy preference, and perceptions of NMR-informed pharmacotherapy selection. RESULTS: Significant positive correlations were observed between NMR and FTCD (r = 0.29;p = .0383) and its abbreviated version Heaviness of Smoking Index (HIS) (r = 0.28;p =.0426). Post-hoc analyses suggest that relationships between dependence and NMR were driven by time to first cigarette. Nonsignificant, but directionally consistent, relationships were observed between NMR and CPD (r = 0.21; p =0.1436) and TNE (r = 0.24;p = .2906). Most participants preferred nicotine replacement therapy (71%) over varenicline (29%) and preference for pharmacotherapy matched NMR-based recommendations in 54% of participants. NMR-informed pharmacotherapy selection was supported by 62% of participants. CONCLUSION: In a sample of AI adults who smoke, NMR was related to cigarette dependence and about one-half of participants' pharmacotherapy preference matched their NMR-informed recommendation. There was lower acceptability of NMR-informed approach in this sample of AI adults than prior studies among white or black/African American people who smoke. IMPLICATIONS: Relationships between NMR, dependence, and self-preference for pharmacotherapy suggest that NMR-informed pharmacotherapy selection may have potential for enhancing smoking quitting success in this Tribe. Lower acceptability of NMR-informed pharmacotherapy in this Tribe suggests that this approach may not be equitably utilized. Future work could include identifying community-driven solutions to mitigate precision medicine concerns.

Immediate Switching to Reduced Nicotine Cigarettes in a U.S.-Based Sample: The Impact on Cannabis Use and Related Variables at 20 Weeks.

INTRODUCTION: The FDA proposed rule-making to reduce nicotine in cigarettes to minimally addictive levels. Research suggests decreasing nicotine levels (i.e. very low nicotine content cigarettes [VLNCs]) produced greater quit attempts, reduced smoking, and reduced exposure to harmful constituents among smokers. The impact of long-term VLNC use among people who co-use cigarettes and cannabis on non-tobacco-specific toxicant and carcinogen exposure has not been investigated. AIMS AND METHODS: This study presents secondary analyses of a controlled clinical trial examining switching to VLNC (versus a normal nicotine cigarettes control group [NNCs]) between people who co-use cigarettes and cannabis (n = 174) versus smoked cigarettes (n = 555). Linear mixed-effects models compared changes in smoking behavior, and tobacco-specific (i.e. total nicotine equivalents [TNE], 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone [NNK; total NNAL]) and non-tobacco-specific (i.e. carbon monoxide (CO), 2-cyanoethylmercapturic acid [CEMA], phenanthrene tetraol [PheT]) toxicant and carcinogen exposure at week 20 (with random intercept for participants). Cannabis use was measured among co-use groups. RESULTS: CO was significantly lower only among the cigarette-only group assigned VLNCs (interaction: p = .015). Although both VLNC groups demonstrated decreased CEMA, greater decreases emerged among the cigarette-only group (interaction: p = .016). No significant interactions emerged for TNE, cigarettes per day (CPD), NNAL, and PheT (ps > .05); both VLNC groups decreased in TNE, CPD, and NNAL. Only the cigarette-only group assigned VLNCs demonstrated decreased PheT (p < .001). The VLNC co-use group showed increased cannabis use over time (p = .012; 0.5 more days per week by week 20). CONCLUSIONS: Those who co-use cannabis and cigarettes may still be at risk for greater exposure to non-tobacco-specific toxicants and carcinogens compared to those who only smoke cigarettes. IMPLICATIONS: The present study is the longest longitudinal, prospective comparison study of smoking behavior and exposure to harmful constituents among those who co-use cigarettes and cannabis versus cigarette-only after immediately switching to very low nicotine content cigarettes (VLNC). Those who co-use experienced similar reductions in CPD and tobacco-specific exposure, compared to those who only use cigarettes. However, co-use groups experienced smaller reductions in non-tobacco-specific toxicants and carcinogens compared to the cigarette-only group, potentially because of combustible cannabis use. Additionally, those who co-use and switched to VLNC may be susceptible to slight increases in cannabis use (approximately two more days per year).

Use of Both Alcohol and Cannabis Protective Behavioral Strategies is Associated with Fewer Negative Consequences: A Moderation Analysis.

Background: Concurrent alcohol and cannabis (i.e. marijuana) use (CAM; use of both substances within the same specified time frame) is prevalent among college students and associated with increased risk of negative substance-related consequences. Extant research supports the use of protective behavioral strategies (PBS) for reducing negative consequences associated with both alcohol and cannabis use. However, limited research exists regarding the efficacy of PBS among CAM users, and it is unknown whether using PBS for both alcohol and cannabis augments protective effects. The present study tested four moderation models to evaluate the interactive effects of alcohol and cannabis PBS on alcohol and cannabis negative consequences and use frequency. Methods: A multisite sample of college students (N = 1705) reporting past-month CAM use completed questionnaires regarding substance use behaviors, PBS use, and substance-related negative consequences. Results: Alcohol and cannabis PBS were negatively associated with alcohol and cannabis use, respectively. However, two-way interactions between PBS on substance use were not supported, such that negative associations between PBS and same-substance use were not augmented as other-substance PBS use increased. Interactive effects of alcohol and cannabis PBS on negative alcohol and cannabis consequences were supported, such that negative associations between alcohol PBS and consequences were augmented as cannabis PBS increased and vice versa. Conclusions: Findings suggest that using both types of PBS may increase protective effects against negative consequences among CAM users. Accordingly, promoting both types of PBS may enhance extant harm reduction interventions.

Cigarette Smokers Versus Cannabis Smokers Versus Co-users of Cigarettes and Cannabis: A Pilot Study Examining Exposure to Toxicants.

INTRODUCTION: Studies suggest tobacco and cannabis co-users may experience greater toxicant exposure than exclusive cigarette (ET) smokers. No study has systematically tested differences in toxicant exposure among co-users, exclusive cannabis (ECa) smokers, and ET smokers. AIMS AND METHODS: Adult daily cigarette smokers and/or weekly cannabis smokers completed two laboratory visits. Co-users (n = 19) tested positive for urinary 11-nor-9-carboxy-Δ 9-tetrahydrocannabinol (THCCOOH), self-reported cannabis use ≥1 per week, and smoked ≥5 cigarettes per day (CPD). ET smokers (n = 18) denied past month cannabis use, tested negative for urinary THCCOOH and smoked ≥5 CPD. ECa smokers (n = 16) tested positive for urinary THCCOOH, self-reported cannabis use ≥1 per week, and denied past month tobacco use (NicAlert <3). Self-reported tobacco and cannabis use were collected at both visits. First morning urinary tobacco and combustion-related biomarkers of exposure were compared following a cannabis or tobacco smoking session (visit 2). RESULTS: Co-users and ET smokers had higher levels of exhaled carbon monoxide, total nicotine equivalents, metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL), and all four measured mercapturic acids (measures of volatile organic compounds) than ECa smokers (ps < .005). ET smokers (geometric mean = 7220.2 pmol/mg) had higher levels of 2-hydroxypropylmercapturic acid than co-users (geometric mean = 5348.7 adjusted p = .009). Phenanthrene tetraol did not differ by group (p > .05). CONCLUSIONS: Co-users and ET smokers demonstrated comparable levels of biomarkers of exposure to harmful constituents despite smoking similar amounts of tobacco. ECa smokers demonstrated lower levels of toxicant exposure for most biomarkers. IMPLICATIONS: Although ECa smokers are exposed to significantly lower levels of harmful constituents compared with co-users and exclusive cigarette smokers, this group is still exposed to higher levels of toxicants than observed in studies of nonsmokers. Additionally, these three groups were exposed to similar levels of phenanthrene tetraol. It is important to account for cannabis use in studies examining biomarkers of exposure among cigarette smokers. Additionally, further research is needed examining exposure to harmful chemicals among various types of cannabis and tobacco users.

An Evaluation of Potential Unintended Consequences of a Nicotine Product Standard: A Focus on Drinking History and Outcomes.

INTRODUCTION: A nicotine product standard reducing the nicotine content in cigarettes could improve public health by reducing smoking. This study evaluated the potential unintended consequences of a reduced nicotine product standard by examining its effects on (1) smoking behaviors based on drinking history; (2) drinking behavior; and (3) daily associations between smoking and drinking. METHODS: Adults who smoke daily (n = 752) in the United States were randomly assigned to smoke very low nicotine content (VLNC) cigarettes versus normal nicotine content (NNC; control) cigarettes for 20 weeks. Linear mixed models determined if baseline drinking moderated the effects of VLNC versus NNC cigarettes on Week 20 smoking outcomes. Time-varying effect models estimated the daily association between smoking VLNC cigarettes and drinking outcomes. RESULTS: Higher baseline alcohol use (vs no use or lower use) was associated with a smaller effect of VLNC on Week 20 urinary total nicotine equivalents (ps < .05). No additional moderation was supported (ps > .05). In the subsample who drank (n = 415), in the VLNC versus NNC condition, daily alcohol use was significantly reduced from Weeks 17 to 20 and odds of binge drinking were significantly reduced from Weeks 9 to 17. By Week 7, in the VLNC cigarette condition (n = 272), smoking no longer predicted alcohol use but remained associated with binge drinking. CONCLUSIONS: We did not support negative unintended consequences of a nicotine product standard. Nicotine reduction in cigarettes generally affected smoking behavior for individuals who do not drink or drink light-to-moderate amounts in similar ways. Extended VLNC cigarette use may improve public health by reducing drinking behavior. IMPLICATIONS: There was no evidence that a VLNC product standard would result in unintended consequences based on drinking history or when considering alcohol outcomes. Specifically, we found that a very low nicotine standard in cigarettes generally reduces smoking outcomes for those who do not drink and those who drink light-to-moderate amounts. Furthermore, an added public health benefit of a very low nicotine standard for cigarettes could be a reduction in alcohol use and binge drinking over time. Finally, smoking VLNC cigarettes may result in a decoupling of the daily associations between smoking and drinking.

Designing and using digital platforms for 21st century learning.

This paper is written in response to the original article "Designing for 21 st century learning online: A heuristic method to enable educator learning support roles" (Nacu et al. 2018). The article presents a guide for teacher interactions with students in networked technologies. It also serves as a guide for network designers who are concerned about the quality of online learning, and want more equitable access to systems that inspire young people "to pursue their interests and take ownership of their learning" (Nacu et al. 2018, p. 1029). During the Covid-19 pandemic, network platforms assumed a central role in the educational process. The article is a timely reminder of the importance of designing and implementing platforms that will address twenty-first century learning goals. This response to the Nacu et al. article reviews their research from a "theory of change" perspective. The authors in the original article present a heuristic that expands the online roles that educators currently use to support young people in building their knowledge. To realize the full potential of the heuristic, a more holistic approach is required, one that repositions online learning as a knowledge-building environment. A theory of change could identify the critical variables needed to help teachers and designers transition to a more comprehensive understanding of online learning. Unfortunately, heuristics by themselves do not prepare network designers or teachers to do this work. Future research can embed the heuristic in a broader, deeper effort to prepare teachers and designers to enact student-centered online learning environments.

A Randomized Clinical Trial of Snus Examining the Effect of Complete Versus Partial Cigarette Substitution on Smoking-Related Behaviors, and Biomarkers of Exposure.

INTRODUCTION: This 8-week multisite, randomized controlled trial of snus examined the differential effects of instructions on (1) snus use, (2) smoking and smoking-related measures, and (3) exposure to tobacco-related constituents. METHOD: US adult daily cigarette smokers (n = 150; 43.3% female; Medianage = 43.5) were recruited from Minneapolis, Minnesota; Columbus and Coshocton, Ohio; and Buffalo, New York. Following a 1-week sampling phase of snus, participants who used at least 7 pouches were randomized to either (1) partial substitution (PS; "use snus as you like with your cigarettes"), (2) complete substitution (CS; "avoid cigarettes"), or (3) usual brand cigarettes (UB). Analyses included between-group analyses (eg, PS vs. CS) using Wilcoxon rank sum test of cigarettes per day and snus pouches per day, and a linear mixed model (biomarkers). RESULTS: Compared to the PS and UB groups, smokers assigned to CS reported greater reductions in cigarettes per day (ps < .001), using more snus pouches per day (p = .02), and more smoke-free days (CS median = 14.5, PS and UB medians = 0, p < .001). In addition, results demonstrated reductions in carbon monoxide (p < .001), total nicotine equivalents (p = .02), and four out of five measured volatile organic compounds (ps < .01) over time among the CS group. Exposure to N'-nitrosonornicotine increased by trial end only among the PS group (p < .04). Phenanthrene tetraol increased among all groups by trial end (p = .02) with no difference between groups. CONCLUSIONS: Instructions to completely switch from cigarettes to snus resulted in the greatest reduction in cigarettes and exposure to harmful constituents. IMPLICATIONS: Directly instructing smokers to switch completely to snus, rather than using ad libitum (with no instructions to avoid cigarettes), is necessary for reductions in smoking and subsequent exposure to harmful constituents.

Cigarette Smokers Versus Cousers of Cannabis and Cigarettes: Exposure to Toxicants.

INTRODUCTION: Cannabis and tobacco couse is common and could expose users to higher levels of toxicants. No studies have examined biomarkers of toxicant exposure in cousers of cannabis and cigarettes, compared with cigarette smokers (CS). AIMS AND METHODS: Adult daily CS were recruited from 10 US sites for a study of reduced nicotine cigarettes. In this analysis of baseline data, participants were categorized as either cousers of cannabis and tobacco (cousers; N = 167; urine positive for 11-nor-9-carboxy-Δ 9-tetrahydrocannnabinol and self-reported cannabis use ≥1×/week), or CS (N = 911; negative urine and no self-reported cannabis use). Participants who did not meet either definition (N = 172) were excluded. Self-reported tobacco and cannabis use and tobacco and/or combustion-related biomarkers of exposure were compared between groups. RESULTS: Compared to CS, cousers were younger (couser Mage = 38.96, SD = 13.01; CS Mage = 47.22, SD = 12.72; p < .001) and more likely to be male (cousers = 67.7%, CS = 51.9%, p < .001). There were no group differences in self-reported cigarettes/day, total nicotine equivalents, or breath carbon monoxide, but cousers had greater use of non-cigarette tobacco products. Compared to CS, cousers had higher concentrations of 3-hydroxypropylmercapturic acid, 2-cyanoethylmercapturic acid, S-phenylmercapturic acid, 3-hydroxy-1-methylpropylmercapturic acid (ps < .05), and phenanthrene tetraol (p < .001). No biomarkers were affected by number of cannabis use days/week or days since last cannabis use during baseline (ps > .05). CONCLUSIONS: Cousers had higher concentrations of biomarkers of exposure than CS, but similar number of cigarettes per day and nicotine exposure. Additional studies are needed to determine whether cannabis and/or alternative tobacco products are driving the increased toxicant exposure. IMPLICATIONS: Cousers of cannabis and tobacco appear to be exposed to greater levels of harmful chemicals (ie, volatile organic compounds and polycyclic aromatic hydrocarbons), but similar levels of nicotine as CS. It is unclear if the higher levels of toxicant exposure in cousers are due to cannabis use or the increased use of alternative tobacco products compared with CS. It is important for studies examining biomarkers of exposure among CS to account for cannabis use as it may have a significant impact on outcomes. Additionally, further research is needed examining exposure to harmful chemicals among cannabis users.

A Randomized Clinical Trial Examining the Effects of Instructions for Electronic Cigarette Use on Smoking-Related Behaviors and Biomarkers of Exposure.

INTRODUCTION: Electronic cigarettes (e-cigarettes) have the potential to significantly reduce exposure to harmful constituents associated with cigarette smoking when smokers completely substitute cigarettes with e-cigarettes. This study examined patterns of e-cigarette and cigarette use, and extent of toxicant exposure, if smokers were instructed and incentivized to completely switch to e-cigarettes compared to instructions to use the product ad libitum. AIMS AND METHODS: US adult daily smokers (n = 264; 49.2% female; Mage = 47.0), uninterested in quitting smoking immediately, were recruited from Minneapolis, MN, Columbus, OH, and Buffalo, NY. Participants were randomized to 8 weeks of instructions for (1) ad libitum use of e-cigarettes (AD-E), (2) complete substitution of cigarettes with e-cigarettes (CS-E), (3) complete substitution of cigarettes with nicotine gum or lozenge (CS-NRT), or (4) continue smoking of usual brand cigarettes (UB). Participants were incentivized for protocol compliance, including complete switching in the CS-E and CS-NRT groups. Outcome variables were cigarette smoking rate and tobacco-related biomarkers of exposure. RESULTS: Smokers in the CS-E and CS-NRT groups showed lower rates of smoking and lower exposure to carbon monoxide, tobacco carcinogens, and other toxicants than smokers in the AD-E group. In general, no significant differences were observed between CS-E versus CS-NRT or between AD-E versus UB for most biomarkers. Significantly higher 7-day point prevalence smoke-free rates were observed for CS-E versus CS-NRT. CONCLUSIONS: Smokers instructed and incentivized to completely switch to e-cigarettes resulted in lower smoking rates and greater reductions in exposures to harmful chemicals than smokers instructed to use the product ad libitum. IMPLICATIONS: Smokers instructed to completely substitute e-cigarettes for cigarettes displayed significantly lower levels of smoking and biomarkers of exposure to carcinogens and toxicants, compared to smokers instructed to use e-cigarettes ad libitum and similar levels as smokers instructed to completely substitute with nicotine replacement therapies. Furthermore, a higher rate of complete switching was achieved with e-cigarettes versus nicotine replacement therapies. Approaches to maximize complete substitution with e-cigarettes are an important area for future research.

Speed of Improvement in Symptoms of Depression With Desvenlafaxine 50 mg and 100 mg Compared With Placebo in Patients With Major Depressive Disorder.

PURPOSE/BACKGROUND: This post hoc analysis examined the time point at which clinically significant improvement in major depressive disorder (MDD) symptoms occurs with desvenlafaxine versus placebo. METHODS: Data were pooled from 9 short-term, double-blind, placebo-controlled studies in adults with MDD randomly assigned to desvenlafaxine 50 mg/d, 100 mg/d, or placebo. A mixed-effects model for repeated-measures analysis of change from baseline score was used to determine the time point at which desvenlafaxine treatment groups separated from placebo on the 17-item Hamilton Rating Scale for Depression and psychosocial outcomes. The association between early improvement and week 8 outcomes was examined using logistic regression analyses. Time to remission for patients with early improvement versus without early improvement was assessed using Kaplan-Meier techniques. Comparisons between groups were performed with log-rank tests. RESULTS: In the intent-to-treat population (N = 4279 patients: desvenlafaxine 50 mg/d, n = 1714; desvenlafaxine 100 mg/d, n = 870; placebo, n = 1695), a statistically significant improvement on the 17-item Hamilton Rating Scale for Depression was observed with desvenlafaxine 50 mg/d at week 1 (P = 0.0129) and with desvenlafaxine 100 mg/d at week 2 (P = 0.0002) versus placebo. Early improvement was a significant predictor of later remission. Treatment assignment, baseline depression scale scores, and race were significantly associated with probability of early improvement. On several measures of depressive symptoms and function, desvenlafaxine 50 mg/d and 100 mg/d separated from placebo as early as week 1 and no later than week 4 in patients with MDD. IMPLICATIONS/CONCLUSIONS: These findings suggest that clinicians may be able to use depression rating scale scores early in treatment as a guide to inform treatment optimization.

A Pilot Randomized Crossover Trial of Electronic Cigarette Sampling Among Smokers.

INTRODUCTION: Electronic cigarette (EC) use is proliferating, but initial uptake patterns and their influence on smoking remains unclear. This study of EC sampling examines naturalistic uptake of ECs, as well as effects on smoking and perceived reward from smoking and vaping. METHODS: Within a double-blind randomized crossover design, smokers (n = 24; 75% male; M age = 48.5 years) smoked as usual for 1 week, followed by two counterbalanced naturalistic (ie, ad libitum use) weeks of either placebo or active first generation ECs. Vaping and regular smoking was measured daily using diaries and at weekly clinic visits. Perceived reward from ECs and intentions/confidence to quit were also assessed. Analyses compared variables during the naturalistic smoking week and each EC week while controlling for sequence and baseline measurements of respective variables. RESULTS: No significant differences emerged between active and placebo EC weeks in vaping or regular smoking, EC reinforcement, and intention/confidence to quit smoking. Satisfaction from smoking (p = .04) and smoking's ability to reduce cravings (p = .003) decreased from the naturalistic to active EC week. Behavioral dependence to cigarettes decreased from the naturalistic (M = 16.5, p = .02) to active (M = 14.7) and placebo (M = 14.2) EC weeks. CONCLUSIONS: Few differences emerged in vaping, regular cigarette use, and overall reactions to ECs between active and placebo ECs. Active ECs appeared to decrease reinforcement from smoking, and both active and placebo ECs reduced behavioral dependence to cigarettes. Nicotine (per labeling) may have minimal influence on the uptake of first generation ECs among smokers. IMPLICATIONS: First generation ECs provide an important behavioral/sensorimotor replacement for cigarettes, regardless of nicotine delivery, but substantial substitution may be minimal when smokers are only asked to use ad libitum. However, newer models of EC devices that provide better nicotine delivery should be examined for potential differential patterns of smoking and vaping (eg, decreased smoking and increased vaping) given their suggested greater ability to provide nicotine and behavior/sensorimotor replacement.

Perceptions of Snus Among US Adult Smokers Given Free Product.

INTRODUCTION: Snus uptake is nominal among US smokers. This longitudinal study examines (1) perceptions of snus among US smokers given free snus for 6 weeks and (2) a method for assessment of an alternative tobacco product at the population level. METHODS: Adult smokers (n = 543; 69.2% female; Mage = 49.3 years), uninterested in quitting, received free snus for ad libitum use. Based on their snus use during a 6-week sampling period, participants included: (1) never users (18.4%, n = 100); (2) experimenters; that is, used ≥ once, but not during the last week of sampling (33.1%; n = 180); and (3) persistent users; that is, used ≥ once during the final week, and ≥ once during any other week of the sampling period. (48.4%; n = 263). RESULTS: Following the sampling period, those who became persistent users were more likely than experimenters to report that switching to alternative tobacco products would lower their risk for health problems (66.5% vs. 50.0%; p = .006). Persistent users also reported greater negative affect relief and craving reduction (ps < .001) than experimenters. Finally, persistent users were more likely than experimenters to describe snus in favorable terms with respect to ease of use, satisfaction, and liking (ps < .05). CONCLUSIONS: Subjective experiences with snus, rather than nicotine dependence, explained experimentation versus persistent use. Even among smokers who became persistent snus users, snus was perceived as a poor substitute for cigarettes. This study design (randomized, yet naturalistic) could be extended to other novel tobacco products, including e-cigarettes, to help understand the role new products may have in the tobacco landscape. IMPLICATIONS: This is the first large scale, US-based naturalistic assessment of smokers' reactions to snus during an extended sampling period. This study is directly in line with FDA goals to better understand predictors of initiation, uptake, and use of other tobacco products such as snus, and serves as model for assessment methods of alternative tobacco products at the population level. Most smokers tried the provided sample of snus (approximately 82%). Subjective experiences with snus, rather than nicotine dependence, explained experimentation versus persistent use. Even among smokers who became persistent snus users, snus was perceived as a poor substitute for cigarettes.

Have combustible cigarettes met their match? The nicotine delivery profiles and harmful constituent exposures of second-generation and third-generation electronic cigarette users.

INTRODUCTION: Electronic cigarettes' (e-cigarettes) viability as a public health strategy to end smoking will likely be determined by their ability to mimic the pharmacokinetic profile of a cigarette while also exposing users to significantly lower levels of harmful/potentially harmful constituents (HPHCs). The present study examined the nicotine delivery profile of third- (G3) versus second-generation (G2) e-cigarette devices and their users' exposure to nicotine and select HPHCs compared with cigarette smokers. METHODS: 30 participants (10 smokers, 9 G2 and 11 G3 users) completed baseline questionnaires and provided exhaled carbon monoxide (eCO), saliva and urine samples. Following a 12-hour nicotine abstinence, G2 and G3 users completed a 2-hour vaping session (ie, 5 min, 10-puff bout followed by ad libitum puffing for 115 min). Blood samples, subjective effects, device characteristics and e-liquid consumption were assessed. RESULTS: Smokers, G2 and G3 users had similar baseline levels of cotinine, but smokers had 4 and 7 times higher levels of eCO (p<0.0001) and total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (i.e., NNAL, p<0.01), respectively, than G2 or G3 users. Compared with G2s, G3 devices delivered significantly higher power to the atomiser, but G3 users vaped e-cigarette liquids with significantly lower nicotine concentrations. During the vaping session, G3 users achieved significantly higher plasma nicotine concentrations than G2 users following the first 10 puffs (17.5 vs 7.3 ng/mL, respectively) and at 25 and 40 min of ad libitum use. G3 users consumed significantly more e-liquid than G2 users. Vaping urges/withdrawal were reduced following 10 puffs, with no significant differences between device groups. DISCUSSION: Under normal use conditions, both G2 and G3 devices deliver cigarette-like amounts of nicotine, but G3 devices matched the amount and speed of nicotine delivery of a conventional cigarette. Compared with cigarettes, G2 and G3 e-cigarettes resulted in significantly lower levels of exposure to a potent lung carcinogen and cardiovascular toxicant. These findings have significant implications for understanding the addiction potential of these devices and their viability/suitability as aids to smoking cessation.

A Proposed Collaboration Against Big Tobacco: Common Ground Between the Vaping and Public Health Community in the United States.

UNLABELLED: An unfortunate conflict is underway between the public health community and the vaping community over e-cigarettes' harmfulness or lack thereof. This conflict is made worse by an information vacuum that is being filled by vocal members on both sides of the debate; a perceived lack of credibility of public health officials by those in the vaping community; the tobacco industry's recent involvement in e-cigarettes; and the constant evolution of different styles and types of e-cigarettes. This conflict is avoidable; common ground exists. If both groups rally around what is in their own and the public's best interest-the end of combustible tobacco--all will benefit significantly. If not, the result may be missed opportunities, misguided alliances, and--ultimately-poorer public health. IMPLICATIONS: This study brings light to the contentious debate between the vaping and public health communities. It addresses how both sides are responsible for bringing misleading information to the public and vocal leaders on both sides are unknowingly intensifying and polarizing the debate-likely at the expense of public health. It also describes how this conflict is avoidable, and provides a starting point for potential positions of common ground against Big Tobacco.

A systematic review of treatment fatigue among HIV-infected patients prescribed antiretroviral therapy.

HIV treatment requires lifelong adherence to medication regimens that comprise inconvenient scheduling, adverse side effects, and lifestyle changes. Antiretroviral adherence and treatment fatigue have been inextricably linked. Adherence in HIV-infected populations has been well investigated; however, little is known about treatment fatigue. This review examines the current state of the literature on treatment fatigue among HIV populations and provides an overview of its etiology and potential consequences. Standard systematic research methods were used to gather published papers on treatment fatigue and HIV. Five databases were searched using PRISMA criteria. Of 1557 studies identified, 21 met the following inclusion criteria: (a) study participants were HIV-infected; (b) participants were prescribed antiretroviral medication; (c) the article referenced treatment fatigue; (d) the article was published in a peer-reviewed journal; and (e) text was available in English. Only seven articles operationally defined treatment fatigue, with three themes emerging throughout the definitions: (1) pill burden; (2) loss of desire to adhere to the regimen; and (3) nonadherence to regimens as a consequence of treatment fatigue. Based on these studies, treatment fatigue may be defined as "decreased desire and motivation to maintain vigilance in adhering to a treatment regimen among patients prescribed long-term protocols." The cause and course of treatment fatigue appear to vary by developmental stage. To date, only structured treatment interruptions have been examined as an intervention to reduce treatment fatigue in children and adults. No behavioral interventions have been developed to reduce treatment fatigue. Further, only qualitative studies have examined treatment fatigue conceptually. Studies designed to systematically assess treatment fatigue are needed. Increased understanding of the course and duration of treatment fatigue is expected to improve adherence interventions, thereby improving clinical outcomes for individuals living with HIV.

Pilot study examining the efficacy of an electronic intervention to promote HIV medication adherence.

Widespread dissemination of current interventions designed to improve HIV medication adherence is limited by several barriers, including additional time and expense burdens on the health care systems. Electronic interventions could aid in dissemination of interventions in the clinic setting. This study developed and tested the feasibility and acceptability of a computer-based adaption of an empirically supported face-to-face adherence promotion intervention. HIV-positive individuals (N = 92) on antiretroviral therapy with self-reported adherence <95% were randomized to the electronic intervention + treatment as usual (TAU) or TAU only. Study outcome variables which included treatment self-efficacy and self-reported medication adherence were assessed at baseline and follow-up. Time × condition interaction effects in mixed model analysis of variance (ANOVAs) examined the differences in patterns of change in the outcome variables over time between the two groups. Participants in the electronic intervention condition reported higher levels of self-efficacy to adhere to their medication at follow-up compared to the control condition. Although nonsignificant, levels of adherence tended to improve over time in the intervention condition, while TAU adherence remained constant. This was the first study to investigate a single-session, computer-based adherence intervention. Results suggest that electronic interventions are feasible and this method may be effective at increasing self-efficacy and adherence among patients reporting suboptimal adherence levels.

Pilot investigation of changes in readiness and confidence to quit smoking after E-cigarette experimentation and 1 week of use.

INTRODUCTION: This study examined changes in smokers' readiness and confidence to quit smoking, smoking behavior, nicotine withdrawal symptoms, and tobacco product preference following electronic cigarette (EC) experimentation and 1 week of ad libitum use. METHODS: Current cigarette smokers, with no prior use of ECs and uninterested in quitting, completed 3 study phases: baseline assessment (N = 20), experimentation (N = 19), and ad libitum use (N = 16). Baseline assessment consisted of completion of assessment measures and exhaled carbon monoxide measurements. Experimentation phases consisted of four, 75-min sessions in which participants completed assessment measures and sampled 3 EC brands and their own brand of cigarette (OBC). Ad libitum use included participants selecting and being provided their preferred EC brand from the experimentation phase to be used "as you want" for 1 week. Outcome measures included readiness and confidence to quit smoking, nicotine withdrawal symptoms, product preference/satisfaction, and smoking behavior items. RESULTS: Readiness and confidence to quit increased significantly during the experimentation period and continued to increase during ad libitum use. There were no significant differences in reported effectiveness in reducing smoking urges and cravings between OBC and EC though OBC were rated as more enjoyable and satisfying. During ad libitum use, regular cigarette smoking decreased by approximately 44% from baseline levels with overall tobacco use (EC + OBC) remaining the same. CONCLUSIONS: Among a small convenience sample of unmotivated cigarette smokers, EC experimentation and 1 week of ad libitum use increased readiness and confidence to quit regular cigarettes and reduced regular cigarette smoking.

Dual tobacco use among college students: contexts of use, self-perceptions, and attitudes toward quitting.

Aggressive marketing of smokeless tobacco (SLT) appears to have led to an increase in dual tobacco use. The current study examines the situational contexts, self-perceptions, and cessation attitudes/behaviors that relate to dual use. Participants (N = 1,242) at a large, Southwestern university completed a self-report measure of demographic and tobacco use variables in 2010. Data were analyzed using chi-square and one-way ANOVA techniques. Findings suggest that type of tobacco use varies by setting and that dual users are more likely than sole users to perceive themselves as regular tobacco users. Limitations and implications for future research and interventions are discussed.

The influence of stress on the affective modulation of the startle response to nicotine cues.

Recent research suggesting that nicotine cues are appetitive in nature promotes the affective modulation of the startle reflex (AMSR) paradigm as a potentially valuable psychophysiological tool for elucidating mechanisms involved in nicotine addiction. Despite numerous studies indicating stress as a key factor in nicotine dependence, specific behavioral mechanisms linking stress and smoking have yet to be explicated. The current study aimed to determine the effects of stress, a negative affective state intimately linked with nicotine use, on the psychophysiological responding of nicotine dependent individuals during smoking cues. Twenty-nine nicotine dependent individuals were randomly assigned to the trier social stress test or control condition directly prior to administration of the AMSR paradigm, which examined their physiological responses to appetitive, neutral, aversive, and nicotine cue images. Both groups evinced significantly decreased startle magnitudes in response to nicotine cues as compared to aversive images. However, exposure to stress did not significantly modulate the startle reflex while viewing nicotine cues. Stress induction does not appear to modulate the AMSR paradigm when evaluating responses to nicotine images. These findings suggest that AMSR is robust to effects of acute stress induction in nicotine dependent individuals which may increase its viability as a clinical tool for assessing success in smoking cessation interventions.