Sales of Electronic Nicotine Delivery Systems (ENDS) and Cigarette Sales in the USA: A Trend Break Analysis.

Electronic nicotine delivery systems (ENDS) are a potentially lower-risk tobacco product which could help smokers switch completely away from cigarettes. However, the lack of strong evidence to date of a measurable, population-level effect on reducing smoking has generated skepticism about ENDS' potential benefits. This study examines whether increased US ENDS sales have been associated with reduced cigarette sales. Retail data on weekly per-capita cigarette and ENDS purchases in the USA during 2014-2019 were obtained from a national sample of brick-and-mortar retail outlets. Trends in cigarette sales were modeled before (2014-2016) ENDS had a substantial market share, and, after adjusting for macroeconomic factors, projected into the post-period (2017-2019). Actual cigarette sales were lower than projected sales (by up to 16% across the post-period), indicating a substantial "cigarette shortfall" in the post-period. To explore whether general (i.e., inclusive of potentially many mechanisms) substitution by ENDS can explain the cigarette shortfall, its association with per-capita ENDS volume sales was examined. Higher ENDS sales were significantly associated with a greater cigarette shortfall: for every additional per-capita ENDS unit, cigarette sales were 1.4 packs-per-capita lower than expected (B = 1.4, p < .0001). Error correction models which account for spurious correlation yielded similar results. These findings support ENDS serving as a substitute for cigarettes (through potentially many mechanisms including cigarette price), causing cigarette consumption to decline. Since ENDS potentially pose lower risk than cigarettes, this general substitution effect suggests that risk-proportionate tobacco regulation could mitigate the tobacco-related health burden. Supplementary Information: The online version contains supplementary material available at 10.1007/s10603-022-09533-4.

Switching to "lighter" cigarettes and quitting smoking.

OBJECTIVE: Smokers who switch to "lighter" cigarettes may be diverted from quitting smoking. We assessed factors associated with switching and the association between switching and (1) making a quit attempt, and (2) recent quitting, yielding a measure of net quitting (attempts x recent quitting). DESIGN: In 2003, a total of 30 800 ever-smokers who smoked in the past year provided history of switching and 3 reasons for switching: harm reduction, quitting smoking and flavour. Among those who made a past-year quit attempt, recent quitting was defined as >or=90-day abstinence when surveyed. Multivariable logistic regression identified determinants of outcomes. RESULTS: In all, 12 009 (38%) of ever-smokers switched. Among switchers, the most commonly cited reasons were flavour only (26%) and all 3 reasons (18%). Switchers (vs non-switchers) were more likely to make a quit attempt between 2002 and 2003 (51% vs 41%, p<0.001, adjusted odds ratio (AOR) 1.58, (95% confidence interval (CI) 1.48 to 1.69)), but less likely to have recently quit (9% vs 17%, p<0.001; AOR 0.40 (95% CI 0.35 to 0.45)), yielding lower overall net quitting (4.3% vs 7.0%, p<0.001; AOR 0.54, (95% CI 0.47 to 0.61)). The effects of switching on outcomes were most pronounced for reasons including quitting smoking, whereas switching for harm reduction alone had no association with outcomes. CONCLUSION: Compared with no switching, a history of switching was associated with 46% lower odds of net quitting.

Nicotine exposure among nondependent smokers.

Most theories of dependence imply that repeated exposure to an addictive drug leads inexorably to dependence. We examined nicotine exposure in "tobacco chippers," who smoke regularly without developing dependence. Blood samples were obtained before and after 10 chippers (smoking up to 5 cigarettes per day) and 12 dependent smokers (20 to 40 cigarettes per day) smoked a cigarette. Chippers' blood nicotine levels increased significantly, in amounts equaling those of dependent smokers. Assays of cotinine (a long-lasting nicotine metabolite) also suggested that chippers' per-cigarette nicotine absorption equaled that of dependent smokers. Chippers' cotinine levels were also compared with those of heavy smokers (38 cigarettes per day) whose consumption was reduced to 5 cigarettes per day in a previously published study. The heavy smokers compensated by tripling their per-cigarette nicotine intake. Chippers did not seem to be compensating; their cotinine values equaled those expected when regular smokers were not compensating for reduced cigarette availability.

Physiological and psychological effects of methadone in man.

Methadone hydrochloride-maintenance outpatients were compared to abstinent exaddicts on physiological and psychological measures, and to normal subjects on physiological measures. The battery of psychological tests measure cognitive abilities and mental state. Methadone depressed respiration rate below other groups; abstinent subjects had higher heart rates than methadone or control subjects. No other physiological differences appeared. Electroencephalographic spectral analysis disclosed that the location of the alpha peak was at the lowest frequency in the methadone group, next lowest being the abstinent group. Discriminant functions based on a weighted combination of variables (frequencies) successfully distinguished the EEGs of the three groups. Both discriminant analysis and multiple regression analysis indicated that EEG changes were dose-dependent. Methadone subjects performed significantly poorer on several tests of learning and immediate recall compared to absitinent subjects.

Characteristics of selectors of nicotine replacement therapy.

OBJECTIVE: To assess differences in demographic and smoking characteristics between smokers who have and have not used nicotine replacement therapy (NRT). DESIGN: Mail survey of US smokers from a national research panel. PARTICIPANTS: Smokers 18 years and over who returned a survey on smoking (n = 9630). The sample was weighted to match the US smoker population on age and sex. MAIN OUTCOME MEASURES: Compared smokers who had/had not used NRT in a quit attempt (ever NRT use or over the counter (OTC) NRT use) on: demographic characteristics, nicotine dependence, history of craving and withdrawal, expected difficulty quitting, and self reported history of smoking related medical illness and psychopathology. RESULTS: NRT users (both ever-users and OTC users) were more likely to be older, male, and better educated. They were also heavier smokers, had experienced more craving and withdrawal upon quitting, and scored higher on measures of dependence. These differences were evident among light smokers, and remained even when smoking rate and time to first cigarette were controlled. CONCLUSION: Smokers who elect to use NRT differ from non-NRT users in ways that predispose them to failure in cessation. Controlling for smoking rate and time to first cigarette does not eliminate these differences, even among light smokers. These differences must be considered when comparing the effectiveness of NRT among samples of smokers who self select their treatment and are likely to bias such outcome comparisons.

The efficacy of computer-tailored smoking cessation material as a supplement to nicotine polacrilex gum therapy.

BACKGROUND: Standard, generic self-help materials have been largely ineffective as behavioral treatments for smoking cessation. In contrast, self-help programs tailored to the needs of specific smokers have shown promise in facilitating quitting. OBJECTIVE: To evaluate the incremental efficacy of the Committed Quitters Program (CQP), a set of computer-tailored materials offered to purchasers of nicotine polacrilex gum, compared with a briefuntailored user's guide and audiotape, both as supplements to nicotine replacement therapy. METHODS: We conducted a randomized, open-label trial with 3 parallel arms. Subjects were smokers who purchased 2- or 4-mg nicotine polacrilex gum and called the CQP toll-free enrollment line. Three thousand six hundred twenty-seven subjects consented to participate in 1 of 3 study arms: (1) those receiving the CQP materials (CQP group, n= 1,217), (2) those receiving CQP materials and an outbound telephone call (CQP + C group, n= 1,207); and (3) those receiving no supplemental intervention beyond the user's guide and audiotape that were prepackaged with the nicotine polacrilex gum (UG group, n= 1,203). Twenty-eight-day continuous abstinence rates were assessed by telephone interviews at 6 weeks and 10-week continuous rates at 12 weeks into treatment. RESULTS: Abstinence rates among respondents at the 6- and 12-week assessments were significantly higher for the CQP (36.2% and 27.6%) and CQP + C (35.5% and 27.3%) groups compared with the UG group (24.7% and 17.7%) at both intervals. The quit rates for the CQP and CQP + C groups were almost identical. CONCLUSIONS: The CQP proved to be an effective behavioral treatment, enhancing quit rates over and above nicotine replacement therapy and a brief untailored written guide and audiotape.

Naltrexone: physiological and psychological effects of single doses.

An ascending series of single doses of the narcotic antagonist naltrexone, ranging from 20 to 160 mg, was administered to 8 abstinent former addicts in order to assess agonistic activity and any toxic side effects. There was little alteration of normal body function. Significant, but small, changes in sublingual temperature (0.4 degrees F decrease), and diastolic blood pressure (1.7 mm Hg increase) were induced. Among the battery of tests assessing behavioral or mood-feeling variables, only 2 showed significant between-condition effects: facilitated performance on the Cross-out Test (attention and perception), and a dose-related decrease in Morphine-Benzedrine Group (MBG) scores of the Addiction Research Center Inventory (ARCI) (mild euphoria). On the whole, subjects had few subjective reactions or unpleasant side effects. Naltrexone appears to be a safe, nontoxic medication in the dosage range examined.

Effects of cigarette smoking and oral nicotine on hand tremor.

The effect of nicotine on hand tremor was assessed by measuring the current induced in a coil by a magnet attached to the finger. Experiment 1 assessed the amplitude of tremor induced by smoking two cigarettes in a group of 33 subjects drawn from two age groups. Smoking increased tremor significantly. Age, sex, and anxiety levels had no effect. Experiment 2 assessed the effect of smoking on tremor frequency. Analog recordings of tremor in 10 subjects were processed to yield the total power in 20 1-Hz bands from 1 to 20 Hz. The log amplitude showed a strong linear relationship to the log frequency, but this relationship was not affected by smoking. Smoking also had no effect on peak frequency in the frequency spectrum. Experiment 3 confirmed that the effects of smoking on tremor were attributable to nicotine. Twelve subjects were tested before and after smoking a cigarette and before and after chewing gum containing 4 mg nicotine. The two conditions induced comparable increases in tremor. A 2-mg nicotine preparation tested in eight subjects had no effect on tremor. Tremor may be a useful index of the central activity of nicotine and may help illuminate its mechanism of action.

The effect of nicotine on the delay of gastric emptying.

The effect of cigarette smoking and its active component, nicotine, on the gastric emptying of solid food was assessed in a randomized double-blind crossover design. Ten regular smokers were studied after a 6 h fast and least 18 h after their last cigarette. Subjects smoked a total of three high (1.91 mg) or low (0.17 mg) nicotine cigarettes, before and after a technetium-labelled solid meal and were scanned by gamma camera periodically over a 2-h period. All calculations of gastric emptying revealed a significant delay after smoking high versus low nicotine cigarettes in: mean per cent isotope remaining in the stomach at each measurement point from 90-120 min; amount of meal remaining in the stomach at 2 h; and mean time at which 50% of the meal had emptied (T1/2). Delay in gastric emptying was significantly correlated with increase in serum nicotine concentration on the high nicotine day.

Tobacco "chippers"--individual differences in tobacco dependence.

This study explores the behavior of tobacco "chippers"--very light smokers who regularly use tobacco without developing dependence. Eighteen chippers (CHs) who averaged a maximum of five cigarettes per day, but who smoked at least 4 days per week, were compared to 29 dependent smokers (DSs). Laboratory data showed that CHs inhale cigarette smoke and are exposed to nicotine. In both experimental and retrospective self-report data, CHs showed no signs of tobacco withdrawal when abstinent. CHs also differed from DSs in their pattern of smoking: their smoking was less linked with mood states. However, the hypothesis that they were "social" smokers was contradicted. CHs also differed on psychosocial variables relevant to a stress-coping model of smoking: they reported less stress, better coping, and more social support, but these differences were small. Although the two groups were demographically similar, smoking behavior differences between CHs and DSs were long-standing: the two groups differed in their responses to initial smoking and in their family histories of smoking and cessation. CHs' smoking behavior challenges classical theories of dependence; further research is needed on the factors that may protect CHs from addiction.

Effect of oral nicotine dosing forms on cigarette withdrawal symptoms and craving: a systematic review.

RATIONALE: Oral nicotine dosing forms such as nicotine gum have been found to be effective in helping smokers to stop. Some, but not all studies have also found that they reduce the severity of withdrawal discomfort. With new oral nicotine products being developed and use of existing products widening, it is important to determine the strength of evidence that these forms of nicotine replacement reduce overall withdrawal discomfort and individual withdrawal symptoms including craving. OBJECTIVES: To assess the strength of evidence that oral nicotine reduces the severity of overall withdrawal discomfort and individual withdrawal symptoms, including craving. METHODS: All published studies reporting effects of nicotine gum, inhaler, lozenge and sublingual tablet on recognised withdrawal symptoms were scanned and those that met a set of quality criteria were included in the review. The key characteristics of these studies were summarised and their findings tabulated. RESULTS: Of 27 studies that reported effects of oral nicotine products on at least one withdrawal symptom, 12 met the quality criteria (eight for nicotine gum, three for inhaler, one for microtab, none for 1 mg lozenge). Because of limitations on the reporting of the studies it was not possible to carry out meta-analyses and good data were available only for the first week of abstinence. Six out of seven studies reporting it found an effect on total withdrawal discomfort, nine out of nine found an effect on irritability, three out of four found an effect on anxiety and the only study that looked at it found an effect on depressed mood. Seven of 11 studies that looked at it found an effect on craving, but only three out of seven of the studies of nicotine gum. For other withdrawal symptoms the findings were more mixed. CONCLUSIONS: We conclude that the strength of evidence that oral nicotine forms reduce total withdrawal discomfort, irritability and anxiety is high. There is some evidence for an effect on depressed mood and craving although in the latter case the evidence is less good for gum than other forms. Future studies of nicotine effects on withdrawal should meet minimum quality standards for design and reporting to enable results to be combined and compared across studies.

Smoking withdrawal symptoms in two weeks of abstinence.

In order to study trends in smoking withdrawal symptoms, 35 participants in a smoking cessation clinic completed four questionnaires daily for 2 weeks. The questionnaire dealt with a variety of symptoms which a factor analysis showed could be grouped into four factors: stimulation, desire to smoke, and physical and psychological symptoms. Changes were observed in reports of symptoms over days. Trend analyses found that each symptom group except stimulation showed significant patterns or changes as a function of days in abstinence. These symptom clusters were all found to have U-shaped functions. In addition, desire to smoke and psychological symptoms showed linear decreases as abstinence proceeded. Light and heavy smokers were found to differ in the pattern of reported stimulation. Ss who were totally abstinent reported less severe craving overall for cigarettes than those who only reduced their cigarette consumption by an average of 60%. Also, the craving of totally abstinent Ss dropped off more sharply as abstinence proceeded. The import of these patterns and trends in withdrawal symptoms as a function of time is discussed.

Nicotine elimination and tolerance in non-dependent cigarette smokers.

Although most smokers are nicotine-dependent, recent studies suggest that some very light smokers ("chippers", who smoke fewer than five cigarettes per day) may smoke for decades without developing dependence. It was considered that slowed nicotine elimination and/or reduced nicotine tolerance might underlie chippers' ability to maintain smoking at such low levels. To evaluate this hypothesis, we studied the elimination kinetics and pharmacodynamics of nicotine in chippers and matched regular smokers. Plasma nicotine levels and cardiovascular responses were observed for several hours after subjects were administered uniform doses of tobacco smoke. Chippers did show less chronic nicotine tolerance, but only on some response measures. Their rates of nicotine elimination equaled those of regular smokers. This finding, when coupled with other data about chippers' smoking patterns and nicotine absorption, establish that chippers cannot maintain substantial plasma nicotine levels between cigarettes, and thus suggest that attempts to maintain minimal trough levels of nicotine do not underlie chippers' smoking.

The effect of bupropion on nicotine craving and withdrawal.

RATIONALE AND OBJECTIVES: Bupropion has demonstrated efficacy for smoking cessation. Given the importance of nicotine craving and withdrawal in the smoking cessation process, the current study examined the effects of bupropion on these parameters during smoking abstinence. METHODS: During a 2-day Baseline phase with ad lib smoking, 91 non-depressed smokers (who were not trying to quit permanently) were administered measures of nicotine craving, withdrawal symptoms, and timed measures of cognitive performance five times daily. Participants were then assigned randomly to a 14-day treatment regimen with bupropion 300 mg/day, bupropion 150 mg/day, or placebo. Thereafter, the above measures were re-administered during 3 days of abstinence on a closed research ward. RESULTS: Relative to placebo, 300 mg bupropion significantly reduced abstinence-associated increases in rated depression, difficulty concentrating, and irritability, and attenuated a decrease in positive affect. The results also suggested that bupropion might have a positive effect on performance measures during the withdrawal period. No effects were observed on craving, anxiety, restlessness, or hunger. The lack of findings on craving measures may be explained by a floor effect; except on the first day of abstinence, neither drug nor placebo groups showed much craving elevation during abstinence. CONCLUSIONS: Study results indicate that bupropion ameliorates some nicotine withdrawal symptoms.

Tobacco dependence. Global public health potential for new medications development and indications.

Current trends indicate that approximately 500 million of the world's existing cigarette smokers will prematurely die of causes that could be prevented by treatment of their addiction to tobacco delivered nicotine. Initial pharmacologically based treatment offerings and approaches have proven the concept that increasing the accessibility and diversity of treatment modalities helps more people quit smoking. These treatments have also shown, however, that the vast majority of smokers continues to find treatment less attractive and less accessible than cigarettes whose appeal is constantly stimulated by new formulations, marketing strategies, and implied claims of reduced risk. There appears to be considerable untapped potential public health benefit, as well as commercial opportunity, for medication developers to reach an increasing fraction of smokers who find current treatments unacceptable, inaccessible, or ineffective. The global opportunities to serve public health via medication development are growing even more rapidly as country after country recognizes the impending economic and health care problems posed by tobacco dependence and are opening their doors to treatment. Three areas of medications development offer particular promise: new forms of nicotine delivery, non-nicotine based medications, and new indications to reach those who are unable or unwilling to completely quit. This article discusses the biobehavioral rationale for medication development, the opportunities, and some of the prominent technical and regulatory challenges.

A continuous-speech interface to a decision support system: I. Techniques to accommodate for misrecognized input.

OBJECTIVE: Develop a continuous-speech interface that allows flexible input of clinical findings into a medical diagnostic application. DESIGN: The authors' program allows users to enter clinical findings using their own vernacular. It displays from the diagnostic program's controlled vocabulary a list of terms that most closely matches the input, and allows the user to select the single best term. The interface program includes two components: a speech-recognition component that converts utterances into text strings, and a language-processing component that matches recognized text strings with controlled-vocabulary terms. The speech-recognition component is composed of commercially available speech-recognition hardware and software, and developer-created grammars, which specify the language to be recognized. The language-processing component is composed of a translator, which extracts a canonical form from both recognized text strings and controlled-vocabulary terms, and a matcher, which measures the similarity between the two canonical forms. RESULTS: The authors discovered that grammars constructed by a physician, who could anticipate how users might speak findings, supported speech recognition better than did grammars constructed programmatically from the controlled vocabulary. However, this programmatic method of grammar construction was more time efficient and better supported long-term maintenance of the grammars. The authors also found that language-processing techniques recovered some of the information lost due to speech misrecognition, but were dependent on the completeness of supporting synonym dictionaries. CONCLUSIONS: The authors' program demonstrated the feasibility of using continuous speech to enter findings into a medical application. However, improvements in speech-recognition technology and language-processing techniques are needed before natural continuous speech becomes an acceptable input modality for clinical applications.

BrainImageJ: a Java-based framework for interoperability in neuroscience, with specific application to neuroimaging.

The Human Brain Project consortium continues to struggle with effective sharing of tools. To facilitate reuse of its tools, the Stanford Psychiatry Neuroimaging Laboratory (SPNL) has developed BrainImageJ, a new software framework in Java. The framework consists of two components-a set of four programming interfaces and an application front end. The four interfaces define extension pathways for new data models, file loaders and savers, algorithms, and visualization tools. Any Java class that implements one of these interfaces qualifies as a BrainImageJ plug-in-a self-contained tool. After automatically detecting and incorporating new plug-ins, the application front end transparently generates graphical user interfaces that provide access to plug-in functionality. New plug-ins interoperate with existing ones immediately through the front end. BrainImageJ is used at the Stanford Psychiatry Neuroimaging Laboratory to develop image-analysis algorithms and three-dimensional visualization tools. It is the goal of our development group that, once the framework is placed in the public domain, it will serve as an interlaboratory platform for designing, distributing, and using interoperable tools.

A continuous-speech interface to a decision support system: II. An evaluation using a Wizard-of-Oz experimental paradigm.

OBJECTIVE: Evaluate the performance of a continuous-speech interface to a decision support system. DESIGN: The authors performed a prospective evaluation of a speech interface that matches unconstrained utterances of physicians with controlled-vocabulary terms from Quick Medical Reference (QMR). The performance of the speech interface was assessed in two stages: in the real-time experiment, physician subjects viewed audiovisual stimuli intended to evoke clinical findings, spoke a description of each finding into the speech interface, and then chose from a list generated by the interface the QMR term that most closely matched the finding. Subjects believed that the speech recognizer decoded their utterances; in reality, a hidden experimenter typed utterances into the interface (Wizard-of-Oz experimental design). Later, the authors replayed the same utterances through the speech recognizer and measured how accurately utterances matched with appropriate QMR terms using the results of the real-time experiment as the "gold standard." MEASUREMENTS: The authors measured how accurately the speech-recognition system converted input utterances to text strings (recognition accuracy) and how accurately the speech interface matched input utterances to appropriate QMR terms (semantic accuracy). RESULTS: Overall recognition accuracy was less than 50%. However, using language-processing techniques that match keywords in recognized utterances to keywords in QMR terms, the semantic accuracy of the system was 81%. CONCLUSIONS: Reasonable semantic accuracy was attained when language-processing techniques were used to accommodate for speech misrecognition. In addition, the Wizard-of-Oz experimental design offered many advantages for this evaluation. The authors believe that this technique may be useful to future evaluators of speech-input systems.

Trans-situational consistency in smoking relapse.

This article explores the question of consistency in ex-smokers' experiences of temptation to smoke. Data were collected from 57 ex-smokers who called a relapse-prevention hotline on two occasions. Relapse situations were classified through cluster analysis and were also coded on McKennel's Smoking Motivation factors. Cognitive and behavioral coping efforts were recorded. Only modest trans-situational consistency was observed. The two relapse episodes did not systematically fall into the same cluster. Data suggested that social aspects of relapse situations might be most consistent. Behavioral coping showed modest trans-situational consistency, whereas cognitive coping showed no stability. The implications of these findings for the prospect of individually tailored interventions are discussed.

Attentional mediation of cigarette smoking's effect on anxiety.

It was hypothesized that smoking's calming effects are cognitively mediated and depend on the presence of a benign distractor, smoking narrows the focus of attention, thereby reducing anxiety by facilitating distraction from stressful cognitions (cf. C. M. Steele & R. A. Josephs's [1988] attention-allocation model of alcohol reinforcement). This notion was tested by examining the effect of smoking (vs. not smoking) on anxiety with and without a concurrent distraction in 82 smokers; distraction effects were also assessed in 42 nonsmokers. As predicted, smoking reduced anxiety only when paired with a distractor. Further, these findings could not be explained by direct nicotine effects or nicotine withdrawal. Several measures of attention allocation failed to confirm the hypothesized cognitive mechanisms, however. Implications of the findings are discussed.