Reactions to a Nicotine Reduction Policy Among Adolescents Who Smoke: A Qualitative Study.

INTRODUCTION: The Biden administration is pursuing a nicotine reduction policy in the U.S. to render cigarettes less addictive. In this study, we qualitatively investigated adolescents' subjective responses to very low nicotine content (VLNC) cigarettes, reasons for incomplete adherence to using them, and their expected responses to a nicotine reduction policy. METHODS: Adolescents who smoke cigarettes daily (ages 15-19; N=60) were enrolled in a three-week double-blind randomized clinical trial and assigned to smoke either normal nicotine content (NNC) or VLNC research cigarettes. Following the trial, 52 participants completed qualitative interviews about their reactions to the cigarettes and to the idea of a nicotine reduction policy. We utilized a template style approach to thematic analysis involving immersion in the data, codebook development with both inductive and deductive codes, and iterative refinement of themes. RESULTS: Reasons for incomplete adherence to smoking only research cigarettes focused on dislike for cigarette taste and lower satisfaction compared to usual brand cigarettes. Negative evaluations of research cigarettes were common across both groups. Many participants in both groups reported that they would decrease their smoking or quit entirely if the research cigarettes were the only ones legally available for purchase in the U.S. CONCLUSIONS: Adolescents may respond to a cigarette nicotine reduction policy by decreasing their cigarette smoking and eventually quitting. These findings suggest a need for public health strategies to reduce smoking initiation and progression in young people and to encourage cessation in the context of a nicotine reduction policy. IMPLICATIONS: Participants' negative subjective responses and challenges with research cigarette adherence offer insight into factors that might influence young people's reactions to a real-world nicotine reduction policy. Adolescents who smoke may increase their use of alternative tobacco products, especially e-cigarettes, if this policy were implemented. Specifically, themes identified across participant responses highlight important considerations for how such a policy might be implemented with specific attention to the unique smoking behaviors and needs of this vulnerable population.

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

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

Disruption of circadian rhythms promotes alcohol use: a systematic review.

This systematic review investigates the bidirectional relationship between alcohol consumption and disrupted circadian rhythms. The goal of this study was to identify (i) the types of circadian rhythm disruptors (i.e. social jet lag, extreme chronotypes, and night shift work) associated with altered alcohol use and (ii) whether sex differences in the consequences of circadian disruption exist. We conducted a search of PubMed, Embase, and PsycINFO exclusively on human research. We identified 177 articles that met the inclusion criteria. Our analyses revealed that social jet lag and the extreme chronotype referred to as eveningness were consistently associated with increased alcohol consumption. Relationships between night shift work and alcohol consumption were variable; half of articles reported no effect of night shift work on alcohol consumption. Both sexes were included as participants in the majority of the chronotype and social jet lag papers, with no sex difference apparent in alcohol consumption. The night shift research, however, contained fewer studies that included both sexes. Not all forms of circadian disruption are associated with comparable patterns of alcohol use. The most at-risk individuals for increased alcohol consumption are those with social jet lag or those of an eveningness chronotype. Direct testing of the associations in this review should be conducted to evaluate the relationships among circadian disruption, alcohol intake, and sex differences to provide insight into temporal risk factors associated with development of alcohol use disorder.

The Impact of Reducing Nicotine Content on Adolescent Cigarette Smoking and Nicotine Exposure: Results From a Randomized Controlled Trial.

INTRODUCTION: As the science base around the potential benefits of a reduced-nicotine standard for cigarettes grows, information on the potential effects on adolescent smokers is a high priority. The aim of this randomized trial was to test the influence of 3-week exposure to reduced nicotine cigarettes in a sample of adolescent daily smokers. AIMS AND METHODS: In this double-blind, two-arm, randomized controlled trial (NCT0258731), following a 1-week baseline, adolescent daily smokers not currently intending to quit (ages 15-19 years, n = 66 randomized) were urn randomized to use either very low nicotine content (VLNC; 0.4 mg/g; n = 33) or normal nicotine content (NNC, 15.8 mg/g; n = 33) research cigarettes for 3 weeks. Participants attended five study sessions at our clinical laboratory. The primary outcome was average total cigarettes smoked per day (CPD; including both study and non-study cigarettes) at week 3. RESULTS: Stepwise regression results demonstrated that compared with NNC cigarettes (n = 31), assignment to VLNC cigarettes (n = 29), was associated with 2.4 fewer CPD on average than NNC assignment (p < .05) week 3 when controlling for covariates (p < .01, Cohen's d = 0.52 n = 60 completed all procedures). VLNC cigarettes were also associated with lower levels of craving reduction than NNC cigarettes (Questionnaire on Smoking Urges Factor 2, p < .05). No group differences were found for secondary outcomes. CONCLUSIONS: Adolescent participants assigned to VLNC use for 3 weeks smoked fewer total CPD relative to the NNC group. Overall, data suggest that a VLNC policy would reduce cigarette smoking in adolescents who smoke, but high rates of incomplete adherence suggest that youth may seek alternative sources of nicotine in this scenario. IMPLICATIONS: The US Food and Drug Administration may enact a reduced-nicotine product standard that would affect all commercially available cigarettes. One important population affected by this policy would be adolescents who smoke. This study, the first clinical trial of VLNC cigarettes in adolescents, demonstrates that adolescents switched to VLNC cigarettes for 3 weeks reduced their CPD relative to the normal-nicotine cigarette control group, without leading to increased respiratory symptoms or increased withdrawal. Biomarkers indicated the use of other sources of nicotine, suggesting that such a policy will need to consider approaches to assist in transitioning away from smoking.

Effects of very low nicotine content cigarettes on smoking across vulnerable populations.

There has been long-standing interest in a reduced-nicotine product standard for combusted tobacco, which is within the regulatory purview of the Food and Drug Administration (FDA). In weighing whether to establish this standard, it is important to consider potential responses among people who are at elevated risk for tobacco-related health harms. In this narrative review, we summarize studies of very low nicotine content (VLNC) cigarettes conducted between 2010 and 2021 in groups that the FDA has identified as vulnerable populations. Studies conducted to date in adults with mental health conditions, adults with opioid use disorder, socioeconomically-disadvantaged adults, and youth or young adults indicate that immediate switching to VLNC cigarettes decreases smoking, with minimal or no unintended negative consequences. Few studies have investigated the effects of VLNC cigarettes in racial or ethnic minorities, people who smoke menthol cigarettes, and pregnant women, but initial findings suggest that responses of these individuals are similar to responses observed in other vulnerable populations. We are not aware of studies that have investigated VLNC cigarettes in military/veteran populations, sexual or gender minority individuals, or people living in underserved rural environments. Future research directions include understanding how to promote cessation in the context of a reduced-nicotine standard, and how to correct VLNC misperceptions in vulnerable populations. Nevertheless, the evidence to date indicates that a reduced-nicotine standard is likely to have the same beneficial effects on smoking reductions as it does in less vulnerable populations, which should provide some confidence in pursuing this regulatory approach.

Tuberculosis diagnosis and treatment under uncertainty.

In 2017, 1.6 million people worldwide died from tuberculosis (TB). A new TB diagnostic test-Xpert MTB/RIF from Cepheid-was endorsed by the World Health Organization in 2010. Trials demonstrated that Xpert is faster and has greater sensitivity and specificity than smear microscopy-the most common sputum-based diagnostic test. However, subsequent trials found no impact of introducing Xpert on morbidity and mortality. We present a decision-theoretic model of how a clinician might decide whether to order Xpert or other tests for TB, and whether to treat a patient, with or without test results. Our first result characterizes the conditions under which it is optimal to perform empirical treatment; that is, treatment without diagnostic testing. We then examine the implications for decision making of partial knowledge of TB prevalence or test accuracy. This partial knowledge generates ambiguity, also known as deep uncertainty, about the best testing and treatment policy. In the presence of such ambiguity, we show the usefulness of diversification of testing and treatment.

Evaluation of Chemcatcher® passive samplers for pesticide monitoring using high-frequency catchment scale data.

Passive samplers (PS) have been proposed as an enhanced water quality monitoring solution in rivers, but their performance against high-frequency data over the longer term has not been widely explored. This study compared the performance of Chemcatcher® passive sampling (PS) devices with high-frequency sampling (HFS: 7-hourly to daily) in two dynamic rivers over 16 months. The evaluation was based on the acid herbicides MCPA (2-methyl-4-chlorophenoxyacetic acid), mecoprop-P, fluroxypyr and triclopyr. The impact of river discharge parameters on Chemcatcher® device performance was also explored. Mixed effects modelling showed that time-weighted mean concentration (TWMC) and flow-weighted mean concentration (FWMC) values obtained by the HFS approach were both significantly higher (p < 0.001) than TWMC values determined from PS regardless of river or pesticide. Modelling also showed that TWMCPS values were more similar to TWMCHFS than FWMCHFS values. However, further testing revealed that MCPA TWMC values from HFS and PS were not significantly different (p > 0.05). There was little indication that river flow parameters altered PS performance-some minor effects were not significant or consistent. Despite this, the PS recovery of very low concentrations indicated that Chemcatcher® devices may be used to evaluate the presence/absence and magnitude of acid herbicides in hydrologically dynamic rivers in synoptic type surveys where space and time coverage is required. However, a period of calibration of the devices in each river would be necessary if they were intended to provide a quantitative review of pesticide concentration as compared with HFS approaches.

Responses to Gradual and Immediate Reduction of Nicotine in Cigarettes in Young Versus Older Adult Smokers.

INTRODUCTION: As the FDA works to determine whether a nicotine reduction policy would benefit public health, one key question is whether to mandate an immediate or gradual reduction in nicotine levels in cigarettes. The aim of this study was to determine whether the effects of gradual versus immediate nicotine reduction on cigarettes per day (CPD), total nicotine equivalents, and subjective responses differed in younger adults versus older adults. METHODS: Using data from a recent randomized trial conducted in the United States (N = 1250) that switched smokers over a 20-week period to very low nicotine content (VLNC) cigarettes either immediately, gradually (via monthly reductions in nicotine content), or not at all (control condition, normal nicotine content research cigarette), we analyzed the moderating effect of age (age 18-24 or 25+). RESULTS: For both age groups, CPD in the immediate condition was significantly lower relative to gradual condition (estimated mean difference of 6.3 CPD in young adults, 5.2 CPD in older adults; p's < .05). Younger and older adults in the immediate and gradual reduction conditions had lower total nicotine equivalents at Week 20 (all p's < .05) than those in the control condition; age group did not moderate this effect. Positive subjective responses to cigarettes were lower among young adults relative to older adults in the immediate condition. CONCLUSIONS: These results indicate that an immediate reduction in nicotine would result in beneficial effects in both young and older adults. Young adults show less positive subjective effects of smoking following switching to VLNC cigarettes relative to older adults. IMPLICATIONS: As researchers work to understand how a potential reduced-nicotine product standard for cigarettes may affect public health, one question is whether nicotine should be reduced immediately or gradually. This study demonstrates that both young and older adults who were switched immediately to the lowest content of nicotine smoked fewer CPD and had lower nicotine intake than those in the gradual condition. Furthermore, young adults appear to show lower positive subjective effects following switching to VLNC cigarettes relative to older adults. This is consistent with previous work demonstrating that young people appear to show lower abuse liability for VLNC cigarettes.

Mapping the Current and Future Noncommunicable Disease Burden in Kenya by Human Immunodeficiency Virus Status: A Modeling Study.

BACKGROUND: The noncommunicable disease (NCD) burden in Kenya is not well characterized, despite estimates needed to identify future health priorities. We aimed to quantify current and future NCD burden in Kenya by human immunodeficiency virus (HIV) status. METHODS: Original systematic reviews and meta-analyses of prevalence/incidence of cardiovascular disease (CVD), chronic kidney disease, depression, diabetes, high total cholesterol, hypertension, human papillomavirus infection, and related precancerous stages in Kenya were carried out. An individual-based model was developed, simulating births, deaths, HIV disease and treatment, aforementioned NCDs, and cancers. The model was parameterized using systematic reviews and epidemiological national and regional surveillance data. NCD burden was quantified for 2018-2035 by HIV status among adults. RESULTS: Systematic reviews identified prevalence/incidence data for each NCD except ischemic heart disease. The model estimates that 51% of Kenyan adults currently suffer from ≥1 NCD, with a higher burden in people living with HIV (PLWH) compared to persons not living with HIV (62% vs 51%), driven by their higher age profile and partly by HIV-related risk for NCDs. Hypertension and high total cholesterol are the main NCD drivers (adult prevalence of 20.5% [5.3 million] and 9.0% [2.3 million]), with CVD and cancers the main causes of death. The burden is projected to increase by 2035 (56% in persons not living with HIV; 71% in PLWH), with population growth doubling the number of people needing services (15.4 million to 28.1 million) by 2035. CONCLUSIONS: NCD services will need to be expanded in Kenya. Guidelines in Kenya already support provision of these among both the general and populations living with HIV; however, coverage remains low.

Biopsychosocial mechanisms associated with tobacco use in smokers with and without serious mental illness.

Smokers with serious mental illness (SMI) are less responsive to cessation treatments than those without SMI. In this study, we compared smokers with and without SMI on validated measures of biological and psychosocial factors associated with tobacco use. Smokers with (n = 58) and without SMI (n = 83) who were enrolled in parallel clinical trials were compared on measures of carbon monoxide (CO) exposure, nicotine exposure, tobacco-specific nitrosamine exposure, craving, smoking motives, affect, perceived stress, environmental exposure to smoke/smokers, respiratory symptoms, tobacco-related health risk perceptions, and whether they had received recent advice to quit smoking from a health care provider. Data were collected between 2013 and 2017 in Providence, Rhode Island, USA. Samples were compared using independent-sample t-tests and chi-squared tests. Smokers with SMI had higher CO, nicotine, and tobacco-specific nitrosamine exposure levels, greater cigarette dependence, higher craving, and higher scores on eight out of eleven smoking motives (p's < 0.05). Smokers with SMI reported more severe respiratory symptoms but lower perceived health risks of tobacco (p's < 0.05). These smokers were more likely to report having received advice to quit from a medical provider in the past 6 weeks (p < 0.05). Affect, stress, and exposure to smoke/smokers did not differ across samples. Our findings advance the understanding of the elevated smoking rates of people with SMI by comparing smokers with and without SMI on validated biopsychosocial measures. There is a need for interventions that reduce craving, reduce smoking motives, and increase risk awareness among smokers with SMI.

Exclusive E-Cigarette Users Report Lower Levels of Respiratory Symptoms Relative to Dual E-Cigarette and Cigarette Users.

INTRODUCTION: Exclusive e-cigarette use has been shown to be associated with reduced levels of respiratory symptoms relative to smoking combustible cigarettes; this association has been less frequently studied in smokers using advanced-generation e-cigarette devices. Advanced-generation devices generate denser vapor than either early generation or pod-style devices, and engender longer inhalations; these vaping topography patterns may contribute to respiratory symptoms. METHODS: In a single-session, cross-sectional study of exclusive e-cigarette users (N = 59) and dual users of e-cigarettes and cigarettes (N = 54), participants completed questionnaires, including the American Thoracic Society Questionnaire (ATSQ) and were videotaped vaping their own device in the lab for 1 hour. Using a hierarchical regression method, we examined whether topography variables, level of nicotine concentration used in their e-cigarette device in the past month, e-cigarette dependence, amount of e-cigarette use in the past month, and smoking status (any smoking in the last month vs. none) predicted ATSQ score severity. RESULTS: There was a significant mean difference in ATSQ score across smoking status, with greater ATSQ scores for vapers who also smoked cigarettes (19.0, SD = 6.7) than for exclusive vapers (13.4, SD = 5.3). In the final model, of the predictors of interest, only cigarette smoking status predicted significantly greater ATSQ scores (overall F = 2.51, p = .006; R2 = .26; smoking status ß = 0.39, p < .0001). CONCLUSIONS: Findings suggest that differences in respiratory symptoms between dual and exclusive e-cigarette users appear to be attributable to combustible cigarette smoking, rather than more intense or frequent e-cigarette use across groups. IMPLICATIONS: In this comparison of exclusive advanced-generation vape device users (N = 59) versus dual users of these devices and combustible cigarettes (N = 54), we set out to determine the extent to which smoking status and e-cigarette use variables predicted self-reported respiratory symptom severity. We found that dual users showed greater respiratory symptom severity (ATSQ scores) than exclusive vapers. Despite examining vaping topography and other variables, smoking status and race were the only significant predictor of respiratory symptoms. We conclude that combustible cigarette use, not individual vaping topography, likely accounts for differences in respiratory symptoms between dual users and exclusive vapers.

Validation of an E-cigarette Purchase Task in Advanced Generation Device Users.

INTRODUCTION: Behavioral economic purchase tasks are used to estimate the reinforcing value of drugs by asking participants how much they would purchase across a range of increasing prices. We sought to validate such a task for e-cigarettes in experienced users of advanced generation, tank-style devices. METHODS: Dual users of cigarettes and e-cigarettes (N = 54) and exclusive e-cigarette users (N = 59) attended one session during which they completed assessments including two versions of the E-cigarette Purchase Task: one that asked how many puffs of their e-cigarette they would purchase in 24 hours at varying prices and one that asked how many mLs of e-liquid they would purchase. We correlated purchase task outcomes with other measures of e-cigarette use. We also compared the tasks across dual and exclusive users. RESULTS: Indices derived from the mLs-based task were more likely to be correlated with self-reported use rates, e-cigarette dependence, and cotinine levels than the puffs-based task. Exclusive users showed greater demand on than dual users only on the mLs version when using an F-test comparison method, while multivariate analysis of variance (MANOVA) results showed that dual users showed greater demand only on the puffs task. CONCLUSIONS: Results indicate that the mLs version had greater validity than the puffs version in terms of clinical indices. Dual users may still be on a trajectory to fully switching to e-cigarettes; thus, puffs as a measure may be more intuitive, as this measure is shared by cigarettes and e-cigarettes. For exclusive users, the unit they purchase their e-liquid in may be the most relevant unit and better capture their demand for that product. IMPLICATIONS: Behavioral economic purchase tasks have been widely used to understand nicotine use. We have developed two versions of a purchase task for e-cigarette use and compared the two versions in users of advanced generation e-cigarette devices. We found that the mLs version of the task better-reflected use patterns relative to a puffs version, which suggests that participants struggle to place monetary value on a unit of consumption (ie, puffs). Validated measures of e-cigarette reinforcement will be important as researchers and regulators determine which features of these products contribute to reinforcing efficacy.

Anticipated Effects of Nicotine Reduction on Youth Smoking Initiation and Maintenance.

This commentary summarizes emerging findings on the potential impact of a nicotine reduction policy on youth and young adults. We conclude that: (1) adolescent smokers and nonsmokers alike are likely to be less sensitive to reinforcement from very low nicotine content (VLNC) cigarettes compared with adults; (2) reducing nicotine in cigarettes to 0.4 mg/g would reduce the abuse potential of cigarettes in adolescents and young adults; (3) findings to date do not support concerns that nicotine reduction leads to compensatory smoking in young smokers; and (4) if the scope of a reduced nicotine product standard were applied to all combusted tobacco products, that would likely maximize public health benefit of this policy.

Effects of Cigarette Nicotine Content and Menthol Preference on Perceived Health Risks, Subjective Ratings, and Carbon Monoxide Exposure Among Adolescent Smokers.

INTRODUCTION: Minimal research exists on adolescent smokers' perceptions of very low-nicotine-content (VLNC) cigarettes. As approximately half of adolescent smokers prefer menthol cigarettes, it is important to consider the influence of menthol preference on VLNC cigarette perceptions and to what extent menthol preference may affect VLNC smoking behavior. This study examined the effects of cigarette nicotine content and menthol preference or menthol smoking on health risk perceptions, subjective ratings, and carbon monoxide (CO) boost in adolescent smokers. METHODS: Across two counterbalanced sessions, adolescent smokers sampled VLNC and normal nicotine content (NNC) research cigarettes following overnight abstinence. Cigarettes were mentholated or non-mentholated consistent with participants' usual brand. In each session, participants smoked the research cigarette and then completed the Perceived Health Risk Scale and Cigarette Evaluation Scale. Breath CO readings were obtained pre- and post-smoking. Mixed-factor ANOVA tests compared outcomes with cigarette type (VLNC vs. NNC) as the within-subjects factor and menthol preference as the between-subjects factor. RESULTS: Participants (N = 50) were M = 17.7 years old, smoked M = 8.2 cigarettes/day, and 56% typically smoked menthol cigarettes. Participants reported lower risk of developing lung cancer, other cancers, emphysema, bronchitis, and heart disease (ps ≤ .05) when smoking VLNC cigarettes relative to NNC cigarettes. Perceived risk of addiction and stroke did not differ by nicotine content. Menthol preference or menthol smoking did not moderate risk perceptions, subjective ratings, or CO boost. CONCLUSIONS: Adolescents may incorrectly perceive that VLNC cigarettes are less harmful products. Health communication campaigns could help to correct VLNC misperceptions and potentially minimize unintended consequences of a nicotine reduction policy.

Age Moderates Smokers' Subjective Response to Very-Low Nicotine Content Cigarettes: Evidence from a Randomized Controlled Trial.

INTRODUCTION: Reducing the level of nicotine in cigarettes is a regulatory strategy that has the potential to greatly improve public health. If nicotine levels are reduced in all commercially available cigarettes, current smokers might find it easier to quit and young people might be less likely to become dependent. However, it is not yet known whether age moderates subjective or behavioral responses to low-nicotine cigarettes. METHODS: Recently, a large, multisite randomized clinical trial was conducted to compare the effects of cigarettes differing in nicotine content (either usual-brand or research cigarettes containing 15.8, 5.2, 2.4, 1.3, or 0.4 mg nicotine/g tobacco) across 6 weeks of exposure. In this secondary analysis, we tested whether age moderated smokers' subjective (measures of psychological reward, smoking satisfaction) and behavioral (cigarettes smoked per day, smoking topography, and nicotine exposure) responses to cigarettes varying in nicotine content after 2 and 6 weeks of use, while controlling for baseline dependence and demographic factors. RESULTS: Results indicated that younger adults (age 18-24) who smoked cigarettes with 2.4-0.4 mg/g nicotine reported significantly less smoking satisfaction and psychological reward, and smoked fewer cigarettes per day, than older adults (25+ years) after 2 weeks of use. No differences in topography were observed at either time point. After 6 weeks of use, differences had diminished on all measures. CONCLUSIONS: The reduced positive effects of reduced-nicotine content cigarettes in young adults suggests that this regulatory policy may reduce smoking reinforcement in this vulnerable population. IMPLICATIONS: As the FDA considers reducing the level of nicotine in cigarettes to make them less addictive, understanding the potential impact of this policy on young people is of crucial importance. We found that young adults had significantly lower positive subjective effects to very-low nicotine content (VLNC) cigarettes and smoked fewer VLNC cigarettes than older adults after 2 weeks of use, indicating that this policy may reduce smoking reinforcement more quickly in young adults. These data add to the growing body of evidence on the potential for this policy to positively affect public health.

Effects of 6-Week Use of Very Low Nicotine Content Cigarettes in Smokers With Serious Mental Illness.

INTRODUCTION: The US Food and Drug Administration is considering implementing a reduced-nicotine standard for cigarettes. Given the high rate of smoking among people with serious mental illness (SMI), it is important to examine the responses of these smokers to very low nicotine content (VLNC) cigarettes. METHODS: This trial compared the effects of VLNC (0.4 mg nicotine/g tobacco) and normal nicotine content cigarettes (15.8 mg/g) over a 6-week period in non-treatment-seeking smokers with schizophrenia, schizoaffective disorder, or bipolar disorder (n = 58). Linear regression was used to examine the effects of cigarette condition on cigarettes per day, subjective responses, nicotine and tobacco toxicant exposure, craving, withdrawal symptoms, and psychiatric symptoms. RESULTS: At week 6, participants in the VLNC condition smoked fewer cigarettes per day, had lower breath carbon monoxide levels, lower craving scores, and rated their study cigarettes lower in satisfaction, reward, enjoyment, and craving reduction than those in the normal nicotine content condition (ps < .05). Week 6 psychiatric and extrapyramidal symptoms did not differ by condition, except for scores on a measure of parkinsonism, which were lower in the VLNC condition (p < .05). There were no differences across conditions on total nicotine exposure, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, withdrawal symptoms, or responses to abstinence. CONCLUSIONS: These results suggest that a reduced-nicotine standard for cigarettes would reduce smoking among smokers with SMI. However, the lack of effect on total nicotine exposure indicates VLNC noncompliance, suggesting that smokers with SMI may respond to a reduced-nicotine standard by substituting alternative forms of nicotine. IMPLICATIONS: Results from this trial suggest that a reduced-nicotine standard for cigarettes would reduce smoking rates and smoke exposure in smokers with SMI, without increasing psychiatric symptoms. However, noncompliance with VLNC cigarettes was observed, suggesting that these smokers might respond to a reduced-nicotine standard by substituting alternative forms of nicotine.

Mathematical modelling for health systems research: a systematic review of system dynamics and agent-based models.

BACKGROUND: Mathematical modelling has been a vital research tool for exploring complex systems, most recently to aid understanding of health system functioning and optimisation. System dynamics models (SDM) and agent-based models (ABM) are two popular complementary methods, used to simulate macro- and micro-level health system behaviour. This systematic review aims to collate, compare and summarise the application of both methods in this field and to identify common healthcare settings and problems that have been modelled using SDM and ABM. METHODS: We searched MEDLINE, EMBASE, Cochrane Library, MathSciNet, ACM Digital Library, HMIC, Econlit and Global Health databases to identify literature for this review. We described papers meeting the inclusion criteria using descriptive statistics and narrative synthesis, and made comparisons between the identified SDM and ABM literature. RESULTS: We identified 28 papers using SDM methods and 11 papers using ABM methods, one of which used hybrid SDM-ABM to simulate health system behaviour. The majority of SDM, ABM and hybrid modelling papers simulated health systems based in high income countries. Emergency and acute care, and elderly care and long-term care services were the most frequently simulated health system settings, modelling the impact of health policies and interventions such as those targeting stretched and under resourced healthcare services, patient length of stay in healthcare facilities and undesirable patient outcomes. CONCLUSIONS: Future work should now turn to modelling health systems in low- and middle-income countries to aid our understanding of health system functioning in these settings and allow stakeholders and researchers to assess the impact of policies or interventions before implementation. Hybrid modelling of health systems is still relatively novel but with increasing software developments and a growing demand to account for both complex system feedback and heterogeneous behaviour exhibited by those who access or deliver healthcare, we expect a boost in their use to model health systems.

Effects of 6-Week Use of Reduced-Nicotine Content Cigarettes in Smokers With and Without Elevated Depressive Symptoms.

BACKGROUND: The FDA recently acquired regulatory authority over tobacco products, leading to renewed interest in whether reducing the nicotine content of cigarettes would reduce tobacco dependence in the United States. Given the association between depressive symptoms and cigarette smoking, it is important to consider whether smokers with elevated depressive symptoms experience unique benefits or negative consequences of nicotine reduction. METHODS: In this secondary analysis of a randomized clinical trial that examined the effects of cigarettes varying in nicotine content over a 6-week period in non-treatment-seeking smokers, we used linear regression to examine whether baseline depressive symptom severity (scores on the Center for Epidemiologic Studies Depression Scale [CES-D]) moderated the effects of reduced-nicotine content (RNC) cigarettes, relative to normal-nicotine content (NNC) cigarettes, on smoking rates, depressive symptom severity, and related subjective and physiological measures. RESULTS: Of the 717 participants included in this analysis, 109 (15.2%) had CES-D scores ≥ 16, indicative of possible clinical depression. Relative to NNC cigarettes, RNC cigarettes reduced smoking rates, nicotine dependence, and cigarette craving, and these effects were not significantly moderated by baseline CES-D score. A significant interaction between baseline CES-D score and cigarette condition on week 6 CES-D score was observed (p < .05); among those with CES-D scores ≥ 16 at baseline, those assigned to RNC cigarettes had lower week 6 CES-D scores than those assigned to NNC cigarettes. Among those in the lowest nicotine content conditions, biochemically confirmed compliance with the RNC cigarettes was associated with an increase in CES-D score for those with baseline CES-D scores < 16 and no change in CES-D score for those with baseline CES-D scores ≥ 16. CONCLUSIONS: These findings provide initial evidence that a reduced-nicotine standard for cigarettes may reduce smoking, without worsening depressive symptoms, among smokers with elevated depressive symptoms. IMPLICATIONS: This secondary analysis of a recent clinical trial examined whether depressive symptom severity moderated the effects of reduced-nicotine cigarettes on smoking and depressive symptoms. Results indicate that, regardless of baseline depressive symptoms, participants randomized to reduced-nicotine cigarettes had lower smoking rates, nicotine intake, nicotine dependence, and craving at week 6 post-randomization than those assigned to normal-nicotine cigarettes. In participants with higher baseline depressive symptoms, those assigned to reduced-nicotine cigarettes had lower week 6 depressive symptoms than those assigned to normal-nicotine cigarettes. These results suggest that a nicotine reduction policy could have beneficial effects for smokers, regardless of depressive symptom severity.

Smoking Topography Characteristics of Very Low Nicotine Content Cigarettes, With and Without Nicotine Replacement, in Smokers With Schizophrenia and Controls.

INTRODUCTION: Reducing the nicotine content of cigarettes to a minimally addictive level has been proposed as a regulatory strategy for reducing tobacco dependence. However, smokers with schizophrenia (SS) may be prone to changing their smoking topography in efforts to compensate for the reduction in nicotine content. The aims of this study were to compare smoking topography characteristics of usual-brand and very low nicotine content (VLNC) cigarettes in SS and control smokers without psychiatric illness (CS), and to determine whether nicotine replacement reversed any changes in topography produced by VLNC cigarettes. METHODS: Using a within-subjects, counter-balanced design, SS (n = 27) and CS (n = 23) smoked usual brand cigarettes, VLNC cigarettes while wearing placebo patches (VLNC + PLA), or VLNC cigarettes while wearing transdermal nicotine patches totaling 42mg (VLNC + NIC) during 5-hour ad libitum smoking sessions. Cigarettes were smoked through topography measurement devices. RESULTS: Across conditions, SS smoked more puffs per session and per cigarette, had higher cigarette volumes, and had shorter inter-puff intervals than CS (Ps < .01). During VLNC cigarette sessions, puff duration increased and time between puffs decreased, but participants smoked fewer puffs, resulting in a net decrease in cigarette and total session volume (Ps < .001). There were no significant interactions between group and condition. CONCLUSIONS: These findings indicate that acute use of VLNC cigarettes does not increase intensity of smoking in SS, and support the feasibility of a nicotine reduction policy. IMPLICATIONS: Reducing the nicotine in cigarettes to a minimally addictive level has been proposed as a means of reducing tobacco dependence. However, smokers, particularly those with schizophrenia (SS) may alter their puffing in an attempt to extract more nicotine from VLNC cigarettes. This study compared smoking topography of usual brand versus VLNC cigarettes, combined with placebo or transdermal nicotine patches, in SS and controls. Although some changes in topography were indicative of compensatory smoking, total puffs and total cigarette volume were reduced with VLNC cigarettes, indicating that acute VLNC cigarette use does not increase smoking in SS.

Increasing the Value of an Alternative Monetary Reinforcer Reduces Cigarette Choice in Adolescents.

INTRODUCTION: Smoking can be conceptualized as an operant behavior maintained by the reinforcing effects of cigarettes. Changing the magnitude and availability of alternative reinforcers should shift behavior away from smoking. Adults' smoking behavior is sensitive to the magnitude and availability of alternative reinforcers; however, the extent to which the same is true for adolescents has not yet been shown in the laboratory. METHODS: To test the sensitivity of adolescent smoking behavior to changes in the magnitude of alternative reinforcement, we gave adolescents who abstained overnight the opportunity to make 20 choices between receiving two puffs of their usual-brand cigarette or money. The magnitude of the monetary reinforcer was varied across sessions in counterbalanced order ($0.00, $0.10, and $0.50). RESULTS: Results indicated that adolescents' choices for puffs decreased as a function of increasing monetary reinforcer magnitude, while money choices increased. This effect was moderated by baseline smoking level and by gender, such that heavier-smoking participants and males made more cigarette choices when the alternative monetary value was zero, and decreased their choices more steeply in response to increasing monetary value. CONCLUSIONS: The current study validates a laboratory choice procedure for studying smoking in adolescents, and demonstrates that adolescent smoking behavior is sensitive to changes in the magnitude of concurrently available monetary reinforcers. The current paradigm can be adapted and applied to explore the effects of other variables that may affect cigarette choice in adolescents.