Randomized Controlled Trial of Aerobic Exercise for Smoking Cessation among Individuals with Elevated Depressive Symptoms.

INTRODUCTION: Adults with depression have higher rates of cigarette smoking and are more likely to relapse than those without depression. Pharmacological, psychological, and combined interventions have largely yielded small improvements in smoking outcomes for adults with depression. Aerobic exercise (AE) may facilitate smoking cessation in this subpopulation. METHODS: This study was a 12-week two-arm randomized controlled trial that evaluated the effect of a moderate-intensity AE program compared to a health education contact (HEC) control on smoking cessation in adults with elevated depressive symptoms (mild to severe). Participants (n=231) were randomized to AE or HEC and received smoking cessation treatment (telephone counseling and nicotine replacement therapy). Primary (biologically confirmed 7-day point prevalence abstinence) and secondary (depressive symptoms, objective and self-reported physical activity, and cardiorespiratory fitness) outcomes were assessed at baseline, 3-, 6-, and 12-months. Data were analyzed with mixed-effects generalized linear models controlling for age, gender, nicotine dependence, history of major depression disorder, and month of follow-up assessment. RESULTS: There were no significant differences in primary or secondary outcomes between the AE and HEC groups. CONCLUSIONS: The AE program was not superior to HEC in facilitating smoking cessation, increases in physical activity, or improved depressive symptoms. Given evidence for the positive acute effects of exercise on mood and smoking urges, future research should consider testing alternative exercise approaches for aiding smoking cessation beyond structured, aerobic exercise programs. IMPLICATIONS: This study found that an adjunctive aerobic exercise (AE) program was not superior to a health education contact control for adults with elevated depressive symptoms, all of whom also received standard smoking cessation treatment. This finding adds to the growing body of literature that structured aerobic exercise programs for smoking cessation may have limited efficacy for cessation outcomes. Future research is needed to test alternative methods of integrating AE into smoking cessation treatment, such as strategically using exercise to manage cravings and low mood in the moment.

An examination of the effects of distress intolerance and rating of perceived exertion on changes in mood and anxiety following aerobic exercise among treatment-seeking smokers.

Aerobic exercise is frequently used as an intervention for depression and smoking cessation because of its antidepressant and anxiolytic effects. Distress intolerance (DI) is a proposed individual difference factor that, coupled with a higher rating of perceived exertion during exercise, may significantly impact the acute mood and anxiolytic effects of exercise. The current study examined the interactive effect of maximum rating of perceived exertion (RPE) and DI on change in mood and anxiety. Treatment-seeking smokers (Mage = 45.32; 72% female) with elevated depressive symptoms completed a 1-mile treadmill walk at their preferred intensity and self-reported their RPE during the test. Analyses were conducted to examine whether there was an interactive effect of maximum RPE and DI on change in self-reported mood and anxiety from before to after the walk test. Findings indicate a significant moderating effect of RPE at lower ratings. Individuals reporting a low maximum RPE and higher DI exhibit a greater change in mood over the course of an exercise session, whereas individuals reporting a low maximum RPE and a lower DI exhibit smaller changes in mood. These results indicate that the subjective effects of exercise within a population of cigarette smokers could be improved by tailoring exercise intensity to individual characteristics. Mild to moderate-intensity exercise, as compared to high-intensity exercise, may result in greater changes in mood for individuals endorsing difficulty tolerating affective and physical distress.

Readiness to Quit Smoking among Smokers in Substance Use Treatment: Associations with Stress, Substance Use Severity, Relapse Concerns and Gender.

Smoking prevalence among individuals in substance use treatment remains higher than in the general population. Given that many smokers in substance use treatment are reluctant to quit smoking, it is important to understand the factors that impede smokers' readiness to quit. The current study used baseline data from a randomized controlled trial involving 60 adult smokers receiving substance use treatment to investigate relations between the severity of substance use problems (SSUP), perceived stress (PS), concerns about relapse (i.e., concerns that quitting smoking would hurt one's recovery process (CR)), and readiness to quit smoking. This study also investigated moderating roles of concerns about relapse and gender. Regression analyses showed a significant main effect of concerns about relapse on readiness to quit in the next 30 days, but no effect for either severity of substance use problems, perceived stress, or the SSUPxCR interaction. There were significant interaction effects between PS and both gender and CR. Among men and those with lower concerns about relapse, higher perceived stress was significantly associated with lower readiness to quit. Findings suggest that psychoeducation to alleviate concerns that quitting smoking could limit substance use recovery could be beneficial. Stress management interventions may be especially beneficial to men.

A Pilot Randomized Controlled Trial of Distress Tolerance Treatment for Weight Concern in Smoking Cessation Among Women.

INTRODUCTION: The majority of women who smoke cigarettes report that concern about weight gain is a barrier to quitting. We developed an intervention incorporating distress tolerance, appetite awareness, and mindful eating skills to target concerns about post-cessation weight gain and emotional eating (DT-W). In the current study, we conducted a pilot randomized controlled trial of DT-W versus a smoking health education (HE) intervention. METHODS: Participants (N = 69 adult female, weight-concerned smokers) were recruited in cohorts of 4-11. Cohorts were randomized to DT-W or HE. DT-W and HE were matched on format (single individual session followed by eight group sessions), inclusion of cognitive behavioral therapy for smoking cessation (CBT) content, and pharmacotherapy (nicotine patches). Follow-up assessments occurred at 1-, 3-, and 6-months post-treatment. RESULTS: The recruitment goal was met; 61 of the 69 participants attended at least one group session. There were no significant differences between DT-W and HE in the number of group sessions attended (DT-W adjusted M = 5.09, HE adjusted M = 5.03, p = .92), ratings of treatment effectiveness or usefulness of skills, or retention at 6-month follow-up (79% in DT-W vs. 78% in HE) (ps > .05), but comprehension ratings were lower in DT-W than in HE (p = .02). CONCLUSIONS: Overall, these results suggest that the study procedures and interventions were feasible and acceptable, but changes to the DT-W intervention content to improve comprehension should be considered prior to conducting a fully powered trial. IMPLICATIONS: A distress tolerance-based treatment targeting fear of weight gain after smoking cessation and post-cessation emotional eating was feasible and acceptable relative to a smoking HE comparison condition, but changes should be considered before conducting a larger trial. Continued innovation in treatment development for weight-concerned smokers is needed.

Anxiety sensitivity and daily cigarette smoking in relation to sleep disturbances in treatment-seeking smokers.

Although the association between anxiety and sleep disturbance is well-documented, the underlying mechanisms are less clear. Anxiety sensitivity (AS), the fear of physiological arousal and bodily sensations, is a risk factor for anxiety and poor sleep. Smoking also contributes to poor sleep and may compound the effects of AS on sleep quality. This study evaluated the main and interactive effects of AS and cigarettes/day on sleep quality among smokers. Participants (n = 190) were adult treatment-seeking daily smokers who completed a baseline assessment as part of a larger smoking cessation trial. Sleep quality was self-reported. Results indicated that AS was significantly correlated with greater disturbance in sleep duration, subjective sleep quality, sleep onset latency, sleep disturbance, daytime dysfunction, and sleep medication use. There was a significant interaction between AS and cigarettes/day in terms of sleep onset latency, but not other sleep quality indices. AS was associated with significantly longer sleep onset latency minutes among heavier smokers, but not lighter smokers. Specifically, the association between AS and sleep onset latency was significant for those who smoked ≥ 33 cigarettes/day. AS is a psychological factor that may contribute to poor sleep quality, especially in heavy smokers, and thus may be a promising intervention target.

CT-Derived Fractional Flow Reserve (FFRCT): From Gatekeeping to Roadmapping.

Coronary computed tomography angiography (CCTA) has emerged as the preferred modality in the diagnosis of coronary artery disease, but it is limited by modest specificity. By applying principles of computational fluid dynamics, flow fraction reserve, a measure of lesion-specific ischemia that is used to guide revascularization, can be noninvasively derived from CCTA, the so-called computed tomography-derived flow fractional reserve (FFRCT). The accuracy of FFRCT in discriminating ischemia has been extensively validated, and it has been shown to improve the specificity of CCTA. Compared to other stress myocardial perfusion imaging, FFRCT has superior or comparable accuracy. Clinical studies have provided strong evidence that FFRCT has significant prognostic implications and informs clinical decisions for revascularization, serving as a gatekeeper to invasive coronary angiography. In addition, FFRCT-based tools can be used to simulate the physiological consequences of different revascularization strategies, thus providing the roadmap to achieve complete revascularization. Although challenges remain, ongoing research and randomized controlled trials are expected to address current limitations and better define its role in clinical practice.

Impact of Mon2 monocyte-platelet aggregates on human coronary artery disease.

BACKGROUND: Monocyte-platelet aggregates (MPAs) form when Mon1, Mon2 or Mon3 monocyte subsets adhere to platelets. They are pathophysiologically linked to coronary artery disease (CAD). However, their individual roles in the occurrence of diffuse CAD remain unknown. MATERIALS AND METHODS: Peripheral blood from 50 patients with diffuse CAD, 40 patients with focal CAD and 50 age-matched patients with normal coronary arteries was analysed by flow cytometry to quantify MPAs associated with individual monocyte subsets. Cutaneous forearm microcirculation was assessed using laser Doppler flowmetry at rest and after iontophoresis of acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) at 100 µA for 60 seconds. Patients with CAD had repeat assessment at 6 and 12 months. RESULTS: Baseline counts of MPAs with Mon2 subset (CD14++CD16+CC2+ monocytes) were significantly higher in patients with diffuse CAD compared to focal CAD (P = .001) and patients without CAD (P = .006). On multivariate regression, MPAs with Mon2 independently predicted diffuse CAD (odds ratio 1.10, 95% confidence interval 1.02-1.19, P = .01) and correlated negatively with endothelium-dependent microvascular vasodilation (r = -.37, P = .008), an association which persisted after adjustment for covariates. Longitudinal observation confirmed the persistence of an inverse relationship between MPAs with Mon2 and endothelium-dependent microvascular function. CONCLUSION: Monocyte-platelet aggregates with Mon2 are increased in patients with diffuse CAD and therefore could represent an important contributor to accelerated coronary atherosclerotic progression by a mechanism involving microvascular endothelial dysfunction.

Acute Effects of Aerobic Exercise on Affect and Smoking Craving in the Weeks Before and After a Cessation Attempt.

Introduction: Aerobic exercise may improve smoking abstinence via reductions in craving and negative affect and increases in positive moods. Acute changes in craving and affect before and after structured exercise sessions have not been examined during the weeks prior to and following quit attempts nor has smoking status been examined in relation to these effects. Given that regular cigarette smoking can be perceived as affect enhancing and craving reducing, it is not known whether exercise could contribute additional affective benefit beyond these effects. Method: Participants (N = 57; 68.4% women) were low-active daily smokers randomized to cessation treatments plus either group-based aerobic exercise (AE) or a health-education control (HEC). Mood, anxiety, and craving were assessed before and after each intervention session for each of the 12 weeks. Carbon monoxide (CO) breath samples ≤ 5ppm indicated smoking abstinence. Results: During the prequit sessions, significantly greater decreases in anxiety following AE sessions relative to HEC sessions were observed. Changes in mood and craving were similar after AE and HEC sessions prior to quitting. Postquit attempt, significant reductions in craving and anxiety were observed after AE sessions but not following HEC. During the postquit period, positive mood increased following AE sessions relative to HEC only among individuals who were abstinence on that day. Conclusions: AE may be effective in acutely reducing anxiety prior to a quit attempt and both anxiety and craving following the quit attempt regardless of abstinence status. The mood-enhancing effects of AE may occur only in the context of smoking abstinence. Implications: The current findings underscore the importance of examining the acute effects of aerobic exercise prior to and after a cessation attempt and as a function of smoking status. Given the equivocal results from previous studies on the efficacy of exercise for smoking cessation, increasing our understanding of how aerobic exercise produces its reinforcing benefits for smokers attempting to quit could potentially inform the refinement (e.g., timing/sequencing) of exercise interventions within smoking cessation programs.

Effects of Negative Affect, Urge to Smoke, and Working Memory Performance (n-back) on Nicotine Dependence.

BACKGROUND: Three key domains including negative emotionality, incentive salience, and executive function form the core functional elements of addictive behaviors. Variables related to these broader domains have been studied extensively in relation to one another; however, no studies to date, have examined models including variables from all three domains, in relation to nicotine dependence. METHOD: Smokers (N = 117), 65.8% female, 78% white, mean age of 44.4 (SD = 10.8), enrolled in a smoking cessation program completed measures of negative affect (a component of negative emotionality), urge to smoke (incentive salience), and working memory (WM; a core executive function), during a baseline assessment period prior to initiating treatment. RESULTS: Negative affect was associated with greater urge to smoke, and this elevated urge to smoke was associated with higher levels of nicotine dependence. Further, a significant moderated mediation indicated that WM moderated the relationship between increased urge to smoke and nicotine dependence. For those with low to average WM, urge to smoke was significantly related to nicotine dependence; however, for those with higher WM (+1 SD), urge to smoke stemming from negative affect was not associated with nicotine dependence. CONCLUSIONS: To our knowledge, this is the first reported relationship between negative affect, urge to smoke, WM, and nicotine dependence. Although preliminary, results indicate that WM may moderate the relationship between urge to smoke associated with negative affect and nicotine dependence. Treatments targeting WM may be particularly useful for individuals with average to low WM who experience urge to smoke related to negative affect.

Testing the Feasibility of a Mindfulness-Based Intervention With Underserved Adolescents at Risk for Depression.

This study tested the feasibility, acceptability, and preliminary effects of a mindfulness-based intervention with at-risk adolescents from a predominantly Hispanic/Latino community. Seven adolescents (57% female, 85% Hispanic/Latino) completed the mindfulness-based intervention, demonstrating feasibility, and reported acceptability as well as sustained improvements in depressive symptoms, perceived stress, and self-esteem.

Physical Activity Preferences and Attitudes of Individuals With Substance Use Disorders: A Review of the Literature.

Substance use disorders (SUDs) are prevalent in the United States and costly to society. SUDs contribute significantly to decreased quality of life and overdose deaths. Physical activity (PA) interventions may be one efficacious method to improve recovery and long-term abstinence from substance use; although PA interventions have resulted in positive physical and psychological outcomes, their adherence and attrition rates have been problematic. To address lack of adherence and high attrition rates, it is important to understand the preferences and attitudes for PA among patients in SUD treatment. We, therefore, conducted a literature review to examine preferences and attitudes for PA among adults with SUDs. Five articles met inclusion and exclusion criteria. The findings from this small sample of studies suggest that adults with SUDs are interested in PA. Walking, strength training, and cycling were the activities preferred most frequently. Participants said that they would like to engage in these activities either alone or with small groups and would prefer their exercise options to be located at facilities they already frequented, such as treatment clinics. Nurses are well positioned to assess patient preferences and attitudes and to enhance recovery efforts in this population. Further exploration of this population's unique preferences and attitudes regarding PA may lay the groundwork for efficacious PA interventions with improved adherence and attrition rates, which may lead to improved recovery outcomes.

A Double-Blind Randomized Placebo-Controlled Trial of Oral Naltrexone for Heavy-Drinking Smokers Seeking Smoking Cessation Treatment.

BACKGROUND: Post hoc analyses of 2 randomized controlled trials suggest naltrexone may reduce alcohol use and improve smoking cessation outcomes among heavy drinkers receiving smoking cessation treatment. However, no studies have been conducted specifically to examine naltrexone for this purpose or to test whether naltrexone has benefit when added to smoking cessation counseling that explicitly addresses heavy drinking. METHODS: We recruited heavy-drinking smokers from the community and randomized them to receive 10 weeks of either (i) 50 mg naltrexone (n = 75) or (ii) placebo (n = 75) daily. Participants received 6 weeks of transdermal nicotine patch and 6 sessions of counseling that addressed both heavy drinking and smoking. Participants were followed for 26 weeks after their target quit smoking date. RESULTS: Across medication conditions, there were substantial reductions at follow-up in percent heavy drinking days (primary outcome) and average drinks per week (secondary outcome). However, participants receiving naltrexone did not differ significantly from those receiving placebo on percent heavy drinking days (effect size d = -0.04, 95% CI [-0.30, 0.22], p = 0.76) or average drinks per week (d = -0.09, 95% CI [-0.35, 0.18], p = 0.54) during follow-up. Naltrexone compared to placebo was not associated with a significant increase in smoking abstinence rates during follow-up, odds ratio = 0.93, 95% CI [0.46, 1.86], p = 0.83. The effect of naltrexone on these outcomes was not significantly moderated by current alcohol dependence or gender. CONCLUSIONS: Results indicate that heavy-drinking smokers, including those with current alcohol dependence, can make substantial reductions in drinking in the context of smoking cessation treatment. However, this study provided no evidence that naltrexone is efficacious for enhancing reductions in drinking or improving smoking cessation in this population. Limitations of this study included lower-than-desired sample size and modest adherence to study medication.

Development and preliminary pilot evaluation of a brief tablet computer intervention to motivate tobacco quitline use among smokers in substance use treatment.

BACKGROUND AND OBJECTIVES: The majority of individuals in substance use disorder (SUD) treatment also smoke cigarettes; yet, the availability of smoking cessation services in SUD treatment remains limited. In this study, we developed and piloted a brief intervention for smokers in SUD treatment intended to motivate engagement in tobacco quitline treatment (TIME-TQ). METHODS: First, we interviewed 19 smokers in SUD treatment to inform the development of TIME-TQ (Phase 1). Second, we delivered a prototype TIME-TQ to 16 smokers in the same SUD treatment program and followed them for 3 months post-discharge (Phase 2). RESULTS: Feedback from Phase 1 participants was used to refine response choices and video segments included in the prototype TIME-TQ. Phase 2 participants rated TIME-TQ high on relevance, interest, respectfulness, and helpfulness. Additionally, they reported significant increases in readiness to quit and perceived importance of quitting after receiving TIME-TQ. A total of 8 of the 16 accepted a quitline referral, and 8 of 13 reached for follow-up (four referral acceptors, four decliners) reported efforts to quit or reduce smoking during the follow-up period. However, only three received quitline counseling and none achieved a sustained period of abstinence. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Our results suggest that TIME-TQ activated these patients to quit smoking, but our referral method (standard fax referral) was unsuccessful in helping participants fully engage in quitline treatment or achieving a period of abstinence. SCIENTIFIC SIGNIFICANCE: We are now conducting an RCT to evaluate TIME-TQ with a revised referral procedure intended to increase treatment engagement and, ultimately, abstinence rates. (Am J Addict 2017;26:587-594).

Anxiety sensitivity predicts increased perceived exertion during a 1-mile walk test among treatment-seeking smokers.

Smoking increases risk of early morbidity and mortality, and risk is compounded by physical inactivity. Anxiety sensitivity (fear of anxiety-relevant somatic sensations) is a cognitive factor that may amplify the subjective experience of exertion (effort) during exercise, subsequently resulting in lower engagement in physical activity. We examined the effect of anxiety sensitivity on ratings of perceived exertion (RPE) and physiological arousal (heart rate) during a bout of exercise among low-active treatment-seeking smokers. Adult daily smokers (n = 157; M age  = 44.9, SD = 11.13; 69.4% female) completed the Rockport 1.0 mile submaximal treadmill walk test. RPE and heart rate were assessed during the walk test. Multi-level modeling was used to examine the interactive effect of anxiety sensitivity × time on RPE and on heart rate at five time points during the walk test. There were significant linear and cubic time × anxiety sensitivity effects for RPE. High anxiety sensitivity was associated with greater initial increases in RPE during the walk test, with stabilized ratings towards the last 5 min, whereas low anxiety sensitivity was associated with lower initial increase in RPE which stabilized more quickly. The linear time × anxiety sensitivity effect for heart rate was not significant. Anxiety sensitivity is associated with increasing RPE during moderate-intensity exercise. Persistently rising RPE observed for smokers with high anxiety sensitivity may contribute to the negative experience of exercise, resulting in early termination of bouts of prolonged activity and/or decreased likelihood of future engagement in physical activity.

Quality of life after quitting smoking and initiating aerobic exercise.

Quitting smoking and aerobic exercise each improve health. Although smokers may be concerned that quitting smoking will reduce their quality of life (QOL), recent research has shown that cessation is associated with QOL benefits. Elements of smoking cessation interventions, such as exercise, may contribute to changes in QOL. However, it is unknown whether initiating exercise in the context of smoking cessation is associated with greater or different effects on QOL than smoking cessation alone. The current study is a secondary analysis of data from a randomized trial (n = 61) of an exercise intervention for smoking cessation. We hypothesized that smoking abstinence and engagement in exercise would have positive, additive effects on QOL at end-of-treatment, 6- and, 12-month follow-ups. Sedentary adult smokers were randomized to the exercise intervention or a health education control (HEC) group. Additionally, all participants received smoking cessation counseling and nicotine patches. Data were analyzed using actual engagement in exercise, rather than group assignment as a proxy for exercise engagement, because some HEC participants also began exercising. Abstinence was positively associated with higher total and physical health QOL at follow-up. Exercise was not associated with total QOL and only marginally associated with physical health QOL, but was positively related to overall sense of well-being. Emphasizing that smoking cessation is associated with higher QOL may help motivate smokers to initiate quit attempts.

The Efficacy of Vigorous-Intensity Exercise as an Aid to Smoking Cessation in Adults With High Anxiety Sensitivity: A Randomized Controlled Trial.

OBJECTIVES: High anxiety sensitivity predicts poor smoking cessation outcomes. Aerobic exercise reduces anxiety sensitivity and aspects of the risk conferred by anxiety sensitivity. In the current study, we examined whether exercise can aid smoking cessation in adults with high anxiety sensitivity. METHODS: Participants were sedentary and low-activity adult daily smokers (n = 136) with elevated prescreen anxiety sensitivity. Participants received 15 weeks of standard smoking cessation treatment (ST; cognitive behavioral therapy plus nicotine replacement therapy). In addition, participants were simultaneously randomized to 15 weeks of either an exercise intervention (ST + EX; n = 72) or a wellness education control condition (ST + CTRL; n = 64). Self-reported smoking abstinence was assessed weekly during the intervention, at the end of treatment (10 weeks after the target quit date), and at 4 and 6 months after the target quit date. Abstinence was verified by expired carbon monoxide readings and saliva cotinine. RESULTS: Results indicated that point prevalence abstinence (PPA) and prolonged abstinence (PA) rates were significantly higher for ST + EX than for ST + CTRL at each of the major end points among persons with high anxiety sensitivity (PPA: b = -0.91, standard error [SE] = 0.393, t(1171) = -2.33, p = .020; PA: b = -0.98, SE = 0.346, t(132) = -2.84, p = .005), but not among those with low anxiety sensitivity (PPA: b = -0.23, SE = 0.218, t(1171) = -1.06, p = .29; PA: b = -0.31, SE = 0.306, t(132) = -1.01, p = .32). CONCLUSIONS: The present results suggest that exercise facilitates the odds of quit success for smokers with high levels of anxiety sensitivity and therefore may be a useful therapeutic tactic for this high-risk segment of the smoking population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01065506.

Genetic toxicity assessment of engineered nanoparticles using a 3D in vitro skin model (EpiDerm™).

BACKGROUND: The rapid production and incorporation of engineered nanomaterials into consumer products alongside research suggesting nanomaterials can cause cell death and DNA damage (genotoxicity) makes in vitro assays desirable for nanosafety screening. However, conflicting outcomes are often observed when in vitro and in vivo study results are compared, suggesting more physiologically representative in vitro models are required to minimise reliance on animal testing. METHOD: BASF Levasil® silica nanoparticles (16 and 85 nm) were used to adapt the 3D reconstructed skin micronucleus (RSMN) assay for nanomaterials administered topically or into the growth medium. 3D dose-responses were compared to a 2D micronucleus assay using monocultured human B cells (TK6) after standardising dose between 2D / 3D assays by total nanoparticle mass to cell number. Cryogenic vitrification, scanning electron microscopy and dynamic light scattering techniques were applied to characterise in-medium and air-liquid interface exposures. Advanced transmission electron microscopy imaging modes (high angle annular dark field) and X-ray spectrometry were used to define nanoparticle penetration / cellular uptake in the intact 3D models and 2D monocultured cells. RESULTS: For all 2D exposures, significant (p < 0.002) increases in genotoxicity were observed (≥100 µg/mL) alongside cell viability decreases (p < 0.015) at doses ≥200 µg/mL (16 nm-SiO2) and ≥100 µg/mL (85 nm-SiO2). In contrast, 2D-equivalent exposures to the 3D models (≤300 µg/mL) caused no significant DNA damage or impact on cell viability. Further increasing dose to the 3D models led to probable air-liquid interface suffocation. Nanoparticle penetration / cell uptake analysis revealed no exposure to the live cells of the 3D model occurred due to the protective nature of the skin model's 3D cellular microarchitecture (topical exposures) and confounding barrier effects of the collagen cell attachment layer (in-medium exposures). 2D monocultured cells meanwhile showed extensive internalisation of both silica particles causing (geno)toxicity. CONCLUSIONS: The results establish the importance of tissue microarchitecture in defining nanomaterial exposure, and suggest 3D in vitro models could play a role in bridging the gap between in vitro and in vivo outcomes in nanotoxicology. Robust exposure characterisation and uptake assessment methods (as demonstrated) are essential to interpret nano(geno)toxicity studies successfully.

The Role of Self-Efficacy, Adaptive Coping, and Smoking Urges in Long-Term Cessation Outcomes.

OBJECTIVE: Smoking cessation self-efficacy and adaptive coping are posited as two important treatment targets in smoking cessation interventions, especially in the context of handling strong urges to smoke. Yet, less is known about whether intervention-related changes in these constructs predict long-term smoking outcomes. The current study aimed to examine changes in smoking urges, smoking cessation self-efficacy, and adaptive coping following a health-focused and cognitive-behavioral telephone-delivered smoking cessation treatment, and the association to smoking reduction during long-term, 12-month follow-up. METHODS: Participants (n = 61) were daily smokers enrolled in a 12-week pilot trial that tested the efficacy of two different health-focused interventions with an adjunct of traditional telephone-delivered cessation counseling. Smoking urges, smoking cessation self-efficacy, and adaptive coping were assessed as baseline and immediately post-treatment. Average of seven-day cigarettes use per day were assessed at post-treatment, and 6- and 12-months post-baseline follow-up timepoints. RESULTS: Smoking urges were significantly lower post-treatment, and smoking cessation self-efficacy and adaptive coping were significantly higher post-treatment, relative to baseline. After adjusting for baseline values, post-treatment smoking urges were significantly positively associated with cigarette use at post-treatment and 6-month follow-up. Post-treatment smoking cessation self-efficacy, but not adaptive coping, was significantly negatively predictive of cigarette use at post-treatment and 6- and 12-month follow-up timepoints. Post-treatment smoking cessation self-efficacy emerged as significant indirect predictor of the association between post-treatment smoking urges and post-treatment cigarette use. CONCLUSIONS: Interventions that target smoking cessation self-efficacy may facilitate long-term reductions in smoking among daily smokers undergoing a quit attempt.

Positive Psychotherapy for Smoking Cessation: A Pilot Randomized Controlled Trial.

OBJECTIVE: Greater depressive symptoms and low positive affect (PA) are associated with poor smoking cessation outcomes. Smoking cessation approaches that incorporate a focus on PA may benefit smokers trying to quit. The purpose of this study was to conduct a pilot randomized clinical trial to compare standard smoking cessation treatment (ST) with smoking cessation treatment that targets positive affect, termed positive psychotherapy for smoking cessation (PPT-S). METHOD: Smokers who were seeking smoking cessation treatment were assigned by urn randomization to receive, along with 8 weeks of nicotine replacement therapy, either ST (n = 31) or PPT-S (n = 35). Seven-day point prevalence smoking abstinence was biochemically confirmed at 8, 16, and 26 weeks. RESULTS: Compared to ST, a greater percentage of participants in PPT-S were abstinent at 8 weeks, 16 weeks, and 26 weeks, but these differences were nonsignificant. In a more statistically powerful longitudinal model, participants in PPT-S had a significantly higher odds of abstinence (adjusted odds ratio [AOR] = 2.75; 95% CI = 1.02, 7.42; p = .046) across follow-ups compared to those in ST. The positive effect of PPT-S was stronger for those higher in PA (OR = 6.69, 95% CI = 1.16, 38.47, p = .03). Greater use of PPT-S strategies during the initial 8 weeks of quitting was associated with a less steep decline in smoking abstinence rates over time (OR = 2.64, 95% CI = 1.06, 6.56, p =.04). CONCLUSION: This trial suggests substantial promise for incorporating PPT into smoking cessation treatment.

Gender differences in a randomized controlled trial treating tobacco use among adolescents and young adults with mental health concerns.

INTRODUCTION: Treatment of tobacco use in mental health settings is rare despite high rates of comorbidity. With a focus on early intervention, we evaluated a tobacco treatment intervention among adolescents and young adults recruited from outpatient, school-based, and residential mental health settings and tested for gender differences. METHODS: Intervention participants received computerized motivational feedback at baseline, 3 months, and 6 months and were offered 12 weeks of cessation counseling and nicotine patches. Usual care participants received a self-help guide and brief cessation advice. We examined 7-day point prevalence abstinence with biochemical confirmation at 3, 6, and 12 months; smoking reduction; and 24-hr quit attempts. RESULTS: At baseline, the sample (N = 60, 52% female, mean age = 19.5±2.9 years, 40% non-Hispanic Caucasian) averaged 7±6 cigarettes/day, 62% smoked daily, 38% smoked ≤ 30 min of waking, 12% intended to quit in the next month, 47% had a parent who smoked, and 3 of 5 of participants' closest friends smoked on average. During the 12-month study, 47% of the sample reduced their smoking, 80% quit for 24 hr, and 11%, 13%, and 17% confirmed 7-day point prevalence abstinence at 3-, 6-, and 12-month follow-up, respectively, with no differences by treatment condition (ps > .400). Over time, abstinence was greater among girls (adjusted odds ratio [AOR] = 8.9) than among boys, and abstinence was greater for lighter smokers than heavier smokers (AOR = 4.5) (p < .05). No mental health or other measured variables predicted abstinence. CONCLUSIONS: Adolescent and young adult smokers with mental health concerns are a challenging group to engage and to effectively treat for tobacco addiction, particularly heavier smokers and boys. Innovative approaches are needed.