Development and evaluation of visualizations of smoking data for integration into the Sense2Quit app for tobacco cessation.

IMPORTANCE: Due to insufficient smoking cessation apps for persons living with HIV, our study focused on designing and testing the Sense2Quit app, a patient-facing mHealth tool which integrated visualizations of patient information, specifically smoking use. OBJECTIVES: The purpose of this paper is to detail rigorous human-centered design methods to develop and refine visualizations of smoking data and the contents and user interface of the Sense2Quit app. The Sense2Quit app was created to support tobacco cessation and relapse prevention for people living with HIV. MATERIALS AND METHODS: Twenty people living with HIV who are current or former smokers and 5 informaticians trained in human-computer interaction participated in 5 rounds of usability testing. Participants tested the Sense2Quit app with use cases and provided feedback and then completed a survey. RESULTS: Visualization of smoking behaviors was refined through each round of usability testing. Further, additional features such as daily tips, games, and a homescreen were added to improve the usability of the app. A total of 66 changes were made to the Sense2Quit app based on end-user and expert recommendations. DISCUSSION: While many themes overlapped between usability testing with end-users and heuristic evaluations, there were also discrepancies. End-users and experts approached the app evaluation from different perspectives which ultimately allowed us to fill knowledge gaps and make improvements to the app. CONCLUSION: Findings from our study illustrate the best practices for usability testing for development and refinement of an mHealth-delivered consumer informatics tool for improving tobacco cessation yet further research is needed to fully evaluate how tools informed by target user needs improve health outcomes.

Pilot Testing of an mHealth App for Tobacco Cessation in People Living With HIV: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: An estimated 40% of people living with HIV smoke cigarettes. Although smoking rates in the United States have been declining in recent years, people living with HIV continue to smoke cigarettes at twice the rate of the general population. Mobile health (mHealth) technology is an effective tool for people living with a chronic illness, such as HIV, as currently 84% of households in the United States report that they have a smartphone. Although many studies have used mHealth interventions for smoking cessation, few studies have recruited people living with HIV who smoke. OBJECTIVE: The objective of the pilot randomized controlled trial (RCT) is to examine the feasibility, acceptability, and preliminary efficacy of the Sense2Quit App as a tool for people living with HIV who are motivated to quit smoking. METHODS: The Sense2Quit study is a 2-arm RCT for people living with HIV who smoke cigarettes (n=60). Participants are randomized to either the active intervention condition, which consists of an 8-week supply of nicotine replacement therapy, standard smoking cessation counseling, and access to the Sense2Quit mobile app and smartwatch, or the control condition, which consists of standard smoking cessation counseling and a referral to the New York State Smokers' Quitline. The Sense2Quit app is a mobile app connected through Bluetooth to a smartwatch that tracks smoking gestures and distinguishes them from other everyday hand movements. In the Sense2Quit app, participants can view their smoking trends, which are recorded through their use of the smartwatch, including how often or how much they smoke and the amount of money that they are spending on cigarettes, watch videos with quitting tips, information, and distractions, play games, set reminders, and communicate with a study team member. RESULTS: Enrollment of study participants began in March 2023 and is expected to end in October 2023. All data collection is expected to be completed by the end of January 2024. This RCT will test the difference in outcomes between the control and intervention arms. The primary outcome will be the percentage of participants with biochemically verified 7-day point prevalence smoking or tobacco abstinence at their 12-week follow-up. Results from this pilot study will be disseminated to the research community following the completion of all data collection. CONCLUSIONS: The Sense2Quit study leverages mHealth so that it can help smokers improve their efforts at smoking cessation. Our research has the potential to not only increase quitting rates among people living with HIV who may need a prolonged, tailored intervention but also inform further development of mHealth for people living with HIV. This mHealth study will contribute significant findings to the greater mHealth research community, providing evidence as to how mHealth should be developed and tested among the target population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05609032; https://clinicaltrials.gov/study/NCT05609032. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49558.

Mifepristone as a pharmacological intervention for stress-induced alcohol craving: A human laboratory study.

Preclinical and clinical work suggests that mifepristone may be a viable treatment for alcohol use disorder (AUD). This was a Phase 1/2, outpatient, cross-over, randomized, double-blind, placebo-controlled trial with non-treatment-seeking individuals with AUD (N = 32). We assessed safety, alcohol craving and consumption, after 1-week mifepristone 600 mg/day administration, in a human laboratory study comprised of a single oral yohimbine administration (32.4 mg), a cue-reactivity procedure and alcohol self-administration. Safety was monitored by adverse events and hemodynamic parameters, alcohol craving by alcohol craving questionnaire and cue-induced saliva output. During the alcohol self-administration, we assessed alcohol pharmacokinetics, subjective effects and consumption. Outcomes were assessed using Generalized Estimating Equations and mediation analysis. Mild-moderate adverse events were reported in both conditions. There was no statistically significant difference between mifepristone and placebo in alcohol pharmacokinetics and subjective effects. Furthermore, blood pressure increased only in the placebo condition after the stress-induced laboratory procedures. Mifepristone, compared to placebo, significantly reduced alcohol craving and increased cortisol levels. Mifepristone-induced cortisol increase was not a mediator of alcohol craving. Mifepristone, compared to placebo, did not reduce alcohol consumption in the laboratory or in a naturalistic setting. This study successfully translated a developed preclinical procedure to a human laboratory study, confirming the safety of mifepristone in people with AUD and providing evidence to its role in reducing alcohol craving under stress procedures. The lack of effects on alcohol drinking may be related to the selection of non-treatment seekers and suggests future treatment-oriented trials should investigate mifepristone in people with AUD.

Theoretically Guided Iterative Design of the Sense2Quit App for Tobacco Cessation in Persons Living with HIV.

The use of mobile health (mHealth technology) can be an effective intervention when considering chronic illnesses. Qualitative research methods were used to identify specific content and features for a mobile app for smoking cessation amongst people living with HIV (PWH). We conducted five focus group sessions followed by two Design Sessions with PWH who were or are currently chronic cigarette smokers. The first five groups focused on the perceived barriers and facilitators to smoking cessation amongst PWH. The two Design Sessions leveraged the findings from the focus group sessions and were used to determine the optimal features and user interface of a mobile app to support smoking cessation amongst PWH. Thematic analysis was conducted using the Health Belief Model and Fogg's Functional Triad. Seven themes emerged from our focus group sessions: history of smoking, triggers, consequences of quitting smoking, motivation to quit, messages to help quit, quitting strategies, and mental health-related challenges. Functional details of the app were identified during the Design Sessions and used to build a functional prototype.

App-Delivered Mindfulness Training to Reduce Anxiety in People with HIV Who Smoke: A One-Armed Feasibility Trial.

INTRODUCTION: People with HIV (PWH) who smoke have reported that managing anxiety is a barrier to making a quit attempt and maintaining abstinence post-quit. This study examined the feasibility and acceptability of an app-based mindfulness intervention, Unwinding Anxiety, to reduce anxiety prior to a quit attempt in PWH who were not planning to quit in the next 30 days. METHODS: Sixteen PWH (mean age 51.5 [SD = 13.2]; mean cigarettes per day 11.4 [SD = 5.4]) were enrolled and followed for eight weeks. A smartphone-based app with 30 modules designed to reduce anxiety was introduced at baseline; participants were encouraged to complete one module daily for four weeks. Symptoms of anxiety and readiness to quit smoking were measured at baseline and weeks 4 and 8. The mean number of modules completed, session attendance, and number of study completers were examined. Generalized estimating equations (GEE) were used to examine changes in self-reported anxiety and readiness to quit at baseline, week 4, and week 8. A brief qualitative interview was conducted at week 4 to explore the acceptability of the app. RESULTS: Feasibility was high, with 93% of participants completing the study. The mean number of study sessions completed was 2.7 (SD = 0.59), and the mean number of modules completed was 16.0 (SD 16.8). Anxiety was high at baseline (M = 14.4, SD = 3.9), but lower at week 4 (b = -5.5; CI: [-9.4, -1.7]; p = 0.004) and week 8 (b = -5.1; CI: [-8.8, -1.3]; p = 0.008), and stable between weeks 4 and 8 (b = 0.48; CI: [-2.0, 3.0]; p = 0.706). Readiness to quit significantly increased from baseline M = 5.5 (SD = 1.6) to week 4 (b = 0.56; CI: [0.20, 0.91]; p = 0.002) but was not significantly different from baseline at week 8 (b = 0.34; CI: [-0.30, 1.0]; p = 0.30). Ad-hoc moderation analyses found that anxiety had a small significantly positive association with readiness to quit at baseline (main effect: b = 0.10; SE = 0.03; p < 0.001) and significantly attenuated the increase in readiness to quit observed at week 4 (anxiety by week 4 interaction: b = -0.08; SE = 0.03; p = 0.009). CONCLUSIONS: App-based mindfulness training appears to be feasible and acceptable for PWH who smoke and report baseline anxiety. At week 4, anxiety was reduced and readiness to quit was increased, perhaps a key time point for a smoking cessation attempt.

Mifepristone as a pharmacological intervention for stress-Induced alcohol craving: a translational crossover randomized trial.

Preclinical and clinical work suggests that mifepristone (glucocorticoid receptor antagonist), may be a viable treatment for alcohol use disorder (AUD). The aim of this work was to translate our preclinical mifepristone study using yohimbine (α2 receptor antagonist) stress-induced reinstatement of alcohol-seeking to a clinical setting. This was a Phase 1/2, outpatient, cross-over, randomized, double-blind, placebo-controlled trial with non-treatment-seeking individuals with AUD ( N =32). We investigated the safety, alcohol craving and consumption after oral administration of mifepristone (600mg daily for a week) in a human laboratory study comprised of administration of yohimbine in a cue-reactivity procedure and alcohol self-administration. Outcomes were assessed using Generalized Estimating Equations and mediation and moderation analyses assessed mechanisms of action and precision medicine targets. We did not observe serious adverse events related to the study drugs or study procedure and mild to moderate non-serious adverse events were reported by both study conditions. Also, there was no statistically-significant difference between the mifepristone and placebo in the hemodynamic response, alcohol subjective effects and pharmacokinetics parameters. Mifepristone significantly reduced alcohol craving and increased cortisol levels. Mifepristone-induced cortisol increase was not a mediator of alcohol craving. Moderation analysis with family history density of AUD (FHDA) and mifepristone, suggested that reduced craving was present in individuals with low , but not high FHDA. Mifepristone, compared to placebo, did not reduce alcohol consumption in the laboratory or in a naturalistic setting. This study successfully translated a preclinical paradigm to a human laboratory study confirming safety, tolerability and efficacy of mifepristone in an alcohol paradigm. Mediation analysis showed that the effect of mifepristone on craving was not related to mifepristone-induced increases in cortisol and moderation of FHDA suggested the importance of evaluating AUD endophenotypes for pharmacotherapies. Clinical trial registration: Clinicaltrials.gov ; NCT02243709. IND/FDA: 121984, mifepristone and yohimbine (Holder: Haass-Koffler).

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.

The Impact of the COVID-19 Pandemic on Stress, Isolation, Smoking Behaviors, and Motivation to Quit in People with HIV Who Smoke.

People with HIV (PWH) smoke at higher rates compared with the general population and have lower cessation rates. The primary aim of this study was to examine the impact of the COVID-19 pandemic on smoking in PWH. A survey was administered to participants in two smoking cessation trials in the United States. Mean cigarettes per day was 13.9 (SD 8.6), and participants reported they had smoked on average for 30.93 years (SD 10.4). More than half (55.7%) of participants (N = 140) reported not changing their smoking during the pandemic, while 15% reported decreasing, and 25% reported increasing their smoking. In bivariate analyses, worrying about food due to lack of money (χ2 = 9.13, df 2, p = 0.01) and greater Covid-related worry (rs = 0.19, p = 0.02) were significantly associated with increased smoking. Qualitative research may be needed to more clearly elucidate factors related to smoking behaviors among PWH.

A Smoking Cessation Mobile App for Persons Living With HIV: Preliminary Efficacy and Feasibility Study.

BACKGROUND: The prevalence of smoking in the United States general population has gradually declined to the lowest rate ever recorded; however, this has not been true for persons with HIV. OBJECTIVE: We conducted a pilot test to assess the feasibility and efficacy of the Lumme Quit Smoking mobile app and smartwatch combination with sensing capabilities to improve smoking cessation in persons with HIV. METHODS: A total of 40 participants were enrolled in the study and randomly assigned 1:1 to the control arm, which received an 8-week supply of nicotine replacement therapy, a 30-minute smoking cessation counseling session, and weekly check-in calls with study staff, or to the intervention arm, which additionally received the Lumme Quit Smoking app and smartwatch. RESULTS: Of the 40 participants enrolled, 37 completed the follow-up study assessments and 16 used the app every day during the 56-day period. During the 6-month recruitment and enrollment period, 122 people were screened for eligibility, with 67.2% (82/122) deemed ineligible. Smoking criteria and incompatible tech were the major reasons for ineligibility. There was no difference in the proportion of 7-day point prevalence abstinence by study arm and no significant decrease in exhaled carbon monoxide for the intervention and control arms separately. However, the average exhaled carbon monoxide decreased over time when analyzing both arms together (P=.02). CONCLUSIONS: Results suggest excellent feasibility and acceptability of using a smoking sensor app among this smoking population. The knowledge gained from this research will enable the scientific community, clinicians, and community stakeholders to improve tobacco cessation outcomes for persons with HIV. TRIAL REGISTRATION: ClinicalTrials.gov NCT04808609; https://clinicaltrials.gov/ct2/show/NCT04808609.

Peer navigation for smoking cessation in smokers with HIV: Protocol for a randomized clinical trial.

BACKGROUND: Smoking prevalence in persons with HIV (PWH) is high (40%) and cessation rates remain low. Lack of social support and poor adherence to nicotine replacement therapy (NRT) are related to poor cessation outcomes; thus, both factors represent possible targets for smoking cessation interventions. Peer navigators (PNs) have been integrated into HIV care with great success to improve engagement and adherence to antiretroviral therapy. However, no clinical trial has evaluated the potential for PNs to provide social support and improve NRT adherence for smoking cessation. We developed a treatment protocol that targets social support, adherence, and self-efficacy for quitting by incorporating PNs into a smoking cessation program. This randomized trial will test whether this approach results in higher rates of 7-day point prevalence abstinence at 12- and 24-weeks, compared to standard treatment. METHODS: Seventy-two smokers with HIV will be randomized to either Peer Navigation Social Support for smoking cessation (PNSS-S) or standard cessation counseling. All participants will meet with a nurse for a smoking cessation counseling session, which will include discussion of FDA-approved cessation pharmacotherapy. Participants assigned to PNSS-S will receive weekly phone calls from the PN for 12 weeks. The PN will address readiness to quit, using medication to quit, common barriers to cessation, high risk situations, slip management, and maintaining abstinence. Smoking cessation outcomes will be measured at 4, 12, and 24 weeks following the baseline appointment. CONCLUSION: Results from this study will provide preliminary evidence of whether incorporating a peer navigator-based intervention into smoking cessation treatment can improve smoking cessation outcomes in PWH.

Psychometric Analysis of a Microenvironment Secondhand Smoke Exposure Questionnaire.

BACKGROUND: We conducted a psychometric analysis of an adapted secondhand smoke (SHS) questionnaire by testing the three-component structure of the original scale that measures SHS exposure in home, work and social environments. METHODS: The 15-item questionnaire was administered to 839 daily smokers participating in a multi-site randomized controlled trial. Following parallel analysis, we conducted a confirmatory factor analysis specifying a three-factor structure. Cronbach's alphas and fit indices were calculated to assess internal consistency. Criterion validity was assessed by comparing the Social environments subscale to the Brief Wisconsin Inventory of Smoking Dependence Motives Social/Environmental Goads subscale. Predicative validity of the questionnaire was assessed using linear regressions and tobacco biomarkers of harm; NNAL, expired carbon monoxide and total cotinine. RESULTS: Five items did not load onto any factor and were dropped, resulting in a 10-item questionnaire. The Cronbach's alphas were (0.86), (0.77) and (0.67) for the Work, Social, and Home subscales, respectively. The WISDM subscale was moderately correlated with scores on the Social subscale (r = 0.57, p < 0.001). The questionnaire demonstrated predictive validity of smoke exposure above individual's own reported use as measured by cigarettes smoked per day. CONCLUSIONS: Three constructs emerged; results indicate that a shortened 10-item scale could be used in future studies.

A Review of Chronic Comorbidities in Adults Living With HIV: State of the Science.

ABSTRACT: People living with HIV are living longer, high-quality lives; however, as they age, this population is at increased risk for developing chronic comorbidities, including cardiovascular disease, certain types of cancer (e.g., lung, anal, and liver), and diabetes mellitus. The purpose of this state-of-the-science review is to provide an evidence-based summary on common physical comorbidities experienced by people living and aging with HIV. We focus on those chronic conditions that are prevalent and growing and share behavioral risk factors that are common in people living with HIV. We will discuss the current evidence on the epidemiology, physiology, prevention strategies, screening, and treatment options for people living with HIV across resource settings.

Personalized feedback improves cardiovascular risk perception and physical activity levels in persons with HIV: results of a pilot randomized clinical trial.

People with HIV (PWH) have an elevated risk for cardiovascular disease (CVD) compared with the general population. This study examined the feasibility, acceptability and preliminary efficacy of a tailored intervention aimed at increasing CVD risk perception and the adoption of heart-healthy behaviors in PWH. Forty adults were randomized to receive personalized feedback on CVD risk and discussion of risk reduction or health education. Participants were issued pedometers and seen for two treatment sessions. Participants were 60% male and had a mean age of 51.5 years. Ninety percent of participants completed all study sessions indicating good feasibility and acceptability. A medium effect size for the difference between treatment and control groups was found on both the Perceived Risk for Heart Disease (d = .38) and the Rapid Eating and Activity for Patients scales (d = .56) at 12 weeks. Atherosclerotic cardiovascular disease (ASCVD) risk score moderated the effect of treatment, such that at high (but not low) ASCVD risk, active intervention, compared to control, was associated with a greater increase in steps between baseline and both 8 (d = .38) and 12 weeks (d = .55). Findings provide preliminary evidence that tailored interventions delivered by nurses may be effective for primary prevention of CVD in PWH.

The United States National Cancer Institute's Coordinated Research Effort on Tobacco Use as a Major Cause of Morbidity and Mortality among People with HIV.

The use of antiretroviral therapy for people with HIV (PWH) has improved life expectancy. However, PWH now lose more life-years to tobacco use than to HIV infection. Unfortunately, PWH smoke at higher rates and have more difficulty maintaining abstinence than the general population, compounding their risk for chronic disease. In this Commentary, we describe a United States National Cancer Institute-led initiative to address the relative lack of research focused on developing, testing, and implementing smoking cessation interventions for PWH. This initiative supports seven clinical trials designed to systematically test and/or develop and test adaptations of evidence-based smoking cessation interventions for PWH (eg, combination of behavioral and pharmacological). We summarize each project, including setting/recruitment sites, inclusion/exclusion criteria, interventions being tested, and outcomes. This initiative provides critical opportunities for collaboration and data harmonization across projects. The knowledge gained will inform strategies to assist PWH to promote and maintain abstinence, and ensure that these efforts are adaptable and scalable, thereby addressing one of the major threats to the health of PWH. Reducing smoking behavior may be particularly important during the COVID-19 pandemic given that smokers who become infected with SARS-CoV-2 may be at risk for more severe disease. IMPLICATIONS: This Commentary describes a National Cancer Institute-led initiative to advance the science and practice of treating tobacco use among PWH, which is now responsible for more life years lost than HIV. We describe the scope of the problem, the objectives of the initiative, and a summary of the seven funded studies. Harmonization of data across projects will provide information related to treatment mediators and moderators that was not previously possible. Stakeholders interested in tobacco cessation, including researchers, clinicians and public health officials, should be aware of this initiative and the evidence-base it will generate to advance tobacco treatment among this high-risk population.

Changes in Cigarette Consumption With Reduced Nicotine Content Cigarettes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage: 3 Randomized Clinical Trials.

Importance: This study is part of a programmatic effort evaluating the effects of reducing nicotine content of cigarettes to minimally addictive levels. Objective: To examine whether very low-nicotine-content (VLNC) cigarettes decrease smoking rates and dependence severity among smokers with psychiatric disorders or socioeconomic disadvantage. Design, Setting, and Participants: These 3 randomized clinical trials were performed at the University of Vermont, Brown University, and Johns Hopkins University between October 2016 and September 2019. Participants received 12 weeks of exposure to study cigarettes with nicotine content ranging from levels representative of commercial cigarettes (15.8 mg nicotine/g tobacco) to less than a hypothesized addiction threshold (2.4 mg/g and 0.4 mg/g). Daily smokers from 3 at-risk populations participated: individuals with affective disorders, exemplifying smokers with mental illness; individuals with opioid use disorder, exemplifying smokers with substance use disorders; and women with high school educations or less, exemplifying smokers with socioeconomic disadvantage. Data were analyzed from September 2019 to July 2020. Interventions: Random assignment to 1 of 3 study cigarettes provided weekly at no cost for 12 weeks. Main Outcomes and Measures: The primary outcome was between-group differences in mean total cigarettes smoked daily (CPD) during week 12; secondary outcomes included CPD for study and nonstudy cigarettes and dependence severity across weeks analyzed using analysis of covariance, random coefficients growth modeling, or repeated measures analysis of variance. Results: A total of 775 participants were included (mean [SD] age, 35.59 [11.05] years; 551 [71.10%] women [owing to 1 population being exclusively women]); participants smoked a mean (SD) of 17.79 (9.18) CPD at study intake. A total of 286 participants were randomized to 0.4 mg/g, 235 participants were randomized to 2.4 mg/g, and 254 participants were randomized to 15.8 mg/g. Participants randomized to VLNC cigarettes had decreased mean [SEM] total CPD during week 12 across populations (Cohen d = 0.61; P < .001). At week 12, mean (SEM) CPD decreased to 17.96 (0.98) CPD in the 0.4 mg/g group and to 19.53 (1.07) CPD in the 2.4 mg/g group, both of which were significantly different from the 15.8 mg/g group (25.08 [1.08] CPD at week 12) but not each other (0.4 mg/g adjusted mean difference: -7.54 [95%CI, -9.51 to -5.57]; 2.4 mg/g adjusted mean difference: -5.34 [95% CI, 7.41 to -3.26]). Several secondary outcomes differed across populations randomized to VLNCs, including mean total CPD across weeks, with linear trends lower in participants receiving 0.4 mg/g (-0.28 [95%CI, -0.39 to -0.18]; P < .001) and 2.4 mg/g (-0.13 [95%CI, -0.25 to -0.01]; P < .001) doses compared with those receiving the 15.8 mg/g dose (0.30 [95% CI, 0.19 to 0.41]). Fagerström Test of Nicotine Dependence mean total scores were significantly lower in participants who received VLNCs (Cohen d = 0.12; P < .001), with those who received the 0.4 mg/g dose (mean [SD] score, 3.99 [0.06]; P < .001 vs 15.8 mg/g) or 2.4 mg/g dose (mean [SD] score, 4.07 [0.06]; P = .01 vs 15.8 mg/g) differing from those who received the 15.8 mg/g dose (mean [SD] score, 4.31 [0.06]) but not from each other. Conclusions and Relevance: These findings demonstrate that decreasing the nicotine content of cigarettes to very low levels reduced smoking rate and nicotine-dependence severity in these high-risk populations, effects that may facilitate successful cessation. Trial Registration: ClinicalTrials.gov Identifiers: NCT02232737, NCT02250664, NCT02250534.

Immune Response to an Acute Moderate Dose of Alcohol in Healthy Young Adults.

Prior research on alcohol and the immune system has tended to focus on binge doses or chronic heavy drinking. The aim of this single-session preliminary study was to characterize immune response to moderate alcohol (0.60 g alcohol per kilogram body weight) in healthy, nonchronic drinkers. The sample (N = 11) averaged 26.6 years of age and was balanced in gender. Plasma samples were collected at baseline and 1, 2 and 3 hours postconsumption. Markers of microbial translocation [lipopolysaccharide (LPS)] and innate immune response [LPS-binding protein (LBP), soluble cluster of differentiation 14 (sCD14), and selected cytokines] were measured using immunoassays. Participants completed self-report questionnaires on subjective alcohol response and craving. Linear mixed models were used to assess changes in biomarkers and self-report measures. Breath alcohol concentration peaked at 0.069 ± 0.008% 1 hour postconsumption. LPS showed a significant linear decrease. LBP and sCD14 showed significant, nonlinear (U-shaped) trajectories wherein levels decreased at 1 hour then rebounded by 3 hours. Of nine cytokines tested, only MCP-1 and IL-8 were detectable in ≥50% of samples. IL-8 did not change significantly. MCP-1 showed a significant linear decrease and also accounted for significant variance in alcohol craving, with higher levels associated with stronger craving. Results offer novel evidence on acute immune response to moderate alcohol. Changes in LBP and sCD14, relative to LPS, may reflect their role in LPS clearance. Results also support further investigation into the role of MCP-1 in alcohol craving. Limitations include small sample size and lack of a placebo condition.

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.

Resilience is associated with importance of quitting in homeless adult smokers.

OBJECTIVE: The prevalence of cigarette smoking in homeless populations is disproportionately high with rates between 57 and 80%. Resilience may affect a smoker's ability to successfully quit smoking. This cross-sectional study examined the association between resilience levels and smoking behaviors in homeless adults. METHOD: Fifty-nine homeless adults were recruited from a large multi-service homelessness agency in the northeast United States. Surveys were administered to measure smoking behaviors and resilience. RESULTS: Most participants were current smokers (83.1%), with more than half (67.1%) identifying as "moderate smokers" (smoking 10-20 cigarettes per day). Of the current smokers, 93.9% reported smoking daily and 71.4% had tried to quit at least once in their lifetime. The number of quit attempts was significantly (p < 0.05) associated with one's contemplation of quitting (r = 0.29) and how one viewed importance of quitting (r = 0.33). Resilience levels were significantly associated with how participants ranked importance of quitting (r = 0.37). Smokers reported a high desire to quit smoking, but level of confidence in their ability to quit was low. Difficulty in finding stable housing and social support were reported as barriers to quitting. CONCLUSIONS: This study demonstrates an association between importance of quitting and resilience levels in homeless adult smokers. Future work is needed to examine whether resilience is related to successful smoking cessation in homeless adults, and whether resilience levels can be increased with targeted interventions.