Smoking abstinence and cessation-related outcomes one month after an immediate versus gradual reduction in nicotine content of cigarettes.

The United States Food and Drug Administration has the authority to reduce the nicotine content in cigarettes to minimal or non-addictive levels and could do so immediately or gradually over time. A large clinical trial compared the two approaches. This secondary analysis assesses abstinence and cessation-related outcomes one month after the trial concluded, when participants no longer had access to very low nicotine content (VLNC) research cigarettes. Smokers not interested in quitting (N = 1250) were recruited for the parent trial from 2014 to 2016 across 10 sites throughout the US and randomized to a 20-week study period during which they immediately switched to VLNC cigarettes, gradually transitioned to VLNC cigarettes with five monthly dose reductions, or smoked normal nicotine research cigarettes (control). At the one-month follow-up, both immediate and gradual reduction resulted in greater mean cigarette-free days (4.7 and 4.6 respectively) than the control group (3.2, both p < .05). Immediate reduction resulted in fewer mean cigarettes per day (CPD = 10.3) and lower Fagerström Test for Cigarette Dependence (FTCD = 3.7) than the gradual (CPD = 11.7, p = .001; FTCD = 3.8, p = .039) and control (CPD = 13.5, p < .001; FTCD = 4.0, p < .001) groups. Compared to controls, gradual reduction resulted in reduced CPD (p = .012) but not FTCD (p = .13). Differences in CO-verified 7-day point-prevalence abstinence were not significant. Findings demonstrate that switching to VLNC cigarettes resulted in reduced smoking and nicotine dependence severity that was sustained for at least a month after the VLNC trial period in smokers who were not interested in cessation. The greatest harm reduction endpoints were observed in those who immediately transitioned to VLNC cigarettes.

Educating the Public on the Health Risks of Very Low Nicotine Content Cigarettes: Results From a US-Based Convenience Sample.

INTRODUCTION: US FDA issued an advance notice of proposed rulemaking to reduce nicotine in cigarettes. To maximize the benefits of this potential standard, very low nicotine content (VLNC) cigarettes must be communicated in a way that does not result in misperceptions. AIMS AND METHODS: Adults (n = 567 who smoke; n = 610 non-smokers) from an online platform were randomized to a control message previously associated with accurate addictiveness perceptions of VLNC cigarettes but health misperceptions or to one of five messages that also included messaging on nicotine morbidity effects or VLNC cigarettes morbidity or mortality effects. p value <.01 was significant. RESULTS: In participants who smoke, perceived lung cancer risk (responses: 1, very little risk to 10, very high risk) if smoked VLNC cigarettes regularly was higher in conditions that communicated mortality effects of VLNC cigarettes compared to the control (7.12-7.18 vs. 5.97, p values < .01). In non-smokers, perceived lung cancer risk was higher in all five message conditions when compared with the control (7.58-8.22 vs. 6.35, p values < .01). Proportion who responded accurately (ie, False) to the statement Cigarettes with 95% less nicotine are safer than cigarettes with normal nicotine levels was higher in conditions describing VLNC morbidity or mortality effects when compared with the control in both participants who smoke (52.04-67.37% vs. 30.85%, p values < .01) and do not smoke (62.50-72.38% vs. 32.00%, p values < .01). CONCLUSIONS: Messaging on mortality effects of VLNC cigarettes (ie, cigarettes with 95% less nicotine are as deadly as current cigarettes) was associated with more accurate perceptions of the health risks of VLNC cigarettes than the control; however, misperceptions remained in one-third of participants. IMPLICATIONS: One approach to communicating a VLNC cigarette standard to the public is to include messaging on the mortality effects of VLNC cigarettes. However, further study and possible refinement of this message condition are recommended since approximately one-third of participants exposed to this message still perceived VLNC cigarettes to be safer than normal nicotine content cigarettes.

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.

The Impact of One-week Dietary Supplementation with Kava on Biomarkers of Tobacco Use and Nitrosamine-based Carcinogenesis Risk among Active Smokers.

Tobacco smoking is the primary risk factor for lung cancer, driven by the addictive nature of nicotine and the indisputable carcinogenicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as well as other compounds. The integration of lung cancer chemoprevention with smoking cessation is one potential approach to reduce this risk and mitigate lung cancer mortality. Experimental data from our group suggest that kava, commonly consumed in the South Pacific Islands as a beverage to promote relaxation, may reduce lung cancer risk by enhancing NNK detoxification and reducing NNK-derived DNA damage. Building upon these observations, we conducted a pilot clinical trial to evaluate the effects of a 7-day course of kava on NNK metabolism in active smokers. The primary objective was to compare urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL plus its glucuronides, major metabolites of NNK) before and after kava administration as an indicator of NNK detoxification. Secondary objectives included determining kava's safety, its effects on DNA damage, tobacco use, and cortisol (a biomarker of stress). Kava increased urinary excretion of total NNAL and reduced urinary 3-methyladenine in participants, suggestive of its ability to reduce the carcinogenicity of NNK. Kava also reduced urinary total nicotine equivalents, indicative of its potential to facilitate tobacco cessation. Plasma cortisol and urinary total cortisol equivalents were reduced upon kava use, which may contribute to reductions in tobacco use. These results demonstrate the potential of kava intake to reduce lung cancer risk among smokers.

Very Low Nicotine Content Cigarettes Disrupt the Feedback Loop of Affective States and Smoking Behavior.

INTRODUCTION: Smoking to reduce negative affect has been identified as a key motivational feature of tobacco use. Our recent work suggests that smoking very low nicotine content (VLNC) cigarettes reduces the relationship between negative affect and smoking behavior over a 6-week period. Here, we sought to extend our findings by evaluating whether a gradual or immediate approach to switching to VLNC cigarettes led to a differential reduction in the relationship between affect and smoking behavior over a longer (20-week) period. AIMS AND METHODS: Participants (n = 1250) were adult smokers from 10 US sites randomized to one of three groups: gradual nicotine reduction (15.5, 11.7, 5.2, 2.4, and 0.4 mg of nicotine per gram of tobacco [mg/g]), immediate nicotine reduction (0.4 mg/g), or standard nicotine content cigarettes (15.5 mg/g; control), for 20 weeks. We examined whether the relationship between affect-both negative and positive-and cigarettes per day differed as a function of reduction group. RESULTS: We found that both negative and positive affect were associated with cigarette consumption in the control group, but not in the gradual or immediate reduction groups across the 20 weeks of exposure. CONCLUSIONS: Our results extend previous findings that switching to VLNC cigarettes disrupts the relationship between affect and cigarette consumption by showing that either gradually or immediately reducing cigarette nicotine content achieves this disruption. These findings provide further evidence that switching to VLNC cigarettes reduces nicotine-related reinforcement of cigarette smoking. IMPLICATIONS: These findings support the notion that switching to very low nicotine content cigarettes reduces the association between affect and smoking behavior, and that either a gradual or immediate nicotine reduction approach achieves this reduction. This provides further evidence that switching to very low nicotine content cigarettes weakens reinforcement mechanisms associated with nicotine dependence.

Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure: A Randomized Clinical Trial.

Importance: The optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined. Objectives: To determine the effects of immediate vs gradual reduction in nicotine content to very low levels and as compared with usual nicotine level cigarettes on biomarkers of toxicant exposure. Design, Setting, and Participants: A double-blind, randomized, parallel-design study with 2 weeks of baseline smoking and 20 weeks of intervention was conducted at 10 US sites. A volunteer sample of daily smokers with no intention to quit within 30 days was recruited between July 2014 and September 2016, with the last follow-up completed in March 2017. Interventions: (1) Immediate reduction to 0.4 mg of nicotine per gram of tobacco cigarettes; (2) gradual reduction from 15.5 mg to 0.4 mg of nicotine per gram of tobacco cigarettes with 5 monthly dose changes; or (3) maintenance on 15.5 mg of nicotine per gram of tobacco cigarettes. Main Outcomes and Measures: Between-group differences in 3 co-primary biomarkers of smoke toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT, indicator of polycyclic aromatic hydrocarbons) calculated as area under the concentration-time curve over the 20 weeks of intervention. Results: Among 1250 randomized participants (mean age, 45 years; 549 women [44%]; 958 [77%] completed the trial), significantly lower levels of exposure were observed in the immediate vs gradual reduction group for CO (mean difference, -4.06 parts per million [ppm] [95% CI, -4.89 to -3.23]; P < .0055), 3-HPMA (ratio of geometric means, 0.83 [95% CI, 0.77 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.88 [95% CI, 0.83 to 0.93]; P < .0055). Significantly lower levels of exposure were observed in the immediate reduction vs control group for CO (mean difference, -3.38 [95% CI, -4.40 to -2.36]; P < .0055), 3-HPMA (ratio of geometric means, 0.81 [95% CI, 0.75 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.86 [95% CI, 0.81 to 0.92]; P < .0055). No significant differences were observed between the gradual reduction vs control groups for CO (mean difference, 0.68 [95% CI, -0.31 to 1.67]; P = .18), 3-HPMA (ratio of geometric means, 0.98 [95% CI, 0.91 to 1.06]; P = .64), and PheT (ratio of geometric means, 0.98 [95% CI, 0.92 to 1.04]; P = .52). Conclusions and Relevance: Among smokers, immediate reduction of nicotine in cigarettes led to significantly greater decreases in biomarkers of smoke exposure across time compared with gradual reduction or a control group, with no significant differences between gradual reduction and control. Trial Registration: clinicaltrials.gov Identifier: NCT02139930.

A Qualitative Study of Quality of Life Concerns following a Melanoma Diagnosis.

The goal of this study was to identify a relevant and inclusive list of quality of life issues among long-term survivors of melanoma. Individuals diagnosed with stage I-III cutaneous melanoma and had survived 1-5 years, ages 18-65 years at diagnosis, were recruited. Five focus groups were conducted with 33 participants in total. Discussions centered on participants' experiences at diagnosis, as well as ongoing physical, emotional, and social concerns, and behavioral changes since diagnosis. The majority of participants reported shock, fear, and feeling overwhelmed at the time of diagnosis. Some reported lingering physical concerns, including pain, numbness, and lymphedema, while a few reported no lasting issues. Emotional concerns were common, with most reporting anxiety. Several also noted feeling lonely and isolated. Social concerns included alteration of activities to avoid sun exposure, issues with family communication, and frustration with the lack of appreciation of the seriousness of melanoma by others. Finally, while many participants reported changes to their sun exposure and UV-protection behaviors, some reported little to no change. The shared experiences among participants in this study confirm the unique nature of melanoma and the need for interventions designed to improve the health and quality of life of melanoma survivors.

Sun Exposure and Protection Behaviors among Long-term Melanoma Survivors and Population Controls.

Introduction: Melanoma is considered a generally preventable cancer, with excessive ultraviolet radiation (UVR) exposure being a strong causal factor. UVR exposure following a melanoma diagnosis can be modified to reduce risk of second primary melanomas. The goal of this study was to compare measures of UVR exposure and protection behaviors between long-term melanoma survivors and controls.Methods: Participants from a previously conducted case-control study were recruited for a cross-sectional survey. Melanoma cases were 25 to 59 years old at diagnosis; controls were age and sex matched. Participants were asked about UVR exposure and protection measures used in the past year, and comparisons between melanoma survivors and controls were conducted using logistic regression models, adjusting for potential confounders.Results: A total of 724 (62.0%) long-term melanoma survivors and 660 (59.9%) controls completed the follow-up survey. Melanoma survivors were significantly less likely to report high sun exposure on a typical weekday [OR, 0.72 (0.55-0.94)], sunburns [OR, 0.40 (0.30-0.53)], or indoor tanning [OR, 0.20 (0.09-0.44)] than controls; however, high sun exposure on a typical weekend day was similar. Report of optimal sun protection behaviors was higher in melanoma survivors compared with controls. However, a few melanoma survivors reported indoor tanning, 10% reported intentionally seeking sun to tan, and 20% reported sunburns.Conclusions: Although long-term melanoma survivors reported healthier UVR exposure and protection behaviors compared with controls, a sizeable proportion still reported elevated sun exposure, sunburns, and suboptimal UVR protection behaviors.Impact: Opportunities remain for improving sun protection to reduce future melanoma risk among melanoma survivors. Cancer Epidemiol Biomarkers Prev; 26(4); 607-13. ©2017 AACR.

Comparison of quality of life among long-term melanoma survivors and non-melanoma controls: a cross-sectional study.

PURPOSE: Little is known about specific concerns facing long-term melanoma survivors. The goal of this study was to compare quality of life (QOL) and mental health between long-term melanoma survivors and population controls. METHODS: Participants from a previously conducted case-control study of risk factors for melanoma were recruited for a cross-sectional survey. Generic QOL and emotional health were measured using the SF-36 and Hospital Anxiety and Depression Scale questionnaires. A total of 724 melanoma survivors and 660 controls participated. Most melanoma survivors had stage I disease (85.6%); mean time from diagnosis was 9.6 ± 1.0 years. Comparisons of QOL measures between melanoma survivors and controls were conducted using regression models, adjusting for potential confounders. RESULTS: Melanoma survivors, compared to controls, reported statistically significant but only slightly higher physical functioning and bodily pain QOL subscale scores than controls and otherwise similar QOL as measured by the remaining six SF-36 subscale scores. Prevalence of anxiety (18.1% vs. 19.3%, adjusted OR = 1.00 (0.74, 1.36); p = 1.00) and depression (7.2% vs. 9.8%, adjusted OR = 0.74 (0.48, 1.16); p = 1.00) were similar between melanoma survivors and controls. CONCLUSION: Long-term early stage melanoma survivors report similar general QOL and mental health compared to population controls. Further research is needed to identify concerns more specific to melanoma.