Optimizing Longitudinal Tobacco Cessation Treatment in Lung Cancer Screening: A Sequential, Multiple Assignment, Randomized Trial.

Importance: Nearly half of the 14.8 million US adults eligible for lung cancer screening (LCS) smoke cigarettes. The optimal smoking cessation program components for the LCS setting are unclear. Objective: To assess the effect of adding a referral to prescription medication therapy management (MTM) to the tobacco longitudinal care (TLC) program among patients eligible for LCS who smoke and do not respond to early tobacco treatment and to assess the effect of decreasing the intensity of TLC among participants who do respond to early treatment. Design, Setting, and Participants: This randomized clinical trial included patients who currently smoked cigarettes daily and were eligible for LCS. Recruitment took place at primary care centers and LCS programs at 3 large health systems in the US and began in October 2016, and 18-month follow-up was completed April 2021. Interventions: (1) TLC comprising intensive telephone coaching and combination nicotine replacement therapy for 1 year with at least monthly contact; (2) TLC with MTM, MTM offered pharmacist-referral for prescription medications; and (3) Quarterly TLC, intensity of TLC was decreased to quarterly contact. Intervention assignments were based on early response to tobacco treatment (abstinence) that was assessed either 4 weeks or 8 weeks after treatment initiation. Main outcomes and Measures: Self-reported, 6-month prolonged abstinence at 18-month. Results: Of 636 participants, 228 (35.9%) were female, 564 (89.4%) were White individuals, and the median (IQR) age was 64.3 (59.6-68.8) years. Four weeks or 8 weeks after treatment initiation, 510 participants (80.2%) continued to smoke (ie, early treatment nonresponders) and 126 participants (19.8%) had quit (ie, early treatment responders). The 18 month follow-up survey response rate was 83.2% (529 of 636). Across TLC groups at 18 months follow-up, the overall 6-month prolonged abstinence rate was 24.4% (129 of 529). Among the 416 early treatment nonresponders, 6-month prolonged abstinence for TLC with MTM vs TLC was 17.8% vs 16.4% (adjusted odds ratio [aOR] 1.13; 95% CI, 0.67-1.89). In TLC with MTM, 98 of 254 participants (39%) completed at least 1 MTM visit. Among 113 early treatment responders, 6-month prolonged abstinence for Quarterly TLC vs TLC was 24 of 55 (43.6%) vs 34 of 58 (58.6%) (aOR, 0.54; 95% CI, 0.25-1.17). Conclusions and Relevance: In this randomized clinical trial, adding referral to MTM with TLC for participants who did not respond to early treatment did not improve smoking abstinence. Stepping down to Quarterly TLC among early treatment responders is not recommended. Integrating longitudinal tobacco cessation care with LCS is feasible and associated with clinically meaningful quit rates. Trial Registration: ClinicalTrials.gov Identifier: NCT02597491.

InCISE: Instrument for Comprehensive Incisional and Surgical Evaluation.

OBJECTIVE: The evaluation of healing after head and neck surgery is currently qualitative and non-standardized, limiting the quality of surgical healing assessments in clinical and research settings. We sought to develop an objective, standardized wound assessment score, and hypothesize that a reliable instrument can be developed to evaluate head and neck surgical wounds. METHODS: A prospective cohort study was conducted in a tertiary-care, academic head and neck surgery practice. Patients undergoing head and neck surgery were enrolled. A digital photograph protocol was developed for evaluating healing surgical wounds. A panel of experts developed and refined a wound healing score and established reliability, reproducibility, internal consistency, and validity of the score. RESULTS: InCISE: Instrument for comprehensive incisional and surgical evaluation was created. The utility of our wound healing score was assessed using classical test theory. We performed the major steps of establishing reliability in head and neck surgeons: (1) internal consistency (Cronbach's α = 0.81), (2) inter-observer reliability (intra-class correlation = 0.76), and (3) intra-rater reliability (intra-class correlation = 0.87), and content validity (through focus groups). Our composite measure was found to have strong internal consistency, inter-rater reliability, and intra-rater reliability. Preliminary work suggests criterion validity via associations with physical health related quality of life (SF-12). CONCLUSION: A wound healing score for head and neck surgery, InCISE, has been developed and is reliable, reproducible, and consistent. Although content validity is present and criterion validity is suggested, work continues to establish validity in this instrument to allow for expanded clinical and research use. LEVEL OF EVIDENCE: NA Laryngoscope, 133:2166-2173, 2023.

Design considerations and analytical framework for reliably identifying a beneficial individualized treatment rule.

An individualized treatment rule (ITR) formalizes personalized medicine by assigning treatment as a function of patients' clinical information, which contrasts with a static treatment rule that assigns everyone the same treatment. ITR identification has become a common aim in randomized clinical trials but sample size considerations for this aim are lacking. One approach is to select a sample size that will reliably identify an ITR with a performance close to the theoretical optimal rule. However, this approach could still lead to identifying ITRs that perform worse than the optimal static rule, particularly in the absence of substantial effect heterogeneity. This limitation motivates sample size considerations aimed at reliable identification of a beneficial ITR, which outperforms the optimal static rule, and analysis methods that identify the estimated optimal static rule when there is substantial uncertainty about whether an ITR will improve outcomes. To address these limitations, we propose a sample size approach based on the probability of identifying a beneficial ITR and introduce an approach for selecting the LASSO penalty parameter such that in the absence of treatment effect heterogeneity the estimated optimal static rule is identified with high probability. We apply these approaches to the PLUTO trial aimed at developing methods to assist with smoking cessation.

Latent constructs identified in older individuals who smoke cigarettes and are eligible for lung cancer screening: Factor analysis of baseline data from the PLUTO smoking cessation trial.

Introduction: Lung cancer screening (LCS) combined with smoking cessation intervention is currently recommended for older individuals with a history of heavy smoking. Tailoring tobacco treatment for this patient population of older, people who smoke (PWS) may improve cessation rates while efficiently using limited smoking cessation resources. Although some older people who smoke will need more intensive treatment to achieve sustained abstinence, others may be successful with less intensive treatment. A framework to identify them a priori would be helpful to distribute smoking cessation resources accordingly. Methods: Baseline demographic, smoking, and health data are reported from a randomized clinical trial of longitudinal smoking cessation interventions delivered in the setting of LCS. Candidate variables were factor analyzed to identify latent factors, or constructs, to identify subgroups of older participants among the heterogenous population of older people who smoke. Results: We identified three factor-derived constructs: self-reported health status, heaviness of smoking, and nicotine dependence. Nicotine dependence was moderately correlated with both of the other two factors. Conclusions: This factor analysis of baseline participant characteristics identified a set of latent constructs - based on a few practical clinical variables -- that can be used to classify the heterogenous population of older people who smoke to identify. We propose this framework to identify subgroups of people who smoke who might successfully quit with less intense treatment at the time of lung cancer screening.

National Cancer Institute Smoking Cessation at Lung Examination Trials Brief Report: Baseline Characteristics and Comparison With the U.S. General Population of Lung Cancer Screening-Eligible Patients.

Introduction: The National Cancer Institute Smoking Cessation at Lung Examination (SCALE) Collaboration includes eight clinical trials testing smoking cessation interventions delivered with lung cancer screening (LCS). This investigation compared pooled participant baseline demographic and smoking characteristics of seven SCALE trials to LCS-eligible smokers in three U.S. nationally representative surveys. Methods: Baseline variables (age, sex, race, ethnicity, education, income, cigarettes per day, and time to the first cigarette) from 3614 smokers enrolled in SCALE trials as of September 2020 were compared with pooled data from the Tobacco Use Supplement-Current Population Survey (2018-2019), National Health Interview Survey (2017-2018), and Population Assessment of Tobacco and Health (wave 4, 2016-2017) using the U.S. Preventive Services Task Force 2013 (N = 4803) and 2021 (N = 8604) LCS eligibility criteria. Results: SCALE participants have similar average age as the U.S. LCS-eligible smokers using the 2013 criteria but are 2.8 years older using the 2021 criteria (p < 0.001). SCALE has a lower proportion of men, a higher proportion of Blacks, and slightly higher education and income levels than national surveys (p < 0.001). SCALE participants smoke an average of 17.9 cigarettes per day (SD 9.2) compared with 22.4 (SD 9.3) using the 2013 criteria and 19.6 (SD 9.7) using the 2021 criteria (p < 0.001). The distribution of time to the first cigarette differs between SCALE and the national surveys (p < 0.001), but both indicate high levels of nicotine dependence. Conclusions: SCALE participants smoke slightly less than the LCS-eligible smokers in the general population, perhaps related to socioeconomic status or race. Other demographic variables reveal small but statistically significant differences, likely of limited clinical relevance with respect to tobacco treatment outcomes. SCALE trial results should be applicable to LCS-eligible smokers from the U.S. population.

Gender Distribution of Authors of Evaluation Letters for Promotion at One Medical School.

PURPOSE: Women remain underrepresented in key leadership positions and advanced ranks in academic medicine. This study examines the numbers of men and women letter writers for promotion candidates during a 5-year period across departments, tracks, ranks, and candidate gender. METHOD: A descriptive study characterized the gender of evaluation letter writers for candidates for promotion to associate or full professor at the University of Minnesota Medical School between 2015 and 2020. Letter writer and candidate gender were characterized by self-identified pronouns in the faculty biography or dossier. Letter writer gender was described by candidate department, promotion track, rank, terminal degree, and gender. RESULTS: Among 299 candidates for promotion, 172 (58%) were men and 127 (42%) were women; dossiers included 3,995 evaluation letters. Across all years, men wrote more letters than women (external letters, range, 69% in 2019-2020 to 75% in 2015-2016; internal letters, range, 67% in 2018-2019 to 77% in 2015-2016). Candidates in the family medicine and pediatrics departments had the highest percentages of letters written by women (44% and 40%, respectively). No differences were found in the number of women letter writers by candidate promotion track; however, differences were found by candidate rank (associate professor, 30%; full professor, 23%) and terminal degree (MD/DO, 25%; PhD, 33%; MD-PhD, 20%). Regardless of candidate gender, most evaluation letters were written by men. Women candidates had 15% to 20% more letters authored by women than men candidates (34%-40% vs 18%-23%). CONCLUSIONS: The gender pattern of letter writers may reflect implicit biases regarding gender and perceived leadership status, expertise, and success. Adopting policies that promote or require gender diversity among letter writers for promotion candidates may provide an opportunity to encourage faculty to seek diverse networks and recognize the achievements of women faculty.

Smoking reduction among homeless smokers in a randomized controlled trial targeting cessation.

INTRODUCTION: Homeless populations have high rates of smoking and unique barriers to quitting. General cessation strategies have been unsuccessful in this population. Smoking reduction may be a good intermediate goal. We conducted a secondary analysis to identify predictors of smoking reduction in a cohort of homeless smokers enrolled in a 26-week randomized clinical trial (RCT) targeting smoking cessation. METHODS: Data are from an RCT comparing motivational interviewing counseling plus nicotine replacement therapy (NRT) to brief advice to quit (standard care) plus NRT among homeless smokers. Using bivariate analyses and multinomial logistic regression, we compared demographics, health and psychosocial variables, tobacco use, substance use, and NRT adherence among those who reported: quitting; reducing smoking by 50-99%; and not reducing smoking by 50%. RESULTS: Of 324 participants who completed 26-week follow-up, 18.8% and 63.9% self-reported quitting and reducing, respectively. Compared to those who did not reduce smoking, participants reporting reducing indicated higher baseline cigarette use (OR=1.08; CI:1.04-1.12) and menthol use (OR=2.24; CI:1.05-4.77). Compared to participants who reduced, participants reporting quitting were more likely to be male (OR=1.998; CI:1.00-3.98), experience more housing instability (OR=1.97; CI:1.08-3.59), indicate higher importance of quitting (OR=1.27; CI:1.041.55), have higher NRT adherence (OR=1.75; CI:1.00-3.06), and lower odds of reported illicit drug use (OR=0.48; CI:0.24-0.95). CONCLUSIONS: Over half of participants reduced smoking by at least 50%, indicating reduction is feasible among homeless smokers. Further research is required to understand the impact of reduction on future cessation attempts in homeless smokers. This study shows that reduction is achievable and may be a valid intermediate goal.

Proposing a Model of Proactive Outreach to Advance Clinical Research and Care Delivery for Patients Who Use Tobacco.

There are evidence-based treatments for tobacco dependence, but inequities exist in the access to and reach of these treatments. Traditional models of tobacco treatment delivery are "reactive" and typically provide treatment only to patients who are highly motivated to quit and seek out tobacco treatment. Newer models involve "proactive" outreach, with benefits that include increasing access to tobacco treatment, prompting quit attempts among patients with low motivation, addressing health disparities, and improving population-level quit rates. However, the definition of "proactive" is not clear, and adoption has been slow. This commentary introduces a comprehensive yet flexible model of proactive outreach and describes how proactive outreach can optimize clinical research and care delivery in these domains: (1) identifying the population, (2) offering treatment, and (3) delivering treatment. Dimensions relevant to each domain are the intensity of proactive outreach (low to high) and the extent to which proactive outreach activities rely on human interaction or are facilitated by information technology (IT). Adoption of the proposed proactive outreach model could improve the precision and rigor with which tobacco cessation research and tobacco treatment programs report data, which could have a positive effect on care delivery and patient outcomes.

The effect of pre-aggregation scale on spatially adaptive filters.

Choropleth mapping continues to be a dominant mapping technique despite suffering from the Modifiable Areal Unit Problem (MAUP), which may distort disease risk patterns when different administrative units are used. Spatially adaptive filters (SAF) are one mapping technique that can address the MAUP, but the limitations and accuracy of spatially adaptive filters are not well tested. Our work examines these limitations by using varying levels of data aggregation using a case study of geocoded breast cancer screening data and a synthetic georeferenced population dataset that allows us to calculate SAFs at the individual-level. Data were grouped into four administrative boundaries (i.e., county, Zip Code Tabulated Areas, census tracts, and census blocks) and compared to individual-level data (control). Correlation assessed the similarity of SAFs, and map algebra calculated error maps compared to control. This work describes how pre-aggregation affects the level of spatial detail, map patterns, and over and under-prediction.

A Randomized Trial of Nicotine versus No-nicotine E-cigarettes Among African American Smokers: Changes in Smoking and Tobacco Biomarkers.

INTRODUCTION: The objective of this clinical trial was to compare the effects of e-cigarettes with and without nicotine on patterns of combustible cigarette use and biomarkers of exposure to tobacco toxicants among African American smokers. METHODS: African American smokers (n = 234) were enrolled in a 12-week, single blind, randomized controlled trial and assigned to ad lib use of nicotine e-cigarettes with or without menthol (2.4% nicotine [equivalent to combustible cigarettes], n = 118), or no-nicotine e-cigarettes (n = 116) for 6 weeks. Surveys were administered at baseline, 2, 6, and 12 weeks, and urinary biomarkers 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and total nicotine equivalents (TNE) were assessed at baseline and 6 weeks. RESULTS: Participants smoked an average of 11.4 cigarettes per day (CPD) and 88% used menthol cigarettes at baseline. At Week 6, the nicotine group reported using e-cigarettes 9.1 times per day compared to 11.4 times in the no-nicotine group (p = 0.42). Combustible cigarette smoking decreased 3.0 CPD in the nicotine group compared to 2.7 CPD in the no-nicotine group (p = 0.74). Neither TNE nor NNAL changed significantly between baseline and Week 6. There were no differences in nicotine withdrawal symptoms between treatment groups. Smoking reduction persisted in both groups at Week 12. CONCLUSIONS: Contrary to our hypotheses, nicotine e-cigarettes did not significantly reduce the use of combustible cigarettes compared to no-nicotine e-cigarettes in this cohort of African American smokers. Findings suggest e-cigarettes are modestly associated with the decreased use of combustible cigarettes among non-treatment seeking smokers, regardless of nicotine content, but without a reduction in tobacco toxicants. IMPLICATIONS: Although e-cigarettes have the potential to reduce harm if substituted for combusted cigarettes (or if they promoted cessation) because of lower levels of tobacco toxicants, this study suggests ad lib use of e-cigarettes among African American smokers, with or without nicotine, results in modest smoking reduction but does not change toxicant exposure in a cohort where smoking cessation or reduction is not the goal. These data suggest that testing future harm reduction interventions using e-cigarettes should include more specific behavioral change coaching, including substituting for or completely stopping combusted cigarettes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov - NCT03084315.

Self-reported exercise capacity among current smokers eligible for lung cancer screening: Distribution and association with key comorbidities.

ONE CONCERN: as lung cancer screening (LCS) is implemented is that patients will be screened who are too ill to benefit. Poor exercise capacity (EC) predicts adverse outcomes following lung resection. OBJECTIVE: Describe the distribution of EC among smokers eligible for LCS and examine associations with comorbidities. METHODS: Cross-sectional analysis of baseline data from a randomized controlled trial of tobacco treatment in the context of LCS. Participants responded regarding limitations in moderate activities, ability to climb stairs, and frequency of dyspnea on a scale from never/almost never to all or most of the time. Responses were assigned a numeric score and summed to categorize exercise limitation. Associations between poor EC and key comorbidities were examined using adjusted logistic regression. RESULTS: 660 participants completed a survey with the following characteristics: 64.4% male, 89.5% white, mean age 64.5. Overall EC categories were: good 39.0%, intermediate 41.6%, and poor 19.4%.  Prevalence of poor EC was higher among patients with COPD (OR 4.62 95%CI 3.05-7.02), heart failure (OR 3.07 95%CI 1.62-5.82) and cardiovascular disease (OR 2.24, 95%CI 1.45-3.47), and was highest among patients with multimorbidity. Among patients with COPD and heart failure, 57% had poor and 0% had good EC. In adjusted logistic regression, only COPD and Charlson comorbidity index remained significantly associated with poor EC. CONCLUSIONS: Many patients eligible for LCS reported poor EC, with increased odds of poor EC among patients with comorbidities. More research is needed to determine how to best integrate EC and comorbidity into eligibility and shared decision-making conversations.

Novel mapping methods to describe utilization of free breast cancer screening from a state program.

INTRODUCTION: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) is a cancer screening program whose mission is to reduce cancer morbidities for uninsured and underinsured women. A primary activity is to connect women to breast cancer screening. The eligible population and utilization of NBCCEDP screening services have never been quantified at a sub-state level, which hampers effective program evaluation. Here, the Minnesota NBCCEDP, "Sage", serves as a case study to demonstrate novel spatial analysis methods that depict variation of screening rates at the local level. METHODS: Women who received breast cancer screening through Sage between 2011 and 2015 were geocoded (N = 74,712 screenings); analysis occurred between 2017 and 2019. We determine an eligible population using a synthetic population dataset that provides geographic residence and demographic information. We introduce a novel spatial analysis technique, spatially adaptive filters (SAFs), to create a utilization map of Sage breast screening services by Minnesota women. RESULTS: Between 2011 and 2015, an average of 36,979 women per year were eligible for NBCCEDP breast cancer screening services, representing 3% of the Minnesota female population 40 and older. For Minnesota NBCCEDP eligible women, the state average breast cancer screening utilization rate was 37.2%, but varied considerably by local regions within the state (range 0% to 131%, SD = 18.7%). CONCLUSIONS: This geospatial model estimated screening service utilization at the local level and enables Minnesota's Sage program to target specific areas they have yet to reach. Similar programs could employ this model to direct program activities.

Predictors of Enrollment of Older Smokers in Six Smoking Cessation Trials in the Lung Cancer Screening Setting: The Smoking Cessation at Lung Examination (SCALE) Collaboration.

SIGNIFICANCE: Increased rates of smoking cessation will be essential to maximize the population benefit of low-dose CT screening for lung cancer. The NCI's Smoking Cessation at Lung Examination (SCALE) Collaboration includes eight randomized trials, each assessing evidence-based interventions among smokers undergoing lung cancer screening (LCS). We examined predictors of trial enrollment to improve future outreach efforts for cessation interventions offered to older smokers in this and other clinical settings. METHODS: We included the six SCALE trials that randomized individual participants. We assessed demographics, intervention modalities, LCS site and trial administration characteristics, and reasons for declining. RESULTS: Of 6285 trial- and LCS-eligible individuals, 3897 (62%) declined and 2388 (38%) enrolled. In multivariable logistic regression analyses, Blacks had higher enrollment rates (OR 1.5, 95% CI 1.2,1.8) compared to Whites. Compared to "NRT Only" trials, those approached for "NRT + prescription medication" trials had higher odds of enrollment (OR 6.1, 95% CI 4.7,7.9). Regarding enrollment methods, trials using "Phone + In Person" methods had higher odds of enrollment (OR 1.6, 95% CI 1.2,1.9) compared to trials using "Phone Only" methods. Some of the reasons for declining enrollment included "too busy" (36.6%), "not ready to quit" (8.2%), "not interested in research" (7.7%), and "not interested in the intervention offered" (6.2%). CONCLUSION: Enrolling smokers in cessation interventions in the LCS setting is a major priority that requires multiple enrollment and intervention modalities. Barriers to enrollment provide insights that can be addressed and applied to future cessation interventions to improve implementation in LCS and other clinical settings with older smokers. IMPLICATIONS: We explored enrollment rates and reasons for declining across six smoking cessation trials in the lung cancer screening setting. Offering multiple accrual methods and pharmacotherapy options predicted increased enrollment across trials. Enrollment rates were also greater among Blacks compared to Whites. The findings offer practical information for the implementation of cessation trials and interventions in the lung cancer screening context and other clinical settings, regarding intervention modalities that may be most appealing to older, long-term smokers.

Testing the Feasibility and Acceptability of a Religiously-Tailored Text Messaging Intervention to Reduce Smoking Among Somali Muslim Men During Ramadan.

INTRODUCTION: The prevalence of smoking among Somali Muslim male immigrants residing in Minnesota is estimated at 44%, however smoking reduction is common during the month of Ramadan. This study evaluated the feasibility and impact of a religiously tailored text message intervention delivered during Ramadan to encourage smoking reduction among Somali Muslim men who smoke. METHODS: Fifty Somali men were recruited. Participants received two text messages per day starting 1 week prior to and throughout the month of Ramadan. Approximately half were religiously tailored and half were about the risks of smoking and benefits of quitting. Smoking behavior was assessed at baseline, and at weeks 4 (end of Ramadan), 8, and 16. Outcomes included feasibility, acceptability, and preliminary impact of the text message intervention on smoking reduction and bioverified abstinence. RESULTS: The average age was 41 years. Average time to first cigarette was 1.8 hours at baseline, and 46% of participants smoked menthol cigarettes. Eighteen of 50 participants selected English and 32 selected Somali text messages. Subjects significantly reduced self-reported cigarettes per day (CPD) from 12.4 CPD at baseline to 5.8 CPD at week 16 (p < 0.001). Seven subjects reported quitting at week 16, five completed CO testing, confirming self-reported abstinence. The majority of participants found the cultural and religious references encouraging at the end of the week 16 survey. CONCLUSIONS: Religiously tailored text messages to decrease smoking are feasible and acceptable to Somali Muslim men who smoke during Ramadan. This intervention for addressing smoking disparities is worthy of further study. IMPLICATIONS: Recruitment of Somali Muslim men who smoke is feasible and supports the idea that further studies targeting smoking during Ramadan are practical. Ramadan presents a window of opportunity upon which to build smoking cessation interventions for smokers who identify as Muslim. These preliminary findings suggest that text messaging is a feasible and acceptable intervention strategy, and that religious tailoring was well received. Such an approach may offer potential for addressing smoking disparities among Somali Muslim male smokers. TRIAL REGISTRATION: ClinicalTrial.gov: NCT03379142.

Defining and Measuring Abstinence in Clinical Trials of Smoking Cessation Interventions: An Updated Review.

BACKGROUND: Changes in tobacco products, use patterns, and assessment technology in the last 15 years led the Society for Research on Nicotine and Tobacco (SRNT) Treatment Research Network to call for an update to the 2003 SRNT recommendations for assessing abstinence in clinical trials of smoking cessation interventions. METHODS: The SRNT Treatment Research Network convened a group of investigators with decades of experience in conducting tobacco treatment clinical trials. To arrive at the updated recommendations, the authors reviewed the recommendations of the prior SRNT Workgroup as well as current literature. Ten additional experts in the field provided feedback on this paper and these recommendations. RESULTS: With respect to defining abstinence, the authors recommend: (1) continuing to use the definition of no use of combustible tobacco products (regardless of use of noncombustible tobacco products [e.g., snus] and alternative products [e.g., e-cigarettes]) and collecting additional data to permit alternate abstinence definitions; (2) no use of combustible or smokeless tobacco products; and (3) no use of combustible or smokeless tobacco products or alternative products, as appropriate for the research question being addressed. The authors also recommend reporting point prevalence and prolonged abstinence at multiple timepoints (end of treatment, ≥3 months after the end of treatment, and ≥6 months postquit or posttreatment initiation). CONCLUSIONS: Defining abstinence requires specification of which products a user must abstain from using, the type of abstinence (i.e., point prevalence or continuous), and the duration of abstinence. These recommendations are intended to serve as guidelines for investigators as they collect the necessary data to accurately describe participants' abstinence during smoking cessation clinical trials. IMPLICATIONS: This paper provides updated recommendations for defining abstinence in the context of smoking cessation treatment clinical trials.

Cost-effectiveness of population-level proactive tobacco cessation outreach among socio-economically disadvantaged smokers: evaluation of a randomized control trial.

AIMS: To estimate the cost-effectiveness at population-level of the OPT-IN proactive tobacco cessation outreach program for adult smokers enrolled in publicly funded health insurance plans for low-income persons (e.g. Medicaid). DESIGN: Cost-effectiveness analysis using a state transition model based on data from the Offering Proactive Treatment Intervention (OPT-IN) randomized control trial. SETTING: The trial was conducted in Minnesota, USA, and the economic analysis was conducted from the Medicaid program perspective. PARTICIPANTS: Data were used from 2406 smokers who were randomized into the intervention or comparator groups. INTERVENTION AND COMPARATOR: The intervention was comprised of proactive outreach (mailed invitation and telephone calls) and free cessation treatment (nicotine replacement therapy and intensive telephone counseling). The comparator was usual care, which comprised access to a primary care physician, insurance coverage of Food and Drug Administration (FDA)-approved smoking cessation medications and the state's telephone quitline. MEASUREMENTS: Smoking status, quality of life and health-care use at varying times, including at baseline and 1 year. FINDINGS: The OPT-IN program cost an average of $84 per participant greater than the comparator. One year after randomization, the population-level, 6-month prolonged smoking abstinence rate was 16.5% in the proactive outreach intervention group and 12.1% in the usual care group (P < 0.05). The model projected that the proactive outreach intervention added $78 in life-time cost and generated 0.005 additional quality-adjusted life-years (QALYs), with an expected incremental cost-effectiveness ratio of $4231 per QALY. Probabilistic sensitivity analysis found that the proactive outreach intervention would be cost-effective against a willingness-to-pay threshold of $50 000/QALY approximately 68% of the time. CONCLUSIONS: Population-level proactive tobacco treatment with personal telephone outreach was effective in achieving higher population-level quit rates and was cost-effective at various willingness-to-pay thresholds, compared with usual care (i.e. reactive treatment). Taken together with prior research, population-level proactive tobacco cessation outreach programs are judged to be highly cost-effective over the long term.

Smoking Cessation among Female and Male Veterans before and after a Randomized Trial of Proactive Outreach.

INTRODUCTION: Female veterans smoke cigarettes at high rates compared with both male veterans and nonveteran women. Proactive outreach to smokers may reduce gender disparities in cessation care. The objectives of this study were to compare baseline experiences with VA smoking cessation care for men and women and to assess for gender differences in response to a proactive outreach intervention. METHODS: We conducted a post hoc subgroup analysis of a pragmatic, multisite randomized, controlled trial comparing proactive outreach with usual care (UC). Baseline experiences included physician advice to quit, satisfaction with care, and past-year treatment use. At the 1-year follow-up, treatment use, quit attempts, and 6-month prolonged abstinence for women and men randomized to proactive outreach versus UC were compared using logistic regression. RESULTS: Baseline and follow-up surveys were returned by 138 women and 2,516 men. At baseline, women were less likely than men to report being very or somewhat satisfied with the process of obtaining smoking cessation medications in the VA (47% of women vs. 62% of men), but no less likely to report having used cessation medications from the VA in the past year (39% of women vs. 34% of men). After the intervention, phone counseling and combined therapy increased among both women and men in proactive outreach as compared with UC. At the 1-year follow-up, men in proactive outreach were significantly more likely to report prolonged abstinence than those in UC (odds ratio, 1.65; 95% CI, 1.28-2.14); results for women were in the same direction but not statistically significant (odds ratio, 1.39; 95% CI, 0.48-3.99). CONCLUSIONS: Satisfaction with cessation care in VA remains low. Proactive outreach to smokers was associated with an increased use of cessation therapies, and increased odds of achieving prolonged abstinence. A subgroup analysis by gender did not reveal significant differences in the treatment effect.

Excessive inflammation portends complications: Wound cytokines and head and neck surgery outcomes.

OBJECTIVES/HYPOTHESIS: Postoperative wound-healing complications can be devastating after head and neck surgery. Whereas many patients are expected to have more complications, few objective indicators predict these poorer outcomes. We evaluated wound healing in this population by studying the association between biomarkers and surgical outcomes. STUDY DESIGN: Prospective cohort study. METHODS: A study was performed of head and neck surgery patients at our tertiary care center, from 2012 to 2015. Postsurgical drain fluid was collected 24 hours postoperatively. Biomarkers of wound healing were assayed. These included interleukin (IL)-1, -6, and -8; tumor necrosis factor (TNF)-α; transforming growth factor ß; epidermal growth factor; fibroblast growth factor; C-reactive protein (CRP); vascular endothelial growth factor (VEGF); soluble fms-like tyrosine kinase-1; and placental growth factor. Patient characteristics and clinical outcomes were recorded. Two-sample, two-sided t tests evaluated differences in cytokine levels by clinical outcomes. RESULTS: Twenty-eight patients were enrolled with drain fluid collection. IL-1ß, IL-8, and matrix metalloproteinase (MMP)-9 were significantly higher in the wound fluid of subjects with complications. Patients with longer length of stay in days had statistically higher levels of TNF-α (P = .011), IL-6 (P = .021), IL-8 (P = .004), IL-1ß (P = .004), MMP-1 (P = .002), MMP-2 (P = .022), VEGF-A (P = .038), and CRP (P < .001), and longer length of stay was associated with malignancy. There were no statistically significant associations between baseline clinical characteristics and post-operative complications. CONCLUSIONS: In this head and neck surgical cohort, higher IL-1ß, IL-8, and MMP-9 levels in wound fluid were associated with postoperative complications, and elevation of multiple proinflammatory cytokines was associated with longer length of stay. These findings suggest excessive inflammation in early wound healing may portend poorer clinical outcomes after head and neck surgery. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:E238-E246, 2019.

The relationship between smoking cessation and binge drinking, depression, and anxiety symptoms among smokers with serious mental illness.

INTRODUCTION: Concerns about the adverse effects of smoking cessation on alcohol use and mental health are a barrier to cessation for smokers with serious mental illness (SMI). The purpose of this study is to examine how incident smoking cessation affects binge drinking and symptoms of depression and anxiety among smokers with SMI. METHODS: The present study is a secondary analysis of the OPTIN trial, which demonstrated the effectiveness of proactive outreach for smoking cessation among Minnesota Health Care Programs enrollees. Participants with ICD-9 codes indicating schizophrenia spectrum disorders, psychotic disorders, bipolar disorders, or severe/recurrent major depressive disorder were categorized as having SMI (n = 939); remaining smokers were categorized as non-SMI (n = 1382). Multivariable regressions modeled the association between incident smoking cessation and binge drinking, PHQ-2 depression scores, and PROMIS anxiety scores in the two groups. RESULTS: Quitting smoking was not associated with binge drinking among those with SMI, but was associated with less binge drinking among those without SMI (p = 0.033). Quitting smoking was not associated with PHQ-2 depression scores among those with or without SMI. However, quitting smoking was associated with lower mean PROMIS anxiety scores for those with SMI (p = 0.031), but not those without SMI. CONCLUSION: Quitting smoking was not associated with heightened binge drinking or symptoms of depression and anxiety among smokers with SMI. These findings suggest that quitting smoking is not detrimental for these patients, and provide evidential support for facilitating access to cessation resources for patients with serious mental illness who smoke.