2014 Research Report


OVERVIEW: UW-CTRI releases a research update in January and July of each year. This report summarizes published and in-press manuscripts, presentations, grants, contracts and other research projects.


SUMMARY
:
In 2014, the UW-CTRI research team produced:

37 published papers (p. 1)

3 papers in press (p. 9)
30 presentations or posters (p. 10)

2 new studies (p. 13)

3 active studies (p. 15)

7 studies recently completed (p. 17)

Financials (p. 21)


THANK YOU: UW-CTRI is grateful to its partners, the UW Department of Medicine, the UW School of Medicine and Public Health, the Wisconsin Department of Health Services, NIH, CDC, FDA, ClearWay Minnesota,
Health Resources and Services Administration, the Wisconsin Partnership Program, UW Institute for Clinical and Translational Research, and the Department of Veterans Affairs.

Published Papers

Note: Names in bold are current UW-CTRI employees.

 

Adsit RT, Fox BM, Tsiolis T, Ogland C, Simerson M, Vind LM, Bell SM, Skora AD, Baker TB, Fiore MC. Using the Electronic Health Record to Connect Primary Care Patients to Evidence-Based Telephonic Tobacco Quitline Services: A Closed-Loop Demonstration Project. Translational Behavioral Medicine. Online March 2014. 2014; 4:324-332. Printed September 2014.

 

Summary: A markedly higher percentage of adult tobacco users were referred to the quitline using eReferral than using the previous paper fax referral (14% vs. 0.3%). The eReferral system increased the referral of tobacco users to quitline treatment. This case study suggests the feasibility and effectiveness of a secure, closed-loop EHR-based eReferral system.


Baker TB, Gustafson DH, Shah D. How Can Research Keep Up With e-Health? Ten Strategies for Increasing Efficiency and Quality. Journal of Medical Internet Research. February 19;16(2):e36.

 

Summary: This paper discusses the need for studies that deliver timely data in a wired, fast-paced society. Strategies for efficiency and quality include adapting engineering analysis models, a focus on timeless principles and systems, and incorporating the latest technology into study designs.


Baker TB, McFall RM. The Promise of Science Based Training and Application In Psychological Clinical Science.

Psychotherapy. 2014 Dec;51(4):482-6.

 

Summary: The authors argue for a multidimensional approach to evaluating intervention performance, one that involves an evaluation of efficacy, effectiveness, cost-effectiveness, translation potential, and so on. They discuss how researchers can most efficiently develop quit-smoking intervention methods and delivery systems that are superior to the induction of common factors per se. 

 

Bergen AW, Javitz HS, Krasnow R, Michel M, Nishita D, Conti DV, Edlund CK, Kwok PY, McClure JB, Kim, RB, Hall SM, Tyndale RF, Baker TB, Benowitz NL, Swan GE. Organic Cation Transporter Variation and Response to Smoking Cessation Therapies. Nicotine and Tobacco Research. 2014 Dec;16(12):1638-46.

 

Summary: The functional OCT2 Ser270Ala polymorphism is nominally statistically significantly associated with smoking abstinence after adjustments for pharmacotherapy, demographics, population genetics, and without adjustment for multiple testing of seven SNPs. Replication of these preliminary findings in additional randomized controlled trials of smoking cessation therapies, and from multiple continental populations, would describe another pharmacogenetic role for SLC22A2/OCT2.

 

Bloom AJ, Baker TB, Chen L-S, Breslau N, Hatsukami D, Bierut LJ, Goate A. Variants In Two Adjacent Genes, EGLN2 and CYP2A6, Influence Smoking Behavior Related To Disease Risk Via Different Mechanisms. Human Molecular Genetics. 2014 Jan 15;23(2):555-61.

 

Summary: When CYP2A6 (nicotine metabolism enzyme) and EGLN2 (hypoxia response) genotypes are analyzed together, the key variant, rs3733829, is independently associated with cigarettes per day, and with breath carbon monoxide, a phenotype associated with cigarette consumption. These results indicate a previously unappreciated novel mechanism behind genome-wide significant associations with cigarette consumption and disease risk unrelated to nicotine metabolism.


Bloom AJ, Hartz SM, Baker TB, Chen L-S, Piper ME, Fox L, Martinez M, Hatsukami D, Johnson EO, Laurie CC, Saccone NL, Goate A, Bierut LJ. Beyond Cigarettes-Per-Day: A Genome-Wide Association Study of the Biomarker Carbon Monoxide. Annals of the American Thoracic Society. Online 2014 July 29; 11(7)1003-10.

 

Summary: Exhaled carbon monoxide, a biomarker that is simple to measure, captures aspects of cigarette smoke exposure in current smokers beyond the number of cigarettes smoked per day. Behavioral measures of smoking are therefore insufficient indices of cigarette smoke exposure, suggesting that genetic associations with COPD or lung cancer that persist after adjusting for self-reported smoking behavior may still reflect genetic effects on smoking exposure.


Bold KW, Rasheed AS, McCarthy DE, Jackson TC, Fiore MC, Baker TB. Rates and Predictors of Renewed Quitting After Relapse During a One-Year Follow-Up Among Primary Care Patients. Annals of Behavioral Medicine. Online 2014 May.

 

Summary: Primary care patients in a comparative effectiveness trial reported daily smoking every 6-12 weeks for 12 months to determine relapse, renewed quitting, and 12-month abstinence rates. Of 894 known participants who relapsed, 33% renewed quitting for at least 24 hours. The average latency to renewed quitting was 106 days and longer latencies predicted greater success. Renewed quitting was more likely for older, male, less dependent smokers, and later abstinence was predicted by fewer depressive symptoms and longer past abstinence. Renewed quitting is common and produces meaningful levels of cessation.

 

Boyle R, Solberg L, Fiore MC. Use of Electronic Health Records to Support Smoking Cessation. Cochrane Database Systematic Review. 2014, Issue 12. Article Number: CD008743.

 

Summary: At least in the short term, documentation of tobacco status and increased referral to cessation counseling do appear to increase following the introduction of an expectation to use the EHR to record and treat patient tobacco use at medical visits. There is a need for additional research to further understand the effect of EHRs on smoking treatment in healthcare settings.

 

Chen L-S, Bloom AJ, Baker TB, Smith SS, Piper ME, Martinez M, Saccone N, Hatsukami D, Goate A, Bierut L. Pharmacotherapy Effects on Smoking Cessation Vary with Nicotine Metabolism Gene (CYP2A6). Addiction. 2014 Jan 15;23(2):555-61.

 

Summary: Nicotine replacement therapy is effective among individuals with fast, but not slow, CYP2A6-defined nicotine metabolism. The effect of bupropion on relapse likelihood is unlikely to be affected by nicotine metabolism as estimated from CYP2A6 genotype. The variation in treatment responses among smokers with genes may guide future personalized smoking cessation interventions.

 

Chen L, Baker TB, Piper ME, Smith SS, Gu C, Grucza RA, Smith GD, Munafo M, Bierut LJ. Interplay of Genetic Risk (CHRNA5) and Environmental Risk (partner smoking) on Cigarette Smoking Reduction. Drug and Alcohol Dependence. Online 2014 July 3.

 

Summary: This study tests whether the genetic predictor (CHRNA5 nicotine receptor gene variants) and an environmental risk factor (partner smoking) interact in the prediction of smoking reduction. Smokers with high genetic risk are more likely to continue smoking if a partner smokes. However, quit-smoking medications can overcome these dual risks for some smokers.

 

Christiansen BA, Reeder K, Fiore MC, Baker TB. Changing Low Income Smokers’ Beliefs about Tobacco Dependence Treatment. Substance Use and Misuse. Online 2014 Feb 6. Printed 2014 Jun;49(7):852-63.

 

Summary: This field study tested an intervention that challenged beliefs about the effectiveness of various quit methods held by Salvation Army client smokers from two urban locations. The intervention changed client perceptions about the effectiveness of quitting methods. Compared to controls, intervention participants reported significantly greater smoking reduction, and greater likelihood of contacting the Wisconsin Tobacco Quit Line.

 

Cole H, Fiore MC. The War Against Tobacco: 50 Years and Counting. (Viewpoint) JAMA, 2014; 311(2):131-2.

 

Summary: This viewpoint article marks the 50th anniversary of the first U.S. Surgeon General’s report on smoking. The authors recommend key policy changes, such as increasing tobacco taxes, along with stronger application of FDA regulation of tobacco products—including that of cigars and e-cigarettes, more universal treatment of patients who use tobacco, and massive public health campaigns.

 

Collins LM, Trail JB, Kugler KC, Baker TB, Piper ME, Mermelstein RJ. Evaluating Individual Intervention Components: Making Decisions Based on the Results of a Factorial Screening Experiment. Translational Behavioral Medicine. 2014; 4:238-251.

 

Summary: The multiphase optimization strategy (MOST) is a framework for not only evaluating but also optimizing behavioral interventions. A tool critical for MOST is the screening experiment, which enables efficient gathering of information for deciding which components to include in an optimized intervention. This article outlines a procedure for making decisions based on data from a factorial screening experiment. Future research should develop additional decision-making procedures for a variety of situations.

 

Cook JW, Piper ME, Leventhal AM, Schlam TR, Fiore MC, Baker TB. Anhedonia as a Component of the Tobacco Withdrawal Syndrome. Journal of Abnormal Psychology. Online 2014 November.

 

Summary: After quitting, many smokers suffer from anhedonia, a pervasive inability to experience pleasure during life activities that one normally enjoys. This paper is one of the first to show that anhedonia is a symptom of nicotine withdrawal in humans, and may be a key reason smokers who want to break their addiction to tobacco struggle to do so—especially during the first week after quitting smoking, when anhedonia spikes before eventually falling back to baseline levels. The good news is that researchers found that quit-smoking medications decreased the rise in anhedonia

.

Davis JM, Goldberg SB, Anderson MC, Manley AR, Smith SS, Baker TB. Randomized Trial on Mindfulness Training for Smokers Targeting a Disadvantaged Population. Journal of Substance Use and Misuse. 2014 Apr;49(5):571-85.

 

Summary: Data were collected from 196 low socioeconomic status smokers in 2010-2011 in Madison, Wisconsin. Participants were randomized to either mindfulness training for smokers (MTS) or a telephonic quit line. Among treatment initiators (randomized participants who participated in the intervention), abstinence rates were significantly different between MTS (38.7%) and control (20.6%) groups.

 

Davis JM, Manley AR, Goldberg SB, Smith SS, Jorenby DE. Randomized Trial Comparing Mindfulness Training for Smokers to a Matched Control. Journal of Substance Abuse Treatment. Online 2014 May 1.

 

Summary: A significant difference was not found in the primary outcome; smoking abstinence rates (intent-to-treat, biochemically confirmed at 6 months) were mindfulness=25%, control=17.9%. Researchers did find the mindfulness condition improved measures of urges and changes in mindfulness, perceived stress, and experiential avoidance. While mindfulness may not be right for some smokers, some participants who completed the program found it helpful.

 

Davis JM, Sandgren AJ, Manley AR, Daleo M, Smith SS. Optimizing Clinical Trial Enrollment Methods Through "Goal Programming." Applied Clinical Trials. Online 2014 12 March.

 

Summary: This study encourages researchers to use an iterative process to track return on investment data for study-recruitment strategies. An iterative process is a computational method in which a succession of approximations is used to achieve accuracy. Recruitment studies aren’t one-size-fits-all, but tracking ROI can help make informed decisions.

 

Fiore MC, Schroeder SA, Baker TB. Smoke, The Chief Killer - Strategies For Targeting Combustible Tobacco Use. New England Journal of Medicine. 2014 Jan 23;370(4):297-9.

 

Summary: The authors outlined five key ways to curb tobacco use in the future, including clean indoor air laws, higher tobacco taxes, FDA regulation of tobacco products, media campaigns to keep kids from ever starting, and a focus on eliminating combustible tobacco. The authors also discussed how clinicians could help their patients to become free from combustible tobacco, and ideally free from all nicotine products.

 

Fiore MC, Golden RN. The 50th Anniversary of the Surgeon General's Report on Smoking and Health: Reflections and Lessons to be Learned for Other Public Health Challenges. Wisconsin Medical Journal. Vol. 113, No 2, April 2014. Pages 81-83.

 

Summary: This paper details the progress in tobacco treatment in the 50 years since the original Surgeon General’s Report and the challenges that lie ahead in helping people quit tobacco use.

 

Fraser D, Kobinsky K, Smith SS, Kramer J, Theobald WE, Baker TB. Five Population-Based Interventions for Smoking Cessation: A MOST Trial. Translational Behavioral Medicine. Online August 2014.


Summary: Analyses showed that the NCI Web site (www.smokefree.gov) and NRT both increased abstinence; however, the former increased abstinence significantly only when it was not used with the e-mail messaging intervention (messaging decreased Web site use). There was evidence that mailed nicotine mini-lozenges and the NCI Web site provide benefit as population-based smoking interventions.

 

Gennuso KP, Thraen-Borowski KM, Schlam TR, LaRowe TJ, Fiore MC, Baker TB, Colbert LH. Smokers' Physical Activity and Weight Gain One Year After a Successful Versus Unsuccessful Quit Attempt. Preventive Medicine. 67, 189-192. Online August 2014.

 

Summary: No statistically significant interaction or main effect was found between quitting and physical activity. Moderate increases in physical activity controlled weight gain but often did not prevent it.

 

Lanza ST, Piper ME, Shiffman S. New Methods for Advancing Research on Tobacco Dependence Using Ecological Momentary Assessment. Nicotine & Tobacco Research. 16 Supplement 2, S71-72.

 

Summary: This special issue presents a series of articles on the use of ecological momentary assessment (EMA) methods, which involve collecting real-time data in real-time settings, to study tobacco use and dependence. EMA methods have particular utility for understanding tobacco use because they enable microanalyses of use and can shed light on how behavior unfolds over time.

 

Lanza ST, Vasilenko S, Liu X, Li R, Piper ME. Advancing the Understanding of Craving during Smoking Cessation Attempts: A Demonstration of the Time-Varying Effect Model. Nicotine and Tobacco Research. 16 Supplement 2, S127-134.

 

Summary: During the first 2 days after quitting, the association between negative affect and craving was significantly stronger among individuals in the placebo group, suggesting an early positive impact of treatment. For the monotherapy and combination therapy groups, during the second week of the quit attempt, baseline dependence was less strongly related to craving compared with the placebo group, indicating a different positive impact of treatments later in the quit attempt. The results reveal information about the underlying dynamics that unfold during a quit attempt.

 

Lebrun-Harris LA, Fiore MC, Tomoyasu N, Ngo-Metzger Q. Cigarette Smoking, Desire to Quit, and Tobacco-Related Counseling Among Adult Health Center Patients. American Journal of Public Health. Online March 2014.

 

Summary: Cigarette smoking prevalence is substantially higher among patients at health centers than US adults in general. However, most smokers at health centers desire to quit. Continued efforts are warranted to reduce tobacco use in this vulnerable group. 

 

Leventhal AM, Piper ME, Japuntich SJ, Baker TB, Cook JW. Anhedonia, Depressed Mood, and Smoking Cessation Outcome. Journal of Consulting Clinical Psychology. 2014; 82(1), 122-129.
 

Summary: It may not be that feeling sad directly leads to failed quit attempts, but rather a pervasive inability to experience pleasure surrounding life activities that one normally enjoys. The paper, based on UW-CTRI data from the Wisconsin Smokers’ Health Study, reveals that clinical attention to anhedonia, or the diminished interest or pleasure in normally enjoyable activities, may be a key to helping groups of smokers who struggle so much to quit tobacco use.

 

McAfee T, Babb S, McNabb S, Fiore MC. Helping Smokers Quit: Opportunities Created by the Affordable Care Act. New England Journal of Medicine. Online November 2014.

 

Summary: This perspective piece calls on insurers across the country to comply with the Affordable Care Act (ACA) and do the right thing to help their enrollees who smoke live longer, healthier lives, and reduce healthcare costs. While the ACA called for expanded insurance coverage for treatments to help smokers quit, insurers have been reluctant to actually follow through by adding such benefits to their plans, in part because the ACA didn’t describe in detail how to meet that mandate.

 

Smith SS, Fiore MC, Baker TB. Smoking Cessation in Smokers Who Smoke Menthol and Non-Menthol Cigarettes. Addiction. Online June 2014. 2014;109:2107-2117.

 

Summary: Menthol flavoring appears to make it harder to quit smoking cigarettes, especially for African-American females, according to this long-term study. Researchers controlled for variables such as education, type of medication, and peer smoking, and the findings held true. Researchers biochemically confirmed smoking status among 1500 participants in a five-year study, and 38% of non-menthol smokers quit versus only 31% of menthol smokers. That’s a 20% difference, which is statistically significant, researchers said. These findings could have implications for the FDA’s review of menthol regulations.

 

Smith SS, Rouse LM, Caskey M, Fossum J, Strickland R, Culhane JK, Waukau J. Culturally-Tailored Smoking Cessation for Adult Indian Smokers: A Clinical Trial. The Counseling Psychologist. 2014;42(6):852-86.

 

Summary: This study represents the first randomized smoking cessation clinical trial testing a culturally tailored smoking cessation intervention designed for a specific American Indian/Alaska Native tribal community that combined Food and Drug Administration (FDA)-approved cessation medication (varenicline) and innovative cultural intervention components. The abstinence rate at 6 months was 20%.

 

Stein JH, Asthana A, Smith SS, Piper ME, Loh WY, Fiore MC, Baker TB. Smoking Cessation and the Risk of Diabetes Mellitus and Impaired Fasting Glucose: Three-Year Outcomes After a Quit Attempt. PLoS One. 2014 June 3;9(6):e98278. eCollection 2014.

 

Summary: Weight gain after smoking cessation may increase diabetes mellitus as well as impaired fasting glucose (IFG) risk. Independent risk factors include older age, baseline body weight, baseline glycemic status, and heavier pre-quit smoking. These findings may help target smokers for interventions to prevent dysglycemia.

 

Theobald WE, Fiore MC. Elogio di Tabaccologia (Tribute to Tabaccologia) Editorial. Tabaccologia. 2014; 1-2:5.

 

Summary: This paper pays tribute to Tabaccologia, the leading tobacco-control scientific journal in Italy, and its contributions to science during the past decade, facilitating significant changes in the prevalence of smoking, the protection of public health, and the very culture of smoking in Italy.

 

Timms KP, Rivera DE, Collins LM, Piper ME. A Dynamical Systems Approach to Understanding Self-Regulation in Smoking Cessation Behavior Change. Nicotine & Tobacco Research. 2014 May;16 Supplement 2:S159-68.

 

Summary: How do smokers self-regulate? In this paper, researchers borrow tools from the field of engineering to explain. Topics include craving as well as behaviors before, during, and after quit attempts.

 

Timms KP, Rivera DE, Collins LM, Piper ME. Continuous-time System Identification of a Smoking Cessation Intervention. International Journal of Control. 2014;87(7):1423-1437.

 

Summary: Toward a goal of designing better quit-smoking treatments, researchers used a continuous-time dynamic modelling approach to model the response of craving and smoking rates during a quit attempt, based on data from a quit-smoking clinical trial. The use of continuous-time models saves time, eases data interpretation, and offers the opportunity to work with uneven or missing data.

 

Trail JB, Collins LM, Rivera DE, Li R, Piper ME, Baker TB. Functional Data Analysis for Dynamical System Identification of Behavioral Processes. Psychological Methods. 2014 June;19(2):175-87.

 

Summary: The methods presented in this article integrate two innovative, intensive, longitudinal analytic techniques: functional data analysis and dynamical systems modeling. The results, in conjunction with standard engineering control-theory techniques, could potentially be used by tobacco researchers to develop a more effective smoking intervention.

 

Treloar HR, Piasecki TM, McCarthy DE, Baker TB. Relations Among Caffeine Consumption, Smoking, Smoking Urge, and Subjective Smoking Reinforcement in Daily Life. Journal of Caffeine Research. 2014 Sep;4(3):93-99.

 

Summary: Electronic diaries were used to collect momentary reports of smoking, caffeine consumption, temptation/urge to smoke, and subjective smoking reinforcement in 74 pre-quit smokers. Caffeine consumption was also associated with positive cigarette appraisals and reports of strong temptation/urge to smoke. Under the conditions of caffeine consumption versus at other times, smokers were significantly more likely to report their last cigarette as producing a rush/buzz, being pleasant, relaxing, and tasting good.

 

Vasilenko SA, Piper ME, Lanza ST, Xiaoyu L, Yang J, & Li, R. Time-Varying Processes Involved In Smoking Relapse In a Randomized Trial of Smoking Cessation Therapies. Nicotine and Tobacco Research. 2014 May;16 Supplement. 2:S135-43.


Summary:
Cravings were a significant predictor of smoking throughout the entire two weeks post-quit, whereas the effect of baseline dependence became non-significant by the second week, and the effect of negative affect increased over time.

 

Walton KM, Abrams DB, Bailey WC, Clark D, Connolly GN, Djordjevic MV, Eissenberg TE, Fiore MC, Goniewicz ML, Haverkos L, Hecht SS, Henningfield JE, Hughes JR, Oncken CA, Postow L, Rose JE, Wanke KL, Yang L, Hatsukami DK. NIH Electronic Cigarette Workshop: Developing a Research Agenda. Nicotine and Tobacco Research. Online 2014 October 21.

 

Summary: The research needs identified by the workshop participants included: standards to measure the contents and emissions of e-cigarettes; biomarkers of exposure; physiological effects of e-cigarettes on tissues and organ systems including pulmonary and cardiovascular; information on e-cigarette users, how the devices are used, and identification of the best tools to assess these measures; factors that drive use and influence patterns of use; and appropriate methods to evaluate a potential role for e-cigarettes in smoking or nicotine cessation.

 

Zhang X, Martinez-Donate AP, Cook JW, Piper ME, Berg K, Jones NR. Battling Tobacco Use at Home: An Analysis of Home Smoking Bans Among US Veterans from 2001 to 2011. American Journal of Public Health. Online August 2014. Printed September 2014;104:S572-579.

 

Summary: Despite the general increase in the adoption of smoke-free home rules, veterans lag behind the rest of the US population. Interventions promoting the adoption of complete smoke-free home rules are necessary to protect veterans and their families and to reduce disparities.

 

New Studies

Breaking Addiction to Tobacco for Health (BREATHE). UW-CTRI has received a $12 million grant from the National Cancer Institute of the National Institutes of Health. The grant will fund research designed to test new phased-based treatments to help patients in the Milwaukee and Madison areas quit smoking. Partners in this research include colleagues from Penn State University and the University of Illinois-Chicago, as well as Aurora Health Care, Dean Health System, and Epic. Under the BREATHE project, any smoker who visits a participating clinic, regardless of the initial reason for the visit, is invited to get treatment through BREATHE. This study implements both an EHR system that increases smokers' recruitment into treatment as well as a highly effective chronic-care treatment with intervention components for all smokers. First, the EHR system will be implemented in 18 clinics in 2 health-care systems and experimentally evaluated on its ability to increase the recruitment of smokers into chronic-care treatment (Project 1). Then, using highly efficient research methods, researchers will experimentally compare multiple intervention components and identify especially effective interventions for every phase of smoking treatment. This package of components will: increase quitting motivation amongst smokers initially unwilling to quit and prepare them for cessation (Project 2), enhance quitting success and prevent relapse when smokers are ready to quit (Project 3), and re-engage relapsed smokers in treatment and restore their abstinence (Project 4). Our highly integrated research projects, supported by four cores, will thus implement a powerful new EHR strategy to efficiently recruit primary care patients who smoke into chronic-care treatment. The BREATHE team has unique strengths in: smoking treatment research in healthcare settings, established collaborations with EHR vendors and primary care clinics, and research methods. Project synergy results from shared use of: an EHR-based recruitment and treatment platform; health-care systems, clinics, and patient populations; treatment and research resources; and ground-breaking research methods. These methods will be used to combine data from all projects and produce an optimized comprehensive chronic-care treatment for smoking that can be readily implemented in primary-care settings by project end. Thus, this research will simultaneously advance both smoking treatment and treatment research methods. June 2014-July. 2019, $12 million. Funded by NCI. Michael Fiore and Tim Baker, PIs.


PTSD and Veterans Merit Award
. UW-CTRI Researcher Dr. Jessica Cook has reached a major career milestone, receiving a merit award from the Veterans Administration (VA). The primary objective of her research is to produce an empirically validated treatment that increases smoking cessation in veterans with posttraumatic stress disorder (PTSD), one that can be easily integrated into smoking cessation clinics and/or mental health clinics within VA facilities. PTSD is highly prevalent in the VA patient population and is associated with a rate of smoking (53% - 66%) that far exceeds that of VA enrollees in general (22%). PTSD is also associated with unusually high rates of smoking-cessation-treatment failure. The disparity in smoking cessation outcomes amongst veterans with PTSD may occur because standard smoking cessation treatment does not address PTSD-specific vulnerabilities. Veterans with smoking-PTSD comorbidity may respond better to treatment that addresses their PTSD and associated affective symptoms, because such symptoms can both reinforce smoking and undermine quit attempts. Recent evidence shows that behavioral activation therapy (BA), a behavioral treatment that increases engagement in reinforcing activities, significantly reduces PTSD symptoms. BA may improve smoking cessation outcomes amongst veterans with PTSD because it reduces overall PTSD symptom severity and affective distress (low positive affect, high negative affect), which can cause smoking relapse. The funded research will determine whether BA, as an adjunct to standard smoking cessation treatment, (ST+BA) is superior to a comparably intense combination of standard smoking cessation treatment + health and smoking education (ST+HSE) in improving smoking cessation outcomes among veterans with PTSD. The HSE intervention is intended to constitute a credible intervention that controls for contact time. Secondary objectives are to determine if BA improves PTSD symptomatology and associated affective distress, and to identify potential mediators of BA on smoking outcomes. A total of 120 veterans with PTSD who are motivated to quit smoking will attend an initial diagnostic and baseline assessment session. Those who are interested, eligible, and who provide consent will be randomly assigned to receive ST+BA or ST+HSE and will be contacted by their individual study therapist to schedule the first treatment session. Participants will be stratified into treatment groups based on: 1) Major depressive disorder (MDD; present versus absent), and 2) PTSD symptom severity. All participants will receive eight, individual sessions of ST+BA or ST+HSE. All participants will receive 20 minutes of identical standard smoking cessation treatment in each of the eight sessions. Those in the ST+BA condition will receive an additional 30 minutes of behavioral activation therapy; those in the ST+HSE condition will receive an additional 30 minutes of health education and information about smoking. All participants will receive 8 weeks of the nicotine patch. Smoking cessation outcomes will be assessed 2, 4, 8, 16, and 26 weeks after the quit date. This research has important clinical and public health significance because smoking is especially common among veterans with PTSD, and it is the leading preventable cause of disease and disability. Reducing smoking rates among veterans with PTSD would result in substantially lower smoking-related illness and death in this vulnerable group of smokers. It would also reduce tobacco-related health-care costs charged to the VA. The grant will support researcher Kirsten Webster and a study counselor. Jan. 2014-Sept. 2019, $770,500. Funded by the Veterans Administration. Jessica Cook, PI.


Active Studies

Can Smartphone Games Help Smokers Quit? (Status: Recruiting and seeing patients) Most smokers who try to quit do not succeed. Even if they use evidence-based treatment, only approximately 10% to 30% achieve long-term abstinence. It is known that strong craving for cigarettes is a powerful reason many smokers fail in their quit attempts. Unfortunately, medication and cessation counseling are only modestly successful in quelling craving. The objective of the proposed research is to determine whether smartphone games can help smokers distract themselves, suppress their cravings, and increase their chances of quitting. Dr. Schlam will use the findings from this research as pilot data in a grant application for an NIH K23 Career Development Award. Sept. 2013-Aug. 2014. The $20,000 grant from a UW-CTRI Developmental Pilot Grant is part of UW-CTRI's NIH P50 Center Grant. The $6,164 grant is from a UW Department of Family Medicine Small Grant. Dr. Tanya Schlam, PI.

Dr. Schlam is conducting this and other research on smoking cessation as a Primary Care Research Fellow, supported by a National Research Service Award (T32 Postdoctoral Training Grant) from the Health Resources and Services Administration to the University of Wisconsin Department of Family Medicine. July 2012-June 2015. Funded by the Health Resources and Services Administration. Dr. Bruce Barrett, PI.

Wisconsin Smokers Health Study 2 (WSHS 2). (Status: Recruitment complete, still seeing patients) UW-CTRI has been awarded a $10-million NHLBI grant to discover the best ways to help Wisconsin residents stop smoking. The new study essentially extends the Wisconsin Smokers’ Health Study and is known as WSHS 2. It includes potentially life-saving tests—including artery scans that can signal impending risk of a stroke or heart attack—free of charge. Participants get free coaching and medications to help them quit smoking. Dr. Mike Fiore, Dr. Tim Baker, and Dr. James Stein of UW Preventive Cardiology are the lead researchers for this grant. The original Smoker’s Health Study, launched in 2004, revealed how quitting smoking affects nearly every part of a person’s health, lifestyle, and well-being. Many patients from WSHS are continuing participation in WSHS 2, and their participation will culminate in health data spanning 10 years. The media announcement of WSHS 2 garnered 2,500 volunteers. The Center recruited smokers as new study participants for WSHS 2. In addition, everyone from the previous study—whether now smoking or not—was invited to continue their participation. In total, 1,500 individuals will participate in WSHS 2. Each participant gets assistance from a personal quit coach—something many former smokers say is essential because they felt that giving up cigarettes was like “losing my best friend.” The quit coach is a familiar face who ensures that the patient doesn’t feel like s/he is going through the process alone. All participants will be compensated for time and travel. Each individual participant receives test results, such as cholesterol levels, artery scans, blood counts, and diabetes tests. These results could signal imminent trouble and save lives. The study employs medical tests—such as carotid artery ultrasound scans and arterial tonometry—to determine how quitting smoking improves health over time, and how continuing to smoke harms health. These tests concentrate on cardiovascular disease, but will also target conditions such as lung disease and diabetes mellitus. While it is well known that smoking is very dangerous, we know less about how quitting (versus continued smoking) affects health. Every participant gets state-of-the-art active medication: 1) varenicline or 2) nicotine patch + nicotine lozenge or 3) just nicotine patch. The first two medication treatments listed above have offered the highest quit rates of all quit-smoking medications, said Tim Baker. However, these two treatments have never been compared head-to-head. “We’ll not only determine which works better,” Baker said, “but also whether one approach works better with some types of smokers than does the other.” At the end of this study, the researchers hope to enhance knowledge of how to treat smoking optimally, as well as how quitting smoking helps participants to reduce their risk of heart disease, stroke, and cancer, and the mechanisms by which these health benefits occur. Sept. 2011-Nov. 2016, $10 million. Funded by the National Heart, Lung, and Blood Institute. Dr. Tim Baker, Dr. Michael Fiore, Dr. Jim Stein, PIs.

State Medicaid Grant: Striving to Quit. (Status: Recruiting and seeing patients) Wisconsin has received a five-year, $9.2 million grant from the federal Centers for Medicare and Medicaid Services to help Medicaid recipients quit smoking. The project, called Striving to Quit, is designed to test the effects of incentives on engagement in smoking cessation treatment and quitting behavior among adult BadgerCare (Medicaid) members who smoke. It includes two distinct evidence-based approaches to smoking cessation. The first focuses on linking adult BadgerCare Plus members to the Wisconsin Tobacco Quit Line (WTQL) where participants receive up to five proactive coaching calls (plus additional calls initiated by the participant). The second focuses on linking adult BadgerCare Plus members who are pregnant with intensive cessation counseling and support via First Breath (FB), a smoking cessation program of the Wisconsin Women’s Foundation (WWHF), and additional postpartum services. Postpartum services include four home visits and five support phone calls up to 6 months after delivery. In each of the focus areas, WTQL and FB, half of the enrolled members will receive financial incentives for participating in counseling services and for quitting. The WTQL component of Striving to Quit will serve up to 2,000 members who smoke. Members can enroll via WTQL referral from participating clinics in South Central and Northeastern Wisconsin. Additionally, members who reside in participant counties (Dane, Milwaukee, Racine, Kenosha, Brown, Winnebago, Portage, Marathon, Oneida, Vilas, Oconto, Forest, Fond du Lac and La Crosse) can also call the WTQL to enroll. FB will enroll 1,250 pregnant members who smoke and live in 17 counties throughout the state. “This grant offers a tremendous opportunity to improve the health of thousands of Wisconsin residents with low incomes,” said Michael Fiore. “We’re excited to see whether financial incentives increase rates of smoking cessation among BadgerCare Plus members. It’s terrific to be a part of this grant and to partner with our esteemed collaborators.” Sept. 2011-Sept. 2016, $9.2 million. Funded by Centers for Medicare and Medicaid Services. Dr. Tim Baker, PI.

     

Recently Completed Studies (Study completed, data under analysis for dissemination)

Menthol Use Grant. The National Heart, Lung, and Blood Institutes (NHLBI), in collaboration with the FDA, awarded the University of Wisconsin Center for Tobacco Research and Intervention (UW-CTRI) a $368,000 grant to study the use of menthol cigarettes. This project added to the body of research the FDA is examining to determine whether or how to regulate menthol flavoring in tobacco products. About 75% of adult African-American smokers and about 25% of adult Caucasian smokers in the US smoke menthol cigarettes. While common, little is known about the risks of smoking menthol versus non-menthol cigarettes with regard to tobacco dependence or quitting motivation and success. Researchers used the unique resources of the Wisconsin Smokers’ Health Study (WSHS 1 & 2) to determine the associations of menthol-smoking (versus smoking non-menthol cigarettes) with tobacco dependence, attempts to quit smoking, and quitting success. The WSHS 2 is a longitudinal study that has spanned close to 10 years and comprised two clinical trials of 2,500 participants that evaluated the major types of quit-smoking medications. The WSHS 2 entailed comprehensive assessments of tobacco dependence, participant characteristics, quitting attempts and success over time. This research used these data to determine:

  1. The relation of menthol smoking with comprehensive measures of smoking cessation, and whether such relations are stronger for some types of smokers than others (e.g., African Americans, women).
  2. The relation of menthol smoking with making quit attempts.
  3. hich types of smoking cessation medications are most effective for menthol smokers, and whether menthol and non-menthol smokers differ significantly in response to medications.
  4. The causal mechanisms that account for menthol smokers being at a different risk of smoking cessation failure (if they are found to be so) and whether medications work via the same mechanisms in menthol and non-menthol smokers.
  5. The relation of menthol smoking with important participant characteristics such as severity and type of tobacco dependence.

This research compared menthol smoking versus non-menthol smoking with regard to tobacco dependence and quitting success. The results have been highly relevant to decisions regarding public health policy and the regulation of menthol cigarettes. Aug. 2013-June 2014. $368,000. Funded by the National Heart, Lung, and Blood Institutes, in collaboration with the FDA. Dr. Michael Fiore, Dr. James Stein of UW Cardiology, and Dr. Timothy Baker, PIs.

UW Partnership to Assist and Serve Smokers (UW-PASS). A $9 million P-50 grant from the National Cancer Institute provided five years of funding for UW-CTRI to study various quit-smoking treatments in primary-care clinics throughout Wisconsin. In this study, led by Dr. Michael Fiore and Dr. Tim Baker, UW-CTRI delivered seamless, cutting-edge treatments for all smokers, including those who were ready to quit and those who weren’t. Beginning in the summer of 2010, UW-CTRI offered participation to patients who smoked and visited select primary-care clinics within two health-care systems—Dean Health System and Aurora Health Care. Medical assistants at partnering clinics identified smokers and asked if they were interested in being contacted about a study. They invited all smokers whether they were willing to quit or not. If the patient was interested, an e-mail was generated from the electronic medical record to UW-PASS staff, employed by UW-CTRI, who conducted screening, orientation, patient visits and follow up. The electronic medical records were supported by Epic Systems Corp. and Cerner. All participants have completed treatment. UW-PASS included three projects:


Project 1 focused on increasing the smoker’s motivation to quit. This project offered treatment strategies for smokers who weren’t ready to quit now but were willing to participate in treatment to help them get ready to quit. The hope was to increase their motivation to quit smoking as well as to make actual quit attempts. Treatments included behavioral coaching, motivational interviewing, nicotine patches, and nicotine gum.


Project 2 of UW-PASS examined whether use of nicotine-replacement medication and behavioral coaching—before actually quitting smoking—helped the patient remain smoke-free. Typically, those who use nicotine-replacement medications (such as the nicotine patch or lozenge) quit smoking first, then use medications to stave off cravings and remain smoke free. Project 2 also tested coaching types and lengths, including in-person coaching vs. telephone coaching.


Project 3
studied ways to increase the number of patients who take quit-smoking medication at the proper dosage for the prescribed duration. Most smokers don’t use enough medication or use it the right way. The goal was to see what happened when a patient took medication as prescribed vs. skipping doses or ceasing treatment prematurely. Adherence treatments included automated-adherence phone prompts, electronic monitoring/feedback and a cognitive-adherence intervention. Project 3 also examined the outcomes of long-term coaching and medication. 


Sept. 2009-Aug. 2014. NCI P-50 grant.
Dr. Tim Baker and Dr.
Michael Fiore, PIs.


Dual Use of E-Cigarettes and Traditional Cigarettes in Primary Care and Community Settings
. The National Institutes of Health awarded UW-CTRI a $1.8 million supplement to its NCI-funded center grant. With this supplement, researchers investigated questions of importance to the FDA in its role of regulating tobacco products:

 

  • How dual use of tobacco products (both smoking cigarettes and vaping e-cigarettes) is related to outcomes of public health importance, such as cessation attempts and success. 
  • Mechanisms by which dual use affects such outcomes, for instance showing how dual use affects cigarette withdrawal symptoms, smoking reward, and cigarette dependence.

In the NCI Center Grant Primary Care study, UW-CTRI researchers added new measures and analyses to the parent study to see how dual use may (or may not) affect the user’s dependence on cigarettes, withdrawal severity, perception of harm, treatment engagement, and smoking outcomes (smoking reduction and cessation). Participants in the parent grant were recruited through primary-care visits. Dr. Tanya Schlam led this primary care component.

In the Community Sample sub-study, researchers used measures and analyses that elucidated the mechanisms responsible for the associations observed in the Primary Care sub-study.
Dr. Doug Jorenby led this community sample component, which recruited 150 daily smokers via advertisements (e.g., convenience stores, TV, social media) throughout the Milwaukee and Madison areas, half of whom also used e-cigarettes.


These participants generated real-time data (using an innovative smartphone app) to determine how dual users and exclusive smokers compared on hedonic ratings of cigarettes, cigarette use, daytime tobacco use, mood, suppression of cigarette withdrawal, contexts of use, and exposure. Moreover, data from dual users revealed how recent use of other tobacco products (OTP) affected cigarette use and reward, especially during periods of reduced cigarette intake. Researchers used the data to compare risk profiles and determine how to improve cessation. September 2012-August 2014. Funded by NIH and FDA.
Dr. Tim Baker and Dr. Michael Fiore, PIs.

       

Advancing Tobacco Research by Integrating Systems Science and Mixture Models. This project advanced knowledge of how different smoking-cessation treatments worked, for whom, and when. Dr. Stephanie Lanza of Penn State was the lead investigator and Dr. Megan Piper, UW-CTRI Associate Director of Research, was a co-investigator on this R01 grant from the National Cancer Institute. Researchers from The Methodology Center at Penn State integrated time-varying effect models and latent class analysis in order to identify subgroups of smokers who experienced the process of nicotine withdrawal differently. Latent class analysis allowed researchers to gauge the impact of exposure to patterns of multiple risks, as well as the antecedents and consequences of complex behaviors, so that interventions could be tailored to target the subgroups that will benefit most. Results from the project informed the construction of interventions that (1) are tailored to the individual and that (2) adapt to participant response over time. Importantly, the overall impact of this project extended far beyond the proposed analysis; the project’s full potential for accelerating the pace of smoking-cessation research was realized as a result of programmatic dissemination efforts of important new analytic methods to tobacco researchers. August 2012-July 2015. Funded by National Cancer Institute. Dr. Stephanie Lanza, PI. Dr. Megan Piper, co-I.

Clinical Relevance of Stress Neuroadaptation in Tobacco Dependence. The broad goals of this research were to identify the origin of biomarkers related to how the body compensates for the presence of cigarette chemicals so that it can continue to function. Dr. John Curtin of UW Psychology was the principal investigator, while Dr. Megan Piper of UW-CTRI was a co-investigator on this RO1 grant. It examined stress neuroadaptation in the laboratory via startle potentiation during uncertain threats among nicotine-deprived smokers versus non-deprived smokers and non-smokers. Smokers were subsequently assigned to one of three smoking-cessation treatment conditions and reported on episodic stressors, negative feelings, smoking urge, and tobacco consumption in real time from their regular environments via smart phones or other digital devices that prompted them to enter data. Treatment outcomes were assessed at four weeks and end of treatment. Researchers evaluated the impact of this stress neuroadaptation on smokers’ feelings, urge, and tobacco consumption during smoking-cessation treatment. They examined whether first-line pharmacotherapies could dilute the influence of this stress neuroadaptation on smoking-cessation outcomes. August 1, 2012-June 30, 2017. Funded by NIDA. Dr. John Curtin, PI. Dr. Tim Baker and Dr. Megan Piper, Co-I’s.

Tobacco Interventions Delivered by Community Agencies to Those Living in Poverty. UW-CTRI received a $332,000 NIH grant to train staff at four Salvation Army centers (in Green Bay, Appleton, La Crosse and Wausau) to provide a brief intervention with clients who smoked. UW-CTRI Researcher Dr. Bruce Christiansen led this project, which sprouted from pilot data collected via an ICTR grant awarded to Dr. Christiansen. More than 37 million Americans live in poverty, and they smoke at twice the rate of other Americans. As a result, they bear a disproportionate burden from tobacco-related diseases. Research also shows many people who are homeless or very poor have either mental-health or substance-abuse issues. Both of these groups tend to smoke at high rates and struggle to make quit attempts using evidence-based methods. This grant tested a brief intervention that challenged smokers’ beliefs that discouraged quit attempts. These beliefs included:


1) Smoking is both normal and acceptable.

2) Willpower is sufficient to quit, rendering outside help unnecessary and irrelevant.

3) Evidenced-based treatments are not more effective than other methods.

4) Stop-smoking medicines are ineffective, dangerous, addictive and/or too expensive.

5) Help in quitting is not available, hard to access and/or too expensive.


The goal of the intervention was to correct these misconceptions so they would consider quitting smoking. As a control, researchers randomized another 140 clients into a 15-minute intervention wherein a Salvation Army counselor read them a booklet on smoking and health, but without any behavioral or motivational interviewing. Another control group, consisting of 140 clients, received a booklet to peruse by themselves. All three groups were compared with 100 participants who were already set to quit smoking. Researchers made follow-up phone calls after three months. Sept. 2011-Sept. 2014, $332,000. Funded by NCI.
Dr. Bruce Christiansen, PI.

        

Veterans and Smoking Studies. Dr. Jessica Cook led this study at the William S. Middleton Memorial VA Hospital in Madison. The study tested the hypothesis that smokers with posttraumatic stress disorder (PTSD) and depression smoked cigarettes to improve aversive mood states and other mental health symptoms. The effect Dr. Cook was most interested in was whether smoking regulates anhedonia, a common feature of both PTSD and depression characterized by an inability to respond to pleasurable events. The first part of the study examined how nicotine influenced mood responses to positive and negative stimuli. The second part of the study was done at a critical point, 24 and 48 hours after being deprived of nicotine, which can be the peak of withdrawal. The team explored whether veterans with PTSD and depression had a more difficult time experiencing pleasure in response to rewarding events and whether they experienced more withdrawal-related negative affect. 2007-2014. Funded by NIDA. Dr. Jessica Cook, PI.