Effect of Varenicline Added to Counseling on Smoking Cessation Among African American Daily Smokers: The Kick It at Swope IV Randomized Clinical Trial.

Importance: African American smokers have among the highest rates of tobacco-attributable morbidity and mortality in the US, and effective treatment is needed for all smoking levels. Objectives: To evaluate the efficacy of varenicline vs placebo among African American adults who are light, moderate, and heavy daily smokers. Design, Setting, and Participants: The Kick It at Swope IV (KIS-IV) trial was a randomized, double-blind, placebo-controlled clinical trial conducted at a federally qualified health center in Kansas City. A total of 500 African American adults who were daily smokers of all smoking levels were enrolled from June 2015 to December 2017; final follow-up was completed in June 2018. Interventions: Participants were provided 6 sessions of culturally relevant individualized counseling and were randomized (in a 3:2 ratio) to receive varenicline (1 mg twice daily; n = 300) or placebo (n = 200) for 12 weeks. Randomization was stratified by sex and smoking level (1-10 cigarettes/d [light smokers] or >10 cigarettes/d [moderate to heavy smokers]). Main Outcomes and Measures: The primary outcome was salivary cotinine-verified 7-day point prevalence smoking abstinence at week 26. The secondary outcome was 7-day point prevalence smoking abstinence at week 12, with subgroup analyses for light smokers (1-10 cigarettes/d) and moderate to heavy smokers (>10 cigarettes/d). Results: Among 500 participants who were randomized and completed the baseline visit (mean age, 52 years; 262 [52%] women; 260 [52%] light smokers; 429 [86%] menthol users), 441 (88%) completed the trial. Treating those lost to follow-up as smokers, participants receiving varenicline were significantly more likely than those receiving placebo to be abstinent at week 26 (15.7% vs 6.5%; difference, 9.2% [95% CI, 3.8%-14.5%]; odds ratio [OR], 2.7 [95% CI, 1.4-5.1]; P = .002). The varenicline group also demonstrated greater abstinence than the placebo group at the end of treatment week 12 (18.7% vs 7.0%; difference, 11.7% [95% CI, 6.0%-17.7%]; OR, 3.0 [95% CI, 1.7-5.6]; P < .001). Smoking abstinence at week 12 was significantly greater for individuals receiving varenicline compared with placebo among light smokers (22.1% vs 8.5%; difference, 13.6% [95% CI, 5.2%-22.0%]; OR, 3.0 [95% CI, 1.4-6.7]; P = .004) and among moderate to heavy smokers (15.1% vs 5.3%; difference, 9.8% [95% CI, 2.4%-17.2%]; OR, 3.1 [95% CI, 1.1-8.6]; P = .02), with no significant smoking level × treatment interaction (P = .96). Medication adverse events were generally comparable between treatment groups, with nausea reported more frequently in the varenicline group (163 of 293 [55.6%]) than the placebo group (90 of 196 [45.9%]). Conclusions and Relevance: Among African American adults who are daily smokers, varenicline added to counseling resulted in a statistically significant improvement in the rates of 7-day point prevalence smoking abstinence at week 26 compared with counseling and placebo. The findings support the use of varenicline in addition to counseling for tobacco use treatment among African American adults who are daily smokers. Trial Registration: ClinicalTrials.gov Identifier: NCT02360631.

An Exploratory Study of Cognitive Function and Central Adiposity in Men Receiving Androgen Deprivation Therapy for Prostate Cancer.

OBJECTIVES: To prospectively assess cognitive function, anthropomorphic measures, and bone mineral density in men receiving androgen deprivation therapy (ADT) for prostate cancer; explore relationships between cognitive function and central adiposity; and gather preliminary data from a personalized education, exercise, and nutrition intervention. SAMPLE & SETTING: 33 participants consented from a randomized controlled intervention trial. METHODS & VARIABLES: Neurocognitive performance and self-report of cognitive function were assessed at baseline and 6 and 12 months. Dual-energy x-ray absorptiometry (DEXA) scans were obtained at baseline and 6 months. RESULTS: No between-group differences in cognitive function were demonstrated. Increased visceral adiposity was not associated with decrements in visuospatial abilities. Significant increases in fat mass without increases in body mass index or waist-hip ratio provided further evidence for DEXA as the preferred central adiposity measure. IMPLICATIONS FOR NURSING: Well-powered prospective research is needed to fully characterize the effects of ADT on cognitive function and the potential benefits of exercise and nutrition-based interventions.

A framework for personalized mammogram screening.

Breast cancer screening guidelines serve as crucial evidence-based recommendations in deciding when to begin regular screenings. However, due to developments in breast cancer research and differences in research interpretation, screening guidelines can vary between organizations and within organizations over time. This leads to significant lapses in adopting updated guidelines, variable decision making between physicians, and unnecessary screening for low to moderate risk patients (Jacobson and Kadiyala, 2017; Corbelli et al., 2014). For analysis, risk factors were assessed for patient screening behaviors and results. The outcome variable for the first analysis was whether the patient had undergone screening. The risk factors considered were age, marital status, education level, rural versus urban residence, and family history of breast cancer. The outcome variable for the second analysis was whether patients who had undergone breast cancer screening presented abnormal results. The risk factors considered were age, Body Mass Index, family history, smoking and alcohol status, hormonal contraceptive use, Hormone Replacement Therapy use, age of first pregnancy, number of pregnancies (parity), age of first menses, rural versus urban residence, and whether or not patients had at least one child. Logistic regression analysis displayed strong associations for both outcome variables. Risk of screening nonattendance was negatively associated with age as a continuous variable, age as a dichotomous variable, being married, any college education, and family history. Risk of one or more abnormal mammogram findings was positively associated with family history, and hormonal contraceptive use. This procedure will be further developed to incorporate additional risk factors and refine the analysis of currently implemented risk factors.

Coffee and cigarette smoking interactions with lamotrigine.

The objective of this analysis was to determine possible interactions between lamotrigine (LTG) and coffee or cigarette use. As part of the statistical analysis of factors influencing LTG pharmacokinetics (PK) in the Equigen chronic dose study, we collected prospective data from enrolled patients on their use of coffee and cigarettes. Subjects were part of a crossover replication study of generic LTG products with rigorous blood sampling and were instructed to not change their typical consumption of these products for the duration of the study. A total of 35 subjects were enrolled, with 33 subjects having sufficient data for analysis. Higher consumption of coffee was associated with a significantly lower area under the curve (AUC) and maximum concentration (Cmax) of lamotrigine (LTG). Higher cigarette use did not result in a significant change in AUC or Cmax. Coffee, but not cigarette use, either induces LTG metabolism or inhibits LTG absorption.

Improving the efficiency of clinical trials by standardizing processes for Investigator Initiated Trials.

Early phase clinical trials are the first step in testing new medications and therapeutics developed by clinical and biomedical investigators. These trials aim to find a safe dose of a newly targeted drug (phase I) or find out more about the side effects and early signals of treatment efficacy (phase II). In a research institute, many biomedical investigators in oncology are encouraged to initiate such trials early in their careers as part of developing their research portfolio. These investigator-initiated trials (IITs) are funded internally by the University of Kansas Cancer Center or partially funded by pharmaceutical companies. As financial, administrative, and practical considerations play an essential role in the successful completion of IITs, it is imperative to efficiently allocate resources to plan, design, and execute these studies within the allotted time. This manuscript describes monitoring tools and processes to improve the efficiency, cost-effectivness, and reliability of IITs. The contributions of this team to processes such as: participant recruitment, feasibility analysis, clinical trial design, accrual monitoring, data management, interim analysis support, and final analysis and reporting are described in detail. This manuscript elucidates how, through the aid of technology and dedicated personnel support, the efficiency of IIT-related processes can be improved. Early results of these initiatives look promising, and the Biostatistics and Informatics team intends to continue fostering innovative methodologies to enhance cancer research by improving the efficiency of IITs.

Perioperative Factors Affecting Ambulatory Outcomes Following Laparoscopic-Adjustable Gastric Banding.

OBJECTIVE: Morbidly obese patients are traditionally hospitalised following bariatric surgery. However, laparoscopic-adjustable gastric banding (LAGB) is amenable for ambulatory care. We hypothesised that the majority of patients can receive an ambulatory LAGB and that both surgical and anaesthetic perioperative factors will significantly affect non-ambulatory LAGB outcomes. METHODS: Medical records of 201 consecutive LAGB patients performed at the University of Kansas Medical Centre during a 3-y period were reviewed. Demographic, medical, laboratory, anaesthetic, intraoperative and postoperative data were collected. Factors associated with non-ambulatory outcomes were identified and analysed using logistic regression, and a classification tree analysis was used to rank the descriptive model factor to the non-ambulatory outcome. RESULTS: Average patient age was 43.4±11.4 years, and average body mass index was 48.2±10.3 kg m2-1. A total of 155 patients (77.1%; 95% confidence interval, 71%-83%; p<0.0001) were discharged home within 2-3 hours of surgery, whereas 36 stayed for 23 hours and 10 required hospital admission for 1-2 days. Increased surgical port numbers (p=0.007), ≥50% of total intraoperative fentanyl administered in the recovery room (post-anaesthesia care unit) for the treatment of postoperative pain (p=0.007) and a lack of prophylactic beta-blockade (p=0.001) were three factors associated with non-ambulatory outcomes. Obstructive sleep apnoea was not associated with a non-ambulatory outcome (p=0.83). CONCLUSION: The majority of patients received an ambulatory LAGB. Meticulous laparoscopic surgical technique with the least feasible number of access ports and multimodal analgesic technique aimed at reduction of postoperative opioid consumption are the most important factors for a successful ambulatory LAGB outcome.

Examining Smoking Dependence Motives among African American Light Smokers.

INTRODUCTION: Despite smoking fewer cigarettes per day, African American smokers have greater difficulty quitting compared to Caucasian smokers. Further elucidating the impact of smoking motivations on smoking behavior would contribute to understanding the factors that maintain smoking. AIMS: This study examined the factor structure of a brief assessment examining smoking dependence motives among a sample of African American light smokers. METHODS: Data from a double-blind, placebo-controlled randomized smoking cessation trial involving 540 participants. Results were analyzed using an exploratory factor analysis (EFA) and a randomly split EFA. RESULTS/FINDINGS: Findings from the initial EFA analysis produced an 8-factor model, explaining 69% of the variation in responses. The overall Measure of Sampling Adequacy (MSA) was 0.88 with item level MSA ranging 0.68-0.94 across the 30 items. Results from the randomly split EFA replicated the findings of the original EFA; with the exception of the item "I smoke within the first 30 minutes of awakening in the morning". CONCLUSIONS: These findings support the hypothesis of a multidimensional approach to conceptualizing nicotine dependence, and provide information regarding characteristics of nicotine dependence in African American light smokers which may be helpful in identifying targets for cessation treatment in this population of smokers.

Predictors of cessation in African American light smokers enrolled in a bupropion clinical trial.

BACKGROUND: This is the first study to examine predictors of successful cessation in African American (AA) light smokers treated within a placebo-controlled trial of bupropion. METHODS: We analyzed data from a randomized, double-blind, placebo-controlled trial of bupropion and health education for 540 African American light smokers. African American light smokers (≤10 cigarettes per day, cpd) were randomly assigned to receive 150mg bid bupropion SR (n=270) or placebo (n=270) for 7weeks. All participants received health education counseling at weeks 0, 1, 3, 5 and 7. Using chi-square tests, two sample t-tests, and multiple logistic regression analyses, we examined baseline psychosocial and smoking characteristics as predictors of cotinine-verified 7-day point prevalence smoking abstinence among study participants at the end treatment (Week 7) and at the end of follow-up (Week 26). RESULTS: Participants who received bupropion were significantly more likely to quit smoking compared to those who received placebo (OR=2.72, 95% CI=1.60-4.62, P=0.0002). Greater study session attendance (OR=2.47, 95% CI=1.76-3.46, P=0.0001), and smoking non-menthol cigarettes increased the likelihood of quitting (OR=1.84, 95% CI=1.01-3.36, P=0.05); while longer years of smoking (OR=0.98, 95% CI=0.96-1.00, P=0.05) and higher baseline cotinine (OR=0.97, 95% CI=0.95-0.99, P=0.002) significantly reduced the odds of quitting at Week 7. Conversely, at the end of follow-up (Week 26), treatment with bupropion vs. placebo (OR=1.14, 95% CI=0.65-2.02, P=0.64) was not significantly associated with quitting and type of cigarette smoked (menthol vs. non-menthol) did not appear in the final logistic regression model. Greater study session attendance (OR=1.96, 95% CI=1.44-2.66, P=0.0001); BMI (OR=1.03, 95% CI=1.00-1.07, P=0.04); and weight efficacy (OR=1.03, 95% CI=1.01-1.05, P=0.01) increased the likelihood of quitting at Week 26. Similar to our findings at Week 7, longer years of smoking (OR=0.96, 95% CI=0.94-0.99, P=0.01) and higher baseline cotinine (OR=0.97, 95% CI=0.95-0.99, P=0.02) significantly reduced the odds of quitting at Week 26. CONCLUSIONS: Baseline cotinine levels, number of years smoked and study session attendance are associated with both short- and long-term smoking cessation, while bupropion and the type of cigarette smoked were associated with quitting on short term only.

Evaluation of the brief questionnaire of smoking urges in Black light smokers.

INTRODUCTION: This study evaluated the factor structure of the Brief Questionnaire of Smoking Urges (QSU-Brief) within a sample of Black light smokers (1-10 cigarettes per day). METHODS: The QSU-Brief was administered to 540 (mean age = 46.5; 66.1% women) urban Black light smokers upon entering a smoking cessation clinical trial. An exploratory factor analysis (EFA) was conducted to evaluate the factor structure of this 10-item measure. RESULTS: An EFA indicated that as in other samples, the construct of craving in a Black sample is defined by 2 factors; 1 factor emphasizing the positive reinforcement of smoking and the other factor emphasizing the negative reinforcement properties of smoking. CONCLUSIONS: Findings largely replicate a 2-factor structure of craving seen in smokers from other racial/ethnic groups, demonstrating the clinical utility of the QSU-Brief in measuring craving in Black light smokers.

Assessment of depression among African American light smokers.

Given the relationship between depression and smoking, we compared the two-item Patient Health Questionnaire (PHQ-2) and 10-item Center for Epidemiological Studies Depression Scale (CESD-10) in assessing depressive symptoms among African American light smokers in a clinical trial of bupropion. Of 539 participants, 21.3 percent reported significant depressive symptoms on the PHQ-2, 31.0 percent screened positive per CESD-10, 36.8 percent reported symptoms on either, and 15.6 percent screened positive on both (r = 0.47, p < .001). Having depressive symptoms was associated with less education, decreased positive affect and social support, and greater levels of negative affect and perceived stress. Cessation treatment should assess depression and address these symptoms.

Factors associated with smoking menthol cigarettes among treatment-seeking African American light smokers.

BACKGROUND: Smoking menthol cigarettes is more prevalent among African Americans (AA) compared to Whites. Menthol has been found to be inversely related to smoking cessation among AA, yet little is known about the factors associated with menthol smoking among AA light smokers. This study examines baseline demographic, psychological, and smoking factors associated with smoking menthol cigarettes among AA light smokers (≤10 cigarettes per day). METHODS: Participants (n=540) were enrolled in a double blind, placebo-controlled randomized trial of bupropion in combination with health education counseling for smoking cessation. Bivariate differences between menthol and non-menthol smokers were explored and baseline factors associated with smoking menthol cigarettes were identified. RESULTS: Participants averaged 46.5 years in age, predominantly female (66.1%), and smoked an average of 8.0 cpd (SD=2.5). The majority (83.7%) smoked menthol cigarettes. In bivariate analysis, menthol cigarette smokers were younger (mean age: 45 vs. 52 years p<0.0001), were more likely to be female (68% vs. 52% p=0.003) and had smoked for shorter duration (28 vs. 34 years p<0.0001) compared to non-menthol smokers. While depression and withdrawal scores were slightly higher and exhaled carbon monoxide values were lower among menthol smokers, the differences were not statistically significant. CONCLUSIONS: Among AA light smokers, younger individuals and females were more likely to smoke menthol cigarettes and may be more susceptible to the health effects of smoking. Appropriately targeted health education campaigns are needed to prevent smoking uptake in this high-risk population.

Design, baseline characteristics, and retention of African American light smokers into a randomized trial involving biological data.

BACKGROUND: African Americans experience significant tobacco-related health disparities despite the fact that over half of African American smokers are light smokers (use ≤ 10 cigarettes per day). African Americans have been under-represented in smoking cessation research, and few studies have evaluated treatment for light smokers. This paper describes the study design, measures, and baseline characteristics from Kick It at Swope III (KIS-III), the first treatment study of bupropion for African American light smokers. METHODS: Five hundred forty African American light smokers were randomly assigned to receive bupropion (150 mg bid) (n = 270) or placebo (n = 270) for 7 weeks. All participants received written materials and health education counseling. Participants responded to survey items and provided blood samples for evaluation of phenotype and genotype of CYP2A6 and CYP2B6 enzymes involved in nicotine and bupropion metabolism. Primary outcome was cotinine-verified 7-day point prevalence smoking abstinence at Week 26 follow-up. RESULTS: Of 2,628 individuals screened, 540 were eligible, consented, and randomized to treatment. Participants had a mean age of 46.5 years and 66.1% were women. Participants smoked an average of 8.0 cigarettes per day, had a mean exhaled carbon monoxide of 16.4 ppm (range 1-55) and a mean serum cotinine of 275.8 ng/ml. The mean Fagerström Test for Nicotine Dependence was 3.2, and 72.2% of participants smoked within 30 minutes of waking. The average number of quit attempts in the past year was 3.7 and 24.2% reported using pharmacotherapy in their most recent quit attempt. Motivation and confidence to quit were high. CONCLUSION: KIS-III is the first study designed to examine both nicotine and bupropion metabolism, evaluating CYP2A6 and CYP2B6 phenotype and genotype in conjunction with psychosocial factors, in the context of treatment of African American light smokers. Of 1629 smokers screened for study participation, only 18 (1.1%) were ineligible to participate in the study because they refused blood draws, demonstrating the feasibility of recruiting and enrolling African American light smokers into a clinical treatment trial involving biological data collection and genetic analyses. Future evaluation of individual factors associated with treatment outcome will contribute to advancing tailored tobacco use treatment with the goal of enhancing treatment and reducing health disparities for African American light smokers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00666978.

Predictors of positive surgical margins after radical perineal prostatectomy.

INTRODUCTION/OBJECTIVE: Margin positivity has been a well described adverse prognostic factor in patients undergoing radical prostatectomy. Previous studies with regards to predictors of margin positivity after prostatectomy have primarily focused on the retropubic or robotic approach. We sought to examine the predictors of margin positivity in a contemporary series of men undergoing radical perineal prostatectomy (RPP). MATERIALS AND METHODS: We reviewed the records of 103 patients who underwent RPP at our institution from July 1998 until May 2008. A positive surgical margin (PSM) was defined as the presence of cancer cells at the inked margin of the surgical specimen. Records were reviewed for the following preoperative parameters: age at operation, body mass index (BMI), preoperative PSA, clinical stage and biopsy Gleason sum score. Pathological data included prostate weight (PW) and tumor volume. RESULTS: Mean age was 60.9 (range 45-76). Mean BMI was 31.4 kg/m2 (20.9-51.6). The preoperative prevalence of palpable disease was 50.5%. A PSM was found in 23.3%. Age, BMI, clinical stage, biopsy Gleason sum score and preoperative PSA were not found to be independent predictors of a PSM after RPP. Only prostate weight was found to be a significant preoperative predictor of a PSM after RPP with men with smaller prostates at higher risk. CONCLUSIONS: Prostate weight was found to be significantly and inversely related to the PSM rate in this cohort of RPP patients. Patients with smaller volume prostates should be counseled preoperatively that they are at higher risk for a PSM when undergoing a RPP.