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.

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.

Weight management in adults with intellectual and developmental disabilities: A randomized controlled trial of two dietary approaches.

BACKGROUND: The prevalence of obesity among individuals with intellectual and developmental disabilities (IDD) is equal to or greater than the general population. METHODS: Overweight/obese adults (BMI ≥25 kg/m2 ) with mild-to-moderate intellectual and developmental disabilities were randomized to an enhanced stop light diet (eSLD = SLD + portion-controlled meals, n = 78) or a conventional diet (CD, n = 72) for an 18 months trial (6 months weight loss, 12 months maintenance). Participants were asked to increase physical activity (150 min/week), self-monitor diet and physical activity and attend counselling/educational sessions during monthly home visits. RESULTS: Weight loss (6 months) was significantly greater in the eSLD (-7.0% ± 5.0%) compared with the CD group (-3.8% ± 5.1%, p < .001). However, at 18 months, weight loss between groups did not differ significantly (eSLD = -6.7% ± 8.3%; CD = 6.4% ± 8.6%; p = .82). CONCLUSION: The eSLD and CD provided clinically meaningful weight loss over 18 months in adults with intellectual and developmental disabilities.

Weight management in rural health clinics: Results from the randomized midwest diet and exercise trial.

Introduction: Rural living adults have higher rates of obesity compared with their urban counterparts and less access to weight management programs. Previous research studies have demonstrated clinically relevant weight loss in rural living adults who complete weight management programs delivered by university affiliated interventionists. However, this approach limits the potential reach, adoption, implementation, and maintenance of weight management programs for rural residents. Weight management delivered through rural health clinics by non-physician clinic associated staff, for example, nurses, registered dieticians, allied health professionals, etc. has the potential to improve access to weight management for rural living adults. This trial compared the effectiveness of a 6-month multicomponent weight management intervention for rural living adults delivered using group phone calls (GP), individual phone calls (IP) or an enhanced usual care control (EUC) by rural clinic associated staff trained by our research team. Methods: Rural living adults with overweight/obesity (n = 187, age âˆ¼ 50 years 82% female, body mass index ∼35 kg/m2) were randomized (2:2:1) to 1 of 3 intervention arms: GP, which included weekly âˆ¼ 45 min sessions with 7-14 participants (n = 71), IP, which included weekly âˆ¼ 15 min individual sessions (n = 80), or EUC, which included one-45 min in-person session at baseline. Results: Weight loss at 6 months was clinically relevant, that is, ≥5% in the GP (-11.4 kg, 11.7%) and the IP arms (-9.1 kg, 9.2%) but not in the EUC arm (-2.6%, -2.5% kg). Specifically, 6 month weight loss was significantly greater in the IP versus EUC arms (-6.5 kg. p ≤ 0.025) but did not differ between the GP and IP arms (-2.4 kg, p > 0.025). The per participant cost per kg. weight loss for implementing the intervention was $93 and $60 for the IP and GP arms, respectively. Conclusions: Weight management delivered by interventionists associated with rural health clinics using both group and IP calls results in clinically relevant 6 months weight loss in rural dwelling adults with overweight/obesity with the group format offering the most cost-effective strategy. Clinical trial registration: ClinicalTrials.gov (NCT02932748).

Utility of dexmedetomidine in sedation for radiofrequency ablation of atrial fibrillation.

The utility of dexmedetomidine (DEX) as an adjunct to conventional procedural sedation using midazolam and fentanyl was evaluated in 11 adult patients undergoing radiofrequency catheter ablation (RFCA) of atrial fibrillation. In a subsequent comparison to 11 demographically matched controls (n = 22) that previously received only midazolam- and fentanyl-based sedation, no significant differences in consumption of midazolam (median, 5 vs 10 mg; P = .3), fentanyl (median, 275 vs 400 mcg, P = .2), respiratory parameters, and procedural outcome were found. However, median reductions of arterial blood pressure were significant: systolic (-26.1 vs -16.7 mm Hg, P = .006), diastolic (-26.7 vs -2.9 mm Hg, P = .01), and mean (-25.8 vs -8.5 mm Hg, P = .006). Reductions of blood pressure limited utility of DEX as adjunct in sedation for RFCA of atrial fibrillation.

A randomized trial comparing diet and delivery strategies for weight management in adolescents with intellectual disabilities.

BACKGROUND: The literature evaluating multi-component interventions for long-term weight loss in adolescents with intellectual disabilities (ID) is extremely limited. OBJECTIVES: To compare the effectiveness of two delivery strategies, face-to-face (FTF) or remote delivery (RD), and two diets, enhanced Stop Light diet (eSLD) or conventional diet (CD) on weight change across 12 and 18 months. in response to an 18 months. weight management intervention (6 months Weight loss/12 months. Weight maintenance) in adolescents with ID. METHODS: Adolescents with ID were randomized to one of three arms: FTF /CD, RD/CD, RD/eSLD and asked to attend individual education sessions with a health educator which were delivered during FTF home visits or remotely using video conferencing. The CD followed the US dietary guidelines. The eSLD utilized the Stop Light guide and was enhanced with portion-controlled meals. Participants were also asked to increase their physical activity (PA) and to self-monitor diet, PA and body weight across the 18-month. RESULTS: Weight was obtained from 92(84%) and 89(81%) randomized adolescents at 12 and 18 months, respectively. Weight change across 12 months. Differed significantly by diet (RD/eSLD: -7.0% vs. RD/CD: -1.1%, p = 0.002) but not by delivery strategy (FTF/CD: +1.1% vs. RD/CD: -1.1%, p = 0.21). Weight change across 18 months. Was minimal in all intervention arms and did not differ by diet (RD/eSLD: -2.6% vs. RD/CD: -0.5%; p = 0.28) or delivery strategy (FTF/CD: +1.6% vs. RD/CD: -0.5%; p = 0.47). CONCLUSIONS: Additional research is required to identify effective strategies to improve long-term weight loss in adolescents with ID.

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.

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.

Weight Loss Interventions for Adolescents With Intellectual Disabilities: An RCT.

OBJECTIVES: In this randomized trial, we compared the effectiveness of 2 diets (enhanced stop light diet [eSLD] versus conventional meal plan diet [CD]) and 2 delivery strategies (face-to-face [FTF] versus remote delivery [RD]) on weight loss across 6 months in adolescents with intellectual and developmental disabilities who were overweight or obese. METHODS: Participants were randomly assigned to 1 of 3 arms (FTF/CD, RD/CD, or RD/eSLD) and asked to attend one-on-one sessions with a health educator every 2 weeks to aid in maintaining compliance with recommendations for a reduced-energy diet and increased physical activity. The CD followed the US dietary guidelines. The eSLD used the stop light guide and was enhanced with portion-controlled meals. The FTF arm was delivered during in-person home visits. The RD arms were delivered by using video conferencing. RESULTS: A total of 110 adolescents with intellectual and developmental disabilities (aged ∼16 years, 53% female, BMI 33) were randomly assigned to the FTF/CD (n = 36), RD/CD (n = 39), or RD/eSLD (n = 35) group. Body weight at 6 months was obtained from 97%, 100%, and 86% of participants in the FTF/CD, RD/CD, and RD/eSLD arms, respectively. The eSLD elicited significantly greater weight loss than the CD: RD/eSLD (-5.0 ± 5.9 kg; -6.4%) versus RD/CD (-1.8 ± 4.0 kg; -2.4%) (P = .01). However, weight loss did not differ by delivery strategy: FTF/CD (-0.3 ± 5.0 kg; -0.2%) versus RD/CD (-1.8 ± 4.0 kg; -2.4%) (P = .20). CONCLUSIONS: The eSLD elicited significantly greater 6-month weight loss compared with a CD when both interventions were delivered remotely. Minimal 6-month weight loss, which did not differ significantly between FTF delivery and RD, was observed with a CD.

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.

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.

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.

Bioequivalence Between Generic and Branded Lamotrigine in People With Epilepsy: The EQUIGEN Randomized Clinical Trial.

Importance: Switching between generic antiepileptic drugs is a highly debated issue that affects both clinical care and overall health care costs. Objective: To evaluate the single-dose pharmacokinetic bioequivalence of 3 (1 branded and 2 generic drugs) on-market, immediate-release lamotrigine drug products. Design, Setting, and Participants: The Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy (EQUIGEN) single-dose study is a crossover, prospective, sequence-randomized, replicate pharmacokinetic study conducted at 5 US academic epilepsy centers. Fifty adults (≥18 years) with epilepsy who were taking concomitant antiepileptic drugs and not currently receiving lamotrigine were enrolled between July 18, 2013, and January 19, 2015. Every participant was randomly assigned to 1 of 3 equivalent sequences, each comprising 6 study periods, during which they had blood draws before and after medication administration. Forty-nine participants were included in intention-to-treat analyses. Interventions: Participants received a single 25-mg dose of immediate-release lamotrigine at the start of each period, with the branded and the 2 most disparate generic products each studied twice. Lamotrigine was selected as the antiepileptic drug of interest because of its wide use, publications indicating problems with generic switches, and complaints to the US Food and Drug Administration regarding generic products. Both participants and study personnel were blinded to the specific generic products selected. Main Outcomes and Measures: The primary outcome was bioequivalence between products. Maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) were compared, and average bioequivalence (ABE) was established if the 90% CIs of the ratios of the 2 products were within equivalence limits (80%-125%). Results: Of the 50 randomized participants, 49 (98%) received all 3 lamotrigine products and completed at least 3 pharmacokinetic assessments and 46 (92%) completed all 6 pharmacokinetic assessments. Among the 49 participants, 28 (57%) were men and 21 (43%) were women, 42 (86%) self-identified as white, and 46 (16) years was the mean (SD) age. The 3 drug products were considered bioequivalent because the 90% CIs were within equivalence limits (lowest and highest CI limits for Cmax, 92.6% and 110.4%; for AUC0-96, 96.9% and 101.9%). Replicate testing demonstrated no significant differences in within-subject variability across the 3 products (likelihood ratios, χ22 for log-transformed variables: AUC0-96, 2.58; Cmax, 0.64; and AUC0-∞, 4.05; P ≥ .13) and that the 3 products were also bioequivalent according to scaled ABE and individual bioequivalence criteria with no subject × formulation interaction (Cmax, 0.00; AUC0-96, 0.54; and AUC0-∞, 0.36; P ≥ .76). Conclusions and Relevance: This study provides evidence that the disparate lamotrigine products studied are bioequivalent when tested in people with epilepsy taking concomitant antiepileptic drugs. Trial Registration: clinicaltrials.gov Identifier: NCT01733394.

Generic-to-generic lamotrigine switches in people with epilepsy: the randomised controlled EQUIGEN trial.

BACKGROUND: Patients and clinicians share concerns that generic drug substitution might lead to loss of efficacy or emergence of adverse events. In this trial, we assessed US Food and Drug Administration (FDA) bioequivalence standards by studying the effects of switching between two disparate generic immediate-release lamotrigine products in patients with epilepsy. METHODS: The Equivalence among Generic Antiepileptic Drugs (EQUIGEN) chronic-dose study was a randomised, double-blind, crossover study that enrolled adults (aged ≥18 years) with epilepsy from six epilepsy centres at academic institutions across the USA who were receiving immediate-release lamotrigine dosed at 100 mg, 200 mg, 300 mg, or 400 mg twice daily. Eligible patients were randomly allocated (1:1) to one of two treatment sequences (sequence 1 or sequence 2), comprising four study periods of 14 days each. During each 14-day treatment period, patients received balanced doses of an oral generic lamotrigine product every 12 h (200-800 mg total, identical to lamotrigine dose prior to study enrolment); after each 14-day period, patients were crossed over to receive the other generic product. Computer-based randomisation was done using random permuted blocks of size two or four for each site to prevent sequence predictability. Both patients and study personnel were masked to the generic products selected, their predicted exposure (ie, "high" vs "low"), and their group allocation. The primary outcome of this trial was bioequivalence between the generic products, which was assessed at the end of the study through a comparison of maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) for each product in the analysis population (all patients who completed all four treatment periods). Bioequivalence was established if the 90% CIs of the ratios of these two parameters for the two products were within equivalence limits (80-125%) in the analysis population. This study is registered with ClinicalTrials.gov\, number NCT01713777. FINDINGS: Between April 25, 2013, and Aug 12, 2014, 35 eligible patients were enrolled and randomly assigned to treatment sequence 1 (n=15) or treatment sequence 2 (n=20). 33 patients completed all four treatment periods and were included in the primary outcome analysis. The 90% CIs of the ratios of both Cmax and AUC were within equivalence limits (AUC 90% CI 98-103, Cmax 90% CI 99-105), showing that lamotrigine exposures were equivalent between the generic products. No significant changes in seizure frequency or adverse events were recorded. No deaths, study-related serious adverse events, or changes in clinical laboratory values or vital signs occurred during this study. INTERPRETATION: Disparate generic lamotrigine products in patients with epilepsy showed bioequivalence with no detectable difference in clinical effects, confirming that US Food and Drug Administration bioequivalence standards are appropriate. FUNDING: American Epilepsy Society, Epilepsy Foundation, and US Food and Drug Administration.

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.

Random-effects linear modeling and sample size tables for two special crossover designs of average bioequivalence studies: the four-period, two-sequence, two-formulation and six-period, three-sequence, three-formulation designs.

Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the researchers could not find commercial or non-commercial statistical software that quickly allowed computation of sample sizes for their designs, particularly software implementing the FDA requirement of using random-effects linear models for the analyses of bioequivalence studies. This article presents tables for sample-size evaluations of average bioequivalence studies based on the two crossover designs used in the EQUIGEN studies: the four-period, two-sequence, two-formulation design, and the six-period, three-sequence, three-formulation design. Sample-size computations assume that random-effects linear models are used in bioequivalence analyses with crossover designs. Random-effects linear models have been traditionally viewed by many pharmacologists and clinical researchers as just mathematical devices to analyze repeated-measures data. In contrast, a modern view of these models attributes an important mathematical role in theoretical formulations in personalized medicine to them, because these models not only have parameters that represent average patients, but also have parameters that represent individual patients. Moreover, the notation and language of random-effects linear models have evolved over the years. Thus, another goal of this article is to provide a presentation of the statistical modeling of data from bioequivalence studies that highlights the modern view of these models, with special emphasis on power analyses and sample-size computations.

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.