Concurrent Choice Assessment of Preference and Substitutability of E-cigarettes and Heated Tobacco Products for Combustible Cigarettes Among African American and White Smokers.

INTRODUCTION: Alternative nicotine delivery products, including electronic cigarettes (e-cigarettes) and heated tobacco products (HTPs), contain fewer toxicants than combustible cigarettes and offer a potential for harm reduction. Research on the substitutability of e-cigarettes and HTPs is crucial for understanding their impact on public health. This study examined subjective and behavioral preferences for an e-cigarette and HTP relative to participants' usual brand combustible cigarette (UBC) in African American and White smokers naïve to alternative products. AIMS AND METHODS: Twenty-two adult African American (n = 12) and White (n = 10) smokers completed randomized study sessions with their UBC and study provided e-cigarette and HTP. A concurrent choice task allowed participants to earn puffs of the products but placed UBC on a progressive ratio schedule, making puffs harder to earn, and e-cigarette and HTP on a fixed ratio schedule to assess behavioral preference for the products. Behavioral preference was then compared to self-reported subjective preference. RESULTS: Most participants had a subjective preference for UBC (n = 11, 52.4%), followed by an equal preference for e-cigarette (n = 5, 23.8%) and HTP (n = 5, 23.8%). During the concurrent choice task, participants showed a behavioral preference (i.e., more earned puffs) for the e-cigarette (n = 9, 42.9%), followed by HTP (n = 8, 38.1%), and UBC (n = 4, 19.1%). Participants earned significantly more puffs of the alternative products compared to UBC (p = .011) with no difference in earned puffs between e-cigarettes and HTP (p = .806). CONCLUSIONS: In a simulated lab setting, African American and White smokers were willing to substitute UBC for an e-cigarette or HTP when the attainment of UBC became more difficult. TRIAL REGISTRATION: NCT04646668. IMPLICATIONS: Findings suggest that African American and White smokers are willing to substitute their UBC for an alternative nicotine delivery product (e-cigarette or HTP) when the attainment of cigarettes became more difficult in a simulated lab setting. Findings require confirmation among a larger sample under real-world conditions but add to growing evidence suggesting the acceptability of alternative nicotine delivery products among racially diverse smokers. These data are important as policies that limit the availability or appeal of combustible cigarettes are considered or enacted.

Menthol versus non-menthol flavouring and switching to e-cigarettes in black and Latinx adult menthol combustible cigarette smokers: secondary analyses from a randomised clinical trial.

BACKGROUND: As the US Food and Drug Administration takes regulatory action on menthol cigarettes, debate continues about how restricting menthol e-liquids might impact adult menthol smokers in switching to e-cigarettes. METHODS: Switching patterns and e-cigarette acceptability were assessed at week 6 among 64 black and Latinx menthol cigarette smokers who used JUUL menthol (n=39) or non-menthol e-cigarettes ((n=25), primarily mint or mango) as part of a randomised switching trial. RESULTS: No clear evidence of effects was found between menthol versus non-menthol e-cigarettes on use or subjective effects/acceptability, effect sizes for all comparisons were small (effect size=0.0-0.2), and Bayes factor ranged from 0.10 to 0.15. Specifically, 82.1% of participants who used menthol-flavoured e-cigarettes fully or partially switched to e-cigarettes compared with 88.0% of participants who used a non-menthol (p=0.75). Further, both groups demonstrated substantial reductions in cigarettes per day (menthol e-cigarettes: -8.5±10.4 vs non-menthol e-cigarettes: -8.8±5.8, p=0.87), comparable grams of e-liquid consumed (menthol e-cigarettes: 9.2±9.8 g vs non-menthol e-cigarettes: 11.0±11.0 g, p=0.47), and positive subjective effects, including 'just right' throat hit (menthol e-cigarettes: 70.7% vs non-menthol e-cigarettes: 66.7%, p=0.93) and flavour liking (menthol e-cigarettes: 75.6% vs non-menthol e-cigarettes: 66.7%, p=0.32). CONCLUSIONS: Both menthol and non-menthol e-cigarettes were associated with high rates of use and acceptability among menthol smokers. Findings require confirmation in a fully powered non-inferiority or equivalence study but provide preliminary evidence to inform regulatory action on menthol e-cigarettes that could slow youth initiation without impacting black and Latinx menthol cigarette smokers interested in switching to e-cigarettes. TRIAL REGISTRATION NUMBER: NCT03511001.

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.

Harm Reduction Associated with Dual Use of Cigarettes and e-Cigarettes in Black and Latino Smokers: Secondary Analyses from a Randomized Controlled e-Cigarette Switching Trial.

INTRODUCTION: Most adult cigarette smokers who use e-cigarettes are dual cigarette and e-cigarette (CC-EC) users, yet little is known about relative consumption of cigarettes to e-cigarettes and any associated harm reduction. METHODS: Rate of substitution from cigarettes to e-cigarettes at week 6 and change in biomarkers of exposure and potential harm were examined among dual dual cigarette and e-cigarette users [64/114 (56%); 35 Black, 29 Latino] in an e-cigarette switching randomized trial. RESULTS: Dual users averaged 79% substitution of cigarettes for e-cigarettes at week 6, resulting in a reduction from baseline of 70.0 ± 54.1 cigarettes per week (p < .001). Total nicotine consumption remained stable (baseline: 1160.5 ± 1042.1 pg/mL of cotinine, week 6: 1312.5 ± 1725.9 pg/mL of cotinine, p = .47), while significant reductions were seen in the potent lung carcinogen 4-(methylnitrosamino)-1-(3-pyridul)-1-butanol (NNAL) (-55.9 ± 88.6 ng/ml, p < .001), carbon monoxide (-6.3 ± 8.6 ppm, p < .001), and self-reported respiratory symptoms (-3.3 ± 8.0, p = .002). No significant changes were found in blood pressure or spirometry. Greater substitution from cigarettes to e-cigarettes was associated with larger reductions in NNAL (r = -.29, p = .02). CONCLUSIONS: The predominant dual-use pattern was characterized by regular e-cigarette and intermittent cigarette use. Findings demonstrate the short-term harm reduction potential of this dual-use pattern in Black and Latino smokers and suggest that the greatest benefit, aside from cessation of both products, is achieved by higher substitution of e-cigarettes for cigarettes. Findings need confirmation in a larger sample with longer follow-up in dual users with greater variability in the rate of substitution. CLINICALTRIALS.GOV IDENTIFIER: NCT03511001. IMPLICATIONS: Findings suggest short-term harm reduction potential of dual cigarette-e-cigarette use for Black and Latino smokers. Results also demonstrate the heterogeneity of dual-use, with the greatest harm reduction seen in dual users with higher rates of substitution from cigarettes to e-cigarettes. Study results should be confirmed in a full clinical trial with long-term follow-up to evaluate maintenance of dual-use patterns and associated harm reduction potential over time.

Designing and analyzing clinical trials for personalized medicine via Bayesian models.

Patients with different characteristics (e.g., biomarkers, risk factors) may have different responses to the same medicine. Personalized medicine clinical studies that are designed to identify patient subgroup treatment efficacies can benefit patients and save medical resources. However, subgroup treatment effect identification complicates the study design in consideration of desired operating characteristics. We investigate three Bayesian adaptive models for subgroup treatment effect identification: pairwise independent, hierarchical, and cluster hierarchical achieved via Dirichlet Process (DP). The impact of interim analysis and longitudinal data modeling on the personalized medicine study design is also explored. Interim analysis is considered since they can accelerate personalized medicine studies in cases where early stopping rules for success or futility are met. We apply integrated two-component prediction method (ITP) for longitudinal data simulation, and simple linear regression for longitudinal data imputation to optimize the study design. The designs' performance in terms of power for the subgroup treatment effects and overall treatment effect, sample size, and study duration are investigated via simulation. We found the hierarchical model is an optimal approach to identifying subgroup treatment effects, and the cluster hierarchical model is an excellent alternative approach in cases where sufficient information is not available for specifying the priors. The interim analysis introduction to the study design lead to the trade-off between power and expected sample size via the adjustment of the early stopping criteria. The introduction of the longitudinal modeling slightly improves the power. These findings can be applied to future personalized medicine studies with discrete or time-to-event endpoints.

Sample size calculation for two-arm trials with time-to-event endpoint for nonproportional hazards using the concept of Relative Time when inference is built on comparing Weibull distributions.

Sample size calculations for two-arm clinical trials with a time-to-event endpoint have traditionally used the assumption of proportional hazards (PH) or the assumption of exponentially distributed survival times. Available software provides methods for sample size calculation using a nonparametric logrank test, Schoenfeld's formula for Cox PH model, or parametric calculations specific to the exponential distribution. In cases where the PH assumption is not valid, the first-choice method is to compute sample size assuming a piecewise linear survival curve (Lakatos approach) for both the control and treatment arms with judiciously chosen cut-points. Recent advances in literature have used the assumption of Weibull distributed times for single-arm trials, and, newer methods have emerged that allow sample size calculations for two-arm trials using the assumption of proportional time (PT) while considering non-PH. These methods, however, always assume an instantaneous effect of treatment relative to control requiring that the effect size be defined by a single number whose magnitude is preserved throughout the trial duration. Here, we consider the scenarios where the hypothesized benefit of treatment relative to control may not be constant giving rise to the notion of Relative Time (RT). By assuming that survival times for control and treatment arm come from two different Weibull distributions with different location and shape parameters, we develop the methodology for sample size calculation for specific cases of both non-PH and non-PT. Simulations are conducted to assess the operation characteristics of the proposed method and a practical example is discussed.

Utilization of Technology to Improve Efficiency in Investigational Drug Management Processes.

Background: Background: An investigational pharmacy is responsible for all tasks related to receiving, storing, and dispensing of any investigational drugs. Traditional methods of inventory and protocol tracking on paper binders are very tedious and could be error-prone. Objective: To evaluate the utilization of the IDS to efficiently manage the inventory within an investigational Pharmacy. We hypothesize that the IDS will reduce the drug processing time. Methods: Our pharmacy tracked the drug processing time before and after using the IDS including the receiving, dispensing, and inventory. As part of the receiving the study drug pharmacists tracked the time it took a pharmacist to complete the tasks of logging the study drug before and after the implementation of the IDS system. In addition, the pharmacy also timed the process for drug dispensing and a full investigational drug inventory check. Wilcoxon signed-rank test was used to compare the difference in the meantime of total processing before and after the IDS. Results: Utilization of the IDS system showed significant reduction in processing time, and improvement of efficiency in inventory management. Additionally, the usability survey of the IDS demonstrated that the IDS system helped pharmacists capture data consistently across every clinical trial. Conclusion: Our results demonstrates how technology helps pharmacists to focus on their actual day to day medication-related tasks rather than worrying about other operational aspects. Informatics team continues to further enhance the features such as monitor portal, and features related to finance - generation of invoices, billing reconciliation, etc.

Accrual Prediction Program: A web-based clinical trials tool for monitoring and predicting accrual for early-phase cancer studies.

BACKGROUND: Monitoring subject recruitment is key to the success of a clinical trial. Accordingly, researchers have developed accrual-monitoring tools to support the design and conduct of trials. At an institutional level, delays in identifying studies with high risk of accrual failure can lead to inefficient and costly trials with little chances of meeting study objectives. Comprehensive accrual monitoring is necessary to the success of the research enterprise. METHODS: This article describes the design and implementation of the University of Kansas Cancer Center Accrual Prediction Program, a web-based platform was developed to support comprehensive accrual monitoring and prediction for all active clinical trials. The Accrual Prediction Program provides information on accrual, including the predicted completion date, predicted number of accrued subjects during the pre-specified accrual period, and the probability of achieving accrual targets. It relies on a Bayesian accrual prediction model to combine protocol information with real-time trial enrollment data and disseminates results via web application. RESULTS: First released in 2016, the Accrual Prediction Program summarizes enrollment information for active studies categorized by various trial attributes. The web application supports real-time evidence-based decision making for strategic resource allocation and study management of over 120 ongoing clinical trials at the University of Kansas Cancer Center. CONCLUSION: The Accrual Prediction Program makes accessing comprehensive accrual information manageable at an institutional level. Cancer centers or even entire institutions can reproduce the Accrual Prediction Program to achieve real-time comprehensive monitoring and prediction of subject accrual to aid investigators and administrators in the design, conduct, and management of clinical trials.

Comments on "Tutorial on statistical considerations on subgroup analysis in confirmatory clinical trials".

This paper is the letter to the editor regarding several comments on 'Tutorial on statistical considerations on subgroup analysis in confirmatory clinical trials.'

Bayesian design for two-arm randomized Phase II clinical trials with endpoints from the exponential family using multiple constraints.

Frequentist design for two-arm randomized Phase II clinical trials with outcomes from the exponential dispersion family was proposed previously, where the total sample sizes are minimized under multiple constraints on the standard errors of the estimated group means and their difference. This design was generalized from an approach specific for dichotomous outcomes. The two previous approaches measure the central tendency of each group and treatment effect based on mean and difference in means. Other measures such as median or hazard ratio are more appropriate under certain situations. In addition, the frequentist approaches assume that unknown parameters are fixed values. This does not reflect the reality that uncertainty always exists for unknowns. Compared to the frequentist methods, the Bayesian approach offers a flexible way to measure central tendency and treatment effect, and incorporate uncertainty in parameters of interest into considerations. In this article, we generalize a Bayesian design for Phase II clinical trials with endpoints in the exponential family from the two previously developed frequentist approaches. The proposed design minimizes the total sample sizes under pre-specified constraints on the expected length of posterior credible intervals for measures of treatment effect and central tendency in each group. The design is applicable for trials with fixed or optimal randomization allocation ratio and can be applied under adaptive procedure. Examples of method implementations are provided for different types of endpoints from the exponential family in both fixed and adaptive settings.

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.

A clinical trial design using the concept of proportional time using the generalized gamma ratio distribution.

Traditional methods of sample size and power calculations in clinical trials with a time-to-event end point are based on the logrank test (and its variations), Cox proportional hazards (PH) assumption, or comparison of means of 2 exponential distributions. Of these, sample size calculation based on PH assumption is likely the most common and allows adjusting for the effect of one or more covariates. However, when designing a trial, there are situations when the assumption of PH may not be appropriate. Additionally, when it is known that there is a rapid decline in the survival curve for a control group, such as from previously conducted observational studies, a design based on the PH assumption may confer only a minor statistical improvement for the treatment group that is neither clinically nor practically meaningful. For such scenarios, a clinical trial design that focuses on improvement in patient longevity is proposed, based on the concept of proportional time using the generalized gamma ratio distribution. Simulations are conducted to evaluate the performance of the proportional time method and to identify the situations in which such a design will be beneficial as compared to the standard design using a PH assumption, piecewise exponential hazards assumption, and specific cases of a cure rate model. A practical example in which hemorrhagic stroke patients are randomized to 1 of 2 arms in a putative clinical trial demonstrates the usefulness of this approach by drastically reducing the number of patients needed for study enrollment.

Physical activity and academic achievement across the curriculum: Results from a 3-year cluster-randomized trial.

We compared changes in academic achievement across 3years between children in elementary schools receiving the Academic Achievement and Physical Activity Across the Curriculum intervention (A+PAAC), in which classroom teachers were trained to deliver academic lessons using moderate-to-vigorous physical activity (MVPA) compared to a non-intervention control. Elementary schools in eastern Kansas (n=17) were cluster randomized to A+PAAC (N=9, target ≥100min/week) or control (N=8). Academic achievement (math, reading, spelling) was assessed using the Wechsler Individual Achievement Test-Third Edition (WIAT-III) in a sample of children (A+PAAC=316, Control=268) in grades 2 and 3 at baseline (Fall 2011) and repeated each spring across 3years. On average 55min/week of A+PACC lessons were delivered each week across the intervention. Baseline WIAT-III scores (math, reading, spelling) were significantly higher in students in A+PAAC compared with control schools and improved in both groups across 3years. However, linear mixed modeling, accounting for baseline between group differences in WIAT-III scores, ethnicity, family income, and cardiovascular fitness, found no significant impact of A+PAAC on any of the academic achievement outcomes as determined by non-significant group by time interactions. A+PAAC neither diminished or improved academic achievement across 3-years in elementary school children compared with controls. Our target of 100min/week of active lessons was not achieved; however, students attending A+PAAC schools received an additional 55min/week of MVPA which may be associated with both physical and mental health benefits, without a reduction in time devoted to academic instruction.

Adult Cigarette Smokers at Highest Risk for Concurrent Alternative Tobacco Product Use Among a Racially/Ethnically and Socioeconomically Diverse Sample.

INTRODUCTION: Rates of alternative tobacco product use (ATPs; eg, cigars, cigarillos, pipes) among cigarette smokers are on the rise but little is known about the subgroups at highest risk. This study explored interactions between demographic, tobacco, and psychosocial factors to identify cigarette smokers at highest risk for ATP use from a racially/ethnically and socioeconomically diverse sample of adult smokers across the full smoking spectrum (nondaily, daily light, daily heavy). METHODS: Two-thousand three-hundred seventy-six adult cigarette smokers participated in an online cross-sectional survey. Quotas ensured equal recruitment of African American (AA), white (W), Hispanic/Latino (H) as well as daily and nondaily smokers. Classification and Regression Tree modeling was used to identify subgroups of cigarette smokers at highest risk for ATP use. RESULTS: 51.3% were Cig+ATP smokers. Alcohol for men and age, race/ethnicity, and discrimination for women increased the probability of ATP use. Strikingly, 73.5% of men screening positive for moderate to heavy drinking and 62.2% of younger (≤45 years) African American/Hispanic/Latino women who experienced regular discrimination were Cig+ATP smokers. CONCLUSIONS: Screening for concurrent ATP use is necessary for the continued success of tobacco cessation efforts especially among male alcohol users and racial/ethnic minority women who are at greatest risk for ATP use.

Generalized optimal design for two-arm, randomized phase II clinical trials with endpoints from the exponential dispersion family.

For two-arm randomized phase II clinical trials, previous literature proposed an optimal design that minimizes the total sample sizes subject to multiple constraints on the standard errors of the estimated event rates and their difference. The original design is limited to trials with dichotomous endpoints. This paper extends the original approach to be applicable to phase II clinical trials with endpoints from the exponential dispersion family distributions. The proposed optimal design minimizes the total sample sizes needed to provide estimates of population means of both arms and their difference with pre-specified precision. Its applications on data from specific distribution families are discussed under multiple design considerations. Copyright © 2016 John Wiley & Sons, Ltd.

Modeling and validating Bayesian accrual models on clinical data and simulations using adaptive priors.

Slow recruitment in clinical trials leads to increased costs and resource utilization, which includes both the clinic staff and patient volunteers. Careful planning and monitoring of the accrual process can prevent the unnecessary loss of these resources. We propose two hierarchical extensions to the existing Bayesian constant accrual model: the accelerated prior and the hedging prior. The new proposed priors are able to adaptively utilize the researcher's previous experience and current accrual data to produce the estimation of trial completion time. The performance of these models, including prediction precision, coverage probability, and correct decision-making ability, is evaluated using actual studies from our cancer center and simulation. The results showed that a constant accrual model with strongly informative priors is very accurate when accrual is on target or slightly off, producing smaller mean squared error, high percentage of coverage, and a high number of correct decisions as to whether or not continue the trial, but it is strongly biased when off target. Flat or weakly informative priors provide protection against an off target prior but are less efficient when the accrual is on target. The accelerated prior performs similar to a strong prior. The hedging prior performs much like the weak priors when the accrual is extremely off target but closer to the strong priors when the accrual is on target or only slightly off target. We suggest improvements in these models and propose new models for future research.

An application in identifying high-risk populations in alternative tobacco product use utilizing logistic regression and CART: a heuristic comparison.

BACKGROUND: Other forms of tobacco use are increasing in prevalence, yet most tobacco control efforts are aimed at cigarettes. In light of this, it is important to identify individuals who are using both cigarettes and alternative tobacco products (ATPs). Most previous studies have used regression models. We conducted a traditional logistic regression model and a classification and regression tree (CART) model to illustrate and discuss the added advantages of using CART in the setting of identifying high-risk subgroups of ATP users among cigarettes smokers. METHODS: The data were collected from an online cross-sectional survey administered by Survey Sampling International between July 5, 2012 and August 15, 2012. Eligible participants self-identified as current smokers, African American, White, or Latino (of any race), were English-speaking, and were at least 25 years old. The study sample included 2,376 participants and was divided into independent training and validation samples for a hold out validation. Logistic regression and CART models were used to examine the important predictors of cigarettes + ATP users. RESULTS: The logistic regression model identified nine important factors: gender, age, race, nicotine dependence, buying cigarettes or borrowing, whether the price of cigarettes influences the brand purchased, whether the participants set limits on cigarettes per day, alcohol use scores, and discrimination frequencies. The C-index of the logistic regression model was 0.74, indicating good discriminatory capability. The model performed well in the validation cohort also with good discrimination (c-index = 0.73) and excellent calibration (R-square = 0.96 in the calibration regression). The parsimonious CART model identified gender, age, alcohol use score, race, and discrimination frequencies to be the most important factors. It also revealed interesting partial interactions. The c-index is 0.70 for the training sample and 0.69 for the validation sample. The misclassification rate was 0.342 for the training sample and 0.346 for the validation sample. The CART model was easier to interpret and discovered target populations that possess clinical significance. CONCLUSION: This study suggests that the non-parametric CART model is parsimonious, potentially easier to interpret, and provides additional information in identifying the subgroups at high risk of ATP use among cigarette smokers.

Deep brain stimulation lead-contact heating during 3T MRI: single- versus dual-channel pulse generator configurations.

BACKGROUND: Magnetic resonance imaging (MRI) after deep brain stimulation (DBS) carries the risk of heating at the lead-contacts within the brain. OBJECTIVE/HYPOTHESIS: To compare the effect of single- and dual-channel DBS implantable pulse generator (IPG) configurations on brain lead-contact heating during 3T MRI. METHODS: A phantom with bilateral brain leads and extensions connected to two single-channel IPGs or a dual-channel right or left IPG was utilized. Using a transmit/receive head coil, seven scan sequences were conducted yielding a range of head-specific absorption rates (SAR-H). Temperature changes (ΔT) at the bilateral 0 and 3 lead-contacts were recorded, and normalized temperatures (ΔT/SAR-H) and slopes defining the ΔT/SAR-H over the SAR-H range were compared. RESULTS: Greater heating was strongly correlated with higher SAR-H in all configurations. For each scan sequence, the ΔT/SAR-H of single-channel left lead-contacts was significantly greater than the ΔT/SAR-H of either dual-channel configuration. The slope defining the relationship between ΔT and SAR-H for the single-channel left lead (1.68°C/SAR-H) was significantly greater (p < 0.0001) than the ΔT/SAR-H slope for the single-channel right lead (0.97°C/SAR-H), both of which were significantly greater (p < 0.0001) than the ΔT/SAR-H slopes of left or right leads (range 0.68 to 0.70°C/SAR-H) in the dual-channel configurations. There were no significant differences in ΔT/SAR-H slope values between the dual-channel configurations. CONCLUSION: DBS hardware configuration using bilateral single-channel versus unilateral dual-channel IPGs significantly affects DBS lead-contact heating during 3T MRI brain scanning.

The impact of blunt use on smoking abstinence among Black adults: Secondary analysis from randomized controlled smoking cessation clinical trial.

INTRODUCTION: People who smoke cigarettes are more likely than people who do not to use cannabis, including blunts, a tobacco product containing nicotine and marijuana. Blunts represent a challenge for cessation trials because nicotine could make stopping cigarettes more difficult. Few studies have examined the impact of blunt use on individuals actively engaged in a cigarette quit attempt. METHODS: Blunt use was assessed at baseline, Weeks 4, 8, 12, 16, and 26 among Black adult people who smoke enrolled in a double-blind, placebo-controlled, randomized trial of varenicline (VAR, n = 300) versus placebo (PBO, n = 200) for smoking cessation. Participants were categorized as ever blunt (blunt use reported at any timepoint) versus non-blunt (no blunt use reported). The primary outcome was salivary cotinine-verified 7-day point prevalence smoking abstinence at Weeks 12 and 26. Logistic regression examined the effects of treatment and blunt use on abstinence. RESULTS: 75 participants (mean age 45.6 years (SD = 12.5, range: 22,80); 32 (42%) female) reported blunt use. Logistic regression analyses showed no treatment by blunt use interaction or significant main effect of blunt use on smoking abstinence at Weeks 12 or 26 (p > 0.05). After adjusting for treatment, those who used blunts had statistically similar odds of quitting at Week 12 (OR: 0.68, 95% CI: 0.31, 1.5) and Week 26 (OR: 0.84, 95% CI: 0.38, 1.87) as those who never used blunts during the study. DISCUSSION: Blunt use had no statistically significant impact on cessation among participants in a smoking cessation clinical trial. Future trials are needed in which the target of cessation is all combustible products.

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).