A Bayesian hierarchical model for individual participant data meta-analysis of demand curves.

Individual participant data meta-analysis is a frequently used method to combine and contrast data from multiple independent studies. Bayesian hierarchical models are increasingly used to appropriately take into account potential heterogeneity between studies. In this paper, we propose a Bayesian hierarchical model for individual participant data generated from the Cigarette Purchase Task (CPT). Data from the CPT details how demand for cigarettes varies as a function of price, which is usually described as an exponential demand curve. As opposed to the conventional random-effects meta-analysis methods, Bayesian hierarchical models are able to estimate both the study-specific and population-level parameters simultaneously without relying on the normality assumptions. We applied the proposed model to a meta-analysis with baseline CPT data from six studies and compared the results from the proposed model and a two-step conventional random-effects meta-analysis approach. We conducted extensive simulation studies to investigate the performance of the proposed approach and discussed the benefits of using the Bayesian hierarchical model for individual participant data meta-analysis of demand curves.

Two-sample survival probability curves: A graphical approach for the analysis of time to event data in clinical trials.

With the aim to improve the communication of trial results, we introduce a novel graphical approach that complements the analysis of time to event outcomes in two-arm randomized trials. We define the so-called two-sample survival probability curve and propose a nonparametric estimator of the curve based on a random walk using Kaplan-Meier survival estimates for the two arms. We then use the estimated curve to visualize treatment effect as well as potential effect modification of factors of interest. We also propose to estimate two-sample survival probability curves within the framework of the Cox model to graphically assess model fit. The proposed two-sample survival probability plot puts trials in a standardized [0,1] × [0,1] space, allowing for a simple visualization of the main effect, effect modification, and the adequacy of a model fit.

A mixed effects model for analyzing area under the curve of longitudinally measured biomarkers with missing data.

A simple approach for analyzing longitudinally measured biomarkers is to calculate summary measures such as the area under the curve (AUC) for each individual and then compare the mean AUC between treatment groups using methods such as t test. This two-step approach is difficult to implement when there are missing data since the AUC cannot be directly calculated for individuals with missing measurements. Simple methods for dealing with missing data include the complete case analysis and imputation. A recent study showed that the estimated mean AUC difference between treatment groups based on the linear mixed model (LMM), rather than on individually calculated AUCs by simple imputation, has negligible bias under random missing assumptions and only small bias when missing is not at random. However, this model assumes the outcome to be normally distributed, which is often violated in biomarker data. In this paper, we propose to use a LMM on log-transformed biomarkers, based on which statistical inference for the ratio, rather than difference, of AUC between treatment groups is provided. The proposed method can not only handle the potential baseline imbalance in a randomized trail but also circumvent the estimation of the nuisance variance parameters in the log-normal model. The proposed model is applied to a recently completed large randomized trial studying the effect of nicotine reduction on biomarker exposure of smokers.

Variation in Accrual and Race/Ethnicity Reporting in Urological and Nonurological Related Cancer Trials.

PURPOSE: We performed a multiregistry analysis to assess relative differences in accrual sufficiency and race/ethnicity reporting in trials of common urological cancers and other nonurological solid organ tumors. MATERIALS AND METHODS: We queried ClinicalTrials.gov and the ISRCTN (International Standard Randomised Controlled Trial Number) Registry for closed phase III and IV trials focused on prostate, colorectal, kidney, bladder, testicular, breast and lung cancer. Identified trials were cross-verified with appropriate published data sources. Comparative accrual sufficiency and rates of race/ethnicity reporting were calculated. Multivariable logistic regression analysis was performed to determine factors associated with accrual status and race/ethnicity reporting. RESULTS: A total of 326 trials were identified based on our prespecified criteria, of which 63% reported sufficient accrual by time of closure and 58% reported data by race/ethnicity. Nonurological trials were significantly more likely to mention race data than urological trials (OR 3.25, 95% CI 1.24-8.55, p = 0.02). Industry sponsored trials were more likely to meet accrual targets than government funded projects (OR 5.44, 95% CI 1.64-18.20, p = 0.001). Although funding source did not influence race reporting, the reported recruitment of participants of African ethnicity was lower in industry sponsored trials (11.49% vs 3.18%, p <0.01). Two-thirds of the studies did not report baseline characteristics by African American race/ethnicity. CONCLUSIONS: Insufficient accrual and inadequate race/ethnicity reporting are prevalent issues, limiting interpretation of the results of clinical trials of major solid organ malignancies. Addressing these shortcomings would enhance result validity by raising statistical power and improving the transparency of reporting to better evaluate the generalizability of results.

Longitudinal stability in cigarette smokers of urinary eicosanoid biomarkers of oxidative damage and inflammation.

The urinary metabolites (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α), an F2-isoprostane and biomarker of oxidative damage, and "prostaglandin E2 metabolite" (PGE-M), a biomarker of inflammation, are elevated in cigarette smokers. However, there is little information in the literature on the longitudinal stability of these widely used biomarkers. In a large clinical trial involving 10 institutional sites, smokers were given, free of charge over a period of 20 weeks, Spectrum NRC600/601 research cigarettes containing 15.5 mg nicotine/g tobacco. All participants were instructed to smoke these cigarettes for the duration of the study. At weeks 4, 8, 12, 16, and 20, first morning urine voids were collected and analyzed for 8-iso-PGF2α and PGE-M using validated liquid chromatography-electrospray ionization-tandem mass spectrometry methods. The mean level of 8-iso-PGF2α at Week 4 was 1.34 ± 1.08 (S.D.) pmol/mg creatinine (N = 226) while that of PGE-M was 73.7 ± 113 (S.D.) pmol/mg creatinine (N = 232). The corresponding levels at Week 20 were 1.35 ± 0.93 (S.D.) pmol/mg creatinine (N = 209) for 8-iso-PGF2α and 74.2 ± 142 (S.D.) pmol/mg creatinine (N = 210) for PGE-M. There was variation in these values in the intervening weeks. The intra-class correlation coefficients (ICC) were 0.51 (95% CI, 0.45, 0.57) and 0.36 (0.30, 0.43), for 8-iso-PGF2α and PGE-M, respectively, indicating fair longitudinal stability for 8-iso-PGF2α and poorer longitudinal stability for PGE-M in cigarette smokers. Males had higher ICC values than females for both 8-iso-PGF2α and PGE-M. These results indicate that, in addition to cigarette smoking, endogenous processes of oxidative damage and inflammation influence the levels of these biomarkers over time among current smokers.

Longitudinal stability in cigarette smokers of urinary biomarkers of exposure to the toxicants acrylonitrile and acrolein.

The urinary metabolites cyanoethyl mercapturic acid (CEMA) and 3-hydroxypropyl mercapturic acid (3-HPMA) have been widely used as biomarkers of exposure to acrylonitrile and acrolein, respectively, but there are no published data on their consistency over time in the urine of cigarette smokers. We provided, free of charge over a 20 week period, Spectrum NRC600/601 research cigarettes to cigarette smokers in the control arm of a randomized clinical trial of the reduced nicotine cigarette. Urine samples were collected at weeks 4, 8, 12, 16, and 20 and analyzed for CEMA and 3-HPMA, and total nicotine equivalents (TNE) using validated methods. Creatinine-corrected intra-class correlation coefficients for CEMA, 3-HPMA, and TNE were 0.67, 0.46, and 0.68, respectively, indicating good longitudinal consistency for CEMA, while that of 3-HPMA was fair. A strong correlation between CEMA and TNE values was observed. These data support the use of CEMA as a reliable biomarker of tobacco smoke exposure. This is the first report of the longitudinal stability of the biomarkers of acrylonitrile and acrolein exposure in smokers. The data indicate that CEMA, the biomarker of acrylonitrile exposure, is consistent over time in cigarette smokers, supporting its use. While 3-HPMA levels were less stable over time, this biomarker is nevertheless a useful monitor of human acrolein exposure because of its specificity to this toxicant.

Analysis of self-report and biochemically verified tobacco abstinence outcomes with missing data: a sensitivity analysis using two-stage imputation.

BACKGROUND: Missing data are common in tobacco studies. It is well known that from the observed data alone, it is impossible to distinguish between missing mechanisms such as missing at random (MAR) and missing not at random (MNAR). In this paper, we propose a sensitivity analysis method to accommodate different missing mechanisms in cessation outcomes determined by self-report and urine validation results. METHODS: We propose a two-stage imputation procedure, allowing survey and urine data to be missing under different mechanisms. The motivating data were from a tobacco cessation trial examining the effects of the extended vs. standard Quit and Win contests and counseling vs. no counseling under a 2-by-2 factorial design. The primary outcome was 6-month biochemically verified tobacco abstinence. RESULTS: Our proposed method covers a wide spectrum of missing scenarios, including the widely adopted "missing = smoking" imputation by assuming a perfect smoking-missing correlation (an extreme case of MNAR), the MAR case by assuming a zero smoking-missing correlation, and many more in between. The analysis of the data example shows that the estimated effects of the studied interventions are sensitive to the different missing assumptions on the survey and urine data. CONCLUSIONS: Sensitivity analysis has played a crucial role in assessing the robustness of the findings in clinical trials with missing data. The proposed method provides an effective tool for analyzing missing data introduced at two different stages of outcome assessment, the self-report and validation time. Our methods are applicable to trials studying biochemically verified abstinence from alcohol and other substances.

Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure: A Randomized Clinical Trial.

Importance: The optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined. Objectives: To determine the effects of immediate vs gradual reduction in nicotine content to very low levels and as compared with usual nicotine level cigarettes on biomarkers of toxicant exposure. Design, Setting, and Participants: A double-blind, randomized, parallel-design study with 2 weeks of baseline smoking and 20 weeks of intervention was conducted at 10 US sites. A volunteer sample of daily smokers with no intention to quit within 30 days was recruited between July 2014 and September 2016, with the last follow-up completed in March 2017. Interventions: (1) Immediate reduction to 0.4 mg of nicotine per gram of tobacco cigarettes; (2) gradual reduction from 15.5 mg to 0.4 mg of nicotine per gram of tobacco cigarettes with 5 monthly dose changes; or (3) maintenance on 15.5 mg of nicotine per gram of tobacco cigarettes. Main Outcomes and Measures: Between-group differences in 3 co-primary biomarkers of smoke toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT, indicator of polycyclic aromatic hydrocarbons) calculated as area under the concentration-time curve over the 20 weeks of intervention. Results: Among 1250 randomized participants (mean age, 45 years; 549 women [44%]; 958 [77%] completed the trial), significantly lower levels of exposure were observed in the immediate vs gradual reduction group for CO (mean difference, -4.06 parts per million [ppm] [95% CI, -4.89 to -3.23]; P < .0055), 3-HPMA (ratio of geometric means, 0.83 [95% CI, 0.77 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.88 [95% CI, 0.83 to 0.93]; P < .0055). Significantly lower levels of exposure were observed in the immediate reduction vs control group for CO (mean difference, -3.38 [95% CI, -4.40 to -2.36]; P < .0055), 3-HPMA (ratio of geometric means, 0.81 [95% CI, 0.75 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.86 [95% CI, 0.81 to 0.92]; P < .0055). No significant differences were observed between the gradual reduction vs control groups for CO (mean difference, 0.68 [95% CI, -0.31 to 1.67]; P = .18), 3-HPMA (ratio of geometric means, 0.98 [95% CI, 0.91 to 1.06]; P = .64), and PheT (ratio of geometric means, 0.98 [95% CI, 0.92 to 1.04]; P = .52). Conclusions and Relevance: Among smokers, immediate reduction of nicotine in cigarettes led to significantly greater decreases in biomarkers of smoke exposure across time compared with gradual reduction or a control group, with no significant differences between gradual reduction and control. Trial Registration: clinicaltrials.gov Identifier: NCT02139930.

A Bayesian hierarchical model for demand curve analysis.

Drug self-administration experiments are a frequently used approach to assess the abuse liability and reinforcing property of a compound. It has been used to assess the abuse liabilities of various substances such as psychomotor stimulants and hallucinogens, food, nicotine, and alcohol. The demand curve generated from a self-administration study describes how demand of a drug or non-drug reinforcer varies as a function of price. With the approval of the 2009 Family Smoking Prevention and Tobacco Control Act, demand curve analysis provides crucial evidence to inform the US Food and Drug Administration's policy on tobacco regulation because it produces several important quantitative measurements to assess the reinforcing strength of nicotine. The conventional approach popularly used to analyze the demand curve data is individual-specific non-linear least square regression. The non-linear least square approach sets out to minimize the residual sum of squares for each subject in the dataset; however, this one-subject-at-a-time approach does not allow for the estimation of between- and within-subject variability in a unified model framework. In this paper, we review the existing approaches to analyze the demand curve data, non-linear least square regression, and the mixed effects regression and propose a new Bayesian hierarchical model. We conduct simulation analyses to compare the performance of these three approaches and illustrate the proposed approaches in a case study of nicotine self-administration in rats. We present simulation results and discuss the benefits of using the proposed approaches.

Presence of the Carcinogen N'-Nitrosonornicotine in Saliva of E-cigarette Users.

Many harmful constituents are present in e-cigarettes at much lower levels than in cigarette smoke, and the results of analysis of urinary biomarkers in e-cigarette users are consistent with these findings. However, understanding the health effects of chronic exposures to e-cigarette aerosols may require thinking beyond these comparisons. In this study, we investigated the endogenous formation of the tobacco-specific oral and esophageal carcinogen N'-nitrosonornicotine (NNN) in e-cigarette users. Salivary NNN, nornicotine, and nicotine as well as urinary tobacco biomarkers, including total NNN, were analyzed in 20 e-cigarette users, 20 smokers, and 19 nonsmokers. Nornicotine and NNN levels in e-cigarettes used by the study participants were also analyzed. The mean of NNN in saliva of e-cigarette users was 14.6 (±23.1) pg/mL, ranging from nonquantifiable (below the limit of quantitation, LOQ) to 76.0 pg/mL. In smokers, salivary NNN ranged from below LOQ to 739 pg/mL, with 80% of smokers having salivary NNN in the range of levels found in e-cigarette users. Consistent with a previous report, very low levels of urinary total NNN were present in only 5 out of 20 e-cigarette users (ranging from 0.001 to 0.01 pmol/mL urine). Only trace levels of NNN were found in e-cigarette liquids. Together, our findings demonstrate that NNN is formed endogenously in e-cigarette users. While the overall exposure to NNN in e-cigarette users is dramatically lower than in smokers, the known carcinogenic potency of NNN warrants further investigations into the potential consequences of its endogenous formation. Salivary NNN, rather than urinary total NNN, which accounts for only 1-3% of the NNN dose, should be used to monitor e-cigarette users' exposure to this carcinogen.

A Bayesian hierarchical model for demand curve analysis.

Drug self-administration experiments are a frequently used approach to assessing the abuse liability and reinforcing property of a compound. It has been used to assess the abuse liabilities of various substances such as psychomotor stimulants and hallucinogens, food, nicotine, and alcohol. The demand curve generated from a self-administration study describes how demand of a drug or non-drug reinforcer varies as a function of price. With the approval of the 2009 Family Smoking Prevention and Tobacco Control Act, demand curve analysis provides crucial evidence to inform the US Food and Drug Administration's policy on tobacco regulation, because it produces several important quantitative measurements to assess the reinforcing strength of nicotine. The conventional approach popularly used to analyze the demand curve data is individual-specific non-linear least square regression. The non-linear least square approach sets out to minimize the residual sum of squares for each subject in the dataset; however, this one-subject-at-a-time approach does not allow for the estimation of between- and within-subject variability in a unified model framework. In this paper, we review the existing approaches to analyze the demand curve data, non-linear least square regression, and the mixed effects regression and propose a new Bayesian hierarchical model. We conduct simulation analyses to compare the performance of these three approaches and illustrate the proposed approaches in a case study of nicotine self-administration in rats. We present simulation results and discuss the benefits of using the proposed approaches.

Excess Cost of Cervical Cancer Screening Beyond Recommended Screening Ages or After Hysterectomy in a Single Institution.

OBJECTIVE: The aim of the study was to estimate the excess cost of guideline nonadherent cervical cancer screening in women beyond the recommended screening ages or posthysterectomy in a single healthcare system. MATERIALS AND METHODS: All Pap tests performed between September 1, 2012, and August 31, 2014, in women younger than 21 years, older than 65 years, or after hysterectomy, were coded as guideline adherent or nonadherent per the 2012 America Society of Colposcopy and Clinical Pathology guidelines. We assumed management of abnormal results per the 2013 America Society of Colposcopy and Clinical Pathology management guidelines. Costs were obtained from a literature review and Center for Medicare and Medicaid Services data and applied to nonadherent screening and subsequent diagnostic tests. RESULTS: During this period, 1,398 guideline nonadherent Pap tests were performed (257 in women <21 years, 536 in women >65 years, and 605 after hysterectomy), with 88 abnormal results: 35 (13.5%) in women younger than 21 years, 14 (2.6%) in women older than 65 years, and 39 (6.5%) in women after hysterectomy. The excess cost for initial screening, diagnostic tests, and follow-up was US $35,337 for 2 years in women younger than 21 years, US $54,378 for 5 years in women older than 65 years, and US $77,340 for 5 years in women after hysterectomy, resulting in a total excess cost of US $166,100 for 5 years. Of the 1,398 women who underwent guideline nonadherent screening, there were only 2 (0.1%) diagnoses of high-grade dysplasia (VaIN3). CONCLUSIONS: Guideline nonadherent cervical cancer screening in women beyond the recommended screening ages and posthysterectomy resulted in costs exceeding US $160,000 for screening, diagnostic tests, and follow-up with minimal improvement in detection of high-grade dysplasia.

Mobile Phone Multilevel and Multimedia Messaging Intervention for Breast Cancer Screening: Pilot Randomized Controlled Trial.

BACKGROUND: Despite the increasing breast cancer incidence and mortality rates, Korean American immigrant women have one of the lowest rates of breast cancer screening across racial groups in the United States. Mobile health (mHealth), defined as the delivery of health care information or services through mobile communication devices, has been utilized to successfully improve a variety of health outcomes. OBJECTIVE: This study adapted the principles of mHealth to advance breast cancer prevention efforts among Korean American immigrant women, an underserved community. METHODS: Using a randomized controlled trial design, 120 Korean American women aged 40 to 77 years were recruited and randomly assigned to either the mMammogram intervention group (n=60) to receive culturally and personally tailored multilevel and multimedia messages through a mobile phone app along with health navigator services or the usual care control group (n=60) to receive a printed brochure. Outcome measures included knowledge, attitudes, and beliefs about breast cancer screening, readiness for mammography, and mammogram receipt. The feasibility and acceptability of the mMammogram intervention was also assessed. RESULTS: The intervention group showed significantly greater change on scores of knowledge of breast cancer and screening guidelines (P=.01). The intervention group also showed significantly greater readiness for mammography use after the intervention compared with the control group. A significantly higher proportion of women who received the mMammogram intervention (75%, 45/60) completed mammograms by the 6-month follow-up compared with the control group (30%, 18/60; P<.001). In addition, the intervention group rated satisfaction with the intervention (P=.003), effectiveness of the intervention (P<.001), and increase of knowledge on breast cancer and screenings (P=.001) significantly higher than the control group. CONCLUSIONS: A mobile phone app-based intervention combined with health navigator service was a feasible, acceptable, and effective intervention mechanism to promote breast cancer screening in Korean American immigrant women. A flexible, easily tailored approach that relies on recent technological advancements can reach underserved and hard-to-recruit populations that bear disproportionate cancer burdens. TRIAL REGISTRATION: Clinicaltrials.gov NCT01972048; https://clinicaltrials.gov/show/NCT01972048 (Archived by WebCite at https://clinicaltrials.gov/archive/NCT01972048/2013_10_29).

A Randomized Controlled Trial of Green Tea Extract Supplementation and Mammographic Density in Postmenopausal Women at Increased Risk of Breast Cancer.

Epidemiologic and animal studies suggest a protective role of green tea against breast cancer. However, the underlying mechanism is not understood. We conducted a randomized, double-blinded, placebo-controlled phase II clinical trial to investigate whether supplementation with green tea extract (GTE) modifies mammographic density (MD), as a potential mechanism, involving 1,075 healthy postmenopausal women. Women assigned to the treatment arm consumed daily 4 decaffeinated GTE capsules containing 1,315 mg total catechins, including 843 mg epigallocatechin-3-gallate (EGCG) for 12 months. A computer-assisted method (Madena) was used to assess MD in digital mammograms at baseline and month 12 time points in 932 completers (462 in GTE and 470 in placebo). GTE supplementation for 12 months did not significantly change percent MD (PMD) or absolute MD in all women. In younger women (50-55 years), GTE supplementation significantly reduced PMD by 4.40% as compared with the placebo with a 1.02% PMD increase from pre- to postintervention (P = 0.05), but had no effect in older women (Pinteraction = 0.07). GTE supplementation did not induce MD change in other subgroups of women stratified by catechol-O-methyltransferase genotype or level of body mass index. In conclusion, 1-year supplementation with a high dose of EGCG did not have a significant effect on MD measures in all women, but reduced PMD in younger women, an age-dependent effect similar to those of tamoxifen. Further investigation of the potential chemopreventive effect of green tea intake on breast cancer risk in younger women is warranted. Cancer Prev Res; 10(12); 710-8. ©2017 AACR.

Timing of nicotine lozenge administration to minimize trigger induced craving and withdrawal symptoms.

INTRODUCTION: Smokers are often advised to use nicotine lozenge when craving or withdrawal symptoms occur. This may be too late to prevent lapses. This study assessed if nicotine lozenge use prior to a common smoking trigger can minimize trigger induced increases in craving and withdrawal symptoms. METHODS: Eighty-four smokers completed two laboratory sessions in random order. At one session, nicotine lozenge was given immediately after a stressor (to approximate current recommended use - i.e., after craving and withdrawal symptoms occur); at the other session subjects were randomized to receive nicotine lozenge at time points ranging from immediately to 30min prior to the stressor. Withdrawal symptoms and urge to smoke were measured using the Minnesota Nicotine Withdrawal Scale and the Questionnaire of Smoking Urges (QSU). RESULTS: Relative to receiving lozenge after the stressor, a smaller increase in pre-stressor to post-stressor withdrawal symptom scores occurred when lozenge was used immediately (p=0.03) and 10min prior (p=0.044) to the stressor. Results were similar for factors 1 and 2 of the QSU when lozenge was used immediately prior to the stressor (p<0.03) and for factor 1 of the QSU when lozenge was used 10min prior to the stressor (p=0.028). Absolute levels of post-stressor withdrawal symptom and urge to smoke severity were lower when lozenge was given prior to versus after a stressor. CONCLUSIONS: Administering the nicotine lozenge prior to a smoking trigger can decrease trigger induced craving and withdrawal symptoms. Future studies are needed to determine if such use would increase cessation rates. Clinicaltrials.gov # NCT01522963.

Single Health System Adherence to 2012 Cervical Cancer Screening Guidelines at Extremes of Age and Posthysterectomy.

OBJECTIVE: To estimate the proportion of guideline nonadherent Pap tests in women aged younger than 21 years and older than 65 years and posthysterectomy in a single large health system. Secondary objectives were to describe temporal trends and patient and health care provider characteristics associated with screening in these groups. METHODS: A retrospective cross-sectional chart review was performed at Fairview Health Services and University of Minnesota Physicians. Reasons for testing and patient and health care provider information were collected. Tests were designated as indicated or nonindicated per the 2012 cervical cancer screening guidelines. Point estimates and descriptive statistics were calculated. Patient and health care provider characteristics were compared between indicated and nonindicated groups using χ and Wilcoxon rank-sum tests. RESULTS: A total of 3,920 Pap tests were performed between September 9, 2012, and August 31, 2014. A total of 257 (51%; 95% confidence interval [CI] 46.1-54.9%) of tests in the younger than 21 years group, 536 (40%; 95% CI 37.7-43.1%) in the older than 65 years group, and 605 (29%; 95% CI 27.1-31.0%) in the posthysterectomy group were not indicated. White race in the older than 65 years group was the only patient characteristic associated with receipt of a nonindicated Pap test (P=.007). Health care provider characteristics associated with nonindicated Pap tests varied by screening group. Temporal trends showed a decrease in the proportion of nonindicated tests in the younger than 21 years group but an increase in the posthysterectomy group. CONCLUSION: For women aged younger than 21 years and older than 65 years and posthysterectomy, 35% of Pap tests performed in our health system were not guideline-adherent. There were no patient or health care provider characteristics associated with guideline nonadherent screening across all groups.

African Americans and Short-Term Outcomes after Surgery for Crohn's Disease: An ACS-NSQIP Analysis.

BACKGROUND: Previous reports on racial disparities in the treatment of Crohn's disease [CD] in African American [AA] patients have shown differences in both medical and surgical treatments in this population. No study thus far has examined the effect of AA race on outcomes after surgery for CD. METHODS: Utilizing the National Surgical Quality Improvement Program [NSQIP] Participant User File [PUF] for the years 2005-2013, we examined the effect of AA race on postoperative complications in patients with CD undergoing intestinal surgery. RESULTS: AA patients had a significantly higher rate of complications overall compared to non-AA patients [23.5% vs 18.9%, p = 0.002]. Postoperative sepsis [10.9% vs 6.6%, p < 0.001] and surgical site infection [17.6% vs 14.8%, p = 0.037] were most significant. After adjustment for age, sex, preoperative disease severity and lifestyle factors [smoking], race remained a statistically significant factor in postoperative complication rate. Only after additional adjustment was made for comorbidities and American Society of Anesthesiologists class did race lose significance within our model. CONCLUSION: African Americans experience a greater amount of postoperative complications following surgery for Crohn's disease. Preoperative disease management, addressing smoking status and control of comorbid disease are important factors in addressing the racial disparities in the surgical treatment of Crohn's disease.

Impact of smoking reduced nicotine content cigarettes on sensitivity to cigarette price: further results from a multi-site clinical trial.

AIMS: To assess the impact of a reduction in the nicotine content of cigarettes on estimated consumption of reduced nicotine cigarettes and usual brand cigarettes at a variety of hypothetical prices. DESIGN: Double-blind study with participants assigned randomly to receive cigarettes for 6 weeks that were either usual brand or an investigational cigarette with one of five nicotine contents. SETTING: Ten sites across the United States. PARTICIPANTS: A total of 839 eligible adult smokers randomized from 2013 to 2014. INTERVENTION AND COMPARATOR: Participants received their usual brand or an investigational cigarette with one of five nicotine contents: 15.8 (primary control), 5.2, 2.4, 1.3, or 0.4 mg/g. MEASUREMENTS: The Cigarette Purchase Task was completed at baseline and at the week 6 post-randomization visit. FINDINGS: Compared with normal nicotine content controls, the lowest nicotine content (0.4 mg/g) reduced the number of study cigarettes participants estimated they would smoke at a range of prices [mean reduction relative to 15.8 mg/g at a price of $4.00/pack: 9.50, 95% confidence interval (CI) = 6.81,12.19]. The lowest nicotine content also reduced the maximum amount of money allocated to study cigarettes and the price at which participants reported they would stop buying study cigarettes [median reduction relative to 15.8 mg/g, 95% CI = $8.21 (4.27,12.15) per day and $0.44 (0.17,0.71) per cigarette, respectively]. A reduction in nicotine content to the lowest level also reduced the maximum amount of money allocated to usual brand cigarettes (median reduction relative to 15.8 mg/g: $4.39 per day, 95% CI = 1.88,6.90). CONCLUSIONS: In current smokers, a reduction in nicotine content may reduce cigarette consumption, reduce the reinforcement value of cigarettes and increase cessation if reduced nicotine content cigarettes were the only cigarette available for purchase.

A two-part mixed effects model for cigarette purchase task data.

The Cigarette Purchase Task is a behavioral economic assessment tool designed to measure the relative reinforcing efficacy of cigarette smoking across different prices. An exponential demand equation has become a standard model for analyzing purchase task data, but its utility is compromised by its inability to accommodate values of zero consumption. We propose a two-part mixed effects model that keeps the same exponential demand equation for modeling nonzero consumption values, while providing a logistic regression for the binary outcome of zero versus nonzero consumption. Therefore, the proposed model can accommodate zero consumption values and retain the features of the exponential demand equation at the same time. As a byproduct, the logistic regression component of the proposed model provides a new demand index, the "derived breakpoint", for the price above which a subject is more likely to be abstinent than to be smoking. We apply the proposed model to data collected at baseline from college students (N = 1,217) enrolled in a randomized clinical trial utilizing financial incentives to motivate tobacco cessation. Monte Carlo simulations showed that the proposed model provides better fits than an existing model. We note that the proposed methodology is applicable to other purchase task data, for example, drugs of abuse.

Clinical Trial of 2-Phenethyl Isothiocyanate as an Inhibitor of Metabolic Activation of a Tobacco-Specific Lung Carcinogen in Cigarette Smokers.

2-Phenethyl isothiocyanate (PEITC), a natural product found as a conjugate in watercress and other cruciferous vegetables, is an inhibitor of the metabolic activation and lung carcinogenicity of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in F344 rats and A/J mice. We carried out a clinical trial to determine whether PEITC also inhibits the metabolic activation of NNK in smokers. Cigarette smokers were recruited and asked to smoke cigarettes containing deuterium-labeled [pyridine-D4]NNK for an acclimation period of at least 1 week. Then subjects were randomly assigned to one of two arms: PEITC followed by placebo, or placebo followed by PEITC. During the 1-week treatment period, each subject took PEITC (10 mg in 1 mL of olive oil, 4 times per day). There was a 1-week washout period between the PEITC and placebo periods. The NNK metabolic activation ratio [pyridine-D4]hydroxy acid/total [pyridine-D4]NNAL was measured in urine samples to test the hypothesis that PEITC treatment modified NNK metabolism. Eighty-two smokers completed the study and were included in the analysis. Overall, the NNK metabolic activation ratio was reduced by 7.7% with PEITC treatment (P = 0.023). The results of this trial, while modest in effect size, provide a basis for further investigation of PEITC as an inhibitor of lung carcinogenesis by NNK in smokers. Cancer Prev Res; 9(5); 396-405. ©2016 AACR.