Association of Cannabis Use With Cardiovascular Outcomes Among US Adults.

BACKGROUND: We examined the association between cannabis use and cardiovascular outcomes among the general population, among never-tobacco smokers, and among younger individuals. METHODS AND RESULTS: This is a population-based, cross-sectional study of 2016 to 2020 data from the Behavioral Risk Factor Surveillance Survey from 27 American states and 2 territories. We assessed the association of cannabis use (number of days of cannabis use in the past 30 days) with self-reported cardiovascular outcomes (coronary heart disease, myocardial infarction, stroke, and a composite measure of all 3) in multivariable regression models, adjusting for tobacco use and other characteristics in adults 18 to 74 years old. We repeated this analysis among nontobacco smokers, and among men <55 years old and women <65 years old who are at risk of premature cardiovascular disease. Among the 434 104 respondents, the prevalence of daily and nondaily cannabis use was 4% and 7.1%, respectively. The adjusted odds ratio (aOR) for the association of daily cannabis use and coronary heart disease, myocardial infarction, stroke, and the composite outcome (coronary heart disease, myocardial infarction, and stroke) was 1.16 (95% CI, 0.98-1.38), 1.25 (95% CI, 1.07-1.46), 1.42 (95% CI, 1.20-1.68), and 1.28 (95% CI, 1.13-1.44), respectively, with proportionally lower log odds for days of use between 0 and 30 days per month. Among never-tobacco smokers, daily cannabis use was also associated with myocardial infarction (aOR, 1.49 [95% CI, 1.03-2.15]), stroke (aOR, 2.16 [95% CI, 1.43-3.25]), and the composite of coronary heart disease, myocardial infarction, and stroke (aOR, 1.77 [95% CI, 1.31-2.40]). Relationships between cannabis use and cardiovascular outcomes were similar for men <55 years old and women <65 years old. CONCLUSIONS: Cannabis use is associated with adverse cardiovascular outcomes, with heavier use (more days per month) associated with higher odds of adverse outcomes.

Categorizing Vaping Intensity among Youth.

INTRODUCTION: Increasing electronic cigarette use among youth has led to a need for a novel intensity measure of e-cigarette use and its association with nicotine addiction variables. METHODS: Using a cross sectional study of the 2018-2019 PATH Wave 5 Youth survey, a new intensity metric of e-cigarette use, the average number of puffs per month as a function of frequency (days of use per month), number of uses per day and number of puffs per use, was developed for adolescent e-cigarette users. Using logistic regression, standard addiction measures were tested for association with higher quartile (Q) of e-cigarette intensity: Q1 (1-5 puffs), Q2 (6-50 puffs), Q3 (51-528 puffs), and Q4 (529+ puffs). RESULTS: Among 1,051 current youth e-cigarette users, cravings were associated with greater intensity of use (Q2: aOR= 1.90, 95% CI: 0.94-3.87; Q3: aOR = 6.91, 95% CI: 3.25-14.69; Q4: aOR =21.48, 95% CI 10.03-45.97). Craving associations exceeded the corresponding aORs for the identical regression using frequency of use. Higher intensity was significantly associated with being an older adolescent (aOR=1.85), best friend use (aOR: 3.35), not thinking about quitting (aOR: 2.51), and lower perceived addiction (aOR: 1.95). CONCLUSIONS: This study found that an intensity metric (puffs per month) was strongly associated with cravings, best friend use, harm perception, and lack of intention to quit. This metric provides a more accurate picture of the intensity of youth e-cigarette use than other commonly used measures and may be important for understanding the current and future impact of the youth e-cigarette epidemic. IMPLICATIONS: Adolescent addiction to e-cigarettes affects learning, memory, and attention. However, it is unknown whether intensity of use, puffs per month, differs from frequency, days of use per month, in relation to addiction measures. This study provides evidence that high intensity use characterized by puffs per month has a stronger association to cravings compared to frequency, which suggests puffs per month may be a better measure of nicotine exposure. This new intensity metric may give insights into youth e-cigarette use patterns, addiction, and appropriate treatment of intense but intermittent users.

Nicotine Addiction and Intensity of e-Cigarette Use by Adolescents in the US, 2014 to 2021.

Importance: As e-cigarettes have become more effective at delivering the addictive drug nicotine, they have become the dominant form of tobacco use by US adolescents. Objective: To measure intensity of use of e-cigarettes, cigarettes, and other tobacco products among US adolescents and their dependence level over time. Design, Setting, and Participants: This survey study analyzed the cross-sectional National Youth Tobacco Surveys from 2014 to 2021. Confirmatory analysis was conducted using Youth Behavioral Risk Factor Surveillance System from 2015 to 2019. The surveys were administered to national probability samples of US students in grades 6 to 12. Exposures: Use of e-cigarettes and other tobacco products before and after the introduction of e-cigarettes delivering high levels of nicotine. Main Outcomes and Measures: First tobacco product used, age at initiation of use, intensity of use (days per month), and nicotine addiction (measured as time after waking to first use of any tobacco product). Results: A total of 151 573 respondents were included in the analysis (51.1% male and 48.9% female; mean [SEM] age, 14.57 [0.03] years). Prevalence of e-cigarette use peaked in 2019 and then declined. Between 2014 and 2021, the age at initiation of e-cigarette use decreased, and intensity of use and addiction increased. By 2017, e-cigarettes became the most common first product used (77.0%). Age at initiation of use did not change for cigarettes or other tobacco products, and changes in intensity of use were minimal. By 2019, more e-cigarette users were using their first tobacco product within 5 minutes of waking than for cigarettes and all other products combined. Median e-cigarette use also increased from 3 to 5 d/mo in 2014 to 2018 to 6 to 9 d/mo in 2019 to 2020 and 10 to 19 d/mo in 2021. Conclusions and Relevance: The changes detected in this survey study may reflect the higher levels of nicotine delivery and addiction liability of modern e-cigarettes that use protonated nicotine to make nicotine easier to inhale. The increasing intensity of use of modern e-cigarettes highlights the clinical need to address youth addiction to these new high-nicotine products over the course of many clinical encounters. In addition, stronger regulation, including comprehensive bans on the sale of flavored tobacco products, should be implemented.

Sociodemographic Characteristics Associated With and Prevalence and Frequency of Cannabis Use Among Adults in the US.

Importance: Cannabis use has increased, but there are few studies on frequent and daily cannabis use among US adults. Individuals who engage in higher frequency use may suffer more health consequences. Objective: To examine frequency of cannabis use and associated factors among US adults. Design, Setting, and Participants: This survey study included data from 21 US states and 2 US territories reported in the Behavioral Risk Factor Surveillance System surveys from 2016 to 2019. Cross-sectional data on US adults ages 18 years and older were used to estimate demographic, socioeconomic, and behavioral risk factors for cannabis use, taking into account the survey strata and sampling weights for the 4 years of combined data. Using a multivariable ordinal logistic analysis, the association of demographic, socioeconomic status, and behavioral risk factors with past month cannabis frequency were examined. Exposures: Sociodemographic characteristic, ie, age, gender, race and ethnicity, educational attainment, employment status, and annual household income. Main Outcomes and Measures: Ordinal categorization of number of days of cannabis use in the past 30 days in terms of nonuse, infrequent use (1-5 days), frequent use (6-29 days), and daily use. Results: Among the 387 179 respondents, 58 009 (27.9%) were ages 18 to 34 years, 186 923 (50.3%) were ages 35 to 64 years, and 142 225 (21.8%) were age 65 years or older (mean [SD] age, 48.3 [0.1] years). The sample included 28 345 (9.8%) Black, 36 697 (22.6%) Hispanic, and 292 210 (57.3%) White respondents. Smoking was the most common form of cannabis use. The frequency of cannabis use varied significantly by age, gender, race, marital status, education, and employment. Higher frequency cannabis use was associated with younger age (ages 18-34 years: adjusted odds ratio [aOR],4.12; 95% CI, 3.63-4.68; ages 35-64 years: aOR,2.22; 95% CI, 1.98-2.49), Black (aOR, 1.46; 95% CI, 1.33-1.71) and Native American (aOR, 1.25; 95% CI, 1.04-1.52) race, and less educational attainment (high school or less: aOR,1.09; 95% CI, 1.02-1.17; some college: aOR,1.27; 95% CI, 1.19-1.35). Being married (aOR, 0.54; 95% CI, 0.51-0.58) or identifying as Asian (aOR, 0.60; 95% CI, 0.51-0.71) or Hispanic (aOR, 0.71; 95% CI, 0.65-0.77) was associated with lower-frequency cannabis use after accounting for other baseline factors. Conclusions and Relevance: This nationally based study found that higher-frequency cannabis use is more common among young and racial minority populations, as well as respondents with low socioeconomic status. Given the known and emerging negative health effects of cannabis use, more attention may need to be paid to high-frequency use among underserved populations in the form of screening, risk stratification, and treatment.

Breast Cancer Risk and Mammographic Density Assessed with Semiautomated and Fully Automated Methods and BI-RADS.

Purpose To compare three metrics of breast density on full-field digital mammographic (FFDM) images as predictors of future breast cancer risk. Materials and Methods This institutional review board-approved study included 125 women with invasive breast cancer and 274 age- and race-matched control subjects who underwent screening FFDM during 2004-2013 and provided informed consent. The percentage of density and dense area were assessed semiautomatically with software (Cumulus 4.0; University of Toronto, Toronto, Canada), and volumetric percentage of density and dense volume were assessed automatically with software (Volpara; Volpara Solutions, Wellington, New Zealand). Clinical Breast Imaging Reporting and Data System (BI-RADS) classifications of breast density were extracted from mammography reports. Odds ratios and 95% confidence intervals (CIs) were estimated by using conditional logistic regression stratified according to age and race and adjusted for body mass index, parity, and menopausal status, and the area under the receiver operating characteristic curve (AUC) was computed. Results The adjusted odds ratios and 95% CIs for each standard deviation increment of the percentage of density, dense area, volumetric percentage of density, and dense volume were 1.61 (95% CI: 1.19, 2.19), 1.49 (95% CI: 1.15, 1.92), 1.54 (95% CI: 1.12, 2.10), and 1.41 (95% CI: 1.11, 1.80), respectively. Odds ratios for women with extremely dense breasts compared with those with scattered areas of fibroglandular density were 2.06 (95% CI: 0.85, 4.97) and 2.05 (95% CI: 0.90, 4.64) for BI-RADS and Volpara density classifications, respectively. Clinical BI-RADS was more accurate (AUC, 0.68; 95% CI: 0.63, 0.74) than Volpara (AUC, 0.64; 95% CI: 0.58, 0.70) and continuous measures of percentage of density (AUC, 0.66; 95% CI: 0.60, 0.72), dense area (AUC, 0.66; 95% CI: 0.60, 0.72), volumetric percentage of density (AUC, 0.64; 95% CI: 0.58, 0.70), and density volume (AUC, 0.65; 95% CI: 0.59, 0.71), although the AUC differences were not statistically significant. Conclusion Mammographic density on FFDM images was positively associated with breast cancer risk by using the computer assisted methods and BI-RADS. BI-RADS classification was as accurate as computer-assisted methods for discrimination of patients from control subjects. © RSNA, 2016.

Predicting Prostate Cancer Recurrence After Radical Prostatectomy.

BACKGROUND: Prostate cancer prognosis is variable, and management decisions involve balancing patients' risks of recurrence and recurrence-free death. Moreover, the roles of body mass index (BMI) and race in risk of recurrence are controversial [1,2]. To address these issues, we developed and cross-validated RAPS (Risks After Prostate Surgery), a personal prediction model for biochemical recurrence (BCR) within 10 years of radical prostatectomy (RP) that includes BMI and race as possible predictors, and recurrence-free death as a competing risk. METHODS: RAPS uses a patient's risk factors at surgery to assign him a recurrence probability based on statistical learning methods applied to a cohort of 1,276 patients undergoing RP at the University of Pennsylvania. We compared the performance of RAPS to that of an existing model with respect to calibration (by comparing observed and predicted outcomes), and discrimination (using the area under the receiver operating characteristic curve (AUC)). RESULTS: RAPS' cross-validated BCR predictions provided better calibration than those of an existing model that underestimated patients' risks. Discrimination was similar for the two models, with BCR AUCs of 0.793, 95% confidence interval (0.766-0.820) for RAPS, and 0.780 (0.745-0.815) for the existing model. RAPS' most important BCR predictors were tumor grade, preoperative prostate-specific antigen (PSA) level and BMI; race was less important [3]. RAPS' predictions can be obtained online at https://predict.shinyapps.io/raps. CONCLUSION: RAPS' cross-validated BCR predictions were better calibrated than those of an existing model, and BMI information contributed substantially to these predictions. RAPS predictions for recurrence-free death were limited by lack of co-morbidity data; however the model provides a simple framework for extension to include such data. Its use and extension should facilitate decision strategies for post-RP prostate cancer management. Prostate 77:291-298, 2017. © 2016 Wiley Periodicals, Inc.

The impact of body mass index on treatment outcomes for patients with low-intermediate risk prostate cancer.

BACKGROUND: Little is known about the relationship between preoperative body mass index and need for adjuvant radiation therapy (RT) following radical prostatectomy. The goal of this study was to evaluate the utility of body mass index in predicting adverse clinical outcomes which require adjuvant RT among men with organ-confined prostate cancer (PCa). METHODS: We used a prospective cohort of 1,170 low-intermediate PCa risk men who underwent radical prostatectomy and evaluated the effect of body mass index on adverse pathologic features and freedom from biochemical failure (FFbF). Clinical and pathologic variables were compared across the body mass index groups using an analysis of variance model for continuous variables or χ(2) for categorical variables. Factors related to adverse pathologic features were examined using logistic regression models. Time to biochemical recurrence was compared across the groups using a log-rank survivorship analysis. Multivariable analysis predicting biochemical recurrence was conducted with a Cox proportional hazards model. RESULTS: Patients with elevated body mass index (defined as body mass index ≥25 kg/m(2)) had greater extraprostatic extension (p = 0.004), and positive surgical margins (p = 0.01). Elevated body mass index did not correlate with preoperative risk groupings (p = 0.94). However, when compared with non-obese patients (body mass index <30 kg/m(2)), obese patients (body mass index ≥30 kg/m(2)) were much more likely to have higher rate of adverse pathologic features (p = 0.006). In patients with low- and intermediate- risk disease, obesity was strongly associated with rate of pathologic upgrading of tumors (p = 0.01 and p = 0.02), respectively. After controlling for known preoperative risk factors, body mass index was independently associated with ≥2 adverse pathologic features (p = 0.002), an indicator for adjuvant RT as well as FFbF (p = 0.001). CONCLUSIONS: Body mass index of ≥30 kg/m(2) is independently associated with adverse pathologic features, which is an indicator for additional RT, particularly in patients with low-intermediate risk disease. Future studies may determine if this select group of patients may be best treated with definitive RT to reduce toxicity from additional RT following radical prostatectomy. We propose including body mass index in clinical decision-making for appropriate treatment recommendation for patients with low-intermediate risk PCa.

Cost-Effectiveness of Integrating Tobacco Cessation Into Post-Traumatic Stress Disorder Treatment.

INTRODUCTION: We examined the cost-effectiveness of smoking cessation integrated with treatment for post-traumatic stress disorder (PTSD). METHODS: Smoking veterans receiving care for PTSD (N = 943) were randomized to care integrated with smoking cessation versus referral to a smoking cessation clinic. Smoking cessation services, health care cost and utilization, quality of life, and biochemically-verified abstinence from cigarettes were assessed over 18-months of follow-up. Clinical outcomes were combined with literature on changes in smoking status and the effect of smoking on health care cost, mortality, and quality of life in a Markov model of cost-effectiveness over a lifetime horizon. We discounted cost and outcomes at 3% per year and report costs in 2010 US dollars. RESULTS: The mean of smoking cessation services cost was $1286 in those randomized to integrated care and $551 in those receiving standard care (P < .001). There were no significant differences in the cost of mental health services or other care. After 12 months, prolonged biochemically verified abstinence was observed in 8.9% of those randomized to integrated care and 4.5% of those randomized to standard care (P = .004). The model projected that Integrated Care added $836 in lifetime cost and generated 0.0259 quality adjusted life years (QALYs), an incremental cost-effectiveness ratio of $32 257 per QALY. It was 86.0% likely to be cost-effective compared to a threshold of $100 000/QALY. CONCLUSIONS: Smoking cessation integrated with treatment for PTSD was cost-effective, within a broad confidence region, but less cost-effective than most other smoking cessation programs reported in the literature.

Cost-effectiveness of smoking cessation treatment initiated during psychiatric hospitalization: analysis from a randomized, controlled trial.

OBJECTIVE: We examined the cost-effectiveness of smoking cessation treatment for psychiatric inpatients. METHOD: Smokers, regardless of intention to quit, were recruited during psychiatric hospitalization and randomized to receive stage-based smoking cessation services or usual aftercare. Smoking cessation services, quality of life, and biochemically verified abstinence from cigarettes were assessed during 18 months of follow-up. A Markov model of cost-effectiveness over a lifetime horizon was constructed using trial findings and parameters obtained in a review of the literature on quit and relapse rates and the effect of smoking on health care cost, quality of life, and mortality. RESULTS: Among 223 smokers randomized between 2006 and 2008, the mean cost of smoking cessation services was $189 in the experimental treatment group and $37 in the usual care condition (P < .001). At the end of follow-up, 18.75% of the experimental group was abstinent from cigarettes, compared to 6.80% abstinence in the usual care group (P < .05). The model projected that the intervention added $43 in lifetime cost and generated 0.101 additional quality-adjusted life-years (QALYs), an incremental cost-effectiveness ratio of $428 per QALY. Probabilistic sensitivity analysis found the experimental intervention was cost-effective against the acceptance criteria of $50,000/QALY in 99.0% of the replicates. CONCLUSIONS: A cessation intervention for smokers identified in psychiatric hospitalization did not result in higher mental health care costs in the short-run and was highly cost-effective over the long-term. The stage-based intervention was a feasible and cost-effective way of addressing the high smoking prevalence in persons with serious mental illness. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00136812.

Cost-effectiveness of extended cessation treatment for older smokers.

AIMS: We examined the cost-effectiveness of extended smoking cessation treatment in older smokers. DESIGN: Participants who completed a 12-week smoking cessation program were factorial randomized to extended cognitive behavioral treatment and extended nicotine replacement therapy. SETTING: A free-standing smoking cessation clinic. PARTICIPANTS: A total of 402 smokers aged 50 years and older were recruited from the community. MEASUREMENTS: The trial measured biochemically verified abstinence from cigarettes after 2 years and the quantity of smoking cessation services utilized. Trial findings were combined with literature on changes in smoking status and the age- and gender-adjusted effect of smoking on health-care cost, mortality and quality of life over the long term in a Markov model of cost-effectiveness over a lifetime horizon. FINDINGS: The addition of extended cognitive behavioral therapy added $83 in smoking cessation services cost [P = 0.012, confidence interval (CI) = $22-212]. At the end of follow-up, cigarette abstinence rates were 50.0% with extended cognitive behavioral therapy and 37.2% without this therapy (P < 0.05, odds ratio 1.69, CI 1.18-2.54). The model-based incremental cost-effectiveness ratio was $6324 per quality-adjusted life year (QALY). Probabilistic sensitivity analysis found that the additional $947 in lifetime cost of the intervention had a 95% confidence interval of -$331 to 2081; the 0.15 additional QALYs had a confidence interval of 0.035-0.280, and that the intervention was cost-effective against a $50 000/QALY acceptance criterion in 99.6% of the replicates. Extended nicotine replacement therapy was not cost-effective. CONCLUSIONS: Adding extended cognitive behavior therapy to standard cessation treatment was cost-effective. Further intensification of treatment may be warranted.

Rapid and transient activation of gene expression in peripheral blood mononuclear cells from Johne's disease positive cows exposed to Mycobacterium paratuberculosis in vitro.

Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of Johne's disease in ruminants. M. paratuberculosis is a slow-growing intracellular bacterium and infections with M. paratuberculosis can persist in a subclinical state for several years. An early and appropriate T cell-mediated cytotoxic response (Th1-like) to M. paratuberculosis infection is often replaced with an antibody or Th 2-like response as infected animals move toward a progressively more clinical state. The reasons for this shift in immune response are unknown. Recent studies suggest that in vitro exposure of peripheral blood mononuclear cells (PBMCs) from Johne's disease positive cows to M. paratuberculosis for 18-24 h results in suppressed expression of numerous immune cell genes. This effect appears at odds with the notion that immune cells from infected cows would respond to M. paratuberculosis-specific antigens in a vigorous and positive manner. In this report, we detail experiments designed to test the hypothesis that many positive changes in PBMC gene expression induced by M. paratuberculosis in vitro are transient, being rapidly suppressed by as yet unknown mechanisms. Our results demonstrate that, indeed, in vitro stimulation with M. paratuberculosis induces rapid changes in infected cow PBMC gene expression (within 2-4 h of exposure) and that many of these changes are no longer evident by 8-16 h of exposure to M. paratuberculosis. Although precise mechanisms responsible for rapid M. paratuberculosis-mediated activation of PBMC gene expression and the loss thereof remain to be determined, our novel results suggest that PBMCs from Johne's disease positive cows are indeed capable of vigorously responding to M. paratuberculosis and that, for many genes, this response is tempered within 8 h of exposure.

Development and testing of a high-density cDNA microarray resource for cattle.

A cDNA microarray resource has been developed with the goal of providing integrated functional genomics resources for cattle. The National Bovine Functional Genomics Consortium's (NBFGC) expressed sequence tag (EST) collection was established in 2001 to develop resources for functional genomics research. The NBFGC EST collection and microarray contains 18,263 unique transcripts, derived from many different tissue types and various physiologically important states within these tissues. The NBFGC microarray has been tested for false-positive rates using self-self hybridizations and was shown to yield robust results in test microarray experiments. A web-accessible database has been established to provide pertinent data related to NBFGC clones, including sequence data, BLAST results, and ontology information. The NBFGC microarray represents the largest cDNA microarray for a livestock species prepared to date and should prove to be a valuable tool in studying genome-wide gene expression in cattle.