Which tobacco control policies do smokers support? Findings from the International Tobacco Control Four Country Smoking and Vaping Survey.

As governments consider policy action to reduce smoking, a key factor in creating political will is the level of public support, particularly among smokers who are most affected by the policies. The goal of this paper is to assess and compare the level of support in Canada, the United States, England, and Australia for five smoking control policies: 1) banning menthol in cigarettes, 2) banning cigarette additives, 3) reducing nicotine in cigarettes to make them less addictive, 4) raising the minimum age to purchase cigarettes to 21 years and older, and 5) requiring pictorial warning labels on cigarette packs (examined in the US only). Data for these analyses come from 8165 daily cigarette smokers who responded to the 2016 International Tobacco Control Four Country Smoking and Vaping Survey. In all countries, the highest level of support was for raising the legal age for purchase to 21 years and older (62-70%) and reducing the nicotine content of cigarettes to make them less addictive (57-70%). Smokers who were less dependent on cigarettes and those expressing interest in quitting were more likely to support all policies. When asked how they would respond to a nicotine reduction policy, the most common response given was to try the non-nicotine cigarettes to see how they liked them (42-48%), with the next most common response being to quit smoking entirely (16-24%). The high level of support for these proposed policies among daily smokers provides important evidence for policymakers to counteract claims that such policies would be unpopular.

Social and clinical determinants of physical activity in prostate cancer survivors.

PURPOSE: Physical activity is important for enhancing quality of life and cancer control among prostate cancer survivors. The purpose of this study was to characterize adherence to physical activity guidelines among African American and white prostate cancer survivors based on social and clinical determinants and psychosocial factors. METHODS: Observational study of meeting guidelines for moderate intensity physical activity in a retrospective cohort of African American and white prostate cancer survivors (n = 89). RESULTS: Thirty-four percent of survivors met the recommended guidelines for moderate intensity physical activity. There were no racial differences in physical activity between African American and white prostate cancer survivors; however, the likelihood of meeting guidelines was associated significantly with stage of disease, self-rated health, and perceptions of stress. Survivors who had stage pT2c or higher disease had a significantly reduced likelihood of meeting recommended guidelines for physical activity (OR = 0.27, 95% CI = 0.08, 0.86, p = 0.03). The likelihood of meeting guidelines was also reduced among survivors who rated their health as being the same or worse than before they were diagnosed with prostate cancer (OR = 0.32, 95% CI = 0.11, 0.96, p = 0.04). As perceived stress increased, the likelihood of being physically active according to guidelines also decreased (OR = 0.48, 95% CI = 0.26, 0.89, p = 0.02). CONCLUSION: The results of this study underscore the need to develop, implement, and evaluate strategies to enhance physical activity among prostate cancer survivors, regardless of their racial background. Complementary and alternative strategies for physical activity may be one strategy for enhancing activity levels and managing stress among prostate cancer survivors.

State Tobacco Excise Taxation, Comprehensive Smoke-free Air Laws, and Tobacco Control Appropriations as Predictors of Smoking Cessation Success in the United States.

The purpose of the present study was (1) to examine demographic differences between smokers who successfully quit (n = 1809), who relapsed (n = 6548), and who did not attempt to quit (n = 11 102) within the last year, and (2) to examine state-level tobacco policies/programs as predictors of quit success. Data were utilized from the 2014-2015 Tobacco Use Supplement to the Current Population Survey, which were paired with 2014 data on taxation, appropriations, and smoke-free air laws. As compared with smokers who relapsed, those who successfully quit were more likely to be white, married, more highly educated, of higher income, and heavier smokers. Compared with those who did not attempt to quit, those who attempted to quit, regardless of success, were younger and more likely to be Hispanic. State comprehensive smoke-free air laws and tobacco excise taxation significantly predicted quit success. Thus, expansions of these policies should be considered to promote successful quitting.

Effect of an Evidence-based Inpatient Tobacco Dependence Treatment Service on 1-Year Postdischarge Health Care Costs.

BACKGROUND: In 2014, the Medical University of South Carolina (MUSC) implemented a Tobacco Dependence Treatment Service (TDTS) consistent with the Joint Commission (JC) standards recommending that hospitals screen patients for smoking, provide cessation support, and follow-up contact for relapse prevention within 1 month of discharge. We previously demonstrated that patients exposed to the MUSC TDTS were approximately half as likely to be smoking one month after discharge and 23% less likely to have a 30-day hospital readmission. This paper examines whether exposure to the TDTS influenced downstream health care charges 12 months after patients were discharged from the hospital. METHODS: Data from MUSC's electronic health records, the TDTS, and statewide health care utilization datasets (eg, hospitalization, emergency department, and ambulatory surgery visits) were linked to assess how exposure to the MUSC TDTS impacted health care charges. Total health care charges were compared for patients with and without TDTS exposure. To reduce potential TDTS exposure selection bias, propensity score weighting was used to balance baseline characteristics between groups. The cost of delivering the MUSC TDTS intervention was calculated, along with cost per smoker. RESULTS: The overall adjusted mean health care charges for smokers exposed to the TDTS were $7299 lower than for those who did not receive TDTS services (P=0.047). The TDTS cost per smoker was modest by comparison at $34.21 per smoker eligible for the service. DISCUSSION: Results suggest that implementation of a TDTS consistent with JC standards for smoking cessation can be affordably implemented and yield substantial health care savings that would benefit patients, hospitals, and insurers.

Effect of an Evidence-based Inpatient Tobacco Dependence Treatment Service on 30-, 90-, and 180-Day Hospital Readmission Rates.

INTRODUCTION: Smoking is a risk factor for hospitalization and interferes with patient care due to its effects on pulmonary function, wound healing, and interference with treatments and medications. Although benefits of stopping smoking are well-established, few hospitals provide tobacco dependence treatment services (TDTS) due to cost, lack of mandatory tobacco cessation standards and lack of evidence demonstrating clinical and financial benefits to hospitals and insurers for providing services. METHODS: This study explored the effect of an inpatient TDTS on 30-, 90-, and 180-day hospital readmissions. To carry out this work, 3 secondary datasets were linked, which included clinical electronic health record data, tobacco cessation program data, and statewide health care utilization data. Odds ratios (ORs) were calculated using inverse propensity score-weighted logistic regression models, with program exposure as the primary independent variable and 30 (90 and 180)-day readmission rates as the dependent variable, and adjustment for putative covariates. RESULTS: Odds of readmission were compared for patients who did and did not receive TDTS. At 30 days postdischarge, smokers exposed to the TDTS had a lower odds of readmission (OR=0.77, P=0.031). At 90 and 180 days, odds of readmission remained lower in the TDTS group (ORs=0.87 and 0.86, respectively), but were not statistically significant. DISCUSSION: Findings from the current study, which are supported by prior studies, provide evidence that delivery of TDTS is a strategy that may help to reduce hospital readmissions.

Feasibility of Implementing a Hospital-Based "Opt-Out" Tobacco-Cessation Service.

OBJECTIVE: To assess the feasibility and outcomes of implementing a hospital-based "opt-out" tobacco-cessation service. METHODS: In 2014, the Medical University of South Carolina adopted a policy that all hospitalized patients who self-report using tobacco be referred to tobacco-cessation service. This is a descriptive study of a real-world effort to implement guidelines for a hospital-based cessation service consistent with Joint Commission's standards. Between February 2014 and May 2015, 42 061 adults were admitted to the Medical University of South Carolina Hospital. Eligible current cigarette smokers were referred to the tobacco-cessation service, which consisted of a bedside consult and phone follow-up 3, 14, and 30 days after hospital discharge using interactive-voice-response. The primary study outcomes evaluated the proportions of smokers reached by the bedside counselor and/or phone follow-up, smokers who opted out, and smokers who self-reported not smoking when last contacted by phone. RESULTS: Records identified 8423 smokers, of whom 69.4% (n = 5843) were referred into the service. One full-time bedside counselor was able to speak with 1918 (32.8%) patients, of whom 96 (5%) denied currently smoking and 287 (14.9%) refused counselling. Reach at follow-up was achieved for 703 (55%) smokers who received bedside counselling and 1613 (49%) who did not, yielding an overall follow-up reach rate of 60%. Of those reached by phone, 36.4% reported not smoking (51% vs. 27% for those who did and did not receive bedside counselling, respectively). Intent-to-treat abstinence rate was 13.5% according to the last known smoking status. CONCLUSIONS: Findings from this study suggest that an inpatient smoking-cessation service with an "opt-out" approach can positively impact short-term cessation outcomes. IMPLICATIONS: (1) The findings demonstrate the feasibility of implementing an automated large-scale opt-out tobacco-cessation service for hospitalized patients that is consistent with the Joint Commission recommended standards for treating tobacco dependence. (2) Receiving a bedside tobacco-cessation consult while hospitalized increased the use of stop smoking medications and abstinence from smoking after discharge from the hospital. (3) Even in those patients who did not receive a bedside consult, 5% accepted a referral to the South Carolina Tobacco Quitline to get help to stop smoking.

Tobacco Use Prevalence and Outcomes Among Perinatal Patients Assessed Through an "Opt-out" Cessation and Follow-Up Clinical Program.

Purpose Cigarette smoking in the perinatal period is associated with costly morbidity and mortality for mother and infant, yet many women continue to smoke throughout their pregnancy and following delivery. This report describes tobacco use prevalence among perinatal smokers identified through an "opt-out" inpatient smoking cessation clinical service. Description Adult women admitted to the peripartum, delivery, and postpartum units at a large academic hospital were screened for tobacco use. Smokers were identified through their medical record and referred to a bedside consult and follow-up using an interactive voice response (IVR) system to assess smoking up to 30 days post-discharge. Assessment Between February 2014 and March 2016, 533 (10%) current and 898 (16%) former smokers were identified out of 5649 women admitted to the perinatal units. Current smokers reported an average of 11 cigarettes per day for approximately 12 years. Only 10% reported having made a quit attempt in the past year. The majority of smokers (56%) were visited by a bedside tobacco cessation counselor during their stay and 27% were contacted through the IVR system. Those counselled in the hospital were twice as likely (RR 1.98, CI 1.04-3.78) to be abstinent from smoking using intent-to-treat analysis at any time during the 30 days post-discharge. Conclusions This opt-out service reached a highly nicotine-dependent perinatal population, many of whom were receptive to the service, and it appeared to improve abstinence rates post-discharge. Opt-out tobacco cessation services may have a significant impact on the health outcomes of this population and their children.

Novel high-risk acute myeloid leukemia subgroup with ERG amplification and Biallelic loss of TP53.

ETS-related gene (ERG) amplification, observed in 4-6% of acute myeloid leukemia (AML), is associated with unfavorable prognosis. To determine coincident effects of additional genomic abnormalities in AML with ERG amplification (ERGamp), we examined 11 ERGamp cases of 205 newly diagnosed AML using chromosomal microarray analysis and next generation sequencing. ERGamp cases demonstrated a distinct pattern of high genetic complexity: loss of 5q, chromothripsis and TP53 loss of function variants. Remarkably, allelic TP53 loss or loss of heterozygosity (LOH) co-occurring with TP53 inactivating mutation dramatically effected ERGamp tumor patient outcome. In the presence of homozygous TP53 loss of function, ERGamp patients demonstrated no response to induction chemotherapy with median overall survival (OS) of 3.8 months (N = 9). Two patients with heterozygous loss of TP53 function underwent alloSCT without evidence of relapse at one year. Similarly, a validation TCGA cohort, 6 of the 8 ERGamp cases with TP53 loss of function demonstrated median OS of 2.5 months. This suggests that with TP53 mutant ERGamp AML, successive loss of the second TP53 allele, typically by 17p deletion or LOH identifies a specific high-risk subtype of AML patients who are resistant to standard induction chemotherapy and need novel approaches to avert the very poor prognosis.

Smokeless Tobacco Use and Prevalence of Cardiovascular Disease Among Males in the Population Assessment of Tobacco and Health (PATH) Study, Waves 1-4.

The purpose of this period prevalence study is to compare the prevalence of cardiovascular disease (CVD) in current/former established smokeless tobacco (SLT) users (ever SLT users who have used the product fairly regularly) to those who were: 1) never established cigarette smokers and SLT users, and 2) current/former established exclusive cigarette smokers (have smoked at least a 100 or more cigarettes in lifetime) only, adjusting for known risk factors for CVD. Analyses included 4,703 men ≥ 40 years of age who participated in the Population Assessment of Tobacco and Health (PATH) Study, Waves: 1-4, conducted between 2013 and 2017. Current users were those using SLT products daily or on some days, whereas former users had not used SLT and/or cigarettes in the past 12 months. CVD prevalence was defined as a self-reported diagnosis of congestive heart failure, stroke, or myocardial infarction. Among current/former established SLT users, years of use defined exposure history, while pack-years defined exposure history for smokers. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were reported with trend tests to examine dose-response associations. Current/former established exclusive SLT users were not significantly more likely to have had any CVD compared to never established cigarette and SLT users (OR = 1.7 [0.8-3.7]), or current/former established exclusive cigarette smokers (OR = 0.9 [0.5-1.8]). Current/former established exclusive cigarette smokers were more likely to have had any CVD compared to those who were never established cigarette and SLT users (OR = 1.6 [1.1-2.3]).

Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive Liposomes.

GOAL: The impact of hyperthermia (HT) method on tumor drug uptake with thermosensitive liposomes (TSL) is not well understood. METHODS: We created realistic three-dimensional (3-D) computer models that simulate TSL-encapsulated doxorubicin (TSL-DOX) delivery in mouse tumors with three HT methods (thermistor probe (T), laser (L) and water bath (WB), at 15 min and 60 min HT duration), with corroborating in vivo studies. RESULTS: Average computer model-predicted tumor drug concentrations (µg/g) were 8.8(T, 15 min), 21.0(T, 60 min), 14.1(L, 15 min), 25.2(L, 60 min), 9.4(WB, 15 min), and 8.7(WB, 60 min). Tumor fluorescence was increased by 2.6 × (T) and 1.6 × (L) when HT duration was extended from 15 to 60 min (p < 0.05), with no increase for WB HT. Pharmacokinetic analysis confirmed that water bath HT causes rapid depletion of encapsulated TSL-DOX in systemic circulation due to the large heated tissue volume. CONCLUSIONS: Untargeted large volume HT causes poor tumor drug uptake from TSL.

Associations between cancer diagnosis and patients' responses to an inpatient tobacco treatment intervention.

BACKGROUND: Diagnosis of a chronic illness, such as cancer may influence health behavior changes, such as smoking cessation. The present analyses examine associations between a cancer diagnosis (i.e., yes or no) and response to an opt-out smoking cessation bedside intervention provided to hospitalized patients. It was hypothesized that patients with a past or present cancer diagnosis would report higher motivation and engagement with quitting smoking, and higher rates of smoking abstinence after hospital discharge, compared to those without a cancer diagnosis. METHODS: Chart review was conducted on 5287 inpatients who accepted bedside treatment from a counselor and opted-in to automated follow-up calls from July 2014 to December 2019. RESULTS: At the time of inpatient assessment, those with a past or present cancer diagnosis (n = 419, 7.9%) endorsed significantly higher levels of importance of quitting than those without a cancer diagnosis (3.92/5 vs. 3.77/5), and were more likely to receive smoking cessation medication upon discharge (17.9% vs. 13.3%). Follow-up data from 30-days post-discharge showed those with a cancer diagnosis endorsed higher rates of self-reported abstinence (20.5%) than those without a cancer diagnosis (10.3%; p < 0.001). CONCLUSION: Being hospitalized for any reason provides an opportunity for smokers to consider quitting. Having a previous diagnosis of cancer appears to increase intention to quit and lead to higher rates of smoking cessation in patients who are hospitalized compared to patients without cancer. Future research needs to work toward optimizing motivation for smoking cessation while admitted to a hospital and on improving quit rates for all admitted patients, regardless of diagnosis.

Preinvasive Colorectal Lesions of African Americans Display an Immunosuppressive Signature Compared to Caucasian Americans.

BACKGROUND: African Americans (AAs) have higher colorectal cancer (CRC) incidence and mortality rate than Caucasian Americans (CAs). Recent studies suggest that immune responses within CRCs contribute to the disparities. If racially distinct immune signatures are present in the early phases of carcinogenesis, they could be used to develop interventions to prevent or slow disease. METHODS: We selected a convenience sample of 95 patients (48 CAs, 47 AAs) with preinvasive colorectal adenomas from the surgical pathology laboratory at the Medical University of South Carolina. Using immunofluorescent-conjugated antibodies on tissue slides from the lesions, we quantified specific immune cell populations: mast cells (CD117+), Th17 cells (CD4+RORC+), and NK cell ligand (MICA/B) and inflammatory cytokines, including IL-6, IL-17A, and IFN-γ. We compared the mean density counts (MDCs) and density rate ratios (RR) and 95% CI of immune markers between AAs to CAs using negative binomial regression analysis. We adjusted our models for age, sex, clinicopathologic characteristics (histology, location, dysplasia), and batch. RESULTS: We observed no racial differences in age or sex at the baseline endoscopic exam. AAs compared to CAs had a higher prevalence of proximal adenomas (66% vs. 40%) and a lower prevalence of rectal adenomas (11% vs. 23%) (p =0.04) but no other differences in pathologic characteristics. In age, sex, and batch adjusted models, AAs vs. CAs had lower RRs for cells labeled with IFNγ (RR 0.50 (95% CI 0.32-0.81); p=0.004) and NK cell ligand (RR 0.67 (0.43-1.04); p=0.07). In models adjusted for age, sex, and clinicopathologic variables, AAs had reduced RRs relative to CAs for CD4 (p=0.02), NK cell ligands (p=0.01), Th17 (p=0.005), mast cells (p=0.04) and IFN-γ (p< 0.0001). CONCLUSIONS: Overall, the lower RRs in AAs vs. CAs suggests reduced effector response capacity and an immunosuppressive ('cold') tumor environment. Our results also highlight the importance of colonic location of adenoma in influencing these differences; the reduced immune responses in AAs relative to CAs may indicate impaired immune surveillance in early carcinogenesis. Future studies are needed to understand the role of risk factors (such as obesity) in influencing differences in immune responses by race.

Comparative analysis of antibodies to SARS-CoV-2 between asymptomatic and convalescent patients.

The SARS-CoV-2 viral pandemic has induced a global health crisis, which requires more in-depth investigation into immunological responses to develop effective treatments and vaccines. To understand protective immunity against COVID-19, we screened over 60,000 asymptomatic individuals in the Southeastern United States for IgG antibody positivity against the viral Spike protein, and approximately 3% were positive. Of these 3%, individuals with the highest anti-S or anti-RBD IgG level showed a strong correlation with inhibition of ACE2 binding and cross-reactivity against non-SARS-CoV-2 coronavirus S-proteins. We also analyzed samples from 94 SARS-CoV-2 patients and compared them with those of asymptomatic individuals. SARS-CoV-2 symptomatic patients had decreased antibody responses, ACE2 binding inhibition, and antibody cross-reactivity. Our study shows that healthy individuals can mount robust immune responses against SARS-CoV-2 without symptoms. Furthermore, IgG antibody responses against S and RBD may correlate with high inhibition of ACE2 binding in individuals tested for SARS-CoV-2 infection or post vaccination.

What Is Accounting for the Rapid Decline in Cigarette Sales in Japan?

This study describes how trends in the sale of cigarettes in Japan between 2011 and 2019 correspond to the sales of heated tobacco products (HTPs) that were introduced into the Japanese market in late 2015. Data used for this study come from the Tobacco Institute of Japan and Philip Morris International. The findings show that the accelerated decline in cigarette only sales in Japan since 2016 corresponds to the introduction and growth in the sales of HTPs.

How are adolescents getting their vaping products? Findings from the international tobacco control (ITC) youth tobacco and vaping survey.

OBJECTIVE: To examine the sources of vaping products reported by adolescents, and the characteristics of adolescents who reported purchasing a vaping product in the past year in the United States (US), Canada (CA), and England (EN). METHODS: Data were from the 2017 ITC Youth Tobacco and Vaping Survey, a web-based survey of 12,128 respondents aged 16-19 years recruited from commercial panels in the US, CA, and EN. Respondents who have vaped in the past 12 months were asked whether they had purchased a vaping product, and from where (vape shop, online, retail), as well as whether anyone refused to sell them a vaping product because of their age. Respondents who reported vaping in the past 30 days were asked where they had obtained their vaping product from a social and/or commercial source. RESULTS: Only about 7.5% of respondents reported having purchased a vaping product in the past year. Among those who had vaped in the past year, 32.6% reported having purchased a vaping product in the past year. Purchasing prevalence was significantly higher among US respondents compared to those from CA and EN; purchase prevalence was also higher among Canadian adolescents than respondents from England. The most commonly reported purchase location for vaping products in all counties was vape shops. Among past 30-day vapers, 42.5% reported getting their vaping products only from social sources, 41.4% only from commercial sources, and 13.4% from both types of sources. Purchasing a vaping product in the past year was associated with being male, of legal age to buy tobacco and vaping products, and greater frequency of smoking and vaping in the past 30 days. CONCLUSIONS: Most adolescents have not purchased a vaping product, but among those who had, vape shops were the mostly commonly reported location for buying a vaping product. Purchasing of a vape product was more commonly reported by those who vape more frequently and by those of legal age to buy a vaping product.

Cole Relaxation Frequency as a Prognostic Parameter for Breast Cancer.

We previously reported successful classification of breast cancer versus benign tissue using the Cole relaxation frequency measured on tissue excised during breast surgery as part of a study at two urban hospitals in the U.S. Midwest. Using that health system's cancer registry, we have discovered retrospectively that outcomes for patients who participated in the initial study can be classified correctly in 3 well-differentiated categories: nonrecurrent (NR); recurrent with no metastasis (RNM); and recurrent with metastasis (RM). As Cole relaxation frequency increases, the classification moves from NR to RNM and finally to RM. Multivariate analysis showed a significant association of "time-cancer-free" for all patients in these recurrent categories, with P-values ranging between 0.0001 to 0.0047. Thus, this follow-up report shows the potential feasibility of using Cole relaxation frequency as a prognostic parameter in a larger prospective study.

Financial toxicity and strain among men receiving prostate cancer care in an equal access healthcare system.

PURPOSE: To examine financial toxicity and strain among men in an equal access healthcare system based on social determinants and clinical characteristics. METHODS: Observational study among men receiving prostate cancer care (n = 49) at a Veterans Health Administration (VHA) facility. Financial hardship included overall financial strain and financial toxicity due to healthcare costs. Financial strain was measured with one item asking how much money they have leftover at the end of the month. Financial toxicity was measured with the Comprehensive Score for Financial Toxicity (COST) scale. RESULTS: Comprehensive Score for Financial Toxicity scores among participants indicated moderate levels of financial toxicity (M = 24.4, SD = 9.9). For financial strain, 36% of participants reported that they did not have enough money left over at the end of the month. There were no racial or clinically related differences in financial toxicity, but race and income level had significant associations with financial strain. CONCLUSION: Financial toxicity and strain should be measured among patients in an equal access healthcare system. Findings suggest that social determinants may be important to assess, to identify patients who may be most likely to experience financial hardship in the context of obtaining cancer care and implement efforts to mitigate the burden for those patients.

Assessing an intervention to increase knowledge related to cervical cancer and the HPV vaccine.

Human papillomavirus (HPV) infection is the primary risk factor for cervical cancer. While the HPV vaccine significantly reduces the risk of HPV infection and subsequent cervical cancer diagnosis, underuse is linked to lack of knowledge of its effectiveness in preventing cervical cancer. The purpose of this study was to evaluate a cancer educational intervention (titled "MOVENUP") to improve knowledge of cervical cancer, HPV, and the HPV vaccine among predominantly African American communities in South Carolina. The MOVENUP cancer educational intervention was conducted among participants residing in nine South Carolina counties who were recruited by community partners. The 4.5-h MOVENUP cancer educational intervention included a 30-min module on cervical cancer, HPV, and HPV vaccination. A six-item investigator-developed instrument was used to evaluate pre- and post-intervention changes in knowledge related to these content areas. Ninety-three percent of the 276 participants were African American. Most participants reporting age and gender were 50+ years (73%) and female (91%). Nearly half of participants (46%) reported an annual household income <$40,000 and 49% had not graduated from college. Statistically significant changes were observed at post-test for four of six items on the knowledge scale (P<0.05), as compared to pre-test scores. For the two items on the scale in which statistically significant changes were not observed, this was due primarily due to a baseline ceiling effect.

Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma.

Androgen Receptor (AR) signaling is a critical driver of hormone-dependent prostate cancer and has also been proposed to have biological activity in female hormone-dependent cancers, including type I endometrial carcinoma (EMC). In this study, we evaluated the preclinical efficacy of a third-generation AR antagonist, enzalutamide, in a genetic mouse model of EMC, Sprr2f-Cre;Ptenfl/fl. In this model, ablation of Pten in the uterine epithelium leads to localized and distant malignant disease as observed in human EMC. We hypothesized that administering enzalutamide through the diet would temporarily decrease the incidence of invasive and metastatic carcinoma, while prolonged administration would result in development of resistance and loss of efficacy. Short-term treatment with enzalutamide reduced overall tumor burden through increased apoptosis but failed to prevent progression of invasive and metastatic disease. These results suggest that AR signaling may have biphasic, oncogenic and tumor suppressive roles in EMC that are dependent on disease stage. Enzalutamide treatment increased Progesterone Receptor (PR) expression within both stromal and tumor cell compartments. Prolonged administration of enzalutamide decreased apoptosis, increased tumor burden and resulted in the clonal expansion of tumor cells expressing high levels of p53 protein, suggestive of acquired Trp53 mutations. In conclusion, we show that enzalutamide induces apoptosis in EMC but has limited efficacy overall as a single agent. Induction of PR, a negative regulator of endometrial proliferation, suggests that adding progestin therapy to enzalutamide administration may further decrease tumor burden and result in a prolonged response.

Where Do Vapers Buy Their Vaping Supplies? Findings from the International Tobacco Control (ITC) 4 Country Smoking and Vaping Survey.

Aim: This study examines where vapers purchase their vaping refills in countries having different regulations over such devices, Canada (CA), the United States (US), England (EN), and Australia (AU). Methods: Data were available from 1899 current adult daily and weekly vapers who participated in the 2016 (Wave 1) International Tobacco Control Four Country Smoking and Vaping. The outcome was purchase location of vaping supplies (online, vape shop, other). Adjusted odds ratios and 95% confidence intervals were reported for between country comparisons. Results: Overall, 41.4% of current vapers bought their vaping products from vape shops, 27.5% bought them online, and 31.1% from other retail locations. The vast majority of vapers (91.1%) reported using nicotine-containing e-liquids. In AU, vapers were more likely to buy online vs other locations compared to CA (OR = 6.4, 2.3⁻17.9), the US (OR = 4.1, 1.54⁻10.7), and EN (OR = 7.9, 2.9⁻21.8). In the US, they were more likely to buy from vape shops (OR = 3.3, 1.8⁻6.2) or online (OR = 1.9, 1.0⁻3.8) vs other retail locations when compared to those in EN. In CA, vapers were more likely to purchase at vape shops than at other retail locations when compared to vapers in EN (5.9, 3.2⁻10.9) and the US (1.87, 1.0⁻3.1). Conclusions: The regulatory environment and enforcement of such regulations appear to influence the location where vapers buy their vaping products. In AU, banning the retail sale of nicotine vaping products has led vapers to rely mainly on online purchasing sources, whereas the lack of enforcement of the same regulation in CA has allowed specialty vape shops to flourish.