Exploring Patterns of the Use of Electronic Nicotine Delivery Systems among Adolescents in High-Risk Appalachian (U.S.A) Communities.

Background: Electronic nicotine delivery systems (ENDS) use among adolescents in the United States (U.S.) has surpassed conventional tobacco products (CTPs), including cigarettes. Increasingly, ENDS are used concurrently with CTPs and substances such as cannabis. However, few studies involve Central Appalachia, a region with historically high rates of tobacco and other substance use. Objective:  To examine prevalence of concurrent use of ENDS and cannabis among school-going adolescents in Appalachian Tennessee and delineate associations between ENDS use and substance-related risk behavior (cannabis use), social relations (peer use), and school-related risk behavior (academic performance). Methods: Data were obtained from a survey conducted with youth aged 13-17 years in 2018 in a county in Appalachian Tennessee (n = 280). A multivariable logistic regression model was fit to evaluate associations between ENDS and cannabis use, and other factors. Results: Overall, lifetime ENDS and cannabis prevalence estimates were 31.1% and 18.6%, respectively. Lifetime ENDS users had increased odds of also being lifetime cannabis users [OR = 9.22, 95% confidence interval (CI): 3.44-24.75]. Lifetime ENDS users had increased odds of reporting ENDS use among peers [OR = 12.11; 95% CI: 5.40-27.12] and lower academic performance (OR associated with mostly C or D vs. A grades was 4.28, 95% CI: 1.68-10.90). Conclusion: This study found an association between ENDS and cannabis use among adolescents in Appalachian Tennessee exists. Additionally, peer use and academic performance were associated with ENDS use. The findings have implications for public health intervention planning to address not only ENDS but also substance use among Appalachian youth.

Exploring Associations between Susceptibility to the Use of Electronic Nicotine Delivery Systems and E-Cigarette Use among School-Going Adolescents in Rural Appalachia.

Electronic nicotine delivery systems (ENDS) use, including e-cigarettes, has surpassed the use of conventional tobacco products. Emerging research suggests that susceptibility to e-cigarette use is associated with actual use among adolescents. However, few studies exist involving adolescents in high-risk, rural, socioeconomically distressed environments. This study examines susceptibility to and subsequent usage in school-going adolescents in a rural distressed county in Appalachian Tennessee using data from an online survey (N = 399). Relying on bivariate analyses and logistic regression, this study finds that while 30.6% of adolescents are ever e-cigarette users, 15.5% are current users. Approximately one in three adolescents are susceptible to e-cigarettes use, and susceptibility is associated with lower odds of being a current e-cigarette user (OR = 0.03; CI: 0.01-0.12; p < 0.00). The age of tobacco use initiation was significantly associated with decreased current use of e-cigarettes (OR = 0.89; CI: 0.83-0.0.97; p < 0.01). Overall, the results of this exploratory study suggest the need for larger studies to identify unique and generalizable factors that predispose adolescents in this high-risk rural, socioeconomically disadvantaged region to ENDS use. Nevertheless, this study offers insight into e-cigarette usage among U.S adolescents in rural, socioeconomically disadvantaged environments and provides a foundation for a closer examination of this vulnerable population.

Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women.

BACKGROUND: The effect of raloxifene, a selective estrogen-receptor modulator, on coronary heart disease (CHD) and breast cancer is not established. METHODS: We randomly assigned 10,101 postmenopausal women (mean age, 67.5 years) with CHD or multiple risk factors for CHD to 60 mg of raloxifene daily or placebo and followed them for a median of 5.6 years. The two primary outcomes were coronary events (i.e., death from coronary causes, myocardial infarction, or hospitalization for an acute coronary syndrome) and invasive breast cancer. RESULTS: As compared with placebo, raloxifene had no significant effect on the risk of primary coronary events (533 vs. 553 events; hazard ratio, 0.95; 95 percent confidence interval, 0.84 to 1.07), and it reduced the risk of invasive breast cancer (40 vs. 70 events; hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.83; absolute risk reduction, 1.2 invasive breast cancers per 1000 women treated for one year); the benefit was primarily due to a reduced risk of estrogen-receptor-positive invasive breast cancers. There was no significant difference in the rates of death from any cause or total stroke according to group assignment, but raloxifene was associated with an increased risk of fatal stroke (59 vs. 39 events; hazard ratio, 1.49; 95 percent confidence interval, 1.00 to 2.24; absolute risk increase, 0.7 per 1000 woman-years) and venous thromboembolism (103 vs. 71 events; hazard ratio, 1.44; 95 percent confidence interval, 1.06 to 1.95; absolute risk increase, 1.2 per 1000 woman-years). Raloxifene reduced the risk of clinical vertebral fractures (64 vs. 97 events; hazard ratio, 0.65; 95 percent confidence interval, 0.47 to 0.89; absolute risk reduction, 1.3 per 1000). CONCLUSIONS: Raloxifene did not significantly affect the risk of CHD. The benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke. (ClinicalTrials.gov number, NCT00190593 [ClinicalTrials.gov].).

Effect of raloxifene on cardiovascular adverse events in postmenopausal women with osteoporosis.

The impact of selective estrogen receptor modulators on cardiovascular disease outcomes in postmenopausal women remains unclear. This analysis assessed the effect of raloxifene on the incidence of cardiovascular adverse events in postmenopausal women followed for < or =8 years as participants in a 4-year osteoporosis treatment trial and a subsequent 4-year follow-up trial. The Continuing Outcomes Relevant to Evista (CORE) trial, designed to determine the effect of raloxifene on the incidence of invasive breast cancer, was a 4-year follow-up study to the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) osteoporosis treatment trial. Of the 7,705 participants originally enrolled in MORE, 4,011 were enrolled in CORE and thus participated in both trials (MORE-CORE participants). The incidence of serious cardiovascular (i.e., coronary and cerebrovascular) adverse events during 8 years, confirmed by external adjudication in the 2 trials, was compared between treatment groups using Cox proportional hazards models. The 8-year incidence of serious cardiovascular adverse events did not differ significantly between the raloxifene (5.5%) and placebo (4.7%) groups (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.86 to 1.56). Similar results were obtained when coronary (HR 1.22, 95% CI 0.82 to 1.83) or cerebrovascular (HR 1.19, 95% CI 0.78 to 1.84) events were analyzed separately, and when cardiovascular events were analyzed in the 459 MORE-CORE participants who were at increased risk of cardiovascular events by previously established criteria (HR 1.03, 95% CI 0.58 to 1.82). In conclusion, we found no evidence of a beneficial or harmful effect of raloxifene on the incidence of cardiovascular events overall, or coronary or cerebrovascular events, in postmenopausal osteoporotic women at relatively low risk of cardiovascular events.

Relationship between osteoporosis and cardiovascular disease in postmenopausal women.

UNLABELLED: In the placebo group of the MORE study, including 2576 postmenopausal women (mean age, 66.5 years), the authors describe a strong linear association between the severity grade of osteoporosis (from low BMD to presence of severe vertebral fractures) and the future risk of cardiovascular events. Accordingly, treatment of postmenopausal osteoporosis should include consideration of measures to prevent adverse cardiovascular outcomes. INTRODUCTION: Observations indicate an inverse association between BMD and the severity of peripheral atherosclerosis in postmenopausal women. The predictive value of osteoporosis and its different severity stages for the risk of acute cardiovascular events remains unknown. MATERIALS AND METHODS: Participants were 2576 women (mean age, 66.5 years) assigned to placebo and followed for 4 years in an osteoporosis treatment trial. Those with at least one vertebral fracture or total hip BMD T score < or = -2.5 at baseline were defined as having osteoporosis, whereas those without vertebral fracture and total hip BMD T score between -2.5 and -1 were defined as having low bone mass. The primary outcome for these posthoc analyses was the incidence of adjudicated fatal or nonfatal cardiovascular events. RESULTS: After adjustment for potential confounders, women with osteoporosis had a 3.9-fold (95% CI, 2.0-7.7; p < 0.001) increased risk for cardiovascular events compared with women with low bone mass. Under the same boundaries, a total hip BMD T score < or = -2.5 versus a T score between -2.5 and -1 was associated with a 2.1-fold (95% CI, 1.2-3.6; p < 0.01) increase in risk, whereas presence of at least one vertebral fracture versus no vertebral fracture at baseline was associated with a 3.0-fold (95% CI, 1.8-5.1; p < 0.001) increase in risk. The risk of cardiovascular events increased incrementally with the number and increasing severity of baseline vertebral fractures (both p < 0.001). CONCLUSIONS: Postmenopausal women with osteoporosis are at an increased risk for cardiovascular events that is proportional to the severity of osteoporosis at the time of the diagnosis. Treatment of postmenopausal osteoporosis should include consideration of measures to prevent cardiovascular outcomes.

The role of selective estrogen receptor modulators in the prevention of breast cancer: comparison of the clinical trials.

The role of estrogen in the development of breast cancer is well recognized, and the use of selective estrogen receptor modulators (SERMs) to reduce breast cancer risk continues to be evaluated. Tamoxifen is the only SERM approved for the reduction of breast cancer incidence in women at high risk. This approval was based on results from the Breast Cancer Prevention Trial. Although initial results from the Royal Marsden Hospital tamoxifen trial and Italian Tamoxifen Prevention Study did not show a similar overall effect of tamoxifen, recent updates from these two trials and initial results from the International Breast Cancer Intervention Study are consistent with a risk reduction effect of tamoxifen for estrogen-receptor-positive breast cancer. Raloxifene, approved for the prevention and treatment of postmenopausal osteoporosis, is another SERM being evaluated for breast cancer risk reduction. The recently completed Continuing Outcomes Relevant to Evista trial and the Raloxifene Use for The Heart trial, have breast cancer risk reduction as a primary end point. A third, ongoing trial, the Study of Tamoxifen and Raloxifene trial, is evaluating the relative efficacy and adverse event profile of these two agents in a population at high risk. The study populations of these raloxifene breast cancer prevention trials and the four tamoxifen prevention trials are quite diverse in terms of breast cancer risk. Completion of these trials will provide important information about the occurrence of invasive breast cancer in postmenopausal women and the efficacy of raloxifene for breast cancer risk reduction.

Comparison of the effect of raloxifene and continuous-combined hormone therapy on mammographic breast density and breast tenderness in postmenopausal women.

OBJECTIVE: The objectives were to evaluate mammographic changes in breast density that are associated with raloxifene or hormone therapy and to compare the safety profiles of the two therapies. STUDY DESIGN: Postmenopausal women older than 60 years who had a bone mineral density T-score of < or =-1 were assigned randomly to receive raloxifene hydrochloride 60 mg/day or continuous-combined hormone therapy that consisted of conjugated equine estrogen 0.625 mg/day plus medroxyprogesterone acetate 2.5 mg/day in a 1-year, open-label study. Radiologists who were blinded to the treatment assignment assessed the mammograms according to the American College of Radiology Breast Image Reporting and Data System breast density categories. Breast density changes were analyzed for treatment differences. RESULTS: After 12 months of treatment, 0.9% of the women who received raloxifene had increased mammographic breast density compared with 27.4% of the women who received continuous-combined hormone therapy (P <.001). In the continuous-combined hormone therapy group, 77% of the women reported breast tenderness at any time during the study, compared to 22% of the women in the raloxifene group. CONCLUSION: In postmenopausal women with low bone mass, raloxifene therapy for 12 months does not increase mammographic breast density, whereas continuous-combined hormone therapy substantially increases breast density in a significant number of women.

Incidência de eventos adversos e seu impacto sobre a descontinuidade do tratamento entre mulheres tratadas com raloxifeno ou terapia da reposição hormonal / Impact of adverse events on discontinuation among postmenopausal women treated with raloxifene or estrogen-progestin

Avaliar os perfis de eventos adversos do tratamento com raloxifeno e com reposição hormonal e seu impacto sobre a descontinuidade entre mulheres na pós-menopausa com 60 anos ou mais. Mulheres na pós-menopausa com osteopenia ou osteoporose vivendo na América Latina foram randomizadas para tratamento com raloxifeno 60 mg/dia (RLX, n=140) ou terapia hormonal combinada contínua (TRH, n=140) neste estudo aberto, de um ano. A freqüência e o tempo até a descontinuidade de todos os eventos adversos (EA)espontâneos e dos nove eventos adversos solicitados (sangramento uterino, ondas de calor, sensibilidade mamária, suores noturnos, sensação de inchaço, desconforto pélvico, transtornos do humor, cãibra nas pernas, e secura vaginal) foram determinados para ambos os grupos. Um Questionário de Qualidade de Vida Específico para Menopausa (Menopause-Specific Quality of Life Questionnaire(MENQOL) também foi completado. Sensibilidade mamária e sangramento vaginal foram os EAs mais freqüentes entre as usuárias de TRH, enquanto ondas de calor foram mais freqüentes entre as pacientes tratadas com RLX (p<0,001). Não houve diferenças entre os grupos em relação a outros EAs. As pacientes recebendo RLX apresentaram menor probabilidade de descontinuar o tratamento devido a um EA espontâneo ou solicitado (4 por cento vs. 18 por cento, p<0,001). Das pacientes recebendo RLX, 0,7 por cento descontinuaram o tratamento devido a um EA solicitado (cãibra nas pernas) e 3,6 por cento devido a um EA espontâneo. As pacientes recebendo TRH descontinuaram devido a sangramento vaginal (5,7 por cento), sensibilidade mamária (2,1 por cento), transtornos do humor (0,7 por cento) ou a um EA espontâneo (9,3 por cento). A probabilidade de descontinuidade por qualquer razão foi menor entre as pacientes recebendo RLX (RR=0,60; 95 por cento CI, 0,40-0,89). A maioria dos sub-escores do MENQOL melhoraram no final do tratamento em ambos os grupos. Mulheres na pós-menopausa com 60 anos ou mais, com baixa massa óssea e recebendo RLX apresentaram menor probabilidade de descontinuar o tratamento devido a um EA que as recebendo TRH. Conseqüentemente, o tratamento com RLX pode melhorar a aderência ao tratamento a longo-prazo.