Variation in breast cancer risk in BRCA1 and BRCA2 mutation carriers

Genetic testing for BRCA1 and BRCA2 (BRCA1/2) mutations can provide important information for women who are concerned about their breast and ovarian cancer risks and need to make relevant prevention and medical management decisions. However, lifetime risks of breast cancer in individual BRCA1/2 mutation carriers have been confusing to apply in clinical decision-making. Published risk estimates vary significantly and are very dependent on the characteristics of the population under study. Recently, Begg and colleagues estimated cancer risks in a population-based study of BRCA1/2 mutation carriers. Here, we discuss the clinical decision-making implications of this research in the context of risk factors that may influence risk estimates in BRCA1/2 mutation carriers

The in vitro toxicology of Swedish snus

Three commercial brands of Swedish snus (SWS), an experimental SWS, and the 2S3 reference moist snuff were each tested in four in vitro toxicology assays. These assays were: Salmonella reverse mutation, mouse lymphoma, in vitro micronucleus, and cytotoxicity. Water extractions of each of the 5 products were tested using several different concentrations; the experimental SWS was also extracted using dimethyl sulfoxide (DMSO). Extraction procedures were verified by nicotine determinations. Results for SWS in the mutagenicity assays were broadly negative: there were occasional positive responses, but these were effectively at the highest concentration only (concentrations well above those suggested by regulatory guidelines), and were often associated with cytotoxicity. The 2S3 reference was unequivocally positive in one of the three conditions of the micronucleus assay (MNA), at the highest concentration only. Positive controls produced the expected responses in each assay. The SWS data are contrasted with data reported for combusted tobacco in the form of cigarettes, where strongly positive responses have been routinely reported for mutagenicity and cytotoxicity. These negative findings in a laboratory setting concur with the large amount of epidemiological data from Sweden, data showing that SWS are associated with considerably lower carcinogenic potential when compared with cigarettes

Relapse prevention for addictive behaviors

The Relapse Prevention (RP) model has been a mainstay of addictions theory and treatment since its introduction three decades ago. This paper provides an overview and update of RP for addictive behaviors with a focus on developments over the last decade (2000-2010). Major treatment outcome studies and meta-analyses are summarized, as are selected empirical findings relevant to the tenets of the RP model. Notable advances in RP in the last decade include the introduction of a reformulated cognitive-behavioral model of relapse, the application of advanced statistical methods to model relapse in large randomized trials, and the development of mindfulness-based relapse prevention. We also review the emergent literature on genetic correlates of relapse following pharmacological and behavioral treatments. The continued influence of RP is evidenced by its integration in most cognitive-behavioral substance use interventions. However, the tendency to subsume RP within other treatment modalities has posed a barrier to systematic evaluation of the RP model. Overall, RP remains an influential cognitive-behavioral framework that can inform both theoretical and clinical approaches to understanding and facilitating behavior change

State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy

Who is using snus? - Time trends, socioeconomic and geographic characteristics of snus users in the ageing Swedish population

BACKGROUND: The prevalence of smoking in Sweden has decreased in recent decades, and is now among the lowest in the world. During the same period, the use of Swedish moist oral snuff, a smokeless tobacco called snus, has increased. Few studies have evaluated time trends of the socioeconomic and geographic characteristics of snus users in Sweden. This paper contributes to filling that gap. METHODS: This study utilized the Linnaeus Database, which links national registers with comprehensive individual data on socioeconomic status (SES) to health data from a large ongoing health survey, the Västerbotten Intervention Programme (VIP). The VIP targets the entire middle-aged population of Västerbotten county at ages 40, 50 and 60 years with yearly cross-sectional surveys including self-reported data on tobacco habits. Time trends of snus use among 92,563 VIP-participants across different areas of residence and smoking groups were investigated graphically. Logistic regression was performed to estimate the associations between SES and geographical variables and current use versus non-use of snus. RESULTS: Overall, in parallel to decreasing smoking, the increasing trend of snus use in this middle-aged population continues, particularly in 40-year-olds. In both genders, the highest prevalence of snus use was observed among previous smokers. The prevalence of snus use also increased over time among smokers, and was consistently higher compared to those who had never smoked. Among males - both those who had never smoked and previous smokers - low education (OR 1.21, 95%CI 1.06-1.40 and OR 1.28, 95%CI 1.14-1.43), living alone (OR 1.16, 95%CI 1.07-1.27 and OR 1.13, 95%ci 1.04-1.23), low income and living in rural areas was associated with using snus, while this was not seen among male current smokers. Among women, living alone was associated with using snus irrespective of smoking habits. Among female smokers, the OR for snus use increased with higher education. CONCLUSIONS: A disadvantaged social profile and also higher prevalence in rural areas is observed among male snus users who had never smoked or were previous smokers. Among male smokers there was no association between SES and use of snus. The prevalence of snus use among women is increasing, but is still considerably lower than that of men. The association between snus and SES characteristics is less pronounced among women, although snus is clearly linked to living alone. These patterns should be taken into consideration in tobacco control policies