Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

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A Gonococcal Vaccine Has the Potential to Rapidly Reduce the Incidence of Neisseria gonorrhoeae Infection among Urban Men Who Have Sex with Men

Background: A gonococcal vaccine is urgently needed due to increasing gonorrhea incidence and emerging multidrug-resistant gonococcal strains worldwide. Men who have sex with men (MSM) have among the highest incidences of gonorrhea and may be a key target population for vaccination when available. Methods: An individual-based, anatomical site-specific mathematical model was used to simulate Neisseria gonorrhoeae transmission in a population of 10000 MSM. The impact of vaccination on gonorrhea prevalence was assessed. Results: With a gonococcal vaccine of 100% or 50% protective efficacy, gonorrhea prevalence could be reduced by 94% or 62%, respectively, within 2 years if 30% of MSM are vaccinated on presentation for sexually transmitted infection (STI) testing. Elimination of gonorrhea is possible within 8 years with vaccines of≥50% efficacy lasting 2 years, providing a booster vaccination is available every 3 years on average. A vaccine's impact may be reduced if it is not effective at all anatomical sites. Conclusions: Our study indicates that with a vaccine of modest efficacy and an immunization strategy that targets MSM presenting for STI screening, the prevalence of gonorrhea in this population could be rapidly and substantially reduced

Breast density predicts endocrine treatment outcome in the adjuvant setting

PMCID: PMC3680935See related research article by Kim et al., http://breast-cancer-research.com/content/14/4/R10

Integration of Clinical Variables for the Prediction of Late Distant Recurrence in Patients With Estrogen Receptor-Positive Breast Cancer Treated With 5 Years of Endocrine Therapy: CTS5.

Purpose Estimating risk of late distant recurrence (DR) is an important goal for managing women with hormone receptor-positive breast cancer after 5 years of endocrine treatment without recurrence. We developed and validated a simple clinicopathologic tool (Clinical Treatment Score post-5 years [CTS5]) to estimate residual risk of DR after 5 years of endocrine treatment. Patients and Methods The ATAC (Arimidex, Tamoxifen, Alone or in Combination) data set (N = 4,735) was used to create a prognostic score for post-5-year risk of DR. Validity of CTS5 (ATAC) was tested in the BIG 1-98 data set (N = 6,711). Time to late DR, 5 years after finishing scheduled endocrine therapy, was the primary end point. Cox regression models estimated the prognostic performance of CTS5 (ATAC). Results CTS5 (ATAC) was significantly prognostic for late DR in the ATAC cohort (hazard ratio, 2.47; 95% CI, 2.24 to 2.73; P 10%) identified 43% of the validation cohort as low risk, with an observed DR rate of 3.6% (95% CI, 2.7% to 4.9%) during years 5 to 10. From years 5 to 10, 63% of node-negative patients were low risk, with a DR rate of 3.9% (95% CI, 2.9% to 5.3%), and 24% with one to three positive nodes were low risk, with a DR rate of 1.5% (95% CI, 0.5% to 3.8%). A final CTS5 for future use was derived from pooled data from ATAC and BIG 1-98. Conclusion CTS5 is a simple tool based on information that is readily available to all clinicians. CTS5 was validated as highly prognostic for late DR in the independent BIG 1-98 study. The final CTS5 algorithm identified 42% of women with < 1% per-year risk of DR who could be advised of the limited potential value of extended endocrine therapy

Modelling response strategies for controlling gonorrhoea outbreaks in men who have sex with men in Australia

The ability to treat gonorrhoea with current first-line drugs is threatened by the global spread of extensively drug resistant (XDR) Neisseria gonorrhoeae (NG) strains. In Australia, urban transmission is high among men who have sex with men (MSM) and importation of an XDR NG strain in this population could result in an epidemic that would be difficult and costly to control. An individual-based, anatomical site-specific mathematical model of NG transmission among Australian MSM was developed and used to evaluate the potential for elimination of an imported NG strain under a range of case-based and population-based test-andtreat strategies. When initiated upon detection of the imported strain, these strategies enhance the probability of elimination and reduce the outbreak size compared with current practice (current testing levels and no contact tracing). The most effective strategies combine testing targeted at regular and casual partners with increased rates of population testing. However, even with the most effective strategies, outbreaks can persist for up to 2 years post-detection. Our simulations suggest that local elimination of imported NG strains can be achieved with high probability using combined case-based and population-based test-and-treat strategies. These strategies may be an effective means of preserving current treatments in the event of wider XDR NG emergence

Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers

Introduction: We examined if a combination of proliferation markers and estrogen receptor (ER) activity could predict early versus late relapses in ER-positive breast cancer and inform the choice and length of adjuvant endocrine therapy. Methods: Baseline affymetrix gene-expression profiles from ER-positive patients who received no systemic therapy (n = 559), adjuvant tamoxifen for 5 years (cohort-1: n = 683, cohort-2: n = 282) and from 58 patients treated with neoadjuvant letrozole for 3 months (gene-expression available at baseline, 14 and 90 days) were analyzed. A proliferation score based on the expression of mitotic kinases (MKS) and an ER-related score (ERS) adopted from Oncotype DX® were calculated. The same analysis was performed using the Genomic Grade Index as proliferation marker and the luminal gene score from the PAM50 classifier as measure of estrogen-related genes. Median values were used to define low and high marker groups and four combinations were created. Relapses were grouped into time cohorts of 0-2.5, 0-5, 5-10 years. Results: In the overall 10 years period, the proportional hazards assumption was violated for several biomarker groups indicating time-dependent effects. In tamoxifen-treated patients Low-MKS/Low-ERS cancers had continuously increasing risk of relapse that was higher after 5 years than Low-MKS/High-ERS cancers [0 to 10 year, HR 3.36; p = 0.013]. High-MKS/High-ERS cancers had low risk of early relapse [0-2.5 years HR 0.13; p = 0.0006], but high risk of late relapse which was higher than in the High-MKS/Low-ERS group [after 5 years HR 3.86; p = 0.007]. The High-MKS/Low-ERS subset had most of the early relapses [0 to 2.5 years, HR 6.53; p < 0.0001] especially in node negative tumors and showed minimal response to neoadjuvant letrozole. These findings were qualitatively confirmed in a smaller independent cohort of tamoxifen-treated patients. Using different biomarkers provided similar results. Conclusions: Early relapses are highest in highly proliferative/low-ERS cancers, in particular in node negative tumors. Relapses occurring after 5 years of adjuvant tamoxifen are highest among the highly-proliferative/high-ERS tumors although their risk of recurrence is modest in the first 5 years on tamoxifen. These tumors could be the best candidates for extended endocrine therapy

What explains ethnic organizational violence? Evidence from Eastern Europe and Russia

Why do some ethnopolitical organizations use violence? Research on substate violence often uses the state level of analysis, or only analyzes groups that are already violent. Using a resource mobilization framework drawn from a broad literature, we test hypotheses with new data on hundreds of violent and non-violent ethnopolitical organizations in Eastern Europe and Russia. Our study finds interorganizational competition, state repression and strong group leadership associated with organizational violence. Lack of popularity and holding territory are also associated with violence. We do not find social service provision positively related to violence, which contrasts with research on the Middle East

The use of complementary and alternative medicine by women experiencing menopausal symptoms in Bologna

<p>Abstract</p> <p>Background</p> <p>The present study describes Complementary and Alternative Medicine (CAM) use amongst Italian women transitioning through menopause. Popularity and perceived effectiveness of CAM treatments, use of pharmaceutical medications, characteristics of CAM users, the extent of communication between medical practitioners and women about their use of CAM, and variables associated with CAM use were also investigated.</p> <p>Methods</p> <p>Women, aged 45-65 years attending Family Planning and Women's Health clinics or Menopause Centres in Bologna were invited to complete a voluntary, anonymous, self administered questionnaire, which was used in a previous study in Sydney. The questionnaire was translated and adapted for use amongst Italian women. Data on general demographic and health characteristics, menopause related symptoms and the use of CAM and pharmaceutical treatments during the previous 12 months were collected.</p> <p>Results</p> <p>In total, 1,203 women completed the survey, of which 1,106 were included in the final sample. Of women who had symptoms linked with menopause and/or used remedies to alleviate symptoms, 33.5% reported to have used CAM. Among these, 23.5% had consulted one or more practitioners and 24% had used at least one CAM product.</p> <p>Approximately nine out of ten respondents reported medical practitioners did not seek information about their use of CAM; while one third of CAM users did not disclose the use of CAM to their physician. Nevertheless, medical practitioners were the most popular source of information. From the multivariate analysis, variables associated with CAM use were: professional employment, time since the last natural menses, use of CAM for conditions other than menopause, and presence of some severe symptoms.</p> <p>Conclusions</p> <p>The relatively high prevalence of CAM use by women transitioning through menopause should encourage research initiatives into determining which CAM treatments are the safest and effective. The increasing and likely concomitant use of CAM with HRT and other pharmaceuticals underlines the need for the implementation of a surveillance system to report and monitor possible drug-herb adverse events. The discrepancy between women preferring to seek information about CAM from their medical doctor and the difficulties noted in communication between doctor and patient should encourage educational initiatives on CAM by health-care agencies and institutions.</p

Event-Free Survival, a Prostate-Specific Antigen-Based Composite End Point, Is Not a Surrogate for Overall Survival in Men With Localized Prostate Cancer Treated With Radiation

PURPOSE: Recently, we have shown that metastasis-free survival is a strong surrogate for overall survival (OS) in men with intermediate- and high-risk localized prostate cancer and can accelerate the evaluation of new (neo)adjuvant therapies. Event-free survival (EFS), an earlier prostate-specific antigen (PSA)-based composite end point, may further expedite trial completion. METHODS: EFS was defined as the time from random assignment to the date of first evidence of disease recurrence, including biochemical failure, local or regional recurrence, distant metastasis, or death from any cause, or was censored at the date of last PSA assessment. Individual patient data from trials within the Intermediate Clinical Endpoints in Cancer of the Prostate-ICECaP-database with evaluable PSA and disease follow-up data were analyzed. We evaluated the surrogacy of EFS for OS using a 2-stage meta-analytic validation model by determining the correlation of EFS with OS (patient level) and the correlation of treatment effects (hazard ratios [HRs]) on both EFS and OS (trial level). A clinically relevant surrogacy was defined a priori as an R2 ≥ 0.7. RESULTS: Data for 10,350 patients were analyzed from 15 radiation therapy-based trials enrolled from 1987 to 2011 with a median follow-up of 10 years. At the patient level, the correlation of EFS with OS was 0.43 (95% CI, 0.42 to 0.44) as measured by Kendall's tau from a copula model. At the trial level, the R2 was 0.35 (95% CI, 0.01 to 0.60) from the weighted linear regression of log(HR)-OS on log(HR)-EFS. CONCLUSION: EFS is a weak surrogate for OS and is not suitable for use as an intermediate clinical end point to substitute for OS to accelerate phase III (neo)adjuvant trials of prostate cancer therapies for primary radiation therapy-based trials

MFV Reductions of MSSM Parameter Space

The 100+ free parameters of the minimal supersymmetric standard model (MSSM) make it computationally difficult to compare systematically with data, motivating the study of specific parameter reductions such as the cMSSM and pMSSM. Here we instead study the reductions of parameter space implied by using minimal flavour violation (MFV) to organise the R-parity conserving MSSM, with a view towards systematically building in constraints on flavour-violating physics. Within this framework the space of parameters is reduced by expanding soft supersymmetry-breaking terms in powers of the Cabibbo angle, leading to a 24-, 30- or 42-parameter framework (which we call MSSM-24, MSSM-30, and MSSM-42 respectively), depending on the order kept in the expansion. We provide a Bayesian global fit to data of the MSSM-30 parameter set to show that this is manageable with current tools. We compare the MFV reductions to the 19-parameter pMSSM choice and show that the pMSSM is not contained as a subset. The MSSM-30 analysis favours a relatively lighter TeV-scale pseudoscalar Higgs boson and $\tan \beta \sim 10$ with multi-TeV sparticles.Comment: 2nd version, minor comments and references added, accepted for publication in JHE