Anticancer Activity and Tolerance of Treatments Received Beyond Progression in Men Treated Upfront with Androgen Deprivation Therapy With or Without Docetaxel for Metastatic Castration-naïve Prostate Cancer in the GETUG-AFU 15 Phase 3 Trial

Background

Androgen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are available on the efficacy of treatments used for metastatic castration-resistant prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC.

Concurrent partnerships in Cape Town,South Africa: race and sex differences in prevalence and duration of overlap

Introduction

Concurrent partnerships (CPs) have been suggested as a risk factor for transmitting HIV, but their impact on the epidemic depends upon how prevalent they are in populations, the average number of CPs an individual has and the length of time they overlap. However, estimates of prevalence of CPs in Southern Africa vary widely, and the duration of overlap in these relationships is poorly documented. We aim to characterize concurrency in a more accurate and complete manner, using data from three disadvantaged communities of Cape Town, South Africa.

Methods

We conducted a sexual behaviour survey (n=878) from June 2011 to February 2012 in Cape Town, using Audio Computer-Assisted Self-Interviewing to collect sexual relationship histories on partners in the past year. Using the beginning and end dates for the partnerships, we calculated the point prevalence, the cumulative prevalence and the incidence rate of CPs, as well as the duration of overlap for relationships begun in the previous year. Linear and binomial regression models were used to quantify race (black vs. coloured) and sex differences in the duration of overlap and relative risk of having CPs in the past year.

Results

The overall point prevalence of CPs six months before the survey was 8.4%: 13.4% for black men, 1.9% for coloured men, 7.8% black women and 5.6% for coloured women. The median duration of overlap in CPs was 7.5 weeks. Women had less risk of CPs in the previous year than men (RR 0.43; 95% CI: 0.32–0.57) and black participants were more at risk than coloured participants (RR 1.86; 95% CI: 1.17–2.97).

Conclusions

Our results indicate that in this population the prevalence of CPs is relatively high and is characterized by overlaps of long duration, implying there may be opportunities for HIV to be transmitted to concurrent partners.     

Coital frequency and condom use in monogamous and concurrent sexual relationships in Cape Town,South Africa

Introduction

A decreased frequency of unprotected sex during episodes of concurrent relationships may dramatically reduce the role of concurrency in accelerating the spread of HIV. Such a decrease could be the result of coital dilution – the reduction in per-partner coital frequency from additional partners – and/or increased condom use during concurrency. To study the effect of concurrency on the frequency of unprotected sex, we examined sexual behaviour data from three communities with high HIV prevalence around Cape Town, South Africa.

Methods

We conducted a cross-sectional survey from June 2011 to February 2012 using audio computer-assisted self-interviewing to reconstruct one-year sexual histories, with a focus on coital frequency and condom use. Participants were randomly sampled from a previous TB and HIV prevalence survey. Mixed effects logistic and Poisson regression models were fitted to data from 527 sexually active adults reporting on 1210 relationship episodes to evaluate the effect of concurrency status on consistent condom use and coital frequency.

Results

The median of the per-partner weekly average coital frequency was 2 (IQR: 1–3), and consistent condom use was reported for 36% of the relationship episodes. Neither per-partner coital frequency nor consistent condom use changed significantly during episodes of concurrency (aIRR=1.05; 95% confidence interval (CI): 0.99–1.24 and aOR=1.01; 95% CI: 0.38–2.68, respectively). Being male, coloured, having a tertiary education, and having a relationship between 2 weeks and 9 months were associated with higher coital frequencies. Being coloured, and having a relationship lasting for more than 9 months, was associated with inconsistent condom use.

Conclusions

We found no evidence for coital dilution or for increased condom use during concurrent relationship episodes in three communities around Cape Town with high HIV prevalence. Given the low levels of self-reported consistent condom use, our findings suggest that if the frequency of unprotected sex with each of the sexual partners is sustained during concurrent relationships, HIV-positive individuals with concurrent partners may disproportionately contribute to onward HIV transmission.     

Chronic dietary sodium overload and release of a circulating Na+-K+ pump inhibitor

High Na+ intake has been proposed to induce a rise in the activity of a circulating inhibitor of the Na+, K+-pump. The effects on male Wistar rats of a high sodium diet (8 per cent NaCl) on the activity of such a plasma Na+, K+-ATPase inhibitor were investigated. Systolic blood pressure, body weight, urinary Na+ excretion, haematocrit, intraerythrocytic Na+ content and the activity of a Na+ dependent transport system, i.e. the uptake of 5-HT by blood platelets were measured in parallel. After one week, neither systolic blood pressure nor intraerythrocytic Na+ content were modified, but the ability of the plasma extracts to inhibit renal Na+, K+-ATPase increased (70.9 +/- 1.7 vs 76.3 +/- 2.1 mumol Pi/mg/h; p = 0.05). After two weeks, the plasma inhibitory activity, the systolic blood pressure and the intraerythrocytic Na+ content were higher than that of control animals (65.5 +/- 1.6 vs 79.1 +/- 2.8 mumol Pi/mg/h, p less than 0.001; 132 +/- 2 vs 114 +/- 4 mmHg, p. +/- 0.001 and 4.95 +/- 0.32 vs 3.81 +/- 0.36 mmol/l.cells, p less than 0.05). After three months, the ability of plasma extracts to inhibit the Na+ pump and the systolic blood pressure were still elevated (57.8 +/- 1.8 vs 72.9 +/- 1.8 mumol Pi/mg/h, p less than 0.001; 145 +/- 4 vs 118 +/- 2 mmHg, p less than 0.001) whereas intraerythrocytic Na+ content had returned to control levels and 5-HT uptake was not modified.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preliminary communication on intralymphocyte ionized magnesium in hypertensive patients under treatment with beta-blockers.

We measured free intralymphocyte magnesium (Mgi) in 10 hypertensive subjects (HS) before and after treatment with atenolol (A) and in 16 normotensive control subjects (NC). We also carried out in vitro studies on human lymphocytes to test the effect of catecholamines and beta-antagonists on Mgi. Mgi in HS was not statistically different before and after the treatment with A (M +/- SD, basal: 227 +/- 31 + mumol/l; A: 236 +/- 47 mumol/l; NS). Mgi in NC proved not statistically different as compared to HS without treatment (M +/- SD, NC: 232 +/- 35 mumol/l; HS before treatment: 227 +/- 31 mumol/l; NS). The Mgi of the lymphocytes treated in vitro with noradrenaline (NA) significantly decreased in comparison with the control (M +/- SD, basal: 244 +/- 26 mumol/l; NA: 198 +/- 25 mumol/l; p = 0.0001), whereas it did not change after incubation with NA and propranolol (P) (M +/- SD, basal: 238 +/- 32 mumol/l; NA + P: 239 +/- 30 mumol/l; NS). On the other hand Mgi decreased significantly after incubation with NA and A (M +/- SD, basal: 255 +/- 21 mumol/l; NA + A: 202 +/- 34 mumol/l). Our in vivo data show that the Mgi of HS remains unvaried after treatment with A, and that there is not statistical difference between Mgi of NC and of HS before treatment. The in vitro study demonstrated that catecholamines cause a significant reduction in Mgi. This effect is only inhibited by a non-selective beta-blocker such as P. These results seem to explain the ineffectiveness of treatment with atenolol on our patients' Mgi.     

A retrospective analysis of long-term survival in severe aplastic anemia patients treated with allogeneic bone marrow transplantation or immunosuppressive therapy with antithymocyte globulin and cyclosporin A at a single institution

Severe aplastic anemia can be treated with either bone marrow transplantation (BMT) or immunosuppressive therapy (IST). A retrospective review of patients with severe aplastic anemia treated with both of these modalities was conducted. Fifteen BMT and 16 IST patients were available for analysis, and follow-up of 22 and 15 years was available for the BMT and IST groups, respectively. Median survival was limited to 4.3 months in BMT patients vs. 135.2 months in IST patients, despite the older median age of the latter (22 vs. 55 years). Actuarial survival at 1 and 5 years was 87% and 78% for the IST patients and 40% and 33% for the BMT patients. Hematologic response rates, as defined by achievement of transfusion independence, were similar for the two groups. Long-term responses and survival are possible with antithymocyte globulin/cyclosporin A.     

Prevalence of occupational exposure to asbestos and crystalline silica according to phenotypes of lung cancer from the CaProMat study: A case‐only study

Background

The objective of the study was to compare the prevalence of occupational exposure to asbestos and crystalline silica according to histological types of lung cancer and age at diagnosis.

Methods

CaProMat study is a pooled case‐only study conducted between 1996 and 2011. The current study consisted of 6521 lung cancer cases. Occupational exposure to asbestos and crystalline silica was assessed by two Job‐Exposure Matrices. A weighted prevalence of exposure was derived and compared according to histological types and age at diagnosis.

Results

There was no difference of weighted prevalence of exposure to asbestos and crystalline silica according to histological types of lung cancer. There was a statistically significant difference of weighted prevalence of exposure to asbestos and crystalline silica according to age at diagnosis.

Conclusions

Due to the limited clinical importance of the difference, neither the histological type, nor the age at diagnosis can be used as an indicator for the occupational exposure to asbestos or crystalline silica.

     

Examining Racial/Ethnic Minority Treatment Experiences with Specialty Behavioral Health Service Providers

This study investigated whether satisfaction and helpfulness of treatment by mental health service provider is related to race/ethnicity and psychosocial factors. Data from the National Co morbidity Survey-Replication study, which administered mental health service use questions for the past 12-months (1332), was analyzed. Data were stratified by service provider and analyzed with multiple logistic regressions. Racial/ethnic minorities were generally more likely to be satisfied with services provided by specialty mental health providers compared to white respondents. Racial/ethnic minorities generally perceived the services provided by specialty mental health providers as more helpful than did other racial/ethnic groups. Those who reported high cultural identity were more likely to find their treatment experience less satisfying and less helpful. Greater attention to specialty referrals for racial/ethnic minority groups may fruitfully contribute to improve help-seeking for these groups. The role culture plays in shaping the mental health treatment experience needs to be further investigated.     

A longitudinal investigation of intimate partner violence among mothers with mental illness

OBJECTIVE: Severe mental illness, substance use, and intimate partner violence have emerged as major intersecting public health problems that adversely and disproportionately impact the lives of women in the United States. This longitudinal study investigated the demographic and clinical correlates of intimate partner violence in a sample of 324 mothers with severe mental illness. METHODS: A secondary analysis of longitudinal data was conducted by using multiple logistic regression. Participants were part of a longitudinal, community-based study of mothers with severe mental illness, which was aimed at understanding how these mothers viewed motherhood. The women were interviewed initially at baseline (interviews were conducted between 1995 and 1996) and then about 20 months later at follow-up (interviews were conducted between 1997 and 1998). RESULTS: At follow-up the prevalence rate of intimate partner violence was 19%. Multiple logistic regression analyses showed a significant positive relationship between alcohol and drug misuse at baseline and intimate partner violence at follow-up, indicating that women with a co-occurring diagnosis of a substance use disorder (dual diagnosis) were more likely than women without such a diagnosis to report intimate partner violence. The number of lifetime psychiatric hospitalizations and the number of symptoms related to psychiatric disability exhibited at baseline were positively associated with intimate partner violence at follow-up, and age was inversely associated with intimate partner violence. CONCLUSIONS: Mental health professionals serving mothers with mental health problems need to be aware of and prepared to assess the significant correlation between these intersecting public health problems in order to influence successful interventions. Particular attention must be given to the special treatment needs related to dual diagnosis and victimization and the impact of these factors on this vulnerable population.     

Apoptosis induction by retinoids in eosinophilic leukemia cells: implication of retinoic acid receptor-alpha signaling in all-trans-retinoic acid hypersensitivity

Hypereosinophilic syndrome (HES) has recently been recognized as a clonal leukemic lesion, which is due to a specific oncogenic event that generates hyperactive platelet-derived growth factor receptor-alpha-derived tyrosine kinase fusion proteins. In the present work, the effect of retinoids on the leukemic hypereosinophilia-derived EoL-1 cell line and on primary HES-derived cells has been investigated. We show that all-trans-retinoic acid (ATRA) inhibits eosinophil colony formation of HES-derived bone marrow cells and is a powerful inducer of apoptosis of the EoL-1 cell line. Apoptosis was shown in the nanomolar concentration range by phosphatidylserine externalization, proapoptotic shift of the Bcl-2/Bak ratio, drop in mitochondrial membrane potential, activation of caspases, and cellular morphology. Unlike in other ATRA-sensitive myeloid leukemia models, apoptosis was rapid and was not preceded by terminal cell differentiation. Use of isoform-selective synthetic retinoids indicated that retinoic acid receptor-alpha-dependent signaling is sufficient to induce apoptosis of EoL-1 cells. Our work shows that the scope of ATRA-induced apoptosis of malignancies may be wider within the myeloid lineage than thought previously, that the EoL-1 cell line constitutes a new and unique model for the study of ATRA-induced cell death, and that ATRA may have potential for the management of clonal HES.