Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples

BACKGROUND Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART). OBJECTIVES To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples. SEARCH METHODS We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. SELECTION CRITERIA Randomised controlled trials (RCT), cohort studies and case-control studies of HIV-discordant couples in which the HIV-infected member of the couple was being treated or not treated with ART DATA COLLECTION AND ANALYSIS: Abstracts of all trials identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 3,833 references and examined 87 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. MAIN RESULTS One RCT and nine observational studies were included in the review. These ten studies identified 2,112 episodes of HIV transmission, 1,016 among treated couples and 1,096 among untreated couples. The rate ratio for the single randomised controlled trial was 0.04 [95% CI 0.00, 0.27]. All index partners in this study had CD4 cell counts at baseline of 350-550 cells/µL. Similarly, the summary rate ratio for the nine observational studies was 0.58 [95% CI 0.35, 0.96], with substantial heterogeneity (I(2)=64%). After excluding two studies with inadequate person-time data, we estimated a summary rate ratio of 0.36 [95% CI 0.17, 0.75] with substantial heterogeneity (I(2)=62%). We also performed subgroup analyses among the observational studies to see if the effect of ART on prevention of HIV differed by the index partner's CD4 cell count. Among couples in which the infected partner had ≥350 CD4 cells/µL, we estimated a rate ratio of 0.12 [95% CI 0.01, 1.99]. In this subgroup, there were 247 transmissions in untreated couples and 30 in treated couples. AUTHORS' CONCLUSIONS ART is a potent intervention for prevention of HIV in discordant couples in which the index partner has ≤550 CD4 cells/µL. A recent multicentre RCT confirms the suspected benefit seen in earlier observational studies and reported in more recent ones. Questions remain about durability of protection, the balance of benefits and adverse events associated with earlier therapy, long-term adherence and transmission of ART-resistant strains to partners. Resource limitations and implementation challenges must also be addressed.Counselling, support, and follow up, as well as mutual disclosure, may have a role in supporting adherence, so programmes should be designed with these components. In addition to ART provision, the operational aspects of delivering such programmes must be considered.

Accelerated partial breast irradiation with interstitial brachytherapy as second conservative treatment for ipsilateral breast tumour recurrence: multicentric study of the GEC-ESTRO Breast Cancer Working Group

PURPOSE To analyse the clinical outcome after salvage lumpectomy and multi-catheter brachytherapy (MCB) for ipsilateral breast tumour recurrence (IBTR). MATERIAL AND METHODS Between 09/00 and 09/10, 217 patients presenting an IBTR underwent lumpectomy and MCB (low, pulsed, or high-dose rate). Survival rates without second local recurrence (2nd LR), distant metastasis (DM), and overall survival (OS) were analysed as well as late effects and cosmetic results. Univariate and multivariate analyses (MVA) based on IBTR data were performed to find prognostic factors for 2nd LR, DM, and OS. RESULTS Median follow-up after the IBTR was 3.9 years [range: 1.1-10.3]. Five and 10-year actuarial 2nd LR rates were 5.6% [range: 1.5-9.5] and 7.2% [range: 2.1-12.1], respectively. Five and 10-year actuarial DM rates were 9.6% [range: 5.7-15.2] and 19.1% [range: 7.8-28.3], respectively. Five and 10-year actuarial OS rates were 88.7% [range: 83.1-94.8] and 76.4% [range: 66.9-87.3], respectively. In MVA, histological grade was prognostic factor for 2nd LR (p=0.008) and OS (p=0.02); while tumour size was prognostic factor for DM (p=0.03). G3-4 complication rate was 11%. Excellent/good cosmetic result was achieved in 85%. CONCLUSION This study suggests that in case of IBTR, lumpectomy plus MCB is feasible and effective in preventing 2nd LR with an OS rate at least equivalent to those achieved with salvage mastectomy.

Microbial communities in the respiratory tract of patients with interstitial lung disease

Background Molecular methods based on phylogenetic differences in the 16S rRNA gene are able to characterise the microbiota of the respiratory tract in health and disease. Objectives Our goals were (1) to characterise bacterial communities in lower and upper airways of patients with interstitial lung disease (ILD) and (2) to compare the results with the microbiota of patients with Pneumocystis pneumonia (PCP) and normal controls. Methods We examined the upper and lower respiratory tract of 18 patients with ILD of whom 5, 6, and 7 had idiopathic interstitial pneumonia (IIP), non-IIP and sarcoidosis, respectively. In addition, six immune-compromised patients with PCP and nine healthy subjects were included as controls. Exclusion criteria were recent bacterial/viral respiratory tract infection, HIV-positivity and subjects receiving antibiotic therapy. Bronchoalveolar lavage fluid and oropharyngeal swabs were simultaneously collected, and microbiota was characterised by ultra-deep 16S rRNA gene sequencing. Results The microbiota in lower airways of the majority of patients (30; 90%) primarily consisted of Prevotellaceae, Streptococcaceae and Acidaminococcaceae. α and β diversity measurements revealed no significant differences in airway microbiota composition between the five different groups of patients. Comparison of bacterial populations in upper and lower respiratory tract showed significant topographical discontinuities for 7 (23%) individuals. Conclusions IIP, non-IIP and sarcoidosis are not associated with disordered airway microbiota and a pathogenic role of commensals in the disease process is therefore unlikely. Nevertheless, molecular analysis of the topographical microbiota continuity along the respiratory tract may provide additional information to assist management of individual patients.

HGF Expressing Stem Cells in Usual Interstitial Pneumonia Originate from the Bone Marrow and Are Antifibrotic

BACKGROUND Pulmonary fibrosis may result from abnormal alveolar wound repair after injury. Hepatocyte growth factor (HGF) improves alveolar epithelial wound repair in the lung. Stem cells were shown to play a major role in lung injury, repair and fibrosis. We studied the presence, origin and antifibrotic properties of HGF-expressing stem cells in usual interstitial pneumonia. METHODS Immunohistochemistry was performed in lung tissue sections and primary alveolar epithelial cells obtained from patients with usual interstitial pneumonia (UIP, n = 7). Bone marrow derived stromal cells (BMSC) from adult male rats were transfected with HGF, instilled intratracheally into bleomycin injured rat lungs and analyzed 7 and 14 days later. RESULTS In UIP, HGF was expressed in specific cells mainly located in fibrotic areas close to the hyperplastic alveolar epithelium. HGF-positive cells showed strong co-staining for the mesenchymal stem cell markers CD44, CD29, CD105 and CD90, indicating stem cell origin. HGF-positive cells also co-stained for CXCR4 (HGF+/CXCR4+) indicating that they originate from the bone marrow. The stem cell characteristics were confirmed in HGF secreting cells isolated from UIP lung biopsies. In vivo experiments showed that HGF-expressing BMSC attenuated bleomycin induced pulmonary fibrosis in the rat, indicating a beneficial role of bone marrow derived, HGF secreting stem cells in lung fibrosis. CONCLUSIONS HGF-positive stem cells are present in human fibrotic lung tissue (UIP) and originate from the bone marrow. Since HGF-transfected BMSC reduce bleomycin induced lung fibrosis in the bleomycin lung injury and fibrosis model, we assume that HGF-expressing, bone-marrow derived stem cells in UIP have antifibrotic properties.

Effects of Combined Bevacizumab and Paclitaxel on Tumor Interstitial Fluid Pressure in a Preclinical Breast Cancer Model

Effects of Combined Bevacizumab and Paclitaxel on Tumor Interstitial Fluid Pressure in a Preclinical Breast Cancer Model by Ricardo H. Alvarez Several mechanisms of cell resistance are often accountable for unsuccessful chemotherapy against cancer. Another reason, which has received increased attention, is the inefficient transport of anticancer drugs into tumor tissue. These impaired transports of chemotherapy into the tumor have been attributed to abnormal microvasculature and to pathologically increased tumor hypertension also called: interstitial fluid pressure (IFP). The pathophysiological processes leading to elevated tumor IFP are poorly understood. Here, in a preclinical breast cancer model, it is argued that a condition of raised IFP is a major factor in preventing optimal access of systemically administered chemotherapy agents. In our experimental model, we used a GILM2 human breast cancer in xenografts; mice were treated with different doses of paclitaxel –a widely used antimicrotubular agent, and bevacizumab –monoclonal antibody against vascular endothelial growth factor (VEGF). The proposed research project is designed to test the hypothesis that paclitaxel in combination with bevacizumab decreases the tumor IPF by restoring tumor permeability and increasing chemotherapy delivery. We demonstrated that the combination of paclitaxel and bevacizumab produced greater tumor control than either agent given alone and this combination reduced the IFP, producing an increment of 75% of apoptosis compared with the control arm. In addition, the intra-tumor paclitaxel quantification by liquid chromatography/Mass Spectrometry (LC/MS) demonstrated that lower dose of both agents showed a synergistic effect compared with high dose of treatment, where there is no significantly increase of paclitaxel into the tumor. These preclinical results are likely to have broad implications for the utility of anti-angiogenic therapies alone and in combination with chemotherapeutic agents.

Tel Aviv - Mumbai - Tel Aviv: Same-Sex couples seeking parenthood in India

In Israel religious belonging remains a central category of citizenship. Laws concerning reproductive technologies such as the surrogacy law from 1996 are strongly informed by Orthodox rabbis’ kinship concepts (Kahn 2000, Shalev 1998, Weisberg 2005). A set of regulations secures that heterosexual Jewish couples bring into being children who are unequivocally Jewish themselves. The Israeli surrogacy law can therefore be understood as part of a policy seeking to reproduce the boundaries of the Jewish-Israeli collective. Same-sex couples do not fit this narrow definition of family and have no access to surrogacy in Israel. Yet gay couples maintain that parenthood is a universal civil right and bypass their exclusion through surrogacy arrangements abroad. The proposed paper follows these couples to Mumbai, which has become a popular destination for surrogacy in recent years. After their children’s birth the couples spend three to five weeks in India. In this time they not only take on their new tasks as fathers. They are also occupied with the bureaucracy of disconnecting the children from India and turning them into Israeli citizens. The paper elaborates on the bureaucratic processes and the hurdles same-sex couples encounter when seeking recognition of their parenthood and citizenship for their children. It unveils the intricacies and ramifications of Israel’s contradicting surrogacy policy of enforcing narrow definitions of family inside the country and simultaneously outsourcing problematic cases.

Development of self-esteem and relationship satisfaction in couples: Two longitudinal studies

We examined the effects of self-esteem development on the development of relationship satisfaction in 2 samples of couples. Study 1 used data from both partners of 885 couples assessed 5 times over 12 years, and Study 2 used data from both partners of 6,116 couples assessed 3 times over 15 years. The pattern of results was similar across the 2 studies. First, development of relationship satisfaction could be modeled as a couple-level process. Second, initial level of self-esteem of each partner predicted the initial level of the partners’ common relationship satisfaction, and change in self-esteem of each partner predicted change in the partners’ common relationship satisfaction. Third, these effects did not differ by gender and held when controlling for participants’ age, length of relationship, health, and employment status. Fourth, self-esteem similarity among partners did not influence the development of their relationship satisfaction. The findings suggest that the development of self-esteem in both partners of a couple contributes in a meaningful way to the development of the partners’ common satisfaction with their relationship.

How common is the lipid body-containing interstitial cell in the mammalian lung?

Pulmonary lipofibroblasts are thought to be involved in lung development, regeneration, vitamin A storage, and surfactant synthesis. Most of the evidence for these important functions relies on mouse or rat studies. Therefore, the present study was designed to investigate the presence of lipofibroblasts in a variety of early postnatal and adult mammalian species (including humans) to evaluate the ability to generalize functions of this cell type for other species. For this purpose, lung samples from 14 adult mammalian species as well as from postnatal mice, rats, and humans were investigated using light and electron microscopic stereology to obtain the volume fraction and the total volume of lipid bodies. In adult animals, lipid bodies were observed only, but not in all rodents. In all other species, no lipofibroblasts were observed. In rodents, lipid body volume scaled with body mass with an exponent b = 0.73 in the power law equation. Lipid bodies were not observed in postnatal human lungs but showed a characteristic postnatal increase in mice and rats and persisted at a lower level in the adult animals. Among 14 mammalian species, lipofibroblasts were only observed in rodents. The great increase in lipid body volume during early postnatal development of the mouse lung confirms the special role of lipofibroblasts during rodent lung development. It is evident that the cellular functions of pulmonary lipofibroblasts cannot be transferred easily from rodents to other species, in particular humans.

Promoting physical activity in overweight couples: Effectiveness of a dyadic action control trial (DYACTIC)

Background: Health behavior change models identify effective self-regulatory skills for behavioral change, but the social context is usually neglected. This study investigated the effectiveness of a dyadic conceptualization of action control for promoting physical activity. Methods: 121 overweight individuals and their partners were randomly allocated to one of two experimental (dyadic vs. individual action control) and two control conditions. Participants completed questionnaires at baseline (T1) and four weeks later (T2) including measures of action control and 7-day recall physical activity. Findings: Results showed that action control signi+cantly increased from T1 to T2 and was overall higher in the experimental conditions compared to control conditions. In terms of physical activity, no overall intervention effect emerged. However, post hoc analyses revealed higher mean levels of sport activities in the dyadic intervention group compared to all other groups. Discussion: Overall, +ndings provide +rst support for the usefulness of a dyadic action control intervention, and suggest further investigation of objective measures of physical activity and secondary outcomes

Dyadic action control in overweight and obese couples: Effectiveness of a randomized controlled trial to promote physical activity.

BACKGROUND: Enhancing physical activity in overweight and obese individuals is an important means to promote health in this target population. The Health Action Process Approach (HAPA), which was the theoretical framework of this study, focuses on individual self-regulation variables for successful health behavior change. One key self-regulation variable of this model is action control with its three subfacets awareness of intentions, self-monitoring and regulatory effort. The social context of individuals, however, is usually neglected in common health behavior change theories. In order to integrate social influences into the HAPA, this randomized controlled trial investigated the effectiveness of a dyadic conceptualization of action control for promoting physical activity. METHODS/DESIGN: This protocol describes the design of a single-blind randomized controlled trial, which comprises four experimental groups: a dyadic action control group, an individual action control group and two control groups. Participants of this study are overweight or obese, heterosexual adult couples who intend to increase their physical activity. Blocking as means of a gender-balanced randomization is used to allocate couples to conditions and partners to either being the target person of the intervention or to the partner condition. The ecological momentary intervention takes place in the first 14 days after baseline assessment and is followed by another 14 days diary phase without intervention. Follow-ups are one month and six months later. Subsequent to the six-months follow-up another 14 days diary phase takes place.The main outcome measures are self-reported and accelerometer-assessed physical activity. Secondary outcome measures are Body Mass Index (BMI), aerobic fitness and habitual physical activity. DISCUSSION: This is the first study examining a dyadic action control intervention in comparison to an individual action control condition and two control groups applying a single-blind randomized control trial. Challenges with running couples studies as well as advantages and disadvantages of certain design-related decisions are discussed. This RCT was funded by the Swiss National Science Foundation (PP00P1_133632/1) and was registered on 27/04/2012 at http://www.isrctn.com/ISRCTN15705531.