Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: A randomized clinical trial

This article has been accepted for publication in Clinical Infectious Diseases ©2014 The Authors .Published by Oxford University Press on Clinical Infectious Disease 60.5. DOI: 10.1093/cid/ciu898Background. It is unclear whether metabolic or body composition effects may differ between protease inhibitor-based regimens recommended for initial treatment of HIV infection. Methods. ATADAR is a phase IV, open-label, multicenter randomized clinical trial. Stable antiretroviral-naive HIV-infected adults were randomly assigned to atazanavir/ritonavir 300/100 mg or darunavir/ritonavir 800/100 mg in combination with tenofovir/emtricitabine daily. Pre-defined end-points were treatment or virological failure, drug discontinuation due to adverse effects, and laboratory and body composition changes at 96 weeks. Results. At 96 weeks, 56 (62%) atazanavir/ritonavir and 62 (71%) darunavir/ritonavir patients remained free of treatment failure (estimated difference 8.2%; 95%CI -0.6 to 21.6); and 71 (79%) atazanavir/ritonavir and 75 (85%) darunavir/ritonavir patients remained free of virological failure (estimated difference 6.3%; 95%CI -0.5 to 17.6). Seven vs. five patients discontinued atazanavir/ritonavir or darunavir/ritonavir due to adverse effects. Total and HDL cholesterol similarly increased in both arms, but triglycerides increased more in atazanavir/ritonavir arm. At 96 weeks, body fat (estimated difference 2862.2 gr; 95%CI 726.7 to 4997.7; P=0.0090), limb fat (estimated difference 1403.3 gr; 95%CI 388.4 to 2418.2; P=0.0071), and subcutaneous abdominal adipose tissue (estimated difference 28.4 cm2; 95%CI 1.9 to 55.0; P=0.0362) increased more in atazanavir/ritonavir than in darunavir/ritonavir arm. Body fat changes in atazanavir/ritonavir arm were associated with higher insulin resistance. Conclusions. We found no major differences between atazanavir/ritonavir and darunavir/ritonavir in efficacy, clinically-relevant side effects, or plasma cholesterol fractions. However, atazanavir/ritonavir led to higher triglycerides and total and subcutaneous fat than darunavir/ritonavir and fat gains with atazanavir/ritonavir were associated with insulin resistanceThis is an Investigator Sponsored Research study. It was supported in part by research grants from Bristol‐Myers Squibb and Janssen‐Cilag; Instituto de Salud Carlos III (PI12/01217) and Red Temática Cooperativa de Investigación en SIDA G03/173 (RIS‐EST11), Ministerio de Ciencia e Innovación, Spain. (Registration number: NCT01274780; registry name: ATADAR; EUDRACT; 2010‐021002‐38)

Polyethylene glycol improves current methods for circulating extracellular vesicle-derived DNA isolation

Abstract Background Extracellular vesicles (EVs) are small membrane-bound vesicles which play an important role in cell-to-cell communication. Their molecular cargo analysis is presented as a new source for biomarker detection, and it might provide an alternative to traditional solid biopsies. However, the most effective approach for EV isolation is not yet well established. Results Here, we study the efficiency of the most common EV isolation methods-ultracentrifugation, Polyethlyene glycol and two commercial kits, Exoquick® and PureExo®. We isolated circulating EVs from the bloodstream of healthy donors, characterized the size and yield of EVs and analyzed their protein profiles and concentration. Moreover, we have used for the first time Digital-PCR to identify and detect specific gDNA sequences, which has several implications for diagnostic and monitoring many types of diseases. Conclusions Our findings present Polyethylene glycol precipitation as the most feasible and less cost-consuming EV isolation technique

Intelligent web caching using machine learning methods

Web caching is a technology to improve network traffic on the Internet. It is a temporary storage of Web objects for later retrieval. Three significant advantages of Web caching include reduction in bandwidth consumption, server load, and latency. These advantages make the Web to be less expensive yet it provides better performance. This research aims to introduce an advanced machine learning method for a classification problem in Web caching that requires a decision to cache or not to cache Web objects in a proxy cache server. The challenges in this classification problem include the issues in identifying attributes ranking and improve the classification accuracy significantly. This research includes four methods that are Classification and Regression Trees (CART), Multivariate Adaptive Regression Splines (MARS), Random Forest (RF) and TreeNet (TN) for classification on Web caching. The experimental results reveal that CART performed extremely well in classifying Web objects from the existing log data with a size of Web objects as a significant attribute for Web cache performance enhancement.Web of Science21545242

The use of cost per life year gained as a measurement of cost-effectiveness in Spain: a systematic review of recent publications

The objective of this study was to evaluate the methodological characteristics of cost-effectiveness evaluations carried out in Spain, since 1990, which include LYG as an outcome to measure the incremental cost-effectiveness ratio. METHODS: A systematic review of published studies was conducted describing their characteristics and methodological quality. We analyse the cost per LYG results in relation with a commonly accepted Spanish cost-effectiveness threshold and the possible relation with the cost per quality adjusted life year (QALY) gained when they both were calculated for the same economic evaluation. RESULTS: A total of 62 economic evaluations fulfilled the selection criteria, 24 of them including the cost per QALY gained result as well. The methodological quality of the studies was good (55%) or very good (26%). A total of 124 cost per LYG results were obtained with a mean ratio of 49,529 and a median of 11,490 (standard deviation of 183,080). Since 2003, a commonly accepted Spanish threshold has been referenced by 66% of studies. A significant correlation was found between the cost per LYG and cost per QALY gained results (0.89 Spearman-Rho, 0.91 Pearson). CONCLUSIONS: There is an increasing interest for economic health care evaluations in Spain, and the quality of the studies is also improving. Although a commonly accepted threshold exists, further information is needed for decision-making as well as to identify the relationship between the costs per LYG and per QALY gained