Virological outcomes in ARV-naïve patients switching or not from a first successful boosted PI-regimen to efavirenz, nevirapine or abacavir regimens

International audiencen.

Practices, patients and (im)perfect data - feasibility of a randomised controlled clinical drug trial in German general practices

<p>Abstract</p> <p>Background</p> <p>Randomised controlled clinical (drug) trials supply high quality evidence for therapeutic strategies in primary care. Until now, experience with drug trials in German general practice has been sparse. In 2007/2008, the authors conducted an investigator-initiated, non-commercial, double-blind, randomised controlled pilot trial (HWI-01) to assess the clinical equivalence of ibuprofen and ciprofloxacin in the treatment of uncomplicated urinary tract infection (UTI). Here, we report the feasibility of this trial in German general practices and the implementation of Good Clinical Practice (GCP) standards as defined by the International Conference on Harmonisation (ICH) in mainly inexperienced general practices.</p> <p>Methods</p> <p>This report is based on the experience of the HWI-01 study conducted in 29 German general practices. Feasibility was defined by 1) successful practice recruitment, 2) sufficient patient recruitment, 3) complete and accurate data collection and 4) appropriate protection of patient safety.</p> <p>Results</p> <p>The final practice recruitment rate was 18%. In these practices, 79 of 195 screened UTI patients were enrolled. Recruitment differed strongly between practices (range 0-12, mean 2.8 patients per practice) and was below the recruitment goal of approximately 100 patients. As anticipated, practice nurses became the key figures in the screening und recruitment of patients. Clinical trial demands, in particular for completing symptom questionnaires, documentation of source data and reporting of adverse events, did not agree well with GPs' documentation habits and required support from study nurses. In many cases, GPs and practice staff seemed to be overwhelmed by the amount of information and regulations. No sudden unexpected serious adverse reactions (SUSARs) were observed during the trial.</p> <p>Conclusions</p> <p>To enable drug trials in general practice, it is necessary to adapt the setup of clinical research infrastructure to the needs of GPs and their practice staff. Risk adaption of clinical trial regulations is necessary to facilitate non-commercial comparative effectiveness trials in primary health care.</p> <p>Trial Registration</p> <p>Trial registration number: <a href="http://www.controlled-trials.com/ISRCTN00470468">ISRCTN00470468</a></p

Mass hierarchy discrimination with atmospheric neutrinos in large volume ice/water Cherenkov detectors

Large mass ice/water Cherenkov experiments, optimized to detect low energy (1-20 GeV) atmospheric neutrinos, have the potential to discriminate between normal and inverted neutrino mass hierarchies. The sensitivity depends on several model and detector parameters, such as the neutrino flux profile and normalization, the Earth density profile, the oscillation parameter uncertainties, and the detector effective mass and resolution. A proper evaluation of the mass hierarchy discrimination power requires a robust statistical approach. In this work, the Toy Monte Carlo, based on an extended unbinned likelihood ratio test statistic, was used. The effect of each model and detector parameter, as well as the required detector exposure, was then studied. While uncertainties on the Earth density and atmospheric neutrino flux profiles were found to have a minor impact on the mass hierarchy discrimination, the flux normalization, as well as some of the oscillation parameter (\Delta m^2_{31}, \theta_{13}, \theta_{23}, and \delta_{CP}) uncertainties and correlations resulted critical. Finally, the minimum required detector exposure, the optimization of the low energy threshold, and the detector resolutions were also investigated.Comment: 23 pages, 16 figure

Gravity Wave and Neutrino Bursts from Stellar Collapse: A Sensitive Test of Neutrino Masses

New methods are proposed with the goal to determine absolute neutrino masses from the simultaneous observation of the bursts of neutrinos and gravitational waves emitted during a stellar collapse. It is shown that the neutronization electron neutrino flash and the maximum amplitude of the gravitational wave signal are tightly synchronized with the bounce occuring at the end of the core collapse on a timescale better than 1 ms. The existing underground neutrino detectors (SuperKamiokande, SNO, ...) and the gravity wave antennas soon to operate (LIGO, Virgo, ...) are well matched in their performance for detecting galactic supernovae and for making use of the proposed approach. Several methods are described, which apply to the different scenarios depending on neutrino mixing. Given the present knowledge on neutrino oscillations, the methods proposed are sensitive to a mass range where neutrinos would essentially be mass-degenerate. The 95 % C.L. upper limit which can be achieved varies from 0.75 eV/c2 for large electron neutrino survival probabilities to 1.1 eV/c2 when in practice all electron neutrinos convert into muon or tau neutrinos. The sensitivity is nearly independent of the supernova distance.Comment: 17 pages, 4 figure

Radiotherapy modification based on artificial intelligence and radiomics applied to (18F)-fluorodeoxyglucose positron emission tomography/computed tomography.

peer reviewedOver the last decades, the refinement of radiation therapy techniques has been associated with an increasing interest for individualized radiation therapy with the aim of increasing or maintaining tumor control and reducing radiation toxicity. Developments in artificial intelligence (AI), particularly machine learning and deep learning, in imaging sciences, including nuclear medecine, have led to significant enthusiasm for the concept of "rapid learning health system". AI combined with radiomics applied to (18F)-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) offers a unique opportunity for the development of predictive models that can help stratify each patient's risk and guide treatment decisions for optimal outcomes and quality of life of patients treated with radiation therapy. Here we present an overview of the current contribution of AI and radiomics-based machine learning models applied to (18F)-FDG PET/CT in the management of cancer treated by radiation therapy

Lipid Profiles in HIV-Infected Patients Receiving Combination Antiretroviral Therapy: Are Different Antiretroviral Drugs Associated with Different Lipid Profiles?

Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c), as well as the TC:HDL-c ratio, were compared in patients receiving different antiretroviral therapy regimens. Patients receiving first-line regimens including protease inhibitors (PIs) had higher TC and TG levels and TC:HDL-c ratios than did antiretroviral-naive patients; patients receiving 2 PIs had higher levels of each lipid. Ritonavir-containing regimens were associated with higher TC and TG levels and TC:HDL-c ratios than were indinavir-containing regimens; however, receipt of nelfinavir was associated with reduced risk of lower HDL-c levels, and receipt of saquinavir was associated with lower TC:HDL-c ratios. Patients receiving nonnucleoside reverse-transcriptase inhibitors had higher levels of TC and LDL-c than did antiretroviral-naive patients, although the risk of having lower HDL-c levels was lower than that in patients receiving a single PI. Efavirenz was associated with higher levels of TC and TG than was nevirapin

Les pratiques funéraires de la fin du Néolithique à l’âge du Bronze de la partie centrale du Myanmar (c. 1300-500 cal BC) : définitions et évolutions

En Asie du Sud-est continentale, la fin de la préhistoire est surtout définie à travers l’étude des sites funéraires. Les données disponibles jusqu’à présent concernent presque essentiellement la partie sud et est de la péninsule indochinoise, représentée par le Viet Nam et la Thaïlande. Le Myanmar pâtit d’un état de la recherche beaucoup moins favorable. Pourtant son emplacement est crucial. Il est le seul territoire d’Asie du Sud-est à partager des frontières terrestres avec l’Inde et la Ch..