Durée courte d’antibiothérapie

RésuméLes durées de traitement antibiotique ne reposent pas sur un rationnel scientifique fort. Pourtant à l’heure de l’émergence dramatique de résistance bactérienne, réduire la pression de sélection par la réduction de la durée d’exposition devrait être un enjeu majeur. En outre, la diminution des coûts et des effets indésirables associés renforce l’intérêt des traitements courts. Malheureusement, peu d’études de méthodologie satisfaisante sont disponibles dans la littérature. Nous présentons le rationnel et l’intérêt à un raccourcissement des durées de traitement antibiotique ainsi que les principales données disponibles concernant les infections fréquentes comme les infections urinaires, pulmonaires, ostéoarticulaires et intra-abdominales. Enfin, nous mettons en perspective les difficultés à évaluer les durées de traitement ainsi que les possibles solutions et méthodologies innovantes.AbstractAntibiotic treatment durations are not well documented. Yet, dramatic emergence of multi-drug resistant organisms should lead to tend to decrease antibiotic selection pressure. Furthermore, it could lower health costs and reduce associated adverse events. Unfortunately, only few studies with rigorous methodology have been performed. We present the available data on frequent infections such as urinary tract infections, community acquired pneumonia, bone and joint infections and intra-abdominal infections. We underline the difficulties to perform such trials and discuss original options to a better evaluation of treatment duration

French national cohort of first use of dalbavancin: a high proportion of off-label use

Dalbavancin is a glycopeptide antibiotic with a long half-life, recently marketed in Europe for skin and soft tissue infections (SSTI), but real-life use is not well-known. We aimed to describe all first prescriptions in France over an 18-month period. We performed a retrospective study on all adult patients who received at least one dose of dalbavancin from July 1, 2017 to September 31, 2018. Data were collected thanks to a standard questionnaire. Failure was defined as: persistent or reappearance of signs of infection; and/or switch to suppressive antibiotic treatment; and/or death from infection. We included 75 patients from 29 French hospitals. Main indications were bone and joint infections (BJIs) (64.0%), endocarditis (25.3%), and SSTIs (17.3%). Main bacteria involved were: Staphylococcus aureus (51.4%), including methicillin-resistant S. aureus (MRSA) (19.4%); and coagulase-negative staphylococci (CNS) (44.4%). Median MICs for staphylococci to vancomycin and dalbavancin ranged from 0.875 mg/L to 2.0 mg/L, and 0.040 mg/L to 0.064 mg/L, respectively. Dalbavancin was used after a mean of 2.3 ± 1.2 lines of antimicrobial treatment. Main treatment regimens for dalbavancin were a weekly 2-dose regimen (1500mg each) in 38 (53.2%) cases, and a single-dose regimen (1500mg) in 13 (18.3%) cases. Overall, at the patients\u27 last visit, clinical cure was observed in 54/72 patients, while failure was found in 14/72 patients. First uses of dalbavancin in France were mostly off-label. Most of them were due to BJIs, and often as rescue therapy for severe infections. Even in off-label situations, dalbavancin seems safe and effective

Slow dynamics and aging in a non-randomly frustrated spin system

A simple, non-disordered spin model has been studied in an effort to understand the origin of the precipitous slowing down of dynamics observed in supercooled liquids approaching the glass transition. A combination of Monte Carlo simulations and exact calculations indicates that this model exhibits an entropy vanishing transition accompanied by a rapid divergence of time scales. Measurements of various correlation functions show that the system displays a hierarchy of time scales associated with different degrees of freedom. Extended structures, arising from the frustration in the system, are identified as the source of the slow dynamics. In the simulations, the system falls out of equilibrium at a temperature $T_{g}$ higher than the entropy-vanishing transition temperature and the dynamics below $T_{g}$ exhibits aging as distinct from coarsening. The cooling rate dependence of the energy is also consistent with the usual glass formation scenario.Comment: 41 pages, 16 figures. Bibliography file is correcte

Similar Dark Matter and Baryon abundances with TeV-scale Leptogenesis

We estimate the Baryon Asymmetry of the Universe (BAU) produced in an inverse seesaw model containing extra light singlets, and with lepton number conservation prior to the electroweak phase transition. An order one CP asymmetry epsilon is required to obtain a large enough BAU. We discuss the relation between the baryon and WIMP relic densities in baryogenesis scenarios using the out-of-equilibrium decay of a baryon-parent of mass M: when baryon number violation freezes out, the remaining density of baryon-parents is of order M/m_W times the WIMP relic density. So the baryon/WIMP ratio is or order epsilon M/m_W. A natural explanation of the similar WIMP and baryon densities could be that CP violation is of order the ratio m_W/M.Comment: references adde

Running of Radiative Neutrino Masses: The Scotogenic Model

We study the renormalization group equations of Ma's scotogenic model, which generates an active neutrino mass at 1-loop level. In addition to other benefits, the main advantage of the mechanism exploited in this model is to lead to a natural loop-suppression of the neutrino mass, and therefore to an explanation for its smallness. However, since the structure of the neutrino mass matrix is altered compared to the ordinary type I seesaw case, the corresponding running is altered as well. We have derived the full set of renormalization group equations for the scotogenic model which, to our knowledge, had not been presented previously in the literature. This set of equations reflects some interesting structural properties of the model, and it is an illustrative example for how the running of neutrino parameters in radiative models is modified compared to models with tree-level mass generation. We also study a simplified numerical example to illustrate some general tendencies of the running. Interestingly, the structure of the RGEs can be exploited such that a bimaximal leptonic mixing pattern at the high-energy scale is translated into a valid mixing pattern at low energies, featuring a large value of \theta_{13}. This suggests very interesting connections to flavour symmetries.Comment: 35 pages, 10 figures, 2 table

Operating a full tungsten actively cooled tokamak: overview of WEST first phase of operation

WEST is an MA class superconducting, actively cooled, full tungsten (W) tokamak, designed to operate in long pulses up to 1000 s. In support of ITER operation and DEMO conceptual activities, key missions of WEST are: (i) qualification of high heat flux plasma-facing components in integrating both technological and physics aspects in relevant heat and particle exhaust conditions, particularly for the tungsten monoblocks foreseen in ITER divertor; (ii) integrated steady-state operation at high confinement, with a focus on power exhaust issues. During the phase 1 of operation (2017–2020), a set of actively cooled ITER-grade plasma facing unit prototypes was integrated into the inertially cooled W coated startup lower divertor. Up to 8.8 MW of RF power has been coupled to the plasma and divertor heat flux of up to 6 MW m−2 were reached. Long pulse operation was started, using the upper actively cooled divertor, with a discharge of about 1 min achieved. This paper gives an overview of the results achieved in phase 1. Perspectives for phase 2, operating with the full capability of the device with the complete ITER-grade actively cooled lower divertor, are also described