Safety of dual kidney transplantation compared to single kidney transplantation from expanded criteria donors: a single center cohort study of 39 recipients.

Our objective was to compare the outcomes of dual kidney transplanataion (DKT) to single kidney transplantation (SKT) performed with grafts from expanded criteria donors (ECD) in recipients ≥65 years, focusing on surgical complications. All kidney transplantations (KT) performed between 2006 and 2014 in our institution were analysed. DKT was indicated according to the criteria of the French national Agence de la Biomedecine. Thirty-nine DKT and 155 SKT were included, with a median follow-up of 36 and 26.5 months, respectively. The rate of early surgical revisions was not significantly higher after DKT (23.1% vs 15.5% (P = 0.2593)) but more venous graft thromboses (12.8% vs 3.2% (P = 0.02)) were reported. The glomerular filtration rate (GFR) 24 months after KT was significantly higher after DKT (45.0 ± 16.3 vs 39.8 ± 13.8 ml/min/1.73m2 ; P = 0.04) and allowed shorter waiting time without a significant increased risk of surgical revision, excepted for venous graft thrombosis, more frequent after DKT. Graft survivals were not significantly different and GFR was higher after DKT. DKT seems to remain an appropriate strategy to address the growing graft shortage in elderly patients.

Phase I/II dose-finding design for molecularly targeted agent: Plateau determination using adaptive randomization.

Conventionally, phase I dose-finding trials aim to determine the maximum tolerated dose of a new drug under the assumption that both toxicity and efficacy monotonically increase with the dose. This paradigm, however, is not suitable for some molecularly targeted agents, such as monoclonal antibodies, for which efficacy often increases initially with the dose and then plateaus. For molecularly targeted agents, the goal is to find the optimal dose, defined as the lowest safe dose that achieves the highest efficacy. We develop a Bayesian phase I/II dose-finding design to find the optimal dose. We employ a logistic model with a plateau parameter to capture the increasing-then-plateau feature of the dose-efficacy relationship. We take the weighted likelihood approach to accommodate for the case where efficacy is possibly late-onset. Based on observed data, we continuously update the posterior estimates of toxicity and efficacy probabilities and adaptively assign patients to the optimal dose. The simulation studies show that the proposed design has good operating characteristics. This method is going to be applied in more than two phase I clinical trials as no other method is available for this specific setting. We also provide an R package dfmta that can be downloaded from CRAN website.

dfcomb: An R-package for phase I/II trials of drug combinations.

In this paper, we present the dfcomb R package for the implementation of a single prospective clinical trial or simulation studies of phase I combination trials in oncology. The aim is to present the features of the package and to illustrate how to use it in practice though different examples. The use of combination clinical trials is growing, but the implementation of existing model-based methods is complex, so this package should promote the use of innovative adaptive designs for early phases combination trials.

[Relevance of prison placements based on the perception of primary care medicine interns]. / Pertinence du stage en milieu pénitentiaire a partir du vécu des internes de médecine générale.

INTRODUCTION: The growing need for new placement opportunities for primary care interns has opened the way to placements in prison health centres. No study has previously assessed the educational value of this type of placement and its relevance to primary care for the general population. METHODS: A qualitative pilot study was conducted in the Languedoc-Roussillon region of France by means of semistructured interviews and phenomenological and practical analysis based on all primary care interns completing a prison health centre placement in the region. ANALYSIS AND RESULTS: The key dimensions emerging from the analysis are: exposure to a range of situations that are very similar to primary care in a public health context; learning how to manage complex situations; stronger orientation towards ethical health care; firmer belief in multidisciplinary teams; and enhanced awareness of the social role of primary care physicians. DISCUSSION: All interns considered this type of placement (towards the end of their training) to be a good preparation for their future primary care role, especially in the context of multidisciplinary practices.

Novel chikungunya virus variant in travelers returning from Indian Ocean islands.

Chikungunya virus (CHIKV) emerged in Indian Ocean islands in 2005 and is causing an ongoing outbreak that involves >260,000 patients, including travelers returning home from these islands. We investigated cases in 4 patients returning from Mayotte and Reunion Islands with CHIKV infection and a nurse infected in metropolitan France after direct contact with the blood of a traveler. Four patients had tenosynovitis and pain at wrist pressure, and 1 had life-threatening manifestations. Four CHIKV strains were isolated, including 1 from the patient with the autochthonous case. The complete genomic sequence identified a new CHIKV variant emerging from the East/ central African evolutionary lineage. Aedes albopictus, the implicated vector of CHIKV in Indian Ocean islands, has dispersed worldwide in recent decades. High viral loads in patients returning from Indian Ocean islands to countries where Ae. albopictus is prevalent may be a source of epidemics.

Post-antibiotic and post-beta-lactamase inhibitor effects of ceftazidime plus sulbactam on extended-spectrum beta-lactamase-producing Gram-negative bacteria.

OBJECTIVES: To measure the in vitro post-antibiotic effect (PAE) and post-beta-lactamase inhibitor effect (PLIE) of a ceftazidime-sulbactam combination on bacteria producing extended-spectrum beta-lactamases (ESBLs). METHODS: PAE and PLIE were studied for ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae. Two ATCC beta-lactamase-negative strains of E. coli and K. pneumoniae were used as controls. The MICs of a ceftazidime-sulbactam combination were determined with a fixed concentration of sulbactam (8 mg/L). The organisms were exposed to the antibiotics at twice the MIC for 2 h before removal of the antibiotics by filtration of the culture. Bacteria on the filter were resuspended in drug-free medium to determine the PAE and in medium containing ceftazidime, at the same concentration as originally present, to determine the PLIE. RESULTS: The PAE of ceftazidime was similar for bacteria producing the same ESBL except for E. coli producing CTX-M-1. PLIE values varied according to the type of beta-lactamase but similar results were observed for the strains producing the same ESBLs. PLIEs were longer than PAEs and were longer when the MICs of ceftazidime were lower. CONCLUSIONS: To the best of our knowledge, we describe here for the first time an in vitro PLIE for a ceftazidime-sulbactam combination on different bacteria producing different ESBLs. These findings indicate that suicide inhibitors may be used in combination with third-generation cephalosporins.

[Enzymatic resistance of Escherichia coli to beta-lactams and clinical prevalence]. / Résistance enzymatique d'Escherichia coli aux bêtalactamines et prévalence en clinique.

Escherichia coli (E. coli) is the most frequent bacterium implicated in community-acquired infection as well as in nosocomial infections. This bacterium is characterised by numerous possibilities to acquire resistance mechanisms, even during antibiotic treatment. The main mechanism of resistance is the production of beta-lactamines, enzymes hydrolysing beta-lactam ring. This paper describes enzymatic mechanisms of resistance of E. coli to beta-lactam and indicates the necessity of a good knowledge of the risk factors for resistance to have an adapted good clinical practice in using antibiotics.

Experimental application of the median-effect principle for in vitro quantification of the combined inhibitory activities of clavulanic acid and imipenem against IRT-4 beta-lactamase.

Inhibitor-resistant TEM beta-lactamases (IRT) have been identified in Enterobacteriaceae which, however, remained susceptible to cephalosporins. We evaluated the combined inhibitory activity of clavulanic acid and imipenem at ratios of 1:1 and 1:3 against IRT-4, using the median effect principle of Chou and Talalay. The combination of the two drugs, which produced a nearly additive effect, meant their concentrations could be lowered 1.3-4.9-fold, while maintaining a 50% inhibitory effect against the IRT-4 in comparison with each drug alone. From a therapeutic point of view, such a combination is not efficient but this method of Chou and Talalay, used for the first time to assay combined inhibitory activity of beta-lactamase inhibitors, could be used to evaluate new molecules and/or strategies to inactivate beta-lactamase.