6 research outputs found
Alberta women in the 1920's: an inquiry into four aspects of their lives
Bibliography: p. 162-176
Quelle communication pour les PME industrielles de l'Arc jurassien franco-suisse? Projet Interreg "COM-PME-B2B" ::livre blanc
Partenaires depuis plus de dix ans dans le cadre des JournĂ©es franco-suisses dâintelligence Ă©conomique et de veille stratĂ©gique, lâIUT de Besançon, UniversitĂ© de Franche-ComtĂ© et la Haute Ă©cole de gestion Arc Ă NeuchĂątel ont dĂ©cidĂ© en 2013 de mener un projet de recherche transfrontalier bĂ©nĂ©ficiant dâun financement Interreg sur un sujet trop rarement abordĂ© de maniĂšre scientifique : la communication des PME industrielles fonctionnant en business to business 1 (B2B) ou en sous-traitance 2 de lâArc jurassien franco-suisse
PPARα-mediated fatty acid metabolism reprogramming supports resistance to anti-EGFR targeted therapy in head and neck squamous cell carcinoma
Increased linezolid plasma concentrations are associated with the development of severe toxicity in MDR-TB treatment.
Auteurs : the LZDM groupInternational audienceAbstract Background Treatment of multidrug-resistant (MDR) tuberculosis with linezolid is characterized by high rates of adverse events. Evidence on therapeutic drug monitoring to predict drug toxicity is scarce. This study aimed to evaluate the association of linezolid trough concentrations with severe toxicity. Methods We retrospectively assessed consecutive patients started on linezolid for MDR tuberculosis between 2011 and 2017. The primary outcome was severe mitochondrial toxicity (SMT) due to linezolid, defined as neurotoxicity or myelotoxicity leading to drug discontinuation. The impact of plasma linezolid trough concentrations >2â
mg/L was assessed in multivariate Cox proportional hazards models including time-varying covariates. Results SMT occurred in 57 of 146 included patients (39%) at an incidence rate of 0.38 per person-year (95% confidence interval, .30â.49). A maximum linezolid trough concentration >2â
mg/L was detected in 52 patients (35.6%), while the mean trough concentration was >2â
mg/L in 22 (15%). The adjusted hazard ratio for SMT was 2.35 (95% confidence interval, 1.26â4.38; Pâ=â.01) in patients with a mean trough concentration >2â
mg/L and 2.63 (1.55â4.47; Pâ<â.01) for SMT after the first detection of a trough concentration >2â
mg/L. In an exploratory analysis, higher maximum trough concentrations were dose-dependently associated with toxicity, while lowering elevated trough concentrations did not restore baseline risk. Conclusions Linezolid trough concentrations >2â
mg/L are strongly associated with the development of severe treatment-emergent toxicity in patients treated for MDR tuberculosis. Pending further prospective evidence, an individual risk-benefit assessment on the continuation of linezolid treatment is warranted in any patient with trough concentrations >2â
mg/L