Predictors and indicators of disability and quality of life 4 years after a severe traumatic brain injury. A Structural Equation Modelling analysis from the PariS-TBI study

ObjectiveTo assess the predictors and indicators of disability and quality of life four years after a severe traumatic brain injury (TBI), using a Structural Equation Modelling (SEM). SEM is a multivariate approach permitting to take into account the complex inter-relationships between individual predictors, in order to disentangle factors which have a direct or indirect relationship with the dependant variable.MethodsThe Paris-TBI study is a longitudinal inception cohort study of 504 patients with severe TBI in the Parisian area [1]. Among 245 survivors, 147 patients were assessed four years post-injury. Two outcome measures were analysed separately using SEM: the Glasgow Outcome Scale-extended (GOS-E) [2], which is a global measure of disability after TBI, and the QOLIBRI, a disease-specific measure of quality of life after TBI [3]. Four groups of variable were entered in the model: demographics; injury severity; psychological and cognitive impairments; somatic impairments.ResultsThe GOS-E was directly significantly related to all four groups of variables (age, gender, severity of injury, psycho-cognitive and somatic impairments). Education duration had an indirect effect, mediated by psycho-cognitive impairments. In contrast, the QOLIBRI was only directly predicted by psycho-cognitive impairments. Age and somatic impairments had an indirect influence on the QOLIBRI, via psycho-cognitive impairments.Discussion/ConclusionDisability and quality of life were directly influenced by different factors. While disability appeared to result from an interaction of a wide range of factors, including demographics, injury severity, psycho-cognitive and somatic deficiencies, quality of life was solely directly related to psycho-cognitive factors. Other factors, such as age and somatic impairments only had an indirect effect

Efficacy of generic meropenem products in combination with colistin in carbapenemase-producing Klebsiella pneumoniae experimental osteomyelitis

International audienceGuidelines for the management of carbapenemase-producing Enterobacterales (CPE) infections recommend a combination of two active agents, including meropenem if the minimum inhibitory concentration (MIC) is ≤8 mg/L. The therapeutic equivalence of meropenem generics has been challenged. We compared the bactericidal activity of meropenem innovator (AstraZeneca) and four generic products (Actavis, Kabi, Mylan and Panpharma), both in vitro and in vivo, in association with colistin. In vitro time-kill studies were performed at 4 × MIC. An experimental model of KPC-producing Klebsiella pneumoniae osteomyelitis was induced in rabbits by tibial injection of a sclerosing agent followed by 2 × 10 CFU of K. pneumoniae KPC-99YC (meropenem MIC = 4 mg/L; colistin MIC = 1 mg/L). At 14 days after inoculation, treatment for 7 days started in seven groups of ≥10 rabbits, including a control group, a colistin group, and one group for each meropenem product (i.e. the innovator and four generics), in combination with colistin. In vitro, meropenem + colistin was bactericidal with no viable bacteria after 6 h, and this effect was similar with all meropenem products. In the osteomyelitis model, there was no significant difference between meropenem generics and the innovator when combined with colistin. Colistin-resistant strains were detected after treatment with colistin + meropenem innovator (n = 3) and generics (n = 3). The efficacy of four meropenem generics did not differ from the innovator in vitro and in an experimental rabbit model of KPC-producing K. pneumoniae osteomyelitis in terms of bactericidal activity and the emergence of resistance