Comets E.,University Paris Diderot |
Diquet B.,Angers University Hospital Center |
Legrain S.,University Paris Diderot |
Huisse M.-G.,University Paris Diderot |
And 10 more authors.
Clinical Pharmacology and Therapeutics | Year: 2012
In the PREPA observational study, we investigated the factors influencing pharmacokinetic and pharmacodynamic variability in the responses to fluindione, an oral anticoagulant drug, in a general population of octogenarian inpatients. Measurements of fluindione concentrations and international normalized ratio (INR) were obtained for 131 inpatients in whom fluindione treatment was initiated. Treatment was adjusted according to routine clinical practice. The data were analyzed using nonlinear mixed-effects modeling, and the parameters were estimated using MONOLIX 3.2. The pharmacokinetics (PK) of fluindione was monocompartmental, whereas the evolution of INR was modeled in accordance with a turnover model (inhibition of vitamin K recycling). Interindividual variability (IIV) was very large. Clearance decreased with age and with prior administration of cordarone. Patients who had undergone surgery before the study had lower IC 50 values, leading to an increased sensitivity to fluindione. Pharmacokinetic exposure is substantially increased in elderly patients, warranting a lower dose of fluindione. © 2012 American Society for Clinical Pharmacology and Therapeutics.
Pietrasz D.,Paris-Sorbonne University |
Marthey L.,Antoine Beclere Hospital |
Wagner M.,Paris-Sorbonne University |
Blanc J.-F.,Saint Andre Hospital |
And 12 more authors.
Annals of Surgical Oncology | Year: 2015
Purpose: In view of increased response rates and survivals in patients with metastatic pancreatic adenocarcinoma (PAC) with FOLFIRINOX, many centers proposed this regimen as induction chemotherapy for borderline (BR) or locally advanced (LA) PAC. The aim of this study was to assess surgical and oncological outcomes of patients who underwent resection after induction FOLFIRINOX therapy. Methods: We prospectively identified surgical consecutive BR or LA PAC patients after induction FOLFIRINOX in 20 observational French centers between November 2010 and December 2013. Two independent experts retrospectively evaluated initial CT scan for central review. Results: Eighty patients were included, 47 had BR and 33 had LA PAC. Median number of FOLFIRINOX cycles was 6 (range 1–30) and 65 % of patients received chemoradiation. The 30-day-mortality, major complications, and symptomatic pancreatic fistula rates were 2.5, 22.5, and 4 %, respectively. R0 resection was achieved in 84 %. After a median follow-up of 38.2 months since diagnosis, disease-free survival (DFS) was 17.16 months. The overall survival rates at 12 and 24 months were 92 and 81 %, respectively. A 26 % (n = 21) pathologic major response (pMR) rate was reached. In univariate and multivariate analysis, pMR was a prognostic factor for DFS (hazard ratio 0.33; P = 0.01 and hazard ratio 0.38; P = 0.035). Conclusions: Resection after induction FOLFIRINOX is safe and associated with similar or better outcomes as upfront surgery in patients with PAC. A pMR was observed in 26 % of cases and was prognostic of DFS. This therapeutic design should be investigated in prospective studies. © 2015, Society of Surgical Oncology.
Royer M.,Toulouse 1 University Capitole |
Bodemer C.,Service de dermatologie |
Barbarot S.,Nantes Hospital |
Paul C.,Toulouse 1 University Capitole |
Mazereeuw J.,Toulouse 1 University Capitole
British Journal of Dermatology | Year: 2011
Background Alopecia areata (AA) occurring in childhood is associated with a poorer prognosis than adult AA and may severely affect quality of life. The efficacy of methotrexate (MTX) was reported in adults with AA but there is little information about its use in children. Objectives We aimed to assess the efficacy and safety of MTX in severe childhood AA. Methods We conducted a retrospective study including children with severe AA treated with MTX in the Departments of Paediatric Dermatology in France between November 2005 and December 2009. Results Fourteen children (eight girls and six boys) aged between 8 and 18 years (mean 14·7) were included. AA was present for a mean duration of 5·7 years (range 2 months-11 years 8 months). The treatment was administered once weekly, the mean maximal dose was 18·9 mg weekly (range 15-25) and the mean duration of treatment was 14·2 months (range 1-31). Thirteen children were assessable. Of these 13 children, MTX was considered as successful (regrowth > 50% of hair) for five of them. The remaining eight children were considered treatment failures. No serious side-effects were reported. Conclusions The efficacy of MTX in children with severe AA is variable. MTX may be considered for severe childhood AA in the absence of alternative effective treatments. © 2011 British Association of Dermatologists.
Daculsi G.,University of Nantes |
Briand S.,Nantes Hospital |
Goyenvalle E.,ONIRIS LBBTOC |
Aguado E.,ONIRIS LBBTOC |
Baroth S.,Biomatlante SA
Key Engineering Materials | Year: 2012
A new biphasic calcium phosphate ceramic material Hydros™ has been developed. The main attractive feature of BCP ceramic is their ability to form a strong direct bond with the host bone resulting in a strong interface. Currently, granules are more and more used in moldable, injectable bone substitutes. However, the biological behaviour of the particles can be influenced not only by chemical composition and crystallinity, but also by several parameters as microporosity and nano-micro sized particles. The aim of the study was to assess, in animal experiment, the role played by an Hydrated Putty Bioceramics (Hydros™), based on specific combination of hydrophilic micro and macrosized BCP particles, to obtain high osteogenic Injectable Bone Substitute. No sign of clinical rejection was noticed. In muscular area, no fibrous encapsulation was observed, degradation of the smaller particles is observed by macrophages and giant cells. At 12 weeks, more of 75% of BCP was resorbed. The biocompatibility and safety in human orthopaedic applications (tibial plateau fracture) has been demonstrated. © (2012) Trans Tech Publications.
Beauval J.-B.,Toulouse University Hospital Center |
Ploussard G.,Henri Mondor Hospital |
Soulie M.,Toulouse University Hospital Center |
Pfister C.,Charles Nicolle Hospital |
And 13 more authors.
Urology | Year: 2012
To evaluate the pathologic features of surgical specimens after radical prostatectomy in patients with low-risk prostate cancer fulfilling the strictest pathologic selection criteria for active surveillance. Retrospective analysis of 10 785 consecutive radical prostatectomy performed in 10 university hospitals (January 2003 through December 2008). A total of 919 patients fulfilled the following unique and very stringent criteria: T1c, prostate-specific antigen (PSA) <10 ng/mL, a single positive biopsy, tumor length <3 mm, and Gleason score <7. Clinico-biologic and pathologic data at diagnosis and after radical prostatectomy, prostatic and tumor volume, pathologic Gleason score and stage, positive surgical margins, insignificant prostate cancer, and PSA outcomes were recorded. Median age was 63 years. Mean prebiopsy PSA level was 6.2 ng/mL. At radical prostatectomy, Gleason score was upgraded in 34% of patients, including 1.2% Gleason score 8-9. Pathologic stages were pT2 in 87.3%, pT3 in 11.1%, and pT4 in 1.4% of cases. Extraprostatic extension was found in 12.5%. Only 26% of patients had "insignificant" tumors. Biochemical recurrence-free survival at 5 years was 92.3%. There was no significant difference in survival between patients with "significant" and "insignificant" tumors (90.1% vs 93.4%; P = .06). Despite of a stringent selection of patients with low-risk prostate cancer, active surveillance definition included a significant proportion of patients with upstaged (about 12%) and upgraded (about one-third) disease at diagnosis. Only a quarter of active surveillance patients have a pathologically confirmed "insignificant" cancer. © 2012 Elsevier Inc. All Rights Reserved.