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In 2018, dosing regimens of the two most prescribed immune check point inhibitors (ICI), nivolumab (Opdivo&reg, ) and pembrolizumab (Keytruda&reg, ), in the treatment of lung cancer were changed from weight-based dosing to fixed dosing. The aim of this study was to compare the economic impact of this change in our university hospital group and then across Ile-de-France, the most inhabited French region. A budget impact analysis (BIA) has been performed on the French public health insurance data. The duration of treatment and the weight of the patients were calculated using data from the patients treated at our health facility and from clinical studies. The cost of treatment was calculated at the local level of our health facility and then for Ile-de-France. Our model demonstrates an additional cost of &euro, 550,115 in our hospital and &euro, 9,704,778 in Ile-de-France for a fixed dose prescription in 2018. In 2019, the BIA concluded an additional cost, according to the respective low and high assumptions, of &euro, 556,969 and &euro, 756,544 locally and &euro, 10,201,027 to &euro, 14,486,141 for Ile-de-France for an equivalent efficacy between the two different drug dosing regimens of nivolumab and pembrolizumab. The adoption of the fixed dose regimen would lead, according to the least expensive hypothesis, to an additional cost of 26% for the ICI. These results encourage reflection on the strict adoption of this dosage modification. The option of maintaining the free choice between a prescription adapted to weight or in a fixed dose seems a relevant option and should be considered.

Colistin is a polypeptide antibiotic from the polymyxin E group used for the treatment of infections caused by multidrug-resistant gram-negative bacteria. The main constituents, accounting for approximately 85% of this mixture, are colistin A (polymyxin E1) and colistin B (polymyxin E2). The aim of this study was to develop and validate new and fast methods of quantification of colistin A and B and its precursors [colistin methanesulfonate sodium (CMS) A and B] by ultraperformance liquid chromatography-tandem mass spectrometry in plasma and urine with short pretreatment and run times.Chromatography was performed on an Acquity UPLC-MS/MS system (WATERS) with a WATERS Acquity UPLC C18 column (4.6 × 150 mm, 3.5 μm particle size). The pretreatment of samples consists of precipitation and extraction into microcolumns plate and HLB 96-well plate 30 μm-30 mg (OASIS) with a Positive Pressure-96 (WATERS).Quantification was performed using a multiple reaction monitoring of the following transitions: m/z 390.9 → 385.1 for colistin A, m/z 386.2 → 101.0 for colistin B, and m/z 602.4 → 241.1 for polymyxin B1 sulfate. In plasma and urine, calibration curves were linear from 30 to 6000 ng/mL for colistin A and from 15 to 3000 ng/mL for colistin B. With an acceptable accuracy and precision, the lower limit of quantification were set at 24.0 ng/mL and 12.0 ng/mL for colistin A and B in plasma, and at 18.0 ng/mL and 9.0 ng/mL for colistin A and B in urine.These LC-MS/MS methods of quantification for colistin A and B and its precursors (CMS A and B) in plasma and urine are fast, simple, specific, sensitive, accurate, precise, and reliable. Furthermore, they are linear and repeatable. These procedures were successfully applied to a pharmacokinetic study of a critically ill patient suffering from ventilator-associated pneumonia, who was treated with nebulized CMS.

Introduction Dans le cadre d’une sous-traitance de preparation de medicaments anticancereux pediatriques, une analyse preliminaire des risques (APR) a ete conduite. Cette APR avait permis de realiser une cartographie des risques de notre systeme et d’identifier des situations dangereuses prioritaires conduisant a 41 scenarios d’accident potentiel d’un niveau de criticite elevee. Pour reduire ces risques, 33 mesures correctives ont ete proposees. Un an apres le demarrage de la sous-traitance, l’objectif de ce travail est d’evaluer la pertinence des actions decidees et d’actualiser le plan de reduction de risques initial. Materiels et methode Les non-conformites (NC) observees depuis la mise en place de de la sous-traitance (01/06/2017 au 30/06/2018) sont relevees, analysees et integrees aux scenarios estimes lors de l’APR. Une actualisation du plan de reduction de risques initial est ensuite etablie en tenant compte de ces NC. Enfin, sur les scenarios de criticite initialement elevee, une reevaluation de de leur criticite residuelle est mesuree a l’aide d’echelles de gravite et de vraisemblance a 5 niveaux et une matrice de criticite a 3 niveaux (acceptable, tolerable sous controle et inacceptable). Resultats et discussion Sur la periode etudiee, 458 preparations ont ete realisees dans le cadre de la sous-traitance, 49 NC ont ete declarees correspondant a 6 scenarios d’accident potentiel. Parmi les 41 scenarios envisages dans l’APR, 35 n’ont donc pas ete observes. Les 6 scenarios constates avaient tous ete envisages dans l’APR, mais avec une vraisemblance sous-estimee pour 4 d’entre eux. L’analyse des NC a ainsi permis d’ajouter 4 scenarios conduisant a 45 scenarios d’accident potentiel de criticite elevee. A 1 an, sur les 33 mesures prevues dans le plan initial, 15 mesures n’ont pas ete mises en place. Par ailleurs, au vu des NC observees, 3 mesures nouvelles sont decidees conduisant a un nouveau plan de 18 actions (inclusion alerte poids-taille dans le logiciel CHIMIO, double-controle etiquetage, formation du personnel aux dispositifs medicaux utilises en pediatrie). Avec ce nouveau plan, la mesure a priori de la criticite residuelle sur les 45 scenarios juges prioritaires ne retrouve aucun scenario de criticite inacceptable. Conclusion A 1 an de la mise en place de la sous-traitance, une majorite des accidents potentiels envisages ne se sont pas produits grâce au plan initial. Plus de la moitie des actions decidees dans le plan de reduction de risques initial ont ete realisees. Ce plan etait cependant insuffisant au vu des NC observees sur le retour d’experience, justifiant la mise en place d’un nouveau plan, qui devra a nouveau etre evalue dans 6 mois.