Cost of exome analysis in patients with intellectual disability: a micro-costing study in a French setting.

BACKGROUND: With the development of next generation sequencing technologies in France, exome sequencing (ES) has recently emerged as an opportunity to improve the diagnosis rate of patients presenting an intellectual disability (ID). To help French policy makers determine an adequate tariff for ES, we aimed to assess the unit cost per ES diagnostic test for ID from the preparation of the pre-analytical step until the report writing step and to identify its main cost drivers. METHODS: A micro-costing bottom-up approach was conducted for the year 2018 in a French setting as part of the DISSEQ study, a cost-effectiveness study funded by the Ministry of Health and performed in collaboration with the GAD (Génétique des Anomalies du Développement), a genetic team from the Dijon University Hospital, and a public sequencing platform, the Centre National de Recherche en Génomique Humaine (CNRGH). The analysis was conducted from the point of view of these two ES stakeholders. All of the resources (labor, equipment, disposables and reagents, reusable material) required to analyze blood samples were identified, collected and valued. Several sensitivity analyses were performed. RESULTS: The unit nominal cost per ES diagnostic test for ID was estimated to be €2,019.39. Labor represented 50.7% of the total cost. The analytical step (from the preparation of libraries to the analysis of sequences) represented 88% of the total cost. Sensitivity analyses suggested that a simultaneous price decrease of 20% for the capture kit and 50% for the sequencing support kit led to an estimation of €1,769 per ES diagnostic test for ID. CONCLUSION: This is the first estimation of ES cost to be done in the French setting of ID diagnosis. The estimation is especially influenced by the price of equipment kits, but more generally by the organization of the centers involved in the different steps of the analysis and the time period in which the study was conducted. This information can now be used to define an adequate tariff and assess the efficiency of ES. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03287206 on September 19, 2017.

Consistent and Transferable Force Fields for Statistical Copolymer Systems at the Mesoscale.

The statistical trajectory matching (STM) method was applied successfully to derive coarse grain (CG) models for bulk properties of homopolymers. The extension of the methodology for building CG models for statistical copolymer systems is much more challenging. We present here the strategy for developing CG models for styrene-butadiene-rubber, and we compare the quality of the resulting CG force fields on the structure and thermodynamics at different chemical compositions. The CG models are used through the use of a genuine mesoscopic method called the dissipative particle dynamics method and compared to high-resolution molecular dynamics simulations. We conclude that the STM method is able to produce coarse-grained potentials that are transferable in composition by using only a few reference systems. Additionally, this methodology can be applied on any copolymer system.

[Pharmaceutical supply of human plasminogen replacement therapy for the treatment of ligneous conjunctivitis: Logistics for a university hospital]. / Approvisionnement hospitalier en plasminogène humain substitutif pour le traitement de la conjonctivite ligneuse : comment faire en pratique ?

In order to treat a pediatric patient with ligneous conjunctivitis secondary to congenital plasminogen deficiency, a supply of topically administered replacement human plasminogen has been required. In the absence of market approval, this blood-derived drug is managed by a temporary authorisation for nominative use, allowing monthly hospital dispensations. To ensure regulatory compliance and proper use of the drug, it took two years of interactions between various hospital departments and the laboratory to define the pharmaceutical supply chain in our hospital and allow the patient to receive treatment. The main difficulties lie in respecting the cold chain of this drug stored frozen in the bottles not ready for use. Transportation from the laboratory to the patient's home via the hospital pharmacy is carried out in calibrated conditions, ensuring a temperature below -20°C for 72h. Reception and dispensing steps were combined into a single pharmaceutical service in order to optimise transport time while ensuring the safety and traceability of the drug lots. Each month, a date is scheduled between the hospital pharmacy, the laboratory and the family to ensure that delivery and dispensing take place on the same day. Appropriate use and handling are explained to the family. However, two issues remain to be addressed by the manufacturer to facilitate future use of human plasminogen: the thermostability problem, which does not allow stays away from home longer than three days, and self-administration by the child, which is unlikely to be feasible due to handling difficulties.

[Use of calcium channel blockers (CCB) for tocolysis in France and abroad]. / Utilisation des inhibiteurs des canaux calciques (ICC) en tocolyse en France et à l'étranger.

OBJECTIVES: Calcium channel blockers (CCB) are routinely off-label used for tocolysis. The purpose of this study is to establish an inventory of the use of CCB for tocolysis in France and abroad. MATERIALS AND METHODS: Four complementary approaches were performed: (i) a literature review of clinical practice and guidelines of scientific societies; (ii) a national declarative practice survey among French tertiary care centers; (iii) a regional declarative practice survey among all maternities of the Midi-Pyrénées Perinatal Network (MATERMIP); (iv) an evaluation of outpatient tocolysis prescription, analyzing the departmental database EFEMERIS in order to examine drug prescribing during pregnancy. RESULTS: CCB appear to be currently used as first-line, initial tocolysis, in the majority of French maternity hospitals (82.5% of tertiary care centers). Oral Nifedipine is the predominant regimen (86%). CCB utilization rates appear higher than those reported in 2005 in the EVAPRIMA study. Beta-agonists appear rarely prescribed in 1st line (poor maternal tolerance) and even abandoned by many institutions (75% of tertiary care centers). Using a maintenance tocolysis (usually by long-acting CCB) seems to vary depending on the hospitals. It would be prescribed in more than 50% of cases (and probably more in type 1 or 2 hospitals), despite the lack of demonstrated benefit. Furthermore, we can estimate that about 1.5 to 2% of outpatient pregnant women receive a prescription of Nifedipine LP in France. CONCLUSION: CCB (especially Nifedipine) are widely used in the treatment of threatened preterm labor in France, regardless of the type of hospital. The terms of off-label prescribing are not met.

[A relevant choice for corticoid eye drops: solution or suspension?]. / Quel choix pour un collyre de corticoïdes : solution ou suspension ?

INTRODUCTION: The various forms of ophthalmic pharmaceutical presentation of steroids is proliferating on the market: solutions, gels, and suspensions. Suspensions are characterized by particles in solution and require agitation before instillation. This trial studied the impact of agitation on the corticoid concentration of eye drop solutions, gels, and suspensions. METHODS: Corticosteroid levels in a drop of a dexamethasone solution or suspension or betamethasone suspension or gel were compared using liquid chromatography. These levels were measured after shaking for 5, 10, 30s, and 1 min using a vortex or without shaking. RESULTS: The results of this study show that, whatever shaking time was used, the suspension form seems less suited to instillation of corticosteroids. The suspension did not deliver consistent levels of corticosteroids (mean between 23 and 99%) compared to solutions and gels, which released about 100% of the corticosteroid content in each drop. CONCLUSION: Physicians, ophthalmologists, and pharmacists should remind the patient of the proper use of these suspensions before instillation. In cases of treatment failure, it is necessary to check the instillation method before questioning patient compliance.