[Organising an investigation site: a national training reference document]. / Organiser un site investigateur : un référentiel national de formation pédagogique.

OBJECTIVE: Several surveys have shown a declining performance of French investigators in conducting clinical trials. This is partly due to insufficient and heterogeneous investigator training and site organisation. A multidisciplinary group was set up to propose solutions. We describe the tools developed to improve study site organisation. RESULTS: This working group was made up of clinical research experts from academia, industry, drug regulatory authorities, general practice, and consulting. Methods and tools were developed to improve site organisation. CONCLUSIONS: The proposed tools mainly focus on increasing investigators' awareness of their responsibilities, their research environment, the importance of a thorough feasibility analysis, and the implementation of active patient recruitment strategies. These tools should be able to improve site organisation and performances in conducting clinical trials.

Influence of vitamins, trace elements, and iron on lipid peroxidation reactions in all-in-one admixtures for neonatal parenteral nutrition.

BACKGROUND: The purpose of this study was to evaluate the effect of vitamins, trace elements, or iron on lipid peroxidation in all-in-one parenteral nutrition (PN) admixtures for preterm neonates. METHODS: Malondialdehyde (MDA) concentrations were analyzed over a 24-hour period (H1-H24) in lipid-containing PN solutions that have a composition identical to that used in the routine clinical care of preterm infants. Six different solutions were prepared and evaluated when exposed to ambient light and light-protected conditions as follows: control (without vitamins [Vit], trace elements [TE], or iron [Fe] [Vit-TE-Fe-]), solution 1 (Vit+TE+Fe-), solution 2 (Vit+TE-Fe-), solution 3 (Vit-TE+Fe-), solution 4 (Vit-TE-Fe+), and solution 5 (Vit+TE+Fe+). RESULTS: MDA concentrations in PN solutions were significantly higher at H24 than at H0 when they contained multivitamins (P < .001), trace elements (P = .002), or iron saccharate (P = .018). MDA concentration was particularly high when all 3 micronutrients were present (P < .001) or when the solutions were exposed to ambient light. In solutions containing iron, MDA concentrations were elevated at H0, and levels did not change whether protected from (P < .001) or exposed to (P < .001) from light. CONCLUSIONS: The addition of vitamins and trace elements to PN solutions induces a significant increase in peroxidation products, which are lowered when admixtures are protected from light. Iron should not be included in these solutions, even if solutions are light-protected. By following these conditions it is possible to use all-in-one admixtures in the nutrition management of preterm infants.

Posaconazole-increased vincristine neurotoxicity in a child: a case report.

A 9-year-old girl was managed according to the COPRALL 04 protocol for treatment of a relapse of acute lymphoblastic leukemia. Owing to a previous case of disseminated fusariosis, posaconazole was started 5 days before initiation of chemotherapy. Six days after the last dose of vincristine, the child reported symptoms of severe peripheral neuropathy, abdominal cramps, and constipation. After this, she developed fluctuations in her level of consciousness and seizures. After cessation of therapy with posaconazole, a complete resolution of the above occurred within 7 days. This case illustrates the possibility of vincristine toxicity exacerbated by coadministration of posaconazole. As posaconazole is an inhibitor of the isoenzyme CYP3A4, interactions with drugs that are metabolized via this pathway, such as vincristine, can be anticipated. Another possibility is that, like itraconazole, posaconazole may also inhibit P-glycoprotein-mediated vincristine efflux. Although case reports of neurotoxicity owing to possible interaction between itraconazole and vincristine exist in the literature, only 1 case report relating to the possible interaction between posaconazole and vincristine exists. Clinicians should be made aware of this possible drug-drug interaction.