First evaluation of drug-in-cyclodextrin-in-liposomes as an encapsulating system for nerolidol

International audienc

Impact of a targeted monitoring on data-quality and data-management workload of randomized controlled trials a prospective comparative study

International audienceAims: Monitoring risk‐based approaches in clinical trials are encouraged by regulatory guidance. However, the impact of a targeted source data verification (SDV) on data‐management (DM) workload and on final data quality needs to be addressed.Methods: MONITORING was a prospective study aiming at comparing full SDV (100% of data verified for all patients) and targeted SDV (only key data verified for all patients) followed by the same DM program (detecting missing data and checking consistency) on final data quality, global workload and staffing costs.Results: In all, 137,008 data including 18,124 key data were collected for 126 patients from six clinical trials. Compared to the final database obtained using the full SDV monitoring process, the final database obtained using the targeted SDV monitoring process had a residual error rate of 1.47% [95% confidence interval, 1.41% to 1.53%] on overall data and 0.78% [95% confidence interval, 0.65% to 0.91%] on key data. There were nearly four times more queries per study with targeted SDV than with full SDV (mean±SD: 132±101 vs 34±26; p=0.03). For a handling time of 15 min per query, the global workload of the targeted SDV monitoring strategy remained below that of the full SDV monitoring strategy. From 25 minutes per query, it was above increasing progressively to represent a 50% increase for 45 minutes per query.Conclusion: Targeted SDV monitoring is accompanied by increased workload for DM, which allows to obtain a small proportion of remaining errors on key data (<1%), but may substantially increase trial costs

Extension to one week of verbal memory consolidation assessment.

International audienc

Exome Sequencing Reveals Signal Transduction Genes Involved in Impulse Control Disorders in Parkinson's Disease

International audienceIntroduction: Impulse control disorders (ICDs) frequently complicate dopamine agonist (DA) therapy in Parkinson's disease (PD). There is growing evidence of a high heritability for ICDs in the general population and in PD. Variants on genes belonging to the reward pathway have been shown to account for part of this heritability. We aimed to identify new pathways associated with ICDs in PD.Methods: Thirty-six Parkinsonian patients on DA therapy with (n = 18) and without ICDs (n = 18) matched on age at PD's onset, and gender was selected to represent the most extreme phenotypes of their category. Exome sequencing was performed, and variants with a strong functional impact in brain-expressed genes were selected. Allele frequencies and their distribution in genes and pathways were analyzed with single variant and SKAT-O tests. The 10 most associated variants, genes, and pathways were retained for replication in the Parkinson's progression markers initiative (PPMI) cohort.Results: None of markers tested passed the significance threshold adjusted for multiple comparisons. However, the "Adenylate cyclase activating" pathway, one of the top associated pathways in the discovery data set (p = 1.6 × 10-3) was replicated in the PPMI cohort and was significantly associated with ICDs in a post hoc pooled analysis (combined p-value 3.3 × 10-5). Two of the 10 most associated variants belonged to genes implicated in cAMP and ERK signaling (rs34193571 in RasGRF2, p = 5 × 10-4; rs1877652 in PDE2A, p = 8 × 10-4) although non-significant after Bonferroni correction.Conclusion: Our results suggest that genes implicated in the signaling pathways linked to G protein-coupled receptors participate to genetic susceptibility to ICDs in PD

Comparison of the effect of direct-acting antiviral with and without ribavirin on cyclosporine and tacrolimus clearance values results from the ANRS CO23 CUPILT cohort

International audienc

Necrotizing external otitis: analysis of relapse risk factors in 66 patients managed during a 12 year period

International audienceAbstract Background Necrotizing external otitis (NEO) is a severe infection of the skull base that occurs generally in the elderly and/or in diabetic recipients. There are few data in the literature about the therapeutic management of this complex bone infection. Objectives To analyse relapses after NEO treatment completion, and to describe the clinical features of NEO. Methods We performed a retrospective cohort study in the Lyon regional reference centre for the management of complex bone and joint infections. Consecutive cases of NEO from 1 January 2006 to 31 December 2018 were included. The primary outcome was the relapse of NEO. Variables were analysed using Cox regression survival analysis with adjusted hazard ratio (aHR) and Kaplan–Meier curve. Results Sixty-six patients were included. Median age was 75 (IQR 69–81) years and 46 (70%) patients were diabetic. Eleven patients (17%) had temporomandibular arthritis, 10 (15%) cranial nerve paralysis, 2 (3%) cerebral thrombophlebitis, and 2 (3%) contiguous abscess. Microbiological documentation was obtained in 56 patients and revealed Pseudomonas aeruginosa in 44/56 patients (79%). Nine (14%) cases had no microbiological documentation. Antibiotic therapy was dual for 63 (95%) patients. During a median follow-up of 27 (IQR 12–40) months, 16 out of 63 (25%) patients experienced a relapse. Fungal infection was significantly associated with relapse [aHR 4.1 (95% CI 1.1–15); P = 0.03]. Conclusions NEO is a severe bone infection, mainly (but not exclusively) caused by P. aeruginosa, which occurs in elderly and diabetic recipients. Fungal infections at baseline significantly impact the outcome