Use of the French National Health Data System (SNDS) in pharmacoepidemiology: A systematic review in its maturation phase.

AIM OF THE STUDY: The French National Health Data System (SNDS) comprises healthcare data that cover 99% of the population (over 67 million individuals) in France. The aim of this study was to present an overview of published pharmacoepidemiological studies using the SNDS in its maturation phase. METHODS: We conducted a systematic literature review of original research articles in the Pubmed and EMBASE databases from January 2012 until August 2018. RESULTS: A total of 316 full-text articles were included, with an annual increase over the study period. Only 16 records were excluded after screening because they did not involve the SNDS but other French healthcare databases. The study design was clearly reported in only 66% of studies of which 57% were retrospective cohorts and 22% cross-sectional studies. The reported study objectives were drug utilization (65%), safety (22%) and effectiveness (9%). Almost all ATC groups were studied but the most frequent ones concerned the nervous system in 149 studies (49%), cardiovascular system drugs in 104 studies (34%) and anti-infectives for systemic use in 50 studies (16%). CONCLUSION: The SNDS is of growing interest for studies on drug use and safety, which could be conducted more in specific populations, including children, pregnant women and the elderly, as these populations are often not included in clinical trials.

Evolution of public funding since primary care research was considered as a priority research domain in france.

PURPOSE: Annually, the French Ministry of Health funds clinical research projects based on a national call for projects. Since 2013, the Ministry has prioritized funding of primary care. Projects selected for funding are made public without distinguishing the specific area of research. The objective of this study was to identify and describe the evolution of the primary care research projects funded by the Ministry of Health between 2013 and 2019. METHOD: We reviewed all of the 1796 medical research projects funded between 2013 and 2019 and categorized projects as primary care projects by using a list of specific keywords. This list was established through two approaches: (1) selected by an expert committee, the RECaP primary care working group, and (2) using an automated textual analysis of published articles in the field. The keywords were used to screen the titles of the medical research projects funded. The abstracts (at www. CLINICALTRIALS: gov ) or details (from project leaders) were then analyzed by two independent reviewers to determine true primary care projects. RESULTS: Finally, 49 primary care projects were identified, representing 2.7% of all medical research projects funded, without any significant change over the period. These projects were predominantly interventional (69%), with a median number of patients expected per project of 902. CONCLUSION: Despite the prioritization of primary care research in 2013 by the French ministry of health, the number and proportion of projects funded remains low, with no significant change over the years. TRIAL REGISTRATION: Not applicable.

Hepatitis C virus/human interactome identifies SMURF2 and the viral protease as critical elements for the control of TGF-ß signaling.

TGF-ß signaling induces epithelial to mesenchymal transition (EMT) and plays an important role in hepatocellular carcinoma (HCC) development. Clinical observations indicate that hepatitis C virus (HCV) chronic infection, which is a major cause of HCC, induces TGF-ß signaling perturbations. Here, we investigate the mechanisms by which HCV nonstructural proteins interfere with TGF-ß signaling, in human hepatoma cell lines expressing HCV subgenomic replicon. A transcriptomic study showed that TGF-ß stimulation of these cells resulted in a protumoral gene expression profile and in up-regulation of EMT-related genes compared to control interferon-treated cells not expressing HCV proteins. We found that the viral protease NS3-4A interacted with SMURF2, a negative regulator of TGF-ß signaling. In cells expressing HCV subgenomic replicon or NS3-4A, TGF-ß stimulation induced an increased expression of SMAD-dependent genes compared to control cells. This enhanced signaling was suppressed by SMURF2 overexpression and mimicked by SMURF2 silencing. In addition, NS3-4A expression resulted in an increased and prolonged TGF-ß-induced phosphorylation of SMAD2/3 that was abrogated by SMURF2 overexpression. Neither NS3-4A protease activity nor SMURF2 ubiquitin-ligase activity was required to affect TGF-ß signaling. Therefore, by targeting SMURF2, NS3-4A appears to block the negative regulation of TGF-ß signaling, increasing the responsiveness of cells to TGF-ß.