Clichy Sous Bois

Increasing emergence of multidrug resistant (MDR) bacteria worldwide is now considered one of the most urgent threats to global health. The association between increase of antibiotics consumption and resistance emergence has been well documented for all patients admitted to the Intensive care unit (ICU) who received antibiotic treatment1 and for patients treated for ventilator associated pneumonia (VAP). Reduction of use of antibiotics is a major point in the war against antimicrobial resistance. VAP is the first cause of healthcare-associated infections in ICU and more than half of antibiotics prescriptions in ICU are due to VAP. Current international guidelines define VAP as a pneumonia occurring\>48 hours after endotracheal intubation and distinguishes early onset VAP occurring in the first five days after admission and late VAP, occurring after. Once the diagnosis of pneumonia under MV has been made, initiation of antibiotic treatment must be prompt but there is no clear consensus on its duration. In the case of a good clinical response to treatment, it has been shown in some situations that short course antibiotics can be effective without side effects and antimicrobial stewardship initiatives can be applied successfully and effectively to the management of Community Acquired Pneumonia (CAP). American guidelines strongly recommend a 7-day course of antibiotic therapy rather than a longer duration but remark that "there exist situations in which a shorter or longer duration of antibiotics may be indicated, depending upon the rate of improvement of clinical, radiologic, and laboratory parameters". The hypothesis is that an antimicrobial stewardship is possible in the treatment of VAP with no increase in the rate of all-cause mortality, treatment failure or occurrence of new episode of pneumonia. The objective is to investigate whether an antimicrobial stewardship for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in terms of all-cause mortality, treatment failure or occurrence of new episode of pneumonia. This study will be a prospective, national multicenter (31 centers), phase III, comparative randomized (1:1), single-blinded clinical trial comparing two management strategies of treatment of pneumonia on the basis of two parallel arms: Experimental group: Antimicrobial stewardship based on daily clinical assessment of clinical cure. Control group: standard management: duration of appropriate antibiotic therapy for confirmed VAP according to guidelines. The primary endpoint is a hierarchical endpoint with a first non-inferiority criteria and a second efficacy criteria.

The diagnosis of hereditary pancreatitis (HP) is based on a genetic criterion - identification of a mutation in the PRSS1 gene - or a genealogical criterion - the presence of chronic pancreatitis in at least 2 first-degree relatives or at least 3 second-degree relatives, in the absence of other identified predisposing factors (in particular chronic alcohol consumption). It is now recommended to look for PH in cases of pancreatitis of unknown origin in young patients or those with a family history. The first mutation in the PRSS1 gene, R122H, was described in 1996. Today, \>100 PRSS1 variants are known. Of these, 26 variants are considered 'pathological' and 51 'benign', with the other variants having a less well-defined clinical outcome. PH is a rare cause of pancreatitis (\< 1%). Its prevalence in France is estimated at 0.3/100,000 people. Because of its rarity, there are few studies to decipher this disease. Fewer than 1,000 patients are affected in France. In practice, there is great variability in the phenotypic expression of mutations, even for a similar mutation in the same family. There is a lack of scientific knowledge, which means that patients with PH cannot be treated optimally. In this study, patients carrying a PRSS1 mutation will be identified from the patient lists of the three French genetics laboratories (Brest University Hospital, Cochin-Paris University Hospital, Lille University Hospital) carrying out PRSS1 gene analysis. Patients will be included by the doctors currently treating them. The cohort will be updated as new patients are diagnosed, and the completeness of the cases recorded in the database will be checked every 5 years. Patients are seen annually as part of their care, so medical data can be collected at each visit. Questionnaires will be administered every 5 years during a care visit. The aim of the study is to assess the incidence of pancreatic adenocarcinoma in the cohort and describe the natural history of hereditary pancreatitis linked to a mutation in PRSS1.