Oral 5-aminosalicylic acid for maintenance of surgically-induced remission in Crohn's disease

Background Crohn’s disease (CD) is a chronic inflammatory disorder that can involve any part of the gastrointestinal tract. 5‐Aminosalicylates (5‐ASAs) are locally acting, anti‐inflammatory compounds that reduce inflammation of the colonic mucosa with release profiles that vary among various commercially available formulations. This updated Cochrane review summarizes current evidence on the use of 5‐ASA formulations for maintenance of surgically‐induced remission in CD. Objectives To assess the efficacy and safety of 5‐ASA agents for the maintenance of surgically‐induced remission in CD. Search methods We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register from inception to 16 July 2018. We also searched references, conference abstracts, and trials registers. Selection criteria Randomised controlled trials (RCTs) that included participants with CD in remission following surgery and compared 5‐ASAs to no treatment, placebo or any other active intervention with duration of at least three months were considered for inclusion. Data collection and analysis We used standard methodological procedures expected by Cochrane. The primary outcome was clinical relapse. Secondary outcomes included endoscopic recurrence, radiologic and surgical relapse, adverse events, serious adverse events and withdrawal due to adverse events. Main results Fourteen RCTs (1867 participants) were included in the review. Participants (15 to 70 years) were recruited from gastroenterology hospitals and medical clinics in Europe and North America and followed up between 3 and 72 months. The risk of bias was assessed as 'low' in one study, 'unclear' in seven and as 'high' in six. At 12 months, 36% (20/55) of participants in the 5‐ASA group experienced clinical relapse compared to 51% (28/55) in the no treatment control group (RR 0.71, 95% CI 0.46 to 1.10; low certainty evidence). Moderate certainty evidence suggests that 5‐ASAs are more effective for preventing clinical relapse than placebo. During a follow‐up period of 12 to 72 months, 36% (131/361) of 5‐ASA participants relapsed compared to 43% (160/369) of placebo participants (RR 0.83, 95% CI 0.72 to 0.96; I² = 0%; moderate certainty evidence). At 12 months, 17% (17/101) of the 4 g/day mesalamine group relapsed compared to 26% (27/105) of the 2.4 g/day group (RR 0.65, 95% CI 0.38 to 1.13; moderate certainty evidence). There was no evidence of a difference in clinical relapse rates when 5‐ASA compounds were compared to purine antimetabolites. At 24 months, 61% (103/170) of mesalamine participants relapsed compared to 67% (119/177) of azathioprine participants (RR 0.90, 95% CI 0.76 to 1.07; I² = 28%; low certainty evidence). During 24 months, 50% (9/18) of 5‐ASA participants had clinical relapse compared to 13% (2/16) of adalimumab participants (RR 4.0, 95% CI 1.01 to 15.84; low certainty evidence). The effects of sulphasalazine compared to placebo on clinical relapse rate is uncertain. After 18 to 36 months, 66% (95/143) of participants treated with sulphasalazine relapsed compared to 71% (110/155) in the placebo group (RR 0.88, 95% CI 0.56 to 1.38; I² = 38%; low certainty evidence). The effect of 5‐ASA drugs on safety was uncertain. During 24 months follow‐up, 4% (2/55) of 5‐ASA participants experienced adverse events compared to none (0/55) in the no treatment control group (RR 5.00, 95% CI 0.25 to 101.81; very low certainty evidence). An equal proportion of 5‐ASA participants (10%; 23/241) and placebo (9%; 20/225) groups experienced an adverse event during a follow‐up of 3 to 72 months (RR 1.07, 95% CI 0.60 to 1.91; I² = 0%; low certainty evidence). Adverse event rates were similar in the 5‐ASA and purine analogues groups. However, serious adverse events and withdrawals due to adverse events were more common in participants who received purine analogues than 5‐ASA. At 52 weeks to 24 months, 52% (107/207) of 5‐ASA participants had an adverse event compared to 47% (102/218) of purine analogue participants (RR 1.11, 95% CI 0.97 to 1.27, I² = 0%; low certainty evidence). Four per cent (6/152) of 5‐ASA participants had a serious adverse event compared to 17% (27/159) of purine analogue participants (RR 0.30, 95% CI 0.11 to 0.80; very low certainty evidence). Eight per cent (17/207) of 5‐ASA participants withdrew due to an adverse event compared to 19% (42/218) of purine analogue participants (RR 0.48, 95% CI 0.28 to 0.83; low certainty evidence). Adverse event rates were similar in high and low dose mesalamine participants. After 12 months, 2% (2/101) of 4 g/day mesalamine participants had an adverse event compared to 2% (2/105) of 2.4 g/day participants (RR 1.04, 95% CI 0.15 to 7.24; low certainty evidence). The proportion of participants who experienced adverse events over a 24 month follow‐up in the mesalamine group was 78% (14/18) compared to 69% (11/16) of adalimumab participants (RR 1.13, 95% CI 0.75 to 1.71; very low certainty evidence). None (0/32) of the sulphasalazine participants had an adverse event at 18 months follow‐up compared to 3% (1/34) of the placebo group (RR 0.35, 95% CI 0.01 to 8.38; very low certainty evidence). Commonly reported adverse events in the included studies were diarrhoea, nausea, increased liver function tests, pancreatitis, and abdominal pain. Authors' conclusions 5‐ASA preparations are superior to placebo for the maintenance of surgically‐induced clinical remission in patients with CD (moderate certainty). The number needed to treat to prevent one relapse was 13 patients. The evidence for endoscopic remission is uncertain. The sulphasalazine class of 5‐ASA agents failed to demonstrate superiority against placebo, 5‐ASAs failed to demonstrate superiority compared to no treatment (very low and low certainty). The efficacy of two different doses of the same 5‐ASA and the efficacy of 5‐ASA compared to purine antimetabolites (azathioprine or 6‐mercaptopurine) in maintaining surgically‐induced remission of CD remains unclear. However, purine analogues lead to more serious adverse events and discontinuation due to adverse events. There is a low certainty that 5‐ASA is inferior for maintaining surgically‐induced remission of CD compared to biologics (anti TNF‐ɑ). 5‐ASA formulations appear to be safe with no difference in the occurrence of adverse events or withdrawal when compared with placebo, no treatment or biologics

Analyse de cycle de vie des énergies alternatives pour l'automobile et propositions méthodologiques pour une meilleure évaluation des impacts locaux

Cette thèse, réalisée dans le cadre d'un contrat CIFRE entre l'entreprise Renault et l'Institut PPRIME (UPR CNRS 3346, ISAE-ENSMA-Université de Poitiers), porte sur les analyses de cycles de vie des carburants et énergies alternatives. Le secteur de la mobilité individuelle fait face à de nombreux défis : réchauffement climatique, pollution urbaine, épuisement des ressources, etc. Par conséquent, différentes alternatives se présentent pour répondre à ces défis : agrocarburants, hydrogène, véhicule électrique, etc. L'AVC permet d'évaluer les impacts environnementaux d'un produit ou d'un système. La thèse porte sur la prise en compte des impacts locaux liés à la production et à la consommation des énergies automobiles alternatives en retenant particulièrement les carburants de référence que sont le diesel et l'essence mais aussi les agrocarburants de première génération et l'électricité. Elle traite en particulier des problématiques de pertinence de ces impacts, notamment en cherchant à établie quels impacts retenir et comment les améliorer (prise en compte de la différentiation entre milieu urbain et milieu rural et entre sources hautes et basses). La seconde partie de la thèse étudie l'impact de l'usage du véhicule, en s'intéressant spécialement aux polluants locaux émis selon la norme de dépollution du véhicule et le cycle de roulage utilisé. Le tout vise à obtenir des résultats d'AVC scientifiquement plus robustes et plus facilement interprétables pour une prise de décision fiable, valide dans la durée et cohérente avec les grands enjeux stratégiques de Renault. Les résultats montrent une empreinte environnementale complexe à analyser : alors que l'électricité renouvelable apporte de vrais gains vis-à-vis des carburants conventionnels, l'électricité fossile possède un bilan mitigé selon l'impact regardé. Par ailleurs, les agrocarburants présentent un bilan globalement négatif vis-à-vis des carburants conventionnels. Enfin, la distinction urbain / rural permet de mettre en évidence les gains sur la santé associés au véhicule électrique.This PhD thesis conducted thanks to a CIFRE contract between the company Renault and the PPRIME Institute (UPR CNRS 3346, ISAE-ENSMA-Université de Poitiers), is focused on life cycle analyses for automotive fuels and alternative energies. The individual mobility is facing numerous challenges: global warming, urban pollution, depletion of resources, etc. Therefore, different alternative are now proposed to cope with these challenges: biofuels, hydrogen, electric vehicles, etc. LCA is a tool that allows assessing the environmental impacts of a product system. This PhD thesis is focused on taking into account the local impacts linked with the production and the consumption of diesel, gasoline (these two latters being the reference fuels), biofuels and electricity. It especially deals with the issues associated with the relevance of these impacts, for instance by trying to establish which impacts to select and how to enhance them (difference between urban and rural emissions or between high and near-ground sources). The second part of this PhD thesis studies the impact of the car use, by particularly focusing on the local pollutants emitted according to the aftertreatment standards and the driving cycle. All of this aims at obtaining LCA results that are more relevant and that can be more easily interpreted for a reliable decision-making process compatible with Renault's main strategic issues. The results show a complex environmental footprint: while renewable electricity provides true benefits compared with conventional fuels, fossil electricity has a mixed result, depending on the impact which is considered. Moreover, biofuels have a stronger environmental impact than fossil fuels. Finally, the rural / urban distinction highlights the benefit on human health associated with electric vehicles.POITIERS-ENS Mécanique Aérot (860622301) / SudocPOITIERS-BU Sciences (861942102) / SudocSudocFranceF

Analyse du cycle de vie : évaluation des impacts

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Life cycle risk assessment (LCRA): description of this methodological proposal and a case of study

International audienceThe life cycle of a product is generally characterized by the main following stages: Raw materials acquisition, Manufacturing, processing and formulation, Distribution and transportation, Use, re-use, maintenance, Recycle and Waste management. Considering the life cycle thinking in a risk analysis approach requires the adjustment of the classic risk analysis methodology. In order to build up this new methodology called Life Cycle Risk Assessment (LCRA), we relied on the Life Cycle Assessment (LCA) methodology, which allows the assessment of the potential environmental impacts throughout the life cycle of a system. Once these adjustments made, this LCRA new methodology is explained and applied to two energy pathways for transportation sector: hydrogen (produced from the biomass) and gasoline pathways. The life cycle thinking is not taken into account in the traditional method of risk analysis. To integrate this fundamental concept to the risk analysis methodology following the model of the LCA (Life Cycle Assessment) methodology (ISO 14 040, 14044 and the ILCD Handbook), we made some adjustments to the risk analysis methodology. Each of the LCA's four steps has its counterpart in terms of LCRA (Life Cycle Risk Assessment). The variations between these two methodologies reside on two key steps of the LCA: the inventory (step 2) and the assessment (step 3). The inventory collects data whose nature is different between the two tools. For LCA, collected data are matter and energy flows; these data are qualitative and quantitative ones. For LCRA, the data collected are only qualitative since it is an inventory of dangerous situations. The assessment step consists of three sub-steps: classification, characterization and valuation, and allows a conversion of inventory data into results of impact / risk levels. For LCA, the conversion of inventory data is performed by a calculation using characterization factor. For LCRA, this conversion is done qualitatively by rating and prioritizing risks. However, the goal of sub-step classification is the same in both tools because it links the inventory data and the impacts/risk to be assessed. Just like the flow identified by a LCA that can contribute to different categories of impacts, dangerous situations can cause different types of accidents. Therefore, limitations and hypotheses should be established to make the LCRA methodology usable and relevant in view of the objectives and the applicability of the expected results. Additional file Life Cycle Risk Assessment (LCRA): description of this methodological proposal and a case of study

A new methodology for risk evaluation taking into account the whole life cycle (LCRA): Validation with case study

International audienceThe life cycle of a product is generally characterized by the main following stages: Raw materials acquisition, Manufacturing, processing and formulation, Distribution and transportation, Use, re-use, maintenance, Recycle and Waste management. As regards the process, the following stages are usually distinguished: Raw materials acquisition, Process manufacture, Use and Dismantling at the end of the lifetime. Considering the life cycle concept in a risk analysis approach requires the adjustment of the classic risk analysis methodology. In order to build up this new methodology called LCRA (Life Cycle Risk Assessment), we relied on the LCA (Life Cycle Assessment) methodology, which allows the assessment of the potential environmental impacts throughout the life cycle of a system. Once these adjustments made, this new methodology LCRA is explained and applied to two energy pathways (or life cycles): hydrogen (produced from the biomass) and gasoline pathways

Greenhouse gas emissions of electric vehicles associated with wind and photovoltaic electricity

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Maitrise des risques des cycles de vie : application a l'éolien et au photovoltaïque

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PenDA, a rank-based method for personalized differential analysis: Application to lung cancer

International audienceThe hopes of precision medicine rely on our capacity to measure various high-throughput genomic information of a patient and to integrate them for personalized diagnosis and adapted treatment. Reaching these ambitious objectives will require the development of efficient tools for the detection of molecular defects at the individual level. Here, we propose a novel method, PenDA, to perform Personalized Differential Analysis at the scale of a single sample. PenDA is based on the local ordering of gene expressions within individual cases and infers the deregulation status of genes in a sample of interest compared to a reference dataset. Based on realistic simulations of RNA-seq data of tumors, we showed that PenDA outcompetes existing approaches with very high specificity and sensitivity and is robust to normalization effects. Applying the method to lung cancer cohorts, we observed that deregulated genes in tumors exhibit a cancer-type-specific commitment towards up- or down-regulation. Based on the individual information of deregulation given by PenDA, we were able to define two new molecular histologies for lung adenocarcinoma cancers strongly correlated to survival. In particular, we identified 37 biomarkers whose up-regulation lead to bad prognosis and that we validated on two independent cohorts. PenDA provides a robust, generic tool to extract personalized deregulation patterns that can then be used for the discovery of therapeutic targets and for personalized diagnosis. An open-access, user-friendly R package is available at https://github.com/bcm-uga/penda