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Sainte-Foy-lès-Lyon, France

Marchant I.,University of Valparaiso | Boissel J.-P.,Novadiscovery | Nony P.,CNRS Biometry and Evolutionary Biology Laboratory | Gueyffier F.,CNRS Biometry and Evolutionary Biology Laboratory | And 2 more authors.
PLoS ONE | Year: 2015

Objective: To examine the performances of an alternative strategy to decide initiating BP-lowering drugs called Proportional Benefit (PB). It selects candidates addressing the inequity induced by the high-risk approach since it distributes the gains proportionally to the burden of disease by genders and ages. Study Design and Setting: Mild hypertensives from a Realistic Virtual Population by genders and 10-year age classes (range 35-64 years) received simulated treatment over 10 years according to the PB strategy or the 2007 ESH/ESC guidelines (ESH/ESC). Primary outcomes were the relative life-year gain (life-years gained-to-years of potential life lost ratio) and the number needed to treat to gain a life-year. A sensitivity analysis was performed to assess the impact of changes introduced by the ESH/ESC guidelines appeared in 2013 on these outcomes. Results: The 2007 ESH/ESC relative life-year gains by ages were 2%; 10%; 14% in men, and 0%; 2%; 11% in women, this gradient being abolished by the PB (relative gain in all categories = 10%), while preserving the same overall gain in life-years. The redistribution of benefits improved the profile of residual events in younger individuals compared to the 2007 ESH/ESC guidelines. The PB strategy was more efficient (NNT = 131) than the 2013 ESH/ESC guidelines, whatever the level of evidence of the scenario adopted (NNT = 139 and NNT = 179 with the evidence-based scenario and the opinion-based scenario, respectively), although the 2007 ESH/ESC guidelines remained the most efficient strategy (NNT = 114). Conclusion: The Proportional Benefit strategy provides the first response ever proposed against the inequity of resource use when treating highest risk people. It occupies an intermediate position with regards to the efficiency expected from the application of historical and current ESH/ESC hypertension guidelines. Our approach allows adapting recommendations to the risk and resources of a particular country. © 2015 Marchant et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source

Poret A.,Novadiscovery | Boissel J.-P.,CNRS Biometry and Evolutionary Biology Laboratory
Comptes Rendus - Biologies | Year: 2014

Target identification aims at identifying biomolecules whose function should be therapeu- tically altered to cure the considered pathology. An algorithm for in silico target identification using Boolean network attractors is proposed. It assumes that attractors correspond to phenotypes produced by the modeled biological network. It identifies target combinations which allow disturbed networks to avoid attractors associated with pathological phenotypes. The algorithm is tested on a Boolean model of the mammalian cell cycle and its applications are illustrated on a Boolean model of Fanconi anemia. Results show that the algorithm returns target combinations able to remove attractors associated with pathological phenotypes and then succeeds in performing the proposed in silico target identification. However, as with any in silico evidence, there is a bridge to cross between theory and practice. Nevertheless, it is expected that the algorithm is of interest for target identification. © 2014 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved. Source

Novacare and Novadiscovery | Date: 2011-04-05

This invention relates to computer systems for conducting drug and biomarker discovery, drug development, and personalized medicine, and more generally managing healthcare, and in particular to a system and method for predicting the therapeutic value of a treatment to an individual. The treatment is associated with a function that describes, in a population of individuals, the benefit from a treatment, generally in terms of occurrence of a medical event under treatment, as a function of the risk (e.g., the occurrence of the medical event) without said treatment.

Marchant I.,University of Valparaiso | Marchant I.,IMTh Institute for Theoretical Medicine | Marchant I.,CNRS Biometry and Evolutionary Biology Laboratory | Nony P.,IMTh Institute for Theoretical Medicine | And 17 more authors.
PLoS ONE | Year: 2011

Background: The prediction of the public health impact of a preventive strategy provides valuable support for decision-making. International guidelines for hypertension management have introduced the level of absolute cardiovascular risk in the definition of the treatment target population. The public health impact of implementing such a recommendation has not been measured. Methodology/Principal Findings: We assessed the efficiency of three treatment scenarios according to historical and current versions of practice guidelines on a Realistic Virtual Population representative of the French population aged from 35 to 64 years: 1) BP≥160/95 mm Hg; 2) BP≥140/90 mm Hg and 3) BP≥140/90 mm Hg plus increased CVD risk. We compared the eligibility following the ESC guidelines with the recently observed proportion of treated amongst hypertensive individuals reported by the Etude Nationale Nutrition Santé survey. Lowering the threshold to define hypertension multiplied by 2.5 the number of eligible individuals. Applying the cardiovascular risk rule reduced this number significantly: less than 1/4 of hypertensive women under 55 years and less than 1/3 of hypertensive men below 45 years of age. This was the most efficient strategy. Compared to the simulated guidelines application, men of all ages were undertreated (between 32 and 60%), as were women over 55 years (70%). By contrast, younger women were over-treated (over 200%). Conclusion: The global CVD risk approach to decide for treatment is more efficient than the simple blood pressure level. However, lack of screening rather than guideline application seems to explain the low prescription rates among hypertensive individuals in France. Multidimensional analyses required to obtain these results are possible only through databases at the individual level: realistic virtual populations should become the gold standard for assessing the impact of public health policies at the national level. © 2011 Marchant et al. Source

Monteiro Sousa C.,Novadiscovery | Monteiro Sousa C.,University Claude Bernard Lyon 1 | Boissel J.-P.,Novadiscovery | Gueyffier F.,University Claude Bernard Lyon 1 | Olivera-Botello G.,Novadiscovery
Comptes Rendus - Biologies | Year: 2015

Sepsis is defined as a syndrome combining a systemic inflammatory response with a documented infection. It may progress to more serious cases such as septic shock following the failure of one or more organs and the emergence of hemodynamic defects. Assuming that the emergence of serious septic syndromes may be partially explained by the early loss of regulation of the inflammatory response, we decided to compare, in a transcriptomic perspective, the biological mechanisms expressed during an induced systemic inflammatory response with those expressed during severe septic syndromes. By using open-access transcriptomic databases, we first studied the kinetics of an induced inflammatory response. The use of functional analysis helped us identify discriminating biological mechanisms, such as the mTOR signaling pathway, between the pathological cases of sepsis and non-pathological (i.e., the artificially induced SIRS) cases. © 2015 Académie des sciences. Source

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