Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Two antifibrotic drugs, pirfenidone and nintedanib, are approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis (IPF). In this analysis, treatment patterns of European patients with IPF were investigated to understand antifibrotic prescribing and identify unmet needs in IPF treatment practice. Methods: Between February and March 2016, respiratory physicians from France, Germany, Italy, Spain, and the UK participated in an online questionnaire designed to collect information on IPF treatment patterns in patients under their care. Patients were categorized as treated (received approved antifibrotics) or untreated (did not receive approved antifibrotics, but may have received other unapproved therapies). Classification of IPF diagnosis (confirmed/suspected) and severity ('mild'/'moderate'/'severe') for each patient was based on the individual physician's report. Patients' perspectives were not recorded in this study. Results: In total, 290 physicians responded to the questionnaire. Overall, 54% of patients with IPF did not receive treatment with an approved antifibrotic. More patients had a confirmed IPF diagnosis in the treated (84%) versus the untreated (51%) population. Of patients with a confirmed diagnosis, 40% did not receive treatment. The treated population was younger than the untreated population (67 vs 70 years, respectively; p = 0.01), with more frequent multidisciplinary team evaluation (83% vs 57%, respectively; p = 0.01). A higher proportion of untreated patients had forced vital capacity > 80% at diagnosis versus treated patients. Of patients with 'mild' IPF, 71% did not receive an approved antifibrotic versus 41% and 60% of patients with 'moderate' and 'severe' IPF, respectively. Conclusions: Despite the availability of antifibrotic therapies, many European patients with confirmed IPF do not receive approved antifibrotic treatment. Importantly, there appears to be a reluctance to treat patients with 'mild' or 'stable' disease, and instead adopt a 'watch and wait' approach. More education is required to address diagnostic uncertainty, poor understanding of IPF and its treatments, and issues of treatment access. There is a need to increase physician awareness of the benefits associated with antifibrotic treatment across the spectrum of IPF severity.
ISSN: 1471-2466

hal-01616061
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616061
DOI : 10.1186/s12890-017-0468-5
PUBMED : 28915874

Éditeur(s) : HAL CCSD
Résumé : National audience
The last study describing the epidemiology of malaria in French Guiana was published 20 years ago. Yet French Guiana in the Americas along with Mayotte in the Indian Ocean is the only French territory with persisting endemic malaria. The purpose of this study is to provide an update based on official malaria surveillance data as well as on information from hospital records and various field surveys that have been carried out in recent years. Due to recurrent problems in collecting thorough, continuous, and consistent data, exact determination of incidence by plasmodium species has always been difficult in French Guiana. These problems include not only the remote location of endemic areas and intense unpredictable migration patterns but also poor data collection methods that do not always ensure consistency and homogeneity. Another factor hindering thorough collection of conventional epidemiological data is the requirement for rapid effective treatment in remote regions. The overall incidence of malaria in French Guiana appears to have remained stable since the beginning of the decade with an average of 3,920 case reports per year for an incidence rate of 20 per thousand, noting that three fourths of the 206,000 inhabitants of French Guiana live outside of endemic areas. Overall involvement of P. falciparum and P. vivax appears to be equal with P. malariae accounting for only 2.6% of cases. Trends in recent years indicate an increase in the number of cases involving P. vivax especially in the eastern zones, i.e. in the Oyapock focus where annual incidences in children have reached up to 500 per thousand and in the whole region located between Saint Georges and Cayenne. Conversely a decrease in endemic levels has been observed in western areas, especially for P. falciparum in the upper and middle focuses of the Maroni. Most zones now causing problems are located near migration points, particularly in relation with clandestine gold panning activities. In the coastal strip where the three main cities with most of the population are located, most reported cases are imported but local cases may occur. In general local transmission in these areas has been promptly controlled but trends indicate that incidence of these events may be rising. Anopheles darlingi is still recognized as the main vector but its role in transmission is less obvious in eastern areas where increasing evidence suggests that other species may contribute to maintaining endemic levels. These findings indicate that the extensive resources deployed in this French territory (public financing, health care network, public awareness campaigns, and training of health care personnel in diagnosis and treatment of malaria) have helped reduce the number of severe cases in an unfavorable epidemiological setting.
Médecine tropicale : revue du Corps de santé colonial

pasteur-00583514
https://hal-riip.archives-ouvertes.fr/pasteur-00583514
PUBMED : 19499726

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
INTRODUCTION: Hydroxyurea is an antimetabolite drug used in the treatment of myeloproliferative disorders. Common adverse effects include haematological, gastrointestinal cutaneous manifestations, and fever. Hydroxyurea-induced pneumonitis is unusual. CASE REPORT: A female patient was treated with hydroxyurea for polycythemia vera. She was admitted 20 days after commencing treatment with a high fever, productive cough, clear sputum and nausea. A chest CT-scan showed diffuse ground-glass opacities. Microbiological investigations were negative. The symptoms disappeared a few days after discontinuation of the drug and rechallenge led to a relapse of symptoms. CONCLUSION: Our case and 15 earlier cases of hydroxyurea-induced pneumonitis are reviewed. Two patterns of this disease may exist: an acute febrile form occurring within 1 month of introduction of hydroxyurea and a subacute form without fever. Even if uncommon, one should be aware of this complication of hydroxyurea.
Revue des Maladies Respiratoires

hal-01072996
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01072996
DOI : 10.1016/j.rmr.2013.09.001
PUBMED : 24878159

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The implication of oxidative stress as primary mechanism inducing doxorubicin (DOX) cardiotoxicity is still questionable as many in vitro studies implied supra-clinical drug doses or unreliable methodologies for reactive oxygen species (ROS) detection. The aim of this study was to clarify whether oxidative stress is involved in compliance with the conditions of clinical use of DOX, and using reliable tools for ROS detection. We examined the cytotoxic mechanisms of 2 μM DOX 1 day after the beginning of the treatment in differentiated H9c2 rat embryonic cardiac cells. Cells were exposed for 2 or 24 h with DOX to mimic a single chronic dosage or to favor accumulation, respectively. We found that apoptosis was prevalent in cells exposed for a short period with DOX: cells showed typical hallmarks as loss of anchorage ability, mitochondrial hyperpolarization followed by the collapse of mitochondrial activity, and nuclear condensation. Increasing the exposure period favored a shift to necrosis as the cells preferentially exhibited early DNA impairment and nuclear swelling. In either case, measuring the fluorescence lifetime of 1-pyrenebutyric acid or the intensities of dihydroethidium or amplex red showed a consistent pattern in ROS production which was a slight increased level far from representative of an oxidative stress. Moreover, pre-treatment with dexrazoxane provided a cytoprotective effect although it failed to detoxify ROS. Our data support that oxidative stress is unlikely to be the primary mechanism of DOX cardiac toxicity in vitro.
ISSN: 0300-8177

hal-01285736
https://hal-univ-perp.archives-ouvertes.fr/hal-01285736
DOI : 10.1007/s11010-016-2653-x

Éditeur(s) : HAL CCSD National Academy of Sciences
Résumé : International audience
All evolutionary biologists are familiar with evolutionary units that evolve by vertical descent in a tree-like fashion in single lineages. However, many other kinds of processes contribute to evolutionary diversity. In vertical descent, the genetic material of a particular evolutionary unit is propagated by replication inside its own lineage. In what we call introgressive descent, the genetic material of a particular evolutionary unit propagates into different host structures and is replicated within these host structures. Thus, introgressive descent generates a variety of evolutionary units and leaves recognizable patterns in resemblance networks. We characterize six kinds of evolutionary units, of which five involve mosaic lineages generated by introgressive descent. To facilitate detection of these units in resemblance networks, we introduce terminology based on two notions, P3s (subgraphs of three nodes: A, B, and C) and mosaic P3s, and suggest an apparatus for systematic detection of introgressive descent. Mosaic P3s correspond to a distinct type of evolutionary bond that is orthogonal to the bonds of kinship and genealogy usually examined by evolutionary biologists. We argue that recognition of these evolutionary bonds stimulates radical rethinking of key questions in evolutionary biology (e.g., the relations among evolutionary players in very early phases of evolutionary history, the origin and emergence of novelties, and the production of new lineages). This line of research will expand the study of biological complexity beyond the usual genealogical bonds, revealing additional sources of biodiversity. It provides an important step to a more realistic pluralist treatment of evolutionary complexity.
ISSN: 0027-8424

hal-01544803
https://hal.archives-ouvertes.fr/hal-01544803
DOI : 10.1073/pnas.1206541109

Éditeur(s) : HAL CCSD
Résumé : Weather stations are constantly provided with thousands of satellite images with a view to anticipating the progress of natural phenomenons. This constant flow ofinformation requires speed and a strict analysis. Consequently, it is absolutely necessary to implement systems capable of working night and day, in order to make assessments. In this article, we suggest a method relying on pattern recognition investigation techniques, such as segmentation and classification. These techniques will be used to locate and discriminate the banks of clouds coming from images picked up by the GOES geostationary satellite. Treatment of the cloud shapes which have been found can be carried out, using operations, such as mathematical morphology, so as to draw discriminating characteristics. Classifier systems are used in order to interpret the characteristics which have been obtained and to conduct cloud classification.
15th Meeting of the Caribbean Academy of Sciences
Gosier, Guadeloupe

hal-00524903
https://hal.archives-ouvertes.fr/hal-00524903

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Malaria is a major public health problem in French Guiana, where Plasmodium vivax has become the dominant malaria species since 2000. As in others endemic areas, it is important to specify the pattern of vivax malaria relapses and to try to discriminate efficiently re-infections from relapses. METHODS: This study was conducted in children born between January 1, 2001 and December 31, 2008 in Camopi, an Amerindian village located in the Amazon forest (n = 325), using an open cohort design. Primary and secondary attack rates of P. vivax were calculated using survival analysis. With the difference between the primary and secondary rates, this study aimed to estimate indirectly P. vivax relapse rate and evaluate its time evolution. RESULTS: Of the 1042 malaria attacks recorded, 689 (66%) were due to P. vivax (without mixed infection). One hundred and fifty one children had their primary attack with P. vivax and 106 had their two first attacks with P. vivax. In the absence of primaquine treatment, it was shown that P. vivax relapses mainly occurred during the first three months after the first attack. Thirty percent of children never had a relapse, 42% had a relapse before the first month after primary attack, 59% before the second month and 63% before the third month. CONCLUSION: This study confirmed that the relapse pattern in Camopi was compatible with the pattern described for the P. vivax Chesson (tropical) strain. In addition, due to the relapse rate time evolution, a simple arbitrary classification rule could be constructed: before 90 days after the primary attack, the secondary attack is a relapse; after 90 days, it is a re-infection. Adapted management of malaria cases based on these results could be devised.
ISSN: 1475-2875

inserm-00663913
http://www.hal.inserm.fr/inserm-00663913
http://www.hal.inserm.fr/inserm-00663913/document
http://www.hal.inserm.fr/inserm-00663913/file/1475-2875-8-278.pdf
DOI : 10.1186/1475-2875-8-278

Éditeur(s) : HAL CCSD Consejo Superior de Investigaciones Científicas
Résumé : International audience
The temporal variation in carbon and nitrogen isotopic compositions (noted as δ 13 C and δ 15 N) was investigated in the convict surgeonfish (Acanthurus triostegus) at Moorea (French Polynesia). Over a period of 24 days, juveniles were reared in aquaria and subjected to two different feeding treatments: granules or algae. The dynamics of δ 13 C and δ 15 N in two muscles (the adductor mandibulae complex and the epaxial musculature) having different functions were compared. At the end of experiments, a steady-state isotopic system in each muscle tissue was not reached. Especially for the algal treatment, we found different patterns of variation in isotopic compositions over time between the two muscles. The turnovers of δ 13 C showed opposite trends for each muscle but differences are mitigated by starvation and by the metamorphosis. Our study highlighted that the metabolism of coral reef fish may be subjected to catabolism or anabolism of non-protein precursors at settlement, inducing variation in isotopic compositions that are not linked to diet change. Comparación de la dinámica de variación isotópica en dos músculos de un pez de arrecife de coral durante la fase de asentamiento Resumen: La variación temporal en la composiciones isotópicas del carbono y nitrógeno (δ 13 C y δ 15 N) fue investigada en el pez cirujano Acanthurus triostegus en Moorea (Polinesia Francesa). Durante un período de 24 días, peces juveniles se mantuvieron en acuarios y se sometieron a dos tratamientos de alimentación: gránulos o algas. Se compararon las dinámicas de cambio δ 13 C y δ 15 N en dos músculos con diferentes funciones (complejo aductor mandibular y musculatura epiaxial). Al final de los experimentos, no se alcanzó un sistema isotópico de estado estacionario en ningún tejido. Especialmente para el tratamiento de algas, encontramos distintos patrones de variación en composiciones isotópicas en el tiempo entre los dos músculos. Las variaciones en δ 13 C mostraron tendencias opuestas para cada músculo, pero las diferencias fueron mitigadas por la inanición y la metamorfosis. Nuestro estudio destaca que el metabolismo de los peces de arrecife puede ser sometido a catabolismo o anabolismo por los precursores no proteicos durante el asentamiento, induciendo variación en las composi-ciones isotópicas que no están vinculados al cambio de dieta.
ISSN: 0214-8358

Droits : http://creativecommons.org/licenses/by-nc/
hal-01212253
https://hal-univ-perp.archives-ouvertes.fr/hal-01212253
https://hal-univ-perp.archives-ouvertes.fr/hal-01212253/document
https://hal-univ-perp.archives-ouvertes.fr/hal-01212253/file/1598-3145-1-PB.pdf
DOI : 10.3989/scimar.04225.31A

Éditeur(s) : HAL CCSD WB Saunders
Résumé : International audience
: The apicomplexan parasite Toxoplasma gondii was discovered a little over one hundred years ago and was soon recognized as a pathogen responsible for congenital infection. But detailed understanding of its epidemiology emerged only after 1970 with the discovery of its life cycle. In the last ten years, high resolution molecular tools have allowed the characterization of various strain types with different virulence patterns, and current studies are exploring the distribution of these different genotypes. In parallel, sophisticated diagnostic tools have been developed and awareness of disease burden has led some European countries with high prevalence rates to implement screening of pregnant women. In this article, the screening options and therapies used to prevent congenital toxoplasmosis are dissected in the light of recent data from cohort studies and other epidemiological data.
ISSN: 0163-4453

hal-00875492
https://hal.archives-ouvertes.fr/hal-00875492
https://hal.archives-ouvertes.fr/hal-00875492/document
https://hal.archives-ouvertes.fr/hal-00875492/file/Robert-Gangneux_-_It_is_not_only_the_cat_that_did_it_-_how_to_prevent_and_treat_congenital_toxoplasmosis_HAL.d.pdf
DOI : 10.1016/j.jinf.2013.09.023

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Over the last two decades, climate change has become a major environmental and public health concern due to the increase of the mean temperature on the Earth and its consequences on extreme meteorological events such as floods and droughts. These events induce very low or very high river flows that may impair surface water quality, and therefore result in potential health impacts when used for drinking water production. The present study aims at assessing the impact of hydrologic regime on surface water quality with a particular emphasis on total organic carbon (TOC) and nitrate. Water quality data from three French rivers acquired over a 27 years period, from January 1983 to December 2009, show the influence of extreme flows. Variation in TOC and nitrate concentrations showed opposite patterns for the whole range of flow rate (from less than 10% up to more than 100% of the mean flow). Regarding fluxes, TOC increased continuously with flow rate while nitrate was stable for very high discharges. The C/N ratio expressed from TOC and nitrate concentrations showed high values for extreme flows and particularly for very low flow rates, generally in summer, where nitrate is assimilated by biomass. Considering TOC and nitrate fluxes, it is confirmed that the worst situations were encountered for very high flow rates, namely for TOC exportation during surface runoff which was related to heavy rains or floods. These findings are of great importance with regard to the adaptation for drinking water treatment in facing extreme hydrological conditions, of which the frequency is increasing with climate change.
ISSN: 0022-1694

hal-00878009
https://hal.archives-ouvertes.fr/hal-00878009
DOI : 10.1016/j.jhydrol.2012.11.006

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Hydroxycarbamide (HC) treatment has been shown to improve the clinical course of patients with sickle cell anaemia (SCA), a haemoglobinopathy resulting from a single base substitution in the bêta-globin gene (HBB). SCA is characterized by chronic haemolytic anaemia and recurrent vascular occlusions leading to multisystemic complications. Several beneficial biological effects of HC have been documented (Halsey et al, 2003) but its impact on the concentration of circulating microparticles (MPs), a subtype of extracellular vesicles released from cytoplasmic membrane of activated or apoptotic cells and detected at high levels in sickle plasma, remains controversial (Hebbel et al, 2016). The aim of the present study was to compare the MP pattern in a group of SCA patients treated by HC and followed for 2 years.
ISSN: 0007-1048

hal-01668320
https://hal.univ-antilles.fr/hal-01668320
https://hal.univ-antilles.fr/hal-01668320/document
https://hal.univ-antilles.fr/hal-01668320/file/Garnier%20et%20al%20BJH-2017-00655.pdf
DOI : 10.1111/bjh.14810

Éditeur(s) : HAL CCSD
Résumé : International audience
Background: In French Guiana, a recent study has shown that a major part of the histoplasmosis incidence temporal fluctuations could be explained by climatic factors and thus postulated that disseminated histoplasmosis cases could be in a large proportion due to new infections. The description of the seasonal pattern of histoplasmosis could potentially help to test this new hypothesis. Patients and methods: A study using prospective data from the French Hospital Database for HIV was conducted in order to determine seasonal variations of the incidence of first cases of disseminated histoplasmosis in HIV persons in Cayenne, French Guiana. Single failure Cox proportional hazards models were used. Results: After adjusting for CD4 counts and antiretroviral treatment, the incidence of disseminated histoplasmosis was significantly higher during the Short Wet Season-Long Dry Season than during the Short Dry Season-Long Wet Season (Adjusted Hazard ratio 1.7 (1.1-2.5), P= 0.01). Conclusion: This result gives both valuable epidemiologic information to clinicians and a supplementary argument in favour of the hypothesis that an important proportion of cases were due to recent exposure. Therefore, the use of a primary prophylaxis must be discussed in French Guiana.
J AIDS Clinic Res

Droits : info:eu-repo/semantics/OpenAccess
inserm-00915009
http://www.hal.inserm.fr/inserm-00915009
http://www.hal.inserm.fr/inserm-00915009/document
http://www.hal.inserm.fr/inserm-00915009/file/2012_Hanf_-_Disseminated_Histoplasmosis_seasonal_incidence_variations_a_supplementary_argument_for_recent_infection.pdf
DOI : 10.4172/2155-6113.1000175

Éditeur(s) : HAL CCSD Ecological Society of America
Résumé : CABI:20153174020
Understanding how plants are constructed - i.e., how key size dimensions and the amount of mass invested in different tissues varies among individuals - is essential for modeling plant growth, carbon stocks, and energy fluxes in the terrestrial biosphere. Allocation patterns can differ through ontogeny, but also among coexisting species and among species adapted to different environments. While a variety of models dealing with biomass allocation exist, we lack a synthetic understanding of the underlying processes. This is partly due to the lack of suitable data sets for validating and parameterizing models. To that end, we present the Biomass And Allometry Database (BAAD) for woody plants. The BAAD contains 259634 measurements collected in 176 different studies, from 21084 individuals across 678 species. Most of these data come from existing publications. However, raw data were rarely made public at the time of publication. Thus, the BAAD contains data from different studies, transformed into standard units and variable names. The transformations were achieved using a common workflow for all raw data files. Other features that distinguish the BAAD are: (i) measurements were for individual plants rather than stand averages; (ii) individuals spanning a range of sizes were measured; (iii) plants from 0.01-100 m in height were included; and (iv) biomass was estimated directly, i.e., not indirectly via allometric equations (except in very large trees where biomass was estimated from detailed sub-sampling). We included both wild and artificially grown plants. The data set contains the following size metrics: total leaf area; area of stem cross-section including sapwood, heartwood, and bark; height of plant and crown base, crown area, and surface area; and the dry mass of leaf, stem, branches, sapwood, heartwood, bark, coarse roots, and fine root tissues. We also report other properties of individuals (age, leaf size, leaf mass per area, wood density, nitrogen content of leaves and wood), as well as information about the growing environment (location, light, experimental treatment, vegetation type) where available. It is our hope that making these data available will improve our ability to understand plant growth, ecosystem dynamics, and carbon cycling in the world's vegetation.
ISSN: 0012-9658

hal-01535227
https://hal.archives-ouvertes.fr/hal-01535227
DOI : 10.1890/14-1889.1
PRODINRA : 306122

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The extensive use of tyrosine kinase inhibitors (TKI's) in hematology and oncology has shown that these drugs have a significant potential for drug-drug interactions. Since these drugs have a rather low therapeutic window, some drug interactions are of particular clinical relevance either on drug toxicity or on patient's response. Significant interactions occur with concomitant use of acid-suppressive therapy leading to a decreased oral bioavailability. However, such interactions are drug dependent according to their solubility pattern and to the duration of action of acid-suppressive therapy, which is coprescribed. Significant interactions occur by inhibition or induction of CYP450 3A4 which is the main metabolic pathway of TKIs. However, minor metabolic pathways should also be paid attention to. Interactions involving efflux and influx transporters should also be considered occurring for some TKIs. Genetic polymorphism in drug metabolism as well as in drug transport is a factor of variability in drug exposure, which could modulate the magnitude of drug-drug interactions (DDIs). It should be noticed that TKIs can also be at the origin of drug interactions by altering the pharmacokinetics of coprescribed drugs. Since cancer patients are given many drugs either for supportive care or for the treatment of drug toxicity, and to the fact that the oldest patients are polymedicated, a clear understanding of DDIs with TKIs is of interest. The objectives of this review are to provide an overview of the mechanisms of DDIs with TKIs and to provide to physicians and pharmacists recommendations to manage these DDIs in their clinical practice.
ISSN: 0278-0232

hal-01616064
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616064
DOI : 10.1002/hon.2335
PUBMED : 27925256