Éditeur(s) : HAL CCSD BioMed Central
Résumé : ICARE Study Group
International audience
BackgroundPopulation attributable risks (PARs) are useful tool to estimate the burden of risk factors in cancer incidence. Few studies estimated the PARs of oral cavity cancer to tobacco smoking alone, alcohol drinking alone and their joint consumption but none performed analysis stratified by subsite, gender or age. Among the suspected risk factors of oral cavity cancer, only PAR to a family history of head and neck cancer was reported in two studies. The purpose of this study was to estimate in France the PARs of oral cavity cancer to several recognized and suspected risk factors, overall and by subsite, gender and age.MethodsWe analysed data from 689 oral cavity cancer cases and 3481 controls included in a population-based case–control study, the ICARE study. Unconditional logistic regression models were used to estimate odds ratios (ORs), PARs and 95 % confidence intervals (95 % CI).ResultsThe PARs were 0.3 % (95 % CI −3.9 %; +3.9 %) for alcohol alone, 12.7 % (6.9 %–18.0 %) for tobacco alone and 69.9 % (64.4 %–74.7 %) for their joint consumption. PAR to combined alcohol and tobacco consumption was 74 % (66.5 %–79.9 %) in men and 45.4 % (32.7 %–55.6 %) in women. Among suspected risk factors, body mass index 2 years before the interview <25 kg.m−2, never tea drinking and family history of head and neck cancer explained 35.3 % (25.7 %–43.6 %), 30.3 % (14.4 %–43.3 %) and 5.8 % (0.6 %–10.8 %) of cancer burden, respectively. About 93 % (88.3 %–95.6 %) of oral cavity cancers were explained by all risk factors, 94.3 % (88.4 %–97.2 %) in men and only 74.1 % (47.0 %–87.3 %) in women.ConclusionOur study emphasizes the role of combined tobacco and alcohol consumption in the oral cavity cancer burden in France and gives an indication of the proportion of cases attributable to other risk factors. Most of oral cavity cancers are attributable to concurrent smoking and drinking and would be potentially preventable through smoking or drinking cessation. If the majority of cases are explained by recognized or suspected risk factors in men, a substantial number of cancers in women are probably due to still unexplored factors that remain to be clarified by future studies.
ISSN: 1471-2407

Droits : http://creativecommons.org/licenses/by/
hal-01258466
http://hal.upmc.fr/hal-01258466
http://hal.upmc.fr/hal-01258466/document
http://hal.upmc.fr/hal-01258466/file/BMCC.pdf
DOI : 10.1186/s12885-015-1841-5

Éditeur(s) : HAL CCSD
Résumé : International audience
Background: We examined the association between exposure during pregnancy to trihalomethanes, the most common water disinfection by-products, and birth outcomes in a European cohort study (Health Impacts of Long-Term Exposure to Disinfection By-Products in Drinking Water). We took into account exposure through different water uses, measures of water toxicity, and genetic susceptibility. Methods: We enrolled 14,005 mothers (2002-2010) and their children from France, Greece, Lithuania, Spain, and the UK. Information on lifestyle- and water-related activities was recorded. We ascertained residential concentrations of trihalomethanes through regulatory records and ad hoc sampling campaigns and estimated route-specific trihalomethane uptake by trimester and for whole pregnancy. We examined single nucleotide polymorphisms and copy number variants in disinfection by-product metabolizing genes in nested case-control studies. Results: Average levels of trihalomethanes ranged from around 10 μg/L to above the regulatory limits in the EU of 100 μg/L between centers. There was no association between birth weight and total trihalomethane exposure during pregnancy (β = 2.2 g in birth weight per 10 μg/L of trihalomethane, 95% confidence interval = 3.3, 7.6). Birth weight was not associated with exposure through different routes or with specific trihalomethane species. Exposure to trihalomethanes was not associated with low birth weight (odds ratio [OR] per 10 μg/L = 1.02, 95% confidence interval = 0.95, 1.10), small-for-gestational age (OR = 0.99, 0.94, 1.03) and preterm births (OR = 0.98, 0.9, 1.05). We found no gene-environment interactions for mother or child polymorphisms in relation to preterm birth or small-for-gestational age. Conclusions: In this large European study, we found no association between birth outcomes and trihalomethane exposures during pregnancy in the total population or in potentially genetically susceptible subgroups. © 2016 Wolters Kluwer Health, Inc.
Epidemiology

hal-01392115
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01392115
DOI : 10.1097/EDE.0000000000000544
PUBMED : 27468006

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
Objective Large-scale prospective studies do not support an association between neuroticism and extroversion with cancer incidence. However, research on other personality constructs is inconclusive. This longitudinal study examined the associations between four personality measures, Type 1, "suppressed emotional expression"; Type 5, "rational/antiemotional"; hostility; and Type A with cancer incidence. Methods Personality measures were available for 13,768 members in the GAZEL cohort study (baseline assessment in 1993). Follow-up for diagnoses of primary cancers was obtained from January 1, 1994 to December 31, 2009. Associations between personality and cancer incidence were evaluated using Cox proportional hazards analyses and adjusted for potential confounders. Results During a median follow-up of 16.0 years (range, 9 days-16 years), 1139 participants were diagnosed as having a primary cancer. The mean duration between baseline and cancer diagnosis was 9.3 years. Type 1 personality was associated with a decreased risk of breast cancer (hazard ratio per standard deviation = 0.81, 95% confidence interval = 0.68-0.97, p = .02). Type 5 personality was not associated with prostate, breast, colorectal, or smoking-related cancers, but was associated with other cancers (hazard ratio per standard deviation = 1.17, 95% confidence interval = 1.04-1.31, p = .01). Hostility was associated with an increased risk of smoking-related cancers, which was explained by smoking habits, and Type A was not associated with any of the cancer endpoints. Conclusions Several personality measures were prospectively associated with the incidence of selected cancers. These links may warrant further epidemiological studies and investigations about potential biobehavioral mechanisms.
ISSN: 0033-3174

inserm-00813178
http://www.hal.inserm.fr/inserm-00813178
http://www.hal.inserm.fr/inserm-00813178/document
http://www.hal.inserm.fr/inserm-00813178/file/PersonalityCancer_Lemogne_Psychosom_Med_2013.pdf
http://www.hal.inserm.fr/inserm-00813178/file/inserm-00813178_edited.pdf

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: Recent studies suggest that a Mediterranean dietary pattern during pregnancy may influence pregnancy outcomes. The aim of this study was to evaluate the effect of adherence to a Mediterranean diet (MD) during pregnancy on fetal growth restriction (FGR) and preterm delivery (PTD) in a French Caribbean island where the population is largely of African descent and presents dietary patterns similar to MD. METHODS: Using data from the TIMOUN Mother-Child Cohort Study conducted in Guadeloupe (French West Indies) between 2004 and 2007, we analysed data for 728 pregnant women who delivered liveborn singletons without any major congenital malformations. Degree of adherence to MD during pregnancy was evaluated with a semi-quantitative food frequency questionnaire based on nine dietary criteria. Multiple logistic regression models were used to analyse birth outcomes while taking potential confounders into account. RESULTS: Overall there was no association between MD adherence during pregnancy and the risk of PTD or FGR. However, pre-pregnancy body mass index was a strong effect modifier, and MD adherence was associated with a decreased risk of PTD specifically in overweight and obese women (adjusted odds ratio 0.7, 95% confidence interval 0.6, 0.9) (P heterogeneity <0.01). CONCLUSIONS: These results suggest that Caribbean diet during pregnancy may carry some benefits of MD and may contribute to reduce the risk of PTD in overweight and obese pregnant women.
ISSN: 0269-5022

hal-00988172
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00988172
DOI : 10.1111/ppe.12113
PUBMED : 24754337

Éditeur(s) : HAL CCSD American Academy of Neurology
Résumé : International audience
OBJECTIVE: We examined if the CNS Penetration-Effectiveness (CPE) score of antiretroviral drugs was associated with survival after a diagnosis of HIV-related encephalopathy, progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis, or cryptococcal meningitis. METHODS: Using data from the FHDH-ANRS CO4, we compared the survival of 9,932 HIV-infected patients diagnosed with a first neurologic AIDS-defining event in the pre-combination antiretroviral therapy (cART) (1992-1995), early cART (1996-1998), or late cART (1999-2004) periods. Follow-up was subdivided (CPE < 1.5 and CPE ≥ 1.5), and relative rates (RR) of death were estimated using multivariable Poisson regression models. RESULTS: In the pre-cART and early cART periods, regimens with CPE ≥ 1.5 were associated with lower mortality after HIV-related encephalopathy (RR 0.64; 95% confidence interval [CI] 0.47-0.86 and RR 0.45; 95% CI 0.35-0.58) and after PML (RR 0.79; 95% CI 0.55-1.12 and RR 0.45; 95% CI 0.31-0.65), compared to regimens with CPE < 1.5, while in the late cART period there was no association between the CPE score and the mortality. A higher CPE score was also associated with a lower mortality in all periods after cerebral toxoplasmosis (RR 0.68, 95% CI 0.56-0.84) or cryptococcal meningitis (RR 0.50, 95% CI 0.34-0.74). Whatever the neurologic event, these associations were not maintained after adjustment on updated plasma HIV-RNA (missing, <500, ≥500 copies/mL) with RR ranging from 0.82 (95% CI 0.36-1.91) to 1.02 (0.69-1.52). CONCLUSION: At the beginning of the cART era, the CPE score was of importance for survival after severe neurologic event, while in the late cART period, the additional effect of CPE score vanished with more powerful antiretroviral regimens associated with plasma viral load control.
ISSN: 0028-3878

hal-00875434
https://hal.archives-ouvertes.fr/hal-00875434
DOI : 10.1212/WNL.0b013e31820c3089
PUBMED : 21248274

Éditeur(s) : HAL CCSD American Society of Tropical Medicine and Hygiene
Résumé : International audience
In disease-endemic areas, histoplasmosis is the main differential diagnosis for tuberculosis among human immunodeficiency virus (HIV)-infected patients. However, no study has compared the two diseases. Thus, the objective of this study was to compare tuberculosis and histoplasmosis in HIV-infected patients. A population of 205 HIV-infected patients (99 with tuberculosis and 106 with histoplasmosis) hospitalized in Cayenne, French Guiana during January 1, 1997-December 31, 2008 were selected retrospectively from the French Hospital Database on HIV. Multivariate analysis showed that tuberculosis was associated with cough (adjusted odds ratio [AOR] = 0.20, 95% confidence interval [CI] = 0.05-0.73) and a C-reactive protein level > 70 mg/L (AOR = 0.98, 95% CI = 0.97-0.99). Variables associated with disseminated histoplasmosis were a γ-glutamyl transferase level > 72 IU/L (AOR = 4.99, 95% CI = 1.31-18.99), origin from French Guiana (AOR = 5.20, 95% CI = 1.30-20.73), disseminated localization (AOR = 6.40, 95% CI = 1.44-28.45), a concomitant opportunistic infection (AOR = 6.71, 95% CI = 1.50-29.96), a neutrophil count < 2,750 cells/mm(3) (AOR = 10.54, 95% CI = 2.83-39.24), a CD4 cell count < 60 cells/mm(3) (AOR = 11.62, 95% CI = 2.30-58.63), and a platelet count < 150,000/mm(3) (AOR = 19.20, 95% CI = 3.35-110.14). Tuberculosis and histoplasmosis have similarities, but some factors show a greater association with one of these diseases. Thus, adapted therapeutic choices can be made by using simple clinical and paraclinical criteria.
ISSN: 0002-9637

inserm-01065027
http://www.hal.inserm.fr/inserm-01065027
http://www.hal.inserm.fr/inserm-01065027/document
http://www.hal.inserm.fr/inserm-01065027/file/2014_Adenis_-_Tuberculosis_and_Histoplasmosis_among_HIV.pdf
DOI : 10.4269/ajtmh.13-0084

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: An association between education and preterm delivery has been observed in populations across Europe, but differences in methodology limit comparability. We performed a direct cross-cohort comparison of educational disparities in preterm delivery based on individual-level birth cohort data. METHODS: The study included data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal, and Spain. The cohorts included between 2434 and 99 655 pregnancies. The association between maternal education and preterm delivery (22-36 completed weeks of gestation) was reported as risk ratios, risk differences, and slope indexes of inequality with 95% confidence intervals (CIs). RESULTS: Singleton preterm live delivery proportion varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and maternal characteristics. Nevertheless, there were similar educational differences in risk of preterm delivery in 8 of the 12 cohorts with slope index of inequality varying between 2.2 [95% CI 1.1, 3.3] and 4.0 [95% CI 1.4, 6.6] excess preterm deliveries per 100 singleton deliveries among the educationally most disadvantaged, and risk ratio between the lowest and highest education category varying from 1.4 [95% CI 1.1, 1.8] to 1.9 [95% CI 1.2, 3.1]. No associations were found in the last four cohorts. CONCLUSIONS: Educational disparities in preterm delivery were found all over Europe. Despite differences in the distributions of education and preterm delivery, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics did not explain the differences.
ISSN: 0269-5022

hal-01146842
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146842
DOI : 10.1111/ppe.12185
PUBMED : 25808200

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Prostate cancer disparities have been reported in men of African descent who show the highest incidence, mortality, compared with other ethnic groups. Few studies have explored the genetic and environmental factors for prostate cancer in men of African ancestry. The glutathione-S-transferases family conjugates carcinogens before their excretion and is expressed in prostate tissue. This study addressed the role of GSTM1 and GSTT1 deletions on prostate cancer risk in populations of African descent. This multi-institutional case-control study gathered data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database, the African-Caribbean Cancer Consortium (AC3) and Men of African Descent and Carcinoma of the Prostate Consortium (MADCaP). The analysis included 10 studies (1715 cases and 2363 controls), five in African-Americans, three in African-Caribbean and two in African men. Both the GSTM1 and the GSTT1 deletions showed significant inverse associations with prostate cancer [odds ratio (OR): 0.90, 95% confidence interval (CI) 0.83-0.97 and OR 0.88, 95% CI: 0.82-0.96, respectively]. The association was restricted to Caribbean and African populations. A significant positive association was observed between GSTM1 deletion and prostate cancer in smokers in African-American studies (OR: 1.28, 95% CI: 1.01-1.56), whereas a reduced risk was observed in never-smokers (OR: 0.66, 95% CI: 0.46-0.95). The risk of prostate cancer increased across quartiles of pack-years among subjects carrying the deletion of GSTM1 but not among subjects carrying a functional GSTM1. Gene-environment interaction between smoking and GSTM1 may be involved in the etiology of prostate cancer in populations of African descent.
ISSN: 0143-3334

hal-00682901
https://hal.archives-ouvertes.fr/hal-00682901
DOI : 10.1093/carcin/bgr119
PUBMED : 21705483

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Bronchoalveolar lavage (BAL) is a major diagnostic tool in lung diseases, including viral respiratory infections. We aimed to better define the situations where viral tests should be performed on BAL fluid (BALF). We retrospectively studied all cases where viral tests [immunofluorescence, immunocytochemistry, viral culture, and/or polymerase chain reaction (PCR)] were performed on BALF during a period of 1 year (2008) in our institution. We compared the characteristics of patients with virus-positive versus virus-negative BALF. Of the 636 BALF samples sent to the microbiology laboratory, 232 underwent viral tests. Of these, 70 (30 %) were positive and identified 85 viruses: herpes simplex virus (HSV)-1 (n = 27), cytomegalovirus (CMV, n = 23), Epstein-Barr virus (EBV, n = 18), human herpesvirus (HHV)-6 (n = 12), respiratory syncytial virus (RSV, n = 3), rhinovirus (n = 1), and adenovirus (n = 1). The variables associated with positive viral tests on univariate analysis were immunosuppression [human immunodeficiency virus (HIV), corticosteroids >10 mg/day for ≥3 weeks, or other immunosuppressive therapy], ground-glass attenuations on computed tomography (CT) scanning, late-onset ventilator-associated pneumonia (VAP), and durations of (i) hospital stay, (ii) intensive care unit (ICU) stay, and (iii) mechanical ventilation before BAL (p < 0.01 for each comparison). On multivariate analysis, only immunosuppression [odds ratio (OR) 6.4, 95 % confidence interval (CI) [2.8-14.3], p < 0.0001] and ground-glass attenuations (OR 3.7, 95 % CI [1.8-7.7], p = 0.0004) remained associated with virus-positive BAL. None of the viral tests performed on BALF for the initial assessment of diffuse infiltrative lung disease (n = 15) was positive. PCR improved the diagnostic yield of viral tests on BALF by 50 %. Testing for viruses on BALF should be mostly restricted to immunocompromised patients with acute respiratory diseases and/or patients with unexplained ground-glass attenuations on CT scanning.
ISSN: 0934-9723

hal-00873158
https://hal.archives-ouvertes.fr/hal-00873158
DOI : 10.1007/s10096-012-1791-7
PUBMED : 23238685

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Persistent organic pollutants have not been conclusively associated with length of gestation or with preterm birth. Chlordecone is an organochlorine pesticide that has been extensively used to control the banana root borer population in the French West Indies. Data from the Timoun Mother-Child Cohort Study conducted in Guadeloupe between 2004 and 2007 were used to examine the associations of chlordecone concentrations in maternal plasma with the length of gestation and the rate preterm birth in 818 pregnant women. Data were analyzed using multivariate linear regression for length of gestation and a Cox model for preterm birth. The median plasma chlordecone concentration was 0.39 µg/L (interquartile range, 0.18-0.83). No correlation was observed with plasma concentrations of p,p'-dichlorodiphenyl dichloroethene (ρ = 0.017) or polychlorinated biphenyl 153 (ρ = -0.016), the other main organochlorine compounds detected. A 1-log10 increase in chlordecone concentration was associated with a decreased length of gestation (-0.27 weeks; 95% confidence interval: -0.50, -0.03) and an increased risk of preterm birth (60%; 95% confidence interval: 10, 130). These associations may result from the estrogen-like and progestin-like properties of chlordecone. These results are of public health relevance because of the prolonged persistence of chlordecone in the environment and the high background rate of preterm births in this population.
ISSN: 0002-9262

hal-01010740
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01010740
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01010740/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01010740/file/Chlordecone%20Exposure%20final.pdf
DOI : 10.1093/aje/kwt313

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. METHODS: Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. RESULTS: Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). CONCLUSIONS: There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.
ISSN: 1058-4838

hal-00875143
https://hal.archives-ouvertes.fr/hal-00875143
DOI : 10.1093/cid/cis878
PUBMED : 23074311

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Persistent organic pollutants may affect the immune and respiratory systems, but available evidence is based on small study populations. We studied the association between prenatal exposure to dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyl 153 (PCB 153) and children's respiratory health in European birth cohorts. METHODS: We included 4608 mothers and children enrolled in 10 birth cohort studies from 7 European countries. Outcomes were parent-reported bronchitis and wheeze in the first 4 years of life. For each cohort, we performed Poisson regression analyses, modeling occurrences of the outcomes on the estimates of cord-serum concentrations of PCB 153 and DDE as continuous variables (per doubling exposure) and as cohort-specific tertiles. Summary estimates were obtained through random-effects meta-analyses. RESULTS: The risk of bronchitis or wheeze (combined variable) assessed before 18 months of age increased with increasing DDE exposure (relative risk [RR] per doubling exposure = 1.03 [95% confidence interval = 1.00-1.07]). When these outcomes were analyzed separately, associations appeared stronger for bronchitis. We also found an association between increasing PCB 153 exposure and bronchitis in this period (RR per doubling exposure = 1.06 [1.01-1.12]) but not between PCB 153 and wheeze. No associations were found between either DDE or PCB 153 and ever-wheeze assessed after 18 months. Inclusion of both compounds in the models attenuated risk estimates for PCB 153 tertiles of exposure, whereas DDE associations were more robust. CONCLUSION: This large meta-analysis suggests that prenatal DDE exposure may be associated with respiratory health symptoms in young children (below 18 months), whereas prenatal PCB 153 levels were not associated with such symptoms.
Epidemiology (Cambridge, Mass.)

hal-01063930
https://hal.archives-ouvertes.fr/hal-01063930
DOI : 10.1097/EDE.0000000000000097
PUBMED : 24776790

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Estrogens are thought to play a critical role in prostate carcinogenesis. It has been suggested that polymorphisms of genes encoding enzymes involved in estrogen metabolism are risk factors for prostate cancer. However, few studies have been performed on populations of African ancestry, which are known to have a high risk of prostate cancer. OBJECTIVE: We investigated whether functional polymorphisms of CYP17, CYP19, CYP1B1, COMT and UGT1A1 affected the risk of prostate cancer in two different populations of African ancestry. METHODS: In Guadeloupe (French West Indies), we compared 498 prostate cancer patients and 565 control subjects. In Kinshasa (Democratic Republic of Congo), 162 prostate cancer patients were compared with 144 controls. Gene polymorphisms were determined by the SNaPshot technique or short tandem repeat PCR analysis. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The AA genotype and the A allele of rs4680 (COMT) appeared to be inversely associated with the risk of prostate cancer in adjusted models for both Afro-Caribbean and native African men. For the A allele, a significant inverse association was observed among cases with low-grade Gleason scores and localized clinical stage, in both populations. CONCLUSIONS: These preliminary results support the hypothesis that polymorphisms of genes encoding enzymes involved in estrogen metabolism may modulate the risk of prostate cancer in populations of African ancestry
ISSN: 1932-6203

hal-01305477
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01305477
DOI : 10.1371/journal.pone.0153609
PUBMED : 27074016

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Few studies have explored the consequences of environmental exposure to organochlorine pesticides for gestational hypertension (GH), preeclampsia (PE) and gestational diabetes mellitus (GDM). Chlordecone is a persistent organochlorine pesticide that was used intensively, and almost exclusively, in the French West Indies until 1993. We investigated the impact of prenatal exposure to chlordecone on the occurrence of GDM, GH and PE by studying 779 pregnant women enrolled in a prospective mother-child cohort (Timoun Study) in Guadeloupe between 2004 and 2007. Chlordecone exposure was determined by assaying maternal plasma and information about pregnancy complications was obtained from midwives, pediatricians and hospital medical records after delivery. The risks of GH (n=65), PE (n=31) and GDM (n=71) were estimated by multiple logistic regression including potential confounders. Levels of chlordecone plasma concentration in the third (OR=0.2; 95% confidence interval (CI): 0.1, 0.5) and fourth quartiles (OR=0.3; 95% CI: 0.2, 0.7) were associated with a statistically significant decrease in the risk of GH. A log10 increase in chlordecone concentration was significantly associated with lower risk of GH (OR=0.4; 95% CI: 0.2, 0.6). No significant associations were observed between the chlordecone exposure and the risk of PE or GDM. This study suggests an inverse association between chlordecone exposure during pregnancy and GH. Further studies are required to determine the underlying mechanism, or the potential unknown confounding factors, resulting in this association.
ISSN: 0160-4120

hal-01061391
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061391
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061391/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061391/file/Saunders_et_al._Final_version_main_manuscript.pdf
DOI : 10.1016/j.envint.2014.03.024

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Exposure to solvents during pregnancy has long been suspected to increase the risk of congenital malformations. Glutathione S-transferases (GSTs) are enzymes essential for the detoxification of various chemicals. Our objective here was to assess whether GST polymorphisms might modify the association between maternal solvent exposure and the risk of birth defects. A prospective cohort included 3421 pregnant women in Brittany, France (2002-2006). Occupational exposure to solvents was assessed from a job-exposure matrix. Congenital malformations were diagnosed among livebirths, stillbirths, and medical pregnancy terminations. Using a nested case-control design, 32 babies with major birth defects were compared to 348 normal births for babies' cord blood genotypes (at GSTT1 and GSTM1) and maternal occupational solvent exposure. Logistic models were used to adjust for potential confounders. The risk of major defects increased significantly in women with solvent exposure (20% of controls and 34% of cases). Frequencies of the null genotype of both the GSTT1 and GSTM1 genes were similar among controls and cases. There was a significantly increased risk of birth defects in GSTM1 not-null cord-blood genotype in pregnancies exposed to solvents (odds ratio [OR], 1.0 for not-null, not-exposed; OR, 4.0 for not-null, exposed; 95% confidence interval [CI], 1.4-11.2; OR, 1.6 for null, not-exposed; 95% CI, 0.6-3.9; OR, 1.0 for null, exposed; 95% CI, 0.2-4.7; p = 0.05). This nested case-control study suggests that the child's GSTM1 genotype modifies the risk of major birth defects among offspring of solvent-exposed women. Replication and additional investigations are necessary to confirm and elucidate these findings.
ISSN: 1542-0752

hal-00875957
https://hal.archives-ouvertes.fr/hal-00875957
DOI : 10.1002/bdra.23018
PUBMED : 22570144

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed. Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.
ISSN: 1058-4838

hal-01118447
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118447
PUBMED : 25139963
DOI : 10.1093/cid/ciu659

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
AbstractBackgroundFew epidemiological studies have investigated the link between occupational exposure to solvents and head and neck cancer risk, and available findings are sparse and inconsistent. The objective of this study was to examine the association between occupational exposure to chlorinated solvents and head and neck cancer risk.MethodsWe analyzed data from 4637 men (1857 cases and 2780 controls) included in a population-based case-control study, ICARE (France). Occupational exposure to five chlorinated solvents (perchloroethylene [PCE], trichloroethylene [TCE], methylene chloride [MC], chloroform [CF], and carbon tetrachloride [CT]) was assessed through job-exposure matrices. Odds ratios (ORs) and confidence intervals (95% CI) were estimated by unconditional logistic regression, adjusted for age, tobacco smoking, alcohol consumption, asbestos exposure, and other potential confounders.ResultsWe observed no association between chlorinated solvent exposure and head and neck cancer risk, despite a non-significant increase in risk among subjects who had the highest cumulative level of exposure to PCE, (OR = 1.81; 95% CI = 0.68 to 4.82). In subsite analysis, the risk of laryngeal cancer increased with cumulative exposure to PCE (p for trend = 0.04). The OR was 3.86 (95% CI = 1.30 to 11.48) for those exposed to the highest levels of PCE. A non-significant elevated risk of hypopharyngeal cancer was also observed in subjects exposed to the highest levels of MC (OR = 2.36; 95% CI = 0.98 to 5.85).ConclusionOur findings provide evidence that high exposure to PCE increases the risk of laryngeal cancer, and suggest an association between exposure to MC and hypopharyngeal cancer. Exposure to other chlorinated solvents was not associated with the risk of head and neck cancer.
ISSN: 1476-069X

inserm-01570445
http://www.hal.inserm.fr/inserm-01570445
http://www.hal.inserm.fr/inserm-01570445/document
http://www.hal.inserm.fr/inserm-01570445/file/12940_2017_Article_286.pdf
http://www.hal.inserm.fr/inserm-01570445/file/12940_2017_286_MOESM1_ESM.pdf

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: In the context of recent guidelines on invasive candidiasis (IC), how French intensive care units (ICUs) are managing IC? METHODS: This is a prospective observational multicenter cohort study. During 1 year (2012-2013), 87 French ICUs enrolled consecutive patients with suspected or proven IC (SIC or PIC) and receiving systemic antifungal therapy (SAT). Data were collected up to 28 days after inclusion. RESULTS: We studied 835 patients, 291 with PIC and 544 with SIC. At SAT initiation, patients with SIC were significantly more severe (SAPS II 50.1 ± 18.7 vs. 46.2 ± 18.0). Severe sepsis or septic shock prompted to initiate empiric SAT in 70 % of SIC. Within 4 days in median, the initial SAT was modified in 49 % of patients with PIC vs. 33 % patients with SIC. Modifications were most often motivated by mycological results, and de-escalation was the most frequent change. Regarding compliance to IC management guidelines, echinocandin was used for 182 (62.5 %) patients with PIC, and 287 (52.7 %) of those with SIC; central venous catheter was removed in 87 (54.3 %) of patients with candidaemia, and 43 of the remaining patients received echinocandin; and de-escalation was undertaken after 5 days of SAT in 142 patients, after 10 days in 13 patients. As 20.6 % of SIC were secondarily documented, 403/835 (48 %) patients had finally a proven IC. Candida albicans was the main pathogen (65.3 %), then Candida glabrata (15.9 %). The 28-day mortality rates were 40.0 % in candidaemia, 25.4 % in cIAI, and 26.7 % in deep-seated candidiasis. In the overall population of patients with proven IC, four independent prognostic factors were identified: immunosuppression (Odds Ratio (OR) = 1.977: 1.03-3.794 95 % confidence interval (CI), p = 0.04), age (OR = 1.035; 1.017-1.053 95 % CI; p  extless 0.001), SAPS extgreater46 on ICU admission (OR = 2.894; 1.81-4.626 95 % CI; p  extless 0.001), and surgery just before or during ICU stay (OR = 0.473; 0.29-0.77 95 % CI; p  extless 0.001). CONCLUSION: When SAT is initiated in French ICUs, the IC is ultimately proven for 48 % of patients. Empiric SAT is initiated in severely ill ICU patients. The initial SAT is often adapted, with de-escalation to fluconazole when possible. Mortality rate remains high
ISSN: 2110-5820

hal-01259216
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259216
DOI : 10.1186/s13613-015-0103-7
PUBMED : 26743881

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: HIV cohort collaborations, which pool data from diverse patient cohorts, have provided key insights into outcomes of antiretroviral therapy (ART). However, the extent of, and reasons for, between-cohort heterogeneity in rates of AIDS and mortality are unclear. METHODS: We obtained data on adult HIV-positive patients who started ART from 1998 without a previous AIDS diagnosis from 17 cohorts in North America and Europe. Patients were followed up from 1 month to 2 years after starting ART. We examined between-cohort heterogeneity in crude and adjusted (age, sex, HIV transmission risk, year, CD4 count and HIV-1 RNA at start of ART) rates of AIDS and mortality using random-effects meta-analysis and meta-regression. RESULTS: During 61 520 person-years, 754/38 706 (1.9%) patients died and 1890 (4.9%) progressed to AIDS. Between-cohort variance in mortality rates was reduced from 0.84 to 0.24 (0.73 to 0.28 for AIDS rates) after adjustment for patient characteristics. Adjusted mortality rates were inversely associated with cohorts' estimated completeness of death ascertainment [excellent: 96-100%, good: 90-95%, average: 75-89%; mortality rate ratio 0.66 (95% confidence interval 0.46-0.94) per category]. Mortality rate ratios comparing Europe with North America were 0.42 (0.31-0.57) before and 0.47 (0.30-0.73) after adjusting for completeness of ascertainment. CONCLUSIONS: Heterogeneity between settings in outcomes of HIV treatment has implications for collaborative analyses, policy and clinical care. Estimated mortality rates may require adjustment for completeness of ascertainment. Higher mortality rate in North American, compared with European, cohorts was not fully explained by completeness of ascertainment and may be because of the inclusion of more socially marginalized patients with higher mortality risk.
ISSN: 0300-5771

hal-00875138
https://hal.archives-ouvertes.fr/hal-00875138
DOI : 10.1093/ije/dys164
PUBMED : 23148105

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
OBJECTIVE: The WEGENT trial and other short-term studies suggested that azathioprine or methotrexate could effectively maintain granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) remission. Whether differences in relapse or adverse event rates would appear after discontinuation of those 2 maintenance regimens and longer follow-up remains unknown. METHODS: Long-term outcomes for the patients enrolled in the WEGENT trial were analyzed according to their randomization group. Parameters at trial entry were evaluated as potential prognostic factors for death, relapse or damage in multivariate models. RESULTS: Data were returned for 88.8% of the 126 original participants. Median [95% confidence interval] followup was 11.9 [11.3-12.5] years. For the azathioprine and methotrexate arms, respectively, the 10-year overall survival rates were 75.1% [64.8-86.9] and 79.9% [70.3-90.8] (P = 0.56), and relapse-free survival rates 26.3% [17.3-40.1] and 33.5% [23.5-47.7] (P = 0.29). No between-arm differences were observed for relapse, adverse events, damage, survival rates without severe side effects and survival rates without relapse and severe side effects. Considering only the 97 GPA patients, no between-arm survival differences were observed. Relapse-free survival was shorter for GPA than MPA patients but the multivariate analysis retained anti-PR3-ANCA-positivity, and not GPA, as being independently associated with relapse. CONCLUSION: This long-term analysis confirms that azathioprine and methotrexate are comparable options for maintaining GPA or MPA remission. Despite good overall survival, relapses, adverse events and damage remain matters of concern and further studies are needed to reduce them.
ISSN: 2326-5205

hal-01217989
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989/file/Long-term%20outcomes%20of%20the%20WEGENT%20trial_accepted.pdf
DOI : 10.1002/art.39450