Chronic central nervous system effects of pesticides : epidemiological data in farmers

Compte-tenu de l’importance des populations exposées, les effets à long terme des pesticides sont un enjeu de santé publique majeur. Leur étude pose néanmoins des problèmes méthodologiques complexes. Notre objectif était de contribuer à la connaissance des effets chroniques des pesticides sur le système nerveux central en explorant par une approche épidémiologique innovante le rôle des insecticides organophosphorés dans l’apparition de troubles cognitifs. Nous avons développé et utilisé deux outils de mesure de l’exposition (une matrice culture-exposition : PESTIMAT, et des algorithmes basés sur des études de terrain : PESTEXPO) afin d’estimer l’exposition à 34 insecticides organophosphorés utilisés en vigne, en considérant pour chaque individu l’ensemble des tâches viticoles exposant aux pesticides (préparation, application, nettoyage, réentrée) réalisées au cours de sa vie. Ces outils ont été appliqués dans le cadre du premier suivi (2001-2003) de la cohorte PHYTONER constituée en 1997 par l’inclusion de 925 affiliés à la Mutualité Sociale Agricole de Gironde. L’exposition aux organophosphorés définie par des index cumulés à l’aide de nos deux outils était associée à une baisse des performances cognitives, de manière plus marquée pour les tests explorant la mémoire de travail visuelle et la vitesse de traitement de l’information. Les niveaux de risque variaient en fonction des organophosphorés et étaient plus marqués pour le mévinphos. Cette thèse a confirmé le risque de troubles cognitifs chez les utilisateurs professionnels de pesticides et pose la question d’une évolution ultérieure vers une démence. Elle a également démontré la faisabilité et la pertinence d’une approche s’attachant à établir des scores d’exposition à des matières actives pesticides spécifiques pour en analyser les effets de santé.Given the number of exposed persons, long term effects of pesticides are a foremost Public Health concern. However their study raises complex methodological issues. Our objective was to contribute to the knowledge of the pesticide chronic effects on the central nervous system by exploring the role of organophosphate insecticides in occurence of cognitive disorders by an innovative epidemiological approach. Two exposure assessment tools were developed (a crop exposure matrix: PESTIMAT and algorithms based on field studies: PESTEXPO) to estimate the lifetime cumulated exposure to 34 organophosphate insecticides used in vineyards, taking into account pesticide exposure during tasks (mixing, spraying, cleaning, re-entry) performed by wine-growers. These tools were used in the framework of the first follow-up (2001-2003) of the PHYTONER cohort, initiated in 1997 by the enrollment of 925 workers affiliated to the farmer health insurance system in Gironde, France. Cumulative organophosphate exposure defined by an index using the two tools was associated with poor cognitive performances, particularly for tests exploring the visual working memory and the processing speed. Risk level varied depending on the organophosphate, and was more pronounced for mevinphos. This thesis supports the hypothesis that cognitive impairment may be associated with pesticide occupational use and raises the question of a further evolution towards dementia. It also demonstrated the feasibility and the relevance of an approach based on chemical specific exposure scores to analyze health effects

Chronic central nervous system effects of pesticides : epidemiological data in farmers

Compte-tenu de l’importance des populations exposées, les effets à long terme des pesticides sont un enjeu de santé publique majeur. Leur étude pose néanmoins des problèmes méthodologiques complexes. Notre objectif était de contribuer à la connaissance des effets chroniques des pesticides sur le système nerveux central en explorant par une approche épidémiologique innovante le rôle des insecticides organophosphorés dans l’apparition de troubles cognitifs. Nous avons développé et utilisé deux outils de mesure de l’exposition (une matrice culture-exposition : PESTIMAT, et des algorithmes basés sur des études de terrain : PESTEXPO) afin d’estimer l’exposition à 34 insecticides organophosphorés utilisés en vigne, en considérant pour chaque individu l’ensemble des tâches viticoles exposant aux pesticides (préparation, application, nettoyage, réentrée) réalisées au cours de sa vie. Ces outils ont été appliqués dans le cadre du premier suivi (2001-2003) de la cohorte PHYTONER constituée en 1997 par l’inclusion de 925 affiliés à la Mutualité Sociale Agricole de Gironde. L’exposition aux organophosphorés définie par des index cumulés à l’aide de nos deux outils était associée à une baisse des performances cognitives, de manière plus marquée pour les tests explorant la mémoire de travail visuelle et la vitesse de traitement de l’information. Les niveaux de risque variaient en fonction des organophosphorés et étaient plus marqués pour le mévinphos. Cette thèse a confirmé le risque de troubles cognitifs chez les utilisateurs professionnels de pesticides et pose la question d’une évolution ultérieure vers une démence. Elle a également démontré la faisabilité et la pertinence d’une approche s’attachant à établir des scores d’exposition à des matières actives pesticides spécifiques pour en analyser les effets de santé.Given the number of exposed persons, long term effects of pesticides are a foremost Public Health concern. However their study raises complex methodological issues. Our objective was to contribute to the knowledge of the pesticide chronic effects on the central nervous system by exploring the role of organophosphate insecticides in occurence of cognitive disorders by an innovative epidemiological approach. Two exposure assessment tools were developed (a crop exposure matrix: PESTIMAT and algorithms based on field studies: PESTEXPO) to estimate the lifetime cumulated exposure to 34 organophosphate insecticides used in vineyards, taking into account pesticide exposure during tasks (mixing, spraying, cleaning, re-entry) performed by wine-growers. These tools were used in the framework of the first follow-up (2001-2003) of the PHYTONER cohort, initiated in 1997 by the enrollment of 925 workers affiliated to the farmer health insurance system in Gironde, France. Cumulative organophosphate exposure defined by an index using the two tools was associated with poor cognitive performances, particularly for tests exploring the visual working memory and the processing speed. Risk level varied depending on the organophosphate, and was more pronounced for mevinphos. This thesis supports the hypothesis that cognitive impairment may be associated with pesticide occupational use and raises the question of a further evolution towards dementia. It also demonstrated the feasibility and the relevance of an approach based on chemical specific exposure scores to analyze health effects

Insecticides organophosphorés et troubles cognitifs chez les ouvriers viticoles en Gironde (estimation de l'exposition chronique à l'aide d'indicateurs qualitatifs et quantitatifs)

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Use of oral anticoagulants and risk of prostate cancer: a population-based case-control study in Montreal, Canada.

International audienceA few recent epidemiological observations suggest that anticoagulant medications may protect against prostate cancer development. Most studies have been small or subjected to methodological issues, including potential confounding. We provide here new evidence on this association in the context of a population-based case-control study of prostate cancer conducted in Montreal, Canada. Cases were 1,588 men with incident prostate cancer, aged ≤75 years, diagnosed across French hospitals in the Montreal area between 2005 and 2009. Concurrently, 1,618 population controls from the same residential area and age distribution (±5 years) were randomly selected from the electoral list of French-speaking men. In-person interviews elicited information on socio-demographic, lifestyle and environmental factors, along with a detailed medical history. Unconditional logistic regression was used to assess the association between lifetime use of anticoagulants and prostate cancer risk. 102 subjects (2.6 % of cases and 3.7 % of controls) reported a history of oral anticoagulant therapy. After controlling for age, ancestry, education, family history of prostate cancer, prostate cancer screening frequency, diabetes, body mass index and statin use, ever use of oral anticoagulants showed a weak inverse, non-statistically significant association with prostate cancer (odds ratio 0.76, 95% confidence interval 0.50-1.16). Similar results were observed in analyses considering duration of use or indication for use, restricted to subjects recently screened or stratified by cancer aggressiveness. Our findings provide weak support for a protective effect of oral anticoagulant therapy against prostate cancer. Further confirmation is required, especially in light of potential bleeding complications associated with anticoagulants

Lifetime report of perceived stress at work and cancer among men: A case-control study in Montreal, Canada.

International audienceThe association between perceived workplace psychological stress, over the entire work career, and cancer among men has never been assessed. This was explored in the context of a population-based case-control study conducted in Montreal, Canada.3103 incident cancer cases (11 types) diagnosed in 1979-1985 and 512 population controls were interviewed. Subjects described in detail each job held during their lifetime, including the occurrence of stress, and its reason. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between perceived workplace stress and its duration, and each cancer site, adjusting for lifestyle and occupational factors.Employment in at least one stressful job was associated with increased odds of cancers of the lung (OR=1.33, 95% CI: 1.01-1.75), colon (OR=1.51, 95% CI: 1.15-1.98), bladder (OR=1.37, 95% CI: 1.03-1.81), rectal (OR=1.52, 95% CI: 1.10-2.10), and stomach (OR=1.53, 95% CI: 1.08-2.15). A duration-response trend was found for cancers of the lung, colon, rectum, stomach, and for NHL. Subjects reported changes in stress level over their career. Perceived stress was ascribed to several sources, including high demand and time pressure, financial issues, job insecurity, and hazardous conditions.Prolonged exposure to perceived stress at work was associated with greater odds of cancer at 5 out of 11 sites. While over reporting of stress by cases cannot be fully ruled out, these associations, if substantiated, would bear important public health significance. Prospective studies building on detailed stress assessment protocols considering all sources and changes over the career are necessary

Metabolic syndrome and prostate cancer risk in a population-based case–control study in Montreal, Canada

The role of metabolic syndrome (MetS) in prostate cancer risk is still debated. We investigated it in a large population-based case–control study

Perceived Workplace Stress Is Associated with an Increased Risk of Prostate Cancer before Age 65

BackgroundEvidence is lacking regarding the potential role of chronic psychological stress on cancer incidence. The workplace is reported to be the main source of stress among Canadian men. We examined the association between perceived lifetime workplace stress and prostate cancer (PCa) risk in a large case–control study.MethodsCases were 1,933 men, aged ≤ 75 years, newly diagnosed with PCa in 2005–2009 across hospitals in Montreal, Canada. Concurrently, 1994 population controls frequency-matched on age were randomly selected from the electoral list based on cases’ residential districts. Detailed lifestyle and work histories (including perceived stress, from any type of work stressor, for each job held) were collected during in-person interviews. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between work-related stress and PCa risk in multivariate analyses.ResultsOver the lifetime, 58% of subjects reported at least one job as stressful. Occupations described as stressful were most often among white-collar workers. Perceived workplace stress duration was associated with a higher risk of PCa (OR = 1.12, 95% CI:1.04–1.20 per 10-year increase) among men younger than 65 years, but not among older men. Associations were similar irrespective of PCa aggressiveness. Frequent or recent screening for PCa, age at first exposure and time since exposure to work-related stress, and socioeconomic and lifestyle factors, had little influence on risk estimates.ConclusionFindings are in line with an association between reporting prolonged workplace stress and an increase in risk of PCa before age 65

A French crop-exposure matrix for use in epidemiological studies on pesticides: PESTIMAT

International audiencePesticide exposure assessment is a key methodological issue for epidemiological studies. The history of pesticide has proven difficult to obtain from individuals' report because of the wide range of active ingredients (AIs). We developed a crop-exposure matrix, which intends to reconstitute parameters of pesticide exposure in France since 1950. PESTIMAT is composed of tables crossing crops and AIs by year and providing the following metrics: (1) probability (proportion of farmers having used the AIs); (2) frequency (number of treatment days); and (3) intensity (application rate of the AIs in kg/ha). Metrics were obtained by the combination of six sources: (i) registration information from the Agriculture Ministry; (ii) information from agricultural bodies on products marketed; (iii) agricultural recommendations by the Plant Health Protection body; (iv) treatment calendars provided by farmers; (v) data from associations of farmers; and (vi) data from the industry. To date, 529 AIs usable between 1950 and 2010 are included in PESTIMAT: 160 fungicides; 160 herbicides; and 209 insecticides. When combined with duration and determinants of intensity, the metrics in PESTIMAT will make it possible to calculate exposure scores and to search for dose-effect relationships, an important criterion for causality judgment in epidemiology

Targeting Stereotactic Body Radiotherapy on Metabolic PET- and Immuno-PET-Positive Vertebral Metastases

International audienceBackground: Stereotactic body radiotherapy (SBRT) for vertebral metastases (VM) allows the delivery of high radiation doses to tumors while sparing the spinal cord. We report a new approach to clinical target volume (CTV) delineation based on anti-carcinoembryonic antigen (CEA) positron emission tomography (pretargeted immuno-PET; “iPET”) in patients with metastatic breast cancer (BC) or medullary thyroid cancer (MTC). Methods: All patients underwent iPET, spine magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) using 18F-deoxyglucose (FDG) for BC or 18F-dihydroxy-phenylalanine (F-DOPA) for MTC. Vertebrae locations and vertebral segments of lesions were recorded and the impact on CTV delineation was evaluated. Results: Forty-six VM eligible for SBRT following iPET were evaluated in eight patients (five BC, three MTC). Eighty-one vertebral segments were detected using MRI, 26 with FDG or F-DOPA PET/CT, and 70 using iPET. iPET was able to detect more lesions than MRI for vertebral bodies (44 vs. 34). iPET-based delineation modified MRI-based CTV in 70% (32/46) of cases. Conclusion: iPET allows a precise mapping of affected VM segments, and adds complementary information to MRI in the definition of candidate volumes for VM SBRT. iPET may facilitate determining target volumes for treatment with stereotactic body radiotherapy in metastatic vertebral disease