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Article ; Online: Time-varying associations between an exposure history and a subsequent health outcome

Maude Wagner / Francine Grodstein / Karen Leffondre / Cécilia Samieri / Cécile Proust-Lima

BMC Medical Research Methodology, Vol 21, Iss 1, Pp 1-

a landmark approach to identify critical windows

2021 Volume 15

Abstract: Abstract Background Long-term behavioral and health risk factors constitute a primary focus of research on the etiology of chronic diseases. Yet, identifying critical time-windows during which risk factors have the strongest impact on disease risk is ... ...

Abstract	Abstract Background Long-term behavioral and health risk factors constitute a primary focus of research on the etiology of chronic diseases. Yet, identifying critical time-windows during which risk factors have the strongest impact on disease risk is challenging. To assess the trajectory of association of an exposure history with an outcome, the weighted cumulative exposure index (WCIE) has been proposed, with weights reflecting the relative importance of exposures at different times. However, WCIE is restricted to a complete observed error-free exposure whereas exposures are often measured with intermittent missingness and error. Moreover, it rarely explores exposure history that is very distant from the outcome as usually sought in life-course epidemiology. Methods We extend the WCIE methodology to (i) exposures that are intermittently measured with error, and (ii) contexts where the exposure time-window precedes the outcome time-window using a landmark approach. First, the individual exposure history up to the landmark time is estimated using a mixed model that handles missing data and error in exposure measurement, and the predicted complete error-free exposure history is derived. Then the WCIE methodology is applied to assess the trajectory of association between the predicted exposure history and the health outcome collected after the landmark time. In our context, the health outcome is a longitudinal marker analyzed using a mixed model. Results A simulation study first demonstrates the correct inference obtained with this approach. Then, applied to the Nurses’ Health Study (19,415 women) to investigate the association between body mass index history (collected from midlife) and subsequent cognitive decline (evaluated after age 70), the method identified two major critical windows of association: long before the first cognitive evaluation (roughly 24 to 12 years), higher levels of BMI were associated with poorer cognition. In contrast, adjusted for the whole history, higher levels of BMI became associated ...
Keywords	Landmarking ; Longitudinal outcome ; Measurement error ; Missing data ; Time-varying exposure ; Weighted cumulative index of exposure ; Medicine (General) ; R5-920
Subject code	600
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Improving pre-emptive access to the kidney transplant waiting list between 2017 and 2021: Assessment of a regional program in Aquitaine

Mathilde, Prezelin-Reydit / Karine, Moreau / Frederic, Jambon / Eric, Alezra / Grégoire, Robert / Jean-Christophe, Bernhard / Savva, Assatourian / Cécile, Degryse / Noëlle, Boulonne / Arlette, Communier / Brigitte, Bonpunt / Benjamin, Daviller / Olivier, Delorme / Xabina, Larre / Hannah, Kaminski / Karen, Leffondré / Pierre, Merville / Lionel, Couzi

Nephrologie & therapeutique

2024 Volume 20, Issue 1, Page(s) 1–10

Abstract: Introduction: Pre-emptive access to the kidney transplant (KT) waiting list remains limited in France, with only 3.9% of patients on pre-emptive KT and 5.6% of patients registered at the time of initiation of dialysis. A similar trend was observed in ... ...

Title translation	Amélioration de l’accès préemptif à la liste d’attente de transplantation rénale entre 2017 et 2021 : bilan d’un programme régional en Aquitaine
Abstract	Introduction: Pre-emptive access to the kidney transplant (KT) waiting list remains limited in France, with only 3.9% of patients on pre-emptive KT and 5.6% of patients registered at the time of initiation of dialysis. A similar trend was observed in Aquitaine. The aim of this study was to assess the impact of a regional program in terms of access to the waiting list for patients initiating a kidney replacement therapy (KRT). Methods: We included all patients assessed for registration on the list between 2017 and 2020, 2017 being the reference year and 2018 the beginning of the program. Using the CRISTAL and REIN registries, we assessed changes in the number of patients on the list at the time of initiation of dialysis or transplantation. Results: The number of new assessed candidates increased gradually each year from 255 in 2017 to 352 in 2020 (+38%). The number of patients on the list sharply increased in 2018 from 229 in 2017 to 319 in 2018 (+39.3%) and then remained stable. At the initiation of KRT, the proportion of patients registered on the waiting list increased gradually from 7.1% in 2017 to 18.2% in 2020. The proportion of pre-emptive KT remained stable between 2017 and 2021 (around 7%) with a decrease in 2020 (4.6%). Approximately 60% of patients had a contraindication to transplantation throughout the study. Conclusion: This study showed that a regional program aimed at providing better information to healthcare professionals and patients and encouraging rapid assessment of transplant candidates could increase the rate of pre-emptive registration on the KT waiting list for eligible patients over 4 years.
Language	French
Publishing date	2024-01-30
Publishing country	France
Document type	Journal Article
ZDB-ID	2229575-6
ISSN	1872-9177 ; 1769-7255
ISSN (online)	1872-9177
ISSN	1769-7255
DOI	10.1684/ndt.2024.64
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Article ; Online: A new trajectory approach for investigating the association between an environmental or occupational exposure over lifetime and the risk of chronic disease

Emilie Lévêque / Aude Lacourt / Viviane Philipps / Danièle Luce / Pascal Guénel / Isabelle Stücker / Cécile Proust-Lima / Karen Leffondré

PLoS ONE, Vol 15, Iss 8, p e

Application to smoking, asbestos, and lung cancer.

2020 Volume 0236736

Abstract: Quantifying the association between lifetime exposures and the risk of developing a chronic disease is a recurrent challenge in epidemiology. Individual exposure trajectories are often heterogeneous and studying their associations with the risk of ... ...

Abstract	Quantifying the association between lifetime exposures and the risk of developing a chronic disease is a recurrent challenge in epidemiology. Individual exposure trajectories are often heterogeneous and studying their associations with the risk of disease is not straightforward. We propose to use a latent class mixed model (LCMM) to identify profiles (latent classes) of exposure trajectories and estimate their association with the risk of disease. The methodology is applied to study the association between lifetime trajectories of smoking or occupational exposure to asbestos and the risk of lung cancer in males of the ICARE population-based case-control study. Asbestos exposure was assessed using a job exposure matrix. The classes of exposure trajectories were identified using two separate LCMM for smoking and asbestos, and the association between the identified classes and the risk of lung cancer was estimated in a second stage using weighted logistic regression and all subjects. A total of 2026/2610 cases/controls had complete information on both smoking and asbestos exposure, including 1938/1837 cases/controls ever smokers, and 1417/1520 cases/controls ever exposed to asbestos. The LCMM identified four latent classes of smoking trajectories which had different risks of lung cancer, all much stronger than never smokers. The most frequent class had moderate constant intensity over lifetime while the three others had either long-term, distant or recent high intensity. The latter had the strongest risk of lung cancer. We identified five classes of asbestos exposure trajectories which all had higher risk of lung cancer compared to men never occupationally exposed to asbestos, whatever the dose and the timing of exposure. The proposed approach opens new perspectives for the analyses of dose-time-response relationships between protracted exposures and the risk of developing a chronic disease, by providing a complete picture of exposure history in terms of intensity, duration, and timing of exposure.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Augmented backward elimination

Daniela Dunkler / Max Plischke / Karen Leffondré / Georg Heinze

PLoS ONE, Vol 9, Iss 11, p e

a pragmatic and purposeful way to develop statistical models.

2014 Volume 113677

Abstract: Statistical models are simple mathematical rules derived from empirical data describing the association between an outcome and several explanatory variables. In a typical modeling situation statistical analysis often involves a large number of potential ... ...

Abstract	Statistical models are simple mathematical rules derived from empirical data describing the association between an outcome and several explanatory variables. In a typical modeling situation statistical analysis often involves a large number of potential explanatory variables and frequently only partial subject-matter knowledge is available. Therefore, selecting the most suitable variables for a model in an objective and practical manner is usually a non-trivial task. We briefly revisit the purposeful variable selection procedure suggested by Hosmer and Lemeshow which combines significance and change-in-estimate criteria for variable selection and critically discuss the change-in-estimate criterion. We show that using a significance-based threshold for the change-in-estimate criterion reduces to a simple significance-based selection of variables, as if the change-in-estimate criterion is not considered at all. Various extensions to the purposeful variable selection procedure are suggested. We propose to use backward elimination augmented with a standardized change-in-estimate criterion on the quantity of interest usually reported and interpreted in a model for variable selection. Augmented backward elimination has been implemented in a SAS macro for linear, logistic and Cox proportional hazards regression. The algorithm and its implementation were evaluated by means of a simulation study. Augmented backward elimination tends to select larger models than backward elimination and approximates the unselected model up to negligible differences in point estimates of the regression coefficients. On average, regression coefficients obtained after applying augmented backward elimination were less biased relative to the coefficients of correctly specified models than after backward elimination. In summary, we propose augmented backward elimination as a reproducible variable selection algorithm that gives the analyst more flexibility in adopting model selection to a specific statistical modeling situation.
Keywords	Medicine ; R ; Science ; Q
Subject code	310
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Risk of breast cancer associated with long-term exposure to benzo[a]pyrene (BaP) air pollution

Amina Amadou / Delphine Praud / Thomas Coudon / Floriane Deygas / Leny Grassot / Elodie Faure / Florian Couvidat / Julien Caudeville / Bertrand Bessagnet / Pietro Salizzoni / John Gulliver / Karen Leffondré / Gianluca Severi / Francesca Romana Mancini / Béatrice Fervers

Environment International, Vol 149, Iss , Pp 106399- (2021)

Evidence from the French E3N cohort study

2021

Abstract: Background: Benzo[a]pyrene (BaP) is an endocrine-disrupting pollutant formed during incomplete combustion of organic materials. It has been recognized as a reproductive and developmental toxicant, however epidemiological evidence of the long-term effect ... ...

Abstract	Background: Benzo[a]pyrene (BaP) is an endocrine-disrupting pollutant formed during incomplete combustion of organic materials. It has been recognized as a reproductive and developmental toxicant, however epidemiological evidence of the long-term effect of ambient air BaP on breast cancer (BC) is limited. Thus we evaluated associations between ambient air BaP exposure and risk of BC, overall and according to menopausal status and molecular subtypes (estrogen receptor negative/positive (ER−/ER+) and progesterone receptor negative/positive (PR−/PR+)), stage and grade of differentiation of BC in the French E3N cohort study. Methods: Within a nested case-control study of 5222 incident BC cases and 5222 matched controls, annual BaP exposure was estimated using a chemistry-transport model (CHIMERE) and was assigned to the geocoded residential addresses of participants for each year during the 1990–2011 follow-up period. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Overall, cumulative airborne BaP exposure was significantly associated with the overall risk of BC, for each 1 interquartile range (IQR) increase in the concentration levels of BaP (1.42 ng/m3), the OR = 1.15 (95% CI: 1.04–1.27). However, by menopausal status, the significant positive association remained only in women who underwent menopausal transition (i.e. premenopausal women at inclusion who became postmenopausal at diagnosis), OR per 1 IQR = 1.20 (95% CI: 1.03–1.40). By hormone receptor status, positive associations were observed for ER+, PR + and ER + PR + BC, with ORs = 1.17 (95% CI: 1.04–1.32), 1.16 (95% CI: 1.01–1.33), and 1.17 (95% CI: 1.01–1.36) per 1 IQR, respectively. There was also a borderline positive association between BaP and grade 3 BC (OR per 1 IQR = 1.15 (95% CI: 0.99–1.34). Conclusions: We provide evidence of increased risk of BC associated with cumulative BaP exposure, which varied according to menopausal status, hormone receptor status, and ...
Keywords	Airborne benzo[a]pyrene ; Breast cancer ; Residential history ; Menopausal transition ; Hormone receptor status ; Differentiation grade ; Environmental sciences ; GE1-350
Subject code	616
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Exposure to airborne cadmium and breast cancer stage, grade and histology at diagnosis

Amina Amadou / Delphine Praud / Thomas Coudon / Aurélie M. N. Danjou / Elodie Faure / Floriane Deygas / Lény Grassot / Karen Leffondré / Gianluca Severi / Pietro Salizzoni / Francesca Romana Mancini / Béatrice Fervers

Scientific Reports, Vol 11, Iss 1, Pp 1-

findings from the E3N cohort study

2021 Volume 12

Abstract: Abstract Molecular studies suggest that cadmium due to its estrogenic properties, might play a role in breast cancer (BC) progression. However epidemiological evidence is limited. This study explored the association between long-term exposure to airborne ...

Abstract	Abstract Molecular studies suggest that cadmium due to its estrogenic properties, might play a role in breast cancer (BC) progression. However epidemiological evidence is limited. This study explored the association between long-term exposure to airborne cadmium and risk of BC by stage, grade of differentiation, and histological types at diagnosis. A nested case–control study of 4401 cases and 4401 matched controls was conducted within the French E3N cohort. A Geographic Information System (GIS)-based metric demonstrated to reliably characterize long-term environmental exposures was employed to evaluate airborne exposure to cadmium. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. There was no relationship between cadmium exposure and stage of BC. Also, no association between cadmium exposure and grade of differentiation of BC was observed. However, further analyses by histological type suggested a positive association between cadmium and risk of invasive tubular carcinoma (ITC) BC [ORQ5 vs Q1 = 3.4 (95% CI 1.1–10.7)]. The restricted cubic spline assessment suggested a dose–response relationship between cadmium and ITC BC subtype. Our results do not support the hypothesis that airborne cadmium exposure may play a role in advanced BC risk, but suggest that cadmium may be associated with an increased risk of ITC.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Should we use standard survival models or the illness-death model for interval-censored data to investigate risk factors of chronic kidney disease progression?

Julie Boucquemont / Marie Metzger / Christian Combe / Bénédicte Stengel / Karen Leffondre / NephroTest Study Group

PLoS ONE, Vol 9, Iss 12, p e

2014 Volume 114839

Abstract: Background In studies investigating risk factors of chronic kidney disease (CKD) progression, one may be interested in estimating factors effects on both a fall of glomerular filtration rate (GFR) below a specific level (i.e., a CKD stage) and death. ... ...

Abstract	Background In studies investigating risk factors of chronic kidney disease (CKD) progression, one may be interested in estimating factors effects on both a fall of glomerular filtration rate (GFR) below a specific level (i.e., a CKD stage) and death. Such studies have to account for the fact that GFR is measured at intermittent visit only, which implies that progression to the stage of interest is unknown for patients who die before being observed at that stage. Our objective was to compare the results of an illness-death model that handles this uncertainty, with frequently used survival models. Methods This study included 1,519 patients from the NephroTest cohort with CKD stages 1-4 at baseline (69% males, 59±15 years, median protein/creatinine ratio [PCR] 27.4 mg/mmol) and subsequent annual measures of GFR (follow-up time 4.3±2.7 years). Each model was used to estimate the effects of sex, age, PCR, and GFR at baseline on the hazards of progression to CKD stage 5 (GFR<15 mL/min/1.73 m2, n = 282 observed) and death (n = 168). Results For progression to stage 5, there were only minor differences between results from the different models. The differences between results were higher for the hazard of death before or after progression. Our results also suggest that previous findings on the effect of age on end-stage renal disease are more likely due to a strong impact of age on death than to an effect on progression. The probabilities of progression were systematically under-estimated with the survival model as compared with the illness-death model. Conclusions This study illustrates the advantages of the illness-death model for accurately estimating the effects of risk factors on the hazard of progression and death, and probabilities of progression. It avoids the need to choose arbitrary time-to-event and time-to-censoring, while accounting for both interval censoring and competition by death, using a single analytical model.
Keywords	Medicine ; R ; Science ; Q
Subject code	519
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long-term airborne dioxin exposure and breast cancer risk in a case-control study nested within the French E3N prospective cohort

Aurélie Marcelle Nicole Danjou / Thomas Coudon / Delphine Praud / Emilie Lévêque / Elodie Faure / Pietro Salizzoni / Muriel Le Romancer / Gianluca Severi / Francesca Romana Mancini / Karen Leffondré / Laure Dossus / Béatrice Fervers

Environment International, Vol 124, Iss , Pp 236-

2019 Volume 248

Abstract: Background: Dioxins, Group 1 carcinogens, are emitted by industrial chlorinated combustion processes and suspected to increase breast cancer risk through receptor-mediated pathways. Objectives: We estimated breast cancer risk associated with airborne ... ...

Abstract	Background: Dioxins, Group 1 carcinogens, are emitted by industrial chlorinated combustion processes and suspected to increase breast cancer risk through receptor-mediated pathways. Objectives: We estimated breast cancer risk associated with airborne dioxin exposure, using geographic information system (GIS) methods and historical exposure data. Methods: We designed a case-control study (429 breast cancer cases diagnosed between 1990 and 2008, matched to 716 controls) nested within the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort. Airborne dioxin exposure was assessed using a GIS-based metric including participants' residential history, technical characteristics of 222 dioxin sources, residential proximity to dioxin sources, exposure duration and wind direction. Odds ratios (OR) and 95% confidence intervals (CI) associated with quintiles of cumulative exposure were estimated using multivariate logistic regression models. Results: We observed no increased risk of breast cancer for higher dioxin exposure levels overall and according to hormone-receptor status. We however observed a statistically significant OR for Q2 versus Q1 overall (1.612, 95% CI: 1.042–2.493) and for estrogen-receptor (ER) positive breast cancer (1.843, 95% CI: 1.033–3.292). Conclusions: Overall, as well as according to hormone-receptor status, no increased risk was observed for higher airborne dioxin exposure. The increased risk for low exposure levels might be compatible with non-monotonic dose-response relationship. Confirmation of our findings is required. Our GIS-based metric may provide an alternative in absence of ambient dioxin monitoring and may allow assessing exposure to other pollutants. Keywords: Breast cancer, Endocrine disruptors, Dioxins, Geographic information system, Tumor receptor
Keywords	Environmental sciences ; GE1-350
Subject code	610
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Long-term airborne dioxin exposure and breast cancer risk in a case-control study nested within the French E3N prospective cohort

Danjou, Aurélie Marcelle Nicole / Béatrice Fervers / Delphine Praud / Elodie Faure / Emilie Lévêque / Francesca Romana Mancini / Gianluca Severi / Karen Leffondré / Laure Dossus / Muriel Le Romancer / Pietro Salizzoni / Thomas Coudon

Environment international. 2019 Mar., v. 124

2019

Abstract: Dioxins, Group 1 carcinogens, are emitted by industrial chlorinated combustion processes and suspected to increase breast cancer risk through receptor-mediated pathways.We estimated breast cancer risk associated with airborne dioxin exposure, using ... ...

Abstract	Dioxins, Group 1 carcinogens, are emitted by industrial chlorinated combustion processes and suspected to increase breast cancer risk through receptor-mediated pathways.We estimated breast cancer risk associated with airborne dioxin exposure, using geographic information system (GIS) methods and historical exposure data.We designed a case-control study (429 breast cancer cases diagnosed between 1990 and 2008, matched to 716 controls) nested within the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort. Airborne dioxin exposure was assessed using a GIS-based metric including participants' residential history, technical characteristics of 222 dioxin sources, residential proximity to dioxin sources, exposure duration and wind direction. Odds ratios (OR) and 95% confidence intervals (CI) associated with quintiles of cumulative exposure were estimated using multivariate logistic regression models.We observed no increased risk of breast cancer for higher dioxin exposure levels overall and according to hormone-receptor status. We however observed a statistically significant OR for Q2 versus Q1 overall (1.612, 95% CI: 1.042–2.493) and for estrogen-receptor (ER) positive breast cancer (1.843, 95% CI: 1.033–3.292).Overall, as well as according to hormone-receptor status, no increased risk was observed for higher airborne dioxin exposure. The increased risk for low exposure levels might be compatible with non-monotonic dose-response relationship. Confirmation of our findings is required. Our GIS-based metric may provide an alternative in absence of ambient dioxin monitoring and may allow assessing exposure to other pollutants.
Keywords	breast neoplasms ; carcinogens ; case-control studies ; combustion ; confidence interval ; cumulative exposure ; dioxins ; dose response ; exposure duration ; geographic information systems ; hormone receptors ; monitoring ; odds ratio ; pollutants ; regression analysis ; risk ; wind direction
Language	English
Dates of publication	2019-03
Size	p. 236-248.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2019.01.001
Database	NAL-Catalogue (AGRICOLA)

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