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Poidvin A.,Biostatistics and Epidemiology Unit | Poidvin A.,University of Paris Descartes | Touze E.,University of Caen Lower Normandy | Ecosse E.,Biostatistics and Epidemiology Unit | And 6 more authors.
Neurology | Year: 2014

Objectives: We investigated the incidence of stroke and stroke subtypes in a population-based cohort of patients in France treated with growth hormone (GH) for short stature in childhood. Methods: Adult morbidity data were obtained in 2008-2010 for 6,874 children with idiopathic isolated GH deficiency or short stature who started GH treatment between 1985 and 1996. Cerebrovascular events were validated using medical reports and imaging data and classified according to standard definitions of subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke. Case ascertainment completeness was estimated with capture-recapture methods. The incidence of stroke and of stroke subtypes was calculated and compared with population values extracted from registries in Dijon and Oxford, between 2000 and 2012. Results: Using both Dijon and Oxford population-based registries as references, there was a significantly higher risk of stroke among patients treated with GH in childhood. The excess risk of stroke was mainly attributable to a very substantially and significantly higher risk of hemorrhagic stroke (standardized incidence ratio from 3.5 to 7.0 according to the registry rates considered, and accounting or not accounting for missed cases), and particularly subarachnoid hemorrhage (standardized incidence ratio from 5.7 to 9.3). Conclusions: We report a strong relationship between hemorrhagic stroke and GH treatment in childhood for isolated growth hormone deficiency or childhood short stature. Patients treated with GH worldwide should be advised about this association and further studies should evaluate the potentially causal role of GH treatment in these findings.


Zaanan A.,University Paris - Sud | Gauthier M.,Biostatistics and Epidemiology Unit | Malka D.,Institut Universitaire de France | Locher C.,Meaux Hospital Center | And 6 more authors.
Cancer | Year: 2011

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumor with poor prognosis. First-line platinum-based chemotherapy is active in patients with advanced SBA, but data regarding second-line chemotherapy are lacking. The aim of this study was to evaluate the efficacy and tolerability of fluorouracil, leucovorin, and irinotecan (FOLFIRI regimen) as second-line chemotherapy in patients with advanced SBA. METHODS: We analyzed all consecutive patients who received second-line chemotherapy with FOLFIRI among 93 patients with advanced SBA included from 1996 to 2008 in a previous retrospective multicenter study. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of second-line chemotherapy using the Kaplan-Meier method. Cox models were applied for multivariate analyses. RESULTS: Among 51 patients who received second-line chemotherapy, 28 patients (male, 57%; median age, 54 years; metastatic disease, 96%) were treated with FOLFIRI after progression (n = 24) or limiting toxicity (n = 4) to first-line FOLFOX (n = 19) or LV5FU2-cisplatin (n = 9). Grade 3-4 toxicity was observed in 48% of patients (grade 3-4 neutropenia, 37%). After a median follow-up of 21.5 months, all patients had tumor progression, and 22 patients died. Objective response rate was 20%, and disease control rate was 52%. Median PFS and OS were 3.2 and 10.5 months, respectively. No clinical, biological, or tumor characteristics were associated with PFS or OS by multivariate analysis. CONCLUSIONS: Second-line chemotherapy with FOLFIRI produced disease control in half of patients with advanced SBA after failure with first-line platinum-based chemotherapy. Nevertheless, the short median PFS warrants the evaluation of other treatments including targeted therapies. Cancer 2011. © 2010 American Cancer Society.


Antoun S.,Gustave Roussy | Lanoy E.,Biostatistics and Epidemiology Unit | Albiges-Sauvin L.,Gustave Roussy | Escudier B.,Gustave Roussy
Expert Review of Anticancer Therapy | Year: 2014

According to computed tomography image analysis, skeletal muscle (SM) and adipose tissue areas vary widely in patients with the same body mass index or the same body surface area. Body composition variables such as SM mass, SM density and subcutaneous and visceral adipose tissue have shown value as potential independent predictive factors for survival in cancer patients, although data for patients with renal cell carcinoma (RCC) undergoing targeted therapy remain relatively scarce. Confirmation of their prognostic value is required before they can be considered useful adjuncts to conventional predictive models of survival in RCC patients. In addition, variability in SM mass might affect drug toxicity, with patients with a low rather than high SM mass being at a higher risk of toxicity. A dose tailored to the individual patient's SM mass might lower toxicity in RCC patients, enable completion of the treatment plan and thus impact favorably on treatment effectiveness. © 2014 Informa UK Ltd.


Coste J.,Biostatistics and Epidemiology Unit | Coste J.,University of Paris Descartes | Pouchot J.,University of Paris Descartes | Pouchot J.,University Paris Diderot | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Treatment for short stature in childhood has been recommended with the purpose of improving adult health-related quality of life (HRQoL). However, there are only limited data available concerning the consequences of body height for HRQoL in adulthood. Objective: Our objective was to investigate the relationship between body height and HRQoL. Design, Setting, and Participants: This national representative, cross-sectional household survey of the French general noninstitutionalized population included 8857 men and 9248 women, aged 18-50 yr, in 2003. Main Outcome Measures: Scores on the eight subscales of the Medical Outcomes Study 36-item Short Form (SF-36) were the primary outcomes. Univariate and multivariate linear regression analyses were used to evaluate the effect of height on HRQoL while controlling for age and various socioeconomic variables and pathological conditions. Results: Height was found to be a very weak predictor of HRQoL both for men and women. Only heights lower than 149.2 and 136.0 cm and higher than 203.6 and 188.7cm, in men and women, respectively, were associated with a clinically significant reduction in physical functioning. The effects of body height on other (mental and social) dimensions of HRQoL were negligible or undetectable. Conclusions: Height appears to have minimal consequences for physical functioning and negligible effects on other dimensions of HRQoL. These results contrast with widely popularized stereotypes and common beliefs and should be carefully considered to avoid further stigmatization and unnecessary medical care of individuals who are at the lower end of the growth distribution. Copyright © 2012 by The Endocrine Society.


Coste J.,Biostatistics and Epidemiology Unit | Coste J.,University of Paris Descartes | Quinquis L.,Biostatistics and Epidemiology Unit | Audureau E.,Biostatistics and Epidemiology Unit | And 2 more authors.
Health and Quality of Life Outcomes | Year: 2013

Background: Health-related quality of life (HRQoL) measures are increasingly used in the general population. However, little is known about patterns and determinants of unanswered or unusable questionnaires and their consequences on estimates of HRQoL.Methods: The 2003 Decennial Health Survey collected socio-demographic and health information, including HRQoL, for 30,782 adults representative of the French population. The pattern, determinants and impact on estimate validity of non, incomplete and inconsistent responses to the SF-36 questionnaire were determined. For this, phi coefficients, polytomous logistic regression models and multiple imputation methods were used.Results: Only 48% of the subjects eligible for the HRQoL measurement provided a complete and consistent SF-36 questionnaire. Three patterns of non-response and five of partial (incomplete or inconsistent) response were identified, sharing largely similar socio-demographic profiles (higher age, lower educational level and economic status, foreign background, and isolated). The consequences of non and partial responses on HRQoL estimates were large in several groups of subjects although these biases ran in opposite directions and partially neutralized each other.Conclusions: When measuring HRQoL in the general population, missing and inconsistent data are frequent, especially in elderly, educationally and socio-economically deprived, foreign and isolated groups. Methods for handling missing data are required to correct for potentially the associated and serious selection and non-differential information biases in studies targeting or investigating these groups. © 2013 Coste et al.; licensee BioMed Central Ltd.


Audureau E.,Biostatistics and Epidemiology Unit | Audureau E.,University of Paris Descartes | Pouchot J.,University of Paris Descartes | Coste J.,Biostatistics and Epidemiology Unit | Coste J.,University of Paris Descartes
Circulation: Cardiovascular Quality and Outcomes | Year: 2016

Background - Negative effects of obesity on health-related quality of life (HRQoL) have been reported, especially in women, but the relative contribution of cardiometabolic and other obesity-related comorbidities to such effects remains unclear. Our objective was to model the association by sex between body mass index and HRQoL and to precisely quantify the indirect effects mediated by obesity-related comorbidities. Methods and Results - Data were drawn from the latest French Decennial Health Survey, a nationwide cross-sectional study conducted in 2003 (21 239 adults aged 25-64 years analyzed). HRQoL was measured by the 36-item short-form health survey questionnaire. A mediation analysis based on the counterfactual framework was performed to quantify the proportion of obesity effects on HRQoL mediated by related comorbidities, including cardiometabolic risk factors (diabetes mellitus, hypertension, dyslipidemia) and diseases (ischemic heart disease, cerebrovascular, and peripheral vascular disease), musculoskeletal disorders, and asthma. After multiple linear regression, inverse associations were found between increasing body mass index category and physically oriented and most mentally oriented 36-item short-form health survey dimensions, with evidence of greater effects in women. Mediation analysis revealed that obesity effects were significantly mediated by several comorbidities, more apparently in men (eg, proportion of obesity class II total effect mediated via cardiometabolic factors: general health 27.0% [men] versus 13.6% [women]; proportion of obesity class II total effect mediated via total count of comorbidities: physical functioning 17.8% [men] versus 7.7% [women] and general health 37.1% [men] versus 20.3% [women]). Conclusions - Women have a greater overall impact of obesity on HRQoL, but with proportionally lower effects mediated by cardiometabolic and other obesity-related conditions, suggesting the possible role of other specific psychosocial processes. © 2016 American Heart Association, Inc.


Coste J.,Biostatistics and Epidemiology Unit | Quinquis L.,Biostatistics and Epidemiology Unit | D'Almeida S.,Biostatistics and Epidemiology Unit | Audureau E.,University of Paris Descartes
PLoS ONE | Year: 2014

Background: Relationships between smoking and health-related quality of life (HRQoL) in the general population remain unclear. Objectives: To quantify the independent associations between smoking patterns and HRQoL and to identify any threshold or non-linear tendencies in these associations. Methods: A national representative, cross-sectional household survey of the French general non institutionalized population included 7525 men and 8486 women, aged 25-64 year in 2003. Scores on the eight subscales of the Medical Outcomes Study 36-item Short Form were the primary outcomes. Linear regression analyses were used to evaluate the associations between HRQoL and smoking history, quantity of smoking and smoking cessation while controlling for various socio-economic variables, depression, alcohol dependence and pathological conditions. Analyses were conducted in 2013. Results: Independent associations between smoking and HRQoL were found, including small positive associations for occasional or light smoking (up to 5 cigarettes per day), and larger and diffuse negative associations above this threshold. Much weaker associations and higher thresholds for negative HRQoL were found for women than for men. For ex-smokers of both genders, HRQoL was found to be better between 2 and 5 years after quitting. Conclusions: Smoking was independently related to HRQoL, with large differences according to the pattern and quantity of smoking, and to gender. These results may have considerable relevance both for public health action and care of smokers. Copyright: © 2014 Coste et al.


Pasqualini C.,Gustave Roussy Cancer Campus | Dufour C.,Gustave Roussy Cancer Campus | Goma G.,Biostatistics and Epidemiology Unit | Raquin M.-A.,Gustave Roussy Cancer Campus | And 2 more authors.
Bone Marrow Transplantation | Year: 2016

High-risk neuroblastoma is characterised by poor long-term survival, especially for very high-risk (VHR) patients (poor response of metastases after induction therapy). We report the results of an intensified high-dose chemotherapy (HDC) strategy to improve the prognosis of VHR patients. This strategy was based on tandem HDC with thiotepa and busulfan-melphalan (Bu-Mel) followed by autologous stem cell transplantation (ASCT). All data were prospectively recorded in the Gustave Roussy Paediatric ASCT database. From April 2004 to August 2011, 26 patients were eligible for tandem HDC. The median age at diagnosis was 4.4 years (1-15.9). All patients had metastatic disease. MYCN was amplified in 5/26 tumours. Despite the cumulative toxicity of alkylating agents, the toxicity of the intensified HDC strategy was manageable. Thiotepa-related toxicity was mainly digestive, whereas sinusoidal obstruction syndrome was the main toxicity observed after Bu-Mel. The 3-year event-free survival of this cohort was 37.3% (21.3-56.7). This strategy will be compared with combined 131 I-mIBG/Bu-Mel in the upcoming SIOPEN VHR Neuroblastoma Protocol. © 2016 Macmillan Publishers Limited All rights reserved.


Purpose: Missing items are common in quality of life (QoL) questionnaires and present a challenge for research in this field. It remains unclear which of the various methods proposed to deal with missing data performs best in this context. We compared personal mean score, full information maximum likelihood, multiple imputation, and hot deck techniques using various realistic simulation scenarios of item missingness in QoL questionnaires constructed within the framework of classical test theory. Methods: Samples of 300 and 1,000 subjects were randomly drawn from the 2003 INSEE Decennial Health Survey (of 23,018 subjects representative of the French population and having completed the SF-36) and various patterns of missing data were generated according to three different item non-response rates (3, 6, and 9%) and three types of missing data (Little and Rubin's "missing completely at random," "missing at random," and "missing not at random"). The missing data methods were evaluated in terms of accuracy and precision for the analysis of one descriptive and one association parameter for three different scales of the SF-36. Results: For all item non-response rates and types of missing data, multiple imputation and full information maximum likelihood appeared superior to the personal mean score and especially to hot deck in terms of accuracy and precision; however, the use of personal mean score was associated with insignificant bias (relative bias <2%) in all studied situations. Conclusions: Whereas multiple imputation and full information maximum likelihood are confirmed as reference methods, the personal mean score appears nonetheless appropriate for dealing with items missing from completed SF-36 questionnaires in most situations of routine use. These results can reasonably be extended to other questionnaires constructed according to classical test theory. © 2010 Springer Science+Business Media B.V.


Audureau E.,Biostatistics and Epidemiology Unit | Rican S.,University of Paris Ouest Nanterre | Coste J.,Biostatistics and Epidemiology Unit
Health and Place | Year: 2013

Although small area effects on health-related quality of life (HRQoL) have been extensively studied, less is known at the regional level, particularly in France where no multilevel evidence is available. Using data from a large representative cross-sectional survey conducted in 2003 (N=16 732), this study explores individual and regional determinants of the SF-36 Physical Functioning and Mental Health subscales. We considered a causal pathway leading from deindustrialization to HRQoL and assessed the roles of net migratory flows, deprivation, and the social and physical environments. Worse HRQoL results were found in regions most affected by deindustrialization, with evidence for mediating effects of migration, voter abstention rate and individual health-related behaviors. Cross-level interactions and intraregional heterogeneity were also found, confirming the complexity of individual-area relationships and the need for carefully conceptualized multilevel analyses to guide health policies effectively. © 2013 Elsevier Ltd.

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