High quality standards for a large-scale prospective population-based observational cohort: Constances.

BACKGROUND: Long-term multicentre studies are subject to numerous factors that may affect the integrity of their conclusions. Quality control and standardization of data collection are crucial to minimise the biases induced by these factors. Nevertheless, tools implemented to manage biases are rarely described in publications about population-based cohorts. This report aims to describe the processes implemented to control biases in the Constances cohort taking lung function results as an example. METHODS: Constances is a general-purpose population-based cohort of 200,000 participants. Volunteers attend physical examinations at baseline and then every 5 years at selected study sites. Medical device specifications and measurement methods have to comply with Standard Operating Procedures developed by experts. Protocol deviations are assessed by on-site inspections and database controls. In February 2016, more than 94,000 participants yielding around 30 million readings from physical exams, had been covered by our quality program. RESULTS: Participating centres accepted to revise their practices in accordance with the study research specifications. Distributors of medical devices were asked to comply with international guidelines and Constances requirements. Close monitoring enhanced the quality of measurements and recordings of the physical exams. Regarding lung function testing, spirometry acceptability rates per operator doubled in some sites within a few months and global repeatability reached 96.7 % for 29,772 acceptable maneuvers. CONCLUSIONS: Despite Constances volunteers being followed in multiple sites with heterogeneous materials, the investment of significant resources to set up and maintain a continuous quality management process has proved effective in preventing drifts and improving accuracy of collected data.

Metabolic syndrome and social deprivation: results of a French observational multicentre survey.

BACKGROUND: Deprivation, a process that prevents people to assume their social responsibilities, is a main cause of inequalities in health. Metabolic syndrome has a growing prevalence in France. OBJECTIVES: To assess the association between deprivation and the metabolic syndrome and to identify the most relevant waist circumference cut-off point. METHODS: A cross-sectional multicentre study was carried out of data extracted from health examination centres of two French areas in 2008. The harmonized definition of the metabolic syndrome contained five criteria with two thresholds for waist circumference. Deprivation was calculated by the Evaluation of Deprivation and Inequalities in Health Examination Centres score (EPICES). Eligible patients were at least 16 years old. The methodology of time to event analysis was used on patients having two criteria to identify the most relevant waist circumference threshold, taking waist circumference as event and computing it as a continuous variable. The median corresponded to the waist circumference threshold for which half of the patients switched from two to three criteria and so metabolic syndrome. RESULTS: Of the 32374 persons included in the study, 39.4% were socially deprived. The prevalence of the metabolic syndrome varied from 16.3% to 22.2% in the overall sample depending on the published waist circumference thresholds chosen. Deprivation was an independent factor associated with the metabolic syndrome. The cut-off point for waist circumference was between 95 and 99 cm for men and 88 and 97 cm for women. CONCLUSION: Deprivation is associated with a higher prevalence of the metabolic syndrome. The most relevant threshold for waist circumference could be 94 cm for men and 88 cm for women.

Fat-free mass predictions through a Bayesian Network enable body composition comparisons in various populations.

The respective contribution of fat-free mass (FFM) and fat mass to body weight (Wgt) is a relevant indicator of risk for major public health issues. In an earlier study, a Bayesian Network (BN) was designed to predict FFM from a DXA database (1999-2004 NHANES, n = 10,402) with easily accessible variables [sex, age, Wgt, and height (Hgt)]. The objective of the present study was to assess the robustness of these BN predictions in different population contexts (age, BMI, ethnicity, etc.) when covariables were stochastically deduced from population-based distributions. BN covariables were adjusted to 82 published distributions for age, Wgt, and Hgt from 16 studies assessing body composition. Anthropometric adjustments required a surrogate database (n = 23,411) to get the missing correlation between published Wgt and Hgt distributions. Published BMI distributions and their predicted BN counterparts were correlated (R(2) = 0.99; P < 0.001). Predicted FFM distributions were closely adjusted to their published counterparts for both sexes between 20 and 79 y old, with some discrepancies for Asian populations. In addition, BN predictions revealed a very good agreement between FFM assessed in different population contexts. The mean difference between published FFM values (61.1 ± 3.44 and 42.7 ± 3.32 kg for men and women, respectively) and BN predictions (61.6 ± 3.11 and 42.4 ± 2.76 kg for men and women, respectively) was <1% when FFM was assessed by DXA; the difference rose to 3.6% when FFM was assessed by bioelectric impedance analysis or by densitometry methods. These results suggest that it is possible, within certain anthropometric limitations, to use BN predictions as a complementary body composition analysis for large populations.

The CONSTANCES cohort: an open epidemiological laboratory.

BACKGROUND: Prospective cohorts represent an essential design for epidemiological studies and allow for the study of the combined effects of lifestyle, environment, genetic predisposition, and other risk factors on a large variety of disease endpoints. The CONSTANCES cohort is intended to provide public health information and to serve as an "open epidemiologic laboratory" accessible to the epidemiologic research community. Although designed as a "general-purpose" cohort with very broad coverage, it will particularly focus on occupational and social determinants of health, and on aging. METHODS: The CONSTANCES cohort is designed as a randomly selected representative sample of French adults aged 18-69 years at inception; 200,000 subjects will be included over a five-year period. At inclusion, the selected subjects will be invited to fill a questionnaire and to attend a Health Screening Center (HSC) for a comprehensive health examination: weight, height, blood pressure, electrocardiogram, vision, auditory, spirometry, and biological parameters; for those aged 45 years and older, a specific work-up of functional, physical, and cognitive capacities will be performed. A biobank will be set up. The follow-up includes a yearly self-administered questionnaire, and a periodic visit to an HSC. Social and work-related events and health data will be collected from the French national retirement, health and death databases. The data that will be collected include social and demographic characteristics, socioeconomic status, life events, behaviors, and occupational factors. The health data will cover a wide spectrum: self-reported health scales, reported prevalent and incident diseases, long-term chronic diseases and hospitalizations, sick-leaves, handicaps, limitations, disabilities and injuries, healthcare utilization and services provided, and causes of death. To take into account non-participation at inclusion and attrition throughout the longitudinal follow-up, a cohort of non-participants will be set up and followed through the same national databases as participants. A field-pilot was performed in 2010 in seven HSCs, which included about 3,500 subjects; it showed a satisfactory structure of the sample and a good validity of the collected data. DISCUSSION: The constitution of the full eligible sample is planned during the last trimester of 2010, and the cohort will be launched at the beginning of 2011.

[Psychological support for socially vulnerable people in the context of a periodic health examination]. / Soutien psychologique chez des personnes en fragilité sociale dans le cadre d'un examen périodique de santé.

Social vulnerability often leads to the expression of psychological distress. The Health Examination Center of Côtes d'Armor, in Quimper, experimented with the development and implementation of psychological counseling for a highly socio-economically vulnerable population. As part of a periodic health examination, the center offers psychological counseling to patients with pathological sleep disorders and who lack sufficient psychological support. The Health Examination Center's framework and the context of the periodic health examination have facilitated the establishment of a tailored non-stigmatizing intervention well-embedded within the institutional environment. Marginalized people in situations of psychological distress are offered an opportunity to be listened to, and to receive counseling, appropriate prevention services and access to care.

Phenotypic expression in detected C282Y homozygous women depends on body mass index.

BACKGROUND/AIMS: In HFE-related haemochromatosis, a large proportion of C282Y homozygotes, especially women, are not detected by phenotypic screening using transferrin saturation. The aim of this study was to identify the clinical and biochemical factors associated with non-expression of the disease as defined as transferrin saturation <45%. METHODS: The study was performed in 78 (57 women and 21 men) C282Y homozygotes identified through a large-scale screening program conducted on 19,644 French subjects. Biometric, clinical and biochemical variables including those susceptible to influence body iron stores were tested for association with transferrin saturation levels <45%. RESULTS: Non-expression was observed in 26/57 (46%) women and in 5/21 (24%) men. At multivariate analysis, female gender (OR: 16.5, 95%CI 1.8-146.5; P = 0.012), body mass index (OR: 1.21, 95%CI 1.02-1.44; P = 0.027), haemoglobin levels (OR: 0.88, 95%CI 0.81-0.97; P = 0.012) and serum ferritin levels (OR: 0.99, 95%CI 0.98-1.00; P = 0.007) were significantly and independently associated with a non-expressing phenotype. CONCLUSIONS: Excess body mass is commonly associated with the lack of phenotypic expression in detected C282Y homozygotes. This should be kept in mind with respect to the design and cost-effectiveness of phenotypic screening programs for haemochromatosis.

Gender-specific phenotypic expression and screening strategies in C282Y-linked haemochromatosis: a study of 9396 French people.

Most features of C282Y-linked haemochromatosis support the implementation of population screening of the disorder in Caucasians. However, the penetrance of C282Y homozygosity is poorly documented and the strategy for population screening remains debated. Nine thousand three hundred and ninety-six subjects (3367 men, aged 25-40 years, and 6029 women, aged 35-50 years), attending three Health Appraisal Centres, were genotyped and assessed with respect to clinical and biochemical signs of haemochromatosis. Discriminant, logistic regression and graphic analysis were used to predict homozygosity. Results were validated in 135 homozygotes detected through other family and population studies. Fifty-four subjects (10 men and 44 women) were homozygous for C282Y. All men had abnormal iron status and most had mild clinical symptoms compatible with haemochromatosis. Identification of all homozygous men required a transferrin saturation (TS) threshold of 50% in the study group (90% specificity) and of 40% in the validation group. Homozygous women differed clinically from non-homozygotes for the presence of distal arthralgias only (18%vs 6%, P < 0.03). Thirteen (29%) were iron-deficient (serum ferritin < 13 micro g/l) and undetectable by biochemical tests. Although the population studied was not fully representative of the general population, our data strongly suggests that, in young men, large-scale screening for C282Y homozygosity is justified and can be achieved by using TS prescreening. However, in premenopausal women, large-scale screening remains to be justified with respect to the natural history of haemochromatosis and should be directly genotypic.