Age at death during the Covid-19 lockdown in French metropolitan regions: a non parametric quantile regression approach.

BACKGROUND: Lockdowns have been implemented to limit the number of hospitalisations and deaths during the first wave of 2019 coronavirus disease. These measures may have affected differently death characteristics, such age and sex. France was one of the hardest hit countries in Europe with a decreasing east-west gradient in excess mortality. This study aimed at describing the evolution of age at death quantiles during the lockdown in spring 2020 (17 March-11 May 2020) in the French metropolitan regions focusing on 3 representatives of the epidemic variations in the country: Bretagne, Ile-de-France (IDF) and Bourgogne-Franche-Comté (BFC). METHODS: Data were extracted from the French public mortality database from 1 January 2011 to 31 August 2020. The age distribution of mortality observed during the lockdown period (based on each decile, plus quantiles 1, 5, 95 and 99) was compared with the expected one using Bayesian non-parametric quantile regression. RESULTS: During the lockdown, 5457, 5917 and 22 346 deaths were reported in Bretagne, BFC and IDF, respectively. An excess mortality from + 3% in Bretagne to + 102% in IDF was observed during lockdown compared to the 3 previous years. Lockdown led to an important increase in the first quantiles of age at death, irrespective of the region, while the increase was more gradual for older age groups. It corresponded to fewer young people, mainly males, dying during the lockdown, with an increase in the age at death in the first quantile of about 7 years across regions. In females, a less significant shift in the first quantiles and a greater heterogeneity between regions were shown. A greater shift was observed in eastern region and IDF, which may also represent excess mortality among the elderly. CONCLUSIONS: This study focused on the innovative outcome of the age distribution at death. It shows the first quantiles of age at death increased differentially according to sex during the lockdown period, overall shift seems to depend on prior epidemic intensity before lockdown and complements studies on excess mortality during lockdowns.

Regional excess mortality in France during COVID-19 pandemic: the first three epidemic periods (March 2020-June 2021).

BACKGROUND: This study aimed to describe the mortality excess during the three first epidemic periods of COVID-19 in all regions of France. METHODS: Two complementary approaches were implemented. First, we described the number of death of patients infected with or diagnosed with COVID-19 in health care (HC) and medico-social (MS) institutions. Then, we estimated general all-cause mortality excess (all ages) by comparing the mortality observed with the expected mortality. We used a daily number of death model according to a negative binomial distribution, as a function of the long-term trend in mortality (penalized spline function of time) and its seasonal variation (cyclic spline function). The model provided expected mortality during epidemic periods with a 95% credibility interval. Each region defined three epidemic periods, including the overseas territories. RESULTS: The two approaches were consistent in the most affected regions but there are major regional disparities that vary according to the epidemic period. There is an east-west gradient in the relative excess of deaths from all-causes during each epidemic period. The deaths observed in HC and MS institutions alone do not explain the excess (or deficit) of mortality in each region and epidemic period. CONCLUSION: An analysis by age group according to the two approaches and a comparison of death specific causes could provide a better understanding of these differences. Electronic death registration system (mortality by medical causes) would allow a rapid mortality related estimation to an emerging pathology like Coronavirus Disease-2019 (COVID-19) but is still insufficient for real-time medical causes of death monitoring.

On the supra-linearity of the relationship between air pollution, mortality and hospital admission in 18 French cities.

PURPOSE: Understanding the relationship between an environmental determinant and a given health outcome is key to inform public health policies. The short-term mortality and morbidity responses to outdoor air pollutants are traditionally assessed as a log-linear relationship, but few studies suggest a possible deviation from linearity. This paper investigates the shape of the relationship between ozone, NO2 and fine particulate matter (PM10 and PM2.5), mortality and hospital admissions in 18 French cities between 2000 and 2017. METHOD: A multi-centric time series design, using quasi-Poisson generalized additive models, was used. Four approaches were compared to model concentration-response curves (log-linear, piecewise-linear with a priori defined breakpoints, piecewise-linear with no a priori breakpoint and cubic spline). RESULTS: All the models indicated evidence of supra-linearity between PM10, PM2.5, NO2, mortality and hospital admissions. For instance, with a log-linear model, a 10 µg/m3 increase in PM2.5 was associated with a 0.4% [95% CI 0.2; 0.7] increase in non-accidental mortality. When using a piecewise model with a priori set breakpoint at 10 µg/m3, the mortality increase was 3.8% [4.4; 6.3] below 10 µg/m3, and 0.3% [0; 0.6] above. Non-significant impacts of ozone were found for concentrations below 90 µg/m3 to 120 µg/m3, with some variability in the identified threshold across the heath indicator studied. CONCLUSION: The supra-linearity of the relationship between PM10, PM2.5, NO2, mortality and hospital admissions supports the need to further reduce air pollution concentrations well below regulatory values.

Influence of exposure assessment methods on associations between long-term exposure to outdoor fine particulate matter and risk of cancer in the French cohort Gazel.

BACKGROUND: Many studies investigated the relationship between outdoor fine particulate matter (PM2.5) and cancer. While they generally indicated positive associations, results have not been fully consistent, possibly because of the diversity of methods used to assess exposure. OBJECTIVES: To investigate how using different PM2.5 exposure assessment methods influences risk estimates in the large French general population-based Gazel cohort (20,625 participants at enrollment) with a 26-year follow-up with complete residential histories. METHODS: We focused on two cancer incidence outcomes: all-sites combined and lung. We used two distinct exposure assessment methods: a western European land use regression (LUR), and a chemistry-dispersion model (Gazel-Air) for France, each with a time series ≥20-years annual concentrations. Spearman correlation coefficient between the two estimates of PM2.5 was 0.71 across all person-years; the LUR tended to provide higher exposures. We used extended Cox models with attained age as time-scale and time-dependent cumulative exposures, adjusting for a set of confounders including sex and smoking, to derive hazard ratios (HRs) and their 95% confidence interval, implementing a 10-year lag between exposure and incidence/censoring. RESULTS: We obtained similar two-piece linear associations for all-sites cancer (3711 cases), with a first slope of HRs of 1.53 (1.24-1.88) and 1.43 (1.19-1.73) for one IQR increase of cumulative PM2.5 exposure for the LUR and the Gazel-Air models respectively, followed by a plateau at around 1.5 for both exposure assessments. For lung cancer (349 cases), the HRs from the two exposure models were less similar, with largely overlapping confidence limits. CONCLUSION: Our findings using long-term exposure estimates from two distinct exposure assessment methods corroborate the association between air pollution and cancer risk.

Identification of Workers at Increased Risk of Infection During a COVID-19 Outbreak in a Meat Processing Plant, France, May 2020.

On 13 May 2020, a COVID-19 cluster was detected in a French processing plant. Infected workers were described. The associations between the SARS-CoV-2 infection and the socio-demographic and occupational characteristics were assessed in order to implement risk management measures targeting workers at increased risk of contamination. Workers were tested by RT-PCR from samples taken during screening campaigns. Workers who tested positive were isolated and their contacts were quarantined. Workers were described and associations with the SARS-CoV-2 infection were assessed through risk ratios using multivariable Poisson regression. Of the 1347 workers, 87.5% were tested: 140 cases were identified; 4 were hospitalised, including 2 admitted to intensive care. In the company, the cluster remained limited to deboning and cutting activities. The attack rate was 11.9% in the company, reaching 16.6% in the cutting department. Being an employee of a subcontractor significantly increased the risk of infection by 2.98 [1.81-4.99]. In the cutting department, an association with virus infection was found for a group of non-French speaking workers from the same Eastern European country (RR = 2.67 [1.76-4.05]). They shared accommodation or carpooled more frequently than the other cases. The outbreak investigation revealed a significantly increased risk of SARS-CoV-2 infection for workers of subcontractors and some foreign-born workers. There are many such populations in meat processing plants; the observed associations and the ways in which these workers are contaminated need to be confirmed by further work. Prevention campaigns should now target these workers. Environmental risk factors in the workplace setting remain to be clarified.

Evolving heat waves characteristics challenge heat warning systems and prevention plans.

This paper analyses how recent trends in heat waves impact heat warning systems. We performed a retrospective analysis of the challenges faced by the French heat prevention plan since 2004. We described trends based on the environmental and health data collected each summer by the French heat warning system and prevention plan. Major evolutions of the system were tracked based on the evaluations organized each autumn with the stakeholders of the prevention plan. Excess deaths numbering 8000 were observed during heat waves between 2004 and 2019, 71% of these between 2015 and 2019. We observed major changes in the characteristics, frequency and the geographical spread of heat waves since 2015. Feedbacks led to several updates of the warning system such as the extension of the surveillance period. They also revealed that risk perception remained limited among the population and the stakeholders. The sharp increase in the number of heat warnings issued per year since 2015 challenges the acceptability of the heat warnings. Recent heat waves without historical equivalent interfere with the development of evidence-based prevention strategies. The growing public health impacts heat waves emphasize the urgent need to act to adapt the population, at different levels of intervention, from individual comportments to structural modifications. A specific attention should be given to increase the resources allocated to the evaluation and the management of heat-related risks, especially considering the needs to catch with the rapid rhythm of the changing climate.

Implementation of various hypothetical low emission zone scenarios in Greater Paris: Assessment of fine-scale reduction in exposure and expected health benefits.

OBJECTIVES: Literature assessing the effects of policies aimed at reducing traffic-related air pollution is scarce. The aims of this study were to evaluate the expected impacts, in terms of air quality and health effects, of various hypothetical low-emission zone (LEZ) scenarios in Greater Paris for a planned intervention in 2018/2019 which combine two different perimeters and two levels of vehicles ban, and to assess those impacts according to the socioeconomic status (SES) of the population. METHODS: We evaluated the effects of four hypothetical LEZ scenarios on various stages of the full-chain model, more specifically, road traffic modelling (traffic flow, type of vehicles and related number of kilometers driven), emissions, fine scale PM2.5 and NO2 concentrations, related resident population exposure, and health effects. We computed the overall benefits of expected air pollution improvements in terms of preventable deaths and a decrease in new cases of the following three major chronic diseases: ischemic heart diseases in adults, asthma in children and low weight in full-term newborns. RESULTS: The most stringent LEZ scenario would lower the maximum level of exposure from 55 µg/m3 to 42 µg/m3 in Paris. In one year, this scenario would help prevent: 340 deaths (-0.6%) representing 114,300 life years gained, 170 low-weight full-term births (-4.9%), 130 new cases of ischemic heart disease (IHD) (-1.8%) and 2930 new cases of asthma (-3.0%) among 9.4 million residents. Residents outside the LEZ would also benefit from this scenario. Results indicated that the intervention could contribute to increasing inequalities. The comparison of scenarios underlined the value of extending the LEZ to include a wider zone (including 80 more municipalities surrounding Paris). This would lead to a more equitable spread of the benefits over the population. CONCLUSION: Traffic control policies such as LEZ are difficult to accept for some categories of commuters and economic stakeholders. As of June 2019, the concertation process for the proposed Paris LEZ is still ongoing. This work provides authorities with detailed analyses of the options for this measure as well as information on related implications. It will help decision makers prioritize which preventive measures to introduce.

The fraction of lung cancer incidence attributable to fine particulate air pollution in France: Impact of spatial resolution of air pollution models.

Outdoor air pollution is a leading environmental cause of death and cancer incidence in humans. We aimed to estimate the fraction of lung cancer incidence attributable to fine particulate matter (PM2.5) exposure in France, and secondarily to illustrate the influence of the input data and the spatial resolution of information on air pollution levels on this estimate. The population attributable fraction (PAF) was estimated using a nationwide spatially refined chemistry-transport model with a 2-km spatial resolution, neighbourhood-scale population density data, and a relative risk from a published meta-analysis. We used the WHO guideline value for PM2.5 exposure (10 µg/m3) as reference. Sensitivity analyses consisted in attributing the nation-wide median exposure to all areas and using alternative input data such as reference of PM2.5 exposure level and relative risk. Population-weighted median PM2.5 level in 2005 was 13.8 µg/m3; 87% of the population was exposed above the guideline value. The burden of lung cancer attributable to PM2.5 exposure corresponded to 1466 cases, or 3.6% of all cases diagnosed in 2015. Sensitivity analyses showed that the use of a national median of PM2.5 exposure would have led to an underestimation of the PAF by 11% (population-weighted median) and by 72% (median of raw concentration), suggesting that our estimates would have been higher with even more finely spatially-resolved models. When the PM2.5 reference level was replaced by the 5th percentile of country-scale exposure (4.9 µg/m3), PAF increased to 7.6%. Other sensitivity analyses resulted in even higher PAFs. Improvements in air pollution are crucial for quantitative health impacts assessment studies. Actions to reduce PM2.5 levels could substantially reduce the burden of lung cancer in France.

Quantitative health impact of indoor radon in France.

Radon is the second leading cause of lung cancer after smoking. Since the previous quantitative risk assessment of indoor radon conducted in France, input data have changed such as, estimates of indoor radon concentrations, lung cancer rates and the prevalence of tobacco consumption. The aim of this work was to update the risk assessment of lung cancer mortality attributable to indoor radon in France using recent risk models and data, improving the consideration of smoking, and providing results at a fine geographical scale. The data used were population data (2012), vital statistics on death from lung cancer (2008-2012), domestic radon exposure from a recent database that combines measurement results of indoor radon concentration and the geogenic radon potential map for France (2015), and smoking prevalence (2010). The risk model used was derived from a European epidemiological study, considering that lung cancer risk increased by 16% per 100 becquerels per cubic meter (Bq/m3) indoor radon concentration. The estimated number of lung cancer deaths attributable to indoor radon exposure is about 3000 (1000; 5000), which corresponds to about 10% of all lung cancer deaths each year in France. About 33% of lung cancer deaths attributable to radon are due to exposure levels above 100 Bq/m3. Considering the combined effect of tobacco and radon, the study shows that 75% of estimated radon-attributable lung cancer deaths occur among current smokers, 20% among ex-smokers and 5% among never-smokers. It is concluded that the results of this study, which are based on precise estimates of indoor radon concentrations at finest geographical scale, can serve as a basis for defining French policy against radon risk.

Epidemiology of Childhood Hyperthyroidism in France: A Nationwide Population-Based Study.

Context: Hyperthyroidism affects all age groups, but epidemiological data for children are scarce. Objective: To perform a nationwide epidemiological survey of hyperthyroidism in children and adolescents. Design: A cross-sectional descriptive study. Setting: Identification of entries corresponding to reimbursements for antithyroid drugs in the French national insurance database. Participants: All cases of childhood hyperthyroidism (6 months to 17 years of age) in 2015. Main Outcome Measures: National incidence rate estimated with a nonlinear Poisson model and spatial distribution of cases. Results: A total of 670 cases of childhood hyperthyroidism were identified. Twenty patients (3%) had associated autoimmune or genetic disease, with type 1 diabetes and Down syndrome the most frequent. The annual incidence for 2015 was 4.58/100,000 person-years (95% CI 3.00 to 6.99/100,000). Incidence increased with age, in both sexes. This increase accelerated after the age of 8 in girls and 10 in boys and was stronger in girls. About 10% of patients were affected before the age of 5 years (sex ratio 1.43). There was an interaction between age and sex, the effect of being female increasing with age: girls were 3.2 times more likely to be affected than boys in the 10 to 14 years age group and 5.7 times more likely to be affected in the 15 to 17 years age group. No conclusions about spatial pattern emerged. Conclusion: These findings shed light on the incidence of hyperthyroidism and the impact of sex on this incidence during childhood and adolescence. The observed incidence was higher than expected from the results published for earlier studies in Northern European countries.

Prenatal exposure to lead in France: Cord-blood levels and associated factors: Results from the perinatal component of the French Longitudinal Study since Childhood (Elfe).

BACKGROUND: As a result of the ban on lead in gasoline on 2nd January 2000, the French population's exposure to lead has decreased in recent years. However, because of the acknowledged harmful cognitive effects of lead even at low levels, lead exposure remains a major public health issue. In France, few biomonitoring data are available for exposure to lead in pregnant women and newborn. The purpose of the perinatal component of the French human biomonitoring (HBM) program was to describe levels of various biomarkers of exposure to several environmental pollutants, including lead, among mother-baby pairs. In this paper, we aimed to describe the distribution of cord blood lead levels (CBLL) in French mother-baby pairs, and to estimate the contribution of the main lead exposure risk factors to these levels. METHOD: A total of 1968 mother-baby pairs selected from the participants of the perinatal component of the French HBM program were included in the study on lead. Lead levels were analyzed in cord blood collected at child delivery by inductively coupled plasma-mass spectrometry (ICP-MS). The data collected included biological sample, socio-demographic characteristics, environmental and occupational exposure, and information on dietary factors. RESULTS: CBLL were quantified for 99.5% of the sample. The CBLL geometric mean was 8.30 µg/l (95% CI [7.94-8.68]) with a 95th percentile of 24.3 µg/l (95% CI [20.7-27.1]). Factors significantly associated with CBLL were tap water consumption, alcohol consumption, shellfish consumption, vegetable consumption, bread consumption, smoking, and the mother being born in countries where lead is often used. CONCLUSION: This study provides the first reference value for CBLL in a random sample of mother-baby pairs not particularly exposed to high levels of lead (24.3 µg/l). A substantial decrease in CBLL over time was observed, which confirms the decrease of exposure to lead among the general population. CBLL observed in this French study were in the range of those found in recent surveys conducted in other countries.

Marked geographic patterns in the incidence of idiopathic central precocious puberty: a nationwide study in France.

OBJECTIVES: Precocious puberty seems to be increasing but epidemiological data are scarce. Our objective was to improve the epidemiologic knowledge on this disease. We analyzed the national incidence and spatial trends of idiopathic central precocious puberty in France in 2011-2013 in a cross-sectional descriptive study. DESIGN: We used an indicator based on treatment reimbursements recorded in the national insurance database, in girls under the age of nine years and in boys under the age of 10 years. We considered a time lag of up to one year from the onset of puberty to first drug delivery. We tested four different predictive spatial models at the département scale, selecting the model best fitting the data. We carried out semi-structured interviews with qualified hospital teams in five selected regions to investigate spatial differences in medical practices. RESULTS: The national annual incidence was 2.68 (95% CI: 2.55, 2.81) per 10 000 girls under the age of 9 years and 0.24 (95% CI: 0.21, 0.27) per 10 000 boys under the age of 10 years. Incidence rates conformed to a purely spatial heterogeneity model in girls, consistent between age groups, with a large incidence range. A similar pattern was observed for boys, with peaks in the South West and Center East. Differences in medical practices may have slightly affected incidence locally, but could not entirely explain the marked geographic pattern. CONCLUSIONS: The results suggest that the risk factors are similar for boys and girls and justify further investigations of the role of the environment.

A new efficient method to monitor precocious puberty nationwide in France.

Clinical precocious puberty (PP) is a disease, reputed to be on the increase and suspected to be linked to endocrine disrupting chemicals (EDC) exposure. Population-based epidemiological data are lacking in France and scarce elsewhere. We accessed the feasibility of monitoring PP nationwide in France in this context, using a nationwide existing database, the French National Health Insurance Information System. Here, we present the method we used with a step-by-step approach to build and select the most suitable indicator. We built three indicators reflecting the incidence of idiopathic central precocious puberty (ICPP), the most frequent form of PP, and we compared these indicators according to their strengths and weaknesses with respect to surveillance purposes. CONCLUSION: Monitoring ICPP in France proved feasible using a Drug reimbursement indicator. Our method is cost efficient and highly relevant in public health surveillance. Our step-by-step approach proved helpful to achieve this project and could be proposed for assessing the feasibility of monitoring health outcomes of interest using existing data bases. What is known: • Precocious puberty (PP) is suspected to be related to EDC exposure and it is believed to be on the increase in France and in others countries. • Very few epidemiologic data on PP are currently available in the world at the national scale. What is new: • This is the first study describing a method to monitor the most frequent form of PP, idiopathic central PP (ICPP) nationwide in a cost-efficient way, using health insurance databases. • This cost-effective method will allow to estimate and monitor the incidence of ICPP in France and to analyze spatial variations at a very precise scale, which will be very useful to examine the role of environmental exposures, especially to EDCs.

Biomarkers of exposure to environmental contaminants in French pregnant women from the Elfe cohort in 2011.

BACKGROUND: As part of the perinatal component of the French Human Biomonitoring (HBM) program, biomarkers levels of various chemicals have been described among pregnant women having given birth in continental France in 2011 and who have been enrolled in the Elfe cohort (French Longitudinal Study since Childhood). This paper describes the design of the study and provides main descriptive results regarding exposure biomarkers levels. METHODS: Exposure biomarkers were measured in biological samples collected at delivery from pregnant women randomly selected among the participants in the clinical and biological component of the Elfe cohort (n=4145). The geometric mean and percentiles of the levels distribution were estimated for each biomarker. The sampling design was taken into account in order to obtain estimates representative of the French pregnant women in 2011. RESULTS: Results provide a nation-wide representative description of biomarker levels for important environmental contaminants among pregnant women who gave birth in France in 2011. Bisphenol A (BPA), and some metabolites of phthalates, pesticides (mainly pyrethroids), dioxins, furans, polychlorobiphenyls (PCBs), brominated flame retardants (BFRs), perfluorinated compounds (PFCs) and metals (except uranium) were quantified in almost 100% of the pregnant women. Some compounds showed a downward trend compared to previous studies (lead, mercury), but others did not (pyrethroids) and should be further monitored. CONCLUSION AND PERSPECTIVES: The present results show that French pregnant women are exposed to a wide variety of pollutants, including some that have been banned or restricted in France.

The mortality impacts of fine particles in France.

INTRODUCTION: Worldwide, air pollution has become a main environmental cause of premature mortality. This burden is largely due to fine particles. Recent cohort studies have confirmed the health risks associated with chronic exposure to PM2.5 for European and French populations. We assessed the mortality impact of PM2.5 in continental France using these new results. METHODS: Based on a meta-analysis of French and European cohorts, we computed a shrunken estimate of PM2.5-mortality relationship for the French population (RR 1.15 [1.05:1.25] for a 10µg/m(3) increase in PM2.5). This RR was applied to PM2.5 annual concentrations estimated at a fine spatial scale, using a classical health impacts assessment method. The health benefits associated with alternative scenarios of improving air quality were computed for 36,219 French municipalities for 2007-2008. RESULTS: 9% of the total mortality in continental France is attributable to anthropogenic PM2.5. This represents >48,000 deaths per year, and 950,000years of life lost per year, more than half occurring in urban areas larger than 100,000 inhabitants. If none of the municipalities exceeded the World Health Organization guideline value for PM2.5 (10µg/m(3)), the total mortality could be decreased by 3%, corresponding to 400,000years of life saved per year. CONCLUSION: Results were consistent with previous estimates of the long-term mortality impacts of fine particles in France. These findings show that further actions to improve air quality in France would substantially improve health.

Screening for Elevated Blood Lead Levels in Children: Assessment of Criteria and a Proposal for New Ones in France.

The decline in children's Blood Lead Levels (BLL) raises questions about the ability of current lead poisoning screening criteria to identify those children most exposed. The objectives of the study were to evaluate the performance of current screening criteria in identifying children with blood lead levels higher than 50 µg/L in France, and to propose new criteria. Data from a national French survey, conducted among 3831 children aged 6 months to 6 years in 2008-2009 were used. The sensitivity and specificity of the current criteria in predicting blood lead levels higher than or equal to 50 µg/L were evaluated. Two predictive models of BLL above 44 µg/L (for lack of sufficient sample size at 50 µg/L) were built: the first using current criteria, and the second using newly identified risk factors. For each model, performance was studied by calculating the area under the ROC (Receiver Operating Characteristic) curve. The sensitivity of current criteria for detecting BLL higher than or equal to 50 µg/L was 0.51 (0.26; 0.75) and specificity was 0.66 (0.62; 0.70). The new model included the following criteria: foreign child newly arrived in France, mother born abroad, consumption of tap water in the presence of lead pipes, pre-1949 housing, period of construction of housing unknown, presence of peeling paint, parental smoking at home, occupancy rates for housing and child's address in a cadastral municipality or census block comprising more than 6% of housing that is potentially unfit and built pre-1949. The area under the ROC curve was 0.86 for the new model, versus 0.76 for the current one. The lead poisoning screening criteria should be updated. The risk of industrial, occupational and hobby-related exposure could not be assessed in this study, but should be kept as screening criteria.

Association between long-term exposure to air pollution and mortality in France: A 25-year follow-up study.

INTRODUCTION: Long-term exposure to air pollution (AP) has been shown to have an impact on mortality in numerous countries, but since 2005 no data exists for France. OBJECTIVES: We analyzed the association between long-term exposure to air pollution and mortality at the individual level in a large French cohort followed from 1989 to 2013. METHODS: The study sample consisted of 20,327 adults working at the French national electricity and gas company EDF-GDF. Annual exposure to PM10, PM10­2.5, PM2.5, NO2, O3, SO2, and benzene was assessed for the place of residence of participants using a chemistry-transport model and taking residential history into account. Hazard ratios were estimated using a Cox proportional-hazards regression model, adjusted for selected individual and contextual risk factors. Hazard ratios were computed for an interquartile range (IQR) increase in air pollutant concentrations. RESULTS: The cohort recorded 1967 non-accidental deaths. Long-term exposures to b aseline PM2.5, PM10-25, NO2 and benzene were associated with an increase in non-accidental mortality (Hazard Ratio, HR = 1.09; 95% CI: 0.99, 1.20 per 5.9 µg/m3, PM10-25; HR=1.09; 95% CI: 1.04, 1.15 per 2.2 µg/m3, NO2: HR=1.14; 95% CI: 0.99, 1.31 per 19.3 µg/m3 and benzene: HR=1.10; 95% CI: 1.00, 1.22 per 1.7 µg/m3).The strongest association was found for PM10: HR = 1.14; 95% CI: 1.05, 1.25 per 7.8 µg/m3. PM10, PM10-25 and SO2 were associated with non-accidental mortality when using time varying exposure. No significant associations were observed between air pollution and cardiovascular and respiratory mortality. CONCLUSION: Long-term exposure to fine particles, nitrogen dioxide, sulfur dioxide and benzene is associated with an increased risk of non-accidental mortality in France. Our results strengthen existing evidence that outdoor air pollution is a significant environmental risk factor for mortality. Due to the limited sample size and the nature of our study (occupational), further investigations are needed in France with a larger representative population sample.

An original imputation technique of missing data for assessing exposure of newborns to perchlorate in drinking water.

INTRODUCTION: Incompleteness of epidemiological databases is a major drawback when it comes to analyzing data. We conceived an epidemiological study to assess the association between newborn thyroid function and the exposure to perchlorates found in the tap water of the mother's home. Only 9% of newborn's exposure to perchlorate was known. The aim of our study was to design, test and evaluate an original method for imputing perchlorate exposure of newborns based on their maternity of birth. METHODS: In a first database, an exhaustive collection of newborn's thyroid function measured during a systematic neonatal screening was collected. In this database the municipality of residence of the newborn's mother was only available for 2012. Between 2004 and 2011, the closest data available was the municipality of the maternity of birth. Exposure was assessed using a second database which contained the perchlorate levels for each municipality. We computed the catchment area of every maternity ward based on the French nationwide exhaustive database of inpatient stay. Municipality, and consequently perchlorate exposure, was imputed by a weighted draw in the catchment area. Missing values for remaining covariates were imputed by chained equation. A linear mixture model was computed on each imputed dataset. We compared odds ratios (ORs) and 95% confidence intervals (95% CI) estimated on real versus imputed 2012 data. The same model was then carried out for the whole imputed database. RESULTS: The ORs estimated on 36,695 observations by our multiple imputation method are comparable to the real 2012 data. On the 394,979 observations of the whole database, the ORs remain stable but the 95% CI tighten considerably. DISCUSSION: The model estimates computed on imputed data are similar to those calculated on real data. The main advantage of multiple imputation is to provide unbiased estimate of the ORs while maintaining their variances. Thus, our method will be used to increase the statistical power of future studies by including all 394,979 newborns.

Environmental determinants of different blood lead levels in children: a quantile analysis from a nationwide survey.

Blood lead levels (BLLs) have substantially decreased in recent decades in children in France. However, further reducing exposure is a public health goal because there is no clear toxicological threshold. The identification of the environmental determinants of BLLs as well as risk factors associated with high BLLs is important to update prevention strategies. We aimed to estimate the contribution of environmental sources of lead to different BLLs in children in France. We enrolled 484 children aged from 6months to 6years, in a nationwide cross-sectional survey in 2008-2009. We measured lead concentrations in blood and environmental samples (water, soils, household settled dusts, paints, cosmetics and traditional cookware). We performed two models: a multivariate generalized additive model on the geometric mean (GM), and a quantile regression model on the 10th, 25th, 50th, 75th and 90th quantile of BLLs. The GM of BLLs was 13.8µg/L (=1.38µg/dL) (95% confidence intervals (CI): 12.7-14.9) and the 90th quantile was 25.7µg/L (CI: 24.2-29.5). Household and common area dust, tap water, interior paint, ceramic cookware, traditional cosmetics, playground soil and dust, and environmental tobacco smoke were associated with the GM of BLLs. Household dust and tap water made the largest contributions to both the GM and the 90th quantile of BLLs. The concentration of lead in dust was positively correlated with all quantiles of BLLs even at low concentrations. Lead concentrations in tap water above 5µg/L were also positively correlated with the GM, 75th and 90th quantiles of BLLs in children drinking tap water. Preventative actions must target household settled dust and tap water to reduce the BLLs of children in France. The use of traditional cosmetics should be avoided whereas ceramic cookware should be limited to decorative purposes.

Controlling for seasonal patterns and time varying confounders in time-series epidemiological models: a simulation study.

An important topic when estimating the effect of air pollutants on human health is choosing the best method to control for seasonal patterns and time varying confounders, such as temperature and humidity. Semi-parametric Poisson time-series models include smooth functions of calendar time and weather effects to control for potential confounders. Case-crossover (CC) approaches are considered efficient alternatives that control seasonal confounding by design and allow inclusion of smooth functions of weather confounders through their equivalent Poisson representations. We evaluate both methodological designs with respect to seasonal control and compare spline-based approaches, using natural splines and penalized splines, and two time-stratified CC approaches. For the spline-based methods, we consider fixed degrees of freedom, minimization of the partial autocorrelation function, and general cross-validation as smoothing criteria. Issues of model misspecification with respect to weather confounding are investigated under simulation scenarios, which allow quantifying omitted, misspecified, and irrelevant-variable bias. The simulations are based on fully parametric mechanisms designed to replicate two datasets with different mortality and atmospheric patterns. Overall, minimum partial autocorrelation function approaches provide more stable results for high mortality counts and strong seasonal trends, whereas natural splines with fixed degrees of freedom perform better for low mortality counts and weak seasonal trends followed by the time-season-stratified CC model, which performs equally well in terms of bias but yields higher standard errors.