Density and proximity of oil and gas wells and concentrations of trace elements in urine, hair, nails and tap water samples from pregnant individuals living in Northeastern British Columbia.

BACKGROUND: Oil and gas exploitation can release several contaminants in the environment, including trace elements, with potentially deleterious effects on exposed pregnant individuals and their developing fetus. Currently, there is limited data on pregnant individuals' exposure to contaminants associated with oil and gas activity. OBJECTIVES: We aimed to 1)measure concentrations of trace elements in biological and tap water samples collected from pregnant individuals participating in the EXPERIVA study; 2)compare with reference populations and health-based guidance values; 3)assess correlations across matrices; and 4)evaluate associations with the density/proximity of oil and gas wells. METHODS: We collected tap water, hair, nails, and repeated urine samples from 85pregnant individuals, and measured concentrations of 21trace elements. We calculated oil and gas well density/proximity (Inverse Distance Weighting [IDW]) for 4buffer sizes (2.5 km, 5 km, 10 km, no buffer). We performed Spearman's rank correlation analyses to assess the correlations across elements and matrices. We used multiple linear regression models to evaluate the associations between IDWs and concentrations. RESULTS: Some study participants had urinary trace element concentrations exceeding the 95th percentile of reference values; 75% of participants for V, 29% for Co, 22% for Ba, and 20% for Mn. For a given trace element, correlation coefficients ranged from -0.23 to 0.65 across matrices; correlations with tap water concentrations were strongest for hair, followed by nails, and urine. Positive (e.g., Cu, Cr, Sr, U, Ga, Ba, Al, Cd) and negative (e.g., Fe) associations were observed between IDW metrics and the concentrations of certain trace elements in water, hair, and nails. SIGNIFICANCE: Our results suggest that pregnant individuals living in an area of oil and gas activity may be more exposed to certain trace elements (e.g., Mn, Sr, Co, Ba) than the general population. Association with density/proximity of wells remains unclear.

The Influence of Smoking and Occupational Risk Factors on DNA Methylation in the AHRR and F2RL3 Genes.

BACKGROUND: AHRR and F2RL3 hypomethylation has been associated with lung cancer. In this study, we investigated the cross-sectional association between smoking and occupational exposures, and AHRR and F2RL3 methylation. METHODS: A case-control study was nested in CARTaGENE to examine the association between AHRR and F2RL3 methylation and lung cancer risk (200 cases; 400 controls). A secondary analysis was conducted using the data collected from this nested study; namely, baseline information on participants' smoking behavior and longest-held job was obtained. A cumulative smoking index summarized information on the number of cigarettes smoked, duration of smoking, and time since cessation. Exposure to 13 occupational agents was estimated using the Canadian Job Exposure Matrix. In baseline blood samples, methylation ratios of 40 CpG sites in the AHRR and F2RL3 genes were measured using Sequenom EpiTYPER. Separate least squares regression models were used to estimate the associations between smoking and occupational exposures, and average AHRR and F2RL3 methylation levels, while adjusting for confounders identified from directed acyclic graphs. RESULTS: In both genes, smoking was associated with lower average methylation levels. Occupational exposure to aromatic amines, cadmium, and formaldehyde were associated with lower AHRR methylation while, only benzene was associated with F2RL3 hypomethylation; these associations were stronger among ever smokers. CONCLUSIONS: Our findings support that smoking and occupational exposures to some agents are associated with AHRR and F2RL3 hypomethylation. IMPACT: Our results inform on mechanisms underlying environmental exposures in lung cancer etiology; future studies should prioritize studying joint exposures.

Evaluation of a national e-booking system for medical consultation in primary care in a universal health system.

PURPOSE: The Rendez-vous Santé Québec is a national online booking (e-booking) system of medical appointments in primary care rolled out in 2018 in Québec (Canada). The objectives of this study were to describe the adoption by targeted users, and analyze the facilitating and limiting factors at the technological, individual and organizational levels to inform policy makers. METHODS: A mixed methods evaluation was conducted involving interviews with key stakeholders (n = 40), audit logs of the system in 2019, and a population-based survey (n = 2 003). All data were combined to analyze facilitating and limiting factors, based on the DeLone and McLean framework. RESULTS: The RVSQ e-booking system had a low adoption across the province mainly because it was poorly aligned with the diversity of organizational and professional practices. The other commercial e-booking systems already used by clinics seemed better adapted to interdisciplinary care, patient prioritization and advanced access. e-Booking system was appreciated by patients, but has implications for the performance of primary care organization that goes beyond scheduling management issues, with potential detrimental consequences for care continuity and appropriateness. Further research is needed to define how e-booking systems could support a better alignment between primary care innovative practices and improve the fit between patients' needs and resources availability in primary care.

Assessing gestational exposure to trace elements in an area of unconventional oil and gas activity: comparison with reference populations and evaluation of variability.

BACKGROUND: Located in Northeastern British Columbia, the Montney formation is an important area of unconventional oil and gas exploitation, which can release contaminants like trace elements. Gestational exposure to these contaminants may lead to deleterious developmental effects. OBJECTIVES: Our study aimed to (1) assess gestational exposure to trace elements in women living in this region through repeated urinary measurements; (2) compare urinary concentrations to those from North American reference populations; (3) compare urinary concentrations between Indigenous and non-Indigenous participants; and (4) evaluate inter- and intra-individual variability in urinary levels. METHODS: Eighty-five pregnant women participating in the Exposures in the Peace River Valley (EXPERIVA) study provided daily spot urine samples over 7 consecutive days. Samples were analyzed for 20 trace elements using inductively-coupled mass spectrometry (ICP-MS). Descriptive statistics were calculated, and inter- and intra-individual variability in urinary levels was evaluated through intraclass correlation coefficient (ICC) calculation for each trace element. RESULTS: When compared with those from North American reference populations, median urinary levels were higher in our population for barium (~2 times), cobalt (~3 times) and strontium (~2 times). The 95th percentile of reference populations was exceeded at least 1 time by a substantial percentage of participants during the sampling week for barium (58%), cobalt (73%), copper (29%), manganese (28%), selenium (38%), strontium (60%) and vanadium (100%). We observed higher urinary manganese concentrations in self-identified Indigenous participants (median: 0.19 µg/g creatinine) compared to non-Indigenous participants (median: 0.15 µg/g of creatinine). ICCs varied from 0.288 to 0.722, indicating poor to moderate reliability depending on the trace element. SIGNIFICANCE: Our results suggest that pregnant women living in this region may be more exposed to certain trace elements (barium, cobalt, copper, manganese, selenium, strontium, and vanadium), and that one urine spot sample could be insufficient to adequately characterize participants' exposure to certain trace elements. IMPACT STATEMENT: Unconventional oil and gas (UOG) is an important industry in the Peace River Valley region (Northeastern British Columbia, Canada). Information on the impacts of this industry is limited, but recent literature emphasizes the risk of environmental contamination. The results presented in this paper highlight that pregnant women living near UOG wells in Northeastern British Columbia may be more exposed to some trace elements known to be related to this industry compared to reference populations. Furthermore, our results based on repeated urinary measurements show that one urine sample may be insufficient to adequately reflect long-term exposure to certain trace elements.

Proximity and density of unconventional natural gas wells and mental illness and substance use among pregnant individuals: An exploratory study in Canada.

BACKGROUND: Hydraulic fracturing (fracking) is a method used to extract unconventional natural gas (UNG). Living near UNG operations has been associated with various health outcomes, but few have explored the association between UNG and mental health and substance use. Our objective was to evaluate the association between metrics of residential UNG well density/proximity and mental illness and substance use among pregnant individuals in Northeastern British Columbia, Canada. METHODS: Individuals who gave birth at the Fort St John hospital between December 30, 2006 and December 29, 2016 (n = 6278) were included in the study. Exposure was determined using inverse distance weighting (IDW) to calculate the density and proximity of UNG wells to the postal code centroid ofindividual's residential address at delivery. Four exposure metrics, categorized by quartiles, were calculated based on 50, 10, 5 and 2.5 km buffer zones around each postal code centroid. Logistic regression was used to separately evaluate associations between IDW quartiles of each metric and diagnosis of depression and anxiety prior to or during pregnancy, and self-reported substance use during pregnancy, controlling for relevant and available confounders. RESULTS: The second and third quartile (Q) of the 10 km IDW were associated with greater odds of depression (Q2: adjusted (aOR) 1.30, 95% (confidence interval) CI 1.03-1.64; Q3: aOR 1.35, 95% CI 1.07-1.70) compared to the first quartile, but not the fourth. Using the 5 km IDW, we observed a suggestive positive association with depression in the second and third quartile (aOR Q2: 1.21, 95% CI 0.96-1.53; aOR Q3: 1.24, 95% CI 0.98-1.57) compared to the first quartile. No statistically significant association was observed using the 2.5 km IDW exposure metric. CONCLUSION: We observed some evidence of greater odds of mental illness prior to or during pregnancy, and substance use during pregnancy in pregnant individuals living in postal codes with increased UNG well density/proximity, although associations were not observed in smaller buffer zones. This study adds to the growing literature on the adverse health outcomes surrounding living in proximity to UNG operations.

The TRACTOR Project: TRACking and MoniToring Occupational Risks in Agriculture Using French Insurance Health Data (MSA).

OBJECTIVES: A vast data mining project called 'TRACking and moniToring Occupational Risks in agriculture' (TRACTOR) was initiated in 2017 to investigate work-related health events among the entire French agricultural workforce. The goal of this work is to present the TRACTOR project, the challenges faced during its implementation, to discuss its strengths and limitations and to address its potential impact for health surveillance. METHODS: Three routinely collected administrative health databases from the National Health Insurance Fund for Agricultural Workers and Farmers (MSA) were made available for the TRACTOR project. Data management was required to properly clean and prepare the data before linking together all available databases. RESULTS: After removing few missing and aberrant data (4.6% values), all available databases were fully linked together. The TRACTOR project is an exhaustive database of agricultural workforce (active and retired) from 2002 to 2016, with around 10.5 million individuals including seasonal workers and farm managers. From 2012 to 2016, a total of 6 906 290 individuals were recorded. Half of these individuals were active and 46% had at least one health event (e.g. declared chronic disease, reimbursed drug prescription) during this 5-year period. CONCLUSIONS: The assembled MSA databases available in the TRACTOR project are regularly updated and represent a promising and unprecedent dataset for data mining analysis dedicated to the early identification of current and emerging work-related illnesses and hypothesis generation. As a result, this project could help building a prospective integrated health surveillance system for the benefit of agricultural workers.

Density and proximity to hydraulic fracturing wells and birth outcomes in Northeastern British Columbia, Canada.

BACKGROUND: Hydraulic fracturing, a method used in Northeastern British Columbia (Canada) to extract natural gas, can release contaminants with potential deleterious health effects on fetal development. To date, the association between hydraulic fracturing activity and birth outcomes has not been evaluated in this region. OBJECTIVE: To evaluate the association between the hydraulic fracturing well density/proximity and birth outcomes (birthweight, head circumference, preterm birth and small for gestational age (SGA)). METHODS: We used birth records from the Fort St John hospital between December 30, 2006 and December 29, 2016 (n = 6333 births). To estimate gestational exposure, we used inverse distance weighting (IDW) to calculate the density/proximity of hydraulic fracturing wells to pregnant women's postal code centroid. For each birth, we calculated three IDWs using 2.5, 5, and 10 km buffer zones around women's postal code centroid. We used linear and logistic regressions to evaluate associations between quartiles of postal code well density/proximity and birth outcomes, controlling for relevant covariates. RESULTS: No associations were found between postal code well density/proximity and head circumference or SGA. A negative association was found between postal code well density/proximity and birthweight for infants born to women in the 2nd quartile of the 10 km buffer (ß [95% confidence interval (CI)]: -47.28 g [-84.30; -10.25]), and in the 2nd (ß [95% CI]: -40.87 g [-78.01; -3.73]) and 3rd (ß [95% CI]: -42.01 g [-79.15; -4.87]) quartiles of the 5 km buffer. Increased odds of preterm birth were observed among women in the 2nd quartile of the 2.5 km buffer (odds ratio (OR) [95% CI]: 1.60 [1.30; 2.43]). CONCLUSIONS: This is the first epidemiological study in Northeastern British Columbia evaluating associations between hydraulic fracturing and health outcomes. Our results show inconsistent patterns of association between hydraulic fracturing, preterm birth and reduced birthweight, and effect estimates did not match expected dose-response relationships.

Estimated postnatal p,p'-DDT and p,p'-DDE levels and body mass index at 42 months of age in a longitudinal study of Japanese children.

BACKGROUND: Children are exposed to p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) through placental and lactational transfer. Some studies have suggested that early-life exposure to these compounds could lead to increased body mass index (BMI) during childhood. Our aim was to assess whether children's exposure during the first 2 years of life is associated with BMI z-score in Japanese children at 42 months of age. METHODS: We used data from a birth cohort (n = 290) of the Tohoku Study of Child Development. p,p'-DDT and p,p'-DDE levels were measured in breast milk samples collected 1 month after birth, and levels in children were estimated using a toxicokinetic model for three exposure periods (0-6 months, 6-12 months, 12-24 months). Associations between exposure estimates and BMI z-score at 42 months of age were assessed using multivariate linear regression models. RESULTS: We found no significant association between levels of p,p'-DDT measured in breast milk or estimated in children and BMI z-score. However, we observed associations between estimated p,p'-DDE levels in girls during all postnatal exposure periods and BMI z-score; for each log increase in the estimated p,p'-DDE levels, BMI z-score increased by 0.23 (C.I. 95%: 0.01, 0.45) for the 0-6 months exposure period, 0.26 (C.I. 95%: 0.06, 0.47) for the 6-12 months exposure period, and 0.24 (C.I. 95%: 0.05, 0.43) for the 12-24 months exposure period. CONCLUSION: In this study of Japanese children, estimated postnatal p,p'-DDE levels were associated with increased BMI z-score at 42 months of age, mostly in girls. These results are in line with previous studies supporting that early-life exposure to p,p'-DDE may be associated with higher BMI during childhood.

Correction to: Estimated postnatal p,p'-DDT and p,p'-DDE levels and body mass index at 42 months of age in a longitudinal study of Japanese children.

An amendment to this paper has been published and can be accessed via the original article.

Occupational Co-exposures to Multiple Chemical Agents from Workplace Measurements by the US Occupational Safety and Health Administration.

OBJECTIVES: The occupational environment represents an important source of exposures to multiplehazards for workers' health. Although it is recognized that mixtures of agents may have differenteffects on health compared to their individual effects, studies generally focus on the assessment ofindividual exposures. Our objective was to identify occupational co-exposures occurring in the United States using the multi-industry occupational exposure databank of the Occupational Safety and Health Administration (OSHA). METHODS: Using OSHA's Integrated Management Information System (IMIS), measurement data from workplace inspections occurring from 1979 to 2015 were examined. We defined a workplace situation (WS) by grouping measurements that occurred within a company, within the same occupation (i.e. job title) within 1 year. All agents present in each WS were listed and the resulting databank was analyzed with the Spectrosome approach, a methodology inspired by network science, to determine global patterns of co-exposures. The presence of an agent in a WS was defined either as detected, or measured above 20% of a relevant occupational exposure limit (OEL). RESULTS: Among the 334 648 detected exposure measurements of 105 distinct agents collected from 14 513 US companies, we identified 125 551 WSs, with 31% involving co-exposure. Fifty-eight agents were detected with others in >50% of WSs, 29 with a proportion >80%. Two clusters were highlighted, one for solvents and one for metals. Toluene, xylene, acetone, hexone, 2-butanone, and N-butyl acetate formed the basis of the solvent cluster. The main agents of the metal cluster were zinc, iron, lead, copper, manganese, nickel, cadmium, and chromium. 68 556 WS were included in the analyses based on levels of exposure above 20% of their OEL, with 12.4% of co-exposure. In this analysis, while the metal cluster remained, only the combinations of toluene with xylene or 2-butanone were frequently observed among solvents. An online web application allows the examination of industry specific patterns. CONCLUSIONS: We identified frequent co-exposure situations in the IMIS databank. Using the spectrome approach, we revealed global combination patterns and the agents most often implicated. Future work should endeavor to explore the toxicological effects of prevalent combinations of exposures on workers' health to prioritize research and prevention efforts.

Medico-administrative data combined with agricultural practices data to retrospectively estimate pesticide use by agricultural workers.

This work is part of a global project aiming to use medico-administrative big data from the whole French agricultural population (~3 millions), collected through their mandatory health insurance system (Mutualité Sociale Agricole), to highlight associations between chronic diseases and agricultural activities. At the request of the French Agency for Food, Environmental and Occupational Health & Safety (ANSES), our objective was to estimate which pesticides were probably used by each agricultural worker, in order to include this information in our analyses and search for association with diseases. We selected five databases to achieve this objective: the Graphical Land Parcel Registration (RPG), the French Agricultural Census, "Cultivation Practice" surveys from the Agriculture ministry, the MATPHYTO crop-exposure matrix and the Compilation of Phytosanitary Indexes from the French Public Health Agency. A geographical grid was designed to use geographical location while maintaining worker anonymity, dividing France into square tracts of variable surface each containing a minimum of 1500 agricultural workers. We developed an automated algorithm to predict each individual potential exposure by crossing her/his occupational activity, the geographical grid and the RPG to deduce cultivation practices and use it as a gateway to estimate pesticides use. This approach allowed drawing, from administrative data, a list of substances potentially used by each agricultural worker throughout France. Results of the algorithm are illustrated at collective level (descriptive statistics for the whole population), as well as at individual level (some workers taken as examples). The generalization of this method in other national contexts is discussed. By linking this information with the health insurance databases, this approach could contribute to the agricultural workers health surveillance.

Observational Surveillance Approach to Detect Novel Work-Related Diseases and Hazards: An Application to a Belgian Occupational Health and Safety Database.

OBJECTIVES: Rapid changes in working conditions give rise to new occupational health risks. We applied the Spectrosome approach, a network-based analysis, to investigate associations between disease and multiple occupational exposures. METHODS: We investigated work and health's associations in a specific sector: the agricultural sector and for a specific and frequent health complaint: sore throat; using PRECUBE dataset of the Belgian Occupational Health and Safety, containing 381.615 occupational health observations. We compared the results of the spectrosome with classic frequency analyses. RESULTS: Spectrosome approach reports more significant signals of multiple associations of agents compare to the frequency analysis. CONCLUSION: This difference justifies the usefulness of taking into account the multiplicity of causes leading to a health event, which is a clear asset of the Spectrosome method.

The spectrosome of occupational health problems.

Given the increased prevalence of cancer, respiratory diseases, and reproductive disorders, for which multifactorial origins are strongly suspected, the impact of the environment on the population represents a substantial public health challenge. Surveillance systems have become an essential public health decision-making tool. Networks have been constructed to facilitate the development of analyses of the multifactorial aspects of the relationships between occupational contexts and health. The aim of this study is to develop and present an approach for the optimal exploitation of observational databases to describe and improve the understanding of the (occupational) environment-health relationships, taking into account key multifactorial aspects. We have developed a spectral analysis (SA) approach that takes into account both the multi-exposure and dynamic natures of occupational health problems (OHPs) and related associations. The main results of this paper are to present the construction method of the "spectrum" and "spectrosome" of OHPs (range and structured list of occupational exposures) and describe the information contained therein with an illustrative example. The approach is illustrated using the case of non-Hodgkin lymphoma (NHL) from the French National Occupational Diseases Surveillance and Prevention Network database as a working example of an occupational disease. We found that the NHL spectrum includes 40 sets of occupational exposures characterized by important multi-exposures, especially solvent combinations or pesticide combinations, but also specific exposures such as polycyclic aromatic hydrocarbons, formaldehyde and ionizing radiation. These findings may be useful for surveillance and the assessment of occupational exposure related to health risks.