Urinary biomonitoring of glyphosate exposure among male farmers and nonfarmers in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study.

Glyphosate is the most widely applied herbicide worldwide. Glyphosate biomonitoring data are limited for agricultural settings. We measured urinary glyphosate concentrations and assessed exposure determinants in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study. We selected four groups of BEEA participants based on self-reported pesticide exposure: recently exposed farmers with occupational glyphosate use in the last 7 days (n = 98), farmers with high lifetime glyphosate use (>80th percentile) but no use in the last 7 days (n = 70), farming controls with minimal lifetime use (n = 100), and nonfarming controls with no occupational pesticide exposures and no recent home/garden glyphosate use (n = 100). Glyphosate was quantified in first morning void urine using ion chromatography isotope-dilution tandem mass spectrometry. We estimated associations between urinary glyphosate concentrations and potential determinants using multivariable linear regression. Glyphosate was detected (≥0.2 µg/L) in urine of most farmers with recent (91 %) and high lifetime (93 %) use, as well as farming (88 %) and nonfarming (81 %) controls; geometric mean concentrations were 0.89, 0.59, 0.46, and 0.39 µg/L (0.79, 0.51, 0.42, and 0.37 µg/g creatinine), respectively. Compared with both control groups, urinary glyphosate concentrations were significantly elevated among recently exposed farmers (P < 0.0001), particularly those who used glyphosate in the previous day [vs. nonfarming controls; geometric mean ratio (GMR) = 5.46; 95 % confidence interval (CI): 3.75, 7.93]. Concentrations among high lifetime exposed farmers were also elevated (P < 0.01 vs. nonfarming controls). Among recently exposed farmers, glyphosate concentrations were higher among those not wearing gloves when applying glyphosate (GMR = 1.91; 95 % CI: 1.17, 3.11), not wearing long-sleeved shirts when mixing/loading glyphosate (GMR = 2.00; 95 % CI: 1.04, 3.86), applying glyphosate exclusively using broadcast/boom sprayers (vs. hand sprayer only; GMR = 1.70; 95 % CI: 1.00, 2.92), and applying glyphosate to crops (vs. non-crop; GMR = 1.72; 95 % CI: 1.04, 2.84). Both farmers and nonfarmers are exposed to glyphosate, with recency of occupational glyphosate use being the strongest determinant of urinary glyphosate concentrations. Continued biomonitoring of glyphosate in various settings is warranted.

Exposure to Per- and Polyfluoroalkyl Substances and Breast Cancer Risk: A Systematic Review and Meta-analysis of Epidemiologic Studies.

We synthesized the epidemiologic evidence on the associations between per- and polyfluoroalkyl substances (PFAS) exposure and breast cancer risk. Our systematic review and meta-analysis included 18 and 11 articles, respectively, covering studies up to February 2023. The summary relative risks (RR) estimated by random-effects meta-analyses did not support an association between PFAS and overall breast cancer risk (e.g., a natural log (ln)-unit increase in serum/plasma concentrations [ng/mL] for perfluorooctanoate [PFOA] RR=0.95, 95% confidence interval [CI]:0.77-1.18; perfluorooctane sulfonate [PFOS] RR=0.98, 95%CI: 0.87-1.11). However, when limiting to studies that assessed exposures prior to a breast cancer diagnosis, we observed a positive association with PFOA (a ln-unit increase, RR=1.16, 95%CI: 0.96-1.40). We also observed some possible heterogeneous associations by tumor estrogen and progesterone receptor status among postmenopausal breast cancer cases. No meaningful changes were observed after excluding the studies with high risk-of-bias (Tier 3). Based on the evaluation tool developed by the National Toxicology Program, given the heterogeneity across studies and the variability in timing of exposure measurements, the epidemiologic evidence needed to determine the association between PFAS exposure and breast cancer remains inadequate. Our findings support the need for future studies with improved study designs to determine this association.

Glyphosate Use and Mosaic Loss of Chromosome Y among Male Farmers in the Agricultural Health Study.

BACKGROUND: Glyphosate is the most commonly used herbicide worldwide and has been implicated in the development of certain hematologic cancers. Although mechanistic studies in human cells and animals support the genotoxic effects of glyphosate, evidence in human populations is scarce. OBJECTIVES: We evaluated the association between lifetime occupational glyphosate use and mosaic loss of chromosome Y (mLOY) as a marker of genotoxicity among male farmers. METHODS: We analyzed blood-derived DNA from 1,606 farmers ≥50 years of age in the Biomarkers of Exposure and Effect in Agriculture study, a subcohort of the Agricultural Health Study. mLOY was detected using genotyping array intensity data in the pseudoautosomal region of the sex chromosomes. Cumulative lifetime glyphosate use was assessed using self-reported pesticide exposure histories. Using multivariable logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between glyphosate use and any detectable mLOY (overall mLOY) or mLOY affecting ≥10% of cells (expanded mLOY). RESULTS: Overall, mLOY was detected in 21.4% of farmers, and 9.8% of all farmers had expanded mLOY. Increasing total lifetime days of glyphosate use was associated with expanded mLOY [highest vs. lowest quartile; OR=1.75 (95% CI: 1.00, 3.07), ptrend=0.03] but not with overall mLOY; the associations with expanded mLOY were most apparent among older (≥70 years of age) men [OR=2.30 (95% CI: 1.13, 4.67), ptrend=0.01], never smokers [OR=2.32 (95% CI: 1.04, 5.21), ptrend=0.04], and nonobese men [OR=2.04 (95% CI: 0.99, 4.19), ptrend=0.03]. Similar patterns of associations were observed for intensity-weighted lifetime days of glyphosate use. DISCUSSION: High lifetime glyphosate use could be associated with mLOY affecting a larger fraction of cells, suggesting glyphosate could confer genotoxic or selective effects relevant for clonal expansion. As the first study to investigate this association, our findings contribute novel evidence regarding the carcinogenic potential of glyphosate and require replication in future studies. https://doi.org/10.1289/EHP12834.

Serum concentrations of per- and polyfluoroalkyl substances and risk of renal cell carcinoma in the Multiethnic Cohort Study.

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. We previously reported a positive association between serum perfluorooctanoate (PFOA) concentrations and risk of renal cell carcinoma (RCC) within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, comprising predominantly White individuals enrolled in 1993-2001. To extend our investigations to a larger and more racially and ethnically diverse population, we conducted a nested case-control study of serum PFAS concentrations and RCC within the Multiethnic Cohort Study. We measured pre-diagnostic serum concentrations of nine PFAS among 428 RCC cases and 428 individually matched controls. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for risk of RCC in relation to each PFAS using conditional logistic regression, adjusting for RCC risk factors and other PFAS. PFOA was not associated with RCC risk overall [doubling in serum concentration, ORcontinuous = 0.89 (95 %CI = 0.67, 1.18)]. However, we observed suggestive positive associations among White participants [2.12 (0.87, 5.18)] and among participants who had blood drawn before 2002 [1.49 (0.77, 2.87)]. Furthermore, higher perfluorononanoate (PFNA) concentration was associated with increased risk of RCC overall [fourth vs. first quartile, OR = 1.84 (0.97, 3.50), Ptrend = 0.04; ORcontinuous = 1.29 (0.97, 1.71)], with the strongest association observed among African American participants [ORcontinuous = 3.69 (1.33, 10.25)], followed by Native Hawaiian [2.24 (0.70, 7.19)] and White [1.98 (0.92, 4.25)] participants. Most other PFAS were not associated with RCC. While PFOA was not associated with RCC risk overall in this racially and ethnically diverse population, the positive associations observed among White participants and those with sera collected before 2002 are consistent with previous PLCO findings. Our study also provided new evidence of a positive association between PFNA and RCC risk that was strongest in African American participants. These findings highlight the need for additional epidemiologic research investigating PFAS exposures and RCC in large racially and ethnically diverse populations.

Serum perfluorooctane sulfonate and perfluorooctanoate and risk of postmenopausal breast cancer according to hormone receptor status: An analysis in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Per- and polyfluoroalkyl substances (PFAS) are highly persistent endocrine-disrupting chemicals that may contribute to breast cancer development; however, epidemiologic evidence is limited. We investigated associations between prediagnostic serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and postmenopausal breast cancer risk, overall and by hormone receptor status, in a nested case-control study of 621 cases and 621 matched controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. PFOS and PFOA levels were determined based on serum metabolomic profiling performed using ultraperformance liquid chromatography-tandem mass spectrometry. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each PFAS and breast cancer risk, overall, by estrogen receptor (ER) or progesterone receptor (PR) status, and by joint ER/PR status. We found little evidence of association between PFOS or PFOA and breast cancer risk overall. However, in subtype-specific analyses, we observed statistically significant increased risks of ER+, PR+, and ER+/PR+ tumors for the third vs lowest quartile of serum PFOS (ORs [95% CIs] = 1.59 [1.01-2.50], 2.34 [1.29-4.23], and 2.19 [1.21-3.98], respectively) and elevated but nonstatistically significant ORs for the fourth quartile. Conversely, for PFOA, modest positive associations with ER-, PR-, ER+/PR-, and ER-/PR- tumors were generally seen in the upper quartiles. Our findings contribute evidence supporting positive associations between serum PFOS and hormone receptor-positive tumors, and possibly between PFOA and receptor-negative tumors. Future prospective studies incorporating tumor hormone receptor status are needed to better understand the role of PFAS in breast cancer etiology.

Iron Status and Associated Factors among Canadian Women: Results from the Canadian Health Measures Survey.

BACKGROUND: Iron deficiency and overload may negatively impact women's health. There has been limited assessment of iron status and its associated factors among Canadian women. OBJECTIVES: This study investigated associations of various sociodemographic, lifestyle, medication, and dietary factors with body iron stores among pre- and postmenopausal women in Canada. METHODS: Analyses were conducted using cross-sectional, nationally representative survey and biomarker data from women aged 20-79 y (n = 6362) in the Canadian Health Measures Survey (2009-2017). Body iron stores were assessed by measuring serum concentrations of ferritin (SF). Information on potential correlates was collected during an in-home interview. Multivariable linear regression analyses were performed to evaluate associations with SF concentration, and logistic regression was used to estimate associations with iron deficiency (SF <15 µg/L) or elevated iron stores (SF >150 µg/L). RESULTS: Geometric mean SF concentrations were significantly higher in postmenopausal than in premenopausal women (73.2 versus 33.8 µg/L; P < 0.001). The prevalence of iron deficiency among pre- and postmenopausal women was 16.0% and 4.0%, respectively, whereas that of elevated iron stores was 2.7% and 21.0%, respectively. After simultaneous adjustment for multiple factors, including high-sensitivity CRP (inflammation marker), we found that age, East/Southeast Asian (versus White) race/ethnicity, alcohol, and red meat consumption were positively associated with SF concentration among pre- and postmenopausal women. In addition, aspirin use and dairy consumption were inversely associated with SF concentration among postmenopausal women only. Similar patterns were observed for associations with elevated iron stores among postmenopausal women, whereas higher grain consumption was associated with an increased prevalence of iron deficiency among premenopausal women. CONCLUSIONS: Sociodemographic, lifestyle, medication, and dietary factors are correlated with iron status determined by SF concentration among Canadian women. The findings may have implications for intervention strategies aimed at optimizing body iron stores in pre- and postmenopausal women.

Glyphosate exposure and urinary oxidative stress biomarkers in the Agricultural Health Study.

BACKGROUND: Glyphosate is the most widely applied herbicide worldwide, and its use has been associated with increased risks of certain hematopoietic cancers in epidemiologic studies. Animal and in vitro experiments suggest that glyphosate may induce oxidative stress, a key characteristic of carcinogens; however, evidence in human populations remains scarce. We investigated associations between glyphosate exposure and urinary oxidative stress biomarkers in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiologic subcohort in the Agricultural Health Study. METHODS: This analysis included 268 male farmers selected based on self-reported recent and lifetime occupational glyphosate use and 100 age- and geography-matched male nonfarmers. Concentrations of glyphosate and oxidative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-iso-prostaglandin-F2α, and malondialdehyde [MDA]) were quantified in first-morning-void urine. We performed multivariable linear regression to evaluate associations of urinary glyphosate and self-reported glyphosate use with each oxidative stress biomarker. RESULTS: Urinary glyphosate concentrations were positively associated with levels of 8-OHdG (highest vs lowest glyphosate quartile; geometric mean ratio = 1.15, 95% confidence interval = 1.03 to 1.28; Ptrend = .02) and MDA (geometric mean ratio = 1.20, 95% confidence interval = 1.03 to 1.40; Ptrend = .06) overall. Among farmers reporting recent glyphosate use (last 7 days), use in the previous day was also associated with statistically significantly increased 8-OHdG and MDA levels. Compared with nonfarmers, we observed elevated 8-iso-prostaglandin-F2α levels among farmers with recent, high past 12-month, or high lifetime glyphosate use. CONCLUSIONS: Our findings contribute to the weight of evidence supporting an association between glyphosate exposure and oxidative stress in humans and may inform evaluations of the carcinogenic potential of this herbicide.

Risk factors for early-onset colorectal cancer: a population-based case-control study in Ontario, Canada.

PURPOSE: There has been an alarming increase in colorectal cancer (CRC) incidence among young adults aged < 50 years, and factors driving this upward trend are unknown. This study investigated associations between various medical, lifestyle, and dietary factors and risk of early-onset CRC (EO-CRC). METHODS: A population-based case-control study was conducted in Ontario, Canada during 2018-2019. EO-CRC cases aged 20-49 years (n = 175) were identified from the Ontario Cancer Registry; sex- and age group-matched controls (n = 253) were recruited through random digit dialing. Data on potential a priori risk factors were collected using a web-based self-reported questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. RESULTS: Family history of CRC in a first- or second-degree relative (OR 2.37; 95% CI 1.47-3.84), longer sedentary time (≥ 10 vs. < 5 h/day, OR 1.93; 95% CI 1.02-3.65), greater consumption of sugary drinks (≥ 7 vs. < 1 drinks/week, OR 2.99; 95% CI 1.57-5.68), and a more Westernized dietary pattern (quartile 4 vs. 1, OR 1.92; 95% CI 1.01-3.66) were each associated with an increased risk of EO-CRC. Conversely, calcium supplement use (OR 0.53; 95% CI 0.31-0.92), history of allergy or asthma (OR 0.62; 95% CI 0.39-0.98), and greater parity in females (≥ 3 vs. nulliparity, OR 0.29; 95% CI 0.11-0.76) were each associated with a reduced risk. CONCLUSION: Modifiable factors, particularly sedentary behavior and unhealthy diet including sugary drink consumption, may be associated with EO-CRC risk. Our findings, if replicated, may help inform prevention strategies targeted at younger persons.

Iron intake, oxidative stress-related genes and breast cancer risk.

Iron has been suggested to contribute to breast cancer development through oxidative stress generation. Our study investigated associations between iron intake and breast cancer risk, overall and by menopausal and estrogen receptor/progesterone receptor (ER/PR) status, and modification by oxidative stress-related genetic polymorphisms (MnSOD, GSTM1 and GSTT1). A population-based case-control study (3,030 cases and 3,402 controls) was conducted in Ontario, Canada. Iron intake (total, dietary, supplemental, heme, nonheme) was assessed using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. Interactions between iron intake and genotypes were assessed among 1,696 cases and 1,761 controls providing DNA. Overall, no associations were observed between iron intake and breast cancer risk. Among premenopausal women, total, dietary and dietary nonheme iron were positively associated with ER-/PR- breast cancer risk (all ptrend < 0.05). Among postmenopausal women, supplemental iron was associated with reduced breast cancer risk (OR>18 vs. 0 mg/day = 0.68, 95% CI: 0.51-0.91), and dietary heme iron was associated with an increased risk, particularly the ER-/PR- subtype (ORhighest vs. lowest quintile = 1.69, 95% CI: 1.16-2.47; ptrend = 0.02). Furthermore, GSTT1 and combined GSTM1/GSTT1 polymorphisms modified some of the associations. For example, higher dietary iron was most strongly associated with increased breast cancer risk among women with GSTT1 deletion or GSTM1/GSTT1 double deletions (pinteraction < 0.05). Findings suggest that iron intake may have different effects on breast cancer risk according to menopausal and hormone receptor status, as well as genotypes affecting antioxidant capacity.

Surveillance of concussion-related injuries using electronic medical records from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN): a proof-of-concept.

INTRODUCTION: Previous studies on traumatic brain injury trends in Canada have been restricted to hospitalization and emergency department visit data. However, many concussion patients may present first, or only, to family physicians. Therefore, the true burden of concussion in Canada is likely underestimated. The Canadian Primary Care Sentinel Surveillance Network (CPCSSN) collects information electronically from family physicians across Canada and can potentially be used for concussion surveillance. The objective of this study is to explore the feasibility of using data collated from CPCSSN for concussion surveillance purposes and examine trends over time. METHODS: Electronic medical records housed by CPCSSN from 2010 to 2016 were analyzed. Case ascertainment was determined through a combination of International Classification of Diseases, Ninth Revision codes. Binomial regression models were used to calculate the prevalence ratio (PR) of concussion by age, sex, deprivation indices, body mass index, and comorbid conditions. RESULTS: Concussion prevalence rates increased from 2010 to 2016 (p < 0.001). Based on 2016 data, males had a higher prevalence of concussion compared with females (PR = 1.09; 95% CI 1.02, 1.18), and those aged 10-14 (PR = 8.52; 95% confidence interval [CI] 6.34, 11.44) and 15-19 (PR = 7.75; 95% CI 5.84, 10.28) had higher prevalence of concussion compared with those aged 0-4 years. CONCLUSION: This pilot study demonstrates the feasibility of using the CPCSSN system for surveillance of concussion in the Canadian population. The initial findings on prevalence are in agreement with previous studies that have used hospitalization or emergency department data.

Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysis.

BACKGROUND: Iron has been shown to promote breast carcinogenesis in animal models through generation of oxidative stress and interaction with estrogen. Heme iron, which is found exclusively in animal-sourced foods, is suggested to have a more detrimental effect. Epidemiological evidence of the association between iron and breast cancer risk remains inconclusive and has not been comprehensively summarized. This systematic review and meta-analysis evaluated associations between both iron intake and body iron status and breast cancer risk. METHODS: Four electronic databases (MEDLINE, EMBASE, CINAHL, and Scopus) were searched up to December 2018 for studies assessing iron intake and/or biomarkers of iron status in relation to breast cancer risk. Using random-effects meta-analyses, pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated comparing the highest vs. lowest category of each iron measure. Dose-response meta-analyses were also performed to investigate linear and nonlinear associations. RESULTS: A total of 27 studies were included in the review, of which 23 were eligible for meta-analysis of one or more iron intake/status measures. Comparing the highest vs. lowest category, heme iron intake was significantly associated with increased breast cancer risk, with a pooled RR of 1.12 (95% CI: 1.04-1.22), whereas no associations were found for dietary (1.01, 95% CI: 0.89-1.15), supplemental (1.02, 95% CI: 0.91-1.13), or total (0.97, 95% CI: 0.82-1.14) iron intake. Associations of iron status indicators with breast cancer risk were generally in the positive direction; however, a significant pooled RR was found only for serum/plasma levels (highest vs. lowest) of iron (1.22, 95% CI: 1.01-1.47), but not for ferritin (1.13, 95% CI: 0.78-1.62), transferrin saturation (1.16, 95% CI: 0.91-1.47), or total iron-binding capacity (1.10, 95% CI: 0.97-1.25). In addition, a nonlinear dose-response was observed for heme iron intake and serum iron (both Pnonlinearity < 0.05). CONCLUSIONS: Heme iron intake and serum iron levels may be positively associated with breast cancer risk. Although associations were modest, these findings may have public health implications given the widespread consumption of (heme) iron-rich foods. In light of methodological and research gaps identified, further research is warranted to better elucidate the relationship between iron and breast cancer risk.

Effect of Dietary Flaxseed Intake on Circulating Sex Hormone Levels among Postmenopausal Women: A Randomized Controlled Intervention Trial.

Lignan intake, and its richest food source, flaxseed, have been associated with reduced breast cancer risk. Endogenous sex hormones, such as estrogens, play a role in breast cancer development, and lignans may alter these sex hormone levels. To assess the effect of flaxseed on circulating sex hormones, a randomized controlled trial was conducted among 99 postmenopausal women in Toronto, Canada. The intervention arm consumed 2 tablespoons (15 g) of ground flaxseed daily for 7 weeks; the control arm maintained usual diet. Baseline and week 7 concentrations of 14 serum sex hormones were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoassay, and serum enterolignans (lignan biomarker) using LC-MS/MS. Intervention effects on sex hormone levels were assessed using analysis of covariance. Serum enterolignans increased among the flaxseed arm (+516%). Women consuming flaxseed (vs. controls) had increased serum 2-hydroxyestrone [treatment effect ratio (TER) = 1.54; 95% CI: 1.18-2.00] and 2:16α-hydroxyestrone ratio (TER =1.54; 95% CI: 1.15-2.06); effects on other hormones were not statistically significant. Within the flaxseed arm, change in enterolignan level was positively correlated with changes in 2-hydroxyestrone and 2:16α-hydroxyestrone ratio, and negatively with prolactin. Findings suggest flaxseed affects certain circulating sex hormone levels with possible implications for future breast cancer prevention research.

Factors associated with sleep duration across life stages: results from the Canadian Health Measures Survey. / Facteurs associés à la durée du sommeil à différentes étapes de la vie : résultats de l'Enquête canadienne sur les mesures de la santé.

INTRODUCTION: Sleep is essential for both physical and mental well-being. This study investigated sociodemographic, lifestyle/behavioural, environmental, psychosocial and health factors associated with sleep duration among Canadians at different life stages. METHODS: We analyzed nationally representative data from 12 174 Canadians aged 3-79 years in the Canadian Health Measures Survey (2009-2013). Respondents were grouped into five life stages by age in years: preschoolers (3-4), children (5-13), youth (14-17), adults (18-64) and older adults (65-79). Sleep duration was classified into three categories (recommended, short and long) according to established guidelines. Logistic regression models were used to identify life stage-specific correlates of short and long sleep. RESULTS: The proportion of Canadians getting the recommended amount of sleep decreased with age, from 81% of preschoolers to 53% of older adults. Statistically significant factors associated with short sleep included being non-White and having low household income among preschoolers; being non-White and living in a lone-parent household among children; and second-hand smoke exposure among youth. Boys with a learning disability or an attention-deficit/hyperactivity disorder and sedentary male youth had significantly higher odds of short sleep. Among adults and older adults, both chronic stress and arthritis were associated with short sleep. Conversely, mood disorder and poor/fair self-perceived general health in adults and weak sense of community belonging in adults and older men were associated with long sleep. CONCLUSION: Our population-based study identified a wide range of factors associated with short and long sleep at different life stages. This may have implications for interventions aimed at promoting healthy sleep duration.

INTRODUCTION: Le sommeil est essentiel à la fois au bien-être physique et au bien-être mental. Cette étude a examiné les facteurs sociodémographiques, comportementaux, environnementaux, psychosociaux et les facteurs de santé associés à la durée du sommeil chez les Canadiens à différentes étapes de la vie. MÉTHODOLOGIE: Nous avons analysé des données de l'Enquête canadienne sur les mesures de la santé (2009-2013), représentatives à l'échelle nationale et portant sur 12 174 Canadiens de 3 à 79 ans. En fonction de leur âge, les répondants ont été distribués en cinq groupes correspondant à cinq étapes de vie : les enfants préscolaires (3 et 4 ans), les enfants (5 à 13 ans), les adolescents (14 à 17 ans), les adultes (18 à 64 ans) et les aînés (65 à 79 ans). La durée du sommeil a été classée en trois catégories (recommandée, courte et longue) suivant les directives établies. Des modèles de régression logistique ont été utilisés pour dégager des corrélats d'une durée de sommeil courte ou longue propres à chaque étape de vie. RÉSULTATS: La proportion de Canadiens jouissant de la quantité recommandée de sommeil diminue avec l'âge, de 81 % chez les enfants préscolaires à 53 % chez les aînés. Les facteurs statistiquement significatifs associés à un sommeil court sont une ethnicité non blanche et un revenu familial faible chez les enfants préscolaires, une ethnicité non blanche et la résidence avec un seul parent chez les enfants et l'exposition à la fumée secondaire chez les adolescents. Les garçons ayant un trouble d'apprentissage ou un trouble du déficit de l'attention avec hyperactivité et les garçons adolescents sédentaires avaient des chances significativement plus élevées de connaître un sommeil court. Chez les adultes et les aînés, le stress chronique et l'arthrite ont été associés tous deux à un sommeil court. Le sommeil long a été quant à lui associé à un trouble de l'humeur et une autoperception d'une mauvaise santé générale ou passable chez les adultes et à un faible sens d'appartenance communautaire chez les adultes ainsi que chez les aînés de sexe masculin. CONCLUSION: Notre étude de population a dégagé une grande variété de facteurs associés à un sommeil court ou long à différentes étapes de la vie, ce qui pourrait jouer un rôle dans l'élaboration des interventions visant à promouvoir une durée de sommeil saine.

Sentinel surveillance of suspected opioid-related poisonings and injuries: trends and context derived from the electronic Canadian Hospitals Injury Reporting and Prevention Program, March 2011 to June 2017. / Surveillance des cas suspectés d'intoxication et de blessures liées aux opioïdes : tendances et contexte tirés du Système canadien hospitalier d'information et de recherche en prévention des traumatismes, mars 2011 à juin 2017.

INTRODUCTION: The opioid epidemic is currently a major public health problem in Canada. As such, knowledge of upstream risk factors associated with opioid use is needed to inform injury prevention, health promotion and harm reduction efforts. METHODS: We analyzed data extracted from 11 pediatric and 6 general hospital emergency departments (EDs) as part of the electronic Canadian Hospitals Injury Reporting and Prevention Program (eCHIRPP) from March 2011 to June 2017. We identified suspected opioid-related injuries using search strings and manually verified them. We computed age-adjusted and sex-stratified proportionate injury ratios (PIRs) and 95% confidence intervals (CIs) to compare opioid-related injuries to all injuries in eCHIRPP. Negative binomial regression was used to determine trends over time. We conducted qualitative analyses of narratives to identify common themes across life stages. RESULTS: Between March 2011 and June 2017, 583 suspected opioid-related poisoning/ injury cases were identified from eCHIRPP. Most of the cases were females (55%). Many of the injuries occurred in patients' own homes (51%). Forty-five percent of the injuries were intentional self-harm. Among children (aged 1-9 years), most injuries were caused by inadvertent consumption of opioids left unattended. Among youth (aged 10-19 years) and adults (aged 20-49 years), opioid use was associated with underlying mental illness. Overall, the average annual percent change (AAPC) in the rate of injuries (per 100 000 eCHIRPP cases) has been increasing since 2012 (AAPC = 11.9%, p < .05). The increase is particularly evident for males (AAPC = 16.3%, p < .05). Compared to other injuries, people with suspected opioid-related injuries were more likely to be admitted to hospital (PIR = 5.3, 95% CI: 4.6-6.2). CONCLUSION: The upstream determinants of opioid-related injuries are complex and likely vary by subpopulations. Therefore, continued monitoring of risk factors is important in providing the evidence necessary to prevent future overdoses and deaths.

INTRODUCTION: La crise actuelle des opioïdes est un problème de santé publique majeur au Canada. Il est nécessaire de connaître les facteurs de risque en amont associés à la consommation d'opioïdes pour éclairer les efforts de prévention des blessures, de promotion de la santé et de réduction des méfaits. MÉTHODOLOGIE: Nous avons analysé les données sur les blessures subies par des personnes traitées dans les services d'urgence (SU) de onze hôpitaux pédiatriques et de six hôpitaux généraux au Canada et recueillies par le Système canadien hospitalier d'information et de recherche en prévention des traumatismes en ligne (SCHIRPTe) entre mars 2011 et juin 2017. Nous avons identifié les blessures apparemment liées aux opioïdes au moyen de chaînes de recherche et nous les avons vérifiées manuellement. Nous avons calculé des rapports proportionnels de blessures (RPB) en fonction de l'âge et du sexe ainsi que des intervalles de confiance à 95 % pour comparer les blessures liées à la consommation d'opioïdes à l'ensemble des blessures figurant dans le SCHIRPTe. Une régression binomiale négative a été utilisée pour déterminer les tendances au fil du temps. Nous avons effectué des analyses qualitatives des informations descriptives afin d'en dégager les thèmes communs spécifiques à chaque étape de vie. RÉSULTATS: Nous avons identifié 583 cas d'intoxications ou de blessures apparemment liées aux opioïdes dans le SCHIRPTe pour la période allant de mars 2011 à juin 2017. La majorité concernaient des femmes (55 %) et sont survenues au domicile des patients (51 %). Quarante-cinq pour cent des blessures étaient des automutilations intentionnelles. Chez les enfants (1 à 9 ans), la plupart des blessures ont été causées par une consommation accidentelle d'opioïdes laissés sans surveillance. Chez les jeunes (10 à 19 ans) et les adultes (20 à 49 ans), la consommation d'opioïdes était associée à une maladie mentale sous-jacente. Dans l'ensemble, on observe une augmentation de la variation annuelle moyenne en pourcentage (VAMP) du taux de blessures (pour 100 000 cas dans le SCHIRPTe) depuis 2012 (VAMP = 11,9 %, p < 0,05), particulièrement marquée chez les hommes (VAMP = 16,3 %, p < 0,05). Les personnes victimes de blessures apparemment liées à la consommation d'opioïdes étaient plus susceptibles d'être admises à l'hôpital que les personnes victimes d'autres types de blessure (RPB = 5,3, IC à 95 % : 4,6 à 6,2). CONCLUSION: Les déterminants en amont des blessures liées à l'utilisation d'opioïdes sont complexes et varient probablement selon les sous-populations. La surveillance continue des facteurs de risque est donc importante afin d'obtenir les données probantes nécessaires à la prévention d'autres surdoses et décès.

At-a-glance - What can social media tell us about the opioid crisis in Canada? / Aperçu - Que révèlent les médias sociaux au sujet de la crise des opioïdes au Canada?

We explored social media as a potential data source for acquiring realtime information on opioid use and perceptions in Canada. Twitter messages were collected through a social media analytics platform between June 15, 2017, and July 13, 2017, and analyzed to identify recurring topics mentioned in the messages. Messages concerning the medical use of opioids as well as commentary on the Canadian government's current response efforts to the opioid crisis were common. The findings of this study may help to inform public health practice and community stakeholders in their efforts to address the opioid crisis.

RÉSUMÉ: Nous avons utilisé les médias sociaux comme source de données potentielle pour obtenir de l'information en temps réel sur l'usage des opioïdes et sur les perceptions entourant ces substances au Canada. Nous avons recueilli des messages sur Twitter au moyen d'une plateforme d'analyse des médias sociaux entre le 15 juin et le 13 juillet 2017, puis nous les avons analysés afin d'y déceler les thèmes récurrents. Nous avons souvent relevé des messages concernant l'usage d'opioïdes à des fins médicales ainsi que des commentaires sur les efforts d'intervention déployés par le gouvernement du Canada dans le cadre de la crise des opioïdes. Les résultats de l'étude pourraient aider à orienter les pratiques en santé publique ainsi qu'à soutenir les intervenants communautaires dans leurs efforts pour contrer la crise.

Urinary bisphenol A and obesity in adults: results from the Canadian Health Measures Survey. / Concentration urinaire de bisphénol A et obésité chez les adultes : résultats de l'Enquête canadienne sur les mesures de la santé.

INTRODUCTION: Exposure to bisphenol A (BPA) has been shown to affect lipid metabolism and promote weight gain in animal studies. Recent epidemiological studies also support a link between BPA and obesity in human populations, although many were limited to a single adiposity measure or have not considered potential confounding by dietary factors. The purpose of this study is to examine associations between urinary BPA and adiposity measures in a nationally representative sample of Canadian adults. METHODS: We performed analyses using biomonitoring and directly measured anthropometric data from 4733 adults aged 18 to 79 years in the Canadian Health Measures Survey (2007-2011). We used multinomial and binary logistic regression models to estimate associations of urinary BPA with body mass index (BMI) categories (overweight vs. under/normal weight; obesity vs. under/normal weight) and elevated waist circumference (males: ≥ 102 cm; females: ≥ 88 cm), respectively, while controlling for potential confounders. Linear regression analyses were also performed to assess associations between urinary BPA and continuous BMI and waist circumference measures. RESULTS: Urinary BPA was positively associated with BMI-defined obesity, with an odds ratio of 1.54 (95% confidence interval [CI]: 1.002-2.37) in the highest (vs. lowest) BPA quartile (test for trend, p = .041). Urinary BPA was not associated with elevated waist circumference defined using standard cut-offs. Additionally, each natural-log unit increase in urinary BPA concentration was associated with a 0.33 kg/m2 (95% CI: 0.10- 0.57) increase in BMI and a 1.00 cm (95% CI: 0.34-1.65) increase in waist circumference. CONCLUSION: Our study contributes to the growing body of evidence that BPA is positively associated with obesity. Prospective studies with repeated measures are needed to address temporality and improve exposure classification.

INTRODUCTION: Des études chez l'animal ont révélé que l'exposition au bisphénol A (BPA) affecte le métabolisme des lipides et favorise la prise de poids. Des études épidémiologiques récentes appuient aussi l'existence d'un lien entre le BPA et l'obésité chez l'humain, mais la plupart d'entre elles se limitent à une seule mesure de l'adiposité ou ne tiennent pas compte des facteurs de confusion alimentaires possibles. Cette étude vise à examiner les associations entre les concentrations urinaires de BPA et les mesures de l'adiposité dans un échantillon national représentatif des adultes canadiens. MÉTHODOLOGIE: Nous avons réalisé des analyses à l'aide de données de biosurveillance et de données anthropométriques mesurées directement auprès de 4 733 adultes de 18 à 79 ans dans le cadre de l'Enquête canadienne sur les mesures de la santé (2007-2011). Nous avons utilisé des modèles de régression logistique multinomiale et binaire pour estimer les associations entre, d'une part, les concentrations urinaires de BPA et, d'autre part, les diverses catégories d'indice de masse corporelle (IMC) (embonpoint par opposition à poids insuffisant ou normal; obésité par opposition à poids insuffisant ou normal) et un tour de taille élevé (102 cm ou plus pour les hommes; 88 cm ou plus pour les femmes) en tenant compte des facteurs de confusion possibles. Des analyses de régression linéaire ont aussi été effectuées pour évaluer les associations entre les concentrations urinaires de BPA et des mesures de l'IMC et du tour de taille. RÉSULTATS: On a pu associer positivement la concentration urinaire de BPA et l'obésité (définie par l'IMC). Le rapport de cotes s'est situé à 1,54 (intervalle de confiance [IC] à 95 % : 1,002 à 2,37) dans le quartile de BPA le plus élevé par rapport au plus bas (test de tendance, p = 0,041). La concentration urinaire de BPA n'a pas été associée au tour de taille pour les valeurs seuils courantes. Enfin, chaque unité d'augmentation du log naturel de la concentration urinaire de BPA a été associée à une hausse de 0,33 kg/m2 (IC à 95 % : 0,10 à 0,57) de l'IMC et de 1,00 cm (IC à 95 % : 0,34 à 1,65) du tour de taille. CONCLUSION: Notre étude vient enrichir le corpus croissant de données probantes sur l'association positive entre BPA et obésité. Des études prospectives comportant un suivi de mesures sont nécessaires pour définir la dimension temporelle de l'association et améliorer la classification de l'exposition.

CDK12 regulates alternative last exon mRNA splicing and promotes breast cancer cell invasion.

CDK12 (cyclin-dependent kinase 12) is a regulatory kinase with evolutionarily conserved roles in modulating transcription elongation. Recent tumor genome studies of breast and ovarian cancers highlighted recurrent CDK12 mutations, which have been shown to disrupt DNA repair in cell-based assays. In breast cancers, CDK12 is also frequently co-amplified with the HER2 (ERBB2) oncogene. The mechanisms underlying functions of CDK12 in general and in cancer remain poorly defined. Based on global analysis of mRNA transcripts in normal and breast cancer cell lines with and without CDK12 amplification, we demonstrate that CDK12 primarily regulates alternative last exon (ALE) splicing, a specialized subtype of alternative mRNA splicing, that is both gene- and cell type-specific. These are unusual properties for spliceosome regulatory factors, which typically regulate multiple forms of alternative splicing in a global manner. In breast cancer cells, regulation by CDK12 modulates ALE splicing of the DNA damage response activator ATM and a DNAJB6 isoform that influences cell invasion and tumorigenesis in xenografts. We found that there is a direct correlation between CDK12 levels, DNAJB6 isoform levels and the migration capacity and invasiveness of breast tumor cells. This suggests that CDK12 gene amplification can contribute to the pathogenesis of the cancer.

Epidemiology of work-related traumatic brain injury: a systematic review.

OBJECTIVE: This systematic review aimed to describe the burden and risk factors of work-related traumatic brain injury (wrTBI) and evaluate methodological quality of existing literature on wrTBI. METHODS: A search of electronic databases (MEDLINE, EMBASE, PsycINFO, and CINAHL) was conducted to identify articles published between 1980 and 2013 using a combination of terms for work, TBI, and epidemiology, without geographical limitations. RESULTS: Ninety-eight studies were included in this review, of which 24 specifically focused on wrTBI. In general, male workers, those in the youngest and oldest age groups, and those working in the primary (e.g., agriculture, forestry, mining) or construction industries were more likely to sustain wrTBI, with falls being the most common mechanism of injury. CONCLUSIONS: This review identified workers at highest risk of wrTBI, with implications for prevention efforts. Future research of better methodological quality is needed to provide a more complete picture of the epidemiology of wrTBI.

Risk factors for falls among seniors: implications of gender.

Despite extensive literature on falls among seniors, little is known about gender-specific risk factors. To determine the prevalence of falls by gender and sociodemographic, lifestyle/behavioral, and medical factors, we conducted a cross-sectional study in a nationally representative sample of Canadian adults who were 65 years of age or older (n = 14,881) from the Canadian Community Health Survey-Healthy Aging (2008-2009). Logistic regression models were applied to investigate gender-specific associations between potential risk factors and falls. In men, stroke (odds ratio (OR) = 1.91), nutritional risk (OR = 1.86), post-secondary school degree (OR = 1.68), eye disorder (OR = 1.35), widowed/separated/divorced marital status (OR = 1.28), and arthritis (OR = 1.27) were independently associated with significantly higher odds of falls. In women, significant independent correlates of falls included stroke (OR = 1.53), age of 85 years or older (OR = 1.51), nutritional risk (OR = 1.39), consumption of at least 1 alcoholic drink per week (OR = 1.39), use of 5 or more medications (OR = 1.36), arthritis (OR = 1.36), diabetes (OR = 1.31), and osteoporosis (OR = 1.22). Higher physical activity levels were protective in both genders, and higher household income was protective in women. Gender should be considered when planning fall prevention strategies.