Non-asbestiform elongate mineral particles and mesothelioma risk: Human and experimental evidence.

The presentations in this session of the Monticello II conference were aimed at summarizing what is known about asbestiform and non-asbestiform elongate mineral particles (EMPs) and mesothelioma risks based on evidence from experimental and epidemiology studies. Dr. Case discussed case reports of mesothelioma over the last several decades. Dr. Taioli indicated that the epidemiology evidence concerning non-asbestiform EMPs is weak or lacking, and that progress would be limited unless mesothelioma registries are established. One exception discussed is that of taconite miners, who are exposed to grunerite. Drs. Mandel and Odo noted that studies of taconite miners in Minnesota have revealed an excess rate of mesothelioma, but the role of non-asbestiform EMPs in this excess incidence of mesothelioma is unclear. Dr. Becich discussed the National Mesothelioma Virtual Bank (NMVB), a virtual mesothelioma patient registry that includes mesothelioma patients' lifetime work histories, exposure histories, biospecimens, proteogenomic information, and imaging data that can be used in epidemiology research on mesothelioma. Dr. Bernstein indicated that there is a strong consensus that long, highly durable respirable asbestiform EMPs have the potential to cause mesothelioma, but there is continued debate concerning the biodurability required, and the dimensions (both length and diameter), the shape, and the dose associated with mesothelioma risk. Finally, Dr. Nel discussed how experimental studies of High Aspect Ratio Engineered Nanomaterials have clarified dimensional and durability features that impact disease risk, the impact of inflammation and oxidative stress on the epigenetic regulation of tumor suppressor genes, and the generation of immune suppressive effects in the mesothelioma tumor microenvironment. The session ended with a discussion of future research needs.

Systematic literature review of the epidemiology of glyphosate and neurological outcomes.

PURPOSE: Human health risk assessments of glyphosate have focused on animal toxicology data for determining neurotoxic potential. Human epidemiological studies have not yet been systematically reviewed for glyphosate neurotoxicity hazard identification. The objective of this systematic literature review was to summarize the available epidemiology of glyphosate exposure and neurological outcomes in humans. METHODS: As of December 2021, 25 eligible epidemiological studies of glyphosate exposure and neurological endpoints were identified and assessed for five quality dimensions using guidance from the U.S. Environmental Protection Agency. Studies that assessed personal use of glyphosate were prioritized, whereas those assessing indirect exposure (other than personal use) were rated as low quality, since biomonitoring data indicate that indirect metrics of glyphosate exposure almost always equate to non-detectable glyphosate doses. RESULTS: Overall, the scientific evidence on glyphosate and neurotoxicity in humans is sparse and methodologically limited, based on nine included epidemiological studies of neurodegenerative outcomes (two high quality), five studies of neurobehavioral outcomes (two high quality), six studies of neurodevelopmental outcomes (none high quality), and five studies of other and mixed neurological outcomes (one high quality). The five high-quality studies showed no association between glyphosate use and risk of depression, Parkinson disease, or peripheral nerve conduction velocity. Results were mixed among the eight moderate-quality studies, which did not demonstrate consistent associations with any neurological endpoints or categories. Low-quality studies were considered uninformative about possible neurotoxic effects due primarily to questionable assessments of indirect exposure. CONCLUSIONS: No association has been demonstrated between glyphosate and any neurological outcomes in humans. To move the state of science forward, epidemiological studies should focus on scenarios involving direct and frequent use of glyphosate while collecting information on validated health outcomes, concomitant agricultural exposures, and relevant personal characteristics.

Causal and Associational Language in Observational Health Research: A Systematic Evaluation.

We estimated the degree to which language used in the high-profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases imply causality. We searched for and screened 1,170 articles from 18 high-profile journals (65 per journal) published from 2010-2019. Based on written framing and systematic guidance, 3 reviewers rated the degree of causality implied in abstracts and full text for exposure/outcome linking language and action recommendations. Reviewers rated the causal implication of exposure/outcome linking language as none (no causal implication) in 13.8%, weak in 34.2%, moderate in 33.2%, and strong in 18.7% of abstracts. The implied causality of action recommendations was higher than the implied causality of linking sentences for 44.5% or commensurate for 40.3% of articles. The most common linking word in abstracts was "associate" (45.7%). Reviewers' ratings of linking word roots were highly heterogeneous; over half of reviewers rated "association" as having at least some causal implication. This research undercuts the assumption that avoiding "causal" words leads to clarity of interpretation in medical research.

The impact of different approaches to exposure assessment on understanding non-malignant respiratory disease risk in taconite miners.

INTRODUCTION: We examined the association between cumulative silica exposures in taconite mining and non-malignant respiratory disease (NMRD) using a comprehensive assessment of current and historical exposure measurements in a cross-sectional study of Minnesota taconite mining workers. We also explored the impact of exposure measurement methods by comparing estimated exposure risk from two different exposure measurement modeling approaches. METHODS: Miners were screened with an occupational and medical history questionnaire, spirometry testing and chest x-rays per ILO guidelines. Current and historical occupational exposure assessments were obtained, the former measuring about 679 personal samples over the period of the study for respirable dusts, including silica, in 28 major job functions. Cumulative silica exposure ((mg/m3) × years) was estimated as a cumulative product of time worked and year-specific silica job exposure concentrations. Chest x-ray abnormalities were based on B-reader agreement with a third B-reader for arbitration. Forced vital capacity (FVC) less than lower limits of normal for age, height, race and gender was used to determine spirometric restrictive ventilatory defect (RVD). Prevalence ratios (PR) of exposure-outcome associations, with 95% confidence intervals (CI), were estimated using multivariate Poisson regression. RESULTS: Cumulative silica exposure was associated with RVD prevalence (PR = 1.41, 95% CI = 1.09-1.81) and prevalence of parenchymal abnormalities on chest x-ray (PR = 1.30, 95% CI = 1.00-1.69) using exposure estimates based primarily on current study measurements, and assuming unchanged historical exposure trend. Conversely, when exposures were defined incorporating available actual historical values, no associations were observed between silica exposure and either RVD (PR = 0.76, 95% CI = 0.41-1.40) or parenchymal (PR = 0.87, 95% CI = 0.45-1.70) outcomes. CONCLUSIONS: This study demonstrated that the estimated association between silica dust exposure and lung disease is highly sensitive to the approach used to estimate cumulative exposure. Cumulative values based on conservative estimates of past exposure, modeled from recently measured respirable silica, showed an association with restriction RVD on spirometry. Silica exposure was also significantly associated with increased parenchymal findings on chest x-ray using this approach. Conversely, these findings were absent when actual available historical data was used to estimate cumulative silica exposure. These differences highlight the challenges with estimating occupational dust exposure, the potential impact on calculated exposure risk and the need for long term quality exposure data gathering in industries prone to risk from inhaled respirable dusts.

Reproductive Factors and Mammographic Density: Associations Among 24,840 Women and Comparison of Studies Using Digitized Film-Screen Mammography and Full-Field Digital Mammography.

Breast density is a modifiable factor that is strongly associated with breast cancer risk. We sought to understand the influence of newer technologies of full-field digital mammography (FFDM) on breast density research and to determine whether results are comparable across studies using FFDM and previous studies using traditional film-screen mammography. We studied 24,840 screening-age (40-74 years) non-Hispanic white women who were participants in the Research Program on Genes, Environment and Health of Kaiser Permanente Northern California and underwent screening mammography with either Hologic (Hologic, Inc., Marlborough, Massachusetts) or General Electric (General Electric Company, Boston, Massachusetts) FFDM machines between 2003 and 2013. We estimated the associations of parity, age at first birth, age at menarche, and menopausal status with percent density and dense area as measured by a single radiological technologist using Cumulus software (Canto Software, Inc., San Francisco, California). We found that associations between reproductive factors and mammographic density measured using processed FFDM images were generally similar in magnitude and direction to those from prior studies using film mammography. Estimated associations for both types of FFDM machines were in the same direction. There was some evidence of heterogeneity in the magnitude of the effect sizes by machine type, which we accounted for using random-effects meta-analysis when combining results. Our findings demonstrate the robustness of quantitative mammographic density measurements across FFDM and film mammography platforms.

Mesothelioma and other lung disease in taconite miners; the uncertain role of non-asbestiform EMP.

The purpose of this paper was to assess the role of non-asbestiform amphibole EMPs in the etiology of mesotheliomas and other lung disease in taconite (iron ore) miners. Increased mesothelioma rates have been described in Minnesota taconite workers since the late 1990s. Currently, over 100 cases have been reported by the Minnesota Department of Health within the complete cohort of miners in Minnesota. Geologic sampling has indicated that only the eastern part of the iron range contains non-asbestiform amphibole elongate mineral particles (EMPs), in close proximity to the ore. This type of EMP has been less studied and also exists in talc and gold mining. A series of investigations into the state's taconite industry have been recently completed. Results from a cohort mortality study indicated an SMR of 2.77 (95% CI = 1.87-3.96) for mesothelioma. In a case-control study, the odds ratio for mesothelioma for high vs. low EMP exposure was 2.25 (5% CI = 1.13-4.5) but EMPs in this study were counted by phase contrast microscopy. Odds ratios were not elevated in mines located in the eastern part of the Mesabi iron range. The overall findings suggest that mesothelioma in taconite miners is related to EMP exposure. Because of the way EMPs were counted, results from these studies cannot allow a firm conclusion about the association between EMP exposure and the reported excess mesothelioma.

Age at Menarche and Late Adolescent Adiposity Associated with Mammographic Density on Processed Digital Mammograms in 24,840 Women.

Background: High mammographic density is strongly associated with increased breast cancer risk. Some, but not all, risk factors for breast cancer are also associated with higher mammographic density.Methods: The study cohort (N = 24,840) was drawn from the Research Program in Genes, Environment and Health of Kaiser Permanente Northern California and included non-Hispanic white females ages 40 to 74 years with a full-field digital mammogram (FFDM). Percent density (PD) and dense area (DA) were measured by a radiological technologist using Cumulus. The association of age at menarche and late adolescent body mass index (BMI) with PD and DA were modeled using linear regression adjusted for confounders.Results: Age at menarche and late adolescent BMI were negatively correlated. Age at menarche was positively associated with PD (P value for trend <0.0001) and DA (P value for trend <0.0001) in fully adjusted models. Compared with the reference category of ages 12 to 13 years at menarche, menarche at age >16 years was associated with an increase in PD of 1.47% (95% CI, 0.69-2.25) and an increase in DA of 1.59 cm2 (95% CI, 0.48-2.70). Late adolescent BMI was inversely associated with PD (P < 0.0001) and DA (P < 0.0001) in fully adjusted models.Conclusions: Age at menarche and late adolescent BMI are both associated with Cumulus measures of mammographic density on processed FFDM images.Impact: Age at menarche and late adolescent BMI may act through different pathways. The long-term effects of age at menarche on cancer risk may be mediated through factors besides mammographic density. Cancer Epidemiol Biomarkers Prev; 26(9); 1450-8. ©2017 AACR.

Personal Protective Equipment Use and Handwashing Among Animal Farmers: A Multi-site Assessment.

The goal of this study was to compare and contrast the use of personal protective equipment (PPE) and the practice of handwashing among participants of four studies assessing poultry and swine farms in the midwestern United States and in Thailand. This largely descriptive exercise was designed to assess and compare the frequency of these protective practices among the study populations. There were a total of 1113 surveys analyzed across the four studies. The respondents included workers in direct contact with animals as well as flock owners and veterinarians tending to farms. Handwashing was the most common practice observed among all participants with 42% "always" and 35% "sometimes" washing their hands after contact with the animals. This practice was least common among Minnesota swine workers. Even Thai poultry farmers, who demonstrated the lowest overall PPE use, reported a higher frequency of handwashing. Mask use during animal farming activities ("always" or "sometimes") was least commonly practiced, ranging from 1% in Thailand to 26% among backyard poultry farmers in Minnesota. Minnesota poultry and swine farmers had similar frequencies of mask (26%) and glove use (51% and 49%). All other comparisons differed significantly across the four sites (p-values <0.05). The use of PPE in animal farming differed by study location and is likely related to prevalent norms in the respective regions. Overall, the use of PPE did not appear to be influenced by the particular animal (poultry or swine) being farmed. These findings may prove useful to regulating bodies and farm owners in formulating policy or planning strategies for improving personal hygiene practices in animal farming and preparing for influenza and other potential zoonotic disease outbreaks.

Burnout and Physical Activity in Minnesota Internal Medicine Resident Physicians.

BACKGROUND: Regular physical activity plays an important role in the amelioration of several mental health disorders; however, its relationship with burnout has not yet been clarified. OBJECTIVE: To determine the association between achievement of national physical activity guidelines and burnout in internal medicine resident physicians. METHODS: A Web-based survey of internal medicine resident physicians at the University of Minnesota and Hennepin County Medical Center was conducted from September to October 2012. Survey measures included the Maslach Burnout Inventory-Human Services Survey and the International Physical Activity Questionnaire. RESULTS: Of 149 eligible residents, 76 (51.0%) completed surveys, which were used in the analysis. Burnout prevalence, determined by the Maslach Burnout Inventory, was 53.9% (41 of 76). Prevalence of failure to achieve US Department of Health and Human Services physical activity guidelines was 40.8% (31 of 76), and 78.9% (60 of 76) of residents reported that their level of physical activity has decreased since they began medical training. Residents who were able to meet physical activity guidelines were less likely to be burned out than their fellow residents (OR, 0.38, 95% CI 0.147-0.99). CONCLUSIONS: Among internal medicine resident physicians, achievement of national physical activity guidelines appears to be inversely associated with burnout. Given the high national prevalence of burnout and inactivity, additional investigation of this relationship appears warranted.

Estimates of restrictive ventilatory defect in the mining industry. Considerations for epidemiological investigations: a cross-sectional study.

OBJECTIVES: (1) To assess the impact of American Thoracic Society and European Respiratory Society (ATS/ERS) 'acceptability' and 'usability' criteria for spirometry on the estimates of restrictive ventilatory defect in a population of taconite miners. (2) To compare estimates of restrictive ventilatory defect with three different pulmonary function tests (spirometry, alveolar volume (VA) and diffusing capacity (DL,CO)). (3) To assess the role of population characteristics on these estimates. DESIGN: Cross-sectional study. SETTING: Current and former workers in six current taconite mining operations of northeastern Minnesota were surveyed. PARTICIPANTS: We attempted to enrol 3313 participants. Of these, 1353 responded while 1188 current and former workers fully participated in the survey and 1084 performed complete pulmonary function testing and were assessed. PRIMARY AND SECONDARY OUTCOME MEASURES: We applied ATS/ERS acceptability criteria for all tests and categorised participants into groups according to whether they fully met, partially met or did not meet acceptability criteria for spirometry. Obstruction and restriction were defined utilising the lower limit of normal for all tests. When using VA, restriction was identified after excluding obstruction. RESULTS: Only 519 (47.9%) tests fully met ATS/ERS spirometry acceptability criteria. Within this group, 5% had obstruction and 6%, restriction on spirometry. In contrast, among all participants (N=1084), 16.8% had obstruction, while 4.5% had restriction. VA showed similar results in all groups after obstruction was excluded. Impaired gas transfer (reduced DL,CO) was identified in less than 50% of restriction identified by either spirometry or VA. Body mass index (BMI) was significantly related to spirometric restriction in all groups. CONCLUSIONS: Population estimates of restriction using spirometry or VA varied by spirometric acceptability criteria. Other factors identified as important considerations in the estimation of restrictive ventilatory defect included increased BMI and gas transfer impairment in a relatively smaller proportion of those with spirometric restriction. These insights are important when interpreting population-based physiological data in occupational settings.