Organophosphorus (OP) pesticides are used in agriculture and several are registered for home use. As young children age they may experience different pesticide exposures due to varying diet, ...behavior, and other factors. We measured six OP dialkylphosphate (DAP) metabolites (three dimethyl alkylphosphates (DMAP) and three diethyl alkylphosphates (DEAP)) in urine samples collected from ~400 children living in an agricultural community when they were 6, 12, and 24 months old. We examined bivariate associations between DAP metabolite levels and determinants such as age, diet, season, and parent occupation. To evaluate independent impacts, we then used generalized linear mixed multivariable models including interaction terms with age. The final models indicated that DMAP metabolite levels increased with age. DMAP levels were also positively associated with daily servings of produce at 6- and 24-months. Among the 6-month olds, DMAP metabolite levels were higher when samples were collected during the summer/spring versus the winter/fall months. Among the 12-month olds, DMAP and DEAP metabolites were higher when children lived ≤ 60 meters from an agricultural field. Among the 24-month-olds, DEAP metabolite levels were higher during the summer/spring months. Our findings suggest that there are multiple determinants of OP pesticide exposures, notably dietary intake and temporal and spatial proximity to agricultural use. The impact of these determinants varied by age and class of DAP metabolite.
Background Although occupational exposure to cotton dust and endotoxin is associated with adverse respiratory health, associations with cancer are unclear. We investigated cancer mortality in ...relation to cotton dust and endotoxin exposure in the Shanghai textile workers cohort. Methods We followed 444 cotton textile and a reference group of 467 unexposed silk workers for 30 years (26 777 person-years). HRs for all cancers combined (with and without lung cancer) and gastrointestinal cancer were estimated in Cox regression models as functions of cotton textile work and categories of cumulative exposure (low, medium, high), after adjustment for covariates including pack-years smoked. Different lag years accounted for disease latency. Results Risks of mortality from gastrointestinal cancers and all cancers combined, with the exclusion of lung cancer, were increased in cotton workers relative to silk workers. When stratified by category of cumulative cotton exposure, in general, risks were greatest for 20-year lagged medium exposure (all cancers HR=2.7 (95% CI 1.4 to 5.2); cancer excluding lung cancer HR=3.4 (1.7–7.0); gastrointestinal cancer HR=4.1 (1.8–9.7)). With the exclusion of lung cancer, risks of cancer were more pronounced. When stratified by category of cumulative endotoxin exposure, consistent associations were not observed for all cancers combined. However, excluding lung cancer, medium endotoxin exposure was associated with all cancers and gastrointestinal cancer in almost all lag models. Conclusions Cotton dust may be associated with cancer mortality, especially gastrointestinal cancer, and endotoxin may play a causative role. Findings also indirectly support a protective effect of endotoxin on lung cancer.
Marginal structural models (MSMs) and inverse probability weighting can be used to estimate risk in a cohort of active workers if there is a time-varying confounder (e.g., health status) affected by ...prior exposure-a feature of the healthy worker survivor effect. We applied Cox MSMs in a study of incident ischemic heart disease and exposure to particulate matter with aerodynamic diameter of 2.5 μm or less (PM2.5) in a cohort of 12,949 actively employed aluminum workers in the United States. The cohort was stratified by work process into workers in smelting facilities, herein referred to as "smelters" and workers in fabrication facilities, herein referred to as "fabricators." The outcome was assessed by using medical claims data from 1998 to 2012. A composite risk score based on insurance claims was treated as a time-varying measure of health status. Binary PM2.5 exposure was defined by the 10th-percentile cutoff for each work process. Health status was associated with past exposure and predicted the outcome and subsequent exposure in smelters but not in fabricators. In smelters, the Cox MSM hazard ratio comparing those always exposed above the cutoff with those always exposed below the cutoff was 1.98 (95% confidence interval: 1.18, 3.32). In fabricators, the hazard ratio from a traditional Cox model was 1.34 (95% confidence interval: 0.98, 1.83). Results suggest that occupational PM2.5 exposure increases the risk of incident ischemic heart disease in workers in both aluminum smelting and fabrication facilities.
With the increasing understanding of the biology of the disease and the development of targeted therapy, there has been a paradigm shift in the treatment of clear cell metastatic renal cell carcinoma ...(mRCC). Traditionally patients with metastatic RCC have been treated with immunotherapy which has limited efficacy. The multikinase inhibitors sunitinib, sorafenib and pazopanib, the VEGF antibody bevacizumab in combination with interferon and the mTOR inhibitor temsirolimus have all been shown to prolong progression-free survival in phase III studies. Here we review another mTOR inhibitor, everolimus (Afinitor(®); Novartis, USA) which was approved in March 2009 by the US FDA for treatment of targeted-therapy refractory metastatic renal cell cancer. The phase III study of everolimus (the RECORD study) was terminated early after a significant difference in efficacy was noted in the treatment arm with everolimus (progression-free survival of 4.0 months in patients on the treatment arm vs 1.9 months in the placebo arm). The most common adverse events were stomatitis, pneumonitis, fatigue and infections. We review Phase I-III data with a particular emphasis on safety data and patient focused outcomes.
Straight metalworking fluids have been linked to cardiovascular mortality in analyses using binary exposure metrics, accounting for healthy worker survivor bias by using g-estimation of accelerated ...failure time models. A cohort of 38,666 Michigan autoworkers was followed (1941-1994) for mortality from all causes and ischemic heart disease. The structural model chosen here, using continuous exposure, assumes that increasing exposure from 0 to 1 mg/m(3) in any single year would decrease survival time by a fixed amount. Under that assumption, banning the fluids would have saved an estimated total of 8,468 (slope-based 95% confidence interval: 2,262, 28,563) person-years of life in this cohort. On average, 3.04 (slope-based 95% confidence interval: 0.02, 25.98) years of life could have been saved for each exposed worker who died from ischemic heart disease. Estimates were sensitive to both model specification for predicting exposure (multinomial or logistic regression) and characterization of exposure as binary or continuous in the structural model. Our results provide evidence supporting the hypothesis of a detrimental relationship between straight metalworking fluids and mortality, particularly from ischemic heart disease, as well as an instructive example of the challenges in obtaining and interpreting results from accelerated failure time models using a continuous exposure in the presence of competing risks.
Aims: To determine chronic effects of long term exposure to cotton dust and endotoxin on incidence of respiratory symptoms and the effect of cessation of exposure. Methods: Respiratory health in 429 ...Chinese cotton textile workers (study group) and 449 silk textile workers (control group) was followed prospectively from 1981 to 1996. Byssinosis, chest tightness, and non-specific respiratory symptoms were assessed by means of identical standardised questionnaires at four time points. Exposures to cotton dust and endotoxin were estimated using area samples collected at each survey. Incidence and persistence of symptoms were examined in relation to cumulative exposure and exposure cessation using generalised estimating equations (GEE). Results: Among cotton workers, the cumulative incidence of byssinosis and chest tightness was 24% and 23%, respectively, and was significantly more common in smokers than in non-smokers. A high proportion of symptoms was found to be intermittent, rather than persistent. Among silk workers, no typical byssinosis was identified; the incidence of chest tightness was 10%. Chronic bronchitis, cough, and dyspnoea were more common and persistent in the cotton group than in the silk group. Significantly lower odds ratios for symptoms were observed in cotton workers who left the cotton mills; risk was also related to years since last worked. Multivariate analysis indicated a trend for higher cumulative exposure to endotoxin in relation to a higher risk for byssinosis. Conclusion: Chronic exposure to cotton dust is related to both work specific and non-specific respiratory symptoms. Byssinosis is more strongly associated with exposure to endotoxin than to dust. Cessation of exposure may improve the respiratory health of cotton textile workers; the improvement appears to increase with time since last exposure.
A job exposure matrix may be useful for the study of biomechanical workplace risk factors when individual-level exposure data are unavailable. We used job title-based exposure data from a public data ...source to construct a job exposure matrix and test exposure-response relationships with prevalent carpal tunnel syndrome (CTS). Exposures of repetitive motion and force from the Occupational Information Network were assigned to 3,452 active workers from several industries, enrolled between 2001 and 2008 from 6 studies. Repetitive motion and force exposures were combined into high/high, high/low, and low/low exposure groupings in each of 4 multivariable logistic regression models, adjusted for personal factors. Although force measures alone were not independent predictors of CTS in these data, strong associations between combined physical exposures of force and repetition and CTS were observed in all models. Consistent with previous literature, this report shows that workers with high force/high repetition jobs had the highest prevalence of CTS (odds ratio = 2.14-2.95) followed by intermediate values (odds ratio = 1.09-2.27) in mixed exposed jobs relative to the lowest exposed workers. This study supports the use of a general population job exposure matrix to estimate workplace physical exposures in epidemiologic studies of musculoskeletal disorders when measures of individual exposures are unavailable.
Aims: To re-examine aerodigestive cancer risk in a cohort of autoworkers exposed to metal working fluids (MWF), using improved case definition and more recently diagnosed cases. Methods: The ...autoworker cohort included 31 100 hourly workers alive on 1 January 1985 who worked at three automobile plants in Michigan. A case-cohort design was carried out that included incident cases of cancers of the larynx, oesophagus, and stomach, and a 10% sample of the cohort. A Cox proportional hazards model was used to estimate MWF exposure effects. The smoothing method of penalised splines was used to explore the shape of the underlying exposure-response curves. Results: The most important finding was the association between larynx cancer incidence and cumulative straight MWF exposure. The results for oesophageal cancer were less consistent. For stomach cancer there was no evidence of excess risk. Conclusion: This association between larynx cancer and straight MWF exposures was consistent with a previous finding in this cohort, providing further support for a causal relation.
To evaluate the chronic effects of exposure to cotton dust, a 15-yr follow-up study in cotton textile workers was performed in Shanghai, China from 1981 to 1996. Testing occurred four times during ...the 15-yr period. The achieved follow-up rates were 76-88% of the original 447 cotton textile workers, and 70-85% of the original 472 silk textile workers (as a control group). Identical questionnaires, equipment, and methods were used throughout the study. The prevalence of byssinosis increased over time in cotton workers, with 15.3% at the last survey versus 7.6% at the baseline, whereas no byssinosis was found in silk workers. More workers in the cotton group consistently reported symptoms than in the silk group, although symptom reporting varied considerably from survey to survey. Cotton workers had small, but significantly greater, adjusted annual declines in FEV(1) and FVC than did the silk workers. Years worked in cotton mills, high level of exposure to endotoxin, and across-shift drops in FEV(1) were found to be significant determinants for longitudinal change in FEV(1), after controlling for appropriate confounders. Furthermore, there were statistically significant associations between excessive loss of FEV(1) and byssinosis, chest tightness at work, and chronic bronchitis in cotton workers. Workers who consistently (three or four of the surveys) reported byssinosis or chest tightness at work had a significantly greater 15-yr loss of FEV(1). We conclude that long-term exposure to cotton dust is associated with chronic or permanent obstructive impairments. Consistent reporting of respiratory symptoms, including byssinosis and chest tightness at work, is of value to predict the magnitude and severity of chronic impairments in textile workers.
The recently revised ACGIH TLV for Hand Activity (TLV2018) is a widely used tool for assessing risk for upper limb musculoskeletal disorders. The purpose of this analysis was to compare the strength ...of the exposure-response relationships between the TLV2018 and carpal tunnel syndrome (CTS) between men and women and across age strata. Heterogeneity of the effect size by sex or age would be important to specialists using the method for prevention of CTS among working populations. Data from two large prospective studies were combined to allow for stratification of exposure-response models assessing the association between the TLV2018 and CTS by gender and age. Results show greater risk for women than men and for younger workers than older workers for TLV2018 values above the action limit. Although the TLV2018 is an effective surveillance tool for estimating increased risk of CTS with increasing exposure, these analyses show that such increase are not homogeneous across sex and age.
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