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Background The impact of ongoing efforts to decrease opioid use on patients with cancer remains undefined. Our objective was to determine trends in new and additional opioid use in patients with and without cancer. Methods This retrospective cohort study used data from Surveillance, Epidemiology, and End Results program–Medicare for opioid-naive patients with solid tumor malignancies diagnosed from 2012 through 2017 and a random sample of patients without cancer. We identified 238 470 eligible patients with cancer and further focused on 4 clinical strata: patients without cancer, patients with metastatic cancer, patients with nonmetastatic cancer treated with surgery alone ("surgery alone"), and patients with nonmetastatic cancer treated with surgery plus chemotherapy or radiation therapy ("surgery+"). We identified new, early additional, and long-term additional opioid use and calculated the change in predicted probability of these outcomes from 2012 to 2017. Results New opioid use was higher in patients with cancer (46.4%) than in those without (6.9%) (P  < .001). From 2012 to 2017, the predicted probability of new opioid use was more stable in the cancer strata (relative declines: 0.1% surgery alone; 2.4% surgery+; 8.8% metastatic cancer), than in the noncancer stratum (20.0%) (P  < .001 for each cancer to noncancer comparison). Early additional use declined among surgery patients (‒14.9% and ‒17.5% for surgery alone and surgery+, respectively) but was stable among patients with metastatic disease (‒2.8%, P  = .50). Conclusions Opioid prescribing declined over time at a slower rate in patients with cancer than in patients without cancer. Our study suggests important but tempered effects of the changing opioid climate on patients with cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Agricultural work and occupational pesticide use have been associated with increased risk of renal cell carcinoma (RCC), the most common form of kidney cancer. However, few prospective studies have investigated links to specific pesticides. OBJECTIVE: We evaluated the lifetime use of individual pesticides and the incidence of RCC. METHODS: We evaluated the associations between intensity-weighted lifetime days (IWDs) of 38 pesticides and incident RCC in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. Among 55,873 applicators, 308 cases were diagnosed between enrollment (1993-1997) and the end of follow-up (2014-2015). We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounding factors, with lagged and unlagged pesticide exposures. RESULTS: There was a statistically significant increased risk of RCC among the highest users of 2,4,5-T compared with never users [unlagged R[R.sub.IWD Tertile 3] = 2.92 (95% CI: 1.65, 5.17; [p.sub.trend] = 0.001)], with similar risk estimates for lagged exposure [20-y lag R[R.sub.IWD Tertile 3] = 3.37 (95% CI: 1.83, 6.22; [p.sub.trend] = 0.001)]. In 20-y lagged analyses, we also found exposure--response associations with chlorpyrifos [R[R.sub.IWD Quartile 4] = 1.68 (95% CI: 1.05, 2.70; [p.sub.trend] = 0.01)], chlordane [R[R.sub.IWD Tertile 3] = 2.06 (95% CI: 1.10, 3.87; [p.sub.trend] = 0.02)], atrazine [R[R.sub.IWD Quartile 4] = 1.43 (95% CI: 1.00, 2.03; [p.sub.trend] = 0.02)], cyanazine [R[R.sub.IWD Quartile 4] = 1.61 (95% CI: 1.03, 2.50; [p.sub.trend] = 0.02)], and paraquat [R[R.sub.IWD >Median] = 1.95 (95% CI: 1.03,3.70; [p.sub.trend] = 0.04)]. CONCLUSIONS: This is, to our knowledge, the first prospective study to evaluate RCC risk in relation to various pesticides. We found evidence of associations with RCC for four herbicides (2,4,5-T, atrazine, cyanazine, and paraquat) and two insecticides (chlorpyrifos and chlordane). Our findings provide insights into specific chemicals that may influence RCC risk among pesticide applicators. Confirmation of these findings and investigations of the biologic plausibility and potential mechanisms underlying the observed associations are warranted. https://doi.org/10.1289/EHP6334, Introduction The incidence of renal cell carcinoma (RCC), the most common form of kidney cancer, has been steadily increasing in the United States for several decades (Noone et al. 2018; [...]

Background: Farmers have a higher incidence of multiple myeloma, and there is suggestive evidence of an elevated prevalence of its precursor, monoclonal gammopathy of undetermined significance (MGUS), relative to the general population. Pesticide exposures are suspected to play a role; however, the biologic plausibility for associations with multiple myeloma remains unclear. Objectives: Our objectives were to examine the prevalence of MGUS and evaluate associations with a wide range of pesticides in a large sample of farmers. Methods: We obtained sera and assessed MGUS among 1,638 male farmers [greater than or equal to] 50 years of age in the Agricultural Health Study (AHS), a prospective cohort in Iowa and North Carolina. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to estimate associations with MGUS for recent use (within the 12 months before phlebotomy) and cumulative intensity-weighted lifetime days of use of specific pesticides. Results: The age-standardized MGUS prevalence was significantly elevated among AHS farmers (7.7%) compared with demographically similar men in the National Health and Nutrition Examination Survey (2.8%) or Olmsted County, Minnesota (3.8%; p < 0.001). Recent use of permethrin was associated with MGUS [recent use vs. no recent use, OR = 1.82 (95% CI: 1.06, 3.13)], especially among those who had also used it in the past [recent and past use vs. never use, OR = 2.49 (95% CI: 1.32, 4.69)]. High intensity-weighted lifetime use of the organochlorine insecticides aldrin and dieldrin was associated with MGUS relative to those who never used either of these pesticides [OR = 2.42 (95% CI: 1.29, 4.54); ptiend = 0.006]. We also observed a positive association with high lifetime use of petroleum oil/distillates as an herbicide, as well as an inverse association with fonofos use. Discussion: This is the largest investigation of MGUS in farmers and the first to identify an association with MGUS for permethrin, a pyrethroid insecticide previously associated with multiple myeloma. Given the continued widespread use of permethrin in various residential and commercial settings, our findings may have important implications for exposed individuals in the general population. https://doi.org/10.1289/EHP6960, Introduction An excess in the incidence of multiple myeloma (MM), an aggressive plasma cell malignancy, has been consistently observed in studies of farmers and other agricultural workers conducted over the [...]

Background: Though evidence suggests that some pesticides may have thyroid-disrupting properties, prospective studies of associations between specific pesticides and incident thyroid disease are limited. Objective: We evaluated associations between use of specific pesticides and incident hypothyroidism in private pesticide applicators in the Agricultural Health Study (AHS). Methods: Self-reported incident hypothyroidism (n = 829 cases) was studied in relation to ever-use and intensity- weighted cumulative days of pesticide use at study enrollment. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CI) using Cox proportional hazards models applied to 35,150 male and female applicators followed over 20 y. All models were stratified by state and education to meet proportional hazards assumptions (p [less than or equal to] 0.10 for age x covariate interactions). Models of pesticides that did not meet proportional hazards assumptions were stratified by median attained age (62 y). Results: Hypothyroidism risk was significantly increased with ever- vs. never-use of four organochlorine insecticides (aldrin, heptachlor, and lindane among participants with attained age >62 y; chlordane in all participants), four organophosphate insecticides (coumaphos in those >62 y; diazinon, dichlorvos, and malathion in all participants) and three herbicides (dicamba, glyphosate, and 2,4-D in all participants). HRs ranged from 1.21; 95% CI: 1.04, 1.41 (chlordane) to 1.54; 95% CI: 1.23, 19.4 (lindane in those >62 y). Hypothyroidism risk was greatest among those with higher intensityweighted lifetime days of using chlordane, lindane, coumaphos (over age 62), diazinon, permethrin, and 2,4-D. Conclusions: Our findings support associations between exposure to several pesticides and increased hypothyroidism risk. These findings are generally consistent with prior analyses of prevalent hypothyroidism in the AHS., Introduction Thyroid diseases are common in the United States (U.S.); and with prevalence estimates of 5-9% (overt and subclinical disease combined), hypothyroidism is the most common thyroid disease (Garber et [...]

BACKGROUND: Some epidemiologic and laboratory studies suggest that insecticides are related to increased breast cancer risk, but the evidence is inconsistent. Women engaged in agricultural work or who reside in agricultural areas may experience appreciable exposures to a wide range of insecticides. OBJECTIVE: We examined associations between insecticide use and breast cancer incidence among wives of pesticide applicators (farmers) in the prospective Agricultural Health Study. METHODS: Farmers and their wives provided information on insecticide use, demographics, and reproductive history at enrollment in 1993-1997 and in 5-y follow-up interviews. Cancer incidence was determined via cancer registries. Among 30,594 wives with no history of breast cancer before enrollment, we examined breast cancer risk in relation to the women's and their husbands' insecticide use using Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During an average 14.7-y follow-up, 39% of the women reported ever using insecticides, and 1,081 were diagnosed with breast cancer. Although ever use of insecticides overall was not associated with breast cancer risk, risk was elevated among women who had ever used the organophosphates chlorpyrifos [HR= 1.4 (95% CI: 1.0, 2.0)] or terbufos [HR = 1.5 (95% CI: 1.0, 2.1)], with nonsignificantly increased risks for coumaphos [HR = 1.5 (95% CI: 0.9, 2.5)] and heptachlor [HR= 1.5 (95% CI: 0.7, 2.9)]. Risk in relation to the wives' use was associated primarily with premenopausal breast cancer. We found little evidence of differential risk by tumor estrogen receptor status. Among women who did not apply pesticides, the husband's use of fonofos was associated with elevated risk, although no exposure-response trend was observed. CONCLUSION: Use of several organophosphate insecticides was associated with elevated breast cancer risk. However, associations for the women's and husbands' use of these insecticides showed limited concordance. Ongoing cohort follow-up may help clarify the relationship, if any, between individual insecticide exposures and breast cancer risk. https://doi.org/10.1289/EHP1295, Introduction Established environmental and genetic risk factors for breast cancer do not explain a large proportion of the ~247,000 cases diagnosed annually in the United States (Siegel et al. 2016), [...]

Background: Glyphosate is the most commonly used herbicide worldwide, with both residential and agricultural uses. In 2015, the International Agency for Research on Cancer classified glyphosate as "probably carcinogenic to humans," noting strong mechanistic evidence and positive associations for non-Hodgkin lymphoma (NHL) in some epidemiologic studies. A previous evaluation in the Agricultural Health Study (AHS) with follow-up through 2001 found no statistically significant associations with glyphosate use and cancer at any site.Methods: The AHS is a prospective cohort of licensed pesticide applicators from North Carolina and Iowa. Here, we updated the previous evaluation of glyphosate with cancer incidence from registry linkages through 2012 (North Carolina)/2013 (Iowa). Lifetime days and intensity-weighted lifetime days of glyphosate use were based on self-reported information from enrollment (1993-1997) and follow-up questionnaires (1999-2005). We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounders, including use of other pesticides. All statistical tests were two-sided.Results: Among 54 251 applicators, 44 932 (82.8%) used glyphosate, including 5779 incident cancer cases (79.3% of all cases). In unlagged analyses, glyphosate was not statistically significantly associated with cancer at any site. However, among applicators in the highest exposure quartile, there was an increased risk of acute myeloid leukemia (AML) compared with never users (RR = 2.44, 95% CI = 0.94 to 6.32, Ptrend = .11), though this association was not statistically significant. Results for AML were similar with a five-year (RRQuartile 4 = 2.32, 95% CI = 0.98 to 5.51, Ptrend = .07) and 20-year exposure lag (RRTertile 3 = 2.04, 95% CI = 1.05 to 3.97, Ptrend = .04).Conclusions: In this large, prospective cohort study, no association was apparent between glyphosate and any solid tumors or lymphoid malignancies overall, including NHL and its subtypes. There was some evidence of increased risk of AML among the highest exposed group that requires confirmation. [ABSTRACT FROM AUTHOR]

The article offers the authors's response to the comments of Sheppard and Shaffer to their report of glyphosate and cancer risk in the Agricultural Health Study. The authors say that they did not account for health outcome when imputing exposure. They believe that the data in their study demonstrate that the exclusion of outcome information in their amputation of glyphosate exposure did not introduce meaningful bias in cancer risk.

Background: In the developed world, occupational exposures are a leading cause of bladder cancer. A few studies have suggested a link between pesticide exposures among agricultural populations and bladder cancer.Methods: We used data from the Agricultural Health Study, a prospective cohort study which includes 57 310 pesticide applicators with detailed information on pesticide use, to evaluate the association between pesticides and bladder cancer. We used Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) to estimate the association between each of 65 pesticides and 321 incident bladder cancer cases which accrued over the course of follow-up (1993-2011), adjusting for lifestyle and demographic and non-pesticide farm-related exposures, including those previously linked to bladder cancer. We conducted additional analyses stratified by smoking status (never, former, current).Results: We observed associations with bladder cancer risk for two imidazolinone herbicides, imazethapyr and imazaquin, which are aromatic amines. Ever use of imazaquin (RR = 1.54, 95% CI: 1.05, 2.26) was associated with increased risk whereas the excess risk among users of imazethapyr was evident among never smokers (RR in highest quartile vs non-exposed = 3.03, 95% CI: 1.46, 6.29, P-interaction = 0.005). We also observed increased risks overall and among never smokers for use of several chlorinated pesticides including chlorophenoxy herbicides and organochlorine insecticides.Conclusions: Several associations between specific pesticides and bladder cancer risk were observed, many of which were stronger among never smokers, suggesting that possible risk factors for bladder cancer may be more readily detectable in those unexposed to potent risk factors like tobacco smoke. [ABSTRACT FROM AUTHOR]