Objective-Terbufos is the fourth most commonly used organophosphate insecticide (OP) in the United States. Terbufos has not been demonstrated to be carcinogenic in rodents, although nonarsenical insecticides, including OPs, have been associated with excess cancer in epidemiologic studies. We investigated associations between use of terbufos and incidence of cancer. Methods-TheAgricultural Health Study is a prospective cohort study of 57,310 licensed pesticide applicators from Iowa and North Carolina. Detailed information about 50 pesticides, including terbufos, and potential confounders was obtained from self-administered questionnaires. Terbufos intensity-weighted lifetime exposure-days [(lifetime exposure-days) X (exposure intensity score)]. Cases include all first primary cancers diagnosed between enrollment and December 31, 2005. Hazard ratios (HR) and 95% CI were calculated with Cox proportional hazards models, adjusting for potential confounders.Results-Overall cancer risk was slightly increased among terbufos users (HR 1.21 (1.06-1.37). Suggestive associations were observed between terbufos use and cancers of the prostate (HR highest tertile = 1.21; 95% CI = 0.99-1.47) and lung (HR middle tertile = 1.45; 95% CI = 0.95-2.22) and leukemia (HR middle tertile = 2.38; 95% CI = 1.35-4.21) and non-Hodgkin lymphoma (HR middle tertile = 1.94; 95% CI = 1.16-3.22), although the exposure-response gradients were nonmonotonic and p for trends were not significant. Conclusion-We found suggestive associations between occupational terbufos use and several cancer sites. However, cautious interpretation of these results is warranted by the lack of existing experimental and epidemiologic evidence to support carcinogenic effects of terbufos.
Background Multidrug-resistant Enterobacterales (MDR-E) are important pathogens. People with human immunodeficiency virus (HIV) may be at greater risk for MDR-E infection given relatively high antibiotic exposure and burden of comorbidities. Methods Analyses were conducted using data collected on 36,521 patients in a healthcare system in North Carolina, who had at least 1 clinical culture with growth of an Enterobacterales species from 2000-2018; 440 were people with HIV infection (PWH). We used generalized linear models to estimate prevalence ratios and differences contrasting patients with and without HIV for resistance to individual antibiotic classes, as well as MDR-E. We assessed trends in prevalence over time by calculating the 5-year moving average and fitting restricted cubic spline models. Results The overall prevalence of MDR-E was higher among PWH (21.5% [95% CI: 18.2%-25.1%]) versus patients without HIV (16.5% [95% CI: 16.2%-16.9%], with an adjusted prevalence ratio of 1.38 (95% CI: 1.14-1.65). PWH had higher rates of antimicrobial resistance than patients without HIV for all antibiotic classes analyzed, including penicillins, penicillin/beta-lactamase inhibitor combinations, and sulfonamides. MDR-E prevalence was 3 to 10 percentage points higher among PWH than patients without HIV throughout the study period based on the 5-year moving average. Conclusion In a large clinical study population in the southeastern US from 2000-2018, the prevalence of antibacterial resistance among Enterobacterales was consistently higher among PWH than patients without HIV. These data highlight the importance of identifying and mitigating the factors contributing to antimicrobial resistance in PWH, given the potential clinical consequences of these resistant pathogens.
Background Medically vulnerable individuals are at increased risk of acquiring multidrug-resistant Enterobacterales (MDR-E) infections. People with HIV (PWH) experience a greater burden of comorbidities and may be more susceptible to MDR-E due to HIV-specific factors. Methods We performed an observational study of PWH participating in an HIV clinical cohort and engaged in care at a tertiary care center in the southeastern US from 2000-2018. We evaluated demographic and clinical predictors of MDR-E by estimating prevalence ratios (PRs) and employing machine learning classification algorithms. In addition, we created a predictive model to estimate risk of MDR-E among PWH using a machine learning approach. Results Among 4,734 study participants, MDR-E was isolated from 1.6% (95% CI: 1.2-2.1%). In unadjusted analyses, MDR-E was strongly associated with nadir CD4 cell count ≤200 cells/mm 3 (PR: 4.0; 95% CI: 2.3-7.4), history of an AIDS-defining clinical condition (PR: 3.7; 95% CI: 2.3-6.2), and hospital admission in the prior 12 months(PR: 5.0; 95% CI: 3.2-7.9). With all variables included in machine learning algorithms, the most important clinical predictors of MDR-E were hospitalization, history of renal disease, history of an AIDS-defining clinical condition, CD4 cell count nadir ≤200 cells/mm 3 , and current CD4 cell count 201-500 cells/mm 3 . Female gender was the most important demographic predictor. Conclusions PWH are at risk for MDR-E infection due to HIV-specific factors, in addition to established risk factors. Early HIV diagnosis, linkage to care, and antiretroviral therapy to prevent immunosuppression, comorbidities, and coinfections protects against antimicrobial-resistant bacterial infections.
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