Targeting patients for early COVID-19 therapy; Pre-infection metabolic dysfunction, polycystic ovary syndrome and risk of severe disease in patients under 65: A Massachusetts community-based observational study.

INTRODUCTION: The demographics of those developing severe coronavirus disease (COVID-19) outcomes are shifting to younger patients. In an observational study utilizing electronic health records from a Massachusetts group medical practice, we identified 5025 patients with confirmed COVID-19 from March 1 to December 18, 2020. Of these, 3870 were under 65 years of age. We investigated the hypothesis that pre-infection metabolic or immunologic dysregulation including polycystic ovary syndrome (PCOS) increased risk of serious COVID-19 outcomes in patients under 65 years of age. MATERIALS AND METHODS: We compared those with COVID-19 related hospitalization or mortality to all other COVID-19 patients, using a case control approach. Using logistic regression and propensity score modeling, we evaluated risk of developing severe COVID-19 outcomes (hospitalization or death) in those with pre-infection comorbidities, metabolic risk factors, or PCOS. RESULTS: Overall, propensity score matched analyses demonstrated pre-infection elevated liver enzymes alanine aminotransferase (ALT) >40, aspartate aminotransferase (AST) >40 and blood glucose ≥215 mg/dL were associated with more severe COVID-19 outcomes, OR = 1.74 (95% CI 1.31, 2.31); OR = 1.98 (95% CI 1.52, 2.57), and OR = 1.55 (95% CI 1.08, 2.23) respectively. Elevated hemoglobin A1C or blood glucose levels were even stronger risk factors for severe COVID-19 outcomes among those aged < 65, OR = 2.31 (95% CI 1.14, 4.66) and OR = 2.42 (95% CI 1.29, 4.56), respectively. In logistic regression models, women aged < 65 with PCOS demonstrated more than a four-fold increased risk of severe COVID-19, OR 4.64 (95% CI 1.98, 10.88). CONCLUSION: Increased risk of severe COVID-19 outcomes in those < age 65 with pre-infection indicators of metabolic dysfunction heightens the importance of monitoring pre-infection indicators in younger patients for prevention and early treatment. The PCOS finding deserves further investigation. Meanwhile women who suffer from PCOS should be carefully evaluated and prioritized for earlier COVID-19 treatment and vaccination.

Firefighting and Cancer: A Meta-analysis of Cohort Studies in the Context of Cancer Hazard Identification.

Objective: We performed a meta-analysis of epidemiological results for the association between occupational exposure as a firefighter and cancer as part of the broader evidence synthesis work of the IARCMonographs program. Methods: A systematic literature search was conducted to identify cohort studies of firefighters followed for cancer incidence and mortality. Studies were evaluated for the influence of key biases on results. Random-effects meta-analysis models were used to estimate the association between ever-employment and duration of employment as a firefighter and risk of 12 selected cancers. The impact of bias was explored in sensitivity analyses. Results: Among the 16 included cancer incidence studies, the estimated meta-rate ratio, 95% confidence interval (CI), and heterogeneity statistic (I2) for ever-employment as a career firefighter compared mostly to general populations were 1.58 (1.14-2.20, 8%) for mesothelioma, 1.16 (1.08-1.26, 0%) for bladder cancer, 1.21 (1.12-1.32, 81%) for prostate cancer, 1.37 (1.03-1.82, 56%) for testicular cancer, 1.19 (1.07-1.32, 37%) for colon cancer, 1.36 (1.15-1.62, 83%) for melanoma, 1.12 (1.01-1.25, 0%) for non-Hodgkin lymphoma, 1.28 (1.02-1.61, 40%) for thyroid cancer, and 1.09 (0.92-1.29, 55%) for kidney cancer. Ever-employment as a firefighter was not positively associated with lung, nervous system, or stomach cancer. Results for mesothelioma and bladder cancer exhibited low heterogeneity and were largely robust across sensitivity analyses. Conclusions: There is epidemiological evidence to support a causal relationship between occupational exposure as a firefighter and certain cancers. Challenges persist in the body of evidence related to the quality of exposure assessment, confounding, and medical surveillance bias.

If Smoking Were Eliminated, Which US Counties Would Still Have High Rates of Smoking-Related Cancers?

OBJECTIVE: to characterize the county variability of the impact of smoking elimination on rates of smoking-related cancers and explore whether common environmental indices predicted which metropolitan counties would experience high rates of smoking-related cancers even after smoking was eliminated. METHODS: Surveillance, Epidemiology, and End Results Program (SEER) and Environmental Protection Agency (EPA) data were obtained. County level cancer rates for 257 metropolitan SEER counties, including the observed rates and those predicted after eliminating smoking, were derived via multilevel regression modeling and age standardized to the 2016 SEER population. Associations between the EPA's Environmental Quality Index (EQI) scores and "Low Benefit" counties (counties that remain above the top 20th percentile of post-smoking elimination incidence rates) were explored via logistic regression. RESULTS: Reductions in smoking-related cancer incidence ranged from 58.4 to 3.2%. The overall EQI (OR = 1.96, 95% CI [1.34, 2.86]) and the air quality index (OR = 5.99, 95% CI [3.20, 11.22]) scores predicted higher odds of being a "Low Benefit" county. CONCLUSIONS: Substantial inequities in the post-smoking elimination cancer rates were observed; air pollution appears to be a primary explanation for this. Cancer prevention in metropolitan counties with high levels of air pollution should prioritize pollution control at least as much as tobacco control.

Hypertension, medications, and risk of severe COVID-19: A Massachusetts community-based observational study.

It remains uncertain whether the hypertension (HT) medications angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) mitigate or exacerbate SARS-CoV-2 infection. We evaluated the association of ACEi and ARB with severe coronavirus disease 19 (COVID-19) as defined by hospitalization or mortality among individuals diagnosed with COVID-19. We investigated whether these associations were modified by age, the simultaneous use of the diuretic thiazide, and the health conditions associated with medication use. In an observational study utilizing data from a Massachusetts group medical practice, we identified 1449 patients with a COVID-19 diagnosis. In our study, pre-infection comorbidities including HT, cardiovascular disease, and diabetes were associated with increased risk of severe COVID-19. Risk was further elevated in patients under age 65 with these comorbidities or cancer. Twenty percent of those with severe COVID-19 compared to 9% with less severe COVID-19 used ACEi, 8% and 4%, respectively, used ARB. In propensity score-matched analyses, use of neither ACEi (OR = 1.30, 95% CI 0.93 to 1.81) nor ARB (OR = 0.94, 95% CI 0.57 to 1.55) was associated with increased risk of severe COVID-19. Thiazide use did not modify this relationship. Beta blockers, calcium channel blockers, and anticoagulant medications were not associated with COVID-19 severity. In conclusion, cardiovascular-related comorbidities were associated with severe COVID-19 outcomes, especially among patients under age 65. We found no substantial increased risk of severe COVID-19 among patients taking antihypertensive medications. Our findings support recommendations against discontinuing use of renin-angiotensin system (RAS) inhibitors to prevent severe COVID-19.

A Corporate Wellness Program and Nursing Home Employees' Health.

Background: Many employed Americans suffer from chronic conditions like obesity, diabetes, and cardiovascular diseases. Worksite wellness programs provide opportunities to introduce health promotion strategies. While there is evidence of the effectiveness of workplace health promotion, this is tempered by concern that benefits may be less available to low-wage workers with inflexible working conditions. Objective: The aim was to evaluate a workplace health promotion (WHP) in the long-term care sector (skilled nursing facilities). Methods: Nursing home employees from 18 facilities within a single company were surveyed by a standardized, self-administered questionnaire. A company-sponsored WHP program was offered to the facilities, which were free to take it up or not. We categorized the facilities by level of program adoption. Cross-sectional associations were estimated between program category and prevalence of individual-level worker health indicators, adjusting for center-level working conditions. Results: A total of 1,589 workers in 5 job categories completed the survey. Average levels of psychological demands and social support at work were relatively high. Supervisor support stood out as higher in centers with well-developed WHP programs, compared to centers with no programs. There were no differences among program levels for most health outcomes. Workers in centers with well-developed programs had slightly lower average body mass index and (unexpectedly) slightly lower prevalence of non-smoking and regular aerobic exercise. Conclusions: Only small health benefits were observed from well-developed programs and working conditions did not appear to confound the negative results. This low-intensity, low-resourced workplace health promotion program may have benefited a few individuals but seems to have had only modest influence on average levels of the measured health indicators. Many nursing home employees experience obstacles to health behaviors; approaches that provide more environmental and economic supports for healthy behaviors, such as Total Worker Health®, may yield larger health benefits.

Cancer rates not explained by smoking: a county-level analysis.

BACKGROUND: Debates over the importance of "lifestyle" versus "environment" contributions to cancer have been going on for over 40 years. While it is clear that cigarette smoking is the most significant cancer risk factor, the contributions of occupational and environmental carcinogens in air, water and food remain controversial. In practice, most cancer prevention messaging focuses on reducing cigarette smoking and changing other personal behaviors with little mention of environmental chemicals, despite widespread exposure to many known carcinogens. To inform decision-making on cancer prevention priorities, we evaluated the potential impact of smoking cessation on cancer rates. METHODS: Using cancer incidence data from 612 counties in the SEER database, and county-level smoking prevalences, we investigated the impact of smoking cessation on incidence for 12 smoking-related cancer types, 2006-2016. A multilevel mixed-effects regression model quantified the association between county-level smoking prevalence and cancer incidence, adjusting for age, gender and variability over time and among counties. We simulated complete smoking cessation and estimated the effects on county-level cancer rates. RESULTS: Regression models showed the expected strong association between smoking prevalence and cancer incidence. Simulating complete smoking cessation, the incidence of the 12 smoking-related cancer types fell by 39.8% (54.9% for airways cancers; 28.9% for non-airways cancers). And, while the actual rates of smoking-related cancers from 2006 to 2016 declined (annual percent change (APC) = - 0.8, 95% CI = - 1.0 to - 0.5%), under the scenario of smoking elimination, the trend in cancer incidence at these sites was not declining (APC = - 0.1, 95% CI = - 0.4 to + 0.1%). Not all counties were predicted to benefit equally from smoking elimination, and cancer rates would fall less than 10% in some counties. CONCLUSIONS: Smoking prevention has produced dramatic reductions in cancer in the US for 12 major types. However, we estimate that eliminating smoking completely would not affect about 60% of cancer cases of the 12 smoking-related types, leaving no improvement in the incidence trend from 2006 to 2016. We conclude that cancer prevention strategies should focus not only on lifestyle changes but also the likely contributions of the full range of risk factors, including environmental/occupational carcinogens.

The IARC Monographs: Updated Procedures for Modern and Transparent Evidence Synthesis in Cancer Hazard Identification.

The Monographs produced by the International Agency for Research on Cancer (IARC) apply rigorous procedures for the scientific review and evaluation of carcinogenic hazards by independent experts. The Preamble to the IARC Monographs, which outlines these procedures, was updated in 2019, following recommendations of a 2018 expert advisory group. This article presents the key features of the updated Preamble, a major milestone that will enable IARC to take advantage of recent scientific and procedural advances made during the 12 years since the last Preamble amendments. The updated Preamble formalizes important developments already being pioneered in the Monographs program. These developments were taken forward in a clarified and strengthened process for identifying, reviewing, evaluating, and integrating evidence to identify causes of human cancer. The advancements adopted include the strengthening of systematic review methodologies; greater emphasis on mechanistic evidence, based on key characteristics of carcinogens; greater consideration of quality and informativeness in the critical evaluation of epidemiological studies, including their exposure assessment methods; improved harmonization of evaluation criteria for the different evidence streams; and a single-step process of integrating evidence on cancer in humans, cancer in experimental animals, and mechanisms for reaching overall evaluations. In all, the updated Preamble underpins a stronger and more transparent method for the identification of carcinogenic hazards, the essential first step in cancer prevention.

Standardized morbidity ratios of four chronic health conditions among World Trade Center responders: Comparison to the National Health Interview Survey.

PURPOSE: We conducted external comparisons for the prevalence of asthma, hypertension, diabetes, and cancer among World Trade Center (WTC) general responders using the National Health Interview Survey (NHIS) as the reference, along with internal comparisons for the incidence of asthma. METHODS: Standardized Morbidity Ratios (SMRs) were calculated for the prevalence of the health conditions, and risk ratios (RRs) for asthma incidence. RESULTS: Relative to the NHIS, asthma prevalence was in excess in responders over the study years (age-adjusted SMRs = 1.3-2.8). Hypertension prevalence began to exceed expected from 2006 while diabetes was lower than expected. An upward trend towards excess cancer prevalence was observed. Internal comparisons showed elevated asthma incidence among protective service and utility workers compared to construction workers; while those who arrived at the WTC site in the morning of 9/11 had a lower asthma risk than those who arrived in the afternoon. CONCLUSIONS: The use of NHIS data as a reference population demonstrates and reconfirms several important patterns of excess risk in WTC responders. External comparisons are an alternative for disaster cohorts without an established comparison group.

The increasing toll of adolescent cancer incidence in the US.

Cancer incidence is rising among adolescents ("teens"). The causes of the increase are unknown but studying incidence patterns and trends may produce insights into etiology. Using data from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program we described trends of cancer incidence among teens (15-19 year olds). We reviewed and summarized incidence patterns for histologic cancer groups and the most frequently diagnosed sites of cancer among teens during 2008-2012 reported by the SEER Cancer Statistics Review. We calculated annual incidence rates for the years 1975-2012 and used linear regression analysis to evaluate trends and calculate rates of change. Incidence for all sites combined increased annually by 0.67% for males and 0.62% for females during the period 1975 through 2012 -resulting in more than a 25% increase over 38 years. The biggest annual incidence increases occurred in non-Hodgkin lymphoma (NHL) (2.16% females; 1.38% males), thyroid cancer (2.12% females; 1.59% males), acute myeloid leukemia (AML) (1.73% females) and testicular cancer (1.55% males). Incidence rates for most histologic groups and sites showed steady long term increases over the 38 years of data. Despite improvements in survival, rising incidence trends mean growing numbers of young adults are undergoing painful and costly cancer treatments. A concerted research program is vital to investigate causes of steadily rising teen cancer rates.

Environmental and Economic Strategies for Primary Prevention of Cancer in Early Life.

This article summarizes the evidence for environmental toxic exposures contributing to cancers in early life, focusing on the most common cancer sites in this age group. It provides examples of widespread avoidable exposures to human carcinogens through air, water, and food and then describes recent examples of successful initiatives to reduce exposure to chemicals linked to these cancer sites, through government policy, industry initiatives, and consumer activism. State government initiatives to reduce toxic chemical exposures have made important gains; the Toxics Use Reduction Act of Massachusetts is now 25 years old and has been a major success story. There are a growing number of corporate initiatives to eliminate toxics, especially carcinogens, from the products they manufacture and sell. Another important opportunity for cancer prevention is provided by online databases that list chemicals, their toxicity, and lower-toxicity alternatives; these can be used by businesses, health care institutions, consumers, and workers to reduce exposures to chemicals of concern. The article concludes by inviting pediatricians and public health professionals to include elimination of carcinogen exposures in their work to promote primary prevention of cancer in early life.

Vascular risk factors and rhegmatogenous retinal detachment: a follow-up of a national cohort of Swedish men.

BACKGROUND: We aimed to investigate the role of vascular risk factors in the genesis of rhegmatogenous retinal detachment (RRD) using data from a large cohort of Swedish conscripts. METHODS: We used data from a nationwide cohort of 49 321 Swedish men born during 1949-1951, conscripted for compulsory military service in 1969-1970 with nearly complete follow-up to 2009. Information on surgically treated RRD between 1973 and 2009 was collected from the National Patient Register. We fitted Cox regression models stratified on myopia degree and including blood pressure levels, body mass index and cigarette smoking. Population attributable fractions of RRD were estimated through maximum likelihood methods. RESULTS: We observed 262 cases of RRD in 1 725 770 person-years. At multivariate analysis, the number of cigarettes per day showed a reverse association with the risk of RRD (p for trend 0.01). Conscripts with obesity presented a higher risk compared with normal subjects (adjusted HR 2.51, 95% CI 1.02 to 6.13). We found weak evidence of an association between blood pressure and RRD (HR for men with hypertension compared with normotension 1.41, 95% CI 0.93 to 2.13). All the observed associations were stronger when the analysis was restricted to non-myopic conscripts. In particular, the HR for hypertension was 2.33 (95% CI 1.30 to 4.19) compared with normotension. If this association is causal, we estimated that 42.0% of RRD cases (95% CI 11.5% to 62.0%) occurring among non-myopics are attributable to elevated blood pressure. CONCLUSIONS: Vascular risk factors may be important determinants of RRD, particularly among non-myopics. Further investigations on the role of hypertension and obesity are needed.

Risk of mesothelioma following external beam radiotherapy for prostate cancer: a cohort analysis of SEER database.

PURPOSE: To investigate the association between external beam radiotherapy (EBRT) for prostate cancer and mesothelioma using data from the US Surveillance, Epidemiology, and End Results (SEER) cancer registries. METHODS: We analyzed data from the SEER database (1973-2009). We compared EBRT versus no radiotherapy. Incidence rate ratios (IRR) and 95 % confidence intervals (95 % CI) of mesothelioma among prostate cancer patients were estimated with multilevel Poisson models adjusted by race, age, and calendar year. Confounding by asbestos was investigated using relative risk of mesothelioma in each case's county of residence as a proxy for asbestos exposure. RESULTS: Four hundred and seventy-one mesothelioma cases (93.6 % pleural) occurred in 3,985,991 person-years. The IRR of mesothelioma was increased for subjects exposed to EBRT (1.28; 95 % CI 1.05, 1.55) compared to non-irradiated patients, and a population attributable fraction of 0.49 % (95 % CI 0.11, 0.81) was estimated. The IRR increased with latency period: 0-4 years, IRR 1.08 (95 % CI 0.81, 1.44); 5-9 years, IRR 1.31 (95 % CI 0.93, 1.85); ≥10 years, IRR 1.59 (95 % CI 1.05, 2.42). Despite the fairly strong evidence of association with EBRT, the population attributable rate of mesothelioma was modest-3.3 cases per 100,000 person-years. The cumulative incidence of mesothelioma attributable to EBRT was 4.0/100,000 over 5 years, 24.5/100,000 over 10 years, and 65.0/100,000 over 15 years. CONCLUSIONS: Our study provides evidence that EBRT for prostate cancer is a small but detectable risk factor for mesothelioma. Patients should be advised of risk of radiation-induced second malignancies.

Leisure time physical inactivity among Brazilian ragpicker

Ragpickers are informal workers who collect recyclable materials to earn a small wage. Their life and working conditions are extremely difficult. We examined leisure time physical inactivity (PI) among a cohort of ragpickers in Pelotas, a city in southern Brazil. Ragpickers were matched by gender, age, and years of schooling with a sample of nonragpickers from the same poor neighborhoods. The cross-sectional study gathered data by interview on 990 individuals. PI were assessed using a leisure time physical activities section from a standard self-reporting questionnaire (IPAQ long version). The prevalence of PI among ragpickers and non-ragpickers were 70.3% and 65.9, respectively (p=0.16). Among ragpickers PI was more common among females and those with higher ages, and among non-ragpickers with females, lower economic level and positivity to minor psychiatric disorders. Ragpickers report similar PI than other poor workers living in the same neighborhoods, with many of the same life conditions. Provide appropriate places to the practice of physical activities and organized and attractive activities could be alternatives to minimize physical, mental and emotional disorders of these workers

The two-stage clonal expansion model in occupational cancer epidemiology: results from three cohort studies.

OBJECTIVES: The objective of this work was to apply the two-stage clonal expansion model, with the intention to expand the literature on epidemiological applications of the model and demonstrate the feasibility of incorporating biologically based modelling methods into the widely used retrospective cohort study. METHODS: The authors fitted the two-stage clonal expansion model model to three occupational cohort studies: (1) a cohort of textile workers exposed to asbestos and followed for lung cancer mortality; (2) a cohort of diatomaceous earth workers exposed to silica and also followed for lung cancer mortality; and (3) a cohort of automotive manufacturing workers exposed to straight metalworking fluid (MWF) and followed for larynx cancer incidence. The model allowed the authors to estimate exposure effects in three stages: cancer initiation (early effects), promotion or malignant transformation (late effects). RESULTS: In the first cohort, the authors found strong evidence for an early effect of asbestos on lung cancer risk. Findings from analyses of the second cohort suggested early and less evidently late effects of silica on lung cancer risk. In the MWF (third) cohort, there was only weak evidence of straight MWF exposure effects on both early and late stages. The authors also observed a late birth cohort effect on larynx cancer risk. CONCLUSIONS: The findings for asbestos and silica were essentially confirmatory, supporting evidence for their early effects on lung cancer from a large body of literature. The effect of straight MWF on larynx cancer was less clear.

Epidemiology, public health, and the rhetoric of false positives.

BACKGROUND: As an observational science, epidemiology is regarded by some researchers as inherently flawed and open to false results. In a recent paper, Boffetta et al. [Boffetta P, McLaughlin JK, LaVecchia C, Tarone RE, Lipworth L, Blot WJ. False-positive results in cancer epidemiology: a plea for epistemological modesty. J Natl Cancer Inst 100:988-995 (2008)] argued that "epidemiology is particularly prone to the generation of false-positive results." They also said "the tendency to emphasize and over-interpret what appear to be new findings is commonplace, perhaps in part because of a belief that the findings provide information that may ultimately improve public health" and that "this tendency to hype new findings increases the likelihood of downplaying inconsistencies within the data or any lack of concordance with other sources of evidence." The authors supported these serious charges against epidemiology and epidemiologists with few examples. Although we acknowledge that false positives do occur, we view the position of Boffetta and colleagues on false positives as unbalanced and potentially harmful to public health. OBJECTIVE: We aim to provide a more balanced evaluation of epidemiology and its contribution to public health discourse. DISCUSSION: Boffetta and colleagues ignore the fact that false negatives may arise from the very processes that they tout as generating false-positive results. We further disagree with their proposition that false-positive results from a single study will lead to faulty decision making in matters of public health importance. In practice, such public health evaluations are based on all the data available from all relevant disciplines and never to our knowledge on a single study. CONCLUSIONS: The lack of balance by Boffetta and colleagues in their evaluation of the impact of false-positive findings on epidemiology, the charge that "methodological vigilance is often absent" in epidemiologists' interpretation of their own results, and the false characterization of how epidemiologic findings are used in societal decision making all undermine a major source of information regarding disease risks. We reaffirm the importance of epidemiologic evidence as a critical component of the foundation of public health protection.