Risk assessment for PFOA and kidney cancer based on a pooled analysis of two studies.

INTRODUCTION: Perfluorooctanoic acid (PFOA) has been associated with kidney cancer in human studies. METHODS: We conducted a pooled analysis of two large studies of PFOA and renal cell carcinoma (RCC, the most common type of kidney cancer); one from the National Cancer Institute (NCI) (324 cases and controls), and a second from the C8 Science Panel (103 cases and 511 controls). Serum PFOA levels were estimated a median of 8 years before diagnosis. Analyses were conducted via conditional logistic regression. Lifetime risk of kidney cancer per unit serum PFOA concentration and per unit dose were calculated. RESULTS: The 25th, 50th and 75th percentiles of serum PFOA levels were 4.8, 7.3, and 23.9 ng/ml for the pooled analysis. The preferred model for the pooled datawas a two-piece linear spline model (knot at 12.5 ng/ml serum PFOA); the log odds of RCC increased 0.1349 per 1 ng/ml increase in serum PFOA up to the knot (eg, an OR of 2.02 (1.45-2.80) from the median to the knot), and was flat thereafter. The estimated lifetime excess risk (cancer slope factor) with an exposure of 1 ng/ml was 0.0018, similar to the excess risk of 0.0026 recently reported by CalEPA based on different methods. Assuming a serum half-life of 2.3 years and a distribution volume of 170 ml/kg for PFOA, our results are equivalent to 0.0128 per ng/kg/d of PFOA intake. To limit excess lifetime kidney cancer risk to 1/1,000,000, our data suggest a limit of 0.0015 ng/L (0.0015 ppt) for PFOA in drinking water, similar to CalEPA's proposed Public Health Goal and the new US EPA Drinking Water Health Advisory. CONCLUSIONS: Our results correspond reasonably well with cancer slope factors developed by other investigators using published summary data, and suggest drinking water limits similar to new recommendations by the US EPA.

Association between maternal exposure to particulate matter (PM2.5) and adverse pregnancy outcomes in Lima, Peru.

The literature shows associations between maternal exposures to PM2.5 and adverse pregnancy outcomes. There are few data from Latin America. We have examined PM2.5 and pregnancy outcomes in Lima. The study included 123,034 births from 2012 to 2016, at three public hospitals. We used estimated daily PM2.5 from a newly created model developed using ground measurements, satellite data, and a chemical transport model. Exposure was assigned based on district of residence (n = 39). Linear and logistic regression analyzes were used to estimate the associations between air pollution exposure and pregnancy outcomes. Increased exposure to PM2.5 during the entire pregnancy and in the first trimester was inversely associated with birth weight. We found a decrease of 8.13 g (-14.0; -1.84) overall and 18.6 g (-24.4, -12.8) in the first trimester, for an interquartile range (IQR) increase (9.2 µg/m3) in PM2.5. PM2.5 exposure was positively associated with low birth weight at term (TLBW) during entire pregnancy (OR: 1.11; 95% CI: 1.03-1.20), and at the first (OR: 1.11; 95% CI: 1.03-1.20), second (OR: 1.09; 95% CI: 1.01-1.17), and third trimester (OR: 1.10; 95% CI: 1.02-1.18) per IQR (9.2 µg/m3) increase. Higher exposure to PM2.5 was also associated with increased risk of small for gestational age (SGA). There were no statistically significant associations between PM2.5 exposure and preterm births (PTB). Exposure to higher concentrations of PM2.5 in Lima may decrease birth weight and increase the frequency of TLBW and SGA. Our study was inconsistent with the literature in finding no associations with preterm birth.

Time-series analysis of ambient PM2.5 and cardiorespiratory emergency room visits in Lima, Peru during 2010-2016.

INTRODUCTION: There have been no time-series studies of air pollution in Peru. Here we evaluate the effect of ambient PM2.5 on emergency room (ER) visits in Lima. METHODS: We estimated daily PM2.5 levels at a 1 km2 resolution during 2010-2016 using ground measurements, satellite data, and chemical transport model simulations. Population-weighted average daily PM2.5 levels were calculated for each district in Lima (n = 40), and assigned to patients based on residence. ER visits for respiratory and circulatory diseases were gathered from nine large public hospitals. Poisson regression was used to estimate the rate ratio for daily ER visits with change in daily PM2.5, controlling for meteorology, time trends, and district. RESULTS: For each interquartile range (IQR) increase in PM2.5, respiratory disease ER visits increased 4% (95% CI: 0-5%), stroke visits 10% (3-18%), and ischemic heart disease visits (adults, 18-64 years) 11% (-1, 24%). Districts with higher poverty showed significantly stronger associations of PM2.5 and respiratory disease ER visits than districts with lower poverty. Effects were diminished 24-42% using Lima-wide instead of district-specific PM2.5 levels. CONCLUSIONS: Short-term exposure to ambient PM2.5 is associated with increases in ER visits in Lima for respiratory diseases and stroke, and among middle-aged adults, ischemic heart disease.

Challenges and Opportunities for Occupational Epidemiology in the Twenty-first Century.

PURPOSE OF REVIEW: There are many opportunities and challenges for conducting occupational epidemiologic studies today. In this paper, we summarize the discussion of a symposium held at the Epidemiology in Occupational Health (EPICOH) conference, Chicago 2014, on challenges for occupational epidemiology in the twenty-first century. RECENT FINDINGS: The increasing number of publications and attendance at our conferences suggests that worldwide interest in occupational epidemiology has been growing. There are clearly abundant opportunities for new research in occupational epidemiology. Areas ripe for further work include developing improved methods for exposure assessment, statistical analysis, studying migrant workers and other vulnerable populations, the use of biomarkers, and new hazards. Several major challenges are also discussed such as the rapidly changing nature and location of work, lack of funding, and political/legal conflicts. As long as work exists there will be occupational diseases that demand our attention, and a need for epidemiologic studies designed to characterize these risks and to support the development of preventive strategies. Despite the challenges and given the important past contribution in this field, we are optimistic about the importance and continued vitality of the research field of occupational epidemiology.

Organochlorine chemicals and neurodegeneration among elderly subjects in Costa Rica.

BACKGROUND: We previously screened 400 elderly Costa Ricans for neurodegenerative disease. Those reporting occupational pesticide exposure (18%) had an increased Parkinson׳s disease (PD) risk (OR 2.57, 95% CI 0.91-7.26), and worse cognition (Mini-Mental States Exam (MMSE) 24.5 versus 25.9 points, p=0.01). We subsequently measured long-lasting organochlorine pesticides (ß-HCH, DDE, DDT, and dieldrin) in a sub-sample (n=89). Dieldrin and ß-HCH have been linked to PD, and DDE to Alzheimer׳s disease. METHODS: We ran regression models for MMSE and tremor-at-rest to assess associations with pesticides in 89 subjects. RESULTS: The percent of ß-HCH, DDE, DDT (parent compound for DDE), and dieldrin above their limit of detection (LOD) were 100%, 93%, 75%, and 57%, respectively. Tremor-at-rest was found in 21 subjects, and the mean MMSE was 25. Those who reported occupational pesticide exposure (n=36) had more detectable dieldrin samples (p=0.005), and higher mean levels of dieldrin (p=0.01), than those not reporting exposure. Other pesticides did not differ between those with and without self-reported occupational exposure. There was a positive but non-significant trend of higher risk for tremor-at-rest with higher dieldrin (p=0.10 for linear trend). Neither DDE nor DDT showed a relationship with MMSE. However, after excluding two outliers with the lowest MMSE scores, higher DDT levels showed some modest association with lower MMSE (p=0.09 for linear trend). CONCLUSIONS: Our data are limited by small sample size. However, dieldrin was high in our population, has been previously linked to PD, and could be partly responsible for the excess PD risk seen in our population.

Maternal exposure to biomass smoke and carbon monoxide in relation to adverse pregnancy outcome in two high altitude cities of Peru.

BACKGROUND: Exposure to pollution from biomass fuel has been associated with low birthweight in some studies. Few studies have included exposure-response analyses. METHOD: We conducted a case-control study of biomass fuel use and reproductive outcome at high altitude in Peru. Cases (n=101) were full term births who were SGA (birth weight <10th percentile for gestational age). Controls (n=101) had a birthweight ≥10th percentile, and were matched to cases on birth week and residence. Biomass fuel use during pregnancy was determined by questionnaire. Carbon monoxide (CO) in the kitchen was measured in a subgroup (n=72). Logistic regression was used to estimate the effects of biofuel and CO on the risk of SGA, controlling for maternal education and parity. RESULTS: Among cases, 30%, 27% and 44% used gas, gas+biomass, and biomass, respectively, while the figures for controls were 39%, 33%, and 29%. The adjusted odds ratio (OR) for biomass fuel alone compared with gas alone was 4.5 (95% CI: 1.3, 15.5, p=0.02), while the OR for biomass+gas vs. gas alone was 2.1 (0.80-5.5) (p=0.13). Among the subgroup with measured CO, the mean 48-h kitchen CO levels were 4.8, 2.2 and 0.4ppm for biofuel only, biofuel+gas, and gas respectively. ORs by increasing tertile of CO level were 1.0, 1.16, and 3.53 (test for trend, p=0.02). The exposure-response trend corresponds well with one other study with analogous data. CONCLUSION: Despite limited sample size, our data suggest that maternal exposure to biomass smoke and CO, at high altitude, is associated with SGA among term births.

Occupational pesticide exposure and screening tests for neurodegenerative disease among an elderly population in Costa Rica.

BACKGROUND: Pesticides have been associated with Parkinson's disease (PD) in many studies, and with Alzheimer's disease (AD) in a few. METHODS: We conducted screening tests for neurologic disease and occupational pesticide use in a population-based sample of 400 elderly subjects at two government-run clinics in Costa Rica; 361 subjects who failed the initial screen were given both the mini-mental states exam (MMSE) and a modified version of a 10-item united Parkinson's disease rating motor subscale (UPDRS). Among subjects who failed either test, 144 were then examined by a neurologist. RESULTS: Past occupational pesticide exposure was reported by 18% of subjects. Exposed subjects performed worse on the MMSE than the non-exposed (mean 24.5 versus 25.9, p=0.01, adjusted for age, sex, and education). The exposed had significantly elevated risks of abnormal scores on two UPDRS items, tremor-at-rest (OR 2.58, 1.28-5.23), and finger-tapping (OR=2.94, 95% CI 1.03-8.41). Thirty-three (23%) of those examined by the neurologist were diagnosed with possible/probable PD, 3-4 times the expected based on international data; 85% of these cases had not been previously diagnosed. Among subjects who took the UPDRS, the exposed had an increased risk of PD (OR=2.57, 95% CI 0.91-7.26). No excess risk was found for a diagnosis of AD or mild cognitive impairment. CONCLUSIONS: Elderly subjects with past occupational pesticide exposure performed significantly worse on screening tests for dementia and PD, and had an increased risk of an eventual PD diagnosis. Screening may be particularly appropriate among elderly subjects with past pesticide exposure.

Quality of life among men with prostate cancer in rural Georgia.

OBJECTIVES: To perform a population-based study on the quality of life (QOL) after prostate cancer treatment in a rural and disadvantaged population, because these have been sparse. METHODS: We conducted a follow-up study of 260 men with incident prostate cancer in a largely rural area of Southwest Georgia. The subjects underwent interviews at baseline and 6 and 12 months after the diagnosis. The analyses compared the 6- and 12-month QOL to that at baseline using linear and Poisson regression analyses for longitudinal data. RESULTS: Across all treatment groups, the self-reported physical and emotional QOL declined significantly after treatment, with little difference between that at 6 and that at 12 months. The decline in physical/emotional QOL did not differ by age, race, education, or Gleason score but was more pronounced among those with no comorbidities. Patients treated with hormones showed the worst deterioration in physical and emotional QOL, with the watchful waiting and external beam radiotherapy groups were the least affected. After 12 months, the percentage of men reporting that sexual, urinary, and bowel function was a large or very large problem was 53%, 22%, and 9% compared with 27%, 25%, and 4% at baseline, respectively. Worse bowel and urinary function played a stronger role than sexual function in predicting the overall physical and emotional QOL. Urinary obstruction improved but incontinence worsened. The doctors' and patients' assessment of the QOL showed only a low correlation, with patients reporting worse post-treatment QOL than the doctors. CONCLUSIONS: The general and most prostate-specific QOL measures (except for urinary function) in this previously understudied population declined after 6 months and remained about the same at 12 months after treatment of prostate cancer.

Differences in treatment-based beliefs and coping between African American and white men with prostate cancer.

The purpose of the study was to explore racial differences related to treatment-based beliefs (trust in physician, physician bias, access to care, and self-efficacy) and coping (religious coping and social support). The study was conducted in a 33-county area located in southwest Georgia (SWGA). Men living in SWGA and newly diagnosed with prostate cancer were invited to participate in the study. Men were also required to be 75 years of age or younger at the beginning of the study and free of dementia. In collaboration with the Georgia Cancer Registry, potentially eligible participants were identified through pathology reports. Participants completed three interviews during a 12-month period post-diagnosis. The 320 participants in this analysis ranged in age from 44 to 75 years with a mean age of 63 years, and 42% were African American. After controlling for confounders, African American participants were more likely to report physician bias, financial problems with access to care, and use of religious coping strategies. These results, based on a largely rural patient population, support those of other studies noting differences in perception of care, access to care, and coping strategies between African American and white men with prostate cancer.

Adjustment for temporal confounders in a reanalysis of a case-control study of beryllium and lung cancer.

OBJECTIVES: To evaluate potential confounding of the association between beryllium and lung cancer in a reanalysis of data from a published case-control study of workers at a beryllium processing facility. METHODS: The association of cumulative and average beryllium exposure with lung cancer among 142 cases and five age-match controls per case was reanalysed using conditional logistic regression. Adjustment was made independently for potential confounders of hire age and birth year. Alternative adjustments to avoid taking the logarithm of zero were explored. RESULTS: Adjustment for either birth cohort or hire age (two highly correlated factors) attenuated lung cancer risk associated with cumulative exposure; however, lung cancer risk was significantly associated with average exposure using a 10-year lag following adjustment. Stratification of analyses by birth cohort found greater lung cancer risk from cumulative and average exposure for workers born before 1900 than for workers born later. The magnitude of the association between lung cancer and average exposure was not reduced by modifying the method used to take the log of exposure. CONCLUSION: In this reanalysis, average, but not cumulative, beryllium exposure was related to lung cancer risk after adjustment for birth cohort. Confounding by birth cohort is likely related to differences in smoking patterns for workers born before 1900 and the tendency for workers hired during the World War II era to have been older at hire.

Mortality analyses in a cohort of 18 235 ethylene oxide exposed workers: follow up extended from 1987 to 1998.

AIMS: To extend mortality follow up from 1987 to 1998 for cohort of 18 235 men and women exposed to ethylene oxide. METHODS: Standard mortality follow up, life table and Cox regression analysis. RESULTS: There were 2852 deaths, compared with 1177 in the earlier 1987 follow up. There was no overall excess of haematopoietic cancers combined or of non-Hodgkin's lymphoma. However, internal exposure-response analyses found positive trends for haematopoietic cancers which were limited to males (15 year lag). The trend in haematopoietic cancer was driven by lymphoid tumours (non-Hodgkin's lymphoma, myeloma, lymphocytic leukaemia), which also have a positive trend with cumulative exposure for males with a 15 year lag. Haematopoietic cancer trends were somewhat weaker in this analysis than trends in the earlier follow up, and analyses restricted to the post-1987 data did not show any significant positive trends (exposure levels dropped sharply in the early 1980s). Breast cancer did not show any overall excess, although there was an excess in the highest cumulative exposure quartile using a 20 year lag. Internal exposure-response analyses found positive trend for breast cancer using the log of cumulative exposure with a 20 year lag. CONCLUSIONS: There was little evidence of any excess cancer mortality for the cohort as a whole, with the exception of bone cancer based on small numbers. Positive exposure-response trends for lymphoid tumours were found for males only. Reasons for the sex specificity of this effect are not known. There was also some evidence of a positive exposure-response for breast cancer mortality.

Exposure-response analysis and risk assessment for silica and silicosis mortality in a pooled analysis of six cohorts.

AIMS: To study the relation between exposure to crystalline silica and silicosis mortality. Although mortality is an important endpoint for regulators, there have been no exposure-response studies for silicosis mortality, because of the relative rareness of silicosis as an underlying cause of death, and the limited availability of quantitative exposure estimates. METHODS: Data from six occupational cohorts were pooled with good retrospective exposure data in which 170 deaths from silicosis were reported. Standard life table analyses, nested case-control analyses, and risk assessment were performed. RESULTS: The rate of silicosis mortality in the combined data was 28/100 000 py, increasing in nearly monotonic fashion from 4.7/100 000 for exposure of 0-0.99 mg/m(3)-years to 233/100 000 for exposure of >28.1 mg/m(3)-years. The estimated risk of death up to age 65 from silicosis after 45 years of exposure at 0.1 mg/m(3) silica (the current standard in many countries) was 13 per 1000, while the estimated risk at an exposure of 0.05 mg/m(3) was 6 per 1000. Both of these risks are above the risk of 1 per 1000 typically deemed acceptable by the US OSHA. CONCLUSION: The findings from this pooled analysis add further support to the need to control silica exposure and to lower the occupational standards. Our estimates of lifetime silicosis mortality risk are probably underestimates as, in addition to exposure misclassification, our study might have suffered from outcome misclassification in that silicosis deaths might have been coded to other related causes, such as tuberculosis or chronic obstructive pulmonary disease.

Pooled exposure-response analyses and risk assessment for lung cancer in 10 cohorts of silica-exposed workers: an IARC multicentre study.

OBJECTIVES: Silica is one of the most common occupational exposures worldwide. In 1997 the International Agency for Research on Cancer (IARC) classified inhaled crystalline silica as a human carcinogen (group 1), but acknowledged limitations in the epidemiologic data, including inconsistencies across studies and the lack of extensive exposure-response data. We have conducted a pooled exposure-response analysis of 10 silica-exposed cohorts to investigate lung cancer. METHODS: The pooled cohort included 65,980 workers (44,160 miners, 21,820 nominees), and 1,072 lung cancer deaths (663 miners, 409 nonminers). Follow-up has been extended for five of these cohorts beyond published data. Quantitative exposure estimates by job and calendar time were adopted, modified, or developed to permit common analyses by respirable silica (mg/m3) across cohorts. RESULTS: The log of cumulative exposure, with a 15-year lag, was a strong predictor of lung cancer (p = 0.0001), with consistency across studies (test for heterogeneity, p = 0.34). Results for the log of cumulative exposure were consistent between underground mines and other facilities. Categorical analyses by quintile of cumulative exposure resulted in a monotonic trend with odds ratios of 1.0. 1.0, 1.3, 1.5, 1.6. Analyses using a spline curve also showed a monotonic increase in risk with increasing exposure. The estimated excess lifetime risk (through age 75) of lung cancer for a worker exposed from age 20 to 65 at 0.1 mg/m3 respirable crystalline silica (the permissible level in many countries) was 1.1-1.7%, above background risks of 3-6%. CONCLUSIONS: Our results support the decision by the IARC to classify inhaled silica in occupational settings as a carcinogen, and suggest that the current exposure limits in many countries may be inadequate. These data represent the first quantitative exposure-response analysis and risk assessment for silica using data from multiple studies.

Risk assessment for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on an epidemiologic study.

The International Agency for Research on Cancer (Lyon, France) recently concluded that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a human carcinogen. There have been few human studies and risk assessments with quantitative exposure data. The authors previously conducted exposure-response analyses based on estimated external TCDD exposure for 3,538 US male chemical workers and found a positive trend for all cancer with increasing cumulative exposure. In the present study, 1988 data from 170 workers with both estimated external exposure and known serum TCDD levels were used to derive the relation between the two. This derived relation was used to estimate serum TCDD levels over time for all 3,538 workers, and new dose-response analyses were conducted by using cumulative serum level. A positive trend (p = 0.003) was found between estimated log cumulative TCDD serum level and cancer mortality. For males, the excess lifetime (75 years) risk of dying of cancer given a TCDD intake of 1.0 pg/kg of body weight per day, twice the background intake, was an estimated 0.05-0.9% above a background lifetime risk of cancer death of 12.4%. Data from this cohort are consistent with another epidemiologic risk assessment from Germany and support recent conclusions by the US Environmental Protection Agency.

Dioxin and diabetes mellitus: an analysis of the combined NIOSH and Ranch Hand data.

OBJECTIVES: To reanalyze in a similar manner the two principal studies of TCDD (tetrachlorodibenzo-p-dioxin) and diabetes in an attempt to reconcile disparate results. METHODS: Data from 990 United States Air Force veterans (Ranch Hand) and 1275 referents were reanalyzed, and a NIOSH population of 267 chemical workers and 227 referents. The Ranch Hand veterans had lower concentrations of lipid adjusted serum TCDD (median 12 parts per trillion (ppt)) than the NIOSH workers (median 75 ppt) when examined in the late 1980s. An analysis was conducted of the combined data sets, adopting a uniform approach to outcome definition, data analysis, and covariate control. RESULTS: The combined exposed groups did not differ markedly from the combined non-exposed groups for prevalence of diabetes (odds ratio (OR) 1.17, 95% confidence interval (95% CI) 0.92 to 1.48), with no evidence of heterogeneity of exposure effect between studies. Also virtually no difference was found between combined exposed and non-exposed groups in mean fasting serum glucose (difference in log serum glucose 0.002, 95% CI -0.006 to 0.010), and there was little evidence in either study of a dose-response trend for fasting serum glucose. An increasing trend was found (p=0.0001) in prevalence of diabetes with increased TCDD (at the time of examination or at time of last exposure) among the Ranch Hand population, with excess risk largely confined to the highest 8% of the exposed group (>78 ppt serum TCDD), which had an OR of 3.21 (95% CI 1.81 to 5.72) versus those with <10 ppt TCDD. However, no such positive dose-response was found in the NIOSH population. CONCLUSIONS: There was little overall evidence that the exposed workers were at higher risk than the non-exposed workers of diabetes or abnormal fasting glucose. However, the Ranch Hand subjects showed a positive dose-response for diabetes, whereas the more highly exposed NIOSH subjects did not. The reason for the difference in diabetes dose-response trends between the two studies is unknown.

Evaluation of acute sensory--motor effects and test sensitivity using termiticide workers exposed to chlorpyrifos.

Sensory and motor testing was performed on a group of termiticide workers primarily using chlorpyrifos-containing products to evaluate both the acute effects from current exposure and sensitivity of the measures to detect effects. The study group comprised 106 applicators and 52 nonexposed participants. Current exposure was measured by urinary concentrations of 3,5,6-trichloro-2-pyridinol (TCP) collected the morning of testing. The mean TCP value for the 106 applicators was 200 microg/g creatinine. Participants received 4--5 h of testing and were evaluated using a sensory--motor test battery recommended by a National Institute for Occupational Safety and Health (NIOSH)-sponsored advisory panel to be appropriate for testing effects from pesticide exposures. Measurements testing olfactory dysfunction, visual acuity, contrast sensitivity, color vision, vibrotactile sensitivity, tremor, manual dexterity, eye--hand coordination, and postural stability were analyzed. Study results indicated limited acute effects from exposure to chlorpyrifos using urinary TCP as a measure of current exposure. The effects occurred primarily on measures of postural sway in the eyes closed and soft-surface conditions, which suggests a possible subclinical effect involving the proprioceptive and vestibular systems. Several other tests of motor and sensory functions did not show any evidence of acute exposure effects, although statistically significant effects of urinary TCP on the Lanthony color vision test scores and one contrast sensitivity test score were found. The visual measures, however, were not significant when a step-down Bonferroni correction was applied. Information also is presented on the sensitivity of the measures to detect effects in an occupationally exposed population using standard error of the parameter estimates.

Kidney disease and arthritis in a cohort study of workers exposed to silica.

Silica exposure has been associated with kidney disease and rheumatoid arthritis; an autoimmune mechanism has been proposed. Approximately 2 million people are occupationally exposed to silica in the United States, 100,000 at more than twice the National Institute for Occupational Safety and Health recommended exposure limit of 0.05 mg/m(3). We examined renal disease morbidity and mortality, as well as arthritis mortality, in a cohort of 4,626 silica-exposed workers in the industrial sand industry (an industry previously unstudied). We compared the cohort with the U.S. population and also conducted internal exposure-response analyses using a job-exposure matrix based on more than 4,000 industrial hygiene samples. We found excess mortality from acute renal disease [standardized mortality ratio (SMR) = 2.61, 95% confidence intervals (95% CIs) = 1.49--4.24; 16 deaths], chronic renal disease (SMR = 1.61, 95% CI = 1.13--2.22; 36 deaths), and arthritis (SMR = 4.36, 95% CI = 2.76--6.54; 23 deaths) on the basis of multiple-cause mortality data, which considered any mention of disease on a death certificate. Linking the cohort with the U.S. registry of end-stage renal disease for the years 1977-1996, we found an excess of end-stage renal disease incidence (standardized incidence ratio = 1.97, 95% CI = 1.25--2.96; 23 cases), which was highest for glomerulonephritis (standardized incidence ratio = 3.85, 95% CI = 1.55--7.93; 7 cases). We found increasing end-stage renal disease incidence with increasing cumulative exposure; standardized rate ratios by quartile of cumulative exposure were 1.00, 3.09, 5.22, and 7.79. A positive exposure-response trend was also observed for rheumatoid arthritis on the basis of death certificate data. These data represent the largest number of kidney disease cases analyzed to date in a cohort with well-defined silica exposure and suggest a causal link between silica and kidney disease. Excess risk of end-stage renal disease due to a lifetime of occupational exposure at currently recommended limits is estimated to be 14%, above a background end-stage renal disease risk of 2%.

Agreement between clinical examination and quantitative tests of neurologic function among 384 subjects.

BACKGROUND: Quantitative neurological tests are often cheaper and easier than clinical examinations, and provide continuous data which may discriminate between exposed and nonexposed groups with more sensitivity than dichotomous (normal/abnormal) examination data. METHODS: We compare clinical examinations and analogous quantitative tests for arm tremor, postural sway, and vibrotactile sensitivity (finger and toe), for 384 subjects. RESULTS: The "abnormal" clinical outcomes studied were relatively common (range, 3-36%), and did not result in impairment of daily activity for affected subjects. All the quantitative tests were reasonably good predictors of the corresponding clinical outcome. The most predictive test was for toe vibrotactile sensitivity. The probability of an abnormal clinical result for those in the worst quartile for the toe test was 0.63, compared with 0.36 for all subjects. CONCLUSIONS: Our results suggest that certain quantitative tests might be used in epidemiologic studies instead of a physical examination.