Smoothing is soothing, and splines are fine.
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Humans↗
Biomedical subjects
K Steenland
Publications and source records attributed to K Steenland.
Silica: déjà vu all over again?
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Humans↗
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.
Cohort Studies↗
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.
Adult↗
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.
Cohort Studies↗
Lung cancer among industrial sand workers exposed to crystalline silica.
In 1997, the International Agency for Research on Cancer determined that crystalline silica was a human carcinogen but noted inconsistencies in the epidemiology. There are few exposure-response analyses. The authors examined lung cancer mortality among 4,626 industrial sand workers, estimating exposure via a job-exposure matrix based on 4,269 industrial hygiene samples collected in 1974--1995. The average length of employment was 9 years, and estimated average exposure was 0.05 mg/m(3) (the National Institute of Occupational Safety and Health Recommended Exposure Limit). Results confirmed excess mortality from silicosis/pneumoconioses (standardized mortality ratio = 18.2, 95% confidence interval: 10.6, 29.1; 17 deaths). The lung cancer standardized mortality ratio was 1.60 (95% confidence interval: 1.31, 1.93; 109 deaths). Limited data suggested that smoking might account for 10--20% of the lung cancer excess. Exposure-response analyses by quartile of cumulative exposure (15-year lag) yielded standardized rate ratios of 1.00, 0.78, 1.51, and 1.57 (p for trend = 0.07). Nested case-control analyses after exclusion of short-term workers, who had high overall morality, yielded odds ratios by quartile of cumulative exposure (15-year lag) of 1.00, 1.35, 1.63, and 2.00 (p for trend = 0.08) and odds ratios by quartile of average exposure of 1.00, 0.92, 1.44, and 2.26 (p = 0.005). These data lend support to the labeling by the International Agency for Research on Cancer of silica as a human carcinogen. There are approximately 2 million US workers exposed to silica; 100,000 are exposed to more than 0.1 mg/m(3).
Adult↗
Lung cancer case-control study of beryllium workers.
BACKGROUND: Cohort mortality studies have found elevated lung cancer mortality among beryllium-exposed workers, but none evaluated the association between beryllium exposure level and lung cancer risk. A nested case-control study of lung cancer within a beryllium processing plant was conducted to investigate the relationship between level of beryllium exposure and lung cancer. METHODS: Lung cancer cases were identified by mortality follow-up through 1992 of a cohort of male workers at a beryllium alloy production plant. Each of 142 lung cancer cases was age-race-matched to five controls. Calendar-time-specific beryllium exposure estimates were made for every job in the plant and were used to estimate workers' cumulative, average, and maximum exposures. The potential confounding effects of smoking were also evaluated. RESULTS: Lung cancer cases had shorter tenures and lower lifetime cumulative beryllium exposures than controls, but higher average and maximum exposures. However, after applying a 10- and 20-year lag, exposure metrics were higher for cases. Odds ratios in analyses lagged 20 years were significantly elevated for those with higher exposure compared to the lowest exposure category. Significant positive trends were seen with the log of the exposure metrics. Smoking did not appear to confound exposure-response analyses. CONCLUSION: Increased lung cancer among workers with higher lagged beryllium exposures and lack of evidence for confounding by cigarette smoking, provide further evidence that beryllium is a human lung carcinogen. Published 2001 Wiley-Liss, Inc.
Air Pollutants, Occupational↗
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.
Female↗
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.
Air Pollutants, Occupational↗
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%.
Adult↗
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.
Blood Glucose↗
Expanded analysis of injury mortality among unionized construction workers.
BACKGROUND: To evaluate the utility of expanding the number and precision of injury categories used in previous occupational mortality studies, this study reanalyzed data from four previous studies of unionized construction workers (construction laborers, ironworkers, sheet metal workers, and operating engineers), by expanding the number of injury categories from 6 to 33. METHODS: Proportionate mortality ratios (PMRs) were computed using the distribution of deaths from the National Occupational Mortality Surveillance System, a mortality surveillance system from 28 states, as a comparison. A blue collar comparison group was also used in additional analyses to adjust for socioeconomic and other factors. RESULTS: This reanalysis identified significantly elevated PMRs in at least one of the four worker groups for falls, motor vehicle crashes, machinery incidents, electrocutions, being struck by falling objects, being struck by flying objects, explosions, suffocation, and water transport incidents. Limiting the comparison population to deaths among blue collar workers did not change the results substantially. CONCLUSIONS: This study demonstrates that increasing the precision of categories of death from injury routinely used in mortality studies will provide improved information to guide prevention. Am. J. Ind. Med. 37:364-373, 2000. Published 2000 Wiley-Liss, Inc.
Accidental Falls↗
A retrospective job exposure matrix for estimating exposure to 2,3,7, 8-tetrachlorodibenzo-p-dioxin.
BACKGROUND: A job exposure matrix was developed to estimate the 2,3, 7,8-tetrachlorodibenzo-p-dioxin exposure of 3,538 workers who produced 2,4,5-trichlorophenol and its derivatives. METHODS: Daily TCDD exposure scores that were plant, process, and period specific were estimated for each job title as the product of 1) the concentration of TCDD (microg/g); 2) a qualitative factor to account for the extent of worker contact and 3) time exposed to TCDD contamination. Daily scores were summed to compute individual cumulative TCDD exposure scores. RESULTS: Daily TCDD exposure scores ranged from 0.001 to 1,250. Cumulative TCDD scores ranged from 0.002 to 1,559,430. The 393 workers with records of chloracne in the TCDD exposure cohort (11%) had markedly higher cumulative scores than those with no record of chloracne (a median score of 11,546 vs. 77). CONCLUSIONS: The cumulative TCDD exposure scores incorporate both duration and level of exposure, and permit the relative ranking of worker exposures for the evaluation of exposure-response relationships between TCDD exposure and mortality in an updated cohort study analysis.
Algorithms↗
Lead and cancer in humans: where are we now?
BACKGROUND: Lead is only weakly mutagenic, but in vitro it inhibits DNA repair and acts synergistically with other mutagens. Lead acetate administered orally, cutaneously, or intraperitoneally causes kidney cancer, brain cancer (gliomas), and lung cancer in rodents, and acts synergistically with other carcinogens. Most cytogenetic studies of exposed workers have shown increases in chromosome aberrations or sister chromatid exchange, including some studies with positive-exposure response trends. There are eight studies of cancer mortality or incidence among highly exposed workers; most are cohort studies of lead smelter or battery workers exposed decades ago. METHODS: We reviewed the epidemologic studies with regard to cancer. RESULTS: These studies provide some evidence of increased risk of lung cancer (RR = 1.30, 1.15-1.46, 675 observed deaths) and stomach cancer (combined RR = 1.34, 1.14-1.57, 181 observed). However, the lung cancer findings are not consistent across studies, and confounding by arsenic may affect the study with the highest lung cancer RR. Exclusion of that study yields a combined lung cancer RR of 1.14 (1.04-1.73). There is little evidence of increased risk of kidney cancer (combined RR = 1.01, 0. 72-1.42, 40 observed) or brain cancer (combined RR = 1.06, 0.81-1.40, 69 observed). However, two studies show a two-fold increase in kidney cancer, and one study shows a significant excess of gliomas. IARC classified lead as a "possible human carcinogen" based on sufficient animal data and insufficient human data in 1987. Six of the eight studies cited above have been published since 1987. CONCLUSIONS: Overall, there is only weak evidence associating lead with cancer; the most likely candidates are lung cancer, stomach cancer, and gliomas.
Animals↗
Historical respirable quartz exposures of industrial sand workers: 1946-1996.
BACKGROUND: Besides a clear relationship to silicosis, crystalline silica-quartz-has been associated with lung cancer, nonmalignant renal disease, and auto-immune disease. To study diseases associated with crystalline silica further, NIOSH conducted a cohort mortality study of workers from 18 silica sand plants, which had quarry, crushing, and bagging operations to produce industrial sand. Twelve of these plants also had grinding mills to produce fine silica powder. The historical crystalline silica exposures of workers at these plants were estimated to facilitate exposure-response analyses in the epidemiologic study. METHODS: NIOSH obtained personal respirable dust measurement records from Mine Safety and Health Administration (MSHA) compliance inspections at all 18 plants and from the archives of seven plants which had collected samples. These samples had been analyzed for quartz content by x-ray diffraction. Although no personal samples were available before 1974, impinger dust measurements were reported for 19 silica sand plants in 1946; these data were converted and used to estimate exposures prior to 1974. Statistical modeling of the samples was used to estimate quartz exposure concentrations for workers in plant-job-year categories from the 1930s when mortality follow-up of the cohort began until 1988 when follow-up stopped. RESULTS: Between 1974 and 1996, there were 4,269 respirable dust samples collected at these 18 plants. The geometric mean quartz concentration was 25.9 microg/m(3) (GSD = 10.9) with a range from less than 1 to 11,700 microg/m(3). Samples below 1 microg/m(3) were given a value of 0.5 microg/m(3). Over one-third of the samples -37%) exceeded the MSHA permissible exposure limit value for quartz (PEL = 10 mg/m(3)/(%quartz + 2)) and half (51%) of the samples exceeded the NIOSH recommended exposure limit (REL=50 microg/m(3)). The samples were collected from workers performing 143 jobs within the 18 plants, but too few samples were collected from many of the jobs to make accurate estimates. Therefore, samples were combined into 10 categories of jobs performing similar tasks or located within the same plant area. CONCLUSIONS: The quartz concentrations varied significantly by plant, job, and year. Quartz concentrations decreased over time, with measurements collected in the 1970s significantly greater than those collected later. The modeled exposure estimates improve upon duration of employment as an estimate of cumulative exposure and reduce exposure misclassification due to variation in quartz levels between plants, jobs, and over time. Am. J. Ind. Med. 38:389-398, 2000. Published 2000 Wiley-Liss, Inc.
Humans↗
Neurologic function among termiticide applicators exposed to chlorpyrifos.
Chlorpyrifos is a moderately toxic organophosphate pesticide. Houses and lawns in the United States receive a total of approximately 20 million annual chlorpyrifos treatments, and 82% of U.S. adults have detectable levels of a chlorpyrifos metabolite (3,5, 6-trichloro-2-pyridinol; TCP) in the urine. The U.S. Environmental Protection Agency has estimated that there are 5,000 yearly reported cases of accidental chlorpyrifos poisoning, and approximately one-fourth of these cases exhibit symptoms. Organophosphates affect the nervous system, but there are few epidemiologic data on chlorpyrifos neurotoxicity. We studied neurologic function in 191 current and former termiticide applicators who had an average of 2.4 years applying chlorpyrifos and 2.5 years applying other pesticides, and we compared them to 189 nonexposed controls. The average urinary TCP level for 65 recently exposed applicators was 629.5 microg/L, as compared to 4.5 microg/L for the general U.S. population. The exposed group did not differ significantly from the nonexposed group for any test in the clinical examination. Few significant differences were found in nerve conduction velocity, arm/hand tremor, vibrotactile sensitivity, vision, smell, visual/motor skills, or neurobehavioral skills. The exposed group did not perform as well as the nonexposed group in pegboard turning tests and some postural sway tests. The exposed subjects also reported significantly more symptoms, including memory problems, emotional states, fatigue, and loss of muscle strength; our more quantitative tests may not have been adequate to detect these symptoms. Eight men who reported past chlorpyrifos poisoning had a pattern of low performance on a number of tests, which is consistent with prior reports of chronic effects of organophosphate poisoning. Overall, the lack of exposure effects on the clinical examination was reassuring. The findings for self-reported symptoms raise some concern, as does the finding of low performance for those reporting prior poisoning. Although this was a relatively large study based on a well-defined target population, the workers we studied may not be representative of all exposed workers, and caution should be exercised in generalizing our results.
Adult↗
Biases in estimating the effect of cumulative exposure in log-linear models when estimated exposure levels are assigned.
OBJECTIVES: Exposure-response trends in occupational studies of chronic disease are often modeled via log-linear models with cumulative exposure as the metric of interest. Exposure levels for most subjects are often unknown, but can be estimated by assigning known job-specific mean exposure levels from a sample of workers to all workers. Such assignment results in (nondifferential) measurement error of the Berkson type, which does not bias the estimate of exposure effect in linear models but can result in substantial bias in log-linear models with dichotomous outcomes. This bias was explored in estimated exposure-response trends using cumulative exposure. METHODS: Simulations were conducted under the assumptions that (i) exposure level is assigned to all workers based on the job-specific means from a sample of workers, (ii) exposure level and duration are log-normal, (iii) the true exposure-response model is log-linear for cumulative exposure, (iv) the disease is rare, and (v) the variance of job-specific exposure level increases with its job-specific mean. Results Assignment of job-specific mean exposure levels from a sample of workers causes an upward bias in the estimated exposure-response trend when there is little variance in the duration of exposure but causes a downward bias when duration has a large variance. This bias can be substantial (eg, 30-50%). CONCLUSIONS: Berkson errors in exposure result in little bias in estimating exposure-response trends when the standard deviation of duration is approximately equal to its mean, which is common in many occupational studies. No bias occurs when the variance of exposure level is constant across jobs, but such conditions are probably uncommon.
Humans↗
Empirical Bayes adjustments for multiple results in hypothesis-generating or surveillance studies.
Traditional methods of adjustment for multiple comparisons (e.g., Bonferroni adjustments) have fallen into disuse in epidemiological studies. However, alternative kinds of adjustment for data with multiple comparisons may sometimes be advisable. When a large number of comparisons are made, and when there is a high cost to investigating false positive leads, empirical or semi-Bayes adjustments may help in the selection of the most promising leads. Here we offer an example of such adjustments in a large surveillance data set of occupation and cancer in Nordic countries, in which we used empirical Bayes (EB) adjustments to evaluate standardized incidence ratios (SIRs) for cancer and occupation among craftsmen and laborers. For men, there were 642 SIRs, of which 138 (21%) had a P < 0.05 (13% positive with SIR > 1.0 and 8% negative with SIR < or = 1.0) when testing the null hypothesis of no cancer/occupation association; some of these were probably due to confounding by nonoccupational risk factors (e.g., smoking). After EB adjustments, there were 95 (15%) SIRs with P < 0.05 (10% positive and 5% negative). For women, there were 373 SIRs, of which 37 (10%) had P < 0.05 before adjustment (6% positive and 4% negative) and 13 (3%) had P < 0.05 after adjustment (2% positive and 1% negative). Several known associations were confirmed after EB adjustment (e.g., pleural cancer among plumbers, original SIR 3.2 (95% confidence interval, 2.5-4.1), adjusted SIR 2.0 (95% confidence interval, 1.6-2.4). EB can produce more accurate estimates of relative risk by shrinking imprecise outliers toward the mean, which may reduce the number of false positives otherwise flagged for further investigation. For example, liver cancer among chimney sweepers was reduced from an original SIR of 2.2 (range, 1.1-4.4) to an adjusted SIR of 1.1 (range, 0.9-1.4). A potentially important future application for EB is studies of gene-environment-disease interactions, in which hundreds of polymorphisms may be evaluated with dozens of environmental risk factors in large cohort studies, producing thousands of associations.
Analysis of Variance↗