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H Checkoway

Publications and source records attributed to H Checkoway.

At least 37 records · Page 2Linked to original sources

Design and conduct of occupational epidemiology studies: III. Design aspects of case-control studies.

Currently available approaches for the design of occupational case-control studies are reviewed. An accompanying paper reviews methods of analysis. We commence by drawing a distinction between cohort-based and registry-based studies. Methods for selecting cases and controls are then reviewed, including cumulative incidence and incidence density sampling, matching, sources of controls, and issues in control selection. Finally, the advantages and disadvantages of the case-control approach are summarized.

Cohort Studies

Design and conduct of occupational epidemiology studies: IV. The analysis of case-control data.

This paper reviews the basic methods of analysis of data from case-control studies. The standard analytic methods are outlined first for a single stratum. The discussion is then extended to stratified analysis, multiple exposure levels, and analyses allowing for disease induction and latency periods. Finally, logistic regression is discussed as an extension of the more basic forms of analysis. The methods are illustrated with data from a study of lung cancer among asbestos textile plant workers.

Biometry

Estimating the potential disease rate reduction under varying conditions of combined effects.

The disease rate difference between people exposed and not exposed to some factor is the familiar estimate of attributable risk. When there are two or more causal exposures which demonstrate joint effects and are independently distributed, partitioning a population's overall rate between factors requires estimates of the marginal distributions of exposures and the independent (unconditional) and combined rate ratios for each exposure factor. The net potential reduction in the overall disease rate resulting from elimination of one of the exposures depends on these parameters and on the model of combined effect assumed, additive, multiplicative or some departure therefrom. In this paper the authors illustrate the extent to which the assumed model of combined effect of exposures determines which parameters need to be specified to estimate disease rate reductions. The concepts presented are demonstrated algebraically and with simulated hypothetical data. An application of the method is given with data from a case-control study of smoking, asbestos exposure and lung cancer.

Data Interpretation, Statistical

Radiation doses and cause-specific mortality among workers at a nuclear materials fabrication plant.

A historical cohort mortality study was conducted among 6,781 white male employees from a nuclear weapons materials fabrication plant for the years 1947-1979. Exposures of greatest concern are alpha and gamma radiation emanating primarily from insoluble uranium compounds. Among monitored workers, the mean cumulative alpha radiation dose to the lung was 8.21 rem, and the mean cumulative external whole body penetrating dose from gamma radiation was 0.96 rem. Relative to US white males, the cohort experienced mortality deficits from all causes combined, cardiovascular diseases, and from most site-specific cancers. Mortality excesses of lung and brain and central nervous system cancers were seen from comparisons with national and state rates. Dose-response trends were detected for lung cancer mortality with respect to cumulative alpha and gamma radiation, with the most pronounced trend occurring for gamma radiation among workers who received greater than or equal to 5 rem of alpha radiation. These trends diminished in magnitude when a 10-year latency assumption was applied. Under a zero-year latency assumption, the rate ratio for lung cancer mortality associated with joint exposure of greater than or equal to 5 versus less than 1 rem of both types of radiation is 4.60 (95% confidence limits (CL) 0.91, 23.35), while the corresponding result, assuming a 10-year latency, is 3.05 (95% CL 0.37, 24.83). While these rate ratios, which are based on three and one death, respectively, lack statistical precision, the observed dose-response trends indicate potential carcinogenic effects to the lung of relatively low-dose radiation. There are no dose-response trends for mortality from brain and central nervous system cancers.

Adolescent

Case-control studies using other diseases as controls: problems of excluding exposure-related diseases.

Exclusion criteria are examined in case-control studies which include persons with other diseases in the control group. Theoretically, a sample of the study base should not exclude persons who develop exposure-related diseases before, during, or after the time period in which the case occurred. This principle also generally applies when controls are sampled from the subset of persons with other diseases generated by the same study base. In particular, if the incidence rates (assuming completeness of ascertainment) for all other disease combined are similar in the exposed and nonexposed populations, then controls should be sampled from all other diseases, regardless of their relation to exposure. On the other hand, if the composite incidence rate for other diseases is greater (or less) in the exposed population, then it may be necessary to exclude controls with diseases positively (or negatively) associated with exposure. Additionally, considerable care should be taken when sampling controls from persons with specific diseases which are apparently "unrelated" to exposure because confounding may be introduced by exposure-related determinants of the control disease(s). To remove such confounding, it is necessary to control for risk factors for both the study disease and the control disease(s).

Environmental Exposure

Sunlight and other risk factors for cataracts: an epidemiologic study.

A case control study was conducted in North Carolina to explore the relation between individual exposure to sunlight and the risk of cataracts. One hundred thirteen cases and 161 controls aged 40-69 at diagnosis were studied. Sunlight exposure was inferred from interview data on residency and time spent in the sun, combined with solar radiation data from the National Climatic Data Center. Sunlight exposure was very slightly related to all types of opacities combined. Although the numbers of cases with each type of opacity was small, the risk of cataracts was slightly increased in medium and high exposure categories for persons having cortical or posterior subcapsular opacities only, but not nuclear sclerotic changes. Persons with dark brown or hazel eyes are at increased risk. An unexpected finding was that persons who reported using tranquilizers for six months were at increased risk.

Aged

Exponential models for analyses of time-related factors, illustrated with asbestos textile worker mortality data.

In any study based on an occupational cohort, it is important to consider the variation in risk factors over time. Cumulative exposure is the most important time-related factor for exposure-response analyses, whereas other time-related factors such as age at risk, year at risk, and length of follow-up may be confounders and effect modifiers. This paper examines the family of exponential models which can be used for time-related analyses of studies based on an occupational cohort. Analyses using Poisson regression, the proportional hazards model, and the logistic model are presented, and their interrelationships explored. These models are illustrated with data from a cohort study of lung cancer mortality among asbestos textile plant workers. All three approaches yielded similar effect estimates. In particular, Poisson regression and the proportional hazards model yielded very similar findings, but Poisson regression has some conceptual and computational advantages.

Adult

A case-control study of skin cancer in the tire and rubber manufacturing industry.

A case-control study was conducted in the tire and rubber manufacturing industry to examine the association of squamous cell carcinoma of the skin with rubber manufacturing materials presumed to be contaminated by polycyclic aromatic hydrocarbons. Sixty-five cases were compared to 254 matched controls for exposure to carbon black, extender oils, lubricating oils, rubber solvents, and rubber stock. Both magnitude and duration of exposure were compared using data from company personnel records. Rubber stock and lubricating oils were associated with skin cancer. The relative risk (RR) associated with the highest levels of rubber stock exposure was 2.2, and with the highest level of lubricating oil exposure it was 6.5. In analysis of subgroups of study members, the associations were strongest among workers who were born after 1900 (rubber stock, RR = 11.6; lubricating oil, RR = 4.5) and among workers whose skin cancer was diagnosed before the age of seventy (rubber stock, RR = 23.2; lubricating oil, RR = 28.3).

Adult

Medical, life-style, and occupational risk factors for prostate cancer.

Information on suspected risk factors for prostate cancer was obtained from in-person interviews as part of a case-control study of tissue sex hormone receptors and serum hormone levels. The risk factors examined were medical history (including venereal disease), sexual history, smoking, alcohol consumption, and occupational exposures. Study subjects were 40 prostate cancer patients and 64 benign prostatic hyperplasia controls who were newly diagnosed during 1984-1985 at North Carolina Memorial Hospital in Chapel Hill. Subjects were white and black men aged 50 years and older. Comparisons of cases' and controls' past medical histories did not support a venereal disease hypothesis of prostate cancer etiology. The most prominent finding is an association with farming employment: 75% of cases compared to 38% of controls reported farmwork occupations. Exposures to pesticides and herbicides, while more common among the patients, did not account for the association detected for farming. No relationship was observed with cadmium exposure, the most frequently cited occupational risk factor for prostate cancer.

Adenocarcinoma

Androgen receptors detected by autoradiography in prostatic carcinoma and benign prostatic hyperplastic tissue.

Androgen receptor (AR) content in prostatic tissues from patients with either cancer or benign prostatic hyperplasia (BPH) is of interest from at least two standpoints: receptors may be a feature of the pathogenesis of these conditions, and they may be important to the management and prognosis of prostatic cancer patients. For these reasons, a quantitative autoradiographic assay for AR content in prostatic tissues has been developed. Application of autoradiography to rodent tissues yielded results that were highly correlated with those from biochemical assays. Thus, the autoradiographic analyses with human tissues reported in this paper were undertaken. Average AR content in 22 prostatic carcinomas was lower than that in tissues from 14 patients with BPH; the median values of the affinity index, the quantitative estimate of receptor content, were 7.0 and 12.0, respectively. For the cancer tissues, a trend of declining receptor content with advancing stage of disease appeared but was not statistically significant. No association between receptor content and degree of tumor aggressiveness as measured by Gleason score and MD Anderson score was evident. Patient age and race were not related to receptor content in either type of tissue.

Aged

Serum hormone levels among patients with prostatic carcinoma or benign prostatic hyperplasia and clinic controls.

This study sought to identify differences in serum hormone levels between prostatic cancer (CaP) patients, benign prostatic hyperplasia (BPH) patients, and clinic controls (CC). Serum testosterone, estradiol, and prolactin values were obtained from 35 CaP, 42 BPH, and 161 CC patients attending a single medical center between January 1984 and April 1985. Relative risk estimates adjusted for age and race were calculated to compare hormone values between each case group and the CC. The distributions of hormone values and the testosterone to estradiol (T/E) ratios were grouped into thirds with the lowest third forming the reference category. The relative risk estimates for BPH in the middle and high thirds of testosterone were greater than unity (1.26 and 2.10, respectively), whereas the relative risk estimates in the middle and high thirds of estradiol were less than unity (0.63 and 0.35, respectively). For the middle and high thirds of the T/E ratio, the relative risk estimates for BPH showed statistically significant three- to fourfold increases. Modest depression of serum testosterone and estradiol was noted for CaP patients compared to CC, although the differences were not statistically significant. This depression was interpreted to be a likely result of the malignant process rather than a cause of it, whereas the development of clinically evident BPH was felt to be a biologically plausible response to an elevated T/E ratio.

Age Factors

Metabolic modeling of organ-specific doses to carcinogens as illustrated with alpha-radiation emitting radionuclides.

Quantitative estimation of doses of carcinogens delivered to physiologic targets facilities specification of organ-specific dose-response functions. Typically, exposure measurements, such as air or water concentrations of carcinogens, are used as dose surrogates in epidemiologic studies. An illustrative exception to this usual situation is the case of airborne alpha radiation-emitting radionuclides, for which organ-specific doses can be derived. A metabolic modeling approach for estimating doses delivered to the lung, gastrointestinal tract and bone is described for three classes of radionuclides: soluble uranium, insoluble uranium and plutonium. The dose models are defined in terms of biological retention patterns and organ-specific depositions affinities. Application of the metabolic modeling approach is illustrated with a hypothetical example of excess lung cancer risk projection in a cohort of persons exposed to plutonium. Also, a simple example is presented to demonstrate how adherence to the metabolic model structure can avoid gross overestimation of doses in the case of multiple in vivo lung counting measurements taken in close temporal proximity following a large exposure intake.

Dose-Response Relationship, Radiation

A simple computer program for generating person-time data in cohort studies involving time-related factors.

The use of grouped data methods, such as standardized rate ratios and Poisson regression, for the analysis of cohort studies has a number of attractive features. This approach, however, has not been widely used in the past because of the difficulty of generating person-time data required for the computation of rates, particularly when stratification on time-related factors is involved. This paper presents a simple Statistical Analysis System (SAS) program for the generation of such data in a form that can be read directly by GLIM and used in a Poisson regression analysis. In addition to its simplicity, the program has the advantage of considerable flexibility and involves no restrictions on the number of time-related factors or the number of levels of each factor. Furthermore, it can be modified easily for multiple disease outcomes and for analyses of the latency period, or empirical induction time.

Humans

Ocular sarcoidosis. A case-control study among black patients.

A case-control study was conducted to investigate possible environmental risk factors for ocular sarcoidosis. The factors studied were exposures to pine products and occupational histories of employment in the tobacco, lumber, and textile industries. The exposure histories of 29 female and 15 male cases, patients with newly diagnosed ocular sarcoidosis that were attending the Glaucoma/Uveitis Clinic of the North Carolina Memorial Hospital, were compared to those of 110 female and 28 male controls selected from out-patient clinics. Elevated risks for sarcoidosis were detected among those females that were exposed to burning pine or were employed in the tobacco industry. For males, positive associations were observed for chewing pine products and for employment in the lumber and textile industries. These preliminary data are consistent with incomplete phagocytic clearance of nonbiodegradable foreign bodies present within our environment that may become antigenic to the immunologically susceptible host. Confirmation of refutation of these hypotheses awaits additional clinical and epidemiological research within the sarcoidosis belt.

Adolescent

Time-related factors as potential confounders and effect modifiers in studies based on an occupational cohort.

Time-related factors which are potential confounders and effect modifiers in studies based on an occupational cohort are reviewed. The most frequently considered ones include age at first exposure, duration of exposure, interval from exposure to disease recognition, and age at risk. These factors are related to the "healthy worker effect," which appears to be more pronounced among workers with the longest durations of employment and older ages, at date of hire, but weaker with longer length of follow-up and older age at risk. Hence, use of an internal comparison group may not eliminate bias since confounding will occur if the exposed and unexposed groups differ in their distributions across these factors. It is also shown, using the multistage model of carcinogenesis, that these factors may be important effect modifiers. Fortunately, generally straightforward methods of control exist both for stratified analyses and for the commonly used mathematical modeling approaches. Although no firm recommendations can be made, it would appear to be important to control for length of follow-up in the design or analysis of most studies based on an occupational cohort, and controlling for age at first exposure may also be desirable under many circumstances.

Adult

Epidemiologic programs for computers and calculators. Use of Poisson regression models in estimating incidence rates and ratios.

Summarizing relative risk estimates across strata of a covariate is commonly done in comparative epidemiologic studies of incidence or mortality. Conventional Mantel-Haenszel and rate standardization techniques used for this purpose are strictly suitable only when there is no interaction between relative risk and the covariate, and tests for interaction typically are limited to examination for departures from linearity. Poisson regression modeling offers an alternative technique which can be used for summarizing relative risk and for evaluating complex interactions with covariates. A more general application of Poisson regression is its utility in modeling disease rates according to postulated etiologic mechanisms of exposures or according to disease expression characteristics in the population. The applications of Poisson regression analysis to problems of summarizing relative risk and disease rate modeling are illustrated with examples of cancer incidence and mortality data, including an example of a nonlinear model predicted by the multistage theory of carcinogenesis.

Adolescent

Radiation, work experience, and cause specific mortality among workers at an energy research laboratory.

A retrospective cohort mortality study was conducted among 8375 white male employees who had worked at the Oak Ridge National Laboratory for at least one month between 1943 and 1972. This plant has been the site of energy related research, including uranium and plutonium reactor technology and radioisotope production. Radiation doses, primarily from gamma rays, were generally low; the median cumulative exposure for workers was 0.16 rems. Historical follow up was conducted for the years 1943-77 and ascertainment of vital status was achieved for 92.3% of the cohort. Standardised mortality ratios (SMRs) were computed to contrast the subjects' cause specific mortality experience with that of the United States white male population. The observed number of 966 deaths from all causes was 73% of the number expected. Mortality deficits were also seen for arteriosclerotic heart disease (SMR = 0.75; 344 observed) and all cancers (SMR = 0.78; 194 observed). These results are indicative of the healthy worker effect and the favourable influence on health of the cohort's relatively high socioeconomic status. Non-statistically significant raised SMRs were seen for all leukaemias (SMR = 1.49, 16 observed), cancer of the prostate (SMR = 1.16, 14 observed), and Hodgkin's disease (SMR = 1.10, 5 observed). Internal comparisons of mortality (standardised rate ratios, SRRs) were made between subgroups of the cohort according to radiation dose level and duration of employment in various job categories. No consistent gradients of cause specific mortality were detected for radiation exposure. Leukaemia mortality was highest among workers with greater than or equal to 10 years employment in engineering (SRR = 2.40) and maintenance (SRR = 3.12) jobs. The association of leukaemia with employment in engineering was unexpected; maintenance jobs entail potential exposures to radiation and to a wide range of organic chemicals; metals, and other substances.

Adolescent