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Biomedical subjects

N Pearce

Publications and source records attributed to N Pearce.

At least 181 records · Page 10Linked to original sources

Design and conduct of occupational epidemiology studies: I. Design aspects of cohort studies.

Cohort and case-control studies are two standard approaches for investigating the etiology of occupational diseases. This paper, which is the first of a four-part series, contains a review of the design features of occupational cohort studies. Topics discussed include the basic features of prospective and historical cohort studies, options for defining the cohort, disease incidence ascertainment, and considerations involved in planning an occupational cohort study. Subsequent papers in this series will focus on data analysis of occupational cohort studies and the design and analysis of occupational case-control studies.

Cohort Studies

Design and conduct of occupational epidemiology studies: II. Analysis of cohort data.

This paper reviews strategies and statistical methods for analyzing data from occupational cohort studies. Emphasis is placed on the common methods for grouped data analysis involving external and internal comparison populations. Analysis procedures reviewed are standardized mortality ratio, standardized rate ratio, and Mantel-Haenszel techniques for estimating relative risks. Methods for control of confounding, assessment of effect modification, and allowance for disease latency are discussed. These concepts and procedures are illustrated with data from an historical cohort mortality study of workers from an asbestos textile plant.

Biometry

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

Critical discussion in epidemiology: problems with the Popperian approach.

There has been a renewed interest in the philosophical and scientific basis of epidemiology in recent years. In particular, it has been argued that Popper's philosophy should be adopted by epidemiologists, an assertion that has met with some scepticism. However, most criticisms of Popper's approach have been from an inductivist viewpoint, concerned with the generation of theories, whereas Popper's concern is with the testing of theories, and the two schools have been largely "talking past each other". We present a critique of Popper from within his own domain of interest. Examples are presented to show that Popper's philosophy is incomplete even for the physical sciences on which it is based, and that it is particularly inappropriate for epidemiology. Popper's approach makes sense only under the narrow way he has chosen to define science, and thus provides only a possible answer to a small set of fundamental problems of science and its use in society. The recent Popperian "trend" has a positive aspect in that it has fostered deductive thinking, and exposed the shortcomings of induction. However, the restrictive Popperian framework actually inhibits discussion despite its veneer of "critical discussion". A more pluralistic approach is needed at this stage of the development of epidemiology.

Epidemiologic Methods

Case-control studies of cancer in New Zealand electrical workers.

A series of reports, including a New Zealand case-control study, have suggested that electrical workers are at increased risk of leukaemia. We report here a further series of case-control studies based on the New Zealand Cancer Registry. These involved 19,904 male patients registered with cancer for the period 1980-1984 who were aged 20 years or more at time of registration. For each cancer site, the registrations for other sites formed the control group. Three main findings emerged. First, there is an elevated leukaemia risk in New Zealand electrical workers (odds ratio (OR) = 1.62, 95% confidence interval (Cl) 1.04-2.52), but little evidence of increased risks for other cancer sites. Second, contrary to other published studies, the increased risk was primarily for chronic leukaemia (OR = 2.12) rather than acute leukaemia (OR = 1.25), and for lymphatic leukaemia (OR = 1.73) rather than myeloid leukaemia (OR = 1.22). Third, the increased risk was strongest for certain categories of electrical work including radio and television repairers (OR = 7.86, 95% CI 2.20-28.09), electricians (OR = 1.68, 95% Cl = 0.75-3.79), linemen (OR = 2.35, 95% Cl 0.97-5.70) and power station operators (OR = 3.89, 95% Cl 1.00-15.22).

Adult

Cancer risks in New Zealand farmers.

Previous New Zealand case-control studies have found increased risk for leukaemia, non-Hodgkin's lymphoma (NHL) and multiple myeloma in farmers. We report here a further series of New Zealand Cancer Registry based case-control studies of farming and site-specific cancer risks. These involved 19,904 males aged 20 years or more who were registered with cancer between 1980 and 1984. For each cancer site, the registrations for other sites formed the control group. Farmers had elevated risks for malignant melanoma (Odds Ratio [OR] = 1.25, 95% confidence interval [Cl] 1.05-1.50), and for cancer of the lip (OR = 2.43, 95% Cl 1.81-3.27), rectum (OR = 1.19, 95% Cl 1.03-1.38), bone (OR = 1.95, 95% Cl 1.00-3.80), prostate (OR = 1.26, 95% Cl 1.13-1.41) and brain (OR = 1.34, 95% Cl 1.04-1.74). Decreased risks were observed for cancer of the larynx (OR = 0.66, 95% Cl 0.45-0.96), lung (OR = 0.70, 95% Cl 0.63-0.77) and testis (OR = 0.58, 95% Cl 0.39-0.88). Livestock farmers had a relatively high risk for brain cancer, while the risk for cancer of the lip was highest among dairy farmers. Farmers also had increased risks for cancer of the lymphatic and haematopoietic system (International Classification of Disease 9th edn (ICD) 200-208) (OR = 1.24, 95% Cl 1.08-1.42), leukaemia (OR = 1.24, 95% Cl 0.99-1.55) and non-Hodgkin's lymphoma (NHL) (OR = 1.24, 95% Cl 0.99-1.56), as described previously.

Adult

Analytical implications of epidemiological concepts of interaction.

In contrast to definitions based on statistical or biological concepts, Rothman has adopted an unambiguous epidemiological definition of interaction in which two factors are not 'independent' if they are component causes in the same sufficient cause. This leads to the adoption of additivity of incidence rates as the state of 'no interaction'. However, there are other considerations which generally favour the use of multiplicative models. This implies an apparent dilemma as to how an analysis can be conducted which combines the advantages of ratio measures of effect with the assessment of independence in terms of a departure from additivity. These apparently contradictory goals can be reconciled through the analysis of separate and joint effects. This approach is discussed with reference to studies of asbestos exposure, cigarette smoking and lung cancer.

Causality

Incidence density matching with a simple SAS computer program.

Incidence density matching is the method of choice for selecting controls in nested case-control studies, but its use has been limited by its computational complexity. We describe incidence density matching in nested case-control studies with a simple and flexible SAS computer program. The program contains no restrictions on the number of matching factors, although it is usually only necessary to match on age (in incidence density fashion) and on gender. The program is illustrated with data from an historical cohort study of the mortality experience of workers at an asbestos textile manufacturing plant.

Case-Control Studies

Occupational risks for brain cancer: a New Zealand Cancer Registry-based study.

Occupational risks for brain cancer were evaluated in a New Zealand Cancer Registry-based case-control study. The case subjects were 452 men aged 20 years or older registered under classifications 191 (Cancer of the brain) and 192 (Cancer of other and unspecified parts of the nervous system) of the International Classification of Disease (9th ed) from 1980 to 1984 for whom occupational information was available. The remaining 19,452 men with other cancers registered during an excess of professional and technical workers. An increased risk among workers in agriculture, forestry, and fishing was due to an excess of brain cancer in farmers, with the highest risk found for livestock farmers. Although many comparisons have been made, some of the findings support previous studies and several new hypotheses are suggested.

Adult

Hepatitis B virus: the importance of age at infection.

Recent studies have demonstrated the importance of age at infection with hepatitis B virus (HBV). Age affects whether the infection is self-limited or results in the chronic carrier state, the severity of the acute infection, and the incidence of various sequelae of the chronic carrier state. In particular, although the acute infection is more severe in adults, infections in infants and preschool children carry much greater risks of chronic carriage which increases the risk of primary hepatocellular carcinoma and cirrhosis later in life. This has two important implications for areas where HBV is endemic. First, more impact can be gained by vaccinating infants and preschool children than by vaccinating healthy adults. Second, if funds are limited, greater impact will be gained by immunising a larger number of children with low doses of vaccine so that they are protected during the early years of life when the risk of chronic carriage is highest, rather than using the standard dose in a smaller number of children even though protection may be longer lasting with standard doses. These two considerations provide the basis for an efficient strategy for control in communities or countries where HBV is endemic or hyperendemic.

Adolescent

Increased risks of soft tissue sarcoma, malignant lymphoma, and acute myeloid leukemia in abattoir workers.

This paper presents a review and further analysis of a series of New Zealand case-control studies which have found elevated risks for soft tissue sarcoma (STS), non-Hodgkin's lymphoma (NHL), and acute myeloid leukemia (AML) in abattoir workers. The first published study involved 82 cases of STS (ICD 171) and found a relative risk of 2.8 (90% confidence interval 1.3-6.3). Interviews with an additional 51 cases reported here revealed a relative risk of 1.6 (90% confidence interval 0.9-3.0). Two further studies involved interviews with 100 cases of the category of NHL involving lymphosarcoma and reticulosarcoma (ICD 200) and 83 cases of other NHL (ICD 202). Relative risk estimates were 1.8 (90% confidence interval 1.1-2.9) and 1.7 (90% confidence interval 1.0-2.8), respectively. A study of 150 cases of AML (ICD 205.0) found a relative risk of 2.5 for abattoir workers (90% confidence interval 1.3-4.7). Finally, a United States cohort study found a standardized mortality ratio of 2.4 (90% confidence interval 0.8-5.4) for Hodgkin's disease (ICD 201) and 2.2 (90% confidence interval 0.8-4.5) for cancer of other lymphatic tissue (ICD 202, 203, 208) among abattoir workers. Abattoir workers are potentially exposed to oncogenic viruses, including bovine leukemia virus. Some workers may also be exposed to the animal carcinogen 2,4,6-trichlorophenol when treating pelts.

Abattoirs

Multistage modelling of lung cancer mortality in asbestos textile workers.

The Armitage-Doll multistage model of cancer is applied to data from a cohort study of lung cancer in 1261 white male workers from one asbestos textile manufacturing plant. Three approaches are used: induction time analysis; analysis of the relationship of the excess incidence rate to age at first exposure and time since first exposure; and direct fitting of the Armitage-Doll model. Poisson regression was used for all analyses. The induction time analysis was conducted using Rothman's 'window of exposure' method. This suggested that the increase in rate ratio was primarily due to exposures occurring 15-24 years previously, whereas there was little effect from exposures occurring 0-14 or 25+ years previously. The excess incidence rate increased both with age at first exposure and time since first exposure, suggesting that asbestos acted at a stage intermediate between the first and penultimate stages. Direct fitting of the Armitage-Doll model suggested that the best fit was obtained by assuming that asbestos acts at stage 3, 4 or 5 of a six-stage process. Most analyses of the type presented here are unable to determine at which stage a carcinogen acts, due to the small numbers of cancer deaths occurring in typical occupational cohorts. Furthermore, there is reason to doubt the validity of the Armitage-Doll model. However, such analyses can at least suggest whether a carcinogen appears to act at an early, intermediate or late stage, and the general statistical methods applied here will retain their usefulness as further models are developed and larger data sets become available.

Adult

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