Achievement of causal inference in the social medicine in Japan

As a condition to achieving an agreement of recognition on the causal relationship in medicine, we firstly explained Hume's problem and counterfactual model. We, however, emphasized that we believe in the existence of causality on medical issues in our daily lives. Therefore, we illustrated conditions when we usually believe in causality. On the other hand, we criticized two well-known key phrases, "lack of mechanism in epidemiology" and "black box in epidemiology", which have often been used in Japan for skeptic viewpoints against epidemiologic methods even if epidemiology is often used to elucidate a causal effect in medicine in the world. We emphasized that a priori determinations of levels for inference of mechanism is necessary. And, the level and feature of mechanism should be defined in concrete expressions. After explanation of these basic concepts, we mentioned a classic view on specific diseases and non-specific diseases which have not been sufficiently discussed enough yet in Japan. As an example, we used the statements in the Japanese Compensation Law for the Health Effect by Environmental Pollution. In Japan, the classification of these diseases has been confused with that between manifestational criteria of diseases and causal criteria of them. We described the basic concepts to illustrate the causal relationship between non-specific disease and its exposure by using attached figures. Actually, we cannot recognize disease occurrence as a specific disease for several reasons. We indicated that we can recognize the magnitude of effect by causal relationships in medicine as a quantitative continuous variable.     

The family physician looks at occupational health information

Although much is known about occupational and environmental health risks, this information is rarely used by physicians practicing primary-care medicine. As a specialty with roots in the epidemiologic tradition, family medicine should be able to use these data to help care for the individual in the context of the family and community. In this discussion, the historical links between family medicine and epidemiology are reviewed, barriers to the use of epidemiologically derived occupational health information are analyzed, and solutions to the problem of integration are proposed. The relationship between primary care and occupational medicine is a subset of the relationship of clinical practice to epidemiology in general.     

Occupational deafness: the continuing challenge of early German and Scottish research

Systematic studies in occupational deafness were first carried out in the late 19th century, in America, Germany, Russia, and Scotland. The studies by Gottstein and Kayser, in 1881 in Germany, and by Barr, in 1886 in Scotland, are identified as the two principal landmarks. The physicians who carried them out should be seen as occupying a place in the mainstream of development of industrial medicine. Gottstein and Kayser's study of personnel in a railway works reflected a contemporary concern about railway safety; Barr's, of boilermakers, a feeling for the difficulties in hearing in the everyday world experienced by the victims of occupational deafness. Barr's evaluation of such difficulties through self-report, we argue, reveals more of the quality of hearing handicap than the present century's apparently objective tests. Both studies relied on occupation-based epidemiology, which was able to identify occupational deafness, distinguish its etiology, and locate the site of its pathology. We argue that occupation-based epidemiology has since been neglected in favour of dose-response epidemiology to the detriment of research in occupational deafness and in industrial medicine generally. Dose-response epidemiology seems the more scientific but, in practice, it is afflicted by even more uncertainty than occupation-based epidemiology. To compound the uncertainty, there are two incompatible mathematical expressions for the dose-response relation for noise, both separately enshrined in legislation in various parts of the world. We conclude by advocating more secondary research in industrial medicine. Barr points us to a further topic for such research, the place of temporary threshold shift in the development of knowledge about occupational deafness as a problem for industrial medicine.     

Exposure-response relationship in the hand-arm vibration syndrome: an overview of current epidemiology research

The complex of vascular, neurologic, and osteoarticular disorders occurring in the upper limbs of vibration-exposed workers is called hand-arm vibration syndrome. There is epidemiologic evidence for an increased occurrence of peripheral sensorineural disorders in occupational groups working with vibrating tools. An excess risk for wrist osteoarthrosis and for elbow arthrosis and osteophytosis has been reported in workers exposed to shocks and low-frequency vibration of high magnitude from percussive tools. However, there are too few epidemiology data to enable reliable conclusions to be drawn about exposure-response relationships for both sensorineural disturbances and bone and joint disorders caused by hand-transmitted vibration. Cross-sectional and longitudinal epidemiology studies have shown that occupational exposure to hand-transmitted vibration from a great variety of hand-held tools is significantly associated with an increased occurrence of digital vasospastic disorders called vibration-induced white finger (VWF). The proposal of an exposure-response relationship for VWF has been included in an annex to the international standard ISO 5349. The findings of several epidemiology studies have shown a poor agreement between the risk for VWF observed in various occupational groups and that predicted by the ISO 5349 model. Both overestimation and underestimation of the occurrence of VWF have been reported by investigators. It has been argued that the current ISO frequency-weighting curve for hand-transmitted vibration may be inappropriate for the assessment of vibration-induced adverse vascular effects. Alternative exposure-response relationships for VWF have been suggested in recent epidemiology studies. The epidemiology data used to construct current exposure-response relationships for vibration-induced injuries are primarily derived from cross-sectional studies. Future epidemiology research should be based on prospective cohort studies because the design characteristics of such studies permit the study of cause-effect relationships and the formulation of etiologic hypotheses. Received: 16 March 1998 / Accepted: 6 July 1998     

Dermal exposure assessment in occupational epidemiologic research

Recognition of the importance of skin exposure in industrial settings has steadily increased over the last few decades. Unfortunately, the growing attention to dermal exposure in industrial hygiene has often not been reflected in the field of occupational epidemiology. An extensive literature survey was conducted to identify dermal exposure assessment methods that have been applied in epidemiologic studies. Subsequently, methodologies are postulated that could be applied to epidemiologic research. Attention is given to intensity, frequency, and duration of exposure, the exposed surface area, and personal, temporal and spatial variability in dermal exposure and uptake. It is anticipated that, in the near future, dermal exposure assessment in epidemiologic research will be based generally on expert judgment and to some degree on process-specific exposure models. Field studies collecting quantitative dermal exposure data and statistical modeling to identify exposure determinants will, however, be imperative if progress is to be made in the field of dermal exposure assessment for epidemiologic purposes.     

Disease clusters in occupational medicine: a protocol for their investigation in the workplace.

Disease clusters have been an important source of epidemiologic and medical information in the history of occupational medicine. Many accepted disease-exposure linkages were first observed and investigated as disease clusters in the workplace setting. Recent interest in disease cluster methodology has focused on traditional environmental settings. There has been very little work on a similar methodology for the investigation of disease clusters in the workplace, despite the many advantages of workplace cluster investigations for recognizing new etiologic associations. In this paper, a protocol is proposed and discussed which can be implemented in both acute and chronic disease cluster outbreaks in the workplace, where no obvious previously recognized cause is identified. A standardized approach to occupational disease cluster investigation will lead to increased efficiency, decreased social-political tensions, and a greater yield of scientific information.     

The epidemiologic field investigation: science and judgment in public health practice

Epidemiologic field investigations are often done in response to acute public health problems. When outbreaks of disease occur, there usually is an urgent need to identify the source and/or cause of the problem as a basis for control. Alternatively, the identification of environmental or occupational hazards frequently demands evaluation of exposed persons and assessment of the risks of disease. In this commentary, the authors present a perspective on the public-sector practice of epidemiology by considering the factors that influence epidemiologic prospectively planned studies; and examining the complexities of the relations between epidemiology and public health practice.     

Epidemiology of risks in the workplace]

Epidemiologic studies of occupationally exposed subjects allow to detect diseases caused by the work environment and to identify hazardous exposures. They provide the basis for preventive measures and workers compensation. Occupational epidemiology traditionally emphasized the study of work related cancer. Long latency periods for the development of most cancers and limited information about the exposure history of the study subjects are problems for all study types. The specific advantages and limitations of different study designs are discussed. Research strategies in occupational epidemiology are demonstrated using as an example two studies from the American tire and rubber industry. The specific contributions of a historical cohort study and a nested case-control study, concerning the association between lymphosarcoma and exposure to solvents, are discussed. Experiences and first results from a historical cohort study in the German rubber industry are reported. Future research in occupational epidemiology should concentrate more on the study of work related morbidity such as musculoskeletal disorders, hearing loss, accidents and the influence of the work environment on the mental and physical well being. Modern research methods such as prospective cohort studies or workforce monitoring should be used more often. Prospective cohort studies provide quantitatively and qualitatively more precise information about exposures and potential confounders, e.g. cigarette smoking or alcohol consumption, than traditional study methods. The promising perspectives of biological markers warrant further research. The situation of occupational epidemiology in Germany can only be improved if all concerned parties and institutions realize the importance of occupational epidemiology. Laws concerning data confidentiality which seriously hamper epidemiologic research must be modified.     

Listing occupational carcinogens

The occupational environment has been a most fruitful one for investigating the etiology of human cancer. Many recognized human carcinogens are occupational carcinogens. There is a large volume of epidemiologic and experimental data concerning cancer risks in different work environments. It is important to synthesize this information for both scientific and public health purposes. Various organizations and individuals have published lists of occupational carcinogens. However, such lists have been limited by unclear criteria for which recognized carcinogens should be considered occupational carcinogens, and by inconsistent and incomplete information on the occupations and industries in which the carcinogenic substances may be found and on their target sites of cancer. Based largely on the evaluations published by the International Agency for Research on Cancer, and augmented with additional information, the present article represents an attempt to summarize, in tabular form, current knowledge on occupational carcinogens, the occupations and industries in which they are found, and their target organs. We have considered 28 agents as definite occupational carcinogens, 27 agents as probable occupational carcinogens, and 113 agents as possible occupational carcinogens. These tables should be useful for regulatory or preventive purposes and for scientific purposes in research priority setting and in understanding carcinogenesis.     

Maternal arsenic exposure and birth outcomes: A comprehensive review of the epidemiologic literature focused on drinking water

Inorganic arsenic (iAs) is a human toxicant to which populations may be exposed through consumption of geogenically contaminated groundwater. A growing body of experimental literature corroborates the reproductive toxicity of iAs; however, the results of human studies are inconsistent. Therefore, we conducted a comprehensive review of epidemiologic studies focused on drinking water iAs exposure and birth outcomes to assess the evidence for causality and to make recommendations for future study. We reviewed 18 English language papers assessing birth weight, gestational age, and birth size. Thirteen of the studies were conducted among populations with frequent exposure to high-level groundwater iAs contamination (>10 μg/L) and five studies were conducted in areas without recognized contamination. Most studies comprised small samples and used cross-sectional designs, often with ecologic exposure assessment strategies, although several large prospective investigations and studies with individual-level measurements were also reported. We conclude that: (1) the epidemiologic evidence for an increased risk of low birth weight (<2500 g) is insufficient, although there exists limited evidence for birth weight decreases; (2) the evidence for increased preterm delivery is insufficient; and, (3) there exists minimal evidence for decreased birth size. In further investigation of birth weight and size, we recommend incorporation of individual susceptibility measures using appropriate biomarkers, with collection timed to windows of vulnerability and speciated arsenic analysis, as well as consideration of populations exposed primarily to drinking water iAs contamination <10 μg/L. Given the large potential public health impact, additional, high quality epidemiologic studies are necessary to more definitively assess the risk.     

Exposure assessment of risk factors for disorders of the back in occupational epidemiology.

This review describes methods for assessing exposure to postural load of the back in occupational epidemiologic studies. Eighty-one original articles were selected that presented information on the prevalence of back disorders in occupational groups. In 47 (58%) of these studies no data on exposure to risk factors were given. In the remaining 34 studies (42%) exposure assessment was performed by questionnaire (33%), observation (9%), and direct measurement (5%). Measures of exposure were predominantly presented at the nominal and ordinal levels. It is argued that in most epidemiologic studies on disorders of the back in occupational groups the quality of exposure data is poor. Quantitative measurement methods need to be developed for application in occupational epidemiology.     

Utility of inverse probability weighting in molecular pathological epidemiology

As one of causal inference methodologies, the inverse probability weighting (IPW) method has been utilized to address confounding and account for missing data when subjects with missing data cannot be included in a primary analysis. The transdisciplinary field of molecular pathological epidemiology (MPE) integrates molecular pathological and epidemiological methods, and takes advantages of improved understanding of pathogenesis to generate stronger biological evidence of causality and optimize strategies for precision medicine and prevention. Disease subtyping based on biomarker analysis of biospecimens is essential in MPE research. However, there are nearly always cases that lack subtype information due to the unavailability or insufficiency of biospecimens. To address this missing subtype data issue, we incorporated inverse probability weights into Cox proportional cause-specific hazards regression. The weight was inverse of the probability of biomarker data availability estimated based on a model for biomarker data availability status. The strategy was illustrated in two example studies; each assessed alcohol intake or family history of colorectal cancer in relation to the risk of developing colorectal carcinoma subtypes classified by tumor microsatellite instability (MSI) status, using a prospective cohort study, the Nurses’ Health Study. Logistic regression was used to estimate the probability of MSI data availability for each cancer case with covariates of clinical features and family history of colorectal cancer. This application of IPW can reduce selection bias caused by nonrandom variation in biospecimen data availability. The integration of causal inference methods into the MPE approach will likely have substantial potentials to advance the field of epidemiology.     

Modeling epidemiologic studies of occupational cohorts for the quantitative assessment of carcinogenic hazards

Epidemiologic studies of occupational cohorts have played a major role in the quantitative assessment of risks associated with several carcinogenic hazards and are likely to play an increasingly important role in this area. Relatively little attention has been given in either the epidemiologic or the risk assessment literature to the development of appropriate methods for modeling epidemiologic data for quantitative risk assessment (QRA). The purpose of this paper is to review currently available methods for modeling epidemiologic data for risk assessment. The focus of this paper is on methods for use with retrospective cohort mortality studies of occupational groups for estimating cancer risk, since these are the data most commonly used when epidemiologic information is used for QRA. Both empirical (e.g., Poisson regression and Cox proportionate hazards model) and biologic (e.g., two-stage models) models are considered. Analyses of a study of lung cancer among workers exposed to cadmium are used to illustrate these modeling methods. Based on this example it is demonstrated that the selection of a particular model may have a large influence on the resulting estimates of risk.     

The epidemiology of pesticide exposure and cancer: A review

Cancer is a multifactorial disease with contributions from genetic, environmental, and lifestyle factors. Pesticide exposure is recognized as an important environmental risk factor associated with cancer development. The epidemiology of pesticide exposure and cancer in humans has been studied globally in various settings. Insecticides, herbicides, and fungicides are associated with hemopoetic cancers, and cancers of the prostate, pancreas, liver, and other body systems. The involvement of pesticides in breast cancer has not yet been determined. In developing countries, sufficient epidemiologic research and evidence is lacking to link pesticide exposure with cancer development. Agricultural and industrial workers are high-risk groups for developing cancer following pesticide exposure. Children of farm workers can be exposed to pesticides through their parents. Maternal exposure to pesticides can pose a health risk to the fetus and the newborn. The organophosphates are most the commonly used compounds, but the organochlorines are still permitted for limited use in developing countries. Pesticide exposure, independently or in synergism with modifiable risk factors, is associated with several types of cancer.     

Epidemiologic research topics in Germany: a keyword network analysis of 2014 DGEpi conference presentations

Knowledge of epidemiologic research topics as well as trends is useful for scientific societies, researchers and funding agencies. In recent years researchers recognized the usefulness of keyword network analysis for visualizing and analyzing scientific research topics. Therefore, we applied keyword network analysis to present an overview of current epidemiologic research topics in Germany. Accepted submissions to the 9th annual congress of the German Society for Epidemiology (DGEpi) in 2014 were used as data source. Submitters had to choose one of 19 subject areas, and were ask to provide a title, structured abstract, names of authors along with their affiliations, and a list of freely selectable keywords. Keywords had been provided for 262 (82 %) submissions, 1030 keywords in total. Overall the most common keywords were: “migration” (18 times), “prevention” (15 times), followed by “children”, “cohort study”, “physical activity”, and “secondary data analysis” (11 times each). Some keywords showed a certain concentration under one specific subject area, e.g. “migration” with 8 of 18 in social epidemiology or “breast cancer” with 4 of 7 in cancer epidemiology. While others like “physical activity” were equally distributed over multiple subject areas (cardiovascular & metabolic diseases, ageing, methods, paediatrics, prevention & health service research). This keyword network analysis demonstrated the high diversity of epidemiologic research topics with a large number of distinct keywords as presented at the annual conference of the DGEpi.     

Adjustment of risk ratios in case-base studies (hybrid epidemiologic designs)

The recent growth of occupational epidemiology has led to a resurgence of interest in the hybrid epidemiologic study design of Kupper et al., which has come to be termed a 'case-base' or 'case-cohort' design. This paper shows how the adjustment method for the risk ratio estimate given by Kupper et al. may have substantial bias, and also shows how one must modify conventional adjustment techniques (such as the Miettinen, Woolf and Mantel-Haenszel methods) when used with hybrid designs. This paper also provides the necessary modifications for tests and confidence intervals.     

California surveillance for pesticide-related illness and injury: coverage, bias, and limitations

The California Pesticide Illness Surveillance Program (PISP) is a major resource for pesticide illness epidemiology. This work attempts to improve characterization of pesticide illness in California, evaluate case ascertainment of the PISP and identify PISP's limitations and biases for studying the incidence and epidemiology of pesticide-related illness. Abstractors collected standardized information from 1994-1996 PISP files, poison control logs, hospital records, and death certificates. Linkage produced a merged file of all records that documented consideration of pesticide exposure as a cause of ill health. We identified 23 deaths and estimated 1,310 hospitalizations attributable to pesticide exposure, corresponding to 0.024 fatalities and 1.38 hospitalizations (95% confidence interval [CI] = 1.01-1.74) per 100,000 California population person-years. Most intoxications followed domestic exposures and were not reported to the surveillance program, which identified primarily occupational exposures. Excluding groups of five or more, we estimated 16% ascertainment (CI = 0.05-0.27) for non-agricultural occupational cases. Agricultural connections increased the probability of ascertainment to about 50%, cultural and economic barriers notwithstanding. Surveillance records existed for all identified episodes in which five or more people were exposed. California pesticide surveillance data appear complete for mass exposures, and adequate to characterize agricultural and occupational exposures. Work is needed to explore domestic exposures and occurrences beyond the reach of the health care system.     

Occupational hazards to health care workers: report of a conference

Health care workers are exposed to an array of physical, chemical, biological, and psychosocial hazards. At a national conference in Seattle May 11-13, 1983, hospital occupational medicine programs were characterized as lagging far behind those in industries with comparable illness and injury rates. Participants and speakers recommended that health care workers be trained to recognize occupational hazards; that epidemiologic, laboratory, and clinical studies be undertaken to discern trends and establish the mechanisms of effects from hazardous exposures; and that adequate employee health and safety programs be established in health care settings.     

Occupational morbidity and mortality in malignant neoplasms among persons professionally exposed to asbestos dust

Asbestos fibres discharged as a result of machine processing of brakes, are characterized by a lowered biological activity due to the fixation layer which covers them. This has been confirmed through occupational diseases' analysis and new data on malignant neoplasms epidemiology among workers engaged in machine processing of asbestos-moulded machine parts. General mortality caused by malignant neoplasms in these groups higher than in the control group, although statistically is not significant. This necessitates further epidemiologic studies to be performed at similar plants.