[Causal inference in medicine--decision making].

In the field of occupational medicine, either when we consider some preventive plans or when we make decisions to compensate for occupational diseases, it has been necessary to discuss causality between work and disease. Furthermore, epidemiologic causality has recently been used in risk assessment in occupational and environmental settings. We have shown that the law of causality in medicine is recognized as probability and continuous variables. Such a law of causality has been recognized in the same way as probability in physics, too, and has been regarded as a model of science. Physicists and mathematicians had claimed the importance of probability in causal inference as well as the principle of uncertainty before it was discovered. We, then, explained Etiologic Fraction (EF), Attributable Proportion for the Exposed Population (APE), Probability of Causation (PC), and so on. The PC has been used to ascertain the conditional probability in an individual case of a disease having been caused by a particular prior exposure, by using the experience of exposed populations to determine the appropriate relative risk, and this has been used for compensation for exposed cases. Next the applicability of information from a population to individuals was presented. Third, we provided a brief historical aspect of epidemiology. The evolutions in Epidemiology have been very rapid, so we pointed out that, in Japan, we could observe many incommensurable phenomena in epidemiologists and physicians depending on the era which was studied by them. Fourth, we discussed judgement and political application based on epidemiologic evidence, using Yanagimoto's classification is also taken or not should be estimated and compared. We presented several examples of reasoning in judgements. Lastly, we discussed several tasks and assignments for the future of epidemiology.

Smoking and mental health: cross-sectional and cohort studies in an occupational setting in Japan.

BACKGROUND: The relationship between smoking and mental health remains unclear. METHODS: We carried out a cross-sectional study and a cohort study on the possible association of smoking and mental health in 782 workers. Using a questionnaire including the 30-item General Health Questionnaire (GHQ-30) and items related to the smoking state, the association between smoking and mental health was evaluated separately in males and females. The subjects were classified into smokers and nonsmokers, and changes in the GHQ score during a 2-year follow-up period were evaluated. To control potential confounding factors, multiple regression analyses were performed. RESULTS: The cross-sectional study showed no difference in the GHQ score between smokers and nonsmokers among males but a significantly higher GHQ score for smokers than nonsmokers among females. This difference among females was confirmed to be significant by multiple regression analysis. The 2-year cohort study showed a decrease in the GHQ score in each group and no reduction in the difference in the GHQ score between smokers and nonsmokers among females. CONCLUSIONS: No difference was observed in mental health between smokers and nonsmokers in males. However, in females, smokers showed poorer mental health than nonsmokers, and this difference remained unchanged even after 2 years.

A case-control study of the relationships among silica exposure, gastric cancer, and esophageal cancer.

BACKGROUND: We examined the effect of silica exposure on gastric and esophageal cancer mortality using a cancer control series in a population setting. METHODS: Cases and controls were restricted to male subjects and were drawn from death certificates in the Tobi area of Japan. A control group was selected from a series of deaths due to colon cancer, and cancers of other organs. The Japanese death certificate system is comprehensive because all deaths must be reported to the local office and death certificates are written by medical doctors. Age and smoking habits adjusted the Mantel-Haenszel odds ratios were estimated. RESULTS: For gastric cancer, the age-, smoking-adjusted odds ratios were 1.22 (95% CI 0.74-2.01) for colon cancer and the other cancer control for silica exposure work, and 1. 36 (95% CI 0.76-2.43) for silicosis. For esophageal cancer, the age- and smoking-adjusted odds ratios were 1.53 (95% CI 0.59-3.96) for the cancer control for silica exposure, and 2.33 (95% CI 0.87-6.23) for silicosis, respectively. CONCLUSIONS: The results suggest that gastric and esophageal cancer were related to silica exposure and silicosis in the study area, although they did not reach a statistically significant level because of the small sample size. The estimated odds ratios were higher for esophageal cancer and silicotic patients.

[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.

Effects of perceived job stress on mental health. A longitudinal survey in a Japanese electronics company.

We conducted a cohort study for 2 years to examine the causal relationship between perceived job stress and mental health. Questionnaire surveys, including a 30-item General Health Questionnaire (GHQ) and a questionnaire on perceived job stress were carried out every 6 months for 2 years. To clarify the causal relationship between job stress and mental health, we followed a group of workers who initially had a GHQ score < or = 7. Out of 462 workers who were thought to be in a healthy mental state, 282 were successfully followed for 2 years. We considered subjects who developed unhealthy mental health states (GHQ score > or = 8) as hazardous cases. To control potential confounding factors, proportional hazard analysis was done. The overall proportion hazardous cases detected in the development of an unhealthy mental health state over two years was 55.7%. Using Cox's proportional hazard model, workers who complained of perceived job stress had a greater hazard than those without job stress. In particular, the item 'poor relationship with superior' showed the largest adjusted hazard ratio [95% confidence interval (CI)] of 1.51 (1.06-2.15). The item 'too much trouble at work' also had a significant hazardous effect on mental health with an adjusted hazard ratio (95% CI) of 1.43 (1.00-2.04). Some specific items of perceived job stress could cause mental ill health in workers.

Does smoking cessation improve mental health?

There is a possibility that cessation of smoking improves mental health, but there are no studies that have demonstrated this. A cohort study was performed for 1 year in 18 males who spontaneously stopped smoking (cessation group) and 173 who continued to smoke (smoking group). The mental health state was evaluated using the Japanese version of the 30-item General Health Questionnaire (GHQ-30) before the cessation of smoking and 6 months and 1 year after smoking cessation. Changes in the GHQ score were compared between the cessation and smoking groups. In order to control the effects of confounding factors, multiple regression analyses were performed using the GHQ score after 6 months and 1 year as dependent variables. The GHQ score in the cessation group significantly decreased 6 months and 1 year after smoking cessation (P < 0.04 and 0.01, respectively, by paired t-test). In the smoking group, the GHQ score slightly decreased. Repeated measure analysis of variance revealed that the decrease in the GHQ score in the cessation group was significantly larger than in the smoking group. Multiple regression analysis revealed significant effects of smoking cessation on mental health after controlling for other confounding factors. It can be concluded that smoking cessation may improve mental health.

Perceived job stress and mental health in precision machine workers of Japan: a 2 year cohort study.

OBJECTIVES: To determine whether perceived job stress affects mental health in occupational settings. METHODS: A 2 year cohort study was conducted. Initially, a survey including the general health questionnaire (GHQ) and a questionnaire about perceived job stress was carried out. Of 462 workers who initially showed a GHQ score of < or = 7,310 were successfully followed up for 2 years. The 2 year risks of developing mental ill health (a GHQ score > or = 8) were assessed relative to perceived job stress. To control for potential confounding factors, multiple logistic regression analyses were conducted. RESULTS: The overall 2 year risk for developing mental ill health was high at 57.7%. Workers who reported aspects of perceived job stress showed a greater 2 year risk than those without stress. Multiple logistic regression analyses showed that some components of perceived job stress were associated with a higher 2 year risk, among which "not allowed to make mistakes" showed the largest adjusted odds ratio (OR) (95% confidence interval (95% CI) of 2.37 (1.32 to 4.29). "Poor relationship with superior" had a significant effect on mental health only in women, with an adjusted OR (95% CI) of 3.79 (1.65 to 8.73). CONCLUSIONS: Certain specific items of perceived job stress seem to be associated with mental ill health in workers. These could broadly be described as job strain, or job demand items. The type of job stress that predicts mental health may be dependent on the characteristics of the workplace investigated.

The role of perceived job stress in the relationship between smoking and the development of peptic ulcers.

Although smoking has been considered a risk factor in causing pepticulcers, no study has examined the effects of job stress on the relationship between peptic ulcers and smoking. To establish a link between gastric or duodenal ulcers over two years and a state of perceived job stress, a questionnaire, including questions on demographics, smoking, history of peptic ulcer and perceived job stress was conducted. Follow-up surveys were carried out every six months to accumulate the data for this analysis and the time span of this follow up study was two years. To examine the role of perceived job stress on the relationship between smoking and peptic ulcers, stratified analyses were performed. Some specific causes of perceived job stress such as "Too much competition," "Schedule is too tight or pressed to work too hard" had high estimated relative risks: 2.13 with 95% confidence interval (CI) of 1.09-4.16 and 2.50 with 95% CI of 0.98-6.40, respectively. Stratified analyses suggested an effect-measure modification of perceived job stress in the relationship between peptic ulcers and smoking. Multiplicative and additive models suggest positive interaction between perceived job stress and smoking. These results suggest that specific perceived job stress is an effect modifier in the relationship between the history of the peptic ulcer and smoking.

[Causal inference in medicine: a reaction to the report, "incidence of Minamata disease in communities along the Agano River, Niigata, Japan--patterns of the exposure and official diagnosis of patients"].

Kondo's "Incidence of Minamata Disease in Communities along the Agano River, Niigata, Japan (Jap. J. Hyg. 51:599-611;1996)" is critically reviewed. The data of the article were obtained from most of the residents living in the Agano river villages where Minamata disease was discovered in June, 1965. However, sampling proportions were much different between in the population base and in the cases. The method of identification of cases from the data and the reason for the difference were not clearly demonstrated. The citations of reference articles are insufficient despite the fact that other epidemiologic studies on methyl-mercury poisoning have been reported not only in Japan, but also around the world. His "analysis of the recognized patients" is erroneous. Both the sampling scheme of information of hair mercury and the modeling of the analysis are based on Kondo's arbitrary interpretation, not on epidemiologic theory. His "analysis of the rejected applicants" is also erroneous. His calculations of the attributable proportion are incorrect and self-induced in both the assignments of data and analysis of data. Kondo has failed to study the epidemiologic theories in light of changes in the field. Therefore, his article is lacking in epidemiologic theory, a logical base and scientific inference. In Japan, epidemiologic methodology has rarely been used in studies on Minamata Disease in either Kumamoto and Niigata. The government has used neurologically specific diagnosis based on combinations of symptoms to judge the causality between each of symptoms and methyl-mercury poisoning. Epidemiologic data obtained in Minamata, Kumamoto in 1971 indicate that the criteria set by the government in 1977 have produced much more false-negative patients than false-positive patients. As a result, a huge number of symptomatic patients, including those with peripheral neuropathy or with constriction of the visual field, did not receive any help or compensation until 1995. The authors emphasize that the causal relationship between each symptom and methyl-mercury exposure should be reevaluated epidemiologically in Japan.

The relationship between job stress and mental health at work.

In order to evaluate the relationship between job stress and mental health, a cross-sectional study was conducted using a questionnaire relating to demographics, subjective job stress and mental health state. The questionnaire consisted of a 30-item Japanese version of the General Health Questionnaire (GHQ) developed by Goldberg in addition to questions about subjective job stress, to measure mental health and job stress conditions, respectively. All subjects were employees of an electronic company in Japan. Among 782 workers, 763 workers responded to the questionnaire satisfactorily (response rate was 97.6%). People whose GHQ score was more than 7 were classified as having psychiatric problems, while the remaining respondents were considered as having no mental health problems. We employed a multiple logistic regression analysis to estimate the relationship between subjective job stress and mental health, adjusting for gender, age, marital state, familial stress, and physical health state. Subjective job stress was significantly associated with the state of mental health. In particular, the items of "too much trouble at work," "too much responsibility," "are not allowed to make mistakes," "poor relationship with superiors," and "cannot keep up with technology" were significantly related to mental health.

[Family intervention for schizophrenia based on expressed emotion (EE) research: a review of the technique and evaluation].

The present study reviews eight series of trials on psycho-social family intervention for schizophrenia based on Expressed Emotion (EE). All studies used randomized controlled trials (RCT) except one which was non-randomized controlled trial. The relapse risk ratios (intervention/control) for 9-12 months after discharge were 0 to .73 and for 24 months were .20 to .57. Taking into account the shortcomings of the studies, the authors conclude that psycho-social family intervention based on EE is effective in preventing schizophrenic relapse, and discuss four important issues: 1) For effective family intervention, methods for Japanese patients should be established from a trans-cultural view point; 2) The interaction of two or more therapeutic measures should be evaluated quantitatively; 3) The mechanisms of schizophrenic relapse prevention through family psycho-social intervention should be explored. A psycho-physiological study including skin conductance measurement is promising; 4) The authors point out the ethical aspect of family intervention, and discuss the importance of informed consent and the need to place emphasis on family's needs.

[An epidemiologic research design using the Annual of the Pathological Autopsy Cases in Japan].

Epidemiologic research designs using the Annual of the Pathological Autopsy Cases in Japan (APAC hereinafter) are discussed in this paper. The APAC data base has been recommended for use in epidemiologic research. However, it has not often been utilized for such research, even though it covers all pathological autopsy cases in Japan, perhaps because of different sampling proportions of each disease and because of the dead control series in APAC. First, we present epidemiologic measures in using the APAC. We show that the data base can be treated as a case-control design and that the magnitude of the exposure effect should be estimated by an odds ratio. Next, selection bias and information bias in using the APAC are discussed. The independence of the control series from the exposure is important in the determination of the control disease. Because this design is based on internal comparison, non-differential misclassification should be stressed more than differential misclassification.

High-performance liquid chromatographic studies on non-mercapt in equilibrium with mercapt conversion of human serum albumin. II.

High-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) on a GS-520 column with 0.03 M sodium phosphate buffer-0.15 M sodium sulphate (pH 6.87) showed three peaks, the principal component corresponding to human mercaptalbumin (HMA) and the secondary and tertiary components to nonmercaptalbumin (HNA). Using HPLC analysis, the nonmercapt----mercapt conversion of HSA during haemodialysis and the mercapt----nonmercapt conversion after haemodialysis in chronic renal failure were re-confirmed, indicating that HMA is a covalent carrier protein for sulphur-containing amino acids. Fractions of HMA in various liver diseases were significantly lower than those of healthy male adults.