Mistaken information can lead only to misguided conclusions and policies: a commentary regarding Schüz et al.'s response.

BACKGROUND: After reviewing selected scientific evidence, Schüz et al. made two recommendations in the 2018 International Agency for Research on Cancer (IARC) Technical Publication No. 46. Their first recommendation was against population thyroid screening after a nuclear accident, and the second was that consideration be given to offering a long-term thyroid monitoring program for higher-risk individuals (100-500 mGy or more radiation) after a nuclear accident. However, their review of the scientific evidence was inadequate and misrepresented the information from both Chernobyl and Fukushima. We wrote a review article published in Environmental Health in 2022 using the "Toolkit for detecting misused epidemiological methods." Schüz et al. critiqued our 2022 review article in 2023; their critique, based also on their 2018 IARC Technical Publication No. 46, was so fraught with problems that we developed this response. MAIN BODY: Schüz et al. suggest that hundreds of thyroid cancer cases in children and adolescents, detected through population thyroid examinations using ultrasound echo and conducted since October 2011 in Fukushima, were not caused by the 2011 Fukushima Daiichi Nuclear Power Plant accident. Schüz et al. compared thyroid cancers in Fukushima directly with those in Chernobyl after April 1986 and listed up to five reasons to deny a causal relationship between radiation and thyroid cancers in Fukushima; however, those reasons we dismiss based on available evidence. No new scientific evidence was presented in their response to our commentary in which we pointed out that misinformation and biased scientific evidence had formed the basis of their arguments. Their published article provided erroneous information on Fukushima. The article implied overdiagnosis in adults and suggested that overdiagnosis would apply to current Fukushima cases. The IARC report did not validate the secondary confirmatory examination in the program which obscures the fact that overdiagnosis may not have occurred as much in Fukushima. The report consequently precluded the provision of important information and measures. CONCLUSION: Information provided in the IARC Technical Publication No. 46 was based on selected scientific evidence resulting in both public and policy-maker confusion regarding past and present nuclear accidents, especially in Japan. It should be withdrawn.

A population-based longitudinal study on glycated hemoglobin levels and new-onset chronic kidney disease among non-diabetic Japanese adults.

Chronic kidney disease (CKD) is a major global public health problem. Recent studies reported that diabetes and prediabetes are risk factors for developing CKD; however, the exact glycated hemoglobin (HbA1c) cut-off value for prediabetes remains controversial. In this study, we aimed to examine the relationship between HbA1c levels and subsequent CKD development in greater detail than previous studies. Longitudinal data of annual checkups of 7176 Japanese non-diabetic people (male: 40.4%) from 1998 to 2022 was analyzed. HbA1c values were categorized into < 5.0%, 5.0-5.4%, 5.5-5.9%, and 6.0-6.4%. CKD was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m2. The descriptive statistics at study entry showed that higher HbA1c values were associated with male, older, overweight or obese, hypertensive, or dyslipidemic people. During a mean follow-up of 7.75 person-years, 2374 participants (male: 40.0%) developed CKD. The Weibull accelerated failure time model was selected because the proportional hazards assumption was violated. The adjusted time ratios of developing CKD for HbA1c levels of 5.5-5.9% and 6.0-6.4% compared with 5.0-5.4% were 0.97 (95% confidence interval: 0.92-1.03) and 1.01 (95% confidence interval: 0.90-1.13), respectively. There was no association between HbA1c in the prediabetic range and subsequent CKD development.

Diarrhea and related personal characteristics among Japanese university students studying abroad in intermediate- and low-risk countries.

Despite an increasing number of students studying abroad worldwide, evidence about health risks while they are abroad is limited. Diarrhea is considered the most common travelers' illness, which would also apply to students studying abroad. We examined diarrhea and related personal characteristics among Japanese students studying abroad. Japanese university students who participated in short-term study abroad programs between summer 2016 and spring 2018 were targeted (n = 825, 6-38 travel days). Based on a 2-week-risk of diarrhea (passing three or more loose or liquid stools per day) among travelers by country, the destination was separated into intermediate- and low-risk countries. After this stratification, the associations between personal characteristics and diarrhea during the first two weeks of their stay were evaluated using logistic regression models. Among participants in intermediate-risk countries, teenagers, males and those with overseas travel experience were associated with an elevated risk of diarrhea; the odds ratios (95% confidence intervals) were 2.42 (1.08-5.43) for teenagers (vs. twenties), 1.93 (1.08-3.45) for males (vs. females) and 2.37 (1.29-4.33) for those with overseas experience (vs. none). Even restricting an outcome to diarrhea during the first week did not change the results substantially. The same tendency was not observed for those in the low-risk countries. Teenage students, males and those with overseas travel experience should be cautious about diarrhea while studying abroad, specifically in intermediate-risk countries.

Demonstrating the undermining of science and health policy after the Fukushima nuclear accident by applying the Toolkit for detecting misused epidemiological methods.

It is well known that science can be misused to hinder the resolution (i.e., the elimination and/or control) of a health problem. To recognize distorted and misapplied epidemiological science, a 33-item "Toolkit for detecting misused epidemiological methods" (hereinafter, the Toolkit) was published in 2021. Applying the Toolkit, we critically evaluated a review paper entitled, "Lessons learned from Chernobyl and Fukushima on thyroid cancer screening and recommendations in the case of a future nuclear accident" in Environment International in 2021, published by the SHAMISEN (Nuclear Emergency Situations - Improvement of Medical and Health Surveillance) international expert consortium. The article highlighted the claim that overdiagnosis of childhood thyroid cancers greatly increased the number of cases detected in ultrasound thyroid screening following the 2011 Fukushima nuclear accident. However, the reasons cited in the SHAMISEN review paper for overdiagnosis in mass screening lacked important information about the high incidence of thyroid cancers after the accident. The SHAMISEN review paper ignored published studies of screening results in unexposed areas, and included an invalid comparison of screenings among children with screenings among adults. The review omitted the actual state of screening in Fukushima after the nuclear accident, in which only nodules > 5 mm in diameter were examined. The growth rate of thyroid cancers was not slow, as emphasized in the SHAMISEN review paper; evidence shows that cancers detected in second-round screening grew to more than 5 mm in diameter over a 2-year period. The SHAMISEN consortium used an unfounded overdiagnosis hypothesis and misguided evidence to refute that the excess incidence of thyroid cancer was attributable to the nuclear accident, despite the findings of ongoing ultrasound screening for thyroid cancer in Fukushima and around Chernobyl. By our evaluation, the SHAMISEN review paper includes 20 of the 33 items in the Toolkit that demonstrate the misuse of epidemiology. The International Agency for Research on Cancer meeting in 2017 and its publication cited in the SHAMISEN review paper includes 12 of the 33 items in the Toolkit. Finally, we recommend a few enhancements to the Toolkit to increase its utility.

Association of early daycare attendance with allergic disorders in children: a longitudinal national survey in Japan.

The association between early daycare attendance and risk of allergic diseases remains inconclusive. Therefore, we examined the association among Japanese children on a long-term basis using a nationwide longitudinal survey data. We estimated the association between daycare attendance at age 6 or 18 months and allergy development using information on outpatient visits for atopic dermatitis (AD), food allergy (FA), and asthma and admission for asthma up to 12 years of age as a proxy for developing these diseases, with multilevel logistic regression. Early daycare attendance was associated with increased odds of AD at ages 2.5-3.5 years: the adjusted odds ratio (OR) was 1.34 [95% CI: 1.21, 1.47]. The association with FA was equivocal. The odds of asthma was increased before age 3.5 years and afterwards decreased: the adjusted ORs were 1.60 [1.44, 1.77] for ages 1.5-2.5 years and 0.77 [0.69, 0.87] for ages 5.5-7 years. The effect of early daycare attendance depends on the type of allergies.

Combined effects of body mass index and unhealthy behaviors on disability in older Japanese adults: the Okayama study.

BACKGROUND: Body mass index (BMI) is a significant predictor of functional disability in older adults. However, when evaluated, the association between BMI and incident functional disability, considering behaviors only as covariates or not, may not be appropriate. The primary purpose of the study was to investigate the combined effects of BMI and unhealthy behaviors on the risk of incident functional disability. METHODS: This was a retrospective cohort study that took place in Okayama City, Japan. Data on BMI and unhealthy behaviors were obtained using the health check-up questionnaire. The certification of Long-Term Care Insurance was used to measure functional disability. Cox proportional hazard models were used; adjusted hazard ratios (HRs) with 95% confidence interval (CI) were calculated for incidence of functional disability across categories of BMI and number of unhealthy behaviors. RESULTS: The relationship between BMI and incident functional disability was U-shaped (HR = 1.18, 95% CI [1.11-1.25], among the underweight range; and 1.26 [1.19-1.34] among the obesity range), and its risk was significantly higher within the normal-to-overweight range of BMI values with co-occurring unhealthy behaviors (with normal weight range and one, 1.17 [1.01-1.21]; two, 1.29 [1.18-1.41]; and three or four unhealthy behaviors 1.38 [1.24-1.54]; as well as among overweight range and one, 1.16 [1.05-1.27]; two, 1.26 [1.15-1.38]; and three or four unhealthy behaviors, 1.47 [1.31-1.64]). In each BMI category, the risk of incident functional disability increased with increasing number of unhealthy behaviors (p < 0.05 for linear tread), with the highest risk (1.87 [1.58-2.20]) occurring in combination with at least three unhealthy behaviors with BMI ≥ 27.5, for both sexes (2.20 [1.64-2.92] in men and 1.66 [1.35-2.04] in women). CONCLUSION: It is necessary to consider the combined effects of BMI and behaviors on incident functional disability. Furthermore, interventions targeting multiple behaviors should be considered as such interventions may offer greater benefits than simple interventions.

Alcohol consumption and incident dementia in older Japanese adults: The Okayama Study.

AIM: To evaluate the association between the amount and frequency of alcohol consumption and incident dementia in older Japanese adults using large sample size data over a long follow-up period. METHODS: This was a retrospective cohort study carried out in Japan. A total of 53 311 older adults were followed from 2008 to 2014. A health checkup questionnaire was used to assess the amount and frequency of alcohol consumption. The Dementia Scale of long-term care insurance was used as a measure of incident dementia. Cox proportional hazards models were used to calculate adjusted hazard ratios, with their 95% confidence intervals, for the incidence of dementia across the categories of alcohol consumption by sex. RESULTS: During a 7-year follow-up period, 14 479 participants were regarded as having incident dementia. Compared with non-drinkers, the multivariate adjusted hazard ratios for participants with alcohol consumption ≤2 units per day, occasionally (0.88, 95% CI 0.81-0.96 in men and 0.84, 95% 0.79-0.90 in women) and daily (0.79, 95% 0.73-0.85 in men and 0.87, 95% 0.78-0.97 in women) were statistically significant, and the difference between occasional and daily consumption was only statistically significant in men; however, for participants with alcohol consumption >2 units per day, occasionally (0.91, 95% 0.71-1.16 in men and 1.09, 95% 0.72-1.67 in women) and daily (0.89, 95% 0.81-1.00 in men and 1.16, 95% 0.84-1.81 in women) were not significant. CONCLUSIONS: Alcohol consumption of ≤2 units per day, occasionally or daily, could reduce the risk of incident dementia, with greater benefit for men with such daily consumption. Geriatr Gerontol Int 2019; 19: 740-746.

Physical activity and incident dementia in older Japanese adults: The Okayama study.

OBJECTIVE: To evaluate the association between regular physical activity and the risk of incident dementia in older Japanese adults. METHODS: This was a retrospective cohort study performed in Okayama City, Japan. Overall, 51 477 older Japanese adults were followed from 2008 to 2014. A health checkup questionnaire was used to assess regular physical activity. The Dementia Scale of long-term care insurance was used as a measure of incident dementia. Cox proportional hazard models were used to calculate adjusted hazard ratios, with their 95% confidence intervals, for the incidence of dementia across the categories of physical activity. RESULTS: During a 7-year follow-up, 13 816 subjects were considered as having incident dementia. Compared with participants who performed physical activity less than or equal to one time per week, the multivariate adjusted hazard ratio values (95% confidence intervals) for participants who performed physical activity greater than or equal to two times per week but not every day and those who performed physical activity every day were 0.79 (0.75-0.84) and 0.94 (0.89-0.98), respectively. The interaction of physical activity and sex was statistically significant (P < .01). In subgroup analysis, the multivariate-adjusted hazard ratio values (95% confidence intervals) remained low, at 0.76 (0.70-0.84) in males and 0.81 (0.76-0.87) in females who performed physical activity greater than or equal to two times per week but not every day; they were 0.82 (0.76-0.89) in males and 1.01 (0.95-1.07) in females who performed physical activity every day. CONCLUSIONS: Regular physical activity could reduce the risk of incident dementia in older Japanese adults, except females who performed physical activity every day.

Diarrhea and related factors among passengers on world cruises departing from Japan.

BACKGROUND: Despite growth in the number of cruises worldwide, evidence about diarrhea experienced by cruise ship passengers remains sparse. We investigated rates of diarrhea and related factors among passengers on world cruises departing from Japan. METHODS: Targeting passengers on five world cruises (n = 4180) from 2012 to 2013 (85-103 travel days), we calculated rates of health seeking behavior for diarrhea by sex, age group, and number of roommates for each cruise. We estimated rate ratios and 95% confidence intervals, using the group aged 20-39 years, women, and 2-4 roommates as referent categories. RESULTS: We found 5.04-6.00 cases per 10,000 person-days in the five cruises, with an elevated number after calling at ports. Older passengers (>60 years) and passengers with fewer roommates had an elevated risk of health seeking behavior for diarrhea, although passengers aged <20 years had an elevated risk on one cruise. After controlling for covariates (including cruise), significant associations remained for passengers aged >60 years and without roommates. CONCLUSIONS: Older passengers and passengers with fewer roommates may be more likely to seek medical treatment for diarrhea during travel on a world cruise, and should take preventive measures.

Covariate balance for no confounding in the sufficient-cause model.

PURPOSE: To show conditions of covariate balance for no confounding in the sufficient-cause model and discuss its relationship with exchangeability conditions. METHODS: We consider the link between the sufficient-cause model and the counterfactual model, emphasizing that the target population plays a key role when discussing these conditions. Furthermore, we incorporate sufficient causes within the directed acyclic graph framework. We propose to use each of the background factors in sufficient causes as representing a set of covariates of interest and discuss the presence of covariate balance by comparing joint distributions of the relevant background factors between the exposed and the unexposed groups. RESULTS: We show conditions for partial covariate balance, covariate balance, and full covariate balance, each of which is stronger than partial exchangeability, exchangeability, and full exchangeability, respectively. This is consistent with the fact that the sufficient-cause model is a "finer" model than the counterfactual model. CONCLUSIONS: Covariate balance is a sufficient, but not a necessary, condition for no confounding irrespective of the target population. Although our conceptualization of covariate imbalance is closely related to the recently proposed counterfactual-based definition of a confounder, the concepts of covariate balance and confounder should be clearly distinguished.

Evaluating the Effects of Air Pollution from a Plastic Recycling Facility on the Health of Nearby Residents.

We evaluated how exposure to airborne volatile organic compounds emitted from a plastic recycling facility affected nearby residents, in a cross-sectional study. Individuals>10 years old were randomly sampled from 50 households at five sites and given questionnaires to complete. We categorized the subjects by distance from the recycling facility and used this as a proxy measure for pollutant exposure. We sought to improve on a preceding study by generating new findings, improving methods for questionnaire distribution and collection, and refining site selection. We calculated the odds of residents living 500 or 900 m away from the facility reporting mucocutaneous and respiratory symptoms using a reference group of residents 2,800 m away. Self-reported nasal congestion (odds ratio=3.0, 95% confidence interval=1.02-8.8), eczema (5.1, 1.1-22.9), and sore throat (3.9, 1.1-14.1) were significantly higher among residents 500 m from the facility. Those 900 m away were also considerably more likely to report experiencing eczema (4.6, 1.4-14.9). Air pollution was found responsible for significantly increased reports of mucocutaneous and respiratory symptoms among nearby residents. Our findings confirm the effects of pollutants emitted from recycling facilities on residents' health and clarify that study design differences did not affect the results.

Ethical Issues Related to the Promotion of a "100 mSv Threshold Assumption" in Japan after the Fukushima Nuclear Accident in 2011: Background and Consequences.

PURPOSE OF REVIEW: This article describes the debates in Japan regarding the 100 mSv threshold assumption and ethical issues related to it, and explores the background to distorted risk information and absence of risk communication in Japan. Then we seek proper risk communication based on scientific evidence. RECENT FINDINGS: On March 11, 2011 an accident occurred at the Fukushima Daiichi Nuclear Power Plant due to the Great East Japan Earthquake. Since then a number of misunderstandings have become common in Japan as a result of public statements by the Japanese and local governments that have no basis in medical science or are contradictory to medical science. Consequently, not only the population of Fukushima Prefecture, but also others, have been subjected to unnecessary exposure to radiation, against the As Low As Reasonably Achievable (ALARA) principle. The number of cases of thyroid cancer has increased by one or two orders of magnitude since the accident in Fukushima. However, the population has hardly been given any correct information from the central and local governments, medical societies, and media. The center of this problem is a statement on radiation-induced cancer (including thyroid cancer) made by the Japanese Government and Japanese medical academic societies indicating that "exposure of less than 100 mSv gives rise to no excess risk of cancer, and even if there is some resulting cancer it will be impossible to detect it" (this will be referred to as "the 100 mSv threshold assumption" from now onward). They have been saying this since April 2011 and have made no effort to correct it. Many Japanese began to notice this but correct information on radiation protection has reached only one part of the population. Risk communication should be based on scientific evidence, and providing it as information for the public is a key element. In Japan, governments and academic societies tried to communicate with the public without doing it. Ethical problems after the accident in Fukushima can be understood from the consequences of the mistakes in both risk information and risk communication in Japan after 2011.

A typology of four notions of confounding in epidemiology.

Confounding is a major concern in epidemiology. Despite its significance, the different notions of confounding have not been fully appreciated in the literature, leading to confusion of causal concepts in epidemiology. In this article, we aim to highlight the importance of differentiating between the subtly different notions of confounding from the perspective of counterfactual reasoning. By using a simple example, we illustrate the significance of considering the distribution of response types to distinguish causation from association, highlighting that confounding depends not only on the population chosen as the target of inference, but also on the notions of confounding in distribution and confounding in measure. This point has been relatively underappreciated, partly because some literature on the concept of confounding has only used the exposed and unexposed groups as the target populations, while it would be helpful to use the total population as the target population. Moreover, to clarify a further distinction between confounding "in expectation" and "realized" confounding, we illustrate the usefulness of examining the distribution of exposure status in the target population. To grasp the explicit distinction between confounding in expectation and realized confounding, we need to understand the mechanism that generates exposure events, not the product of that mechanism. Finally, we graphically illustrate this point, highlighting the usefulness of directed acyclic graphs in examining the presence of confounding in distribution, in the notion of confounding in expectation.

Is there an obesity paradox in the Japanese elderly population? A community-based cohort study of 13 280 men and women.

AIM: Despite increased interest in an obesity paradox (i.e. a survival advantage of being obese), evidence remains sparse in Japanese populations. We aimed to verify this phenomenon among community-dwelling older adults in Japan. METHODS: Older adults aged 65-84 years randomly chosen from all 74 municipalities in Shizuoka Prefecture completed questionnaires including body mass index information. Participants were followed from 1999 to 2009. Following World Health Organization guidelines, participants were classified using an appropriate body mass index for Asian populations as follows: <18.5 kg/m2 (underweight), 18.5-23.0 kg/m2 (normal weight), 23.0-27.5 kg/m2 (overweight) and ≥27.5 kg/m2 (obesity). We estimated hazard ratios and their 95% confidence intervals for all-cause mortality, controlling for sex, age, smoking status, alcohol consumption, physical activity, hypertension and diabetes mellitus. RESULTS: Compared with normal-weight participants, overweight/obese participants tended to have lower hazard ratios; the multivariate hazard ratios (95% confidence interval) were 0.86 (0.62-1.19) for obesity, 0.83 (0.73-0.94) for overweight and 1.60 (1.40-1.82) for underweight. In subgroup analyses by sex and age, the hazard ratios tended to be lower among obese men, albeit not significantly; hazard ratios (95% confidence interval) were 0.56 (0.25-1.27) in men aged 65-74 years, and 0.78 (0.41-1.45) in men aged 75-84 years. CONCLUSIONS: The present study provides evidence of a conservative obesity paradox among older Japanese people, using the appropriate body mass index cut-off points for Asian populations. In particular, obese older men tend to have a lower risk of all-cause mortality. Geriatr Gerontol Int 2017; 17: 1257-1264.

Maternal smoking location at home and hospitalization for respiratory tract infections among children in Japan.

We examined the effects of maternal smoking location at home on hospitalization for respiratory tract infections among young children in Japan. We used the large nationwide population-based longitudinal survey and restricted study participants to children born after 37 gestational weeks and singleton births (n = 43,851). We evaluated the associations among children between the ages of 6 and 18 months and between the ages of 18 and 30 months, respectively. After adjusting for potential confounders, both maternal outdoor and indoor smoking were associated with the elevated risk. The adjusted odds ratios (95% confidence intervals) of maternal outdoor and indoor smoking (vs nonsmoking mothers) were 1.21 (1.01-1.44) and 1.18 (1.04-1.33), respectively, in children between the ages of 6 and 18 months. We thus encourage a smoke-free home policy to protect children from second- and third-hand smoke exposure.