Concerns about vaccines and vaccination behavior among Japanese budget travelers to India.

BACKGROUND: Low vaccination coverage among travelers poses a critical challenge to global health security. Indeed, public concerns regarding vaccines can lead to vaccine reluctance and refusal, but evidence about the impacts of concerns regarding vaccines on the uptake of travel vaccinations remains sparse. We examined the associations between concerns about vaccines and vaccination behavior among travelers. METHODS: Japanese travelers aged 18 years or older, who stayed at a guesthouse in New Delhi, India, were targeted (n = 153). We conducted cross-sectional surveys from August 23 to September 2, 2019, and from February 19 to March 5, 2020. We examined the associations of three concerns regarding vaccines (5-point scale)-serious side effects from vaccines, vaccine safety, and vaccine effectiveness-with the uptake of travel vaccinations. RESULTS: In total, 60 participants (39.2 %) had been vaccinated for this or a past trip. After adjusting for all potential confounding variables, concerns about serious side effects from vaccines and vaccine safety were negatively associated with the uptake of travel vaccinations. The ORs (95 % CIs) for 1-point increases in concerns about serious side effects from vaccines and vaccine safety were 0.72 (0.52, 0.99) and 0.71 (0.52, 0.96), respectively. Sensitivity analyses did not change the results substantially. CONCLUSIONS: Concerns about vaccine safety issues were negatively associated with the uptake of travel vaccinations among the participants, with no corresponding association observed for vaccine effectiveness. Addressing concerns about vaccine safety issues, rather than vaccine effectiveness may contribute to an increased uptake of travel vaccinations.

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.

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.

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.

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.

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.

Thyroid Cancer Detection by Ultrasound Among Residents Ages 18 Years and Younger in Fukushima, Japan: 2011 to 2014.

BACKGROUND: After the Great East Japan Earthquake and Tsunami in March 2011, radioactive elements were released from the Fukushima Daiichi Nuclear Power Plant. Based on prior knowledge, concern emerged about whether an increased incidence of thyroid cancer among exposed residents would occur as a result. METHODS: After the release, Fukushima Prefecture performed ultrasound thyroid screening on all residents ages ≤18 years. The first round of screening included 298,577 examinees, and a second round began in April 2014. We analyzed the prefecture results from the first and second round up to December 31, 2014, in comparison with the Japanese annual incidence and the incidence within a reference area in Fukushima Prefecture. RESULTS: The highest incidence rate ratio, using a latency period of 4 years, was observed in the central middle district of the prefecture compared with the Japanese annual incidence (incidence rate ratio = 50; 95% confidence interval [CI] = 25, 90). The prevalence of thyroid cancer was 605 per million examinees (95% CI = 302, 1,082) and the prevalence odds ratio compared with the reference district in Fukushima Prefecture was 2.6 (95% CI = 0.99, 7.0). In the second screening round, even under the assumption that the rest of examinees were disease free, an incidence rate ratio of 12 has already been observed (95% CI = 5.1, 23). CONCLUSIONS: An excess of thyroid cancer has been detected by ultrasound among children and adolescents in Fukushima Prefecture within 4 years of the release, and is unlikely to be explained by a screening surge.

Aflatoxins in Rice Artificially Contaminated with Aflatoxin-producing Aspergillus flavus under Natural Storage in Japan.

Aflatoxin (AFT) contamination is frequent in foods grown in tropical regions, including rice. Although AFTs are generally not found in temperate-region foods, global warming has affected typical temperate-region climates, potentially permitting the contamination of foods with AFT-producing Aspergillus flavus (A. flavus). Here we investigated the AFT production in rice during storage under natural climate conditions in Japan. We examined AFTs in brown rice and rough rice artificially contaminated with A. flavus for 1 year in Japan, and we subjected AFTs in white rice to the same treatment in airtight containers and examined the samples in warm and cold seasons, simulating the storage of white rice in general households. In the brown rice, AFTs increased after 2 months (March) and peaked after 9 months (October). The AFT contamination in the rough rice was minimal. After the polishing and cooking of the brown rice, AFTs were undetectable. In the white rice stored in airtight containers, AFTs increased after 1 month (August) and peaked after 2 months (September). Minimal AFTs were detected in the cold season. Thus, AFT contamination in rice may occur in temperate regions following A. flavus contamination. The storage of rice as rough rice could provide be useful for avoiding AFT contamination.

Cancer and non-cancer excess mortality resulting from mixed exposure to polychlorinated biphenyls and polychlorinated dibenzofurans from contaminated rice oil: "Yusho".

PURPOSE: In 1968, rice oil contaminated with polychlorinated biphenyls and polychlorinated dibenzofurans caused a severe outbreak of food poisoning in Japan and was termed locally as "Yusho" (oil disease). In our previous study, we found that area-based standardized mortality ratios (SMRs) of some diseases were elevated shortly after the incident. This previous study, however, was unable to determine whether these elevated SMRs were a result of other area-specific factors. To overcome this limitation, we obtained mortality data from the 5 years before the incident and conducted an area-based study using vital statistics records dating from 1963 to 2002. METHODS: The population of Nagasaki Prefecture was set as the reference population for calculating SMRs. We also included data on cause-specific mortality attributable to cancer and expanded the population to encompass two severely exposed areas where contaminated rice oil was distributed (namely Tamanoura and Naru). We also calculated SMRs in the remainder of the Shimo-Goto region, excluding the exposed area, which was used as a comparison area. RESULTS: Even after considering the time trends in mortality before the incident, mortality due to diabetes mellitus and heart disease, as well as all-cause mortality, was found to be elevated shortly afterward. Additionally, mortalities due to uterine cancer in Tamanoura and leukemia were also elevated at 30-34 and 10-59 years after the event in both exposed areas, respectively. SMRs for leukemia in Tamanoura were as high as 3.0 (95% confidence interval 1.4-6.2) and 2.4 (1.2-4.8) 10-19 years later. In this period, SMRs for leukemia in the comparison area were not elevated. CONCLUSIONS: Further epidemiological studies are needed regarding this rice-oil, "Yusho" outbreak, especially with regard to cancer and non-cancer mortality.

Long-Term Effects of Breastfeeding on Children's Hospitalization for Respiratory Tract Infections and Diarrhea in Early Childhood in Japan.

Whether or not the protective effects of breastfeeding last during or after a shift to a weaning diet is not clear. In the present study, we examined the effects of breastfeeding on hospitalization for respiratory tract infections and diarrhea in early childhood in Japan. Data were extracted from a nationwide longitudinal survey of Japanese children. We restricted the study participants to singleton children who were born after 37 gestational weeks and whose information on feeding practice during infancy were included (n = 43,367). We used logistic regression models to evaluate the associations of breastfeeding with hospitalization for the two diseases among young children (i.e., between ages 6 and 18 months, between ages 18 and 30 months, and between ages 30 and 42 months, respectively), adjusting for children's factors (sex, birth weight, childcare attendance and presence of siblings) and maternal factors (educational attainment and smoking status). Breastfeeding compared with infant formula was not associated with reduced risk of hospitalization for diarrhea during the periods we examined. Although breastfeeding was not associated with reduced risk of hospitalization for respiratory tract infections between ages 6 and 18 months, breastfeeding showed protective effects after that period: the adjusted odds ratios (95% confidence intervals) of exclusive breastfeeding were 0.82 (0.66-1.01) between ages 18 and 30 months and 0.76 (0.58-0.99) between ages 30 and 42 months. Breastfeeding may have long-term protective effects on hospitalization for respiratory tract infections after infancy, but not for diarrhea.

A counterfactual approach to bias and effect modification in terms of response types.

BACKGROUND: The counterfactual approach provides a clear and coherent framework to think about a variety of important concepts related to causation. Meanwhile, directed acyclic graphs have been used as causal diagrams in epidemiologic research to visually summarize hypothetical relations among variables of interest, providing a clear understanding of underlying causal structures of bias and effect modification. In this study, the authors aim to further clarify the concepts of bias (confounding bias and selection bias) and effect modification in the counterfactual framework. METHODS: The authors show how theoretical data frequencies can be described by using unobservable response types both in observational studies and in randomized controlled trials. By using the descriptions of data frequencies, the authors show epidemiologic measures in terms of response types, demonstrating significant distinctions between association measures and effect measures. These descriptions also demonstrate sufficient conditions to estimate effect measures in observational studies. To illustrate the ideas, the authors show how directed acyclic graphs can be extended by integrating response types and observed variables. RESULTS: This study shows a hitherto unrecognized sufficient condition to estimate effect measures in observational studies by adjusting for confounding bias. The present findings would provide a further understanding of the assumption of conditional exchangeability, clarifying the link between the assumptions for making causal inferences in observational studies and the counterfactual approach. The extension of directed acyclic graphs using response types maintains the integrity of the original directed acyclic graphs, which allows one to understand the underlying causal structure discussed in this study. CONCLUSIONS: The present findings highlight that analytic adjustment for confounders in observational studies has consequences quite different from those of physical control in randomized controlled trials. In particular, the present findings would be of great use when demonstrating the inherent distinctions between observational studies and randomized controlled trials.

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.

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.

On the relations between excess fraction, attributable fraction, and etiologic fraction.

It has been noted that there is ambiguity in the expression "attributable fraction," and epidemiologic literature has drawn a distinction between "excess fraction" and "etiologic fraction." These quantities do not necessarily approximate one another, and the etiologic fraction is not generally estimable without strong biologic assumptions. In previous studies, researchers have explained the relations between excess and etiologic fractions in the potential-outcome framework, and few authors have explained the relations between these concepts by showing the correspondence between the potential-outcome model and the sufficient-cause model. In this article, the authors thoroughly clarify the conceptual relations between excess, attributable, and etiologic fractions by explicating the correspondence between these 2 models. In so doing, the authors take into account the potential completion time of each sufficient cause, which contributes to further insight to clarify the 2 types of etiologic fraction, i.e., accelerating etiologic proportion and total etiologic proportion. These 2 measures cannot be distinguished in epidemiologic data, and the differences might be subtle. However, they are closely related to a very fundamental issue of causal inference, that is, how researchers define etiology. Further, the authors clarify the relation between 3 distinct assumptions-positive monotonicity, no preventive action (or sufficient-cause positive monotonicity), and no preventive sequence.

Methyl mercury exposure at Niigata, Japan: results of neurological examinations of 103 adults.

BACKGROUND: Large-scale poisonings caused by methyl mercury (MeHg) have occurred in Japan (Minamata in the 1950s and Niigata in the 1960s) and Iraq (in the 1970s). The current WHO neurological risk standard for adult exposure (hair level: 50 µg/g) was based partly on evidence from Niigata which did not consider any cases who were diagnosed later and/or exposed to low level of MeHg (hair mercury level less than 50 µg/g). METHODS: Early in the Niigata epidemic in June 1965 there were two extensive surveys. From these two surveys, we examined 103 adults with hair mercury measurement who consulted two medical institutions. We compared the prevalence and the distribution of neurological signs related to MeHg poisoning between exposure categories. RESULT: We found 48 subjects with neurological signs related to MeHg poisoning who had hair mercury concentration less than 50 µg/g. Among the neurological signs, sensory disturbance of the bilateral distal extremities was observed more frequently, followed by disequilibrium, hearing impairment, and ataxia, in groups with hair MeHg concentration both below 50 µg/g and over 50 µg/g. CONCLUSION: The present study suggests the possibility that exposure to MeHg at levels below the current WHO limits could cause neurologic signs, in particular, sensory disturbance.

Asian dust and daily all-cause or cause-specific mortality in western Japan.

OBJECTIVE: Desert dust, which is included in course particles, is considered to have potential toxicity. The effect modification of desert dust on associations between anthropogenic air pollution and mortality has been evaluated. However, the independent effects of Asian dust are less clear. Thus, we evaluated the effects of Asian dust on mortality independent of particulate matter (PM) in western Japan. METHODS: We obtained daily mean concentrations of Asian dust using Light Detection and Ranging measurements and suspended particulate matter (SPM) concentrations (approximately PM(8)) during March 2005 to December 2010. We then evaluated city-specific associations of Asian dust and SPM with daily mortality using a time-series analysis targeting 1 379 052 people aged 65 or above living in 47 cities. The city-specific results were then combined with a Bayesian-hierarchical model. RESULTS: Asian dust did not modify the effects of SPM on mortality. Meanwhile, Asian dust was adversely associated with mortality independent of SPM. The excess risk following a 10 µ/m(3) increase in mean of the current to the previous 2 days Asian dust concentration was 0.6% (95% CI 0.1 to 1.1) for heart disease, 0.8% (95% CI 0.1 to 1.6) for ischaemic heart disease, 2.1% (95% CI 0.3 to 3.9) for arrhythmia and 0.5% (95% CI 0.2 to 0.8) for pneumonia mortality. Furthermore, the effects of Asian dust were stronger in northern areas close to the Eurasian continent (source of Asian dust). CONCLUSIONS: Asian dust had adverse effects on circulatory and respiratory mortality independent of PM.

Frequency of antenatal care visits and neonatal mortality in Indonesia.

OBJECTIVE: To examine the relationship between frequency of antenatal care visits, as a whole and in each trimester, and neonatal mortality in Indonesia. SUBJECTS: 13 055 single births from the fifth Indonesia Demographic Health Survey in 2006-07. METHODS: Estimate adjusted odds ratios (ORs) and their 95% confidence intervals (95% CIs). RESULTS: Pregnant women who had more antenatal care visits experienced a lower risk of neonatal mortality and more benefit in the last trimester: the ORs against the 0-1 visit group, were 0.76 (95% CI 0.45-1.29) for 2 visits group, 0.54 (95% CI 0.33-0.87) for 3 visits group and 0.31 (95% CI 0.17-0.57) for 4 visits group, respectively. Individual ORs as a whole period were not significant, but ORs declined markedly at 7 visits or more. CONCLUSION: The results may provide a valuable recommendation for the care of pregnant women in Indonesia.

[Ingestion of contaminated foods and drinks and internal radiation].

Many international agencies have evaluated radiation effects to humans. However, reports on effects of international radiation are not so many. Internal exposure of radiation depends on both physical and chemical properties of the radioactive material. Therefore, we combine several methods for the exposure estimation, including environmental measurements and questionnaires to individual subjects. Then, we must select quantitative effect estimates from actual case examples of internal radiation including all age strata, especially children. Among the residents exposed to radiation from the Chernobyl accident in 1986, increased incidence of thyroid cancer and leukemia has been reported. Quantitative effect estimates were also presented in some of the reports. The estimates may be also useful for individual protection for the Fukushima case.