Tehran environmental and neurodevelopmental disorders (TEND) cohort study: Phase I, feasibility assessment.

PURPOSE: To advance knowledge about childhood neurodevelopmental disorders and study their environmental determinants, we conducted a study in Tehran, Iran to assess the feasibility of prospective birth cohort study. METHODS: We evaluated participation of pregnant women, feasibility of sampling biological material, and health care services availability in Tehran in four steps: (1) first trimester of pregnancy; (2) third trimester of pregnancy; (3) at delivery; and (4) two to three months after delivery. We collected related data through questionnaires, also various biological samples were obtained from mothers (blood, urine, milk and nails-hands and feet) and newborns (umbilical cord blood, meconium, and urine samples) from February 2016 to October 2017. RESULTS: overall 838 eligible pregnant women were approached. The participation rate was 206(25%) in our study and about 185(90%) of subjects were recruited in hospitals. Out of 206 participants in the first trimester, blood, urine, hand nail, and foot nail samples were collected from 206(100%),193(93%), 205(99%), and 205(99%), respectively. These values dropped to 65(54%), 83(69%), 84(70%), and 84(70%) for the remaining participants 120(58%) in the third trimester, respectively. Also, we gathered milk samples from 125(60%) of mothers at two to three months after delivery. CONCLUSION: Our findings suggest that hospitals were better places for recruitment of subjects in a birth cohort in Tehran. We further concluded that birth cohort study recruitment can be improved by choosing appropriate gestational ages. Obtaining the newborn's urine, meconium, and umbilical cord blood were challenging procedures and require good collaboration between hospital staff and researchers.

Comorbidity status in hospitalized elderly in Japan: Analysis from National Database of Health Insurance Claims and Specific Health Checkups.

The detailed comorbidity status of hospitalized elderly patients throughout Japan has remained largely unknown; therefore, our goal was to rigorously explore this situation and its implications as of the 2015 fiscal year (from April 2015 to March 2016). This study was based on a health insurance claims database, covering all insured policy holders in Japan aged ≥60 years (male: n = 2,135,049, female: 1,969,019) as of the 2015 fiscal year. Comorbidity status was identified by applying principal factor analysis to the database. The factors identified in male patients were [1] myocardial infarction, hypertension, dyslipidemia, and diabetes mellitus; [2] congestive heart failure (CHF), cardiac arrhythmia, and renal failure; [3] Parkinson's disease, dementia, cerebrovascular disease, and pneumonia; [4] cancer and digestive disorders; and [5] rheumatoid arthritis and hip fracture. However, in female patients, the results obtained for the quaternary and quinary factors were the opposite of those obtained in male patients. In superelderly patients, dementia, cerebrovascular disease, and pneumonia appeared as the tertiary factor, and hip fracture and osteoporosis appeared as the quaternary factor. The comorbidities in the elderly patients suggest the importance of coronary heart disease and its related metabolic disorders; in superelderly patients, fracture and osteoporosis appeared as factors, in addition to dementia and pneumonia.

National burden of the pharmaceutical cost of wet compresses and its cost predictors: nationwide cross-sectional study in Japan.

BACKGROUND: Although a high number of wet compresses are prescribed daily in medical institutions in Japan, our understanding of the national burden of the cost of wet compresses and the details regarding their prescription is far from complete. We investigated the national burden of the annual pharmaceutical cost of wet compresses prescribed in Japan and estimated the predictors of this cost using nationwide health insurance claims data. METHODS: We extracted the records on wet compress products from summary table files obtained from the second version of the "NDB Open Data Japan" website and calculated the annual pharmaceutical cost of wet compresses by patients' 5-year age group, sex, and prefecture. We also conducted an ecological study treating each prefecture as an individual unit and multiple linear regression analyses using the age-standardized cost of wet compresses per resident as a dependent variable. RESULTS: The annual pharmaceutical cost of wet compresses prescribed in Japan in fiscal year 2015 was 149.0 billion Japanese yen (1.18 billion euros; 1.33 billion USD). Multiple linear regression analyses showed that the number of orthopedists and rehabilitation physicians per 100,000 residents were significantly positively associated with the annual pharmaceutical cost of wet compresses per resident (P = 0.042 and P = 0.008, respectively). CONCLUSIONS: The annual pharmaceutical cost of wet compresses prescribed in Japan has a considerable impact on the nation's limited healthcare resources. The number of orthopedists and rehabilitation physicians per 100,000 residents may be independent predictors of the wet compress cost in Japan.

For making a declaration of countermeasures against the falling birth rate from the Japanese Society for Hygiene: summary of discussion in the working group on academic research strategy against an aging society with low birth rate.

In 1952, the Japanese Society for Hygiene had once passed a resolution at its 22nd symposium on population control, recommending the suppression of population growth based on the idea of cultivating a healthier population in the area of eugenics. Over half a century has now passed since this recommendation; Japan is witnessing an aging of the population (it is estimated that over 65-year-olds made up 27.7% of the population in 2017) and a decline in the birth rate (total fertility rate 1.43 births per woman in 2017) at a rate that is unparalleled in the world; Japan is faced with a "super-aging" society with low birth rate. In 2017, the Society passed a resolution to encourage all scientists to engage in academic researches to address the issue of the declining birth rate that Japan is currently facing. In this commentary, the Society hereby declares that the entire text of the 1952 proposal is revoked and the ideas relating to eugenics is rejected. Since the Society has set up a working group on the issue in 2016, there have been three symposiums, and working group committee members began publishing a series of articles in the Society's Japanese language journal. This commentary primarily provides an overview of the findings from the published articles, which will form the scientific basis for the Society's declaration. The areas we covered here included the following: (1) improving the social and work environment to balance between the personal and professional life; (2) proactive education on reproductive health; (3) children's health begins with nutritional management in women of reproductive age; (4) workplace environment and occupational health; (5) workplace measures to counter the declining birth rate; (6) research into the effect of environmental chemicals on sexual maturity, reproductive function, and the children of next generation; and (7) comprehensive research into the relationship among contemporary society, parental stress, and healthy child-rearing. Based on the seven topics, we will set out a declaration to address Japan's aging society with low birth rate.

[Socioeconomic Factors and Policies Regarding Declining Birth Rates in Japan].

The factors contributing to the declining birthrate in Japan include the declining marriage rate, an increase in the average age of those getting married, economic burden, childcare burden, later child-bearing, and infertility. There is a gender difference in role division, with 70% of unmarried people live with their parents and continue to work while leaving the household chores to their mothers. The loss of these housekeeping services and the increase in the number of irregular workers are factors contributing to the declining marriage rate and the increase in the average age of those getting married. The expansion of the family support policy in Japan from the male breadwinner model to the earner-career model may have been delayed, but it is expected to provide economic benefits as well as actual childcare service benefits in order to reduce the economic and physical burden of childcare for married couples. It is also necessary to provide education in reproductive health to both men and women in schools and workplaces regarding late child-bearing and infertility. Furthermore, it is necessary to evaluate the cost-effectiveness analysis of improvements in fertility and disclose the relevant information in addition to sharing information on medical technology related to pregnancy/childbirth and treatment of diseases. It is urgent to prepare society for natural and healthy pregnancies/childbirths during optimal child-bearing years.

[Effects of Trace Environmental Chemicals on Child Health-Lead as an Example].

The low birthrate and aging population of Japan are entering a serious phase. As measures against the declining birthrate, improvement of the environment is promoted to support childbirth and child-rearing, but even if the birthrate increases in the future, it will take time before the effect is observed as an increase in the population. As the number of children and young people is decreasing, in order to maintain a wealthy and sustainable society, we should create an environment wherein each child can grow healthily and demonstrate sufficient abilities in participating in society. The authors have been studying the influence of exposure to environmental chemical substances on the development of children. Lead is especially considered to impair neurological development even at low concentrations of exposure. In this paper, using lead as an example, we discuss risk assessment and countermeasures for the health effects of trace chemical substances on a society with a declining birthrate. Substances that show neurotoxicity increase social costs even at low concentrations of exposure. To preserve and promote social vitality in Japan despite the declining birthrate and aging population, it is essential that measures are taken on the basis of scientifically reasonable cost/benefit assessment. For this purpose, we think that it is necessary to analyze costs and benefits in addition to the risk assessment of low concentrations of chemical substances.

Discrepancies Between the Supports Needed for Discharge of Patients With Terminal Cancer to Family Caregivers and What Supports Were Actually Provided in Japan: Assessment of Palliative Care Unit Nurses.

OBJECTIVES: Even if patients with terminal cancer hope to spend the rest of their lives at home, they are often unable to leave the hospital early due to their family caregivers' anxiety. This study aimed to investigate in Japan the discrepancies between the supports needed by and actually provided by palliative care unit nurses (PCUNs) to the family caregivers for discharge of patients with terminal cancer. METHODS: In this cross-sectional study, self-administered questionnaires including 6-point Likert-type scales assessing the reasons for difficulties in transition to home-based care were distributed to 1227 PCUNs. Using paired t tests, the differences between the scores on perceived importance and actual supports to family caregivers were examined. The supports actually provided were classified by factor analysis. The relationships between the PCUNs' characteristics and mean scores on the supports in each category were examined using multiple regression analysis. RESULTS: A total of 1023 (83.4%) completed questionnaires were returned. Scores on the actually provided supports for discharge to family caregivers were consistently and significantly lower than the corresponding scores on perceived importance for all 57 items ( P < .001). Factor analysis revealed that the supports actually provided to the family caregivers had a 4-factor structure. Multiple regression analyses revealed that gaining experience in palliative care, receiving necessary training, cooperating with palliative care staff, and cooperating with local service providers were significantly associated with higher levels of actual supply of supports to family caregivers. CONCLUSION: Our findings suggest that PCUNs need to be encouraged to provide further support to family caregivers for the discharge of patients with terminal cancer.

Risk assessment of skin lightening cosmetics containing hydroquinone.

Following reports on potential risks of hydroquinone (HQ), HQ for skin lightening has been banned or restricted in Europe and the US. In contrast, HQ is not listed as a prohibited or limited ingredient for cosmetic use in Japan, and many HQ cosmetics are sold without restriction. To assess the risk of systemic effects of HQ, we examined the rat skin permeation rates of four HQ (0.3%, 1.0%, 2.6%, and 3.3%) cosmetics. The permeation coefficients ranged from 1.2 × 10-9 to 3.1 × 10-7 cm/s, with the highest value superior than the HQ aqueous solution (1.6 × 10-7 cm/s). After dermal application of the HQ cosmetics to rats, HQ in plasma was detected only in the treatment by highest coefficient cosmetic. Absorbed HQ levels treated with this highest coefficient cosmetic in humans were estimated by numerical methods, and we calculated the margin of exposure (MOE) for the estimated dose (0.017 mg/kg-bw/day in proper use) to a benchmark dose for rat renal tubule adenomas. The MOE of 559 is judged to be in a range safe for the consumer. However, further consideration may be required for regulation of cosmetic ingredients.

Cost-benefit analysis of comprehensive mental health prevention programs in Japanese workplaces: a pilot study.

We examined the implementation of mental health prevention programs in Japanese workplaces and the costs and benefits. A cross-sectional survey targeting mental health program staff at 11 major companies was conducted. Questionnaires explored program implementation based on the guidelines of the Japanese Ministry of Health, Labor and Welfare. Labor, materials, outsourcing costs, overheads, employee mental discomfort, and absentee numbers, and work attendance were examined. Cost-benefit analyses were conducted from company perspectives assessing net benefits per employee and returns on investment. The surveyed companies employ an average of 1,169 workers. The implementation rate of the mental health prevention programs was 66% for primary, 51% for secondary, and 60% for tertiary programs. The program's average cost was 12,608 yen per employee and the total benefit was 19,530 yen per employee. The net benefit per employee was 6,921 yen and the return on investment was in the range of 0.27-16.85. Seven of the 11 companies gained a net benefit from the mental health programs.

Estimates of annual medical costs of work-related low back pain in Japan.

Little is reported regarding economic burden of work-related low back pain except for the United States. In the present study, annual medical cost of work-related low back pain in Japan was calculated based on the treatment fee per day, a total of days of treatment received for low-back pain of all causes, employment rates, and an estimated number of work-related low-back cases. The analysis indicated that, in 2011, the total annual medical cost for work-related low back pain was 82.14 billion yen, consisting of 26.48 and 55.66 billion yen for inpatients and outpatients, respectively. As well as for 2011, the costs were also estimated for 2008, 2005, and 2002. Whereas the total medical costs of work-related low back pain monotonically increased during 2002-2011, the costs for spine disorder (including spondylosis) have also increased in recent years. Work-related low back pain entails a considerable economic burden to Japanese society.

Cross-sectional study on the effects of socioeconomic factors on lead exposure in children by gender in Serpong, Indonesia.

To elucidate the socioeconomic factors influencing lead exposure in elementary school children by gender, 108 children (56 male, 52 female), aged 6-7 years, were randomly selected from 39 elementary state schools in Serpong, Banten, Indonesia. Their parents were interviewed to obtain information on sociodemographic characteristics. Their blood lead (BPb) levels were measured by atomic absorption spectrophotometry. BPb concentrations were significantly higher in males than in females, i.e., 6.8 ± 2.0 (2.9-12.5) µg/dL and 5.9 ± 1.9 (3.1-11.7) µg/dL, respectively (p < 0.05). Lower socioeconomic status and well water use were associated with increased BPb concentrations, especially in females. The proportion of well water use was related to lower socioeconomic status. Lower socioeconomic status linked with well water drinking seemed to be associated with increased lead exposure in children in Serpong. Their exposure levels possibly varied according to gender differences in behavior. An intervention should be instituted among children in Serpong with BPb concentrations of 10 µg/dL or above.

Components of social capital and socio-psychological factors that worsen the perceived health of Japanese males and females.

Social capital refers to the quantity and quality of social relationships, such as formal and informal social connections as well as norms of reciprocity and trust that exist in a place or a community. This article analyzed the data from Japan 2004 B Survey in order to elucidate the effects of social capital and socio-psychological factors on the health of Japanese males and females. The Survey was a part of a nationwide random study on Japanese national character, which has been conducted by the Institute of Statistical Mathematics since 1953. A total of 785 (372 males and 413 females) valid data from 1,200 adult samples were used. Logistic regression analysis showed that the self-reported symptoms were increased by negative attitude to generalized trust in males, and by negative attitude to norm of reciprocity in females. Moreover, in females, health dissatisfaction was enhanced by low perceptions of support. In both genders, self-reported symptoms and health dissatisfaction were worsened by anxiety. The self-reported symptoms were increased by an adherence to religion and spirituality in males, whereas in females, the health dissatisfaction increased with low income and a concern about superstitions. Thus, from a viewpoint of social capital, perceived health is susceptible to personal relationships in females and to distrust in males. Anxiety seems a key factor affecting perceived health. In addition, females are influenced by economic status and superstitions, whereas males are more concerned about religion or the mind in relation to health. These findings are useful in developing health policies for Japanese.

Acupuncture can reduce perceived pain, mood disturbances and medical expenses related to low back pain among factory employees.

To investigate the effects of acupuncture on perceived pain, mood disturbances and medical expenses related to low back pain (LBP), an intervention study was performed among 72 employees of a steel company, 70 males and 2 females, aged 53.1+/-7.1 (mean+/-SD) yr, with LBP. They received acupuncture treatment once a week for 8 wk (from October to December 1998) by licensed acupuncturists, adopting a new hypothesis of the Meridian test. Perceived pain scale, and Profile of Mood States (POMS) were administered. Past and present histories of employees' visits to hospitals and their medical expenses for LBP were surveyed from receipts obtained from the subjects' branch factory and from receipts from another nearby branch factory (control) during the period from April 1998 to March 1999. After 8 wk of treatment, patients with LBP reported diminished pain (p<0.01). POMS showed a significant decrease in the total mood disturbance score (p<0.001). The number of visits to conventional hospitals (12.1+/-8.0 vs. 0.8+/-0.8 per month, p<0.05) and standardized medical expenses for LBP (100.1+/-89.6 vs. 7.3+/-6.9 per month, p<0.05) after acupuncture intervention (November 1998 to March 1999) were significantly decreased as compared with those before intervention (April 1998 to October 1998). In contrast, such decreases were not observed in employees from the control branch factory. It is suggested that acupuncture can reduce medical expenses for LBP through improvement in mood and pain.

[Use of complementary and alternative medicines among factory workers: investigation of workers in manufacturing].

To elucidate the situation of complementary and alternative medicines (CAM) in an occupational health setting, workers in a factory of a housing construction business were surveyed using self-administered questionnaires on their utilization of CAM in the past 12 months, out-of-pocket expenditures on CAM and ordinary western medicines (OWM), and reasons for the use of CAM. A total of 263 workers (84.3%) completed the questionnaires. Among them, 134 (51%) had received CAM therapy in the last 12 months: i.e. nutritional and tonic drinks (35.4%), supplements (16.3%), massage (13.7%), chiropractic or osteopathy (8.7%), health-related appliances (6.5%), herb or kampo (3.4%), aromatherapy (1.9%), acupuncture (1.9%), or other therapy (1.5%). Reasons for the use of CAM was "the condition was not serious enough to warrant OWM" and "expectation of health promotion or disease prevention" for 70 (51.9%) and 53 (39.3%) subjects, respectively. Average annual out-of-pocket expenditures for CAM and OWM were 17,500 and 21,300 yen, respectively. It seems important to further widen awareness and knowledge of CAM in occupational health.

Effects of urbanization, economic development, and migration of workers on suicide mortality in Japan.

The relationships between male or female age-adjusted suicide mortality and social life factors for all 47 Japanese prefectures in 1980, 1985 and 1990 were investigated by stepwise multiple regression analysis after classification of 20 social life indicators by factor analysis. During this period, Japan experienced the second economic crisis (the so-called secondary oil crisis) in 1980-1983 and economic prosperity (bubble economy) in 1986-1990. In all the three years, male suicide mortality was significantly related inversely to the urbanization and economic development factor, the result of which was consistent with the data in our previous study for the years 1970 and 1975. Similarly, the male mortality was positively related to the factor of migration of workers in the three years. No factor significantly related to female mortality for all the three years was found. It is suggested that (1) urbanization was a major determinant which prevented male suicide mortality during the past 20 years (1970-1990) in Japan; (2) migration of workers became an important factor for male suicide mortality during these 10 years; and (3) female suicide mortality was less vulnerable to social life factors for these 20 years than the male mortality.

Assessment of urinary cotinine as a marker of nicotine absorption from tobacco leaves: a study on tobacco farmers in Malaysia.

To assess dermal absorption of nicotine from tobacco leaves in relation to Green Tobacco Sickness (GTS), urinary cotinine concentrations were measured in 80 male tobacco-growing farmers and in 40 healthy males (controls) who did not handle wet tobacco leaves in Kelantan, Malaysia. Among non-smokers, urinary cotinine levels in farmers were significantly higher than those of controls; farmers with urinary cotinine of 50 ng/ml/m2 or above showed eye symptoms more frequently than those below this level (p<0.05). Farmers who did not wear protective equipment had subjective symptoms more frequently than those who used the equipment (p<0.05); some of these symptoms were seen more frequently in organophosphate (Tamaron) users than in non-users. As tobacco farmers evidence a risk of nicotine poisoning from tobacco leaves, assessment including GTS together with effects of pesticides will be necessary.

Assessment of the mutations of p53 suppressor gene and Ha- and Ki-ras oncogenes in malignant mesothelioma in relation to asbestos exposure: a study of 12 American patients.

In our previous study, we found no genetic alteration in exons 1 and 2 of Ha- and Ki-ras oncogenes nor in exons 5 to 9 of the p53 suppressor gene in seven Japanese malignant mesothelioma patients exposed to asbestos. To examine further whether malignant mesothelioma due to asbestos has genetic alterations in the p53 suppressor gene and in Ha- and Ki-ras oncogenes, we analyzed point mutations of these genes in paraffin embedded operative open biopsied samples of the primary tumor of malignant mesothelioma in twelve American patients. The genetic analysis was conducted by the PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) method in all patients and by sequencing analysis of DNA bases in the two patients with suspected gene mutation. The analysis of the p53 suppressor gene showed an amino acid converting mutation of exon 7 in one patient and a polymorphism of exon 6 in another patient; the former patient was a heavy smoker with a biphasic cell type. No genetic alteration was found in exons 1 and 2 of Ha- and Ki-ras oncogenes in any of the patients. The results suggest that the effects of asbestos on the p53 suppressor gene and Ha- and Ki-ras oncogenes in malignant mesothelioma are negligible. Further studies are needed to examine whether the observed mutation of the p53 suppressor gene is due to the combined effects of asbestos and smoking or to other unknown factors.