China has long experience using live attenuated and inactivated vaccines against hepatitis A virus (HAV) infection. We summarize this experience and provide recent data on adverse events after immunization (AEFIs) with hepatitis A vaccines in China. We reviewed the published literature (in Chinese and English) and the published Chinese regulatory documents on hepatitis A vaccine development, production, and postmarketing surveillance of AEFI. We described the safety, immunogenicity, and efficacy of hepatitis A vaccines and horizontal transmission of live HAV vaccine in China. In clinical trials, live HAV vaccine was associated with fever (0.4%–5% of vaccinees), rash (0%–1.1%), and elevated alanine aminotransferase (0.015%). Inactivated HAV vaccine was associated with fever (1%–8%), but no serious AEFIs were reported. Live HAV vaccine had seroconversion rates of 83% to 91%, while inactivated HAV vaccine had seroconversion rates of 95% to 100%. Community trials showed efficacy rates of 90% to 95% for live HAV and 95% to 100% for inactivated HAV vaccine. Postmarketing surveillance showed that HAV vaccination resulted in an AEFI incidence rate of 34 per million vaccinees, which accounted for 0.7% of adverse events reported to the China AEFI monitoring system. There was no difference in AEFI rates between live and inactivated HAV vaccines. Live and inactivated HAV vaccines manufactured in China were immunogenic, effective, and safe. Live HAV vaccine had substantial horizontal transmission due to vaccine virus shedding; thus, further monitoring of the safety of virus shedding is warranted.

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Background: There has been increasing interest in the formal review of child deaths in Japan. In this study we examined the causes and scene information regarding child deaths from injury in Tokyo, the capital of Japan, as preparation for implementation of a full-scale review of child deaths.
Methods: Documents on deaths from injury (excluding homicides) investigated by the Tokyo Medical Examiner’s Office during the period from 2006 through 2010 were reviewed. Deaths of children younger than 18 years (N = 217) were selected as the study sample. We examined the cause of and information on the death and were particularly interested in whether a case had preventable factors.
Results: Overall, 67% of the cases were deaths from unintentional injury. The main cause of death among children younger than 1 year was asphyxia, and the proportions of deaths from traffic accidents were higher in older age groups. Thirty percent of deaths from injury were due to suicide, and all cases of suicide were among children older than 10 years. Although analysis of preventable factors was difficult in some cases, owing to limited information on the death scene, 87% of deaths from unintentional injury, excluding those involving traffic accidents, had preventable factors.
Conclusions: Most unintentional child deaths from injury appear to be preventable. Development of a system to collect detailed information on the scene at the time of death will help decrease child deaths in Japan.

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Background: The sentinel surveillance system in Japan provides estimates of nationwide influenza incidence. Although prefectural influenza incidences can be estimated using data from the current surveillance system, such estimates may be imprecise.
Methods: We calculated the numbers of sentinel medical institutions (SMIs) needed in the surveillance system to estimate influenza incidences in prefectures, under the assumption that the standard error rates in 75% of influenza epidemic cases are less than 10%. Epidemic cases observed in 47 prefectures during the 2007/2008, 2008/2009, and 2009/2010 seasons, respectively, were used.
Results: The present total number of SMIs was 6669. With respect to current standards, the increases required in prefectures ranged from 0 to 59, and the total increase required in the number of SMIs was 1668.
Conclusions: We used sentinel surveillance data for Japan to calculate the number of SMIs required to estimate influenza incidence in each prefecture.

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Background: A report of multiple cases of bile duct cancer at a Japanese printing company raised concern about such cancers. We examined long-term trends in bile duct cancer in Japan.
Methods: Data from 4 population-based cancer registries were used to calculate incidence between 1985 and 2007, and vital statistics were used to estimate mortality between 1985 and 2011. Age-standardized rates were calculated and analyzed using a joinpoint regression model.
Results: Among men, the incidence rate of intrahepatic bile duct cancer increased throughout the observation period; among women, it increased until 1996–1998 and remained stable thereafter. The incidence rate of extrahepatic bile duct cancer was stable in men and decreased from 1993–1995 in women. In people aged 30 to 49 years, the incidence rates of intra- and extrahepatic bile duct cancer remained stable or decreased. The mortality rate of intrahepatic bile duct cancer increased in both sexes and in all age groups since 1996, while that of extrahepatic bile duct cancer decreased since 1992. In people aged 30 to 49 years, the mortality rates of intra- and extrahepatic bile duct cancer remained stable and decreased, respectively.
Conclusions: The incidence and mortality rates of intrahepatic bile duct cancer remained stable or increased throughout the observation period. The incidence rate of extrahepatic bile duct cancer remained stable or decreased, and the mortality rate decreased since 1992. In people aged 30 to 49 years, the incidence and mortality rates of intra- and extrahepatic bile cancer remained stable or decreased.

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Background: We investigated the prevalence of hallux valgus (HV) and examined its association with various factors in a cross-sectional study of Japanese female university students.
Methods: A questionnaire survey of foot symptoms, lifestyle, and body mass index (BMI) was administered to 343 women who provided informed consent at a women’s university. Footprints were obtained and bone density was measured. Associations of HV with various factors were analyzed by logistic regression analysis.
Results: Big toe pain was reported in 26.5% of the women. HV (HV angle, ≥15°) was present in the left foot in 22.4%, the right foot in 20.7%, and unilaterally or bilaterally in 29.7% of women. Mild HV (HV angle, ≥15° to <20°) was noted in the left foot and right foot in 13.4% and 13.1% of women, respectively; no severe HV (HV angle, ≥40°) was observed. HV was associated with big toe pain (adjusted OR: 3.56, 95% CI: 2.01–6.32), history of HV in the mother or maternal grandmother (adjusted OR: 2.45, 95% CI: 1.19–5.02), and history of HV in other family members (adjusted OR: 3.09, 95% CI: 1.35–7.06). Moderate HV was associated with big toe pain (adjusted OR: 4.58, 95% CI: 2.17–9.66) and history of HV in the mother or maternal grandmother (adjusted OR: 3.36, 95% CI: 1.40–8.07). The proportion of women with big toe pain increased significantly with HV severity.
Conclusions: HV was present in about 30% of female university students. Young women with big toe pain or a family history of HV should be evaluated for HV.

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Background: The precise contributions of hereditary and environmental factors to bone density are not known. We compared lifestyle predictors of bone density among adopted and biological children.
Methods: The study comprised 18 adopted children (mean [SD] age, 14.0 [4.1] years) with their non-biological parents and 17 children with their biological parents. Bone mineral density (BMD; g/cm²) was measured at the lumbar spine, total femur, and distal radius. Nutritional intake was assessed by food frequency questionnaire. Information on smoking and physical activity was obtained by questionnaire.
Results: Intakes of all nutrients, corrected for energy intake, and all lifestyle characteristics except sleep duration were similar in biological children and their parents. As compared with their parents, adopted children had significantly different energy, protein, and calcium intakes and physical activity levels. In a regression model, BMD z scores of adopted children and their parents were significantly inversely associated at the spine and total femur, whereas BMD z scores of biological children and their parents were significantly positively associated at all measurement sites. The greatest proportion of total variance in BMD was accounted for by calcium intake among adopted children and by parental BMD among biological children.
Conclusions: For some lifestyle characteristics and nutrient intakes, the differences between parents and children were more obvious among adoptive families than among biological families. The most important lifestyle predictor of bone density was calcium intake.

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Background: Breast cancer is the most common cancer in women worldwide. We investigated the association of hormonal contraceptive use and breast cancer in Thai women.
Methods: A cohort study was conducted in Khon Kaen, Thailand. There were 70 cases of histologically confirmed breast cancer among 11 414 women aged 30 to 69 years who were recruited as participants in the cohort study during the period from 1990 through 2001. The study population was followed-up until December 31, 2011. To identify factors associated with incidence of breast cancer, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model.
Results: The 11 414 women provided a total observation time of 157 200 person-years. Breast cancer risk among women with a history of hormonal contraceptive use was 1.31 times that of women without such a history, but the difference was not statistically significant (95% CI, 0.65–2.65). No type of hormonal contraceptive was associated with a significant increase in breast cancer risk as compared with women who had never used hormonal contraceptives (oral contraception: HR = 1.35, 95% CI, 0.65–2.78; injection contraception: HR = 1.25, 95% CI, 0.56–2.80), and there was no relationship between duration of hormonal contraceptive use and breast cancer.
Conclusions: There was no association between hormonal contraceptive use and breast cancer; however, this finding should be viewed with caution due to the small number of cases.

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Background: The prevalence of overweight and underweight is steadily increasing among children and adolescents. To explore the relationship between parental socioeconomic status and body mass index, we examined levels of overweight and underweight among representative samples of children and adolescents in South Korea.
Methods: We analyzed data from the 2009 Korean Survey on the Obesity of Youth and Children, conducted by the National Youth Policy Institute. The sample response rate for this survey was 93.9%. After excluding 745 subjects who had missing information on age, height, or weight, 9411 subjects were included. To measure parental socioeconomic status, 4 categories were assessed by using a structured questionnaire: subjective economic status, parental education level, parental occupational status, and family structure. We used the chi-squared test in univariable analysis and multinomial logistic regression in multivariable analysis.
Results: Multinomial logistic regression analysis identified sex, education level, parental interest in weight management, and parental body shapes as statistically significant characteristics affecting overweight in children, and sex, place of residence, parental interest in weight management, and paternal and maternal body shapes as statistically significant characteristics affecting underweight (P < 0.05).
Conclusions: Underweight and overweight coexist among adolescent Korean males of low socioeconomic status, which indicates that these conditions can coexist in developed countries. Appropriate interventions to address both overweight and underweight in adolescents are required.

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Background: Use of fuel heaters is associated with childhood asthma. However, no studies have evaluated the associations of flue use and mechanical ventilation (ventilation) with asthma symptoms in schoolchildren.
Methods: This cross-sectional study investigated schoolchildren in grades 1 through 6 (age 6–12 years) in Sapporo, Japan. From November 2008 through January 2009, parents completed questionnaires regarding their home environment and their children’s asthma symptoms.
Results: In total, 4445 (69.5%) parents of 6393 children returned the questionnaire. After excluding incomplete responses, data on 3874 children (60.6%) were analyzed. The prevalence of current asthma symptoms and ever asthma symptoms were 12.8% and 30.9%, respectively. As compared with electric heaters, current asthma symptoms was associated with use of flued heaters without ventilation (OR = 1.62; 95% CI, 1.03–2.64) and unflued heaters with ventilation (OR = 1.77; 95% CI, 1.09–2.95) or without ventilation (OR = 2.23; 95% CI, 1.31–3.85). Regardless of dampness, unflued heaters were significantly associated with current asthma symptoms in the presence and absence of ventilation.
Conclusions: Use of unflued heaters was associated with current asthma symptoms, regardless of dampness. In particular, the prevalence of current asthma symptoms was higher in the absence of ventilation than in the presence of ventilation. Ever asthma symptoms was only associated with use of unflued heaters without ventilation. Consequently, use of fuel heaters, especially those that have no flue or ventilation, deserves attention, as their use might be associated with childhood asthma symptoms.

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Objectives: To explore determinants of change in pediatrician supply in Japan, and examine impacts of a 2004 reform of postgraduate medical education on pediatricians’ practice location choice.
Methods: Data were compiled from secondary data sources. The dependent variable was the change in the number of pediatricians at the municipality (“secondary tier of medical care” [STM]) level. To analyze the determinants of pediatrician location choices, we considered the following predictors: initial ratio of pediatricians per 1000 children under five years of age (pediatrician density) and under-5 mortality as measures of local area need, as well as measures of residential quality. Ordinary least-squares regression models were used to estimate the associations. A coefficient equality test was performed to examine differences in predictors before and after 2004. Basic comparisons of pediatrician coverage in the top and bottom 10% of STMs were conducted to assess inequality in pediatrician supply.
Results: Increased supply was inversely associated with baseline pediatrician density both in the pre-period and post-period. Estimated impact of pediatrician density declined over time (P = 0.026), while opposite trends were observed for measures of residential quality. More specifically, urban centers and the SES composite index were positively associated with pediatrician supply for the post-period, but no such associations were found for the pre-period. Inequality in pediatrician distribution increased substantially after the reform, with the best-served 10% of communities benefitting from five times the pediatrician coverage compared to the least-served 10%.
Conclusions: Residential quality increasingly became a function of location preference rather than public health needs after the reform. New placement schemes should be developed to achieve more equity in access to pediatric care.

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Background: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelium nitric oxide synthase (NOS). ADMA binds to a substrate-binding site of NOS and then inhibits nitric oxide production from vascular endothelial cells. Elevated ADMA levels are a risk factor for cardiovascular disease. Recently, it was reported that plasma ADMA levels were negatively correlated with vegetable and fruit consumption. The purpose of this study was to examine the association between serum levels of carotenoids and serum ADMA levels in Japanese subjects.
Methods: We conducted a cross-sectional study of 470 subjects (203 men and 267 women) who attended a health examination in August 2011. Serum levels of several carotenoids were separately measured by high-performance liquid chromatography. Serum ADMA levels were determined by using an enzyme-linked immunosorbent assay kit.
Results: In women, the multivariate-adjusted odds ratios (ORs) of elevated serum ADMA levels were significantly decreased in the highest tertile for β-cryptoxanthin (OR 0.47, 95% CI 0.23–0.95), α-carotene (OR 0.39, 95% CI 0.18–0.79), and β-carotene (OR 0.36, 95% CI 0.17–0.73) compared to the lowest tertile. In men, significantly decreased ORs were observed in the highest tertiles of serum zeaxanthin/lutein (OR 0.23, 95% CI 0.06–0.69) and α-carotene (OR 0.26, 95% CI 0.07–0.82), and in the middle and the highest tertiles of serum β-carotene (OR 0.27, 95% CI 0.09–0.74 and OR 0.20, 95% CI 0.03–0.88, respectively) when the tertile cutoff points of women were extrapolated to men.
Conclusions: Higher serum levels of carotenoids, such as α-carotene and β-carotene, may help to prevent elevated serum ADMA levels in Japanese subjects.

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