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1.  INCIDENCE OF KAWASAKI DISEASE IN NORTHERN EUROPEAN COUNTRIES 
Background
We sought to compare the epidemiologic features of Kawasaki disease (KD) in three Northern European countries and Japan.
Methods
Data were obtained from discharge databases for hospitals in Finland, Norway, and Sweden from 1999–2009 and from nationwide epidemiologic surveys in Japan from 1998–2008. Annual incidence for each country was calculated using regional census data.
Results
During the 11-year period, 1,390 KD patients were recorded in the registries of the three Northern European countries. Average annual incidence rates per 100,000 children less than 5 years were: Finland 11.4, Norway 5.4, and Sweden 7.4. Overall, 86.4% of Japanese KD patients were less than 5 years compared to only 67.8% in the four Northern European countries (p<0.001).
Conclusions
The incidence of KD in Northern Europe was constant over the study period and much lower than in Japan. There was a significant age difference between Northern European and Japanese KD patients that remains unexplained.
doi:10.1111/j.1442-200X.2012.03692.x
PMCID: PMC3467350  PMID: 22726311
coronary artery aneurysm; epidemiology; Kawasaki disease; vasculitis
2.  Graft-related disease progression in dura mater graft-associated Creutzfeldt-Jakob disease: a cross-sectional study 
BMJ Open  2013;3(8):e003400.
Objectives
Details of abnormal prion protein (PrPSc) propagation in the human central nervous system (CNS) are unclear. To assess the spread of PrPSc through the human CNS, we evaluated dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) cases focusing on sites of grafting and dCJD pathological subtypes.
Design
A cross-sectional study.
Setting
nationwide surveillance data of human prion diseases in Japan over the past 12 years were applied for the study.
Participants
Clinical data were obtained from 84 dCJD patients.
Outcome measures
The clinical courses in cases of dCJD were analysed according to the grafting sites (supratentorial and infratentorial groups) and the pathological subtypes (non-plaque and plaque types).
Results
Of the 84 cases of dCJD in this study, 36 (43%) were included in the supratentorial group and 39 (46%) were included in the infratentorial group. As initial manifestations, vertigo (p=0.007) and diplopia (p=0.041) were significantly more frequent in the infratentorial group than in the supratentorial group. During their clinical course, cerebellar signs appeared more frequently in the infratentorial group than in the supratentorial group (p=0.024). In the non-plaque type cases (n=53), the infratentorial group developed vertigo more frequently than the supratentorial group (p=0.017); moreover, cerebellar signs appeared more frequently in the infratentorial group (p=0.014). However, there was no significant difference between groups in the plaque type (n=18).
Conclusions
The high frequency of clinical manifestations related to brain stem and cerebellar dysfunction in the non-plaque type dCJD with infratentorial grafting suggests that PrPSc commonly shows direct propagation into the CNS from contaminated dura mater grafts.
doi:10.1136/bmjopen-2013-003400
PMCID: PMC3753481  PMID: 23975105
Infectious Diseases
3.  Early-life mental disorders and adult household income in the World Mental Health Surveys 
Biological Psychiatry  2012;72(3):228-237.
Background
Better information on the human capital costs of early-onset mental disorders could increase sensitivity of policy-makers to the value of expanding initiatives for early detection-treatment. Data are presented on one important aspect of these costs: the associations of early-onset mental disorders with adult household income.
Methods
Data come from the WHO World Mental Health (WMH) Surveys in eleven high income, five upper-middle income, and six low/lower-middle income countries. Information about 15 lifetime DSM-IV mental disorders as of age of completing education, retrospectively assessed with the WHO Composite International Diagnostic Interview, was used to predict current household income among respondents ages 18-64 (n = 37,741) controlling for level of education. Gross associations were decomposed to evaluate mediating effects through major components of household income.
Results
Early-onset mental disorders are associated with significantly reduced household income in high and upper-middle income countries but not low/lower-middle income countries, with associations consistently stronger among women than men. Total associations are largely due to low personal earnings (increased unemployment, decreased earnings among the employed) and spouse earnings (decreased probabilities of marriage and, if married, spouse employment and low earnings of employed spouses). Individual-level effect sizes are equivalent to 16-33% of median within-country household income, while population-level effect sizes are in the range 1.0-1.4% of Gross Household Income.
Conclusions
Early mental disorders are associated with substantial decrements in income net of education at both individual and societal levels. Policy-makers should take these associations into consideration in making healthcare research and treatment resource allocation decisions.
doi:10.1016/j.biopsych.2012.03.009
PMCID: PMC3402018  PMID: 22521149
epidemiology; mental disorders; early-onset; income; cross-national; WHO World Mental Health (WMH)
4.  Relationships between Clinicopathological Features and Cerebrospinal Fluid Biomarkers in Japanese Patients with Genetic Prion Diseases 
PLoS ONE  2013;8(3):e60003.
A national system for surveillance of prion diseases (PrDs) was established in Japan in April 1999. Here, we analyzed the relationships among prion protein gene (PRNP) mutations and the clinical features, cerebrospinal fluid (CSF) markers, and pathological characteristics of the major genotypes of genetic PrDs (gPrDs). We retrospectively analyzed age at onset and disease duration; the concentrations and incidences of 14-3-3 protein, tau protein, and abnormal prion protein (PrPSc) in the CSF of 309 gPrD patients with P102L, P105L, E200K, V180I, or M232R mutations; and brain pathology in 32 autopsied patients. Three clinical phenotypes were seen: rapidly progressive Creutzfeldt-Jakob disease (CJD), which included 100% of E200K cases, 70% of M232R, and 21% of P102L; slowly progressive CJD, which included 100% of V180I and 30% of M232R; and Gerstmann-Sträussler-Scheinker disease, which included 100% of P105L and 79% of P102L. PrPSc was detected in the CSF of more than 80% of patients with E200K, M232R, or P102L mutations but in only 39% of patients with V180I. V180I was accompanied by weak PrP immunoreactivity in the brain. Patients negative for PrPSc in the CSF were older at disease onset than positive patients. Patients with mutations associated with high 14-3-3 protein levels in the CSF typically had synaptic deposition of PrP in the brain and a rapid course of disease. The presence of small PrP protein fragments in brain homogenates was not correlated with other clinicopathological features. Positivity for PrPSc in the CSF may reflect the pathological process before or at disease onset, or abnormality in the secretion or metabolism of PrPSc. The amount of 14-3-3 protein in the CSF likely indicates the severity of the pathological process and accompanying neuronal damage. These characteristic features of the CSF in cases of gPrD will likely facilitate accurate diagnosis and clinicopathological study of the various disease subtypes.
doi:10.1371/journal.pone.0060003
PMCID: PMC3610658  PMID: 23555862
5.  Cost-effectiveness of a tailored intervention designed to increase breast cancer screening among a non-adherent population: a randomized controlled trial 
BMC Public Health  2012;12:760.
Background
Although the percentage of women who initiate breast cancer screening is rising, the rate of continued adherence is poor. The purpose of this study was to examine the effectiveness and cost-effectiveness of a tailored print intervention compared with a non-tailored print intervention for increasing the breast cancer screening rate among a non-adherent population.
Methods
In total, 1859 participants aged 51–59 years (except those aged 55 years) were recruited from a Japanese urban community setting. Participants were randomly assigned to receive either a tailored print reminder (tailored intervention group) or non-tailored print reminder (non-tailored intervention group). The primary outcome was improvement in the breast cancer screening rate. The screening rates and cost-effectiveness were examined for each treatment group (tailored vs. non-tailored) and each intervention subgroup during a follow-up period of five months. All analyses followed the intention-to-treat principle.
Results
The number of women who underwent a screening mammogram following the reminder was 277 (19.9%) in the tailored reminder group and 27 (5.8%) in the non-tailored reminder group. A logistic regression model revealed that the odds of a woman who received a tailored print reminder undergoing mammography was 4.02 times those of a women who had received a non-tailored print reminder (95% confidence interval, 2.67–6.06). The cost of one mammography screening increase was 2,544 JPY or 30 USD in the tailored intervention group and 4,366 JPY or 52 USD in the non-tailored intervention group.
Conclusions
Providing a tailored print reminder was an effective and cost-effective strategy for improving breast cancer screening rates among non-adherent women.
doi:10.1186/1471-2458-12-760
PMCID: PMC3495210  PMID: 22962858
Mammography; Tailored intervention; Cancer worry; Cost-effectiveness; Non-adherent population
6.  Diagnostic Criteria, Clinical Features, and Incidence of Thyroid Storm Based on Nationwide Surveys 
Thyroid  2012;22(7):661-679.
Background
Thyroid storm (TS) is life threatening. Its incidence is poorly defined, few series are available, and population-based diagnostic criteria have not been established. We surveyed TS in Japan, defined its characteristics, and formulated diagnostic criteria, FINAL-CRITERIA1 and FINAL-CRITERIA2, for two grades of TS, TS1, and TS2 respectively.
Methods
We first developed diagnostic criteria based on 99 patients in the literature and 7 of our patients (LIT-CRITERIA1 for TS1 and LIT-CRITERIA2 for TS2). Thyrotoxicosis was a prerequisite for TS1 and TS2 as well as for combinations of the central nervous system manifestations, fever, tachycardia, congestive heart failure (CHF), and gastrointestinal (GI)/hepatic disturbances. We then conducted initial and follow-up surveys from 2004 through 2008, targeting all hospitals in Japan, with an eight-layered random extraction selection process to obtain and verify information on patients who met LIT-CRITERIA1 and LIT-CRITERIA2.
Results
We identified 282 patients with TS1 and 74 patients with TS2. Based on these data and information from the Ministry of Health, Labor, and Welfare of Japan, we estimated the incidence of TS in hospitalized patients in Japan to be 0.20 per 100,000 per year. Serum-free thyroxine and free triiodothyroine concentrations were similar among patients with TS in the literature, Japanese patients with TS1 or TS2, and a group of patients with thyrotoxicosis without TS (Tox-NoTS). The mortality rate was 11.0% in TS1, 9.5% in TS2, and 0% in Tox-NoTS patients. Multiple organ failure was the most common cause of death in TS1 and TS2, followed by CHF, respiratory failure, arrhythmia, disseminated intravascular coagulation, GI perforation, hypoxic brain syndrome, and sepsis. Glasgow Coma Scale results and blood urea nitrogen (BUN) were associated with irreversible damages in 22 survivors. The only change in our final diagnostic criteria for TS as compared with our initial criteria related to serum bilirubin concentration >3 mg/dL.
Conclusions
TS is still a life-threatening disorder with more than 10% mortality in Japan. We present newly formulated diagnostic criteria for TS and clarify its clinical features, prognosis, and incidence based on nationwide surveys in Japan. This information will help diagnose TS and in understanding the factors contributing to mortality and irreversible complications.
doi:10.1089/thy.2011.0334
PMCID: PMC3387770  PMID: 22690898
7.  Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment 
Emerging Infectious Diseases  2012;18(6):901-907.
The book on iatrogenic Creutzfeldt-Jakob disease (CJD) in humans is almost closed. This form of CJD transmission via medical misadventures was first detected in 1974. Today, only occasional CJD cases with exceptionally long incubation periods still appear. The main sources of the largest outbreaks were tissues from human cadavers with unsuspected CJD that were used for dura mater grafts and growth hormone extracts. A few additional cases resulted from neurosurgical instrument contamination, corneal grafts, gonadotrophic hormone, and secondary infections from blood transfusions. Although the final solution to the problem of iatrogenic CJD is still not available (a laboratory test to identify potential donors who harbor the infectious agent), certain other measures have worked well: applying special sterilization of penetrating surgical instruments, reducing the infectious potential of donor blood and tissue, and excluding donors known to have higher than normal risk for CJD.
doi:10.3201/eid1806.120116
PMCID: PMC3358170  PMID: 22607808
Creutzfeldt-Jakob disease; dura mater; human growth hormone; iatrogenic disease; PRNP codon 129; variant Creutzfeldt-Jakob disease; prions and related diseases
8.  Epidemiologic Features of Kawasaki Disease in Japan: Results of the 2009–2010 Nationwide Survey 
Journal of Epidemiology  2012;22(3):216-221.
Background
Although the number of patients and incidence rate of Kawasaki disease (KD) are increasing in Japan, the most recent epidemiologic features of KD are not known.
Methods
The 21st nationwide survey of KD was conducted in 2011 and included patients treated for the disease in 2009 and 2010. Hospitals specializing in pediatrics, and hospitals with a total of 100 or more beds and a pediatric department, were asked to report all patients with KD during the 2 survey years.
Results
A total of 1445 departments and hospitals reported 23 730 KD patients (10 975 in 2009 and 12 755 in 2010): 13 515 boys and 10 215 girls. The annual incidence rates were 206.2 and 239.6 per 100 000 children aged 0 to 4 years in 2009 and 2010, respectively; the 2010 rate was the highest ever reported in Japan. Monthly number of patients peaked during winter to spring months; lower peaks were noted during summer months. However, the seasonal patterns in 2009 and 2010 differed from those of previous years. The age-specific incidence rate had a monomodal distribution, with a peak during the latter half of the year of birth. The prevalences of cardiac lesions during acute KD and cardiac sequelae were higher among infants and older age groups. Despite a decrease in prevalence, the proportion of patients with giant coronary aneurysms—the most severe sequela of KD—did not substantially decrease.
Conclusions
The incidence rate and number of patients with KD continue to increase in Japan.
doi:10.2188/jea.JE20110126
PMCID: PMC3798622  PMID: 22447211
mucocutaneous lymph node syndrome; incidence; cardiovascular diseases; immunoglobulin, intravenous; epidemiology
9.  Duration of Prion Disease is Longer in Japan Than in Other Countries 
Journal of Epidemiology  2011;21(4):255-262.
Background
Prion diseases are untreatable, progressive, and fatal brain disorders that occur worldwide, and the annual incidence rate is approximately 1 case per 1 million people. The duration of these diseases in Japan is unclear.
Methods
Based on data from 1 April 1999 through 4 September 2008 provided by the Japanese Creutzfeldt-Jakob disease (CJD) surveillance program, we analyzed disease duration and its relationship with clinical features. Duration was assumed to be the time from disease onset to death.
Results
Evaluation by the surveillance committee indicated that during the observed period 1128 individuals received a diagnosis of prion disease and were registered in the surveillance program. Mean disease duration in the 855 patients who died was 17.4 months. Overall, 46.0% of patients died within 1 year and 77.2% died in less than 2 years. Among those with sporadic Creutzfeldt-Jakob disease, which represented 77.0% of cases, mean disease duration was 15.7 months, while that of patients surveyed by the European Creutzfeldt Jakob Disease Surveillance Network (EUROCJD) was only 5 months.
Conclusions
Disease duration among Japanese with prion diseases was much longer than that of patients in Western countries conducting surveillance of prion diseases. This finding suggests that the characteristics of the system for providing life-sustaining treatment for patients with fatal, progressive diseases in Japan are related to the longer duration of these illnesses.
doi:10.2188/jea.JE20100085
PMCID: PMC3899417  PMID: 21628843
prion disease; Creutzfeldt-Jakob Syndrome; epidemiology; disease duration; Japan
10.  Kawasaki Disease in Mongolia: Results From 2 Nationwide Retrospective Surveys, 1996–2008 
Journal of Epidemiology  2011;21(4):293-298.
Background
Kawasaki disease (KD) has been reported in many countries. However, the incidence of KD in Mongolia is not known. This is the first report of incident cases of KD in Mongolia, which were identified using data from 2 nationwide surveys.
Methods
Two nationwide retrospective surveys were conducted: medical histories were collected from patients aged 0 to 16 years who were hospitalized countrywide between 1996 and 2008. Hospital records for these patients were also reviewed. Nationwide training seminars on KD were conducted before each survey.
Results
For the nationwide surveys, the participation rates among all hospitals with pediatric wards were 97% and 94%. Inpatient medical histories from 1996 through 2008 were reviewed, and, among children younger than 16 years, 9 patients with KD were investigated. The age of KD patients ranged from 1.4 to 14 years; 7 of 9 patients were male. Six (67%) patients fulfilled all 6 clinical diagnostic criteria; the other 3 (33%) were defined as having KD based on the presence of 5 such criteria. Fever persisting 5 or more days, bilateral conjunctival congestion, and changes of the lips and oral cavity were the most common symptoms, and cervical lymphadenopathy was the least common symptom. Cardiac sequelae developed in 5 of the patients, 4 of whom were older than 10 years.
Conclusions
The results of these nationwide surveys reveal that KD cases do exist in Mongolia. However, knowledge of KD among Mongolian pediatricians is likely to be poor. Thus, there is a need to augment their understanding to improve management of KD patients. Further studies are crucial to clarify the epidemiologic characteristics of KD in Mongolia.
doi:10.2188/jea.JE20100144
PMCID: PMC3899422  PMID: 21691035
mucocutaneous lymph node syndrome; nationwide survey; Mongolia; children
11.  Frequency of Citrus Fruit Intake Is Associated With the Incidence of Cardiovascular Disease: The Jichi Medical School Cohort Study 
Journal of Epidemiology  2011;21(3):169-175.
Background
It has been reported that fruit intake protects against cardiovascular disease (CVD). However, most of the relevant studies were conducted in Western countries, and only a few investigated Japanese populations. The present cohort study assessed the effect of citrus fruit intake on the incidence of CVD and its subtypes in a Japanese population.
Methods
A baseline examination consisting of physical and blood examinations and a self-administered questionnaire was conducted during the period from April 1992 through July 1995. Dietary habits were assessed using a food frequency questionnaire that was divided into 5 categories. Citrus fruit was examined separately due to its frequent consumption by the general Japanese population. Using the Cox proportional hazards model, data from 10 623 participants (4147 men, 6476 women) who had no history of CVD or carcinoma were analyzed to assess the association between frequency of citrus fruit intake and CVD incidence.
Results
Frequent intake of citrus fruit was associated with a lower incidence of CVD: the hazard ratio for almost daily intake versus infrequent intake of citrus fruit was 0.57 (95% confidence interval: 0.33–1.01, P for trend = 0.04) in men and 0.51 (0.29–0.88, P for trend = 0.02) in women. Frequent intake of citrus fruit was also associated with lower incidences of both all stroke and cerebral infarction, but not hemorrhagic stroke or myocardial infarction.
Conclusions
Frequent intake of citrus fruit may reduce the incidence of CVD, especially cerebral infarction, in men and women.
doi:10.2188/jea.JE20100084
PMCID: PMC3899405  PMID: 21389640
citrus fruit; cardiovascular disease; cerebral infarction; cohort studies; Japan
12.  Distribution of Birth Weight for Gestational Age in Japanese Infants Delivered by Cesarean Section 
Journal of Epidemiology  2011;21(3):217-222.
Background
Neonatal anthropometric charts of the distribution of measurements, mainly birth weight, taken at different gestational ages are widely used by obstetricians and pediatricians. However, the relationship between delivery mode and neonatal anthropometric data has not been investigated in Japan or other countries.
Methods
The subjects were selected from the registration database of the Japan Society of Obstetrics and Gynecology (2003–2005). Tenth centile, median, and 90th centile of birth weight by sex, birth order, and delivery mode were observed by gestational age from 22 to 42 weeks among eligible singleton births.
Results
After excluding 248 outliers and 5243 births that did not satisfy the inclusion criteria, 144 980 births were included in the analysis. The distribution of 10th centile curves was skewed toward lower birth weights during the preterm period among both first live births and second and later live births delivered by cesarean section. More than 40% of both male and female live births were delivered by cesarean section at 37 weeks or earlier.
Conclusions
The large proportion of cesarean sections influenced the skewness of the birth weight distribution in the preterm period.
doi:10.2188/jea.JE20100123
PMCID: PMC3899412  PMID: 21478642
birth weight; distribution; gestational age; cesarean section; preterm
13.  Evaluating the drug use “gateway” theory using cross-national data: Consistency and associations of the order of initiation of drug use among participants in the WHO World Mental Health Surveys* 
Drug and alcohol dependence  2010;108(1-2):84-97.
Background
It is unclear whether the normative sequence of drug use initiation, beginning with tobacco and alcohol, progressing to cannabis and then other illicit drugs, is due to causal effects of specific earlier drug use promoting progression, or to influences of other variables such as drug availability and attitudes. One way to investigate this is to see whether risk of later drug use in the sequence, conditional on use of drugs earlier in the sequence, changes according to time-space variation in use prevalence. We compared patterns and order of initiation of alcohol, tobacco, cannabis, and other illicit drug use across 17 countries with a wide range of drug use prevalence.
Method
Analyses used data from World Health Organization (WHO) World Mental Health (WMH) Surveys, a series of parallel community epidemiological surveys using the same instruments and field procedures carried out in 17 countries throughout the world.
Results
Initiation of “gateway” substances (i.e. alcohol, tobacco and cannabis) was differentially associated with subsequent onset of other illicit drug use based on background prevalence of gateway substance use. Cross-country differences in substance use prevalence also corresponded to differences in the likelihood of individuals reporting a non- normative sequence of substance initiation.
Conclusion
These results suggest the “gateway” pattern at least partially reflects unmeasured common causes rather than causal effects of specific drugs on subsequent use of others. This implies that successful efforts to prevent use of specific “gateway” drugs may not in themselves lead to major reductions in the use of later drugs.
doi:10.1016/j.drugalcdep.2009.12.001
PMCID: PMC2835832  PMID: 20060657
tobacco; alcohol; illicit drugs; gateway; WHO World Mental Health Surveys
14.  Characteristics and Validity of a Web-Based Kawasaki Disease Surveillance System in Japan 
Journal of Epidemiology  2010;20(6):429-432.
Background
Although regular nationwide surveys of Kawasaki disease (KD) are conducted in Japan, there is no system for detecting the real-time epidemic status of this disease.
Methods
A web-based surveillance system for KD was developed. After consideration of the number of patients reported by prefecture to the 19th nationwide survey, 355 pediatric departments were asked to participate in the surveillance, and 225 agreed. Since January 2008, pediatricians in these 225 hospitals have reported KD patient data immediately after diagnosis. The daily numbers of patients are available to the public via the internet at http://www.kawasaki-disease.net/kawasakidata/. The validity of the data in 2008 was evaluated using the Japanese 20th nationwide survey of KD as the gold standard.
Results
A total of 3376 patients were reported to the web-based surveillance system from the 1st week through 52nd week of 2008. The number of patients reported to the nationwide survey during the same period was 11 680: a total of 4950 patients from the hospitals participating in the web-based surveillance and 6730 from other hospitals. The epidemic curves were similar, and the correlation coefficient between the web-based surveillance and the total numbers in the nationwide survey was 0.806 (P < 0.01).
Conclusions
The web-based surveillance system for Kawasaki disease in Japan demonstrated good validity.
doi:10.2188/jea.JE20100006
PMCID: PMC3900818  PMID: 20814164
mucocutaneous lymph node syndrome; incidence; epidemiology; sentinel surveillance; internet
15.  Relationship between the Cumulative Incidence of Kawasaki Disease and the Prevalence of Electrocardiographic Abnormalities in Birth-Year Cohorts 
Journal of Epidemiology  2010;20(6):453-459.
Background
Kawasaki disease (KD) causes systemic vasculitis and coronary aneurysms. It frequently results in electrocardiographic (ECG) abnormalities of short duration. Cardiac sequelae persist beyond the acute stage in a few patients. There are many areas to be investigated concerning the effects on the vascular system of patients suffering from KD and its sequelae.
Methods
The cumulative incidences of KD and its cardiac sequelae were calculated in birth-year cohorts, using data obtained from KD nationwide surveys. The results were compared with the prevalence of ECG abnormalities detected in cardiac examinations conducted at primary and secondary schools for each birth-year cohort. This comparison allowed observation of relationships in these trends for each birth-year cohort.
Results
The cumulative incidence of late-stage cardiac sequelae gradually declined. However, there were increases in the cumulative incidence of ECG abnormalities and in the cumulative incidences of KD and acute-stage cardiac disorders related to KD.
Conclusions
The results suggest that even among children without late cardiac sequelae, KD can have a persistent effect on the cardiovascular system. It thus appears necessary to extend clinical observation of children with a history of KD, even if they developed only acute-stage cardiac lesions.
doi:10.2188/jea.JE20090159
PMCID: PMC3900822  PMID: 20827035
Kawasaki disease; mucocutaneous lymph node syndrome; cumulative incidence; birth-year cohort; prevalence of electrocardiographic abnormalities
16.  Epidemiologic Features of Kawasaki Disease in Japan: Results of the 2007–2008 Nationwide Survey 
Journal of Epidemiology  2010;20(4):302-307.
Background
The most recent epidemiologic features of Kawasaki disease (KD) are unknown.
Methods
The 20th nationwide survey of KD was conducted in 2009, and included patients treated for the disease in 2007 and 2008. Hospitals specializing in pediatrics, and hospitals with pediatric departments and 100 or more beds, were asked to report all patients with KD during the 2 survey years.
Results
From a total of 1540 departments and hospitals, 23 337 patients (11 581 in 2007 and 11 756 in 2008) were reported: 13 523 boys and 9814 girls. The annual incidence rates were 215.3 and 218.6 per 100 000 children aged 0–4 years in 2007 and 2008, respectively. These were the highest annual KD incidence rates ever recorded in Japan. The monthly number of patients peaked during the winter months; smaller increases were noted in the summer months. The age-specific incidence rate showed a monomodal distribution with a peak at age 9–11 months. The prevalences of both cardiac lesions during the acute phase of the disease and cardiac sequelae were higher among infants and older age groups.
Conclusions
The incidence rate and number of patients with KD in Japan continue to increase.
doi:10.2188/jea.JE20090180
PMCID: PMC3900790  PMID: 20530917
mucocutaneous lymph node syndrome; incidence; cardiovascular diseases; immunoglobulin, intravenous; epidemiology
17.  Administration of hepatitis B vaccine in winter as a significant predictor of the poor effectiveness of vaccination in rural Mongolia: evidence from a nationwide survey 
Background
Universal hepatitis B (HB) immunisation is the most effective means for prevention of hepatitis B virus (HBV) infection worldwide. Maintaining the vaccine cold chain is an essential part of a successful immunisation programme. Our recent nationwide survey in Mongolia has observed significant urban–rural differences in the prevalence of HBV infection among vaccinated cohorts.
Objective
To examine whether the administration of HB vaccine in winter contributes to these residential discrepancies on the effectiveness of vaccination.
Design and setting
In 2004, a nationwide serosurvey was carried out covering both urban and rural areas of Mongolia. Sampling was multistage, with random probability from all public schools in the country.
Participants
A random sample of 1145 children (51.7% boys; aged 7–12 years), representative of Mongolian elementary school children.
Results
Multivariate logistic regression analysis identified that total (past and current) HBV infection (OR 2.31, 95% CI 1.20 to 4.42; p = 0.012) was independently associated with the administration of all HB vaccines in winter. An increased OR for current HBV infection was also observed (OR 2.58, 95% CI 0.87 to 7.68; p = 0.089), but without significance. Interestingly, after stratifying by residence, the association between winter vaccination and total HBV infection was evident for rural (p = 0.008) but not for urban areas (p = 0.294). The frequency of vaccine‐induced immunity was significantly (p = 0.007) lower for those who received HB vaccine at birth during winter in rural areas.
Conclusion
Administration of HB vaccine during winter is an important predictor of the low effectiveness of vaccination in rural Mongolia. To improve the effectiveness of HB vaccination in remote areas, cold chain control should be addressed with particular attention to the winter season.
doi:10.1136/jech.2006.051375
PMCID: PMC2465751  PMID: 17568048
18.  Seasonality and Temporal Clustering of Kawasaki Syndrome 
Epidemiology (Cambridge, Mass.)  2005;16(2):220-225.
Background
The distribution of a syndrome in space and time may suggest clues to its etiology. The cause of Kawasaki syndrome, a systemic vasculitis of infants and children, is unknown, but an infectious etiology is suspected.
Methods
Seasonality and clustering of Kawasaki syndrome cases were studied in Japanese children with Kawasaki syndrome reported in nationwide surveys in Japan. Excluding the years that contained the 3 major nationwide epidemics, 84,829 cases during a 14-year period (1987–2000) were analyzed. To assess seasonality, we calculated mean monthly incidence during the study period for eastern and western Japan and for each of the 47 prefectures. To assess clustering, we compared the number of cases per day (daily incidence) with a simulated distribution (Monte Carlo analysis).
Results
Marked spatial and temporal patterns were noted in both the seasonality and deviations from the average number of Kawasaki syndrome cases in Japan. Seasonality was bimodal with peaks in January and June/July and a nadir in October. This pattern was consistent throughout Japan and during the entire 14-year period. Some years produced very high or low numbers of cases, but the overall variability was consistent throughout the entire country. Temporal clustering of Kawasaki syndrome cases was detected with nationwide outbreaks.
Conclusions
Kawasaki syndrome has a pronounced seasonality in Japan that is consistent throughout the length of the Japanese archipelago. Temporal clustering of cases combined with marked seasonality suggests an environmental trigger for this clinical syndrome.
PMCID: PMC2894624  PMID: 15703537
19.  Cross-National Analysis of the Associations between Traumatic Events and Suicidal Behavior: Findings from the WHO World Mental Health Surveys 
PLoS ONE  2010;5(5):e10574.
Background
Community and clinical data have suggested there is an association between trauma exposure and suicidal behavior (i.e., suicide ideation, plans and attempts). However, few studies have assessed which traumas are uniquely predictive of: the first onset of suicidal behavior, the progression from suicide ideation to plans and attempts, or the persistence of each form of suicidal behavior over time. Moreover, few data are available on such associations in developing countries. The current study addresses each of these issues.
Methodology/Principal Findings
Data on trauma exposure and subsequent first onset of suicidal behavior were collected via structured interviews conducted in the households of 102,245 (age 18+) respondents from 21 countries participating in the WHO World Mental Health Surveys. Bivariate and multivariate survival models tested the relationship between the type and number of traumatic events and subsequent suicidal behavior. A range of traumatic events are associated with suicidal behavior, with sexual and interpersonal violence consistently showing the strongest effects. There is a dose-response relationship between the number of traumatic events and suicide ideation/attempt; however, there is decay in the strength of the association with more events. Although a range of traumatic events are associated with the onset of suicide ideation, fewer events predict which people with suicide ideation progress to suicide plan and attempt, or the persistence of suicidal behavior over time. Associations generally are consistent across high-, middle-, and low-income countries.
Conclusions/Significance
This study provides more detailed information than previously available on the relationship between traumatic events and suicidal behavior and indicates that this association is fairly consistent across developed and developing countries. These data reinforce the importance of psychological trauma as a major public health problem, and highlight the significance of screening for the presence and accumulation of traumatic exposures as a risk factor for suicide ideation and attempt.
doi:10.1371/journal.pone.0010574
PMCID: PMC2869349  PMID: 20485530
20.  Physical Activity and Cardiovascular Disease in Japan: The Jichi Medical School Cohort Study 
Journal of Epidemiology  2010;20(3):225-230.
Background
Many studies have reported an association between physical activity and cardiovascular disease (CVD); however, the effect of physical activity remains controversial. Few such studies have been conducted in Japan. Therefore, we examined the relationship between physical activity and death from CVD using prospective data from a Japanese population.
Methods
From a prospective cohort study that comprised 12 490 participants, data from 9810 were analyzed. From April 1992 through July 1995, a baseline survey was conducted in 12 communities in Japan. The participants were followed up until December 2005. Physical activity was assessed using the physical activity index (PAI). PAI scores were grouped in quartiles: Q1 was the lowest PAI quartile and Q4 was the highest. Hazard ratios (HRs) for death from CVD, stroke, and myocardial infarction (MI) were calculated for all PAI quartiles.
Results
The mean follow-up period was 11.9 years, during which time 194 participants died of CVD. With Q1 as the reference, the HRs for death from CVD in Q2, Q3, and Q4, were 0.62 (95% confidence interval, 0.40–0.98), 0.53 (0.31–0.88), and 0.40 (0.22–0.73), respectively, in men, and 0.71 (0.38–1.32), 0.52 (0.26–1.04), and 0.48 (0.22–1.05), respectively, in women. The HRs for death from CVD subtypes were similar but not statistically significant.
Conclusions
Among a Japanese population, physical activity was associated with a decreased risk of death from CVD. However, more evidence is needed to elucidate the relationships between physical activity and CVD subtypes.
doi:10.2188/jea.JE20090051
PMCID: PMC3900845  PMID: 20208400
motor activity; cardiovascular diseases; stroke; cohort studies; Japan
21.  Use of a Population-Based Cancer Registry to Calculate Twenty-Year Trends in Cancer Incidence and Mortality in Fukui Prefecture 
Journal of Epidemiology  2010;20(3):244-252.
Background
There have been only a limited number of trend analyses of incidence and mortality using population-based cancer registry data in Japan, and the national statistics regarding incidence are estimated data. In the present study, data from the Fukui Prefecture cancer registry, which is the most accurate in Japan, were used to observe trends in incidence and mortality rates.
Methods
Cancer incidence and mortality rates from 1984 through 2004 were obtained from the Fukui Prefecture cancer registry. Joinpoint analysis developed for the US National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program was used to compute and graphically present annual percentage changes in age-adjusted incidence and mortality in Fukui Prefecture.
Results
On joinpoint analysis, there were slight increases in incidence at all cancer sites combined for both sexes from 1986, but the trend was not significant in Fukui. Mortality in women appeared to significantly decrease, while mortality in men, which had been increasing until 1999, began to significantly decrease thereafter. In an analysis by anatomical site, both the incidence and mortality of stomach cancer significantly decreased in both sexes. However, the incidence and mortality of breast and prostate cancers significantly increased. The mortality of liver and lung cancers also increased in both sexes.
Conclusions
Cancer mortality has been declining in recent years, and the reduction in mortality from stomach cancer has significantly affected the trends in Fukui. Urgent cancer control planning by the Fukui local government is necessary, especially for cancers of the liver, lung, prostate, and breast.
doi:10.2188/jea.JE20090102
PMCID: PMC3900848  PMID: 20431235
incidence; mortality; population-based cancer registry
22.  Association between Food Group Intake and Serum Total Cholesterol in the Japanese Population: NIPPON DATA 80/90 
Journal of Epidemiology  2010;20(Suppl 3):S576-S581.
Background
Dietary habit is one of the important determinants of health. Investigation of the association between diet and blood lipids at the food product level is more advantageous than that at the nutrient level because the results can be applied more directly to improving dietary habits for disease prevention.
Methods
The integrated datasets of the NIPPON DATA and National Nutrition Surveys in Japan conducted in 1980 and 1990 were used for analysis. The association between serum total cholesterol concentration and food group intake was examined by multiple linear regression analysis separately for sex and survey year with data adjusted for age, body mass index and total energy intake.
Results
Intakes of rice, sugar, sweets and snacks, fruit and vegetables other than green and yellow ones were lower and intakes of green and yellow vegetables, mushrooms, seaweed, eggs and milk were higher in the 1990 survey than in the 1980 survey. Intakes of meat, milk and eggs showed a positive association with serum total cholesterol concentration in both sexes while intake of legumes showed a negative association only in men in both the 1980 and 1990 surveys.
Conclusions
Sex- and age-specific food group intakes for 1980 and 1990 were identified, and positive and negative associations between serum total cholesterol concentration and food group intake were revealed in a representative sample of the Japanese population. The results provide some insights into the improvements in dietary habits that can be made for disease prevention in Japan.
doi:10.2188/jea.JE20090227
PMCID: PMC3920384  PMID: 20351480
serum cholesterol; Japan; nutrition; food; diet; survey
23.  Sleep Duration and Incidence of Cardiovascular Events in a Japanese Population: The Jichi Medical School Cohort Study 
Journal of Epidemiology  2010;20(2):106-110.
Background
Although sleep is one of the most important health-related factors, the relationship between sleep duration and the incidence of cardiovascular events has not been fully described.
Methods
The present study comprised the 11 367 study subjects (4413 men and 6954 women) of the Jichi Medical School Cohort Study, a population-based prospective study. Baseline data were obtained by questionnaire and health examinations between April 1992 and July 1995 in 12 rural areas in Japan, and the main outcome measures were the incidence of cardiovascular diseases (stroke and myocardial infarction [MI]). Cox proportional hazards models were used to analyze the association between sleep duration and the incidence of cardiovascular events.
Results
A total of 481carciovascular events (255 men and 226 women) were observed during an average follow-up period of 10.7 years. After adjusting for age, systolic blood pressure, serum total cholesterol, body mass index, smoking habits, and alcohol drinking habits, the hazard ratios (95% confidence intervals) for the incidence of cardiovascular diseases for individuals sleeping less than 6 hours and 9 hours or longer were 2.14 (1.11–4.13) and 1.33 (0.93–1.92) in men, and 1.46 (0.70–3.04) and 1.28 (0.88–1.87) in women, respectively, relative to those who reported sleeping 7 to 7.9 hours per day.
Conclusions
Our data indicate that men who sleep less than 6 hours a day have a higher risk of cardiovascular events than those sleeping 7 to 7.9 hours.
doi:10.2188/jea.JE20090053
PMCID: PMC3900808  PMID: 20009370
cohort studies; sleep; cardiovascular disease; cerebrovascular disease
24.  Power-Frequency Magnetic Fields and Childhood Brain Tumors: A Case-Control Study in Japan 
Journal of Epidemiology  2010;20(1):54-61.
Background
The strength of the association between brain tumors in children and residential power-frequency magnetic fields (MF) has varied in previous studies, which may be due in part to possible misclassification of MF exposure. This study aimed to examine this association in Japan by improving measurement techniques, and by extending measurement to a whole week.
Methods
This population-based case-control study encompassed 54% of Japanese children under 15 years of age. After excluding ineligible targeted children, 55 newly diagnosed brain tumor cases and 99 sex-, age-, and residential area-matched controls were included in the analyses. The MF exposures of each set of matching cases and controls were measured in close temporal proximity to control for seasonal variation; the average difference was 12.4 days. The mean interval between diagnosis and MF measurements was 1.1 years. The weekly mean MF level was defined as the exposure. The association was evaluated using conditional logistic regression analysis that controlled for possible confounding factors.
Results
The odds ratios (95% CI) for exposure categories of 0.1 to 0.2, 0.2 to 0.4, and above 0.4 µT, against a reference category of <0.1 µT, were 0.74 (0.17–3.18), 1.58 (0.25–9.83), and 10.9 (1.05–113), respectively, after adjusting for maternal education. This dose-response pattern was stable when other variables were included in the model as possible confounding factors.
Conclusions
A positive association was found between high-level exposure—above 0.4 µT—and the risk of brain tumors. This association could not be explained solely by confounding factors or selection bias.
doi:10.2188/jea.JE20081017
PMCID: PMC3900780  PMID: 19915304
childhood brain tumor; magnetic fields; risk; case-control study; population-based
25.  Association Between Stroke and Metabolic Syndrome in a Japanese Population: Jichi Medical School (JMS) Cohort Study 
Journal of Epidemiology  2010;20(1):62-69.
Background
Metabolic syndrome increases the morbidity and mortality of cardiovascular diseases. However, few studies have examined the association between the incidence of stroke and metabolic syndrome, as defined by Japanese criteria. The aim of this study was to identify the association between stroke and metabolic syndrome, as defined by criteria used in Japan.
Methods
A total of 2205 subjects (920 men and 1285 women) were examined between 1992 and 1995 as part of the Jichi Medical School Cohort Study. Metabolic syndrome was defined using the Japanese criteria. Medical records, computed tomography, and magnetic resonance imaging were used to diagnose stroke. The Cox proportional-hazards model was used to analyze the association between metabolic syndrome and incident stroke.
Results
The prevalence of metabolic syndrome at baseline was 9.0% in men and 1.7% in women. There were 96 incident strokes during an 11.2-year follow-up period, 14 of which occurred in subjects with metabolic syndrome. Among subjects with metabolic syndrome, the age-adjusted hazard ratio (95% confidence interval) for stroke was 1.93 (0.94–3.96) in men and 6.85 (2.68–17.47) in women. After adjusting for age, smoking status, and alcohol drinking status, the hazard ratio was 1.89 (0.88–4.08) in men and 7.24 (2.82–18.58) in women. Age-adjusted hazard ratios associated with having 2 or more components of metabolic syndrome, with and without central obesity, were 2.93 (1.21–7.08) and 3.20 (1.23–8.31) in men and 1.75 (0.69–4.44) and 8.64 (2.82–28.03) in women, respectively.
Conclusions
The presence of metabolic syndrome, as defined by Japanese criteria, increases the risk of stroke; this effect was highly significant among women.
doi:10.2188/jea.JE20081041
PMCID: PMC3900781  PMID: 19966508
metabolic syndrome X; stroke; cohort studies; incidence; cardiovascular diseases

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