Izumi Oki

Epidemiologic Features of Kawasaki Disease in Japan: Results from the Nationwide Survey in 2005-2006

Background The most recent epidemiologic features of Kawasaki disease are unknown. Methods The 19th nationwide survey of the disease was conducted in 2007, targeting patients who were affected by this disease in 2005 and 2006. All pediatric departments in hospitals with 100 or more beds and pediatric hospitals were asked to report all Kawasaki disease patients during the 2 survey years. Results From 1543 departments and hospitals, a total of 20475 patients (10041 in 2005 and 10434 in 2006) were reported. There were 11892 male patients and 8583 female patients. The average annual incidence rate was 184.6 per 100000 children aged 0-4 years. The number of patients and the incidence rate have increased significantly during the past 12 years. The age-specific incidence rate was distributed monomodally with a peak at 6-8 months of age. The prevalence of cardiac lesions in the acute phase of the disease and of cardiac sequelae were higher among infants and old patients. Conclusion The number of patients with Kawasaki disease and its incidence rate in Japan are continuously increasing.

Incidence of Kawasaki disease in Japan: the nationwide surveys of 1999-2002.

Objective: The purpose of the present study was to describe the results of nationwide epidemiologic surveys of Kawasaki disease for the 4 year period 1999–2002.

Increasing incidence of Kawasaki disease in Japan: Nationwide survey

Background: The last nationwide survey of Kawasaki disease in Japan was conducted in 2003; the epidemiologic features of the disease in Japan since then are unknown.

Analysis of potential risk factors associated with nonresponse to initial intravenous immunoglobulin treatment among Kawasaki disease patients in Japan.

Background: Some Kawasaki disease (KD) patients do not respond to initial treatment with intravenous immunoglobulin (IVIG). The purpose of this study was to determine potential risk factors associated with IVIG nonresponse among KD patients in Japan. Methods: Data were obtained from questionnaires used for the 18th nationwide KD survey of patients who visited hospitals in Japan from 2003 through 2004. Data for patients who met the case definition for KD and received 2 g/kg single infusion IVIG as the initial treatment within 10 days of illness were analyzed. IVIG nonresponders were defined as patients who needed secondary treatment after initial IVIG administration. Results: Among 15,940 KD patients in Japan during 2003–2004, 6330 patients received 2 g/kg single infusion IVIG within 10 days of illness onset. IVIG nonresponders accounted for 20.3% of them (n = 1286). Male sex [odds ratio (OR), 1.21, 95% confidence interval (CI), 1.06–1.37], receipt of the initial IVIG before the fifth day of illness (OR: 1.89, 95% CI: 1.66–2.15), and having recurrent KD (OR: 1.38, 95% CI: 1.00–1.90) were significantly associated with IVIG nonresponse. In addition, IVIG nonresponders had significantly higher risks for coronary artery aneurysms (OR: 10.38, 95% CI: 6.98–15.45) or giant coronary artery aneurysms (OR: 54.06, 95% CI: 12.84–227.65). Conclusions: Physicians should consider potential IVIG nonresponse among recurrent KD patients or KD patients diagnosed and treated before the fifth day of illness, particularly if they are boys and have laboratory values associated with nonresponse such as low platelet count, and elevated alanine aminotransferase and C-reactive protein. Some of these patients may benefit from administration of the alternative secondary treatment early during the illness along with the initial IVIG treatment.

Use of laboratory data to identify risk factors of giant coronary aneurysms due to Kawasaki disease

Abstract Background : Although some laboratory findings are known to be indicators of the risk of giant coronary aneurysm formation among Kawasaki disease patients, an appropriate cut‐off point to predict aneurysm formation is not clear.

Changes in epidemic patterns of Kawasaki disease in Japan

OBJECTIVE Clustering of cases of Kawasaki disease throughout Japan was noted three times during the period before 1986. During the ensuing 10 years, however, no nationwide epidemic has been recognized. The purpose of this study is to test the hypothesis that local outbreaks have persisted after 1987. METHOD The data on 56 980 patients reported from 1987 through 1996 were classified according to the area of residence. The time trend of the incidence rate was compared by year and by quarter of the year (January to March, April to June, July to September and October to December) in 10 geographical areas in Japan. RESULTS No nationwide outbreaks have been noted since 1987 in Japan, but the existence of local outbreaks of various magnitudes was recognized as occurring in different periods in certain areas. The incidence rates were continuously high in Area 1 between 1987 and 1988 and in Area 4 between 1995 and 1996. In Area 9 local outbreaks were noted on three separate occasions (from 1987 to the first half of 1988, between 1990 and 1991 and from the second half of 1992 to 1993). No clusterings were witnessed in other areas during the 10-year period. CONCLUSION The current annual number of patients ranges from 5000 to 6000, and local epidemics occur in various areas. The current epidemiologic patterns support the infection theory for the etiology of this disease.

Body Mass Index and Risk of Stroke Mortality among a Random Sample of Japanese Adults: 19-Year Follow-Up of NIPPON DATA80

Background: The relationship between body mass index (BMI) and stroke mortality remains unclear. The aim of the present study was to elucidate the relationship between BMI and stroke death in a representative cohort of Japanese men and women. Methods: We analyzed a database of 9,526 men and women aged 30 years and older who were randomly selected throughout Japan in 1980. These individuals had no history of stroke and were followed for 19 years. Hazard ratios (HR) and their 95% confidence intervals (CI) of deaths due to total stroke, cerebral infarction, and intracerebral hemorrhage were examined using Cox’s proportional hazards regression models of BMI levels. Results: A U-shaped association between BMI and cerebral infarction mortality was observed. Participants with the highest BMI category (BMI ≧ 30.0) showed a significantly highest HR for cerebral infarction (HR 2.46, 95% CI 1.01–5.99). The excess risk at the lower extreme of the BMI was confined to men. These associations did not change after excluding deaths occurring in the first 2 years of follow-up. Conclusions: In the Japanese general population, a U-shaped association between BMI and cerebral infarction mortality was found and the excess risk at the lower extreme of the BMI was confined to men.

PCDDs, PCdfs and Co-PCBs in human breast milk samples collected in Tokyo, Japan.

Aim: To observe the distribution of PCDD/Fs and Co‐PCBs in samples of human breast milk collected in Japan. Methods: Using high‐resolution gas chromatography, milk samples for poly‐chlorinated dibenzo‐p‐dioxins (PCDDs; 14 congeners), poly chlorinated dibenzofurans (PCDFs; 15 congeners) and coplanar poly chlorinated biphenyls (Co‐PCBs; 12 congeners) from 240 mothers residing in Tokyo were analysed. There were 120 donors each of primiparae and secundiparae, each group including 60 donors aged 25 to 29 y (“the younger group”) and 60 aged 30 to 34 y (“the older group”). Individual milk samples (about 50 ml) were obtained 30 d after delivery in 1999 and in 2000. Results: The mean toxic equivalent (TEQ) level of PCDD/Fs (the sum of PCDDs and PCDFs) was 14.9 pg TEQ/g fat, of Co‐PCBs 10.6 pg TEQ/g fat, and the total sum of PCDD/Fs and Co‐PCBs was 25.6 pg TEQ/g fat. The mean TEQ levels of PCDD/Fs, Co‐PCBs, and total PCDD/Fs and Co‐PCBs were higher in primiparae than in secundiparae. In each of these, the levels were higher in the subgroup of older mothers. In the secundiparae, the mean levels were lower in the group of mothers who had breastfed their first babies than in those who bottle‐fed or partly bottle‐fed their first born.

Relationship Between BMI and All-cause Mortality in Japan: NIPPON DATA80

As body composition in Asian populations is largely different from Western populations, a healthy BMI could also differ between the two populations. Thus, further study is needed to determine whether a healthy BMI in Asians should be lower than Western populations, as recommended by the World Health Organization (WHO). We investigated the relationship between BMI and mortality in a sample of 8,924 Japanese men and women without stroke or heart disease. During 19 years of follow‐up, 1,718 deaths were observed. We found a U‐shaped relationship between BMI and fatal events. Risk of total mortality was highest in participants with BMI <18.5 kg/m2 and lowest in participants with BMI 23.0–24.9 kg/m2. These findings persisted even after excluding the first 5 years of follow‐up with a focus on healthy participants who never smoked, were aged <70 years, and had total cholesterol (TC) levels ≥4.1 mmol/l (N = 3712). For both the full sample and healthy participants, all‐cause mortality risk did not differ between BMI ranges 21.0–22.9 and 23.0–24.9 kg/m2. Our findings do not support the recent WHO implications that BMIs <23.0 kg/m2 is healthy for Asians. Therefore, further studies are needed to identify an optimal BMI range for Asia.

Factors relating to the cardiac sequelae of Kawasaki disease one month after initial onset

This study aimed to determine the risk factors related to the presence of cardiac sequelae 1 mo after initial onset and to examine the preventive effect of the early administration of high‐dose gamma‐globulin (GG) on cardiac sequelae in patients with Kawasaki disease. Patients treated with high‐dose GG of 2000 ± 100 mg kg‐1 were selected as subjects from the 15th nation‐wide survey in Japan. Univariate and logistic multiple variable analyses were used to test the effects of background variables such as age and gender, variables relating to laboratory findings such as the percentage of neutrophil leucocytes, and variables relating to the GG treatment on the presence of cardiac sequelae. The odds ratios were significantly higher for males (1.48), those younger than 1 y of age (1.71), recurrent cases (2.42), and those with a low haematocrit (>32.5%) (1.45) and high percentage of neutrophil leucocytes (<68%) (1.63). The odds ratio was low for those who started GG administration in less than 6 d from onset between the patients with and without cardiac sequelae. The odds ratio for the duration of GG treatment was not significantly different between those with and without cardiac sequelae.