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No studies have assessed differences between the Japanese and Z score criteria in the echocardiographic detection sensitivity of coronary artery (CA) abnormalities using large-scale data containing samples from multiple facilities engaged in daily clinical practices of Kawasaki disease (KD). We analyzed data from the 25th Japanese nationwide KD survey, which identified 30,415 patients from 1357 hospitals throughout Japan during 2017-2018. Hospitals were classified according to their use of Z score criteria. We assessed differences in hospital and patient background factors and compared the prevalence of CA abnormalities among groups using the Z score criteria. Multivariable logistic regression analyses were performed to evaluate differences in the detection sensitivity for CA abnormalities. The Z score criteria were more likely to be utilized in larger hospitals with more pediatricians and cardiologists. Even after controlling for potential confounders, detection sensitivities by the Z score criteria were significantly higher than by the Japanese criteria in patients with CA dilatations (adjusted odds ratio (95% confidence interval) 1.77 (1.56-2.01)) and aneurysms (1.62 (1.17-2.24)). No significant difference was found in patients with giant CA aneurysms. Compared with the Japanese criteria, the Z score criteria were significantly more sensitive for detecting patients with CA dilatations regardless of age, and for those with CA aneurysms only in patients aged ≤ 1 year. Our results indicate that differences in the detection sensitivity for CA abnormalities between the Z score and the Japanese criteria were dependent on the CA size and patient age.

ObjectiveWe conducted a nationwide epidemiological study to estimate the number of patients with Takayasu arteritis (TAK) and giant cell arteritis (GCA) in Japan and to describe the clinical characteristics of these patients.MethodsThe first survey was designed to estimate the number of patients with TAK and GCA who were treated at medical institutions in Japan in 2017. The second survey was designed to collect data on the clinical characteristics of the patients who were reported in the first survey.ResultsOf the 3495 institutions selected for the first survey, 1960 (56.1%) responded. The number of patients with clinically diagnosed TAK and GCA was estimated to be 5320 (95% confidence interval, 4810–5820) and 3200 (95% confidence interval, 2830–3570), respectively. Aortic regurgitation was reported in 35% of patients with TAK, and eye-related comorbidities were observed in 30.4% of patients with GCA. The common carotid and internal carotid arteries were the most frequently involved in patients with TAK (62.7%). Subclavian artery lesions and thoracic or abdominal aorta lesions were reported in 31% and 42.6% of patients with GCA, respectively.ConclusionsThe number of patients with TAK and GCA was estimated simultaneously, and significant differences in clinical characteristics were observed between the two diseases.

Hyponatremia is a potential risk factor for the development of coronary artery lesions (CALs) identified after acute Kawasaki disease (KD). However, the serum sodium distribution corresponding to the reference intervals differs between infants ( 1 year of age) and older children. We hypothesized the association of serum sodium level with CAL complications differs between infants and older patients with KD.We analyzed 21,610 population-based patients who developed KD throughout Japan during 2013-2014. We performed multivariable logistic regression analyses to evaluate the association between serum sodium and CAL complications. Additionally, we stratified the serum sodium distribution associated with CAL complications by infants and older patients.CALs were identified in 158 (3.6%) infants and 302 (1.8%) older patients. Infants were more likely to develop CALs when within the normal sodium range compared with older patients (75% vs. 29%), whereas most older patients developed CALs with a sodium level lower than the reference interval. Serum sodium ≤ 130 mEq/L indicated significantly higher risk for development of CALs in both groups (adjusted odds ratio [95% confidence intervals] = 3.21 [1.65-6.25] in infants and 1.74 [1.18-2.57] in older patients).Serum sodium distribution associated with CAL complications differed greatly between infants and older patients. Older patients developed CALs with sodium levels lower than the reference interval; however, among infants, hyponatremia was not necessarily a risk factor for developing coronary artery lesion. When considering risk assessments for CALs using serum sodium levels, infants with KD should be distinguished from older patients. Key Points • Hyponatremia is a potential risk factor for the development of coronary artery lesions (CALs) among patients with Kawasaki disease. • However, the serum sodium distribution corresponding to the reference intervals differs between infants ( 1 year of age) and older children. • Most infants developed CALs within the normal sodium range, whereas older patients developed at a range lower than the reference interval. • These findings highlight that when considering risk assessments for CALs using serum sodium levels, infants should be distinguished from older patients.

The long-term prognosis of those with a history of Kawasaki disease (KD) is still unknown.Using a permanent registry system in Japan (koseki), 6,576 persons with a history of KD were followed up. The average follow-up period was 30 years. The endpoint was death.With a 99.5% follow-up rate, 68 deaths (48 males and 20 females) were observed. The overall standardized mortality ratio, of which reference was vital statistics in Japan, was not elevated. However, the observation according to the presence or absence of cardiac sequelae showed that the standardized mortality ratio for those with cardiac sequelae significantly elevated. Nine persons, all of whom were males, died of KD (including those cases where KD was suspected), but all deaths occurred in individuals who were under 30 years of age.This study revealed the long-term prognosis for KD, but almost all participants were younger than 40 years. Continuing follow up of this cohort is required to clarify whether a history of KD relates to the development of atherosclerosis when participants become middle aged or older.

Serum alanine aminotransferase (ALT) elevation is considered a risk factor for resistance to initial intravenous immunoglobulin (IVIG) treatment in patients with Kawasaki disease (KD). However, serum ALT levels change dramatically during acute KD illness. We tested the hypothesis that risk assessment for initial IVIG resistance based on serum ALT elevation may differ by examination day after KD onset.We analyzed 18,492 population-based patients who developed KD throughout Japan. First, we epidemiologically evaluated the serum ALT variation at 1‒10 days after disease onset. Second, we conducted multivariable logistic regression to determine the association between serum ALT level and initial IVIG resistance according to timing of initial hospital visit by stratifying the patients into an early group (1‒5 days after onset) and a late group (6‒10 days after onset).Serum ALT rapidly increased after KD onset, peaked at day 4 of illness, and then declined regardless of IVIG responsiveness. The adjusted odds ratio (OR) increased with increasing serum ALT in the early group (adjusted OR [95% CI]: 1.44 [1.25-1.66], 1.94 [1.65-2.28], and 2.22 [1.99-2.48] for serum ALT 50-99, 100-199, and ≥ 200 IU/L, respectively; reference ALT level: 1-49 IU/L). No significant association was observed in the late group.The findings indicate that risk assessment for initial IVIG resistance based on serum ALT level may only be reliable for patients with KD who visit hospitals during early illness, specifically 1-5 days after disease onset. Key Points Serum alanine aminotransferase level differed markedly according to examination days after Kawasaki disease onset. Serum alanine aminotransferase level declined toward normal range after day 5 of illness regardless of intravenous immunoglobulin responsiveness. Elevated serum alanine aminotransferase level was no longer a significant risk factor for initial intravenous immunoglobulin resistance when measured on delayed hospital visits. Risk assessment for initial intravenous immunoglobulin resistance based on serum alanine aminotransferase level may only be reliable for patients who visit hospitals during early illness, specifically 1-5 days after disease onset.

Background Previous studies demonstrated that coronary artery lesions (CALs) resulting from Kawasaki disease (KD) can improve over time. However, limited information is available on sub-acute outcomes of CALs detected at admission during KD illness. Methods The nationwide Japanese KD survey contained substantial information on KD patients with CALs detected at admission and who received standard IVIG treatment within 10 days of disease onset. Coronary outcomes were evaluated by changes in CALs from admission to the first assessment at 30 days from disease onset in three categories: improved, unchanged, and progressed. Ordinal logistic regression analysis was performed to evaluate factors associated with the outcomes. Results Of 2024 patients with CALs detected at admission, improved, unchanged, and progressed outcomes were found in 1548 (76.5%), 390 (19.3%), and 86 (4.2%), respectively. Over 80% of patients with coronary artery (CA) dilatations had improved outcome. Independent factors associated with worse outcomes were larger-size CALs (adjusted ORs [95% CIs]: CA aneurysm = 5.13 [3.65-7.22] and giant CA aneurysms = 7.49 [3.56-15.72] compared with CA dilatation, respectively), age ≥ 60 months (1.45 [1.08-1.94] compared with 12-59 months), recurrent KD (1.57 [1.07-2.29]), parental history of KD (2.23 [1.02-4.85]), and delayed admission (8-10 days from disease onset: 1.76 [1.21-2.57] compared with 1-4 days). Conclusions KD patients with larger CALs, ≥60 months old, and with recurrent status or parental history may require more rigorous treatment. In addition, delayed admission may result in worse coronary outcome, indicating that prompt diagnosis and treatment are required.

Background Some patients with Kawasaki disease (KD) develop cardiac sequelae, which increase the risk of subsequent ischemic heart events. Knowing the cumulative incidence (CI) of KD with cardiac sequelae may contribute to developing health policies to prevent subsequent ischemic events in these patients. Methods Study participants consisted of 254 984 patients aged 0-9 years with KD who were registered in nationwide surveys in Japan from 1991-2016. We calculated the incidence probabilities by dividing the number of patients with KD aged 0-9 years by the population used in vital statistics of each calendar year. We calculated the cumulative proportion of those not affected by KD, by multiplying each probability in patients aged from age 0-9 years. The CI of KD was obtained by subtracting this value from 1. We also calculated the number of patients in each birth cohort (BC). The same was done to calculate the CI of KD-related cardiac sequelae. Results The CIBC steadily increased from 0.005067 in males and 0.003668 in females in 1991 to 0.011431 in males and 0.0088253 in females in 2007. The CIBC of KD with cardiac sequelae decreased from 0.000478 in males and 0.000213 in females in 1997 to 0.000339 in males and 0.000169 in females in 2007. Conclusion The increasing CIBC of KD indicates an increased susceptibility to KD in accordance with birth year. The decreasing CIBC of cardiac sequelae suggests the efficacy of KD treatment.

BACKGROUND Platelet count is considered as a biomarker for the development of coronary artery abnormalities (CAAs) among Kawasaki disease (KD) patients. However, previous studies have reported inconsistent results. We addressed the controversial association of platelet count with CAAs using a large-scale dataset. METHODS A retrospective cohort study was conducted using KD survey data from Japan (2015-2016; n = 25,448). Classifying patients by intravenous immunoglobulin (IVIG) responsiveness, we described the trends in platelet count using the lowest and highest values along with the specific illness days. Multivariate logistic regression analysis was performed to evaluate the association between platelet count and CAAs, adjusting for relevant factors. RESULTS Platelet counts rapidly decreased from admission, reached the lowest count at 6-7 days, and peaked after 10 days. Platelet counts in IVIG non-responders decreased with a lower minimum value than IVIG responders, but subsequently rebounded toward a higher maximum. Compared with patients with normal platelet counts (150-450 × 10/L), patients with abnormally high platelet counts (>450 × 10/L) were more likely to have CAAs at admission (adjusted odds ratio: IVIG responders, 1.50 [95% confidence interval 1.20-1.87] and non-responders, 1.46 [1.01-2.12]). By contrast, IVIG non-responding patients whose counts were below normal (

ImportanceGlobal studies have reported that the incidence of Kawasaki disease (KD) declined during the COVID-19 pandemic. These studies suggest that the global pandemic and its accompanying mitigation measures may provide an important opportunity to explore the hypothesis of a KD pathogenesis.ObjectiveTo compare changes in KD incidence in Japan before and after the start of the COVID-19 pandemic.Design, Setting, and ParticipantsThis cohort study was conducted using the data set from Japan’s 26th nationwide KD survey that obtained information on patients who were diagnosed with KD in Japan from January 1, 2019, through December 31, 2020.Main Outcomes and MeasuresKawasaki disease incidence rates were calculated by referring to the national population data in the vital statistics data for Japan.ResultsA total of 28 520 patients were identified (16 236 male individuals [56.9%]; median [IQR] age, 26 [14-44] months). A total of 17 347 patients were diagnosed with KD in 2019 and 11 173 were diagnosed in 2020, representing a 35.6% reduction in the number of patients diagnosed in 2020 compared with the previous year. Patient distributions for days of illness at the first hospital visit were almost identical in 2019 and 2020, suggesting that the decrease in KD incidence likely was not associated with pandemic-related delays in seeking treatment. The proportion of patients diagnosed with KD who were younger than 12 months was significantly larger in 2020 than in 2019 (21.6% vs 19.4%; P Conclusions and RelevanceIn this cohort study, the number of patients diagnosed with KD decreased by approximately one-third across Japan in 2020, with no indication that parents avoided a hospital visit. Differences in KD incidence reduction patterns before and after the initiation of COVID-19 pandemic mitigation measures were found in patients with KD aged younger than 12 months compared with those 24 months or older, suggesting a potential KD pathogenesis involving transmission among children.

Background During the COVID-19 pandemic, children with autism spectrum disorders (ASD) and neurotypical siblings of children with ASD and their parents and caregivers have been required to change their daily schedule. In this study, we focused on siblings of children with ASD to reveal their adjustment to their daily life. In addition, we examined their caregivers’ stress. Methods An online Qualtrics survey was given to caregivers of children with ASD on February, 2021 at Thomas Jefferson University in the United States. First, we assessed the severity of children with ASD. In addition, we examined how their neurotypical siblings adjusted to their daily life using the validated Strength and Difficulties Questionnaire (SDQ). Moreover, we analyzed caregivers’ stress and their socioeconomic status. Results Fifteen caregivers responded to the survey. 42% of children with ASD had behavioral issues beforehand, 80% of which showed worse behaviors during this pandemic. Siblings of children with ASD showed higher scores of difficulties in adapting to new routines during COVID-19. Some caregivers lost their jobs and caregivers of those with behavioral issues reported stress levels that were 4.4 points higher on the scale. Conclusions Siblings of children with ASD and their caregivers are facing difficulties in their daily life during this pandemic. Appropriate support systems for children with ASD, their siblings, and their parents and caregivers may help them with their better adjustment. Key messages Siblings of children with ASD show difficulties in adjusting, and their caregivers feel more stress during COVID-19 pandemic.

Background Ankylosing spondylitis (AS) causes severe chronic inflammation of the spine and sacroiliac joints, leading to severe physical dysfunctions. Non-radiographic axial spondyloarthritis (nr-ax SpA) is a newly categorized disease in SpA that shows SpA without definite radiographic findings in sacroiliac joint. Although human leukocyte antigen (HLA) positivity is related to these diseases, little is known about the prevalence of these diseases and HLA-B27 positivity in Japan. Methods A nationwide survey was conducted from January to December 2017. 2221/8456 facilities (26.3%) were selected randomly as a target sample, comprising all three departments: orthopedics, pediatrics, and rheumatology. We estimated the number of these patients by using response and extraction rate, and calculated the HLA-B27 positivity rate. Results We estimated the prevalence of AS and nr-ax SpA as 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively. HLA-B27 test was performed in 60% of patients with AS, of which 55.5% being HLA-B27 positive; however, they were less likely to receive HLA-B27 test if their estimated age of onset was over 50 years. Conclusions The prevalence in AS and nr-ax SpA and their HLA-B27 positivity rate in Japan were lower compared to other countries. Further studies will be required to reveal the association between HLA-B27 and the clinical features. Key messages The prevalence of AS and nr-ax SpA in Japan are estimated to be 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively, and are lower than those in other countries. In addition, HLA-B27 positivity rate was lower.

Background Kawasaki disease (KD) is the most common cause of acquired pediatric heart disease in developed countries. The study aimed to summarize the epidemiologic characteristics, treatments, and cardiac complications of KD, using data from the nationwide survey in Japan. Methods The nationwide survey in Japan has been conducted biennially since 1970. The survey respondents were hospitals specializing in pediatrics and those with ≥100 beds and a pediatric department throughout Japan, where KD patients were eventually hospitalized. The most recent survey was completed in 2019, obtaining information for patients who developed KD during 2017–2018. Results The survey identified 32528 KD patients, which comprised 15164 (47%) in 2017 and 17364 (53%) in 2018. The highest annual incidence rate was recorded in 2018 (359 per 100,000 children aged 0–4 years). After 1982, patients with ≤4 principal KD signs increased, resulting in 6847 (21%) patients diagnosed during 2017–2018. Among 30784 patients who received initial intravenous immunoglobulin administration, 6061 (20%) did not respond. Within 30 days of KD onset, 9.0% of patients were diagnosed with cardiac complications, and consequently, 2.6% of patients developed cardiac sequelae after the acute illness. Conclusions The annual number of patients developing KD in Japan increased from 1970 through 2018, while the proportion of KD patients with cardiac complications decreased. Recent advances in KD treatments might have contributed to preventing the development of cardiac complications. Key messages We analyzed large-scale data and summarized the epidemiologic characteristics, treatments, and cardiac complications of KD in Japan.

Objective This nationwide study aimed to reveal the prevalence of ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-ax SpA), and the positivity rate of human leukocyte antigen (HLA) among such patients in Japan. Methods The first survey was conducted in 2221 randomly selected facilities (26.3%) in September 2018, where the patients with AS/nr-ax SpA were taken care of from January to December 2017. We estimated the total number of these patients using response and extraction rates. A second survey was conducted in 117 facilities (49.8%) to assess for HLA-B27 positivity rate and clinical features. Results The estimated total numbers of the patients with AS and nr-ax SpA were 3200 (95% confidence interval [CI]: 2400–3900) and 800 (530–1100), suggesting that the prevalence values of AS and nr-ax SpA in general population were 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively. Although 55.5% (76/137) of patients with AS were HLA-B27-positive, those whose age of onset was estimated to be over 50 years tended to undergo less HLA-B27 testing. Conclusion This study revealed the lower prevalence of AS/nr-ax SpA in Japan, compared to those in other countries. Further studies are required to reveal the association of HLA-B27 with the clinical features.

Background Detection of coronary artery lesions (CALs) at initial echocardiography can aid in diagnosing Kawasaki disease (KD) and inform primary adjunctive treatments. We aimed to characterize patients with KD with CALs detected at initial echocardiography. Methods and Results We analyzed data from the nationwide Japanese KD survey that contained information on 103 222 population‐based patients diagnosed with KD across Japan during 2011 to 2018. Patients with CALs detected at initial echocardiography were assessed by age, day of illness, and number of principal KD signs (≥3). Multivariable logistic regression analysis was performed to evaluate factors independently associated with CAL detection. Overall, 3707 (3.6%) patients had CALs detected at initial echocardiography. Patients aged Conclusions Timely diagnosis could be beneficial for patients with KD. However, even when the hospital visit occurred early in the course of illness, patients with 3 or 4 principal KD signs, especially younger patients, were at higher risk of CAL detection at initial echocardiography.

A giant coronary artery (CA) aneurysm is a potentially fatal cardiac complication resulting from Kawasaki disease (KD). We aimed to identify epidemiologic characteristics and potential risk factors associated with giant CA aneurysms identified after acute KD. We analyzed 90,252 patients diagnosed with KD from 2011 to 2018, using data obtained in nationwide KD surveys conducted in Japan. Multivariable logistic regression analyses were performed to evaluate potential risk factors associated with subsequent giant CA aneurysm complications (defined as lumen size ≥ 8 mm), adjusting for all potential factors. Giant CA aneurysms were identified in 144 patients (0.16%) after acute KD. The annual prevalence ranged from 0.07 to 0.20% during the study period. In the multivariate analyses, male sex (adjusted odds ratio 2.09 [95% confidence interval 1.41–3.11], recurrent KD (1.90 [1.09–3.33]), IVIG administration at 1–4 days of illness (1.49 [1.04–2.15]) and ≥ 8 days after KD onset (2.52 [1.38–4.60]; reference, 5–7 days), detection of CA dilatations and aneurysms at initial echocardiography (4.17 [1.85–5.41] and 46.5 [28.8–74.8], respectively), and resistance to IVIG treatment (6.09 [4.23–8.75]) were significantly associated with giant CA aneurysm complications identified after acute KD. The annual prevalence of giant CA aneurysms identified after acute KD did not increase during the study period. Patients with larger CA abnormalities detected at initial echocardiography were independently associated with progression to giant CA aneurysm complications after acute KD regardless of the number of days from onset at treatment initiation.

ObjectiveTo investigate whether redness and crusting at the bacille Calmette-Guérin inoculation site (BCGitis), identified during acute illness owing to Kawasaki disease (KD), is an independent risk factor for development of cardiac complications.DesignRetrospective cohort study using data from the nationwide KD survey in Japan.SettingSurvey respondents included hospitals specialising in paediatrics and hospitals with ≥100 beds and a paediatric department throughout Japan.PatientsWe included 17 181 patients with KD across Japan during 2005–2006.Main outcome measuresBCGitis and cardiac complications resulting from KD.ResultsBCGitis was identified in 7549 (44%) patients with KD. Compared with patients without BCGitis, those with BCGitis were younger, more likely to be male, less likely to have recurrent status and visited a hospital and underwent initial intravenous immunoglobulin (IVIG) treatment earlier after KD onset. In the unadjusted model, patients with BCGitis were significantly less likely to have cardiac complications (crude OR 0.81, 95% CI 0.71 to 0.92). However, after including treatment factors (days of illness at initial IVIG and treatment responsiveness) in the adjusted model, the association was no longer significant (adjusted OR 0.89, 95% CI 0.77 to 1.03), indicating that BCGitis was not an independent factor associated with cardiac complication and might be confounded by treatment factors.ConclusionsBCGitis was identified in comparatively early illness stages of KD. Our findings indicated that BCGitis was not an independent factor associated with developing cardiac complications but was confounded by prompt initial IVIG administration, which might result in successful treatment and prevention of cardiac complications.

Background Acute encephalopathy causes various sequelae, including motor disabilities and intellectual delays. Previous studies reported that cognitive impairments can also occur after acute encephalitis. Although the incidence of acute encephalopathy is high in Japan, there have been few reports on its sequelae. Objective To characterize the neurological outcomes of pediatric patients who sought motor rehabilitation for motor dysfunction after acute encephalopathy. Method Subjects were 26 children who were healthy before suffering from motor dysfunction following acute encephalopathy and were referred to our pediatric rehabilitation institute during a 9-year period (August 2007–April 2017). We examined subjects’ neurological status and followed sequelae for at least 8 months. Results Of 26 individuals, 21 became ambulatory after several months or years during the observation period. Patients who could sit without support within 5 months after the onset of acute encephalopathy were able to walk within several months or years. Patients showing high intensity on T2-weighted sequences or “bright tree appearance” in the frontal region took an average of 7 months to develop walking, which was longer than other patients. Among ambulatory subjects, 16(76%) exhibited mild to moderate intellectual delay with a developmental quotient (DQ) under 70, and 20 (95%) exhibited cognitive impairment. There was a significant correlation between DQ scores and motor disability (p = 0.013, r = −0.481). Conclusions Although 80% of patients who had motor dysfunction caused by acute encephalopathy and visited out motor rehabilitation outpatient clinic were eventually able to walk, the time taken to develop walking ability depended on which region exhibited magnetic resonance imaging abnormalities. DQ scores and motor disability were significantly correlated.

Background: Globally, few published studies have tracked the temporal trend of dioxin levels in the human body since 2000. This study describes the annual trend of dioxin levels in human breast milk in Japanese mothers from 1998 through 2015. Methods: An observational study was conducted from 1998 through 2015. Participants were 1,194 healthy mothers following their first delivery who were recruited annually in Japan. Breast milk samples obtained from participants were analyzed using gas chromatography and mass spectrometry for dioxins, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs). Results: Mean age was 29.5 years, and 53% of participants were 20–25 years old. A declining trend in total dioxin levels was found, from a peak of 20.8 pg toxic equivalence (TEQ)/g fat in 1998 to 7.2 pg TEQ/g fat in 2014. Data from the last 5 years of the study indicated a plateau at minimal levels. In contrast, an increasing trend was found in the mean age of participants during the last 5 years. Although significantly higher dioxin levels were observed in samples from older participants, an upward trend in dioxin levels was not observed, indicating that dietary and environmental exposure to dioxins had greatly diminished in recent years. Conclusions: Dioxin levels in human breast milk may be approaching a minimum in recent years in Japan. The findings may contribute to global reference levels for environmental pollution of dioxins, which remains a problem for many developing countries.

BACKGROUND Evidence suggests that seasonal variation in the onset of Kawasaki disease (KD) exists worldwide. Whether a seasonal component to successful i.v. immunoglobulin (IVIG) therapy exists in KD-positive children, however, is unknown. We addressed this question by focusing on patients with primary onset KD who were non-responsive to IVIG treatment, in the large nationwide Japanese KD survey datasets from 2009 to 2016. METHODS In these datasets, the IVIG therapy non-responders were defined as patients whose fever persisted ≥24 h or recurred ≤24 h after the end of the initial IVIG treatment (dosage, 2,000 mg/kg). Those who successfully responded to this treatment were defined as IVIG responders. The consecutive monthly trend of the proportion of IVIG non-responders was analyzed throughout the study period to investigate seasonal periodicity on Fourier analysis, and the monthly distributions of non-responders and responders were compared. RESULTS From a total of 113 691 KD-positive patients, 15.7% were IVIG non-responders, and 61% were male. The proportion of non-responders increased across each calendar year with fluctuation, and Fourier analysis indicated seasonal periodicity. The seasonality effect differed between responders and non-responders, with the proportion of responders tending to increase in autumn through winter, while the non-responders showed a decreasing trend in autumn. The seasonality effect tended to differ by sex. CONCLUSIONS The results indicate that the currently unknown etiological agents of KD might differ between IVIG responders and non-responders. In addition, immune reactivity against such agents possibly differs by sex in the IVIG non-responders.

Objective To report the epidemiologic characteristics, treatments, and cardiac complications of Kawasaki disease, using data from the nationwide survey in Japan. Study design The nationwide Kawasaki disease survey in Japan has been conducted biennially since 1970. The most recent survey was completed in 2019, obtaining information for patients who developed Kawasaki disease during 2017-2018. Survey respondents were hospitals specializing in pediatrics and those with ≥100 beds and a pediatric department throughout Japan, where patients with Kawasaki disease were eventually hospitalized. Results The survey identified 32 528 patients with Kawasaki disease, which consisted of 15 164 (46.6%) in 2017 and 17 364 (53.4%) in 2018. The highest annual incidence rate was recorded in 2018 (359 per 100 000 children aged 0-4 years). After 1982, patients with ≤4 principal Kawasaki disease signs gradually increased, resulting in 6847 (21.1%) patients diagnosed during 2017-2018. Among the 30 784 patients receiving initial intravenous immunoglobulin administration, 6061 (19.7%) did not respond. Within 30 days of Kawasaki disease onset, 9.0% of patients were diagnosed with cardiac complications, and 2.6% of patients developed cardiac sequelae after the acute illness. Conclusions The annual number of patients developing Kawasaki disease in Japan increased from 1970 through 2018, whereas the proportion of patients with Kawasaki disease with cardiac complications decreased in the most recent 2 decades. Early diagnosis of Kawasaki disease as well as advances in initial treatments could explain these findings.

Objective Few studies have reported the influence of clinical background factors on the outcome of Helicobacter pylori eradication therapy in primary care practice. We aimed to determine which clinical background factors influence the outcome of eradication therapy in a primary care setting. Methods This was a retrospective study of patients who received H pylori eradication therapy at Higashiohmi City Gamo Medical Center, Shiga, Japan, from January 2012 to December 2015. We investigated clinical background factors associated with success, failure, and self‐interruption of H pylori eradication therapy: patients’ age, gender, first‐ or second‐line treatment, reasons for receiving gastroenterological endoscopic examination, method of drug administration, and attending physicians’ age and their specialties. Results There were 369 patients (208 females, 161 male), with a mean age of 59 years (range 30‐88 years). The middle‐aged group (50‐69 years) was associated with successful eradication therapy compared with the young group (30‐49 years). The elderly group (>70 years) was associated with eradication therapy failure compared with the middle‐aged group. The young group was associated with self‐interruption of eradication therapy. There was a marginally significant association between male patients and self‐interruption. Older attending physicians (>50 years) were also associated with failure compared with younger physicians. There was no difference in outcome of eradication therapy between generalists and gastroenterology specialists. Conclusion We have identified clinical factors associated with success, failure, and self‐interruption of H pylori eradication therapy in a primary care setting.

Background Approximately 50 years have passed since Kawasaki disease (KD) was first reported. The KD nationwide survey began in 1970. Although >360 000 cases have already been reported in Japan, the cause is still unknown. In Japan, the number of patients and incidence rate of KD has continued to increase. It is necessary to examine the trend of the occurrence in the surveillance of KD. Methods The nationwide survey of patient incidence in 2015 and 2016 was conducted in 2017, as the 24th nationwide survey of KD. A questionnaire was sent to pediatric departments in hospitals with >100 beds and specialized pediatric hospitals, and was responded to by the attending pediatricians. Results The total number of patients in 2 years was 31 595, and the sex ratio (male/female) was 1.34. The incidence rate (/100 000 children aged 0-4 years/year) was 330.2 (371.2 in boys, 287.3 in girls) in 2015, and 309.0 (343.2 in boys, 273.2 in girls) in 2016. The number of patients by month peaked in January. The age-specific incidence rate according to sex was highest in children between 9 and 11 months of age, after which the incidence rate gradually decreased with advancing age. Conclusions We summarize the most recent nationwide survey of KD and consider the change in the epidemiologic picture.

Evidence suggests that seasonal variation in the onset of Kawasaki disease (KD) exists worldwide. Whether a seasonal component to successful i.v. immunoglobulin (IVIG) therapy exists in KD-positive children, however, is unknown. We addressed this question by focusing on patients with primary onset KD who were non-responsive to IVIG treatment, in the large nationwide Japanese KD survey datasets from 2009 to 2016.In these datasets, the IVIG therapy non-responders were defined as patients whose fever persisted ≥24 h or recurred ≤24 h after the end of the initial IVIG treatment (dosage, 2,000 mg/kg). Those who successfully responded to this treatment were defined as IVIG responders. The consecutive monthly trend of the proportion of IVIG non-responders was analyzed throughout the study period to investigate seasonal periodicity on Fourier analysis, and the monthly distributions of non-responders and responders were compared.From a total of 113 691 KD-positive patients, 15.7% were IVIG non-responders, and 61% were male. The proportion of non-responders increased across each calendar year with fluctuation, and Fourier analysis indicated seasonal periodicity. The seasonality effect differed between responders and non-responders, with the proportion of responders tending to increase in autumn through winter, while the non-responders showed a decreasing trend in autumn. The seasonality effect tended to differ by sex.The results indicate that the currently unknown etiological agents of KD might differ between IVIG responders and non-responders. In addition, immune reactivity against such agents possibly differs by sex in the IVIG non-responders.

The number of patients with food allergy in Japan is increasing year by year, although the precise prevalence of them is not clear. We aimed to determine the estimated number of people with food allergies in Japan and produce new methods of the investigation of them.We determined the number of people with food allergies using government data and statistics such as demographic statistic and the number of students.In infants, the number of patients with a food allergy was 800000 as per the self-reported prevalence; however, as per the physician's diagnoses, 300000-500000 of them had a food allergy. In students, the selfreported number was 600000, while 350000 cases were diagnosed by physicians. In adults, the consumer agency investigated the patients who visited the hospital with the immediate hypersensitivity. In this study, the participants were limited to patients who visited the hospital. This made the estimation of the overall prevalence of food allergy in Japan.For children, if we add the questionnaire to the existing study, which questions them regarding the symptoms of food allergy, the diagnosis by the physician, and the blood test, we can better investigate the prevalence of food allergies and changing pattern by the year. In adults, we propose that future investigations consisting of the National Health and Nutrition Survey and a comprehensive survey of living conditions should be conducted, because few studies have reported on food allergies.

Objectives To reveal the features of death and subsequent funeral services, we analyzed self-reported obituaries in The Shimotsuke, a local daily newspaper in Tochigi, Japan. In addition, the usefulness and disadvantages of such a database of deaths based on the obituaries were discussed.Method For a 5-year period, from January 2011 through December 2015, all the obituary columns in The Shimotsuke were computerized as a database and analyzed. Some results were compared with the vital statistics data in the corresponding period of time. Data analyzed were: dead persons' address (municipalities), name, sex, cause of death, age at death, date of death and funeral services, the chief mourner (Moshu), and so on.Results During the observed 5-year period, 69,793 deaths appeared in the columns, which were 67.6% of the all deaths in the vital statistics. No difference was observed in the proportions between the sexes in the published deaths in comparison with the vital statistics. In both sexes, the proportion was low in 0-9 years old, then high among 10-19 years, decreasing in 20s, and after then the proportion increased according to the age. The proportion was low in city areas, such as Utsunomiya and Oyama, and high in some cities and towns in the northern or eastern parts of Tochigi prefecture. The highest was in Motegi Town (88.0%), and the lowest was Nogi Town (38.0%), which is located in the southern-most part of the prefecture and is closest to the Tokyo metropolitan area. Almost all the funeral services were conducted within a week of the death, and no delays were observed to have been caused by the short supply of cremation services, which exists in large cities in Japan. In case where the chief mourner was a child, a parent, or a spouse of a child, the male sex was dominant. Analyses of death from senile decay, suicide, and homicide indicated that the accuracy of the published cause of death was low. The date of the funeral services was strongly influenced by superstitions in this country.Conclusions Observations of the self-reported obituaries in a local daily newspaper over five years revealed the situations of the deaths in the area that could not be observed using vital statistics. Despite limitations, the information was partially useful as a database.

One hundred and three patients with maxillofacial fractures due to work-related accidents were analysed. Ninety-nine patients (96.1%) were male and 4 (3.9%) were female. The average age was 46.8 years (range 18-75 years). The injuries were most commonly sustained during construction (42 patients, 40.8%) followed by agriculture and forestry (31 patients, 30.1%) and manufacturing (15 patients, 14.6%). Being struck by an object was the main cause of injury (43 patients, 41.7%) followed by fall from one level to another (31 patients, 30.1%). Fifty-four patients (52.4%) had fractures in the mandible, 41 (39.8%) in the midface, and 8 (7.8%) in both the mandible and the midface. The most common sites for fractures were the condyle and symphysis in the mandible and zygoma in the midface. The facial injury severity scale ranged from 1 to 6 with an average of 1.99±1.18. There was no difference in the nature of the work being undertaken or the cause of the injury. Fractures in other sites were observed in 22 patients (21.4%). Open reduction and fixation was the most frequent treatment for mandibular fractures (25 patients, 40.3%) followed by maxillomandibular fixation (19 patients, 30.6%). Observation was most commonly used for midface fractures (18 patients, 36.7%) followed by open reduction and fixation (15 patients, 30.6%) and transcutaneous reduction (8 patients, 16.3%).

The fate of developing tooth buds located in relation to mandibular fractures was investigated in three infancy cases. Three infants, 2 girls and a boy, aged from 1 year and 5-months old to 2 years and 6-months old, were treated for dislocated mandibular fracture in the symphyseal region by manual reduction and fixation with a thermoforming splint and circumferential wiring under general anesthesia. Fracture healing was uneventful in all cases. A few years later, no obvious deformity of the jaw or malocclusion was observed; however, malformation of the crown was found in one of the permanent teeth on the fracture line in the first case. In the second case, no abnormality was observed in one of the permanent teeth on the fracture line, but the effect on the other tooth could not be evaluated due to abnormality of the tooth probably not related to the injury. In the third case, root formation was arrested in one of the permanent teeth on the fracture line and the tooth was lost early after eruption. The development of tooth buds on the fracture line is not predictable and therefore, should be monitored by regular follow up.

The fate of developing tooth buds located in relation to mandibular fractures was investigated in three infancy cases. Three infants, 2 girls and a boy, aged from 1 year and 5-months old to 2 years and 6-months old, were treated for dislocated mandibular fracture in the symphyseal region by manual reduction and fixation with a thermoforming splint and circumferential wiring under general anesthesia. Fracture healing was uneventful in all cases. A few years later, no obvious deformity of the jaw or malocclusion was observed; however, malformation of the crown was found in one of the permanent teeth on the fracture line in the first case. In the second case, no abnormality was observed in one of the permanent teeth on the fracture line, but the effect on the other tooth could not be evaluated due to abnormality of the tooth probably not related to the injury. In the third case, root formation was arrested in one of the permanent teeth on the fracture line and the tooth was lost early after eruption. The development of tooth buds on the fracture line is not predictable and therefore, should be monitored by regular follow up.

The appearance of vasculitis is often observed following the use of epirubicin hydrochloride in outpatients. As it is important to continue to provide a safe treatment for outpatient with little or no side effects, the aim of this study was to reveal causes underlying the outbreak of vasculitis or the vasculitic state of patients who had undergone instillation of epirubicin hydrochloride as an adjuvant therapy following a breast cancer surgery. The study was conducted based on past investigation records. We extracted relevant factors such as age, previous illness, physical condition and dosage of epirubicin hydrochloride from past records which may all be connected to the outbreak of vasculitis. We administered one dose of epirubicin hydrochloride that was diluted into 50-100 ml of normal saline solution or 5% glucose and instilled over a period of 30 minutes. As a result of this instillation of epirubicin hydrochloride, 35 out of 45 cases displayed vasculitis. We did not observe any relationship among the aged (over 60), previous illness or physical condition (BMI over 25) and the appearance of vasculitis. When a dosage amount of more than 110 mg of epirubicin hydrochloride was administered, 23 out of 29 cases displayed vasculitis. From the past records, it was observed that the cause of vasculitis was dependent on the administrative method itself. As previous studies reported that vasculitis was low when epirubicin hydrochloride was retained in blood vessels for only a short time, our study, however, concentrated on how to administer epirubicin hydrochloride. Our results suggested that an adoption of a single dosage system may suppress the outbreak of vasculitis.