阿江 竜介

The potential contribution of serum osmolarity in the modulation of blood pressure has not been evaluated. This study was done to examine the relationship between hyperosmolarity and hypertension in a five-year longitudinal design. We enrolled 10,157 normotensive subjects without diabetes who developed hypertension subsequently as determined by annual medical examination in St. Luke's International Hospital, Tokyo, between 2004 and 2009. High salt intake was defined as >12 g/day by a self-answered questionnaire and hyperosmolarity was defined as >293 mOsm/L serum osmolarity, calculated using serum sodium, fasting blood glucose, and blood urea nitrogen. Statistical analyses included adjustments for age, gender, body mass index, smoking, drinking alcohol, dyslipidemia, hyperuricemia, and chronic kidney disease. In the patients with normal osmolarity, the group with high salt intake had a higher cumulative incidence of hypertension than the group with normal salt intake (8.4% versus 6.7%, p = 0.023). In contrast, in the patients with high osmolarity, the cumulative incidence of hypertension was similar in the group with high salt intake and in the group with normal salt intake (13.1% versus 12.9%, p = 0.84). The patients with hyperosmolarity had a higher incidence of hypertension over five years compared to that of the normal osmolarity group (p < 0.001). After multiple adjustments, elevated osmolarity was an independent risk for developing hypertension (OR (odds ratio), 1.025; 95% CI (confidence interval), 1.006-1.044), regardless of the amount of salt intake. When analyzed in relation to each element of calculated osmolarity, serum sodium and fasting blood glucose were independent risks for developing hypertension. Our results suggest that hyperosmolarity is a risk for developing hypertension regardless of salt intake.

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 (<150 × 10/L) after hospitalization were at higher risk for developing CAAs (2.27 [1.44-3.58]). CONCLUSIONS: Platelet count varied widely by illness day and was confounded by IVIG responsiveness, which might have contributed to previous inconsistent findings. KD patients with abnormally high platelet counts at admission or abnormally low counts after hospitalization were at higher risk for CAAs.

Tap water contamination is a growing concern in healthcare facilities, and despite chlorination, tap water in these facilities contains several pathogenic microorganisms causing healthcare-associated waterborne infections or nosocomial outbreaks. Shower units are particularly prone to contamination as they are conducive for bacterial growth and can even produce bioaerosols containing pathogenic bacteria. Shower units coupled with point-of-use (POU) water filters are a simple and safe option; however, their efficacy has been under-reported. Therefore, we determined the efficacy of showerheads attached with a POU filter capsule in preventing infections in our hospital. We investigated the presence of pathogenic bacteria in water sampled from three shower units. After replacing the original shower units with new ones incorporated with a sterile-grade water filter capsule (0.2 µm; QPoint™), the water samples were analyzed for up to 2 months. The POU filters removed several pathogenic bacteria (Mycobacterium, Pseudomonas, Stenotrophomonas, Aeromonas, and Klebsiella spp.). Filter effectiveness depends on regional water quality and we believe that effective tap water treatment combined with the use of POU filters (introduced at a reasonable cost in healthcare facilities) can considerably minimize waterborne diseases in hospitals and improve patient care.

Background: There is no report yet on the application of telemedicine in orthopedic practice in Japan. With a focus on patients with KOA, we investigated the willingness of patients to use telemedicine by assessing factors such as the patient's age, smartphone possession, hospital visiting time, and severity of KOA. Methods: Data of patients who regularly consulted orthopedic surgeons at our institutions from April 2020 to June 2020 were retrospectively analyzed using an electronic medical database. The patients were diagnosed with KOA according to clinical and radiological findings, according to the Kellgren-Lawrence (KL) classification. included were patients with KOA with KL classification above grade 2. All patients were asked: 1) whether they were willing to use telemedicine (Yes or No), 2) the reason why they answered Yes, 3) the reason why they answered No, 4) if they possessed a smartphone, 5) their numeric rating scale for pain at their last outpatient visit after the Sars-CoV-2 epidemic emerged, and 6) the time required for visiting hospital from their house. Patients were stratified into 2 groups depending on whether they answered Yes (Group Y) or No (group N). Comparisons between the groups concerning smartphone possession, NRS pain, hospital visiting times, and distribution of KL grade were made. Results: Only 36.7% of the patients with KOA said they were willing to use telemedicine. The average age of group Y was significantly younger than that of group N (67.9 ± 9.1 vs 73.1 ± 8.0, P = 0.0026) and the cutoff age was 70.0 years. In addition, the rate of smartphone possession was significantly higher in group Y than in group N (82.5% vs 34.5%, P < 0.001). Hospital visit times and the severity of KOA did not differ between the groups. Conclusion: Age is a barrier to the adoption of telemedicine.

OBJECTIVE: To determine whether preventive trials in genetic prion disease could be designed to follow presymptomatic mutation carriers to onset of disease. METHODS: We assembled age at onset or death data from 1,094 individuals with high penetrance mutations in the prion protein gene (PRNP) in order to generate survival and hazard curves and test for genetic modifiers of age at onset. We used formulae and simulations to estimate statistical power for clinical trials. RESULTS: Genetic prion disease age at onset varies over several decades for the most common mutations and neither sex, parent's age at onset, nor PRNP codon 129 genotype provided additional explanatory power to stratify trials. Randomized preventive trials would require hundreds or thousands of at-risk individuals in order to be statistically powered for an endpoint of clinical onset, posing prohibitive cost and delay and likely exceeding the number of individuals available for such trials. CONCLUSION: The characterization of biomarkers suitable to serve as surrogate endpoints will be essential for the prevention of genetic prion disease. Parameters such as longer trial duration, increased enrollment, and the use of historical controls in a postmarketing study could provide opportunities for subsequent determination of clinical benefit.

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: 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.

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.

BACKGROUND: Although intravenous immunoglobulin (IVIG) therapy is the standard therapy for Kawasaki disease (KD) to prevent coronary aneurysms including dilatations, it is unclear whether early IVIG therapy is more efficient in the acute stage of KD. METHODS: We conducted a cohort study using data from the 22nd nationwide survey of KD in Japan from January 2011 to December 2012. We excluded patients with recurrent KD and whose first admission day was later than seven days from the onset of symptoms. Finally, 20,933 patients with echocardiography assessment and IVIG therapy were divided into three groups according to the start of the IVIG therapy: 1) early: ≤4 days, 2) conventional: 5-7 days, and 3) late: 8-10 days. Then we investigated whether the early IVIG therapy prevented coronary dilatation or aneurysm after multiple adjustments for age, sex, total amount of IVIG, use of steroids, infliximab, other immunosuppressive agents, and plasma exchange. RESULTS: After multiple adjustments, conventional therapy had similar risks for coronary dilatation or aneurysm compared with early therapy (odds ratio [OR]:0.95; 95% confidence interval [CI], 0.78-1.16), whereas late therapy had a higher risk (OR:1.66; 95% CI, 1.03-2.68). Other risk factors for coronary dilatation or aneurysm were young male, older age, use of steroids, infliximab, other immunosuppressive agents, and a larger amount of total IVIG. CONCLUSIONS: Early IVIG therapy for KD did not reduce the risk for coronary dilatation or aneurysm compared with conventional therapy. It is recommended to start IVIG therapy within 7 days from the onset of symptoms.

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.

<p>目的 地方紙における遺族の自己申告型死亡記事の記載事項を集計し，その地域での死亡やそれに伴う儀式の実態を明らかにするとともに，死亡記事のデータベースとしての利点と問題点を明らかにする。</p><p>方法 栃木の地方紙である下野新聞の自己申告型死亡記事「おくやみ」欄に掲載された2011～2015年の栃木県内の死亡者全員のデータを集計解析し，一部の結果は人口動態統計と比較した。観察項目は掲載年月日，市町村，住所の表示（市町村名のみ，町名・字まで，番地まで含めた詳細な住所），氏名，性別，死亡年月日，死因，死亡時年齢，通夜・告別式などの名称，通夜などの年月日，告別式などの年月日，喪主と喪主の死亡者との続柄の情報である。</p><p>結果 観察期間中の掲載死亡者数は69,793人で，同時期の人口動態統計による死亡者数の67.6%であった。人口動態統計と比較した掲載割合は男女で差がなく，小児期には掲載割合が低く，10歳代で高く，20歳台で低下し，以降は年齢とともに上昇していた。市町別の掲載割合は宇都宮市や小山市など都市化が進んだ地域では低く，県東部や北部で高い市町がみられた。最も掲載割合が高かったのは茂木町（88.0%），低かったのは野木町（38.0%）であった。死亡日から通夜や告別式などの日数から，東京などで起こっている火葬場の供給不足に起因する火葬待ち現象は起こっていないことが判明した。六曜の友引の日の告別式はほとんどなく，今後，高齢者の増加に伴う死者の増加によって火葬場の供給不足が起こった場合には，告別式と火葬を切り離して友引に火葬を行うことも解決策の1つと考えられた。死亡者の子供，死亡者の両親，死亡者の子供の配偶者が喪主の場合には，喪主は男の方が多いことが判明した。老衰，自殺，他殺の解析から，掲載された死因の妥当性は低いことが示された。</p><p>結論 栃木県の地方紙である下野新聞の自己申告型死亡記事「おくやみ」欄の5年分の観察を行い，実態を明らかにした。約3分の2に死亡が掲載されており，データベースとしての使用に一定の価値があると考えられたが，記載された死因の妥当性は低いことが判明した。</p>

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.