Faculty Profiles - Kazuhiro Uda

Papers - Kazuhiro Uda

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Long-term Effectiveness of Financial Incentives for Not Prescribing Unnecessary Antibiotics to Children with Acute Respiratory and Gastrointestinal Infections: A Japan's Nationwide Quasi-Experimental Study. Reviewed International journal

Yusuke Okubo, Kazuhiro Uda, Isao Miyairi

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2024.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: To address antibiotic overuse, the Japanese government implemented a novel financial incentive policy in 2018. The policy enables eligible healthcare facilities to claim 800 JPY (≈5.7 USD) per case wherein a rationale to not prescribe antibiotics is offered to children aged <3 years with acute upper respiratory tract infections or gastroenteritis. Although the short-term effect of this policy was observed in our previous study, its long-term effects have not been evaluated nationwide. METHODS: We conducted a quasi-experimental study using a staggered difference-in-differences design with propensity score matching. Data from 165,113 children born between April 2017 and March 2019 were extracted from two nationwide administrative databases. The study tracked these children until May 2022, comparing those exposed to the policy with those who were not. RESULTS: The introduction of financial incentives led to a 44.9% reduction (95%CI, 41.1% to 47.7%) in total antibiotic prescriptions within the first month and 19.5% reduction (95%CI, 8.7% to 29.1%) over 48 months. Broad-spectrum antibiotic use also decreased by 24.4% (95%CI, 14.0% to 33.6%) over the same period. The policy did not result in increased hospitalizations, after-hours visits, or healthcare costs, but was associated with a slight increase in the number of office visits. A dose-response relationship was observed, with reductions in antibiotic use leveling off after approximately five incentives. CONCLUSIONS: Financial incentives effectively reduced antibiotic prescriptions in children without adverse health outcomes, demonstrating sustained benefits over four years. This antimicrobial stewardship intervention offers a scalable model for other countries aiming to curb antibiotic overuse and combat antimicrobial resistance.

DOI： 10.1093/cid/ciae577

Nationwide Epidemiology and Outpatient Healthcare Resource Use of Children with Respiratory Syncytial Virus from 2005 to 2021. Reviewed International journal

Yusuke Okubo, Kazuhiro Uda, Yuki Yoshikawa, Chikara Ogimi, Yosuke Nakabayashi, Kenta Ito

Journal of the Pediatric Infectious Diseases Society 2024.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Respiratory syncytial virus (RSV) poses a global health challenge, particularly among younger children. While the disease burden in Japan has been preliminarily quantified in short-term or inpatient settings, a comprehensive understanding of outpatient settings at a national level is still lacking. METHODS: In this retrospective cohort study, we followed 697,802 children until they reached 60 months of age, amounting to 25,680,468 million person-months, using two nationally representative databases from the fiscal years 2005-2021. We analyzed trends in the epidemiology of RSV infections and associated outpatient health resource use. RESULTS: Incidence rates of RSV and associated hospitalizations among infants showed fluctuations of 50-100 cases and 20-30 hospitalizations per 1000 person-years, respectively, during the 2010s. These rates dropped to 8.7 cases and 2.2 hospitalizations per 1000 person-years in 2020, then returned to the same levels in the 2010s. Similar patterns were noted for RSV testing, outpatient visits, healthcare cost and the proportion of cases hospitalized (case-hospitalization risk). Whereas antibiotic use decreased from 56.4% in 2005 to 27.8% in 2021, palivizumab use increased from 95.2-195.9 days of therapy per 1000 person-years. Applying the calculated incidence rates to national data, annual outpatient healthcare costs for RSV infections were estimated to be 7-9 billion JPY (50-64 million USD) for children aged <60 months in the late 2010s. CONCLUSIONS: Our study highlights the changes in epidemiology and outpatient health resource utilization for children with RSV infections. These findings are valuable for policymakers and clinicians aiming to develop strategies, including newly developed maternal vaccines and single-dose long-acting monoclonal antibodies.

DOI： 10.1093/jpids/piae115

Idiopathic Pulmonary Hemosiderosis. Reviewed International journal

Kazuhiro Uda, Masato Yashiro

The New England journal of medicine 2023.6

Correlation between national surveillance and search engine query data on respiratory syncytial virus infections in Japan. Reviewed International journal

Kazuhiro Uda, Hideharu Hagiya, Takashi Yorifuji, Toshihiro Koyama, Mitsuru Tsuge, Masato Yashiro, Hirokazu Tsukahara

BMC public health 22 ( 1 ) 1517 - 1517 2022.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The respiratory syncytial virus (RSV) disease burden is significant, especially in infants and children with an underlying disease. Prophylaxis with palivizumab is recommended for these high-risk groups. Early recognition of a RSV epidemic is important for timely administration of palivizumab. We herein aimed to assess the correlation between national surveillance and Google Trends data pertaining to RSV infections in Japan. METHODS: The present, retrospective survey was performed between January 1, 2018 and November 14, 2021 and evaluated the correlation between national surveillance data and Google Trends data. Joinpoint regression was used to identify the points at which changes in trends occurred. RESULTS: A strong correlation was observed every study year (2018 [r = 0.87, p < 0.01], 2019 [r = 0.83, p < 0.01], 2020 [r = 0.83, p < 0.01], and 2021 [r = 0.96, p < 0.01]). The change-points in the Google Trends data indicating the start of the RSV epidemic were observed earlier than by sentinel surveillance in 2018 and 2021 and simultaneously with sentinel surveillance in 2019. No epidemic surge was observed in either the Google Trends or the surveillance data from 2020. CONCLUSIONS: Our data suggested that Google Trends has the potential to enable the early identification of RSV epidemics. In countries without a national surveillance system, Google Trends may serve as an alternative early warning system.

DOI： 10.1186/s12889-022-13899-y

The consequence of financial incentives for not prescribing antibiotics: a Japan's nationwide quasi-experiment. Reviewed International journal

Yusuke Okubo, Akihiro Nishi, Karin B Michels, Hiroki Nariai, Robert J Kim-Farley, Onyebuchi A Arah, Kazuhiro Uda, Noriko Kinoshita, Isao Miyairi

International journal of epidemiology 2022.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: For addressing antibiotic overuse, Japan designed a health care policy in which eligible medical facilities could claim a financial reward when antibiotics were not prescribed for early-stage respiratory and gastrointestinal infections. The policy was introduced in a pilot manner in paediatric clinics in April 2018. METHODS: We conducted a quasi-experimental, propensity score-matched, difference-in-differences (DID) design to determine whether the nationwide financial incentives for appropriate non-prescribing of antibiotics as antimicrobial stewardship [800 JPY (≈7.3 US D) per case] were associated with changes in prescription patterns, including antibiotics, and health care use in routine paediatric health care settings at a national level. Data consisted of 9 253 261 cases of infectious diseases in 553 138 patients treated at 10 180 eligible or ineligible facilities. RESULTS: A total of 2959 eligible facilities claimed 316 770 cases for financial incentives and earned 253 million JPY (≈2.29 million USD). Compared with ineligible facilities, the introduction of financial incentives in the eligible facilities was associated with an excess reduction in antibiotic prescriptions [DID estimate, -228.6 days of therapy (DOTs) per 1000 cases (95% CI, -272.4 to -184.9), which corresponded to a relative reduction of 17.8% (95% CI, 14.8 to 20.7)]. The introduction was also associated with excess reductions in drugs for respiratory symptoms [DID estimates, -256.9 DOTs per 1000 cases (95% CI, -379.3 to -134.5)] and antihistamines [DID estimate, -198.5 DOTs per 1000 cases (95% CI, -282.1 to -114.9)]. There was no excess in out-of-hour visits [DID estimate, -4.43 events per 1000 cases (95% CI, -12.8 to 3.97)] or hospitalizations [DID estimate, -0.08 events per 1000 cases (95% CI, -0.48 to 0.31)]. CONCLUSIONS: Our findings suggest that financial incentives to medical facilities for not prescribing antibiotics were associated with reductions in prescriptions for antibiotics without adverse health care consequences. Japan's new health policy provided us with policy options for immediately reducing inappropriate antibiotic prescriptions by relatively small financial incentives.

DOI： 10.1093/ije/dyac057

Kawasaki disease following coronavirus disease 2019 with prolonged fecal viral shedding. Reviewed International journal

Kazuhiro Uda, Keiko Okita, Keiko Soneda, Kimihiro Taniguchi, Yuho Horikoshi

Pediatrics international : official journal of the Japan Pediatric Society 63 ( 5 ) 597 - 599 2021.5

Kawasaki disease or Kawasaki-like disease: Influence of SARS-CoV-2 infections in Japan. Reviewed International journal

Kazuki Iio, Kazuhiro Uda, Hiroshi Hataya, Fumihiko Yasui, Tomoko Honda, Takahiro Sanada, Kenzaburo Yamaji, Michinori Kohara, Masanari Itokawa, Masaru Miura

Acta paediatrica (Oslo, Norway : 1992) 110 ( 2 ) 600 - 601 2021.2

Language：English Publishing type：Research paper (scientific journal)

The coronavirus disease 2019 (COVID-19) pandemic witnessed several clusters of children with fever and multisystem inflammation resembling Kawasaki disease (KD). Due to the evidence of a preceding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in most of these patients, post-viral immunological reactions were thought to play an important role in the pathogenesis.1,2 The condition, called "pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS)", has thus far been reported mainly from Europe and the United States,1,2 and no cases have been diagnosed in Asia. We herein analyzed the clinical data on patients in whom KD was diagnosed during a local COVID-19 epidemic to investigate the relationship between KD and SARS-CoV-2 infections in Japan, which has the highest KD incidence in the world.

DOI： 10.1111/apa.15535

High proportion of multidrug-resistant organisms in children hospitalized abroad. Reviewed International journal

Kazuhiro Uda, Takanori Funaki, Kensuke Shoji, Akira Kato, Isao Miyairi

American journal of infection control 48 ( 5 ) 578 - 580 2020.5

Language：English Publishing type：Research paper (scientific journal)

Our infection control team initiated active screening for multidrug-resistant organisms (MDROs) among children who had been hospitalized abroad before their admission to our hospital. MDROs were detected in 19 of 34 cases (56%), including 3 isolates of Enterobacteriaceae harboring carbapenemase genes still rare in Japan. Early recognition of MDROs by screening this population may be required to avoid the introduction of new modes of resistance into the hospital environment.

DOI： 10.1016/j.ajic.2019.08.013

Nationwide survey of indications for oral antimicrobial prescription for pediatric patients from 2013 to 2016 in Japan. Reviewed International journal

Kazuhiro Uda, Yusuke Okubo, Noriko Kinoshita, Naho Morisaki, Masahi Kasai, Yuho Horikoshi, Isao Miyairi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 25 ( 10 ) 758 - 763 2019.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Antimicrobial resistance is a major public health concern. In 2016, the Japanese government launched a national action plan aimed at achieving a 33% and 50% reduction in the number of total and oral antimicrobial prescriptions (cephalosporins, macrolides, and quinolones) from the 2013 figures by 2020, respectively. The purpose of this study was to investigate the indications for recent antimicrobial prescriptions and to identify the primary targets for intervention to achieve the aims of the government's action plan. METHODS: Using the national health claims database, we retrospectively analyzed oral antibiotic prescriptions for Japanese children aged ≦ 15 years from 2013 to 2016. The trends were analyzed based on days of therapy (DOT) per infectious disease-related visit for each antibiotic. For patients whose chief diagnosis was an infectious disease, the number of antimicrobial prescriptions per diagnosis, their proportion, and the details of the type of antimicrobial were investigated. RESULTS: In total, 297,197,328 infectious disease-related visits were identified during 2013-2016. Total antimicrobial prescriptions showed a 3.7% reduction from 1.519 DOT/visitor in 2013 to 1.463 DOT/visitor in 2016 (Ptrend < 0.001). Antimicrobials were prescribed for 31.7% and 36.9% of children with upper and lower respiratory tract infection, accounting for 54.6% and 26.2% of all antimicrobial prescriptions, respectively. Third generation cephalosporins and macrolides comprised the majority of these prescriptions. CONCLUSIONS: Antimicrobials were commonly prescribed for children with respiratory infections. Therefore, promoting appropriate antimicrobial use in this population is required to achieve the 2020 goals set by the action plan.

DOI： 10.1016/j.jiac.2019.03.004

Targets for Optimizing Oral Antibiotic Prescriptions for Pediatric Outpatients in Japan. Reviewed

Kazuhiro Uda, Noriko Kinoshita, Naho Morisaki, Masashi Kasai, Yuho Horikoshi, Isao Miyairi

Japanese journal of infectious diseases 72 ( 3 ) 149 - 159 2019.5

Language：English Publishing type：Research paper (scientific journal)

In Japan, 92.6% of antibiotics consumed are oral agents; most of these are for outpatients. A significant proportion is known to be dispensed for children; however, the specific pattern of antibiotic prescription in accordance with clinical specialty is still unclear. The aim of our study was to identify the key targets for the optimization of oral antibiotic use in children. We analyzed data on oral antimicrobial prescription patterns for children ＜ 16 years old of age in 3 urban districts by using a national database in Japan. Oral prescriptions were categorized according to their class, spectrum, clinical specialty, and type of clinical setting. The antibiotic spectrum was categorized as narrow, broad, or ultra-broad. In total, 132,869,332 antibiotic prescriptions were collected for analysis. The proportions of narrow-spectrum, broad-spectrum, and ultra-broad-spectrum antibiotics were 10.9%, 73.7%, and 15.4% in primary care clinics and 23.4%, 71.1%, and 5.4% in hospitals, respectively. Prescriptions from pediatricians and otolaryngologists in primary care clinics were predominant in the 3 studied areas. Third-generation cephalosporins, quinolones, penems, and carbapenems were prescribed mostly by pediatricians and otolaryngologists. Ultra-broad spectrum antibiotics used in primary care clinics and antibiotics particular to each specialty were identified as key targets for the optimization of oral antibiotic use for pediatric outpatients.

DOI： 10.7883/yoken.JJID.2018.374

Mycobacterium intracellulare Infection in a Japanese Patient with Signal Transducer and Activator of Transcription-3 Gain-of-Function Syndrome: A Case Report.

Hideharu Hagiya, Yoshiaki Soejima, Kazuki Tokumasu, Yoji Hirai, Yuki Otsuka, Marina Kawaguchi, Shinnosuke Fukushima, Kenta Nakamoto, Kohei Oguni, Yusuke Shiode, Kazuhiro Uda, Masato Yashiro, Kousei Hasegawa, Koji Iio, Fumio Otsuka

Internal medicine (Tokyo, Japan) 2025.10

Language：English Publishing type：Research paper (scientific journal)

Signal transducer and activator of transcription-3 (STAT3) gain-of-function (GOF) syndrome predisposes patients to autoimmunity diseases. Yet, nontuberculous mycobacterial (NTM) infections have rarely been described. We herein report a teenage Japanese patient with genetically confirmed STAT3-GOF syndrome who developed Mycobacterium intracellulare disease. Combination antimycobacterial chemotherapy reduced the bacterial burden; however, the refractory NTM infection relapsed after initiation of adjunctive tofacitinib therapy. The present case demonstrates that host-directed therapy must be combined with prolonged antimycobacterial regimens to control drug-resistant NTM in patients with inborn errors of immunity.

DOI： 10.2169/internalmedicine.6174-25

Factors influencing influenza vaccination among childcare and education professionals: A nationwide survey (2023-2024). International journal

Yusuke Okubo, Risa Honjo, Kazuhiro Uda, Isao Miyairi, Masahiko Sakamoto

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 31 ( 10 ) 102808 - 102808 2025.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Influenza remains a major public health issue, leading to millions of severe cases and many deaths annually. Although educational and childcare institutions are key transmission points for the spread of the virus in communities, few studies have comprehensively examined the vaccination rates and their determinants in these settings. METHODS: We conducted a nationwide web-based survey to assess influenza knowledge, perceptions, and determinants of vaccine hesitancy based on the 5C model among childcare and educational professionals in Japan. Multivariable modified Poisson regression, machine learning method of classification and regression tree (CART), and network analysis were employed to identify factors influencing vaccination behavior. RESULTS: Influenza vaccination rates were 74.1 % in 2023 and 78.8 % in 2024. Younger age (RR, 1.33; 95 %CI, 1.04-1.70), perceived unnecessity (RR, 1.31; 95 %CI, 1.01-1.70), concerns over adverse reactions (RR, 1.57; 95 %CI, 1.23-2.01) were associated with consistent non-vaccination, while agreement with collective responsibility (RR, 0.02; 95 %CI, 0.01 to 0.06) and recognition of the importance of vaccination for infection prevention (RR, 0.77; 95 %CI, 0.62 to 0.95) served as protective factor. CART and network analyses further highlighted collective responsibility as the key determinant for receiving vaccination consistently among educational and childcare professionals. CONCLUSIONS: Our study highlights that collective responsibility (willingness to get vaccinated to protect others) and specific hesitancy factors play a pivotal role in influenza vaccination uptake among childcare and educational professionals. Tailored public health strategies addressing these determinants may enhance vaccine coverage and reduce influenza transmission in high-risk settings.

DOI： 10.1016/j.jiac.2025.102808

Skin Infections Caused by Panton-Valentine Leukocidin and Methicillin-Susceptible Staphylococcus aureus in Child, Japan. Reviewed International journal

Kensuke Shoji, Kazue Yoshida, Marie Takenouchi, Junzo Hisatsune, Shoko Kutsuno, Chika Arai, Kanako Masuda, Motoyuki Sugai, Takashi Ishikawa, Toshinao Kawai, Kazuhiro Uda, Isao Miyairi

Emerging infectious diseases 31 ( 6 ) 1227 - 1230 2025.6

Language：English Publishing type：Research paper (scientific journal)

We describe a pediatric case of recurrent skin infections caused by a Panton-Valentine leukocidin and exfoliative toxin E double-positive methicillin-susceptible Staphylococcus aureus clonal complex 188 clone. Most of the patient's family members were infected with the same strain, and intrafamilial transmission was strongly suspected. Decolonization procedures were not effective.

DOI： 10.3201/eid3106.241955

Maternal smoking during infancy increases the risk of allergic diseases in children: a nationwide longitudinal survey in Japan. Reviewed International journal

Kenji Shigehara, Naomi Matsumoto, Mitsuru Tsuge, Kazuhiro Uda, Yukie Saito, Masato Yashiro, Takashi Yorifuji, Masanori Ikeda, Hirokazu Tsukahara

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 21 ( 1 ) 4 - 4 2025.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The incidence of allergic diseases has been increasing in Japan. In particular, a serious decline in the age of onset of allergic rhinitis has been observed. Passive smoking from parental smoking has a significant impact on children's health; however, it is difficult to restrict smoking in the home. While various studies have previously reported on the relationship between passive smoking and the development of allergic diseases in children. However, there have been no reports on passive smoking and allergic diseases on a national scale. METHODS: Using Japanese national longitudinal survey data (n = 38,444) for newborns born between May 10 and 24, 2010, we assessed parental smoking habits when their children were 6 months old and investigated the association with the development of allergic diseases until the age of 5.5 years. The risk ratios and 95% confidence intervals for the development of different allergic diseases were analyzed after adjusting for potential confounders using Poisson regression with a robust error variance. RESULTS: The risk ratio for developing allergic rhinitis/allergic conjunctivitis (AR/AC) in children was significantly higher in the maternal smoking groups ( ≦ 10 cigarettes/day; RR 1.15, 95% CI 1.02-1.30; ≧11 cigarettes/day; RR 1.16, 95% CI 0.93-1.44). Furthermore, associations were found between the maternal smoking group in the presence of paternal smoking and the risk of developing bronchial asthma ( ≦ 10, RR 1.33 95% CI 1.17-1.52; ≧11, RR 1.71 95% CI 1.38-2.1), food allergy ( ≦ 10, RR 1.36 95% CI 1.12-1.63; ≧11, RR 1.25 95% CI 0.84-1.86), atopic dermatitis ( ≦ 10, RR 1.42 95% CI 1.22-1.66; ≧11, RR 1.6 95% CI 1.2-2.13), and AR/AC ( ≦ 10, RR 1.21 95% CI 1.07-1.36; ≧11, RR 1.35 95% CI 1.09-1.67). CONCLUSIONS: Maternal smoking during infancy increases the risk of developing AR/AC in children. Considering paternal smoking, maternal smoking further increased the risk of developing allergic diseases in children, suggesting that reducing parental smoking at home may reduce the risk of developing allergic diseases in children.

DOI： 10.1186/s13223-025-00952-9

School infection control strategy during and after the COVID-19 pandemic: Nationwide trends (2022-2024). International journal

Yusuke Okubo, Risa Honjo, Kazuhiro Uda, Isao Miyairi

Pediatrics international : official journal of the Japan Pediatric Society 67 ( 1 ) e70243 2025

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic required schools, densely populated settings with diverse age groups, to dynamically adjust infection control strategies in response to evolving public health challenges. Despite substantial documentation of such strategies in healthcare facilities, detailed data from school environments remain limited during and after the COVID-19 pandemic. METHODS: A nationwide web-based survey was conducted using a random sample of schools (N = 854) to examine changes in infection control strategies, the implementation of school events, and decision-making influences over fiscal years 2022-2024. To identify longitudinal patterns in preventive behavior, we applied time-series clustering based on dynamic time warping. RESULTS: Between 2022 and 2024, key mitigation efforts such as compulsory mask usage (from 84.3% to 2.2%) and routine disinfection of shared spaces (from 89.7% to 12.3%) saw a steep decline. Meanwhile, hand hygiene and classroom ventilation remained consistently prioritized. The proportion of schools hosting events without restrictions (e.g., sports days, excursions) increased substantially. Around 50% of schools reported using infection prevention tools not officially recommended. While the proportion of schools implementing 7-10 infection prevention measures decreased from 93.4% in 2022 to 50.2% in 2023, schools with 0-3 measures increased from 16.2% in 2023 to 64.8% in 2024. CONCLUSIONS: This study provides nationwide insights into how Japanese schools adjusted their infection control strategies across three academic years. These findings highlight the need for evidence-informed decision-making and closer partnerships with infectious disease experts to improve preparedness for future public health crises.

DOI： 10.1111/ped.70243

突発性発疹関連脳症における免疫応答に関連した宿主遺伝子発現解析

津下充, 濃野優, 宇田和宏, 茂原研司, 塚原宏一

日本小児感染症学会総会・学術集会プログラム・抄録集 56回 211 - 211 2024.11

Pediatric Severe Febrile Thrombocytopenia Syndrome: A Case Report and Literature Review. Reviewed

Yusuke Toyota, Kazuhiro Uda, Komei Shirabe, Tadashi Moriwake

Acta medica Okayama 78 ( 5 ) 401 - 405 2024.10

Language：English Publishing type：Research paper (scientific journal)

Severe febrile thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease that is endemic in parts of eastern Asia. Few pediatric cases have been reported. We describe a case of SFTS in a seven-year-old girl who presented with prolonged fever and gastrointestinal symptoms. Leukopenia and thrombocytopenia on hematology, and a history of outdoor activity led us to diagnose SFTS, although the patient had no tick bite marks. We also review the literature and discuss the characteristics of pediatric SFTS. Physicians should consider SFTS in the differential diagnosis of fever with thrombocytopenia in children living in endemic areas.

DOI： 10.18926/AMO/67664

Nationwide epidemiology and health resource use among children with COVID-19 in Japan. Reviewed International journal

Yusuke Okubo, Yosuke Nakabayashi, Kenta Ito, Kazuhiro Uda, Isao Miyairi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2024.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The COVID-19 pandemic posed substantial challenges to healthcare systems. Understanding the responses of pediatric health services is crucial for future pandemic planning and preparedness, yet such data remains limited. METHODS: In this retrospective cohort study, we analyzed data from administrative databases developed by Japan Medical Data Center and DeSC Healthcare Inc. The dataset comprised records of 2,612,511 children, totaling 60,224,888 person-months, from January 2020 to May 2022. Multivariate generalized estimation equations were used to examine the incidence rates of COVID-19 and associated health resource use. RESULTS: Our analysis revealed that the incidence rates of COVID-19 gradually increased from Wave I (2.2 cases per 100,000 person-months) to Wave V (177.8cases per 100,000 person-months), with a notable elevation during Wave VI (2367.7 cases per 100,000 person-months). While nucleic acid amplification tests were primarily used during Waves I-V, the use of rapid antigen tests markedly increased in Wave VI. The hospitalization rates increased gradually from 0.2 in Wave I to 10.2 events per 100,000 person-months in Wave VI, and the case-hospitalization risk decreased from 14.9% in Wave II to 0.7% in Wave VI. Additionally, we observed decreasing trends in the use of antibiotics (Wave I, 31.8%; Wave VI, 9.0%), whereas antipyretic use rose from Wave I (56.1%) to Wave VI (86.6%). CONCLUSIONS: Our study highlighted essential changes in the nationwide pediatric healthcare system's response to the COVID-19 pandemic. These findings provide valuable insights into the future pandemic planning and preparedness.

DOI： 10.1016/j.jiac.2024.04.005

Structural and organizational determinants of the capacity for COVID-19 testing and diagnoses in children: Insights from the 2009 influenza and COVID-19 pandemics. Reviewed International journal

Yusuke Okubo, Kazuhiro Uda

Respiratory investigation 62 ( 3 ) 426 - 430 2024.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: This study explored factors associated with testing and diagnoses for children with COVID-19 at the hospital level and investigated whether the capacity of testing and diagnoses during the 2009 influenza pandemic was associated with that during COVID-19 pandemic. METHODS: In this observational study, we analyzed data obtained from the Japan Medical Data Center database, comprising 4906 medical facilities and 1.7 million infectious disease-related visits among children aged <20 years in 2020-2021. Multivariable generalized linear models were used to explore determinants of testing and diagnoses capacity for COVID-19 and investigate the association between the capacity during the 2009 influenza and COVID-19 pandemics. RESULTS: Public hospitals (adjusted incidence rate ratio [aIRR], 1.52; 95%CI, 1.26-1.82) and university hospitals (aIRR, 1.44; 95%CI, 1.14-1.80) were more likely to perform testing for COVID-19 among children, compared to clinics. The highest testing rate was observed in the department of internal medicine (aIRR, 1.64; 95%CI, 1.32-2.04), followed by pediatrics (aIRR, 1.40; 95%CI, 1.10-1.78) and otolaryngology (aIRR, 1.21; 95%CI, 0.89-1.64). Cubic spline models demonstrated the dose-response relationships between testing rate for influenza in 2009 and testing rates for COVID-19. Compared to the medical facilities in the lowest quartile of testing rate for influenza in 2009, those in the highest quartile were more likely to perform testing for COVID-19 (aIRR, 1.62; 95%CI, 1.43-1.83). CONCLUSIONS: Our study provides insights into the capacity of testing and diagnoses for children, highlighting the dose-response relationship between the 2009 influenza and COVID-19 pandemics, which could be valuable in preparing healthcare systems for future pandemics.

DOI： 10.1016/j.resinv.2024.03.001

Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature. Reviewed International journal

Mitsuru Tsuge, Kenji Shigehara, Kazuhiro Uda, Seiji Kawano, Masaya Iwamuro, Yukie Saito, Masato Yashiro, Masanori Ikeda, Hirokazu Tsukahara

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 19 ( 1 ) 103 - 103 2023.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs. CASE PRESENTATION: A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone. CONCLUSIONS: Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.

DOI： 10.1186/s13223-023-00859-3

Acute Switchitis: A New Subtype of Nintendinitis. Reviewed International journal

Hiroyoshi Takahashi, Kazuhiro Uda, Masato Yashiro

The Journal of pediatrics 113852 - 113852 2023.11

Clinical Practice Patterns and Risk Factors for Severe Conditions in Pediatric Hospitalizations With Respiratory Syncytial Virus in Japan: A Nationwide Analyses (2018-2022). Reviewed International journal

Yusuke Okubo, Kazuhiro Uda, Chikara Ogimi, Rinshu Shimabukuro, Kenta Ito

The Pediatric infectious disease journal 2023.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Respiratory syncytial virus (RSV) represents a global health challenge, especially among younger children. While the disease burden in Japan has been preliminarily quantified, there remains a lack of comprehensive understanding regarding treatment patterns and the influence of known risk factors at a national scale. MATERIALS AND METHODS: We conducted a retrospective cohort study consisting of 50,482 children under 5 years hospitalized with RSV infections during 2018-2022 using the Medical Data Vision database. We investigated trends in patient characteristics, health resource use, treatment patterns, and laboratory data. Additionally, multivariable modified Poisson regression models were used to investigate the risk factors associated with severe conditions. RESULTS: We observed an increasing trend in the inpatient healthcare costs and decreasing trends in the use of antibiotics, bronchodilators, systemic corticosteroids and other symptomatic medications from 2018 to 2022. Risk factors associated with severe RSV infections were children aged 0 years (risk ratio, 2.90; 95% CI: 2.53-3.32) and the number of complex chronic diseases (risk ratio for 1 disease, 2.68; 95% CI: 2.34-3.06: risk ratio for 2 or more diseases, 6.91; 95% CI: 5.81-8.21). Annual inpatient healthcare costs for RSV infections were estimated at 11-14 billion Japanese Yen for younger children. CONCLUSIONS: Our study observed the changes in practice patterns and health resource use for children hospitalized with RSV infections and identified risk factors associated with severe conditions. These findings provide insights for policymakers and clinicians aiming to devise strategies for further improving clinical practices, including newly developed vaccines and single-dose long-acting monoclonal antibodies.

DOI： 10.1097/INF.0000000000004181

Infection prevention measures and its determinants in childcare facilities during the COVID-19 pandemic: A nationwide survey (2022–2023) Reviewed International journal

Yusuke Okubo, Kazuhiro Uda, Mimori Kaki, Shinobu Miyoshi, Isao Miyairi

Journal of Infection and Chemotherapy 2023.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic presented an unprecedented challenge to societies, necessitating adaptations in infection prevention measures. While there is ample data on infection prevention practices in workplace and healthcare settings, comprehensive data specific to childcare facilities has been lacking. METHODS: We conducted a nationwide web-based survey capturing responses from various childcare facilities (N = 549). This aimed to understand the adaptation in infection prevention measures between fiscal years 2022 and 2023, the status of events and activities, and the factors influencing decision-making related to infection prevention. RESULTS: From 2022 to 2023, most childcare facilities reduced infection prevention practices like mandatory mask-wearing (46.9 %-7.5 %) and eating without conversing (56.5 %-7.4 %), whereas they continued high levels of hand sanitization and checking child's health condition before attendance. The frequency of events and activities (e.g., athletic meets, field trips) increased, with many being held without restrictions. Surprisingly, 62.8 % of facilities used items not recommended for infection prevention. The influence of local government guidelines (risk ratio, 0.69; 95%CI, 0.53-0.90) and the input from junior teachers (risk ratio, 0.85; 95%CI, 0.72-0.99) were associated with reduced risk of using inappropriate items. Furthermore, childcare facilities emphasized the need to collaborate with public health and medical professionals for more accurate and efficient decision-making during pandemics. CONCLUSIONS: The survey provides insights into the evolving practices of Japanese childcare facilities during the COVID-19 pandemic. It underscores the importance of refining information sources, enhancing decision-making processes, and fostering collaboration with the medical community for future pandemics and natural disasters.

DOI： 10.1016/j.jiac.2023.11.008

Roles of Oxidative Injury and Nitric Oxide System Derangements in Kawasaki Disease Pathogenesis: A Systematic Review. Reviewed International journal

Mitsuru Tsuge, Kazuhiro Uda, Takahiro Eitoku, Naomi Matsumoto, Takashi Yorifuji, Hirokazu Tsukahara

International journal of molecular sciences 24 ( 20 ) 2023.10

Language：English Publishing type：Research paper (scientific journal)

Kawasaki disease (KD) is an acute febrile vasculitis that occurs mostly in children younger than five years. KD involves multiple intricately connected inflammatory reactions activated by a cytokine cascade. Despite therapeutic advances, coronary artery damage may develop in some patients, who will be at risk of clinical cardiovascular events and even sudden death. The etiology of KD remains unclear; however, it may involve both genetic and environmental factors leading to aberrant inflammatory responses. Given the young age of onset, prenatal or perinatal exposure may be etiologically relevant. Multisystem inflammatory syndrome in children, a post-infectious hyper-inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2, has features that overlap with those of KD. Available evidence indicates that vascular endothelial dysfunction is a critical step in the sequence of events leading to the development of cardiovascular lesions in KD. Oxidative stress and the dysregulation of the nitric oxide (NO) system contribute to the pathogenesis of inflammatory responses related to this disease. This review provides current evidence and concepts highlighting the adverse effects of oxidative injury and NO system derangements on the initiation and progression of KD and potential therapeutic strategies for cardiovascular pathologies in affected children.

DOI： 10.3390/ijms242015450

Clinical Practice Patterns, Health Resource Use and Risk Factors for Severe Conditions Among Children Hospitalized With COVID-19 in Japan. Reviewed International journal

Yusuke Okubo, Kazuhiro Uda, Isao Miyairi

The Pediatric infectious disease journal 2023.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The trends in clinical practice patterns and health resource use, as well as risk factors for severe conditions among children hospitalized with coronavirus disease-2019 (COVID-19), remain unclear. MATERIALS AND METHODS: We conducted a retrospective observational study consisting of 9876 children hospitalized with COVID-19 during 2020-2022 using the Medical Data Vision database in Japan. We investigated trends in patient characteristics, health resource use, treatment patterns and laboratory data. Additionally, log-binomial regression models were used to investigate the risk factors associated with severe COVID-19 among pediatric inpatients with COVID-19. RESULTS: We observed decreasing trends in the lengths of hospital stays, healthcare costs, computed tomography use, and antibiotic use, and increasing trends in treatment with intravenous hydration and use of antipyretics, antiepileptics, antiemetics and antivirals from the first wave to the seventh wave of COVID-19 pandemic. During the 3-year period, the risk of severe COVID-19 was almost stable at 3%. Risk factors associated with severe COVID-19 were children aged 0 years [risk ratio (RR): 1.69; 95% confidence interval (CI): 1.02-2.78], the number of complex chronic diseases (RR for 1 disease: 4.49; 95% CI: 2.76-7.32; RR for 2 or more diseases: 10.2; 95% CI: 5.19-20.3) and asthma (RR: 1.84; 95% CI: 1.06-3.20). CONCLUSIONS: Our study observed the changes in practice patterns and health resource use for children hospitalized with COVID-19 and identified risk factors associated with severe COVID-19. These findings indicate the importance of vigilant monitoring and tailored treatment strategies in children with these risk factors.

DOI： 10.1097/INF.0000000000004135

小児COVID-19の中等症/重症例の基礎疾患の有無による臨床的特徴 Reviewed

大坪勇人, 芝田明和, 車健太, 多田歩未, 谷口公啓, 舟越葉那子, 木下和枝, 幡谷浩史, 齊藤修, 宇田和宏, 堀越裕歩

日本小児科学会雑誌 127 ( 10 ) 1289 - 1298 2023.10

Idiopathic Pulmonary Hemosiderosis. Reply. Reviewed International journal

Kazuhiro Uda, Masato Yashiro

The New England journal of medicine 389 ( 10 ) 962 - 963 2023.9

Association of Yersinia Infection With Kawasaki Disease: A Prospective Multicenter Cohort Study. Reviewed International journal

Hiroshi Hayashi, Kazuhiro Uda, Yumi Araki, Shogo Akahoshi, Miki Tanaka, Koichi Miyata, Hiroshi Hataya, Masaru Miura

The Pediatric infectious disease journal 42 ( 12 ) 1041 - 1044 2023.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Yersinia infection is known to present with Kawasaki disease (KD)-like symptoms although differentiating the 2 has been a challenge. The present study aimed to describe the clinical characteristics and prevalence of Yersinia infection presenting with KD-like symptoms. METHODS: The present, prospective, multicenter study enrolled patients who received a diagnosis of KD between January 2021 and January 2022 at 2 hospitals in Tokyo. Stool samples were collected within 3 days of the start of KD treatment, and cultures were performed for Yersinia. Clinical history and symptoms suggestive of Yersinia infection were also evaluated. RESULTS: During the study period, 141 KD patients were screened and 117 patients with evaluable stool samples were registered. Only 1 patient was positive for Yersinia pseudotuberculosis, which was detected from both stool and blood cultures. The patient was refractory to KD treatment but improved after initiation of appropriate antibiotic therapy. CONCLUSIONS: Routine screening for Yersinia is not appropriate for patients with KD and should be limited to certain patients in high-risk areas and those who are refractory to the standard KD treatment.

DOI： 10.1097/INF.0000000000004084

Nationwide epidemiology and clinical practice patterns of pediatric urinary tract infections: application of multivariate time-series clustering. Reviewed International journal

Yusuke Okubo, Kazuhiro Uda, Isao Miyairi, Nobuaki Michihata, Ryosuke Kumazawa, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga

Pediatric nephrology (Berlin, Germany) 2023.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The nationwide epidemiology and clinical practice patterns for younger children hospitalized with urinary tract infections (UTIs) were unclear. METHODS: We conducted a retrospective observational study consisting of 32,653 children aged < 36 months who were hospitalized with UTIs from 856 medical facilities during fiscal years 2011-2018 using a nationally representative inpatient database in Japan. We investigated the epidemiology of UTIs and changes in clinical practice patterns (e.g., antibiotic use) over 8 years. A machine learning algorithm of multivariate time-series clustering with dynamic time warping was used to classify the hospitals based on antibiotic use for UTIs. RESULTS: We observed marked male predominance among children aged < 6 months, slight female predominance among children aged > 12 months, and summer seasonality among children hospitalized with UTIs. Most physicians selected intravenous second- or third-generation cephalosporins as the empiric therapy for treating UTIs, which was switched to oral antibiotics during hospitalizations for 80% of inpatients. Whereas total antibiotic use was constant over the 8 years, broad-spectrum antibiotic use decreased gradually from 5.4 in 2011 to 2.5 days of therapy per 100 patient-days in 2018. The time-series clustering distinctively classified 5 clusters of hospitals based on antibiotic use patterns and identified hospital clusters that preferred to use broad-spectrum antibiotics (e.g., antipseudomonal penicillin and carbapenem). CONCLUSIONS: Our study provided novel insight into the epidemiology and practice patterns for pediatric UTIs. Time-series clustering can be useful to identify the hospitals with aberrant practice patterns to further promote antimicrobial stewardship. A higher resolution version of the Graphical abstract is available as Supplementary information.

DOI： 10.1007/s00467-023-06053-2

Impacts of routine varicella vaccination program and COVID-19 pandemic on varicella and herpes zoster incidence and health resource use among children in Japan. Reviewed International journal

Kazuhiro Uda, Yusuke Okubo, Mitsuru Tsuge, Hirokazu Tsukahara, Isao Miyairi

Vaccine 41 ( 34 ) 4958 - 4966 2023.6

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To determine the epidemiological trends in pediatric varicella and herpes zoster incidence and changes in healthcare resource use from 2005 to 2022 using a nationally representative database in Japan. MATERIALS AND METHODS: We conducted a retrospective observational study consisting of 3.5 million children with 177 million person-months during 2005-2022 using Japan Medical Data Center (JMDC) claims database in Japan. We investigated trends in incidence rates of varicella and herpes zoster and changes in healthcare resource use (e.g., antiviral use, office visits, and healthcare costs) over 18 years. Interrupted time-series analyses were used to investigate the impact of the routine varicella vaccination program in 2014 and infection prevention measures against COVID-19 on incidence rates of varicella and herpes zoster and related healthcare utilization. RESULTS: After the introduction of the routine immunization program in 2014, we observed level changes in incidence rates (45.6 % reduction [95 %CI, 32.9-56.0] of varicella cases, antiviral use (40.9 % reduction [95 %CI, 25.1-53.3]), and relevant healthcare costs (48.7 % reduction [95 %CI, 38.2-57.3]). Furthermore, infection prevention measures against COVID-19 were associated with additional level changes in varicella rates (57.2 % reduction [95 %CI, 44.5-67.1]), antiviral use (65.7 % reduction [59.7-70.8]), and healthcare costs (49.1 % [95 %CI, 32.7-61.6]). In contrast, the changes in incidence and healthcare costs for herpes zoster were relatively small, which showed 9.4 % elevated level change with a decreasing trend and 8.7 % reduced level change with a decreasing trend after the vaccine program and the COVID-19 pandemic. The cumulative incidence of herpes zoster in children born after 2014 was lower than that before 2014. CONCLUSIONS: Varicella incidence and healthcare resource use were largely affected by the routine immunization program and infection prevention measures against COVID-19, while these impacts on herpes zoster were relatively small. Our study indicates that immunization and infection prevention measures largely changed pediatric infectious disease practices.

DOI： 10.1016/j.vaccine.2023.06.054

Trends in Influenza and Related Health Resource Use During 2005-2021 Among Children in Japan. Reviewed International journal

Yusuke Okubo, Kazuhiro Uda, Isao Miyairi

The Pediatric infectious disease journal 2023.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: To determine the epidemiological trends in pediatric influenza and changes in healthcare resource use from 2005 to 2021 using nationally representative outpatient database in Japan. METHODS: We conducted a retrospective cohort study consisting of 3.5 million children with 177 million person-months during 2005-2021 using Japan Medical Data Center claims database in Japan. We investigated trends in incidence rates of influenza and changes in healthcare resource use (eg, use of antivirals) over 17 years. Generalized estimation equations were used to investigate the impact of the 2009 influenza pandemic and the coronaviral disease 2019 (COVID-19) pandemic on incidence rates of influenza and related healthcare utilization. RESULTS: Annual incidence rates of influenza were estimated at 55 cases per 1000 person-years with a 93% relative increase [95% confidence interval (CI): 80%-107%] during the 2009 influenza pandemic and a 99.4% relative reduction (95% CI: 99.3%-99.4%) during the COVID-19 pandemic. Similar patterns were observed for health resource use, total healthcare costs, admission rates and antiviral agent use. Approximately 80% of children with influenza received prescriptions for antivirals. The most prescribed antivirals were oseltamivir, but we observed a temporal increase in zanamivir use during 2007-2009, an increasing trend in laminamivir use during 2010-2017, a temporal increase in baloxavir use in 2018. Symptomatic medications with serious side effects (codeine, salicylate, sedative antihistamine) showed decreasing trends over the study period. CONCLUSIONS: Influenza incidence and healthcare resource use were largely affected by the 2009 influenza pandemic and the COVID-19 pandemic. Our study indicates improvement of quality in healthcare delivered to children.

DOI： 10.1097/INF.0000000000003966

Current Prevalence of Antimicrobial Resistance in Okayama from a National Database between 2018 and 2021. Reviewed

Shinnosuke Fukushima, Hideharu Hagiya, Kazuhiro Uda, Kazuyoshi Gotoh, Fumio Otsuka

Acta medica Okayama 77 ( 3 ) 255 - 262 2023.6

Language：English Publishing type：Research paper (scientific journal)

Antimicrobial resistance is an emerging global threat that must be addressed using a multidisciplinary approach. This study aimed to raise awareness of high-level antimicrobial-resistant (AMR) pathogens in Japan by comparing their recent prevalences among prefectures, particularly Okayama. Data for the isolation proportions of meropenem-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae, and levofloxacin-resistant E. coli and K. pneumoniae were collected from the Japan Nosocomial Infections Surveillance, a national database sponsored by the Japanese Ministry of Health, Labour, and Welfare, between 2018 and 2021. The average isolated proportions of the seven AMR pathogens were higher in Okayama compared to other prefectures: the worst (19.9%) was meropenem-resistant P. aeruginosa, the sixth worst (57.2%) was methicillin-resistant S. aureus, the eighth worst (3.3%) was vancomycin-resistant E. faecium, the second (37.8%) and fifth worst (17.6%) were cefotaxime-resistant E. coli and K. pneumoniae, respectively, and the fourth (49.9%) and third worst (8.7%) were levofloxacin-resistant E. coli and K. pneumoniae, respectively. Our study highlights the notably high prevalences of representative AMR pathogens in Okayama, suggesting the need for fundamental infection prevention and control by healthcare professionals, promoting antimicrobial stewardship, and educating undergraduates and postgraduates in Okayama.

DOI： 10.18926/AMO/65490

初診時,手足口病様皮疹を呈した新生児水疱性類天疱瘡の1例

別木祐介, 徳田真優, 前琴絵, 妹尾春佳, 立花宏太, 三宅智子, 平井陽至, 川上佳夫, 森実真, 宇田和宏, 斎藤友希恵, 茂原研司, 津下充, 八代将登

日本皮膚科学会雑誌 133 ( 4 ) 715 - 715 2023.4

Natto intake is a risk factor of Bacillus subtilis bacteremia among children undergoing chemotherapy for childhood cancer: A case-control study. Reviewed International journal

Rui Aoyagi, Keiko Okita, Kazuhiro Uda, Kento Ikegawa, Yuki Yuza, Yuho Horikoshi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 29 ( 3 ) 329 - 332 2023.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Natto, a popular, daily food in Japan, is made from soybeans fermented by Bacillus subtilis. The aim of this retrospective case-control study (matched 1: 4) is to determine whether natto intake is a risk factor of B. subtilis bacteremia in this population. METHODS: The retrospective, matched case-control study was conducted at Tokyo Metropolitan Children's Medical Center between April 2012 and June 2020 and included pediatric patients younger than 15 years who received chemotherapy for cancer. Patients who received hematopoietic stem cell transplantation were excluded. Patients with B. subtilis bacteremia were compared with controls matched for age and underlying diseases. Dietary information within seven days from the date of blood culture collection was extracted from medical records. Multivariate logistic regression was performed to define the risk factors of B. subtilis bacteremia. RESULTS: In total, 23 patients with B. subtilis bacteremia were identified and matched to 92 controls. The percentage of patients and controls who ingested natto within seven days from the date of blood culture collection was 78% and 50%, respectively. On univariate analysis, the odds ratio of natto intake for B. subtilis bacteremia was 3.6 (95% confidence interval [CI]: 1.2-10.5). Multivariable logistic regression tests after controlling for neutropenia revealed that B. subtilis bacteremia was associated significantly with natto intake at odds ratio 3.3 (95% CI: 1.1-9.6). CONCLUSION: Natto intake was associated with B. subtilis bacteremia during chemotherapy for childhood cancer.

DOI： 10.1016/j.jiac.2022.12.010

Successful TCRαβ/CD19-Depleted Hematopoietic Cell Transplantation for a Patient With Artemis Deficiency. Reviewed International journal

Dan Tomomasa, Takeshi Isoda, Noriko Mitsuiki, Kento Inoue, Akira Nishimura, Kazuhiro Uda, Toru Uchiyama, Motoi Yamashita, Takahiro Kamiya, Akifumi Endo, Masatoshi Takagi, Kohsuke Imai, Michiko Kajiwara, Morton J Cowan, Tomohiro Morio, Hirokazu Kanegane

Journal of pediatric hematology/oncology 2023.2

Language：English Publishing type：Research paper (scientific journal)

Artemis deficiency is characterized by DNA double-strand breaks repairing dysfunction and increased sensitivity to ionizing radiation and alkylating reagents. We describe the first successful case of T-cell receptor [TCR]αβ/CD19-depleted hematopoietic cell transplantation [HCT] for Artemis deficiency in Japan. A 6-month-old Korean boy was diagnosed with Artemis-deficient severe combined immunodeficiency. He had no human leukocyte antigen (HLA)-matched sibling or unrelated donor. Therefore, TCRαβ/CD19-depleted HCT from his haploidentical mother was performed. Despite mixed chimerism in whole blood, T cells achieved complete donor chimerism 6 months after HCT. TCRαβ/CD19-depleted HCT could be an effective treatment for patients with radiation-sensitive severe combined immunodeficiency.

DOI： 10.1097/MPH.0000000000002522

Transient Erythroblastopenia of Childhood With Exanthema Subitum Caused by Human Herpesvirus 7. Reviewed International journal

Takuya Wada, Kazuki Iio, Motohiro Matsui, Kazuhiro Uda, Daisuke Hasegawa, Hiroshi Hataya

The Pediatric infectious disease journal 42 ( 2 ) e48-e49 2023.2

Need for re-evaluating the risk of coronavirus disease 2019 transmission to neonates. Reviewed International journal

Kazuhiro Uda, Mitsuru Tsuge, Masato Yashiro, Tomoyuki Honda, Hirokazu Tsukahara

Pediatrics international : official journal of the Japan Pediatric Society 65 ( 1 ) e15460 2022.12

中等症以上のCOVID-19入院患児の臨床的特徴

大坪勇人, 車健太, 多田歩未, 谷口公啓, 芝田明和, 舟越葉那子, 宇田和宏, 幡谷浩史, 齊藤修, 堀越裕歩

日本小児感染症学会総会・学術集会プログラム・抄録集 54回 156 - 156 2022.11

新型コロナウイルス流行による手指衛生用の擦式アルコール製剤の使用量への影響

堀越裕歩, 中村敬子, 舟越葉那子, 芝田明和, 御代川滋子, 宇田和宏

日本小児感染症学会総会・学術集会プログラム・抄録集 54回 246 - 246 2022.11

Financial incentives for infection prevention and antimicrobial stewardship to reduce antibiotic use: Japan's nationwide observational study. Reviewed International journal

Y Okubo, A Nishi, K Uda, I Miyairi, N Michihata, R Kumazawa, H Matsui, K Fushimi, H Yasunaga

The Journal of hospital infection 131 89 - 98 2022.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The Japanese government introduced financial incentives to reduce nationwide antibiotic use in hospital settings. AIM: This study aimed to determine whether the nationwide financial incentives for creating infection prevention and control (IPC) teams introduced in 2012 and antimicrobial stewardship (ASP) teams introduced in 2018 were associated with changes in antibiotic use and health resource utilization at a national level. METHODS: We conducted time-series analyses and a difference-in-differences study consisting of 3,057,517 inpatients with infectious diseases from 472 medical facilities during fiscal years 2011-2018 using a nationally representative inpatient database in Japan. The primary outcome was the days of therapy (DOT) of antibiotic use per 100 patient-days (PDs). The secondary outcomes consisted of types of antibiotic used, health resource utilization, and mortality. RESULTS: A total of 5,201,304 financial incentives were observed during 2012-2018, which resulted in a total of 12.1 billion JPY (≈110 million USD). Time-series analyses found decreasing trends in total antibiotic use (79.3-72.5 DOTs/100 PDs (8.6% reduction)) and carbapenem use (9.0-7.0 DOTs/100 PDs (7.8% reduction)) from 2011 to 2018 without adversely affecting other healthcare outcomes (e.g., mortality). In the difference-in-differences analyses, we did not observe meaningful changes in total antibiotic use between the incentivized and unincentivized hospitals for ASP teams, except for the northern part of Japan. No dose-response relationships were observed between the amount of financial incentives and reductions in antibiotic use during 2011-2019. CONCLUSIONS: Further research and efforts are needed to accelerate antimicrobial stewardship in hospital settings in Japan.

DOI： 10.1016/j.jhin.2022.09.027

Clinical characteristics and treatment of IMP-type carbapenemase-producing Enterobacteriaceae bacteremia: Case series and literature review. Reviewed International journal

Keiko Soneda, Kazuhiro Uda, Kotaro Araki, Takatsugu Murakoshi, Yuki Yuza, Osamu Saito, Kazue Kinoshita, Hiroshi Higuchi, Yuho Horikoshi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 29 ( 1 ) 26 - 32 2022.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Several carbapenemases have been identified globally in Enterobacteriaceae. In Japan, IMP-type carbapenemase is the most prevalent, although cases of carbapenemase-producing Enterobacteriaceae (CPE) bacteremia are still scarce. The present case series and literature review aimed to elucidate the clinical characteristics and treatment strategies for IMP-type CPE bacteremia. METHODS: Clinical data on pediatric cases of IMP-type CPE bacteremia at the Tokyo Metropolitan Children's Medical Center between 2010 and 2020 were collected, and a review of past studies of IMP-type CPE bacteremia has been provided. RESULTS: Five pediatric episodes of IMP-type CPE bacteremia were identified. Our review of previous literature on IMP-type CPE bacteremia revealed 24 adult patients, but no pediatric patients. All 29 cases had underlying diseases, and 23 (79%) received combination therapy. The median duration of antibiotic therapy was 14 days (interquartile range: 9-14 days). The overall mortality rate was 38% (11/29). The mortality rates associated with monotherapy and combination therapy were 67% (4/6) and 30% (7/23), respectively. CONCLUSIONS: We report the first case series of IMP-type CPE bacteremia in children. Our review of past studies suggests that combination therapy might lead to better survival outcomes in patients with IMP-type CPE bacteremia. Further research is needed to establish an optimal treatment strategy for IMP-type CPE bacteremia.

DOI： 10.1016/j.jiac.2022.09.003

Neck Pain with Abdominal Distention in a Patient with Systemic Lupus Erythematosus. Reviewed International journal

Kazuhiro Uda, Kenji Shigehara, Masato Yashiro

Gastroenterology 2022.8

Terry's nails in an infant with liver cirrhosis. Reviewed International journal

Kazuhiro Uda, Mitsuru Tsuge, Kenji Shigehara, Masato Yashiro, Hirokazu Tsukahara

Archives of disease in childhood 107 ( 5 ) 485 - 485 2022.5

Infantile primary sternal osteomyelitis due to group B Streptococcus. Reviewed International journal

Koichiro Okumura, Shun Sakatani, Hanako Funakoshi, Kazuhiro Uda, Hiroshi Hataya

Pediatrics international : official journal of the Japan Pediatric Society 64 ( 1 ) e15030 2022.1

Change in use of pediatric oral antibiotics in Japan, pre- and post-implementation of an antimicrobial resistance action plan. Reviewed International journal

Noriko Iwamoto, Naho Morisaki, Kazuhiro Uda, Masashi Kasai, Eiichi N Kodama, Norio Ohmagari, Isao Miyairi

Pediatrics international : official journal of the Japan Pediatric Society 64 ( 1 ) e15197 2022.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Most antimicrobials are prescribed to outpatients, making outpatient antibiotic prescription an important target for antibiotic stewardship. A national antimicrobial resistance (AMR) action plan was developed in 2016 by the Japanese government with various antimicrobials steawardship activities for pediatric outpatients. We aimed to evaluate changes in antibiotic use pre- and post-implementation of the AMR action plan. METHODS: All antimicrobials prescribed to pediatric outpatients in Japan from 2011 to 2018 were retrospectively analyzed using data from a national database. Antimicrobials dispensed for patients aged ≤19 years were reviewed. Antimicrobial use was surveyed by age, year of use, type of antimicrobial prescribed, and prescribing facility. Five cities were selected as pilot areas to investigate the variations, based on the clinical specialties of the prescribing physicians. RESULTS: Antimicrobial usage varied with age. Specifically, usage decreased post-AMR in patients aged ≤8 years and increased in those aged >15 years. Further, antimicrobial prescriptions tended to decrease after 2016 in primary care clinics and hospitals. In the pilot areas of the study, 35% of all oral antimicrobials were prescribed in otolaryngology departments, and 8% were prescribed in dermatology clinics. Notably, antimicrobial prescriptions from both departments showed an upward trend from 2011 to 2018. CONCLUSION: The use of antimicrobial agents decreased in children younger than 8 years in pediatric clinics, hospitals, and internal medicine clinics. However, use increased in children older than 15 years and in other specialty clinics. Settings with an increasing use of antimicrobials are potential targets for the next antibiotic stewardship program and should be investigated in detail.

DOI： 10.1111/ped.15197

Acute Inguinal Bacterial Lymphadenitis in Infants Younger Than 1 Year of Age. Reviewed International journal

Reiko Yatabe, Kazuki Iio, Kazuhiro Uda, Hiroshi Hataya

The Pediatric infectious disease journal 40 ( 11 ) e450-e451 2021.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Ovid Technologies (Wolters Kluwer Health)

We examined 17 infants under age 1 year with inguinal bacterial lymphadenitis; 8 had a prior episode of omphalitis or an umbilical procedure, and one-third were afebrile and initially received the misdiagnosis of incarcerated hernia. Our findings suggested a possible association between inguinal bacterial lymphadenitis in infants and umbilical problems.

DOI： 10.1097/INF.0000000000003262

Change in clinical practice variations for antibiotic prescriptions across different pediatric clinics: A Japan's nationwide observational study. Reviewed International journal

Yusuke Okubo, Hiroki Nariai, Karin B Michels, Robert J Kim-Farley, Akihiro Nishi, Onyebuchi A Arah, Noriko Kinoshita, Kazuhiro Uda, Isao Miyairi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 11 ) 1621 - 1625 2021.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: In 2016, the Japanese government set the National Action Plan on antimicrobial resistance to reduce antibiotic prescriptions. However, the trends and variations of antibiotic prescription patterns in a routine healthcare setting during the fiscal year 2013-2018 across different clinics at a national level are unclear. METHODS: This retrospective cohort study included all clinics with >100 pediatric outpatients with infectious diseases per month during the fiscal year 2013-2018 using a national database in Japan. We investigated the trends in antibiotic prescription rates and their patterns and variations across different clinics over the six years following the 2019 World Health Organization Access, Watch, Reserve antibiotic groups, and Amoxicillin Index. RESULTS: A total of 2278 clinics with 94,414,170 infectious disease-related visits were eligible for the study. Most clinics showed higher Watch percentages (median 85.4%; IQR, 68.5-95.1) than Access percentages (median, 13.8%; IQR, 4.2-30.7) and Amoxicillin Index (median, 13.3%; IQR, 3.9-30.4). The introduction of the Action Plan changed annual absolute reductions in the antibiotic prescription rates from -16.0 DOTs/1000 visitors (95%CI, -16.4-15.6) to -239.3 per 1000 visitors (95%CI, -240.0-238.6). However, these impacts were heterogeneous across clinics. From 2013 to 2018, 41.4% reduced the antibiotic prescription rates by >33.3% (median, -1035.5 DOTs/1000 visitors; IQR, -1519.4-680.2), 18.7% did not change the rates (median, -40.3 DOTs/1000 visitors; IQR, -168.4-68.6), and 7.3% increased the rates by >10% (499.5 DOTs per 1000 visitors; IQR, 232.6-837.5). CONCLUSIONS: We observed the National Action Plan's impacts and extensive prescription variations across different pediatric clinics. However, one-fourth of clinics did not improve antibiotic prescription patterns even after introducing the Action Plan.

DOI： 10.1016/j.jiac.2021.07.020

小児専門医療施設で2020年に経験したコロナウイルス感染症2019の臨床像 Reviewed

宇田和宏, 榊原裕史, 谷口公啓, 樋口浩, 木下和枝, 堀越裕歩, 舟越葉那子, 芝田明和, 鈴木知子, 幡谷浩史

日本小児科学会雑誌 125 ( 10 ) 1426 - 1433 2021.10

Identification of B.1.346 Lineage of SARS-CoV-2 in Japan: Genomic Evidence of Re-entry of Clade 20C. Reviewed

Kodai Abe, Takako Shimura, Toshiki Takenouchi, Yuka W Iwasaki, Hirotsugu Ishizu, Yoshifumi Uwamino, Shunsuke Uno, Jun Gotoh, Natsuo Tachikawa, Yuriko Takeuchi, Junpei Katayama, Hiroyuki Nozaki, Susumu Fujii, Shikou Seki, Morio Nakamura, Kazuhiro Uda, Takahiko Misumi, Jun Ishihara, Kenichiro Yamada, Toshio Kanai, Shinji Murai, Kazuhiro Araki, Tamotsu Ebihara, Haruhiko Siomi, Naoki Hasegawa, Yuko Kitagawa, Masayuki Amagai, Makoto Suematsu, Kenjiro Kosaki

The Keio journal of medicine 70 ( 2 ) 44 - 50 2021.6

Language：English Publishing type：Research paper (scientific journal)

SARS-CoV-2 whole-genome sequencing of samples from COVID-19 patients is useful for informing infection control. Datasets of these genomes assembled from multiple hospitals can give critical clues to regional or national trends in infection. Herein, we report a lineage summary based on data collected from hospitals located in the Tokyo metropolitan area. We performed SARS-CoV-2 whole-genome sequencing of specimens from 198 patients with COVID-19 at 13 collaborating hospitals located in the Kanto region. Phylogenetic analysis and fingerprinting of the nucleotide substitutions were performed to differentiate and classify the viral lineages. More than 90% of the identified strains belonged to Clade 20B, which has been prevalent in European countries since March 2020. Only two lineages (B.1.1.284 and B.1.1.214) were found to be predominant in Japan. However, one sample from a COVID-19 patient admitted to a hospital in the Kanto region in November 2020 belonged to the B.1.346 lineage of Clade 20C, which has been prevalent in the western United States since November 2020. The patient had no history of overseas travel or any known contact with anyone who had travelled abroad. Consequently, the Clade 20C strain belonging to the B.1.346 lineage appeared likely to have been imported from the western United States to Japan across the strict quarantine barrier. B.1.1.284 and B.1.1.214 lineages were found to be predominant in the Kanto region, but a single case of the B.1.346 lineage of clade 20C, probably imported from the western United States, was also identified. These results illustrate that a decentralized network of hospitals offers significant advantages as a highly responsive system for monitoring regional molecular epidemiologic trends.

DOI： 10.2302/kjm.2021-0005-OA

Mycobacterium avium complex peritonitis in a pediatric patient on peritoneal dialysis: A case report. Reviewed International journal

Shunsuke Yokota, Kentaro Nishi, Sho Ishiwa, Kazuhiro Uda, Kensuke Shoji, Koichi Kamei

Medicine 100 ( 24 ) e26321 2021.6

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Peritonitis due to Mycobacterium avium complex (MAC) is a rare but life-threatening complication in patients on peritoneal dialysis (PD). However, optimal therapeutic regimen, treatment duration, and appropriate timing of kidney transplantation (KT) after treatment are unknown. SYMPTOMS: We herein report a 4-year-old boy on PD due to end-stage kidney disease resulting from bilateral hypoplastic kidneys. He was admitted for peritonitis complaining fever, abdominal pain, and cloudy peritoneal effluent on PD after accidentally biting and opening the PD catheter while in the bath. Initial treatment with vancomycin and ceftazidime for 2 weeks was successful, although peritonitis recurred 37 days after discharge. DIAGNOSIS: Mycobacterial culture was positive 9 days after readmission, and MAC was grown in the PD culture on day 30. We diagnosed him with MAC peritonitis that occurred on PD. INTERVENTIONS: Clarithromycin, ethambutol, and rifampicin were initiated. The PD catheter was removed, and hemodialysis was initiated with a cuffed catheter inserted in the internal jugular vein. Follow-up observation for 8 months after the cessation of 1-year anti-mycobacterial therapy confirmed no recurrence of MAC infection, and the patient received living-donor KT from his father. OUTCOMES: His renal function was stable, with no recurrence of MAC peritonitis at 2 years after the KT. CONCLUSION: To the best of our knowledge, this is the first report of a patient who successfully underwent KT after receiving treatment for MAC peritonitis. One-year anti-mycobacterial therapy, PD catheter removal, 8-month observation after the cessation of therapy led the successful KT, although further investigation is warranted to confirm the efficacy of this approach.

DOI： 10.1097/MD.0000000000026321

Whole-Genome Sequencing of Shiga Toxin-Producing Escherichia coli OX18 from a Fatal Hemolytic Uremic Syndrome Case. Reviewed International journal

Kenichi Lee, Atsushi Iguchi, Kazuhiro Uda, Sohshi Matsumura, Isao Miyairi, Kenji Ishikura, Makoto Ohnishi, Junji Seto, Kanako Ishikawa, Noriko Konishi, Hiromi Obata, Ichiro Furukawa, Hiromi Nagaoka, Hirotaka Morinushi, Natsuki Hama, Ryohei Nomoto, Hiroshi Nakajima, Hideaki Kariya, Mitsuhiro Hamasaki, Sunao Iyoda

Emerging infectious diseases 27 ( 5 ) 1509 - 1512 2021.5

Language：English Publishing type：Research paper (scientific journal)

We report a fatal case of hemolytic uremic syndrome with urinary tract infection in Japan caused by Shiga toxin-producing Escherichia coli. We genotypically identified the isolate as OX18:H2. Whole-genome sequencing revealed 3 potentially pathogenic lineages (OX18:H2, H19, and H34) that have been continuously isolated in Japan.

DOI： 10.3201/eid2705.204162

Kawasaki Disease Initially Presenting as Cervical Lymphadenopathy. Reviewed International journal

Anna Otani, Kazuki Iio, Kazuhiro Uda, Takahiro Matsushima, Hiroshi Sakakibara, Hiroshi Hataya

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 27 ( 3 ) e88-e89 2021.4

WU polyomavirus detection in a pediatric liver transplant recipient with interstitial pneumonitis. Reviewed International journal

Kensuke Shoji, Chitose Koyama-Wakai, Kazuhiro Uda, Akinari Fukuda, Seisuke Sakamoto, Mureo Kasahara, Isao Miyairi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 3 ) 530 - 532 2021.3

Language：English

The WU polyomavirus (WUPyV) was detected by real-time PCR in the sputum of a pediatric liver transplant recipient with interstitial pneumonitis. A lower viral load was observed seven months after the initial detection. The case provides circumstantial evidence suggesting a potential role for WUPyV as a respiratory pathogen in immunocompromised children.

DOI： 10.1016/j.jiac.2020.10.016

A 15-Month-old Boy With Kawasaki Disease-like Symptoms. Reviewed International journal

Hiroshi Hayashi, Kazuhiro Uda, Keiji Akamine, Nanako Kawata, Shogo Akahoshi, Masaki Shimizu, Yuho Horikoshi, Hiroshi Hataya

The Pediatric infectious disease journal 40 ( 2 ) 173 - 174 2021.2

National trends in appropriate antibiotics use among pediatric inpatients with uncomplicated lower respiratory tract infections in Japan. Reviewed International journal

Yusuke Okubo, Kazuhiro Uda, Noriko Kinoshita, Yuho Horikoshi, Isao Miyairi, Nobuaki Michihata, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 26 ( 11 ) 1122 - 1128 2020.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Japan was ranked as the worst country of 36 high-income countries in terms of oral antibiotic consumptions for children. Knowing the patterns and variations of antibiotic use for pediatric inpatients with uncomplicated respiratory infections is an important step to promote judicious antibiotic use. METHODS: Discharge records were extracted for children aged between 3 months and 15 years with acute lower respiratory tract infections for the fiscal years 2010-2014 using a national inpatient database in Japan. We investigated the trends in antibiotic use using mixed effect regression models and ascertained variations and clustering of the practice patterns across different hospitals using unsupervised machine learning methodology. RESULTS: A total of 280,298 children were included in the study. Total and broad-spectrum antibiotic use, except for fluoroquinolone, showed decreasing trends from 2010 to 2014. Additionally, the proportions of patients who received no antibiotics or only penicillin increased from 17.1% to 9.9% in 2010 to 24.5% and 13.7% in 2014, respectively. Cluster analysis showed that only one-quarter of hospitals used no antibiotics for 28.8% of children and only penicillin for 53.7% of children. In the remaining clusters of hospitals, the piperacillin, 3rd generation cephalosporins, and penicillin beta-lactamase inhibitors were used for 68.5%, 68.5%, and 69.6% of the patients who received antibiotics. CONCLUSIONS: Slightly increasing trends in narrow-spectrum antibiotics were observed. However, the treatment strategy in only one-quarter of hospitals was consistent with the current recommendations. Hospital level interventions to promote and monitor antibiotic use could be helpful to improve antibiotic use for pediatric inpatients.

DOI： 10.1016/j.jiac.2020.04.025

Impacts of Primary Care Physician System on Healthcare Utilization and Antibiotic Prescription: Difference-in-Differences and Causal Mediation Analyses. Reviewed International journal

Yusuke Okubo, Nobuaki Michihata, Kazuhiro Uda, Noriko Kinoshita, Yuho Horikoshi, Isao Miyairi

The Pediatric infectious disease journal 39 ( 10 ) 937 - 942 2020.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The overutilization of healthcare and overuse/misuse of antibiotics in Japan are responsible for the increase in healthcare expenditure and the development of antimicrobial resistance. The Japanese government started paying incentives to medical facilities for primary care physician registrations, but the impact of this new policy is still unclear. METHODS: We conducted a retrospective cohort study for all pediatric outpatients from April 2015 to December 2016 in Japan, targeting 1.4 million children under 2 years of age. We investigated the effects of primary care physician registration on physician visits, total antibiotic use and admission rates using difference-in-differences (DID) and causal mediation analyses. RESULTS: DID analyses showed that primary care registration policy contributed to increases in total physician visits, total and broad-spectrum antibiotic use and radiologic study utilization, but reduced out-of-hour visits and did not affect hospitalization rates. Similar results were obtained when we adjusted for and matched on potential confounders. Causal mediation analyses found that the greatest pathway was controlled by direct effects of 53.2 DOTs per 1000 person-months (95% CI: 29.1-77.2), indicating that the effect of new health policy that did not mediate increased outpatient visits mostly contributed to the excess use of antibiotics. CONCLUSIONS: The health policy further increased antibiotic use. On April 2018, a new health policy of paying incentives for not prescribing antibiotics to children with respiratory infection or gastroenteritis was initiated. Further studies are needed whether this new health policy can mitigate the overutilization of healthcare and antibiotic use.

DOI： 10.1097/INF.0000000000002762

Penile cyst. Reviewed International journal

Kazuhiro Uda, Satoko Suzuki, Yujiro Aoki, Hiroshi Sakiyama

Journal of paediatrics and child health 56 ( 8 ) 1317 - 1317 2020.8

A Pediatric Case of Septic Arthritis Caused by Methicillin-Resistant Staphylococcus aureus with Panton-Valentine Leukocidin and Toxic Shock Syndrome Toxin-1. Reviewed

Kazuhiro Uda, Yuki Uehara, Yuh Morimoto, Keiichi Hiramatsu, Isao Miyairi

Japanese journal of infectious diseases 73 ( 3 ) 259 - 262 2020.5

Incidence and aetiology of serious viral infections in young febrile infants. Reviewed International journal

Itaru Hayakawa, Osamu Nomura, Kazuhiro Uda, Yu Funakoshi, Hiroshi Sakakibara, Yuho Horikoshi

Journal of paediatrics and child health 56 ( 4 ) 586 - 589 2020.4

Language：English Publishing type：Research paper (scientific journal)

AIM: While the incidence and aetiology of serious bacterial infections among febrile infants younger than 90 days old are well studied, those concerning viral infection are not. There are severe life-threatening viral infections requiring immediate intense therapy. The objective of the study is to describe the incidence and aetiology of serious viral infections (SVI) among young febrile infants. METHODS: A retrospective audit was performed covering all the febrile infants younger than 90 days old admitted to a paediatric emergency department in Japan from 2011 to 2013. SVI was defined as a viral illness that may result in permanent organ dysfunctions or life-threatening complications. Diagnostic investigation consisted of urine and blood culture for all infants, cerebrospinal fluid cultures for infants who do not fulfil the low-risk criteria, rapid antigen tests for several viruses in infants with specific symptoms and blood and/or cerebrospinal fluid polymerase chain reaction of possible viruses for infants with fever without a localising source. RESULTS: Of 275 cases, 32 and 45 cases were diagnosed as serious viral and bacterial infections, respectively. Intensive care unit admission occurred for three viral and four bacterial infections. Viral aetiology consisted of respiratory syncytial virus (11 cases), aseptic meningitis (9 cases), enterovirus (6 cases), influenza virus (3 cases), rotavirus (2 cases) and herpes simplex virus-1 (1 case). Respiratory (14 cases), central nervous (12 cases) and circulatory (6 cases) systems were affected. CONCLUSION: SVI was observed in 11.6% of febrile young infants in a paediatric emergency department.

DOI： 10.1111/jpc.14692

Response to: Significance of prolonged PR interval in infections. Reviewed International journal

K Uda, Y Horikoshi, M Miura

QJM : monthly journal of the Association of Physicians 113 ( 2 ) 152 - 152 2020.2

小児咽後膿瘍の臨床的特徴 Reviewed

塚本淳也, 宇田和宏, 矢野瑞季, 荒木孝太郎, 福岡かほる, 松島崇浩, 鈴木知子, 榊原裕史, 幡谷浩史, 堀越裕歩

小児感染免疫 32 ( 1 ) 19 - 26 2020.2

Acute Rheumatic Fever and Kawasaki Disease Occurring in a Single Patient. Reviewed International journal

Kazuki Iio, Naoya Fukushima, Keiji Akamine, Kazuhiro Uda, Hiroshi Hataya, Masaru Miura

Frontiers in pediatrics 8 562 - 562 2020

Language：English

Kawasaki disease and acute rheumatic fever are two major causes of acquired heart disease in the pediatric population. Although both conditions are well-known entities, the association between them has never been described. We report herein a case of 6-year-old male patient who first presented with Kawasaki shock syndrome, followed by acute rheumatic fever 1 year later. In contrast to the prompt intervention given for atypical Kawasaki disease, in the present case the diagnosis was significantly delayed during the otherwise typical presentation of acute rheumatic fever. Our case highlights the difficulty experienced by many pediatricians in developed nations in diagnosing acute rheumatic fever due to its comparative rarity. To prevent diagnostic errors, all pediatricians should be alert to the possibility of acute rheumatic fever even if they are practicing in areas where it is not endemic.

DOI： 10.3389/fped.2020.00562

Prolonged PR interval in a patient with acute rheumatic fever. Reviewed International journal

K Uda, Y Horikoshi, M Miura

QJM : monthly journal of the Association of Physicians 112 ( 10 ) 817 - 818 2019.10

Multifocal Infantile Hemangioma. Reviewed International journal

Kazuhiro Uda, Yusuke Okubo, Takahiro Matsushima, Chieko Sadahira, Tatsuo Kono, Hiroshi Hataya

The Journal of pediatrics 210 238 - 238 2019.7

Caterpillar Sign in an Infant with Hypertrophic Pyloric Stenosis. Reviewed International journal

Reiko Kawai, Kazuhiro Uda, Yuho Horikoshi, Hiroshi Hataya

The Journal of pediatrics 208 292 - 292 2019.5

Nationwide study of outpatient oral antimicrobial utilization patterns for children in Japan (2013-2016). Reviewed International journal

Noriko Kinoshita, Naho Morisaki, Kazuhiro Uda, Masashi Kasai, Yuho Horikoshi, Isao Miyairi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 25 ( 1 ) 22 - 27 2019.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Antimicrobial resistance (AMR) is a major multinational public health concern. The Japanese government set goals in its AMR action plan to reduce use of oral cephalosporins, macrolides, and quinolones by half between 2013 and 2020. We aimed to evaluate antimicrobial use in children in Japan by observing prescription patterns as an interim assessment of the national AMR action plan. METHODS: Using the national health claims database, we retrospectively analyzed all oral antimicrobials dispensed from outpatient pharmacies in Japan to children under 15 years old from 2013 to 2016 by age, prefecture, type of antimicrobial, and year. Data were presented as days of therapy (DOTs) per 1000 pediatric inhabitants per day (DOTs/PID). The χ2 test for trends was performed to evaluate annual changes in DOTs/PID overall as well as within each stratum. RESULTS: A total of 721,627,553 oral antimicrobial DOTs were identified during 2013-2016. No statistically significant changes were observed in total antimicrobial use in children (2013: 28.54 DOTs/PID; 2016: 28.70 DOTs/PID; Ptrend = 0.25) and amount of cephalosporins, macrolides, and quinolones prescribed. Prescription rates of all antimicrobials were highest among children 1-5 years old, peaking at 1 year old. Targeted antimicrobials for the AMR action plan showed similar distribution by age. CONCLUSION: The amount of antimicrobials prescribed to children in Japan is not decreasing. Overall antimicrobial prescriptions, as well as prescriptions of cephalosporins, macrolides, and quinolones, were most prevalent in children ≤5 years old. Rigorous antimicrobial stewardship interventions targeting infants and younger children are necessary.

DOI： 10.1016/j.jiac.2018.10.002

Ototoxicity and Nephrotoxicity With Elevated Serum Concentrations Following Vancomycin Overdose: A Retrospective Case Series. Reviewed International journal

Kazuhiro Uda, Junichi Suwa, Kenta Ito, Hiroshi Hataya, Yuho Horikoshi

The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG 24 ( 5 ) 450 - 455 2019

Language：English

Although a high vancomycin serum concentration is known to be associated with nephrotoxicity, its association with ototoxicity is not well known. The purpose of our study was to examine the latter association in pediatric patients, especially in cases of accidental overdose. Pediatric patients who received vancomycin at our facility between March 2010 and December 2015 with a serum trough concentration > 30 mg/L were enrolled. Age, sex, neonatal hearing screening results, estimated peak vancomycin serum concentration, duration of drug exposure, renal function, and hearing test results were collected. The estimated duration of concentrations above 30 or 80 mg/L were simulated with the Sawchuk-Zaske method. We defined a "high concentration" and "toxic concentration" of vancomycin as 30 to 80 mg/L and > 80 mg/L, respectively. Ototoxicity was assessed based on the auditory brain stem response. We identified 4 females and 2 males with normal hearing at birth. Four of the 6 patients were ≤ 3 months old. All the patients reached an estimated peak serum concentration of > 80 mg/L, and 5 exceeded 150 mg/L. The estimated duration of exposure to a high concentration and toxic concentration of vancomycin was 15 to 62 hours and 8 to 43 hours, respectively. All the patients experienced transient renal dysfunction. Although transient ototoxicity was found in 1 patient, prolonged ototoxicity was not observed in any of the patients. All the patients had received an accidental overdose of vancomycin. Prolonged hearing loss due to a high vancomycin serum concentration was not found in any of the subjects in the present report.

DOI： 10.5863/1551-6776-24.5.450

Hamman's Sign in a Patient with Spontaneous Pneumomediastinum. Reviewed International journal

Kazuhiro Uda, Takahiro Matsushima, Yuho Horikoshi, Hiroshi Hataya

The Journal of pediatrics 202 324 - 324 2018.11

Multiple Bullae Associated with Human Parvovirus B19. Reviewed International journal

Shoko Yoshii, Kazuhiro Uda, Isao Miyairi, Hiro Nakao, Naoko Kono, Mitsuru Kubota, Akira Ishiguro

The Journal of pediatrics 202 327 - 327 2018.11

Ultrasound-guided peripheral intravenous access placement for children in the emergency department. Reviewed International journal

Takehito Otani, Yoshihiko Morikawa, Itaru Hayakawa, Yukari Atsumi, Kouki Tomari, Yutaro Tomobe, Kazuhiro Uda, Yu Funakoshi, Chiho Sakaguchi, Shizuka Nishimoto, Hiroshi Hataya

European journal of pediatrics 177 ( 10 ) 1443 - 1449 2018.10

Language：English Publishing type：Research paper (scientific journal)

The usefulness of ultrasound guidance in peripheral intravenous access placement has yet to be established in children. In this prospective comparative study, we investigated success rates of intravenous access placement with ultrasound guidance in a pediatric emergency department. After a failed first attempt with the conventional technique, the second and third attempts were conducted using either the ultrasound guidance (a real-time, dual operator method) or the conventional technique. The success rates within the two interventional attempts were then compared. From a total of 712 participants, those with a failed first attempt were allocated to the ultrasound guidance (n = 99) and conventional technique (n = 100) groups. The success rate was significantly lower for the ultrasound guidance (65%) than for the conventional technique (84%) group (p = 0.002, chi-square test). This remained significant after adjusting for confounders with multiple logistic regression analysis (odds ratio 2.60, 95% confidence interval 1.26-5.37, p = 0.001). CONCLUSION: Ultrasound-guided intravenous access placement using a real-time, dual operator method led to a significantly lower success rate than the conventional technique in children with one failed conventional attempt in the emergency department. TRIAL REGISTRATION: UMIN000014730 What is Known: • Children experience a low success rate (about 60% with 1 attempt and about 90% with 4 attempts) for IV access placement. • Ultrasound guidance may lead to a decreased number of attempts and shorter procedural time with comparable overall IV success rate. What is New: • Ultrasound-guided IV placement (a real-time, dual operator method) actually led to a significantly lower IV success rate than the conventional technique in children in the emergency department. • Our result warrants further trials to determine the precise population who benefits from ultrasound guidance.

DOI： 10.1007/s00431-018-3201-3

WU polyomavirus detected in children with severe respiratory failure. Reviewed International journal

Kazuhiro Uda, Chitose Koyama-Wakai, Kensuke Shoji, Noriyasu Iwase, Daisuke Motooka, Shota Nakamura, Isao Miyairi

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 107 25 - 28 2018.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: WU polyomavirus (WUPyV) is a relatively new virus associated with respiratory infections. However, its role is unclear in children with severe respiratory failure. OBJECTIVES: We aimed to evaluate the characteristics of severe respiratory failure associated with WUPyV infection in children. STUDY DESIGN: We retrospectively reviewed cases of respiratory tract infection at a tertiary children's hospital in Japan and performed real-time polymerase chain reaction (PCR) for WUPyV using residual extracted nucleic acid samples taken from respiratory tract samples of pediatric patients primarily with respiratory failure. We investigated the clinical characteristics of patients positive for WUPyV and assessed samples positive for WUPyV for other respiratory pathogens using multiplex PCR. RESULTS: WUPyV was detected in 14 of 318 specimens of respiratory tract infections. The median age was 34 months and males were predominant (n = 11, 64%). An underlying disease was found in 11 (79%) patients including five preterm and three immunocompromised patients. The most common clinical diagnosis was pneumonia (n = 13, 93%). The majority of the samples were endotracheal tube aspirates (n = 11, 79%). Other viruses were co-detected in nine (64%) patients, while WUPyV was the only pathogen detected in five patients with a history of admission to the neonatal intensive care unit. These five patients presented with fever and cough, and perihilar infiltrates were detected on chest radiograph in several days. CONCLUSIONS: WUPyV was detected in children with severe respiratory failure independently or concurrently with other pathogens. WUPyV can be a pathogen for children with a history of preterm birth or an underlying disease.

DOI： 10.1016/j.jcv.2018.08.003

Clinical characteristics of influenza virus-induced lower respiratory infection during the 2015 to 2016 season. Reviewed International journal

Kazuhiro Uda, Kensuke Shoji, Chitose Koyama-Wakai, Munehiro Furuichi, Noriyasu Iwase, Seiichiro Fujisaki, Shinji Watanabe, Isao Miyairi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 24 ( 6 ) 407 - 413 2018.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Influenza A(H1N1)pdm09 virus infections often manifest severe respiratory symptoms, particularly in patients with a past history of allergic disease. Most of these findings were reported during the 2009 pandemic. The purpose of this study was to detail the clinical characteristics of influenza virus-induced lower respiratory infection (LRI) during the A(H1N1)pdm09-predominant 2015-2016 season. METHODS: We retrospectively reviewed the clinical characteristics of influenza-induced LRI cases in children admitted to a tertiary children's hospital. Molecular diagnostic evaluation was performed on samples obtained from the most severe cases. RESULTS: We identified 66 patients with influenza-associated hospitalization and included 21 patients with influenza virus-induced LRI for analyses. Twelve patients (57%) were admitted to the pediatric intensive care unit, seven (33%) required mechanical ventilation, and three (14%) required extracorporeal membrane oxygenation. Plastic bronchitis (PB) was identified in six patients (29%), among whom a past medical history of asthma or food allergy were noted in all six patients. A past history of allergic disease was more common among patients with, than among those without, PB (p = 0.009). A(H1N1)pdm09 was detected from all the PB cases, and phylogenetic analyses of the hemagglutinin and neuraminidase genes demonstrated that this virus belonged to subclades 6B.1 and 6B.2. In the six PB cases, we found one patient with H275Y mutation in neuraminidase. CONCLUSION: Allergic disease was a risk factor for developing PB due to influenza A(H1N1)pdm09 infection during the 2015-16 season.

DOI： 10.1016/j.jiac.2018.01.002

Trends of neuraminidase inhibitors use in children with influenza related respiratory infections. Reviewed International journal

Kazuhiro Uda, Yusuke Okubo, Kensuke Shoji, Isao Miyairi, Naho Morisaki, Nobuaki Michihata, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga

Pediatric pulmonology 53 ( 6 ) 802 - 808 2018.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Neuraminidase inhibitors are recommended for children hospitalized with influenza-related respiratory infections, and oseltamivir is the first choice of treatment in most situations. However, little is known regarding the recent trend in using neuraminidase inhibitors and their difference in health economy. The aim of this study was to reveal recent trends in neuraminidase inhibitor use and compare hospitalization costs across different treatment regimens. METHODS: We retrospectively obtained the hospital discharge records of inpatients under 18 years of age with a diagnosis of influenza-related respiratory infections using a national inpatient database in Japan. We excluded patients with chronic medical conditions from the analyses. Multivariable mixed effects regression models were used to investigate the recent treatment trends and healthcare costs. RESULTS: We identified 27 771 inpatients with influenza-related respiratory infections. The proportions of neuraminidase inhibitor use increased from 62.6% in 2010 to 71.8% in2014 (Ptrend < 0.001). Correspondingly, the proportions of peramivir use showed an upward trend, ranging from 31.4% to 57.4% (Ptrend < 0.001). In contrast, proportions of oseltamivir and zanamivir use decreased from 26.1% to 12.1% and from 4.9% to 1.5%, respectively (Ptrend < 0.001). Laninamivir use did not change over the period. Total hospitalization costs were higher in the peramivir group than in the oseltamivir group (adjusted difference, $84.3; 95%CI, $70.7-$98.4). CONCLUSIONS: We observed an increasing trend in peramivir use and decreasing trends in use of oseltamivir and zanamivir. Treatment with peramivir required higher hospitalization costs.

DOI： 10.1002/ppul.24021

Recent trends in practice patterns and impact of corticosteroid use on pediatric Mycoplasma pneumoniae-related respiratory infections. Reviewed International journal

Yusuke Okubo, Nobuaki Michihata, Naho Morisaki, Kazuhiro Uda, Isao Miyairi, Yuichi Ogawa, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga

Respiratory investigation 56 ( 2 ) 158 - 165 2018.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Mycoplasma pneumoniae is a major pathogen causing community-acquired pneumonia/bronchitis in children, and macrolide-resistant strains are increasing in East Asian countries. Recent practice patterns, especially for antibiotic selection, and benefits of corticosteroid treatment in pediatric Mycoplasma pneumoniae infections remain unclear. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database, we analyzed recent trends in antibiotic selection and corticosteroid use for pediatric Mycoplasma pneumoniae-related respiratory infections, using multivariable mixed effects logistic regressions. In addition, we compared hospital utilization and readmission between children who received corticosteroids and those who did not, using propensity-score matching and instrumental variable analyses. RESULTS: Overall, 51,633 inpatients were identified. From 2010 to 2014, the use of macrolides and lincosamides decreased from 62.8% to 50.6% and from 25.6% to 13.7% respectively (Ptrend < 0.001), whereas fluoroquinolone use increased from 4.6% to 22.6% (Ptrend < 0.001). Tetracycline use did not demonstrate a significant change in trend. Propensity score matching analysis showed that hospital stay in the steroid group was 0.90 days longer than in the non-steroid group (95% confidence interval, 0.84-0.96). Total hospitalization cost was higher in the steroid compared to the non-steroid group (57.6 US dollars; 95% CI, 48.8-66.8). A significant difference in 30-day readmission risk was observed between the steroid (1.6%) and non-steroid (1.2%) groups (risk difference 0.4%; 95% CI, 0.1-0.7%). Similar results were observed on instrumental variable analyses. CONCLUSIONS: Increasing trends in fluoroquinolone use and decreasing trends in macrolide use were observed. Our study did not prove the benefits of corticosteroid use. Further studies are required to confirm the clinical benefits of corticosteroid treatment.

DOI： 10.1016/j.resinv.2017.11.005

Dose-response relationship between weight status and clinical outcomes in pediatric influenza-related respiratory infections. Reviewed International journal

Yusuke Okubo, Nobuaki Michihata, Kazuhiro Uda, Naho Morisaki, Isao Miyairi, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga

Pediatric pulmonology 53 ( 2 ) 218 - 223 2018.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Associations between underweight/obesity and manifestations of influenza infection remain unclear, especially in children. This study investigated the dose-response relationships between weight status and clinical outcomes among children hospitalized with influenza-related respiratory infections. METHODS: We obtained hospital discharge records of inpatients aged under 18 years with diagnoses of bronchitis/pneumonia and influenza, using a Japanese national inpatient database. The patients were classified as underweight, normal-weight, overweight, or obese groups using weight-for-length, weight-for-height, and body-mass-index for age following World Health Organization criteria. We compared need for intensive care, 30-day readmission, mean total hospitalization costs, and length of hospital stay across the four groups using multivariable regression models and restricted cubic spline functions. RESULTS: Overall, 27 771 patients were identified, including 2637 underweight, 19 701 normal-weight, 2675 overweight, and 2758 obese patients. The underweight group showed a significantly higher 30-day readmission (adjusted odds ratio, 1.68; 95% confidence interval, 1.28-2.18) and a longer length of stay (adjusted difference, 0.23 days; 95% confidence interval, 0.12-0.23 days) than the normal-weight group did. No significant differences in the need for intensive care or hospitalization costs were observed across the four weight status groups. The threshold for a statistically significant association between weight status and 30-day readmission was a z-score for weight-for-length, weight-for-height, or BMI for age of -0.95 (17th percentile). CONCLUSION: These findings demonstrated that underweight status is a risk factor for repeated hospital admissions because of influenza-related respiratory infections in children.

DOI： 10.1002/ppul.23927

Pertussis without apparent cough in a disabled girl with a tracheostomy. Reviewed International journal

Hisataka Nozawa, Kensuke Shoji, Kazuhiro Uda, Tomoo Nakamura, Mitsuru Kubota, Akira Ishiguro, Isao Miyairi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 23 ( 11 ) 782 - 784 2017.11

Language：English Publishing type：Research paper (scientific journal)

Pertussis is characterized by intense, prolonged coughing in children often followed by a distinctive whooping sound on inspiration. However, the clinical manifestations and natural course of pertussis in disabled children are largely unknown. We experienced a case of pertussis in a disabled girl who had previously undergone a tracheostomy and laryngotracheal separation. She presented with increased tracheal secretions and required hospitalization but did not develop a cough. Pertussis was suspected from the sputum Gram stain, which revealed numerous, short gram-negative rods that did not grow on chocolate agar. A nucleic acid amplification test was positive for Bordetella pertussis and the patient improved on azithromycin. Pertussis may present without its cardinal symptoms in disabled children.

DOI： 10.1016/j.jiac.2017.05.007

Pulmonary Calcification in a Congenital Cytomegalovirus Infection. Reviewed International journal

Kazuhiro Uda, Yuka Sasaki, Kensuke Shoji, Isao Miyairi

The Journal of pediatrics 190 286 - 286 2017.11

Febrile status epilepticus due to respiratory syncytial virus infection. Reviewed International journal

Kazuhiro Uda, Katsuhiko Kitazawa

Pediatrics international : official journal of the Japan Pediatric Society 59 ( 8 ) 878 - 884 2017.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Febrile status epilepticus can have neurological sequelae. The type of sequelae, however, depend on the etiology, including infection due to viral agents such as the influenza virus. Respiratory syncytial virus (RSV) infection in childhood may also contribute to this. The aim of this study was therefore to characterize febrile status epilepticus associated with RSV infection, and to determine whether this type of infection is a risk factor for neurological sequelae in febrile status epilepticus. METHODS: We reviewed the medical records of children aged ≤3 years with febrile status epilepticus who were admitted to a tertiary hospital between January 2007 and December 2011. The differences between the RSV-positive and RSV-negative groups were evaluated according to the demographic and clinical data. RESULTS: A total of 99 patients with febrile status epilepticus who had been tested for RSV infection were identified. Three patients in the RSV-positive group (n = 19) and four in the RSV-negative group (n = 80) presented with bronchiolitis. The incidence of intubation and anti-seizure drug treatment in the RSV-positive group was significantly higher than in the -negative group. While all of the patients in the RSV-negative group recovered completely, six patients in the RSV-positive group developed encephalopathy and profound neurological sequelae. In five of the six patients, diffusion-weighted magnetic resonance imaging showed subcortical white matter lesions. CONCLUSIONS: RSV infection in the absence of bronchiolitis can initially present as febrile status epilepticus and subsequently develop into acute encephalopathy with profound neurological sequelae.

DOI： 10.1111/ped.13300

Early diagnosis of scurvy based on radiology and dietary history. Reviewed International journal

Kazuhiro Uda, Masahiro Goto, Ayako Nigo, Tatsuo Kono

Pediatrics international : official journal of the Japan Pediatric Society 59 ( 3 ) 357 - 358 2017.3

Ulceration at Bacillus Calmette-Guérin Inoculation Site in a Patient with Kawasaki Disease. Reviewed International journal

Kazuhiro Uda, Hiroshi Hataya

The Journal of pediatrics 167 ( 5 ) 1167 - 7 2015.11

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