吉川 哲史

Herpes simplex encephalitis (HSE) is an acute form of encephalitis that can lead to poor neurological outcomes. Although the exact pathogenesis of HSE remains elusive, recent reports suggest a significant role for postinfectious immune-inflammatory processes in the central nervous system (CNS). This study aimed to clarify the association between CNS autoimmune responses and clinical presentation in patients with HSE, focusing on cerebrospinal fluid (CSF) characteristics, particularly the IgG index. We retrospectively analyzed 176 consecutive patients suspected of having aseptic meningitis /encephalitis for chronological changes in CSF findings and clinical presentations. These patients underwent PCR screening for herpesviruses (HV) in their CSF. We identified seven patients positive for herpes simplex virus type 1 (HSV-1), 20 patients positive for varicella-zoster virus, and 17 patients who met the criteria for aseptic meningitis but were PCR-negative for HV. Patients in the HSV-1-positive group exhibited a significant increase in the IgG index at the time of PCR-negative conversion compared with on admission (p = 0.0156), while such a change was not observed in the other two groups. Additionally, all patients in the HSV-1-positive group tested negative for anti-neural autoantibodies in CSF and serum samples collected approximately 3 weeks after onset. This study, therefore, highlights that CSF IgG index elevation occurs even after PCR-confirmed HSV-1 clearance, which might indicate immunopathogenesis that is independent of antibody-mediated mechanisms.

To elucidate the seroprevalence and rate of asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Japanese children, serological analysis was performed using serum samples collected from March 2020 to February 2023. A total of 1493 serum samples were collected during the first study period (March 2020 to February 2021). None of the serum samples was positive for SARS-CoV-2 antibody. In the second period (March 2021 to February 2022), seven of the 1055 patients (0.7%) experienced SARS-CoV-2 infection. The third period (March 2022 to February 2023) was divided into three terms: from March to June 30, 2022; from July to October 2022; and from November 2022 to February 2023. The seroprevalence gradually increased throughout this period, with rates of 6.0%, 18.6%, and 30.4% in the three terms, respectively. Pediatric cases of asymptomatic SARS-CoV-2 infection occurred after the surge of Omicron variants. Since none of the SARS-CoV-2 antibody-positive patients had a previous history of coronavirus disease 2019, the seroprevalence rate in this study may represent the rate of asymptomatic infection.

Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in developed countries. Although a standard therapy has not yet been established, evidence for the management of cCMV infection has been accumulating. The first edition of the "Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection" was published in Japan in 2023. This summary outlines the clinical questions (CQs) in the guidelines, with reference to the Japanese Medical Information Distribution Service Manual. Overall, 20 CQs with statements regarding prenatal risk assessment, prevention and management at diagnosis (CQs 1-1-1-3), diagnosis (CQs 2-1-2-6), treatment (CQs 3-1-3-7) and follow-up requirements (CQs 4-1-4-4) have been discussed. For each statement, the levels of recommendation, evidence and consensus rates were determined. These guidelines will assist in the management of patients with cCMV infection.

The live attenuated human rotavirus vaccine strain RIX4414 (Rotarix®) is used worldwide to prevent severe rotavirus-induced diarrhea in infants. This strain was attenuated through the cell culture passaging of its predecessor, human strain 89-12, which resulted in multiple genomic mutations. However, the specific molecular reasons underlying its attenuation have remained elusive, primarily due to the absence of a suitable reverse genetics system enabling precise genetic manipulations. Therefore, we first completed the sequencing of its genome and then developed a reverse genetics system for the authentic RIX4414 virus. Our experimental results demonstrate that the rescued recombinant RIX4414 virus exhibits biological characteristics similar to those of the parental RIX4414 virus, both in vitro and in vivo. This novel reverse genetics system provides a powerful tool for investigating the molecular basis of RIX4414 attenuation and may facilitate the rational design of safer and more effective human rotavirus vaccines.

INTRODUCTION: Insurance coverage for oral valganciclovir (VGCV) began in Japan in April 2023 on the basis of results, including our clinical trials for symptomatic congenital cytomegalovirus (CMV) disease. The VGCV treatment is available throughout Japan, so clinicians must consider the likelihood of hearing improvement and the possibility of neutropenia before dosing. MATERIALS AND METHODS: We performed a substudy of an investigator-initiated, single-arm, prospective, multicenter, clinical trial in which 24 infants with symptomatic congenital CMV disease were orally administered 16 mg/kg VGCV twice daily for 6 months as an intervention. We examined the infants' baseline characteristics associated with improved hearing impairment or a severely reduced neutrophil count. RESULTS: Of the 24 patients, 4 had normal hearing on assessment of their ear with the best hearing. Hearing impairment improved in 14 patients and did not respond to VGCV treatment in 6 patients at the 6-month hearing assessment. CMV DNA levels in plasma at baseline were higher in patients in whom hearing did not respond to treatment. A neutrophil count <500/mm3 occurred in 5 (21%) patients for the first 6 weeks and in 8 (33%) patients for the first 6 months. A neutrophil count at screening and the lowest neutrophil count over the 6 months showed the highest correlation (r = 0.477, p = 0.019). CONCLUSIONS: Infants with a low plasma viral load at screening tend to have an improvement in hearing impairment. Clinicians should be aware of neutropenia during VGCV treatment particularly in patients with a low neutrophil count during screening.

We encountered a previously healthy 3-year-old girl with interstitial pneumonitis that initially developed due to human adenovirus type 2 infection and exacerbated by primary human herpesvirus 7 infection. A comprehensive serum biomarker analysis showed patterns that differed by viral infection, suggesting that respiratory and lymphotropic viral infections might have different pathophysiology in interstitial pneumonitis.

Vaccine development for herpes simplex virus 2 (HSV-2) has been attempted, but no vaccines are yet available. A plasmid-based reverse genetics system for Rotavirus (RV), which can cause gastroenteritis, allows the generation of recombinant RV containing foreign genes. In this study, we sought to develop simian RV (SA11) as a vector to express HSV-2 glycoprotein D (gD2) and evaluated its immunogenicity in mice. We generated the recombinant SA11-gD2 virus (rSA11-gD2) and confirmed its ability to express gD2 in vitro. The virus was orally inoculated into suckling BALB/c mice and into 8-week-old mice. Serum IgG and IgA titers against RV and gD2 were measured by ELISA. In the 8-week-old mice inoculated with rSA11-gD2, significant increases in not only antibodies against RV but also IgG against gD2 were demonstrated. In the suckling mice, antibodies against RV were induced, but gD2 antibody was not detected. Diarrhea observed after the first inoculation of rSA11-gD2 in suckling mice was similar to that induced by the parent virus. A gD2 expressing simian RV recombinant, which was orally inoculated, induced IgG against gD2. This strategy holds possibility for genital herpes vaccine development.

UNLABELLED: This study aimed to identify the appropriate dose of aspirin to be prescribed to patients with acute Kawasaki disease (KD). Using a Japanese national inpatient database, we identified patients with KD treated with intravenous immunoglobulin between 2010 and 2021.The outcomes included the occurrence of coronary artery abnormalities and intravenous immunoglobulin resistance, length of hospital stay, and medical costs. Restricted cubic spline functions were performed to examine the association between aspirin dose and the outcomes. Data of 82,109 patients were extracted from the database. Non-linear associations were observed between aspirin dose and the outcomes. In comparison with an aspirin dose of 30 mg/kg/day, the odds ratio (95% confidence interval) for coronary artery abnormalities was 1.40 (1.13-1.75) at 5 mg/kg/day. An aspirin dose of ≥ 30 mg/kg/day did not significantly change the odds ratio for coronary artery abnormalities. Intravenous immunoglobulin resistance was significantly lower at a dose of 60 mg/kg/day or higher. CONCLUSION:  The results showed no significant association between aspirin escalation over standard-dose and coronary artery abnormalities in patients with acute KD. High-dose aspirin showed the potential to reduce hospital stay and medical costs without increasing complications. WHAT IS KNOWN: • Aspirin is used as a standard treatment together with intravenous immunoglobulin for acute Kawasaki disease (KD). However, few studies have shown the most effective dosage of aspirin to prevent coronary artery abnormalities (CAAs). WHAT IS NEW: • There was no significant association between aspirin dose escalation and CAAs in patients with acute KD.

OBJECTIVES: The Gunma score is used to predict the severity of Kawasaki disease (KD), including coronary artery aneurysm (CAA) as a cardiac complication, in Japan. Additionally, the characteristic ratio of ventricular repolarization (T-peak to T-end interval to QT interval [Tp-e/QT]) on a surface electrocardiogram reflects myocardial inflammation. This study aimed to determine whether the Tp-e/QT can be used to predict CAA in children with KD. METHODS: We analyzed chest surface electrocardiograms of 112 children with KD before receiving intravenous immunoglobulin therapy using available software (QTD; Fukuda Denshi, Tokyo, Japan). RESULTS: The Tp-e/QT (lead V5) was positively correlated with the Gunma score (r=0.352, p<0.001). The Tp-e/QT was larger in patients with CAA (residual CAA at 1 month after onset) than in those without CAA (0.314±0.026 versus 0.253±0.044, p=0.003). A receiver operating characteristic curve analysis was performed to assess whether the Gunma score and Tp-e/QT could predict subsequent CAA. The area under the curve of the Gunma score was 0.719 with the cutoff set at 5 points. The area under the curve of the Tp-e/QT was 0.892 with a cutoff value of 0.299. The fit of the prediction models to the observed probability was tested by the Hosmer-Lemeshow test with calibration plots using Locally weighted scatterplot smoothing (LOESS) fit. The Gunma score (p=0.95) and Tp-e/QT (p=0.95) showed a good fit. CONCLUSIONS: The Tp-e/QT is a useful biomarker in predicting coronary aneurysm complications in KD.

川崎病では冠動脈だけでなく多臓器にさまざまな症状が出現し,しばしば関節炎を呈することがある.その際,臨床像が類似し疾患特異的マーカーもない若年性特発性関節炎や,また,ステロイド・免疫抑制薬を使用している症例においては化膿性関節炎・大腿骨頭壊死などとの鑑別が重要となる.川崎病の病態は,いまだ不明な点が多いが,過剰な免疫応答と炎症性サイトカインの過剰産生により全身の血管炎が惹起されると考えられており,過去に30種類以上の血清サイトカインの解析がなされてきた.しかし,関節炎を合併した川崎病患者において経時的にサイトカインを測定し検討した報告はない.今回,川崎病の回復期に股関節炎を発症した症例において,後方視的に複数ポイントで各種サイトカインを測定したところ,関節症状が出現する前にinterleukin(IL)-1βが上昇していた.最終的に各種検査で化膿性関節炎などの他疾患は否定され,川崎病に合併した関節炎と診断されたことから,IL-1βは川崎病における関節炎の発症予測や病態評価に有用な可能性が示唆された.今後,関節炎を合併しない川崎病ならびに鑑別を要する化膿性関節炎などの他疾患について解析し,臨床応用に向けた研究を進めていきたい.(著者抄録)

Multisystem inflammatory syndrome in children (MIS-C) was reported as a severe complication of coronavirus disease 2019; an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and was suggested to be associated with Kawasaki disease (KD) in terms of severe systemic inflammation and mucocutaneous symptoms. Because severe gastrointestinal symptoms and systemic shock are more frequently observed with MIS-C, patients with mild MIS-C might have been diagnosed with KD. In this study, titers of IgG antibodies against the SARS-CoV-2 S (S-IgG) and N proteins (N-IgG) were measured in 99 serum samples collected from patients with KD treated between January 2020 and December 2021 to evaluate the relationship between KD and SARS-CoV-2 infection. S-IgG were detected in only one patient out of 99 patients. This patient had coronavirus disease 2019 (COVID-19) 10 months before KD onset, and was unlikely MIS-C. According to characters of S-IgG and N-IgG, the patients was unlikely infected with SARS-CoV-2 just before the onset of KD. In addition to this study, the 26th Nationwide Survey and previous studies showed an association between KD and SARS-CoV-2 to be unlikely. In conclusion, SARS-CoV-2 infection was not observed in patients with KD until Delta predominance in Japan by the method of detecting SARS-CoV-2 IgG.

OBJECTIVES: Intestinal rotavirus (RV) vaccine replication and host immune response are suggested to be affected by several factors, including maternal antibodies, breastfeeding history, and gut microbiome, which are thought to be similar in pairs of twins. The aim of this study was to determine whether viral shedding from the fecal RV vaccine strain Rotarix® (RV1) and IgG and IgA responses to RV show similarity in pairs of twins. METHODS: Quantitative reverse transcription polymerase chain reaction specific to RV vaccine strain RV1 was used to monitor fecal RV1 viral shedding. RV IgG and IgA titers were measured using an in-house enzyme-linked immunosorbent assay. Fecal RV1 viral shedding and immune responses were compared between twins and singletons with mixed effects and fixed effects models. RESULTS: A total of 347 stool and 54 blood samples were collected from four pairs of twins and twelve singletons during the observation period. Although the kinetics of fecal RV1 viral shedding and immune responses differed among vaccinated individuals, they appeared to be similar within twin pairs. RV shedding after the first dose (P=0.049) and RV IgG titers during the entire observation period (P=0.015) had a significantly better fit in the fixed effect model that assumed that twins have the same response versus the model that assumed that twins have a different response. CONCLUSIONS: The similarity of RV vaccine viral replication in intestine and host immune responses in twin pairs was demonstrated using statistical analysis.

Abstract Nonpharmaceutical interventions (NPIs) to control COVID‐19 have decreased the incidence of many pediatric infectious diseases. The epidemiology of β‐ and γ‐herpesvirus infections might have been affected by NPIs. The aim of this study was to elucidate changes in trends in β‐ and γ‐herpesvirus infections and complex febrile seizures (cFS) of viral etiology before and during the COVID‐19 pandemic. Between April 2017 and March 2021, febrile children aged ≤5 years were enrolled. Detection of EBV, CMV, HHV‐6B, and HHV‐7 DNA in serum was performed using real‐time PCR. The epidemiology of viral infections and cFS were compared between the prepandemic and pandemic periods. During the observation period, 1432 serum samples were collected. The mean number of febrile children decreased during the pandemic period, but the number of patients with HHV‐6B infection increased from 35 (9.3% of all febrile children) per year before the pandemic to 43 (15.5%) during the pandemic. The change in the proportion of patients with primary HHV‐6B infection was 6.50% (95% confidence interval [CI], 2.05%–11.3%; p = 0.0047). The mean number of patients with cFS decreased during the pandemic period, but the number of patients with HHV‐6B–associated cFS was stable throughout the observation period. Therefore, the change in proportion of patients with cFS caused by primary HHV‐6B infection was 49.5% (95% CI, 12.2%–60.5%; p = 0.0048). The disease burden of primary HHV‐6B infection among patients in the emergency room remained unchanged, with a significant increase in the relative proportion after the COVID‐19 pandemic began.

Several studies have shown an association between varicella-zoster virus infection and ischemic stroke. We analyzed the trends in the numbers of patients with varicella, herpes zoster and ischemic stroke before and after the universal vaccination program using a Japanese database of hospitalized patients. The number of patients with varicella decreased but those of herpes zoster and ischemic stroke did not change.

We report an autopsy case of anti-N-methyl-D-aspartate (NMDA) receptor (NMDAR) encephalitis with concurrent human herpes virus-6 (HHV-6) A deoxyribonucleic acid (DNA) detection in cerebrospinal fluid (CSF). A 38-year-old previously healthy Japanese man presented with a generalized seizure. Brain magnetic resonance imaging (MRI) findings were unremarkable, but CSF revealed pleocytosis. On Day 11, HHV-6 DNA was detected in CSF, and IgG antibodies against the NR1 subunit of the NMDAR (GluN1) were subsequently detected. Since HHV-6 encephalitis was initially suspected, the patient was treated with foscarnet and ganciclovir, but the HHV-6A copy number increased from 200 (Day 22) to 2000 copies/mL (Day 47), and the therapy was ineffective. As typical symptoms of anti-NMDAR encephalitis developed, we changed the patient's treatment to combat anti-NMDAR encephalitis. He was repeatedly treated with first-line immunotherapy, and GluN1 antibody titer decreased. He was not treated with second-line immunotherapy because of recurrent infections; he died on Day 310. Postmortem examinations did not show systemic tumors. Microscopic examination of the brain revealed only severe neuronal rarefaction in the hippocampal cornu ammonis (CA) 3-4 areas with gliosis. Early initiation of aggressive immunotherapy may be required in a refractory case of anti-NMDAR encephalitis, even with HHV-6A DNA detection, because the significance of this concurrent detection in autoimmune encephalitis remains unclear.

Central nervous system (CNS) involvement in anaplastic large cell lymphoma (ALCL) at diagnosis is rare and leads to poor prognosis with the use of the standard ALCL99 protocol alone. CNS-directed intensive chemotherapy, such as an increased dose of intravenous MTX, increased dose of dexamethasone, intensified intrathecal therapy, and high-dose cytarabine, followed by cranial irradiation, has been shown to improve survival in this population. In this paper, the authors describe a 14-year-old male with an intracranial ALCL mass at onset who received CNS-directed chemotherapy followed by 23.4 Gy of whole-brain irradiation. After the first systemic relapse, the CNS-penetrating ALK inhibitor, alectinib, was applied; it has successfully maintained remission for 18 months without any adverse events. CNS-penetrating ALK inhibitor therapy might prevent CNS relapse in pediatric ALK-positive ALCL. Next-generation ALK inhibitors could be introduced as a promising treatment option, even for primary ALCL with CNS involvement, which could lead to the omission of cranial irradiation and avoid radiation-induced sequalae. Further evidence of CNS-penetrating ALK inhibitor combined therapy for primary ALK-positive ALCL is warranted to reduce radiation-induced sequalae in future treatments.

予防接種後有害事象(AEFI)および予防接種ストレス関連反応(ISRR)に関連する動画講義視聴が小児科医の予防接種に対する知識、態度、自信、役割認識、自己効力感、行動に与える影響を調査した。介入前評価(pre study)に回答した日本小児科学会会員368名をA群とB群に分けてA群にのみオンラインでISRRに関する約20分間の動画講義を配布し、pre studyから約1ヵ月後にA群・B群に介入後評価(Post study)を行った。Post studyの回答者A群74名、B群95名を対象に動画講義視聴による介入効果について検討した。その結果、AEFIおよびISRRに関連する調査によってA群・B群の知識レベルが向上したが、予防接種に対する態度、自信、役割認識、自己効力感、実際の接種行動に与える影響は限定的であった。

予防接種後有害事象(AEFI)および予防接種ストレス関連反応(ISRR)に関連する動画講義視聴が小児科医の予防接種に対する知識、態度、自信、役割認識、自己効力感、行動に与える影響を調査した。介入前評価(pre study)に回答した日本小児科学会会員368名をA群とB群に分けてA群にのみオンラインでISRRに関する約20分間の動画講義を配布し、pre studyから約1ヵ月後にA群・B群に介入後評価(Post study)を行った。Post studyの回答者A群74名、B群95名を対象に動画講義視聴による介入効果について検討した。その結果、AEFIおよびISRRに関連する調査によってA群・B群の知識レベルが向上したが、予防接種に対する態度、自信、役割認識、自己効力感、実際の接種行動に与える影響は限定的であった。

In the era of universal varicella vaccination, diagnosis of varicella is challenging, especially for breakthrough cases. We sought to clarify the reliability of direct varicella-zoster virus (VZV) loop-mediated isothermal amplification (LAMP) and DermaQuick® VZV using the immunochromatography technique as rapid diagnostic tests for varicella. In addition, the usefulness of saliva as a sample type for direct LAMP was investigated. Among the 46 enrolled patients with suspected VZV infection, 31 patients (67.3%) were positive for the nucleic acid test based on real-time PCR from skin swab samples. Direct LAMP of skin swabs was positive in 29 (63.0%) of 46 patients. DermaQuick® VZV was positive in 25 (54.3%) of 46 patients. VZV DNA was detected in only 48.4% of oral swabs with the direct LAMP method. With real-time polymerase chain reaction (PCR) as the standard for diagnosing varicella, the sensitivity and specificity of DermaQuick® VZV were 80.7% and 100%, respectively. The sensitivity and specificity of direct LAMP from skin swabs were 93.6% and 100%, respectively. The sensitivity and specificity of real-time PCR for DNA extracted from oral swabs were 74.2% and 93.3%, respectively. Thus, oral swab samples are not suitable for breakthrough varicella diagnosis. Although DermaQuick® VZV is considered the most convenient point-of-care test for varicella, its sensitivity and specificity were lower than those of direct VZV LAMP.

BACKGROUND: Congenital cytomegalovirus (CMV) infection (cCMV) can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Oral valganciclovir (VGCV) therapy has been reported to improve long-term audiological and neurodevelopmental outcomes in patients with cCMV. The levels of CMV DNA in whole blood have been monitored in previous studies. However, quantitative methods using whole blood have not been standardized. Recently, the plasma viral load has been standardized and widely used in CMV-associated diseases. METHODS: CMV viral loads in whole blood and plasma were serially measured in 24 patients with a confirmatory diagnosis of cCMV during oral VGCV therapy using an in-house real-time PCR assay. Plasma samples were assayed using the Cobas 6800 system (Roche Diagnostics) in addition to an in-house assay. RESULTS: Plasma CMV viral loads were remarkably decreased at the end of therapy compared to before therapy. A significant correlation of CMV levels between whole blood and plasma was observed (Spearman's ρ = 0.566). The levels of CMV DNA before therapy were significantly correlated with the period of decreasing the viral loads to below the detection limit, not only in whole blood (Spearman's ρ = 0.901) but also in plasma (Spearman, ρ = 0.804). Finally, CMV viral loads between the in-house assay and commercially available standardized assay in 75 plasma samples with positive PCR results for CMV were compared; a significant correlation was observed between the results of both assays. CONCLUSIONS: There was a significant correlation between the two assays (Spearman, ρ = 0.882), suggesting that CMV plasma viral loads measured by the standardized assay are widely used to monitor the levels of CMV DNA in patients with cCMV during oral VGCV therapy.

Eczema herpeticum (EH) is a disseminated cutaneous infection with herpes simplex virus (HSV) that develops in patients with atopic dermatitis. The kinetics and clinical significance of HSV viremia in EH are poorly understood. Herein, we report HSV DNAemia in a child with EH 12 months after the completion of chemotherapy for Hodgkin lymphoma.

Multisystem inflammatory syndrome in children (MIS-C) has been widely reported, mainly in Western countries. The clinical features of MIS-C and Kawasaki disease are similar. The latter is common in Asian countries, including Japan. Meanwhile, the incidence of MIS-C seems to be low in Japan. Retropharyngeal edema is relatively common in older patients with Kawasaki disease and has been reported in a few patients with MIS-C. We describe a case of severe retropharyngeal edema after coronavirus disease 2019 (COVID-19) that improved quickly with high-dose of intravenous immunoglobulin treatment. Onset of retropharyngeal edema was 3 weeks after COVID-19. The patient received appropriate intravenous antibiotics for 5 days, but his symptoms worsened. Therefore, we suspected that his retropharyngeal edema was caused by suspected MIS-C even though he did not have the typical clinical symptoms of suspected MIS-C such as gastrointestinal symptoms and shock. Retropharyngeal edema was refractory to antibiotic therapy but lessened quickly with high-dose immunoglobulin therapy, without other typical clinical manifestations of MIS-C, suggesting that early immunoglobulin therapy might prevent the progression of MIS-C.

BACKGROUND: Scholarship is recognized as important in residency training worldwide. The Japan Pediatric Society (JPS) enacted a reform in 2017 to require publication of an article as a prerequisite for taking the board certification test, with the goal of increasing scholarly activity. METHODS: The purpose of this study was to provide a detailed description of the trends in residents' scholarly activities related to the JPS reform. A secondary analysis was performed on the cross-sectional database of pediatrics residents who took the certification test in 2015-2018. RESULTS: The enrolled participants were 2399 residents of which 79.7% passed the test. Publication of any type of article increased significantly (21%-22% to 100%; 0.1 to 0.3/person-year) after the implementation of the JPS reform, whereas academic presentations did not (89% to 91%; 1.2 to 1.3/person-year), both in terms of the percentage of the number of those who created them and the average rate of research production. Not only Japanese articles (11%-13% to 49%-53%; 0.04 to 0.15-0.17/person-year) or case reports (10%-14% to 51%-52%; 0.03-0.05 to 0.16-0.17/person-year), but also English articles (4%-5% to 15%-16%; 0.01-0.02 to 0.05/person-year) and original articles (5% to 11%-17%; 0.01 to 0.03-0.05/person-year) increased significantly. The number of each type of article publication was correlated with success in the board certification test (odds ratio 1.5-1.8). CONCLUSIONS: Scholarly activities of pediatrics residents were enhanced by the JPS implementation of the article requirement policy, which is crucial to fostering a scholarly culture. The most efficient measures to promote scholarship need to be persistently investigated.

BACKGROUND: Although many child death review (CDR) systems have been developed in Japan, the optimal system is still being identified. The aim of this study is to identify the etiologies of child deaths and to propose a screening method for initiating the CDR process in Japan. METHODS: Clinical medical records (CMRs) in hospitals and autopsy records were surveyed for cases of deaths of children aged less than 15 years between 2014 and 2016 in Aichi Prefecture, Japan. The data were analyzed in three steps, and the findings were compared with the vital statistics. RESULTS: Of the 695 children whose death certificates were submitted to Aichi Prefecture, 590 could be traced to pediatric care hospitals. The distribution of causes of death was slightly different from the vital statistics, with 11.5% dying of extrinsic causes and 19.7% dying of unknown causes. Maltreatment was suspected in 64 cases, which was much higher than that in government statistics. Overall, 158 (26.8%) deaths were considered preventable. The number of unnatural deaths, which might be screened in, was calculated as 172 (29.2%) in the vital statistics, whereas the survey of CMRs revealed that 241 (40.8%) to 282 (47.8%) should be screened in. CONCLUSIONS: Surveying CMRs in hospitals may be a suitable method to detect and screen deaths to start the CDR process in Japan.