Epidemiology of child mortality and challenges in child death review in Japan: The Committee on Child Death Review: A Committee Report: The Committee on Child Death Review: A Committee Report.

We performed a retrospective survey and verification of the medical records of death cases of children (and adolescents; aged <18 years) between 2014 and 2016 in pediatric specialty training facilities in Japan. Of the 2,827 registered cases at 163 facilities, 2,348 cases were included. The rate of identified deaths compared with the demographic survey, was 18.2%-21.0% by age group. The breakdown of deaths was determined as follows: 638 cases (27.2%) were due to external factors or unknown causes, 118 (5.0%) were suspected to involve child maltreatment, 932 (39.7%) were of moderate or high preventability or were indeterminable. Further detailed verification was required for 1,333 cases (56.8%). Comparison of the three prefectures with high rates of identified deaths in Japan revealed no significant differences, such as in the distribution of diseases, suggesting that there was little selection bias. The autopsy rate of deaths of unknown cause was 43.4%, indicating a high ratio of forensic autopsies. However, sufficient clinical information was not collected; therefore, thorough evaluations were difficult to perform. Cases with a moderate or high possibility of involvement of child maltreatment accounted for 5%, similar to previous studies. However, more objective evaluation is necessary. Preventable death cases including potentially preventable deaths accounted for 25%, indicating that proposals need to be made for specific preventive measures. Individual primary verification followed by secondary verification by multiple organizations is effective. It is anticipated that a child death review (CDR) system with such a multi-layered structure will be established; however, the following challenges were revealed: The subjects of CDR are all child deaths. Even if natural death cases are entrusted to medical organizations, and complicated cases to other special panels, the numbers are very high. Procedures need to be established to sufficiently verify these cases. Although demographic statistics are useful for identifying all deaths, care must be taken when interpreting such data. Detailed verification of the cause of death will affect the determination of subsequent preventability. Verification based only on clinical information is difficult, so a procedure that collates non-medical information sources should be established. It is necessary to organize the procedures to evaluate the involvement of child maltreatment objectively and raise awareness among practitioners. To propose specific preventive measures, a mechanism to ensure multiprofessional diverse perspectives is crucial, in addition to fostering the foundation of individual practitioners. To implement the proposed measures, it is also necessary to discuss the responsibilities and authority of each organization. Once the CDR system is implemented, verification of the system should be repeated. Efforts to learn from child deaths and prevent deaths that are preventable as much as possible are essential duties of pediatricians. Pediatricians are expected to undertake the identified challenges and promote and lead the implementation of the CDR system. This is a word-for-word translation of the report in J. Jpn. Pediatr. Soc. 2019; 123 (11): 1736-1750, which is available only in the Japanese language.

Early eradication of factor VIII inhibitor in patients with congenital hemophilia A by immune tolerance induction with a high dose of immunoglobulin.

The production of factor VIII (FVIII) inhibitory antibodies is a serious problem in patients with hemophilia A. Immune tolerance induction (ITI) is the only strategy proven to eradicate persistent inhibitors and has been shown to be successful in 70 % of patients with hemophilia A. However, a minority of hemophilia patients present life-long inhibitors. To eliminate such inhibitors, we designed an intravenous immunoglobulin (IVIG) strategy in combination with high dose recombinant FVIII for ITI in hemophilia A children with inhibitors. Four previously untreated patients produced inhibitors within 16 exposures to FVIII. The peak inhibitor titers in these patients ranged from 3 to 14 BU/mL. The patients received ITI combined with IVIG within 1.5 months after the inhibitors were detected. All patients showed a negative titer for inhibitors by 28 days, with no anamnestic responses. The recovery of FVIII in the plasma concentration was normalized within three months after initiation of ITI. An additional course of IVIG administration led to induction of complete tolerance by 20 months after initiation of ITI therapy in all patients. ITI treatment with high-dose FVIII combined with IVIG may be effective for the early elimination of inhibitors.

Maternal breast milk odour induces frontal lobe activation in neonates: a NIRS study.

We used near-infrared spectroscopy (NIRS) to examine differences in neonates' orbito-frontal cortical activation in response to the odours of maternal breast milk and formula milk in terms of changes in the oxygenation of cerebral blood flow. Twenty-six healthy neonates were tested in their cribs while they slept in a silent room. The neonates were exposed to each olfactory stimulus by an experimenter. NIRS monitoring was performed using optodes placed above the bilateral anterior orbito-frontal gyri. The differences in oxygenated haemoglobin (oxy-Hb) values between baseline and stimulation were defined as the change in oxy-Hb. The degrees of change were calculated by an analysis of variance (ANOVA). A 2 (stimulus: breast milk and formula milk) × 2 (probe location: right and left) ANOVA showed that the odour of maternal breast milk (right/left: M=0.28/0.48) induced a significantly (F=6.36, p<0.05) greater increase in the oxygenated blood of the orbito-frontal region than did the odour of formula milk (right/left: M=-0.03/-0.07). Differences in the intensity of odour had no significant influence on the blood oxygenation of the orbito-frontal region. Maternal breast milk odour increased oxygenated blood flow in the orbito-frontal region to a greater extent than did formula milk odour. These results suggest that neonates can distinguish between the odours of maternal breast milk versus formula.

The guideline of the personal health data structure to secure safety healthcare. The balance between use and protection to satisfy the patients' needs.

PURPOSE: To inform about the impact of a recent movement towards a policy to develop integrative networked electronic health record (EHR) as a basis for cooperation among care teams and with patients and in support of safe patient care in Japan. METHODS: The author headed a commission developing policy for health record (HR) structure and its computerization. It executed two questionnaire surveys as the basis for its work. One survey assessed the current state of computerization of health record in the hospitals certified by Japan Council for Quality Health Care (JCQHC). The other survey assessed the attitudes towards a specific EHR system in the Hiroshima University Hospital and its affiliate hospitals. RESULTS: The survey of the above hospitals showed that most have computer supported administrative procedures, but only few computer-based health records. The attitudes of the Hiroshima EHR users show that while they expect efficiency and quality improvements, there is also apprehension that the system in use might lower practical efficiency and compromise patient safety. Accordingly, health recording requirements and storage policy have been restructured and communicated to the hospitals. CONCLUSION: These insights led to the initiation of curricula educating "Health Information Technologist" which is promoted by Japan Association Medical Informatics and the criterion of Chart Review Promotion of JCQHC. They will also lead to recommendation for improved and advanced EHR.

The function of the frontal lobe in neonates for response to a prosodic voice.

We examined how neonates responded at the brain level to an element of acoustic stimulation using near-infrared spectroscopy (NIRS). Twenty full-term, healthy neonates were included in the study. The neonates were tested in their cribs while they slept in a silent room. First, two probe holders were placed on the left and right sides of the forehead over the eyebrows using double-sided adhesive tape. Then the neonates were exposed to the auditory stimuli from an external auditory speaker. The stimuli, readings of the first scene of "Little Red Riding Hood," were made with a digital voice. The stimuli consisted of two conditions: variably pitched speech (variable speech: VS) and monotonous flat-pitched speech (monotonous speech: MS). The analyses focused on changes in O(2)Hb because O(2)Hb is the most sensitive indicator of changes in cerebral blood flow in NIRS measurement. The O(2)Hb level promptly increased at the beginning of the VS condition, and then returned to baseline again, while O(2)Hb did not show any changes during the MS condition. Differences between baseline-stimulation relative values were used to perform a 2 (condition)x2 (recording site)x2 (gender) analysis of variance. The results show that VS (M=0.45, S.D.=1.33) produced a greater increase of oxygenated blood to the frontal area of the brain area than MS (M=-0.19, S.D.=1.28). Neonates' brain activation patterns suggest that they can discriminate differences in the prosodic patterns of utterances.

A clinical management system for patient participatory health care support. Assuring the patients' rights and confirming operation of clinical treatment and hospital administration.

We conducted a drastic change in our hospital information system to support patient participatory health care provided in the New Hiroshima University Hospital (HUH). The new information system in HUH (HU-MIND II-Hiroshima University Hospital Medical Intelligence and Notice Delivery system II) is designed as "clinical management system" (CMS). The core of this CMS is the electronic health record (EHR), which aims to assure both the patients' right to know, and the attendants' accountability. It is evident that the team practice including patients requires close communication. Data in the EHR are written not only by physicians, but also by all coworkers, which will enable them to realize the team communication and the ordering in a reliable way and to leave the evidence of conducted practices. Moreover, the bedside information systems were set-up at all 700 beds. Patients can access their anamnesis and future clinical care procedures themselves. Based on the demand outlined above, the new regulations of HUH are composed of 21 requirements, conditions of information collection, accumulation and use. Our focus was how to make patients' right compatible with attendants' accountability. As the data owners, patients have the facility to access their own data at their bedsides. They can view their own health condition and treatment program and can control the data flow.

Dysregulation of transcriptions in primary granule constituents during myeloid proliferation and differentiation in patients with severe congenital neutropenia.

We examined the expression of granule constituent genes in myeloid progenitor cells during proliferation and differentiation in patients with severe congenital neutropenia (SCN). The heterozygous mutation of the neutrophil elastase gene was identified in two of four patients. The CD34+/granulocyte-colony stimulating factor receptor (G-CSFR)+ cells of SCN patients showed defective responsiveness to G-CSF in serum-deprived culture. The CD34+/G-CSFR+ cells expressed low levels of the granule constituent mRNAs. The transcription levels of primary granule enzyme genes in CD34+/G-CSFR+ cells were gradually enhanced and then decreased when cells were induced toward myeloid lineage with G-CSF in normal subjects. However, the primary up-regulation and the following down-regulation of these enzyme transcriptions were not clearly observed in SCN patients. No differences in expressions of the lactoferrin gene were seen between normal subjects and patients with SCN. We hypothesize that the abnormal regulation of the transcription in primary granule constituents might involve the defective proliferation and differentiation of myeloid cells in patients with SCN.

Defects of granulopoiesis in patients with severe congenital neutropenia.

To confirm the abnormalities of primitive myeloid progenitor cells in patients with severe congenital neutropenia (SCN), we studied their responsiveness to hematopoietic factors including granulocyte colony-stimulating factor (G-CSF). In all SCN patients studied no abnormalities of granulocyte colony-stimulating factor receptor (G-CSFR) gene were detected by polymerase chain reaction-single-strand conformation polymorphism analysis and sequence analysis. A flow cytometric analysis of bone marrow cells based on the expression of CD34, Kit receptor, and G-CSFR demonstrated a reduced frequency of CD34+/Kit+/G-CSFR+ cells in patients with SCN. The granulocyte/macrophage (GM)-colony formation of CD34+/Kit+/G-CSFR+ cells in patients was markedly decreased at all concentrations of G-CSF in serum-deprived semisolid culture. The responsiveness of CD34+/Kit+/G-CSFR+ cells in patients showed a reduced response to the combination of stem cell factor, the ligand for flk2/flt3, and interleukin-3 with or without G-CSF in serum-deprived semisolid and liquid suspension cultures. In contrast, no difference in the responsiveness of CD34+/Kit+/G-CSFR- cells was noted between SCN patients and normal subjects. The bone marrow cells from a patient who underwent bone marrow transplantation showed a restoration of both the reduced frequency and the decreased level of GM-colony formation of CD34+/Kit+/G-CSFR+ cells. These results demonstrate that the presence of qualitative and quantitative abnormalities of primitive myeloid progenitor cells expressing G-CSFR may play an important role in the impairment of granulopoiesis in patients with SCN.