Search

Although play is an essential occupation for children, parents of children with autistic traits tend to struggle with play-based interpersonal interaction with them. Tickling play appears to be one of the most interpersonal forms of play because nobody can tickle themselves. However, atypical tactile processing (e.g. tactile sensitivity) has been reported in children with autistic traits, who may exhibit atypical behavioral responses during tickling play. Our aim was to investigate the association between autistic traits and behavioral responses during parent-child tickling play in Japanese young children. We recorded tickling interaction between children and their parents using behavior coding with six behavioral items. Autistic traits and tactile sensitivity were measured using parent-reported questionnaires. Results showed two behavioral responses were significantly associated with autistic traits in all children: "approach with positive emotional response" and "no response" were negatively and positively correlated with autistic traits, respectively. This exploratory study suggests that behavioral responses during tickling play may be associated with autistic traits. [ABSTRACT FROM AUTHOR]

Background: Food allergy children and their families tend to have emotional distress and anxiety. There have been few reports of differences in parenting stress and a child's food allergy phenotypes. Methods: We examined the associations between food allergy phenotypes in children and parenting stress assessed by the Parenting Stress Index‐Short Form (PSI‐SF) from a national birth cohort (Japan Environment and Children's Study). Results: We included 65,805 children for statistical analysis. Of them, 7.2% of children had a food allergy diagnosis at 2 years old. The means of the total PSI‐SF (39.9 ± 10.3, 39.1 ± 9.9), CD‐SF (19.5 ± 5.4, 19.1 ± 5.2), and PD‐SF (20.5 ± 6.3, 20.0 ± 6.1) scores are similar for caregivers in the with and without food allergy groups. Food allergy diagnosis resulted in significantly higher total PSI scores (coefficient.47, 95% CI 0.19–0.75, p =.001), CD‐SF (coefficient.22, 95% CI 0.07–0.38, p =.004), and PD‐SF (coefficient.24, 95% CI 0.08–0.41, p =.004). A similar trend was observed for allergy reactions to hen's egg. However, there was no clear relationship between allergic reactions to milk, wheat, nuts, and PSI‐SF. Conclusions: Parental stress was significantly related to a child's food allergy. Furthermore, hen's egg allergy increased parental stress. Multiple food avoidance might also increase parental stress. Healthcare providers need to be aware of parental stress in our daily clinic. [ABSTRACT FROM AUTHOR]

Human adenovirus (HAdV) infections present diverse clinical manifestations upon infecting individuals, with respiratory infections predominating in children. We surveyed pediatric hospitalizations due to respiratory HAdV infections across 18 hospitals in Hokkaido Prefecture, Japan, from July 2019 to March 2024, recording 473 admissions. While hospitalizations remained below five cases per week from July 2019 to September 2023, a notable surge occurred in late October 2023, with weekly admissions peaking at 15−20 cases from November to December. There were dramatic shifts in the age distribution of hospitalized patients: during 2019−2021, 1‐year‐old infants and children aged 3−6 years represented 51.4%−54.8% and 4.1%−13.3%, respectively; however, in 2023−2024, while 1‐year‐old infants represented 19.0%−20.1%, the proportion of children aged 3−6 years increased to 46.2%−50.0%. Understanding the emergence of significant outbreaks of respiratory HAdV infections and the substantial changes in the age distribution of hospitalized cases necessitates further investigation into the circulating types of HAdV in Hokkaido Prefecture and changes in children's neutralizing antibody titers against HAdV. [ABSTRACT FROM AUTHOR]

This study investigates the impact of the COVID-19 pandemic on pediatric out-of-hospital cardiac arrest (OHCA) outcomes in Japan, aiming to address a critical research gap. Analyzing data from the All-Japan Utstein registry covering pediatric OHCA cases from 2018 to 2021, the study observed no significant changes in one-month survival, neurological outcomes, or overall performance when comparing the pre-pandemic (2018–2019) and pandemic (2020–2021) periods among 6765 cases. However, a notable reduction in pre-hospital return of spontaneous circulation (ROSC) during the pandemic (15.1–13.1%, p =.020) was identified. Bystander-initiated chest compressions and rescue breaths declined (71.1–65.8%, 22.3–13.0%, respectively; both p <.001), while bystander-initiated automated external defibrillator (AED) use increased (3.7–4.9%, p =.029). Multivariate logistic regression analyses identified factors associated with reduced pre-hospital ROSC during the pandemic. Post-pandemic, there was no noticeable change in the one-month survival rate. The lack of significant change in survival may be attributed to the negative effects of reduced chest compressions and ventilation being offset by the positive impact of widespread AED availability in Japan. These findings underscore the importance of innovative tools and systems for safe bystander cardiopulmonary resuscitation during a pandemic, providing insights to optimize pediatric OHCA care. [ABSTRACT FROM AUTHOR]

Background: Little information is available on the association between gender nonconformity during adolescence and subsequent mental health. While the distress related to gender nonconformity may be socially produced rather than attributed to individual-level factors, further research is needed to better understand the role of psychosocial factors in this context. Method: We analyzed data from the Tokyo Teen Cohort, obtained through random sampling of adolescents born between 2002 and 2004. We used inverse probability weighting to examine the association of gender nonconformity at ages 12 and 14 as a time-varying variable with subsequent mental health at age 16, while accounting for time-fixed and time-varying confounders. Furthermore, we used a weighting approach to investigate the mediating role of modifiable psychosocial factors in this association, addressing exposure-mediator and mediator–mediator interactions. Results: A total of 3171 participants were analyzed. Persistent gender nonconforming behavior at ages 12 and 14 was associated with subsequent depression (β = 2.02, 95% confidence interval [CI] 0.85 to 3.19) and psychotic experiences (β = 0.33, 95% CI 0.14 to 0.52) at age 16. The results remained robust in sensitivity analyses. Approximately 30% of the association between gender nonconformity and depression was consistently mediated by a set of psychosocial factors, namely loneliness, bullying victimization, and relationships with mother, father, and friends. Conclusions: Persistent gender nonconformity during adolescence is associated with subsequent mental health. Psychosocial factors play a vital mediating role in this association, highlighting the essential need for social intervention and change to reduce stigmatization and ameliorate mental health challenges. [ABSTRACT FROM AUTHOR]

Survival rates of patients with Philadelphia chromosome-positive ALL (Ph+ALL) have improved considerably with the introduction of tyrosine kinase inhibitors (TKI); however, hematopoietic stem cell transplantation (HSCT) continues to play an important role. Reduced-intensity conditioning (RIC) regimens have been widely applied particularly for older patients, but their validity for children and adolescents with Ph+ALL has not been investigated. In this study, data from patients receiving HSCT for de novo Ph+ALL in first or second remission at ages younger than 25 years and with a history of pre-HSCT TKI therapy were retrospectively collected through the nationwide registry in Japan. In 265 patients who received myeloablative conditioning (MAC) and 33 patients receiving RIC, 5-year leukemia-free survival (LFS) rates were 67.3% and 79.8%, respectively (p = 0.142). Multivariate analysis of LFS, focusing on patients with good performance status, identified RIC as a significant prognostic factor for LFS (hazard ratio 0.32, p = 0.032), as well as older age, higher leukocyte count at diagnosis, and disease with additional chromosomal abnormalities. These trends were similar when we focused on patients who received prophylactic post-HSCT TKI treatment, as 5-year LFS was 81.0% for MAC and 84.4% for RIC (p = 0.748). In summary, HSCT with RIC regimen showed at least comparable LFS to HSCT with MAC regimen, and RIC was an independent favorable prognostic factor on multivariate analysis adjusting potential prognostic factors. While patient numbers were limited, our data suggest that RIC may be safely applied in this group, particularly combined with prophylactic post-HSCT TKI maintenance therapy. [ABSTRACT FROM AUTHOR]

Purpose: Recently, direct communication with children about cancer seems to have shifted, but little is known about communication regarding discussions of future infertility risk due to cancer therapy. This study conducted cross-cultural comparisons between Japan and the United States to clarify communication patterns about cancer notification and develop appropriate information about fertility issues. Methods: An online survey was distributed to members of the Japanese Society of Pediatric Hematology/Oncology in July 2019 and the American Society of Pediatric Hematology/Oncology in July 2020. Based on the results from the survey, we developed three types of educational videos: a prepubertal version A, B, and a pubertal version. Next, we conducted a survey to assess whether these were appropriate for clinical practice. Results: We analyzed 325 physicians in Japan and 46 in the United States. In Japan, 80.5%, 91.7%, and 92.1% of the physicians notified patients aged 7–9, 10–14, and 15–17 years of their cancer diagnosis directly, respectively, compared within the United States, where the rate was 100%, regardless of age. Further, 9% and 45% of physicians in Japan and the United States, respectively, discuss fertility issues directly with patients aged 7–9 years. In the survey to assess the educational videos, 85% of the physicians preferred to use the educational videos in clinical practice. Conclusion: This is the first step in bringing concordance to communication patters for emerging cancer care around the globe and that this study and its intervention arm provide guidance in ways that ensure global equity in care. [ABSTRACT FROM AUTHOR]

The present study investigated the association between pre- and postnatal maternal hair dye use and the risk of wheeze and asthma in Japanese children aged 5 years. Study participants were 1199 mother-child pairs. Information on the variables under study was obtained using repeated questionnaires completed by parents. Prenatal maternal hair dye use was associated with an increased risk of current wheeze and ever doctor-diagnosed asthma; the adjusted odds ratios (ORs) (95% confidence intervals [CIs]) were 1.44 (1.02–2.02) and 1.51 (1.00–2.25), respectively. Postnatal maternal hair dye use was related to the risk of doctor-diagnosed asthma; the adjusted OR (95% CI) was 1.58 (1.03–2.40). Children who were exposed to maternal hair dye use both prenatally and postnatally had an increased risk of childhood current wheeze and ever doctor-diagnosed asthma; the adjusted ORs (95% CIs) were 1.59 (1.03–2.42) and 1.76 (1.06–2.88), respectively. Our findings suggest that perinatal maternal hair dye use is associated with the risk of wheeze and asthma in children. [ABSTRACT FROM AUTHOR]

Following the coronavirus disease 2019 (COVID‐19) outbreak in February 2020, incidences of various infectious diseases decreased notably in Hokkaido Prefecture, Japan. However, Japan began gradually easing COVID‐19 infection control measures in 2022. Here, we conducted a survey of children hospitalized with human metapneumovirus (hMPV), influenza A and B, and respiratory syncytial virus infections in 18 hospitals across Hokkaido Prefecture, Japan, spanning from July 2019 to June 2023. From March 2020 to June 2022 (28 months), only 13 patients were hospitalized with hMPV, and two patients had influenza A. However, in October to November 2022, there was a re‐emergence of hMPV infections, with a maximum of 27 hospitalizations per week. From July 2022 to June 2023 (12 months), the number of hMPV‐related hospitalizations dramatically increased to 317 patients, with the majority aged 3–6 years (38.2%, [121/317]). Influenza A also showed an increase from December 2022, with a peak of 13 hospitalizations per week in March 2023, considerably fewer than the pre‐COVID‐19 outbreak in December 2019, when rates reached 45 hospitalizations per week. These findings suggest the possibility of observing more resurgences in infectious diseases in Japan after 2023 if infection control measures continue to be relaxed. Caution is needed in managing potential outbreaks. [ABSTRACT FROM AUTHOR]

Background: Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance. Some patients with PJS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood and sometimes have serious complications that significantly reduce their quality of life. Hamartomatous polyps in the small bowel may cause bleeding, intestinal obstruction, and intussusception. Novel diagnostic and therapeutic endoscopic procedures such as small-bowel capsule endoscopy and balloon-assisted enteroscopy have been developed in recent years. Summary: Under these circumstances, there is growing concern about the management of PJS in Japan, and there are no practice guidelines available. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour and Welfare with specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of PJS together with four clinical questions and corresponding recommendations based on a careful review of the evidence and involved incorporating the concept of the Grading of Recommendations Assessment, Development and Evaluation system. Key Messages: Herein, we present the English version of the clinical practice guidelines of PJS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with PJS. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic skin condition that is associated with significant patient burden and decreased health‐related quality of life (HRQoL). We report results of the real‐world Epidemiology of Children with Atopic Dermatitis Reporting on their Experience study in Japanese pediatric patients, focusing on the impact of AD severity on disease burden. Methods: Children and adolescents aged 6 months to 17 years (or their caregivers/parents) completed an online survey between September 26, 2018, and March 5, 2019. Patients with diagnosed AD (i.e., met International Study of Asthma and Allergies in Childhood criteria and had a self‐reported AD diagnosis) were evaluated for disease severity using the Patient‐Oriented Eczema Measure (POEM). Impact of AD severity on AD symptoms (itching, pain, and sleep disturbance), disease flares, atopic comorbidities, healthcare resource utilization, school days missed, and HRQoL were assessed. Results: Of 5702 Japanese pediatric patients, 547 had diagnosed AD and were included in this analysis. Based on POEM scores, AD severity was clear/mild in 346 patients (63.3%), moderate in 177 (32.5%), and severe in 24 (4.4%). Across all age groups (i.e., less than 6, 6–11, and 12–17 years), increased AD severity was associated with increased AD symptom severity, number of flares, atopic comorbidities, healthcare resource utilization, and school absences, as well as worsened HRQoL. Conclusions: This population‐based study of Japanese children and adolescents showed that greater AD severity had a high impact on disease burden. [ABSTRACT FROM AUTHOR]

In this study, we compared the success rate of eradicating Helicobacter pylori (H. pylori) in adults and children using vonoprazan (VPZ)-based H. pylori regimens to that of proton pump inhibitors (PPIs). In Japan, the success rate of a VPZ-based regimen as first-line therapy was lower in children than in adults. Compared with adults, children around puberty have higher CYP2C19 and CYP3A4 enzymatic activity to metabolize PPIs and VPZ. Further, children generally have shorter intestinal transit times than adults and may absorb antibiotics to a lesser extent. When comparing success rates of pediatric and adult eradication therapy using VPZ, it is very important to maintain a higher intragastric pH with sufficient gastric acid suppression to maintain H. pylori in a replicating state and amoxicillin and clarithromycin in the intestinal tract for as long as possible by reducing diarrhea as a side effect. Based on the above, it is reasonable that VPZ, which can suppress stomach acids more strongly than PPI, is a more relevant H. pylori eradication therapy. [ABSTRACT FROM AUTHOR]

• In healthy Japanese infants/toddlers, V114 given subcutaneously was well tolerated. • The V114 safety profile was comparable to that of PCV13. • V114 elicited immune responses to all 15 serotypes in healthy infants/toddlers. • V114 was non-inferior for the 13 PCV13 serotypes after the three-dose infant series. • V114-elicited immune responses were higher than PCV13 for serotypes 22F and 33F. This phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in Japanese infants. V114 contains all 13 serotypes in PCV13 plus additional serotypes 22F and 33F. Healthy Japanese infants were randomized to receive three primary doses of V114 or PCV13 (dose 1 at 2–6 months of age; doses 2 and 3 ≥ 27 days after prior dose), plus a toddler dose at 12–15 months of age. Adverse events (AEs) were collected on Days 1–14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-dose 3, pre-dose 4, and 30 days post-dose 4. Primary objectives included non-inferiority of V114 to PCV13 for the 13 shared serotypes based on serotype-specific IgG response rates (IgG ≥ 0.35 μg/mL) and geometric mean concentration (GMC) ratios, and for serotypes 22F and 33F based on IgG response rates and compared with the lowest response of any serotype in the PCV13 group, at 30 days post-dose 3. Overall, 694 infants were randomized to V114 (n = 347) or PCV13 (n = 347). Proportions of participants with solicited and serious AEs were comparable between vaccination groups. V114 met non-inferiority criteria for all 13 shared serotypes, based on difference in proportion of responders (lower bound of two-sided 95 % confidence interval [CI] > −10.0) and IgG GMC ratios (V114/PCV13, lower bound of two-sided 95 % CI > 0.5) at 30 days post-dose 3. The non-inferiority criterion based on IgG response rates was met for serotype 22F, but narrowly missed for serotype 33F (90.9 %, lower bound of two-sided 95 % CI −10.6). In Japanese infants, a four-dose series of V114 was generally well tolerated. Compared with PCV13, V114 provided non-inferior immune responses to the 13 shared serotypes and higher immune responses to serotype 22F and 33F post-primary series. Trial registration: ClinicalTrials.gov : NCT04384107; EudraCT 2019-003644-68. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between maternal combined spinal‐epidural analgesia during vaginal delivery and neurodevelopment in 3‐year‐old children. Methods: Using data from the Japan Environment and Children's Study, a birth cohort study on pregnant women and their offspring, we described the background, perinatal outcomes, and neurodevelopmental outcomes of participants with a singleton pregnancy who received combined spinal‐epidural analgesia during vaginal delivery and those who did not. The association between maternal combined spinal‐epidural analgesia and abnormalities in five domains of the Ages and Stages Questionnaire, Third Edition, was analyzed using univariable and multivariable logistic regression analyses. Crude and adjusted odds ratios with 95% confidence intervals (95% CI) were calculated. Results: Among 59 379 participants, 82 (0.1%) children (exposed group) were born to mothers who received combined spinal‐epidural analgesia during vaginal delivery. In the exposed versus control groups, 1.2% versus 3.7% had communication abnormalities (adjusted odds ratio [95% CI]: 0.30 [0.04–2.19]), 6.1% versus 4.1% exhibited gross‐motor abnormalities (1.36 [95% CI: 0.55–3.36]), 10.9% vs. 7.1% had fine‐motor abnormalities (1.46 [95% CI: 0.72–2.96]), 6.1% vs. 6.9% showed difficulties with problem‐solving (0.81 [95% CI: 0.33–2.01]), and 2.4% vs. 3.0% had personal‐social problems (0.70 [95% CI: 0.17–2.85]). Conclusions: Exposure to combined spinal‐epidural analgesia during vaginal delivery was not associated with the risk of neurodevelopmental abnormalities; however, the sample size of our study might not be appropriate for the study design. [ABSTRACT FROM AUTHOR]

Pediatric atopic dermatitis (AD) can negatively impact the family quality of life (QoL). We report data from the real-world Epidemiology of Children with Atopic Dermatitis Reporting on their Experience (EPI-CARE) study in Japanese pediatric patients, focusing on disease impact on family QoL. Children and adolescents aged 6 months to <18 years completed an online survey between September 2018–December 2019. The impact of disease severity on family QoL and its effect on parents' time were assessed using the dermatitis family impact (DFI) questionnaire. The impact of a family history of allergic conditions, current residency, second-hand smoke exposure, and household pets on AD prevalence and severity was also assessed. Family QoL decreased as AD severity increased, particularly in families with children aged <6 years; but had the greatest impact on sleep and tiredness in families with children aged <12 years. Parents spent at least 4.6 h/week caring for children <6 years, including those with mild symptoms. Most children (>80%) had a family history of allergic conditions; AD prevalence was increased in those exposed to second-hand smoke or household pets. This study demonstrated that pediatric AD in Japanese individuals has negative impacts on family QoL and that family and household environments can influence pediatric AD prevalence. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to examine the long-term effects of parenting practice during preschool years on children's movement performance in primary school. Methods: This three-year longitudinal study included 225 children aged 3-6-years-old. Parents reported baseline parenting practice and evaluated children's movement performance three years later. Latent class analysis was used to explore latent classes of movement performance. A post hoc test was used to identify the characteristics of different patterns. Finally, adjusted multinomial logistic regression models were used to test the influence of parenting practice on identified patterns of movement performance. Results: Children in this study were grouped into three movement performance patterns, labelled as 'least difficulties' (n = 131, 58.2%), 'low back pain' (n = 68, 30.2%) and 'most difficulties' (n = 26, 11.6%). After controlling for age, gender, having siblings or not, family structure, standardised body mass index, sleep condition and dietary habits, the researchers found that if parents played games with children frequently, the children would have a 0.287 times lower probability of being in the 'low back pain' class (95% confidence interval [CI]: 0.105--0.783). In addition, if parents take children to meet peers of a similar age frequently, children would have a 0.339 times lower probability of being in 'most difficulties' class (95% CI: 0.139-0.825). Conclusion: Primary healthcare providers should pay careful attention to children with movement difficulties. The study provides longitudinal evidence to support the applicability of positive parenting practice in early childhood to prevent children's movement difficulties. [ABSTRACT FROM AUTHOR]

Background: The semi‐automatic intraosseous device (EZ‐IO®) is useful for safely securing intraosseous access. There are some complications associated with its use but few studies have examined the risk factors. The present study aimed to investigate the risk factors for extravasation as a complication of EZ‐IO use in pediatric patients. Methods: This study is a secondary analysis of a previous, monocentric, retrospective study conducted in Japan describing the use of EZ‐IO in a pediatric emergency department. The patients included in the study were younger than 16 years of age with EZ‐IO use at the Tokyo Metropolitan Children's Medical Center between January, 2013 and August, 2018. The factors analyzed included demographic information (sex, age, weight), Glasgow Coma Scale (GCS), diagnosis, bolus infusion, and lidocaine use. The primary endpoint was the odds ratio (OR) and 95% confidence interval (CI) for extravasation incidence. Results: Seventy‐two patients were enrolled; 14 of these had extravasation, 39 (54.2%) had a diagnosis of cardiac arrest, and 50 (69.4%) had a GCS score of 8 or less. Statistical analysis demonstrated that the group with a high GCS score was significantly associated with extravasation: GCS (<13) versus GCS (13≦) (OR: 12.25; 95% CI: 2.54–59.15; p < 0.01), GCS (<8) versus GCS (8≦) (OR: 4.78; 95% CI: 1.34–17.01; p = 0.03). Conclusions: A high GCS score was associated with extravasation in EZ‐IO use significantly more often than a low GCS score. No significant difference was found in the other endpoints. [ABSTRACT FROM AUTHOR]

Background: After the Great East Japan Earthquake on March 11, 2011 and the subsequent accident at the Tokyo Electric Power Company‐operated Daiichi Nuclear Power Plant, the Fukushima Prefecture government initiated the Fukushima Health Management Survey (FHMS) to assess the long‐term health effects of the disaster on Fukushima residents. The blood tests of children aged ≤15 years between 2011 and 2012 did not reveal any changes regarding peripheral blood data; however, long‐term monitoring is still necessary. Therefore, this study aimed to investigate the long‐term health status of children aged ≤15 years who had evacuated the Fukushima Prefecture. Methods: From 2011 to 2018, 71,250 evacuees aged 15 years or younger participated in the FMHS and were subjected to blood tests. By analyzing the data of the comprehensive health check survey managed by the FHMS, we examined the changes in hemoglobin (Hb) levels, white blood cell (WBC) counts, including fractions, and platelet (PLT) counts among children from 2011 to 2018. Results: Minor fluctuations in Hb levels, PLT counts, and WBC counts were observed during the study period, but the central 95% intervals of distribution of the laboratory values were generally within previously reported reference intervals. In particular, there was no increase in the proportions of patients with anemia, polycythemia, or deviating WBC counts. Conclusion: From 2011 to 2018, there was no increase in the percentages of children with anemia, polycythemia, or deviating WBC counts among the Fukushima Prefecture evacuees. [ABSTRACT FROM AUTHOR]

Background: Ocular injury is a leading cause of monocular blindness in children. However, data on the association of injury type with ophthalmological complications are lacking. This study aimed to investigate the risk factors of pediatric ocular injuries related to ophthalmological complications. Methods: This retrospective, observational study was conducted in a pediatric emergency department (ED) in Japan from March 2010 to March 2021. Patients aged less than 16 years presenting with ocular trauma, diagnosed on the basis of the International Classification of Diseases 10: S05, 0–9, were enrolled. Emergency department follow‐up visits for the same complaint were excluded. The patients' sex, age, arrival time, injury mechanism, symptoms, examinations, diagnosis, history of urgent ophthalmological consultation, outcomes, and ophthalmological complications were investigated. The primary endpoints were the odds ratio (OR) and 95% confidence interval (CI) of the incidence of ophthalmological complications, defined as any new acute complaint or worsening/persistence of an initial complaint following or resulting from ocular trauma. Results: In total, 469 patients were analyzed. The median age was 7.3 years; the interquartile range (IQR) was 3.1–11.5 years. The most common diagnosis was contusion (79.3%), followed by lamellar laceration (11.7%). Seven patients (1.5%) had ophthalmological complications during follow up. Bivariate analysis demonstrated that daytime ED visit, impact with a sharp object, animal‐related injury, visual impairment, decreased visual acuity, and open globe injury were factors significantly associated with ophthalmological complications. Conclusion: Daytime ED visit, impact with a sharp object, animal‐related injury, visual impairment, decreased visual acuity, and open globe injury were independent factors of ophthalmological complications. [ABSTRACT FROM AUTHOR]

Background: An in‐depth understanding of the epidemiology of ill or injured children transported between hospitals is crucial in building regional medical transport services in public health. Although the epidemiological situation varies by nation and region, it has not been well documented in Japan. In this report we described the number of pediatric interhospital transportations and examined the regional variations and trends in the recent decade. Methods: We performed repeated, cross‐sectional analyses of children (<15 years) undergoing interhospital transportation in 2010, 2013, and 2016–19, using the national database of public ambulances of the Fire and Disaster Management Agency in Japan. We stratified the cases into critical care transport (CCT) or non‐critical care transport (NonCCT) by the illness/injury severity of the transported children. We calculated the national population‐adjusted number of CCTs and described prefectural variations in CCT numbers with analytical thinking. Results: There were 23,506 CCTs and 138,347 NonCCTs. The national average of population‐adjusted CCT numbers was 255 per 1,000,000 person‐years. The statistics varied by prefectures, ranging from 25–536 per 1,000,000 person‐years. The annual trends were also diverse across prefectures, increasing in nine, decreasing in six, and static in 31 prefectures. In analytical thinking of regional variations, potential contributing factors included available interhospital transport services and the threshold of direct admission and referral to tertiary‐care hospitals, whereas regional variations were not well associated with geographical patterns or population size. Conclusions: Public ambulance services were substantially used for CCTs and NonCCTs in Japan. Regional variations should be taken into account for the future policymaking on pediatric interhospital transportation. [ABSTRACT FROM AUTHOR]

Background: Serum anti‐tissue transglutaminase immunoglobulin A antibody (tTG‐IgA) is a screening test for celiac disease (CeD). In recent years, there have several reports of combined inflammatory bowel disease (IBD) and CeD in children. The purposes of this study are to research the positivity of the tTG‐IgA antibody in Japanese children, and whether IBD and CeD co‐occur. Methods: We examined tTG‐IgA as a screening test for CeD in symptomatic pediatric patients with IBD (cases) and those without IBD (controls, non‐IBD). Those with tTG‐IgA levels of 10 U/mL or higher were considered positive. All patients had routine biopsy specimens taken from the second part and bulbus of the duodenum, and were evaluated histologically based on the Marsh classification. Results: Thirty‐one patients in the IBD group and 53 patients in the non‐IBD group were included. The tTG‐IgA was positive in five cases (5.9%) and median titer of positive cases was 12.3 U/mL (10.2–41.7). One patient in the IBD group (3.2%) and four patients in the non‐IBD group (7.8%) were positive for tTG‐IgA. No cases showed histological features of CeD. There were no statistically significant differences in age, sex, symptoms and laboratory tests between the tTG‐IgA positive and negative groups. Patients among the IBD and the non‐IBD groups that were tTG‐IgA positive demonstrated symptoms after wheat consumption. Conclusions: We identified a patient who was positive for tTG‐IgA antibodies who experienced abdominal symptoms due to wheat ingestion, indicative of subclinical CeD. Further investigation is needed to clarify the co‐occurrence of IBD and CeD among Japanese children. [ABSTRACT FROM AUTHOR]

Background: Acute coronavirus disease 2019 (COVID‐19) is associated with chronic symptoms. These have been termed the "post COVID‐19 condition." The data on this condition in children are still limited. We therefore aimed to elucidate the characteristics of this post COVID‐19 condition. Methods: Children referred to a long COVID‐19 clinic were included at Tokyo Metropolitan Children's Medical Center between October 2021 and July 2022. Children with another diagnosis and those who failed to meet criteria for post COVID‐19 condition were excluded. Demographic and clinical data were collected retrospectively. Results: Of 33 referrals, nine were excluded, and 24 fulfilled the criteria for post COVID‐19 condition. The median age and percentage of girls were 12.5 (IQR: 11–13) years and 29.2%, respectively. All the patients had mild, acute COVID‐19. Dysgeusia and brain fog was observed more frequently during the Delta and Omicron variant periods, respectively. School absenteeism >4 weeks was observed in 41.6% of the patients. Common symptoms included malaise, headache, dysgeusia, and dysosmia. The median duration of post COVID‐19 condition was 4.5 (IQR: 2.8–5.2) months. Pain management and counseling using the pacing approach were the most commonly offered treatments. Symptom resolution and improvement was observed in 29.2% and 54.2% of the patients, respectively. Conclusions: One third of the patients referred for long COVID did not fit the definition of the post COVID‐19 condition. After a median follow up of 4.5 months, the majority of the cases resolved or improved. [ABSTRACT FROM AUTHOR]

Children's exercise habits have changed during the COVID-19 pandemic. This study aimed to examine the physical function and physical activity of preadolescent children before and during the COVID-19 pandemic. This cross-sectional study compared time spent in moderate-to-vigorous physical activity (MVPA), grip strength, single-leg standing time, and two-step tests of healthy children aged 10 to 12 years, enrolled from January 2018 to January 2020 (pre-COVID-19 group, n = 177) and from January 2021 to September 2022 (during-COVID-19 group, n = 69). The during-COVID-19 group had weaker grip strength (median: 14.4 vs. 15.8 kg; p = 0.012), worse performance on the two-step test (mean: 1.56 vs. 1.60; p = 0.013), and less MVPA (median: 4 vs. 7 h per week; p = 0.004). Logistic regression showed that the during-COVID-19 group was significantly related to weaker grip strength (odds ratio: 0.904, 95% CI: 0.829–0.986; p = 0.022) and worse performance in the two-step test (odds ratio: 0.976, 95% CI: 0.955–0.997; p = 0.028). The COVID-19 pandemic decreased exercise opportunities for preadolescent children, which may have had a negative impact on muscle strength and balance. It is essential to increase the amount of MVPA among preadolescent children. [ABSTRACT FROM AUTHOR]

Background: In Japan, cancer education utilizing external lecturers are being promoted as part of cancer control measures. The objective of this study was to clarify children's perceptions of cancer and survivors and their awareness of actions for early prevention and detection of cancer after participating in a cancer education program engaging with survivors. Methods: This study was conducted during January and March 2020, using the qualitative analysis method. Homeroom teachers gave a lesson on cancer to sixth-grade students (n=69) at an elementary school in Japan. Two weeks later, a cancer survivor gave a follow-up class. Then an inductive content analysis was conducted on the content of the post-class reflection worksheets written by students. Results: After analyzing the worksheets of 59 students, they learned that "to reduce the risk of developing cancer, one should lead a healthy lifestyle" and "strive for early detection through cancer screening" through the education program. As things they can do themselves in the future, they listed "encourage family members to get cancer screenings," "quit smoking," and "cut back on alcohol." In addition, children have deepened their understanding of cancer survivors and learned the importance of their own and others' lives. Conclusion: The results suggested that children gained practical knowledge about cancer through the program and deepened their understanding of cancer and survivors by directly interacting with and listening to survivors. [ABSTRACT FROM AUTHOR]

Background and Objectives: All 4 previous nationwide surveys of multiple sclerosis (MS) in Japan were conducted before the discovery of anti-aquaporin-4 (AQP4) antibodies; thus, neuromyelitis optica spectrum disorder (NMOSD) was included in MS, as optic-spinal MS. We aimed to clarify the epidemiologic features and trends of MS and NMOSD in Japan separately using a fifth nationwide survey., Methods: The primary survey, in which a questionnaire was sent to 3,799 selected departments (including neurology/internal medicine, pediatrics, and ophthalmology), explored the estimated number and prevalence of patients with MS or NMOSD in 2017, and the secondary survey collected detailed characteristics of the patients using a second questionnaire., Results: The response rates for the primary and secondary surveys were 60.1% and 53.9%, respectively. The estimated total number of patients with MS or NMOSD was 24,800, 2.5-fold higher than that in the fourth survey in 2003. The crude prevalence was 19.6 per 100,000 patients (14.2 for MS and 5.4 for NMOSD), compared with 7.7 per 100,000 patients in the fourth survey. Patients with MS showed milder disability (median Expanded Disability Status Scale [EDSS] score: 2.0 [interquartile range 1.0-4.5] vs 2.5 [1.0-6.0]), decreased secondary progression (8.5% vs 15.2%), and increased usage of disease-modifying drugs (63.7% vs 37.2%) compared with those with conventional MS in the fourth survey. The proportions of oligoclonal bands and Barkhof criteria fulfillment on MRI, which are features of classical MS, increased with advancing year of birth. Patients with NMOSD also showed less disability and shorter disease duration than patients with optic-spinal MS in the fourth survey (EDSS score: 3.5 [2.0-5.5] vs 3.8 [2.0-6.0]; disease duration: 8.0 [3.9-14.8] vs 10.0 [5.0-16.0]). Among patients with NMOSD, disability was exacerbated by a history of longitudinally extensive spinal cord lesions and anti-AQP4 antibody positivity, which both decreased with advancing year of birth., Discussion: The prevalences of MS (particularly with classical features) and NMOSD have been increasing in Japan, suggesting the contribution of environmental factors. However, disabilities in patients with MS and NMOSD have been mitigated. Extensive usage of various disease-modifying drugs could be a factor contributing to this disability mitigation in MS.

Background: With the recent advent of technology, it is important to confirm the health and safety of the youth. This study aimed to prospectively evaluate the relationship between Wi-Fi, cordless phones, and mobile phone usage patterns and behavioral problems., Methods: This study involved 2465 children aged 8-17 years from the Hokkaido Study on Environment and Children's Health from October 2020 to January 2021, with a follow-up from September 2021 to March 2022. The mother-child dyad provided information on the presence of residential Wi-Fi and cordless phones, cordless phone call duration, and mobile phone usage pattern (duration of calls using mobile network and internet, online audio streaming, online video streaming, and playing online games) via a baseline questionnaire. Based on the scores on Strength and Difficulties Questionnaire at baseline and follow-up, the children were categorized into four groups: normal, persistent, improved, and concurrent., Results: No significant association was found between Wi-Fi, mobile phone calls via mobile networks, and behavioral problems. Cordless phone at home had higher odds for improvement in total difficulty scores, and cordless phone for calling more than 4 min per week had lower odds of persistent problematic prosocial behavior. Longer duration of mobile phone calling via the internet (>40 min/week) had higher odds of concurrent total difficulties. Mobile phone calling via mobile network for <5 min per week had higher odds for improved total difficulty scores. Audio streaming via mobile phones for 60-120 min had lower odds of persistent total difficulties., Conclusion: Our results showed sporadic findings between residential RF-EMF indoor sources and mobile phone usage pattern. These observed findings could be affected by residual confounding and chance findings. Ongoing follow-up studies are necessary to further explore this association through detailed exposure assessment and addressing the potential limitations of our study., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Reiko Kishi reports financial support was provided by Japanese Ministry of Internal Affairs and Communications. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy characterized by prominent trabeculations. Detailed characteristics of biventricular noncompaction (BiVNC) remain unknown. This study aimed to elucidate the clinical characteristics and genetic landscape of BiVNC., Methods and Results: We recruited children with left ventricular noncompaction from Japanese multi-institutional centers from 2013 to 2021. Left ventricular noncompaction was classified as BiVNC, congenital heart disease, arrhythmia, dilated cardiomyopathy, or normal function. In these patients, cardiomyopathy-associated genes were screened. A total of 234 patients (127 male; mean age, 4 months [range, 0-6.6 years]) were enrolled in this study, of whom 25 had BiVNC; 55, normal function; 84, dilated cardiomyopathy; 38, congenital heart disease; and 32, arrhythmia. BiVNC was diagnosed during the perinatal period in 10 patients, in whom the prevalence was higher than that in other patients. A total of 14 patients in the group with BiVNC had congenital heart disease, but not necessarily right heart lesions. Left ventricular dyskinesis was frequently observed in the lateral wall (24%) and apex (28%). Eleven pathogenic variants were found in 11 patients with BiVNC (44.0%). The group with BiVNC had a higher ratio of mitochondrial and developmental gene variants than the other groups. Among all groups, the group with BiVNC had the worst survival rate ( P =0.0009)., Conclusions: Pediatric patients with BiVNC had a high rate of ventricular dyskinesis and poor outcome. A comprehensive and careful screening for disease-causing genes and phenotype may help identify specific patients with left ventricular noncompaction and mortality-related cardiac phenotypes.

Background: The influence of the coronavirus disease 2019 (COVID-19) pandemic on dental care utilization may have differed according to individual characteristics or type of dental care provision. This study aimed to evaluate the changes in dental care utilization and per-attendance costs by age group and type of dental care during the COVID-19 pandemic in Japan., Methods: This time-series study used healthcare insurance claims data from 01/07/2019 to 09/27/2021 (143 weeks) from nine municipalities in Japan. Dental care utilization rate per week and average dental care cost per attendance by age groups (0-19 years/20-64 years/65-74 years/≥75 years) and types of dental care (outpatient/visiting) were used as outcome variables. COVID-19 pandemic waves in Japan were used as predictors: 1 st (03/23/2020-05/17/2020), 2 nd (06/22/2020-09/27/2020), 3 rd (10/26/2020-02/21/2021), 4 th (02/22/2021-06/07/2021), and 5 th (07/05/2021-09/13/2021) waves. Fixed-effects models were employed to estimate the proportional changes., Results: In the fixed-effects model, we observed large declines in dental care utilization during the 1 st (17.0-22.0%) and 2 nd waves (3.0-13.0%) compared to the non-pandemic wave period in all age groups. In contrast, the average dental care cost per attendance increased in all age groups by 5.2-8.6% during the 1 st wave., Conclusion: During the initial wave of the COVID-19 pandemic in Japan, dental care utilization decreased in all age groups, whereas the average dental care cost per attendance increased. The COVID-19 pandemic may have changed the dental care provision pattern towards less frequent and more concentrated dental care to avoid the risk of infection.

Background: No previous reports have characterized national profiles of soft-tissue sarcoma overall. We examined the nationwide statistics for soft-tissue sarcoma in Japan using data from the population-based National Cancer Registry., Methods: We identified 23 522 soft-tissue-sarcoma patients who were entered in the National Cancer Registry during 2016-19 using International Classification of Diseases-Oncology, Third Edition codes for cancer topography and morphology. We extracted data on patient demographics, tumor details (reason for diagnosis, tumor location, histology, extent of disease), hospital volume/type, treatment, and prognosis for each patient., Results: Soft-tissue sarcoma showed a slight male preponderance. Approximately 5500-6000 new cases were diagnosed as soft-tissue sarcoma per year, with the age-adjusted incidence of soft-tissue sarcoma being 3.22/100000/year. The age distribution showed a single peak in the 70-79 age range, and sex-stratified data showed it was higher in men. The most common histologic subtype was liposarcoma. The most frequent tumor locations were the soft tissue and skin, followed by the retroperitoneum. Extent of disease was categorized as: "localized" (31.3%), "regional" (38.9%), or "distant" (10.5%). We found significant associations between overall survival and sex, age, tumor location, facility type, hospital volume, reason for diagnosis, extent of disease, and surgical treatment., Conclusions: This is the first study to outline the epidemiology, clinical features, treatment, prognosis, and significant factors affecting prognosis of soft-tissue sarcoma in Japan using the National Cancer Registry. Documenting our data regarding elderly patients' outcomes is essential so other countries showing similar population-aging trends can learn from our experiences., Level of Evidence: Prognostic studies, Level III., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

During the COVID-19 pandemic, widespread school closures were implemented globally based on the assumption that transmission among children in the school environment is common. However, evidence regarding secondary infection rates by school type and level of contact is lacking. Our study estimated the frequency of SARS-CoV-2 infection in school settings by examining the positivity rate according to school type and level of contact by using data from a large-scale school-based PCR project conducted in Okinawa, Japan, during 2021-2022. Our results indicate that, despite detection of numerous positive cases, the average number of secondary infections remained relatively low at ≈0.5 cases across all types of schools. Considering the profound effects of prolonged closures on educational access, balancing public health benefits against potential long-term effects on children is crucial.

Purpose: We validated claims-based algorithms using the International Classification of Diseases, Tenth Revision (ICD-10) to identify patients with the first-ever coronavirus disease (COVID-19) onset between May 2020 and August 2022., Methods: The study cohort was comprised of residents of one municipality enrolled in a public insurance program. This study used data provided by the municipality, including residents' insurer-based medical claims data linked to the Health Center Real-time Information-Sharing System (HER-SYS). The HER-SYS data included positive results from COVID-19 tests and were used as reference standards. Claims-based algorithms #1 and #2 were U07.1, B34.2, with and without suspicious diagnoses, respectively. Claims-based algorithms #3 and #4 were U07.1 with and without suspicious diagnoses, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each algorithm., Results: The study cohort included 165 038 residents, including 13 402 residents were the reference standard. For the entire period, the sensitivity, specificity, PPV, and NPV were 55.7% (95% confidence interval: 54.8%-56.5%), 65.4% (65.2%-65.6%), 11.5% (11.3%-11.8%), and 98.9% (98.8%-99.0%) for Algorithm #1, and 67.0% (66.2%-67.8%), 88.1% (87.9%-88.3%), 31.6% (31.1%-32.2%), and 97.8% (97.7%-97.8%) for Algorithm #2, and 52.9% (52.0%-53.7%), 67.1% (66.9%-67.3%), 11.5% (11.2%-11.8%), and 98.3% (98.3%-98.4%) for Algorithm #3, 62.6% (61.8%-63.4%), 88.5% (88.3%-88.7%), 30.9% (30.3%-31.4%), and 97.3% (97.2%-97.4%) for Algorithm #4, respectively., Conclusions: Our study showed that the validity of claims-based algorithms consisting of COVID-19-related ICD-10 codes to identify patients with first-onset COVID-19 is limited., (© 2024 John Wiley & Sons Ltd.)

Introduction: The purpose of this epidemiological study was to assess the prevalence, comorbidities, and real-world management of childhood epilepsy to provide insights for enhancing epilepsy management and medical resource planning., Materials and Methods: The study encompassed insured individuals aged 0-17 years as of December 2018 who were registered at any point in 2018, for at least part of the year, in a Japanese health claims database spanning January-December 2018. Epilepsy was defined as a diagnosis of epilepsy based on the International Classification of Diseases, 10th Revision codes, and a claimed management fee for epilepsy or an anti-seizure medication (ASM) prescription for longer than 4 weeks. The prevalence of epilepsy, patient characteristics, including comorbidities, and management status, such as prescription of ASMs, were evaluated., Results: Among 1528,905 registered children, 9279 were identified as having epilepsy. The prevalence of epilepsy was the lowest at 1.97 per 1000 population (95 % confidence interval [CI] 1.80-2.15) in the 0-2-year age group and increased with age to 9.34 per 1000 population (95 % CI 8.98-9.72) in the 15-17-year age group, with a significantly higher prevalence in boys than in girls in the ≥12-year age group. ASMs were prescribed to 88.3 %-91.9 % of the patients. Moreover, 27 (0.29 %) patients underwent epilepsy surgery. The frequency of claiming intravenous ASMs and long-term electroencephalogram fees increased with a decrease in age., Conclusions: Our findings indicate that young children receive more medical resources than adolescents and that epilepsy surgery is underutilized. Further investigations will help improve the management of and develop measures against epilepsy., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Although generic drugs are essential in reducing medical costs, their use in epilepsy therapy remains a subject of ongoing debate. In this study, we analysed prescription trends of generic drugs using data from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) Open Data Japan., Methods: The number of generic drug prescriptions from 2017-2021 was extracted from the NDB Open Data Japan, with data for each medication stratified by prefectural region, sex, and age, allowing for the analysis of the impact of each factor. We analysed the correlation between the prescription volumes of generic antiseizure medications (ASMs) and the number of clinical epileptologists registered with the Japan Epilepsy Society per 100,000 population., Results: In 2021, the prescription volume of generic ASMs was 49 %, whereas that for other pharmacological agents was between 70-80 %. Notably, for children < 15 years of age, generics made up approximately 20 % of prescriptions, which was significantly less than that in other age groups. Analysis by prefecture revealed a negative correlation between prescription volumes of ASMs and the number of clinical epileptologists across prefectural regions in Japan (R = -0.47, p < 0.01)., Conclusion: Our findings indicate that the higher the proportion of clinical epileptologists in each prefecture, the lower the number of prescribed generic ASMs. Clinical epileptologists in Japan therefore prescribe antiseizure agents in accordance with the Japanese epilepsy treatment guidelines that do not recommend the use of generic agents., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Buccal midazolam (buc MDL) is the first buccal mucosal delivery formulation applied for status epilepticus in Japan. Herein, we aimed to investigate the effectiveness and adverse events of buc MDL as a pre-hospital treatment for epileptic seizures in real-world clinical practice., Methods: This study involved a retrospective review based on medical records. We included children who received buc MDL as pre-hospital treatment for epileptic seizures and were subsequently transported to the emergency department between April 2021 and November 2023., Results: This study included 26 patients (136 episodes). The overall efficacy rate, which was defined as seizure cessation within 10 min after buc MDL administration with no recurrence within 30 min, was 43 %. Moreover, 70 % of the episodes did not require additional medications. None of the episodes required bag-mask ventilation or intubation following seizure cessation with buc MDL alone. The efficacy was decreased when buc MDL was administered longer than 15 min from seizure onset. Furthermore, the efficacy did not decrease as long as it was within 0.2-0.5 mg/kg, even if the dose was smaller than the appropriate dose for the specific age., Conclusions: The response rate was significantly higher in episodes where buc MDL was administered within 15 min. Additionally, there was no concern regarding respiratory depression with buc MDL alone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Tapinarof is a nonsteroidal, topical, aryl hydrocarbon receptor agonist. We evaluated the efficacy and safety of tapinarof cream 1% in Japanese patients aged ≥12 years with atopic dermatitis (AD) in two phase 3 trials, ZBB4-1 and ZBB4-2. ZBB4-1 (N = 216) consisted of an 8-week, double-blind, vehicle-controlled treatment period (period 1) and a 16-week extension treatment period (period 2). Patients were randomized 2:1 to tapinarof or vehicle in period 1; subsequently, all patients who enrolled in period 2 received tapinarof. ZBB4-2 (N = 291) was a 52-week, open-label, uncontrolled trial in which all patients received tapinarof. In period 1 of ZBB4-1, the proportion of patients who achieved an Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with ≥2-grade improvement from baseline at week 8 (IGA treatment success, the primary end point) was 20.24% in the tapinarof group and 2.24% in the vehicle group (p = 0.0007). The proportion of patients with ≥75% improvement from baseline in Eczema Area and Severity Index (EASI) score at week 8 (EASI-75 response, the key secondary end point) was 40.3% in the tapinarof group and 4.3% in the vehicle group (p < 0.0001). In ZBB4-2, IGA treatment success rate was 28.1% at week 16, 32.3% at week 24, and 41.3% at week 52, and EASI-75 response rate was 53.3% at week 16, 63.7% at week 24, and 76.6% at week 52, indicating that efficacy responses improved over time and were maintained over 52 weeks. Across the two trials, most adverse events (AEs) were mild or moderate; common AEs included folliculitis, acne, and headache. In summary, tapinarof cream 1% was effective and generally safe for up to 52 weeks of treatment in Japanese patients with AD., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Introduction/aims: Multifocal motor neuropathy (MMN) is a rare disease for which epidemiological and clinical data are limited. We conducted a nationwide survey to determine disease prevalence, incidence, clinical profile, and current treatment status in Japan., Methods: A nationwide survey was conducted in 2021 using an established epidemiological method. Questionnaires were sent to all neurology and pediatric neurology departments in Japan. An initial questionnaire was administered to determine the number of patients with and incidence of MMN. A second questionnaire was administered to collect detailed clinical information. The European Federation of Neurological Societies/Peripheral Nerve Society 2010 guidelines were used as diagnostic criteria., Results: The estimated number of patients with MMN was 507. The estimated prevalence was 0.40 per 100,000 individuals. Detailed clinical profiles were available for 120 patients. The male-to-female ratio was 2.3:1 and the median onset age was 42 years. The median disease duration at diagnosis was 25 months. Most patients presented with upper limb-dominant muscle weakness. Motor nerve conduction blocks were found in 62% of patients and positive anti-GM1 IgM antibody results in 54%. A total of 117 (98%) patients received immunoglobulin therapy, and 91% of them showed improvement. At the time of the last visit (median, 82 months from treatment initiation), 89 (74%) patients were receiving maintenance immunoglobulin therapy. A slight progression of neurological deficits was observed during follow-up., Discussion: Most patients with MMN in Japan received induction and maintenance immunoglobulin therapies, which appear to suppress long-term disease progression., (© 2024 Wiley Periodicals LLC.)

Purpose: This study is to investigate whether angiotensin type 1 receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEis) can regress coronary artery aneurysm (CAA) in patients with Kawasaki disease (KD)., Methods: This multicenter, prospective, observational study was conducted at 53 institutions throughout Japan. We enrolled patients who were diagnosed with KD after January 2015 and had a medium or large CAA (maximum luminal diameter ≥ 4 mm or z score ≥  + 5) 30 days or later after KD onset., Results: Of the 209 patients, 47 (22%) were taking ARBs/ ACEis. Compared with those in the non-ARB/ACEi group, the baseline CAA diameter was significantly greater (6.7 mm vs. 5.5 mm, p < 0.01), and bilateral CAA (70% vs. 59%, p = 0.01) and giant CAA (32% vs. 20%, p = 0.08) were more frequently observed in the ARB/ACEi group. Although the overall regression rates did not differ between the groups (67% vs. 65%), the regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group (36% vs. 23%). Multivariate Cox regression analysis after adjustment for other clinical variables suggested that ARBs/ACEis may be a factor in CAA regression (hazard ratio [HR]: 1.5, 95% confidence interval [CI]: 0.91-2.46)., Conclusions: Although ARBs/ ACEis were used more frequently in patients with severe CAA, these patients had similar CAA regression rates to patients not taking ARBs/ACEis. ARBs/ACEis may be beneficial agents aimed at inducing CAA regression in KD patients., What Is Known: • Large CAAs are less likely to regress and are always at risk of life-threatening cardiac events. • Moderate CAA, age less than 1 year, and female sex have been reported to be factors that promote the regression of CAA., What Is New: • Although ARBs/ACEis were used more frequently in patients with severe CAA, these patients had a similar rate of CAA regression to patients who did not take ARBs/ACEis. • The regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To reconstruct age-structured case counts of COVID-19 using sentinel reporting, which replaced universal reporting of COVID-19 from May 2023 in Japan., Methods: Using COVID-19 sentinel data stratified by discrete age groups in selected prefectures and referring to universal case count data up to May 8, 2023, we fitted a statistical model to handle weekly growth rates as a function of age and time so as to convert sentinel data to case counts after cessation of universal reporting., Results: The age distribution of cases in sentinel reporting was significantly biased toward younger age groups compared to universal reporting. When comparing the epidemic size of the 9th wave (May 8 to September 18, 2023) to the 8th wave (October 3, 2022 to April 10, 2023), using the wave-on-wave ratio of total cumulative sentinel cases led to a significant underestimation of the wave-on-wave in Tokyo (0.975, vs 1.461 by universal reporting) and Okinawa (1.299, vs 1.472). The estimates of growth rates, scaling factors between universal and sentinel cases, and expected universal case count showed robustness to changes in the ending week of the data period., Conclusion: Our model quantified COVID-19 dynamics, comparably to universal reporting that ended in May 2023, enabling detailed and up-to-date health burden analysis using sentinel reports. The cumulative incidence was greater than that suggested from sentinel data in Tokyo, Nara, and Okinawa. Per-population burdens among children were particularly high in Osaka and Nara, indicating a strong bias in sentinel reporting toward pediatric cases., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study aimed to translate and validate the Japanese Sleep Questionnaire for Preschoolers (JSQ-P) into a Thai version and to evaluate factors associated with sleep problems in preschoolers., Methods: The cross-cultural adaptation of JSQ-P into Thai version of JSQ-P (TH-JSQ-P) was performed including forward translation, reconciliation, backward translation, and final approval by the original creator. Children aged 2-6 years from community and clinical settings were enrolled. The TH-JSQ-P was completed by parents of preschool children twice within 10-14 days to assess its reliability and validity. Six validity tests including face validity, content validity, structural validity, construct validity, criterion validity and predictive validity were assessed. Demographic data, Epworth sleepiness scale (ESS), medical and behavior problems, and socioeconomic status were collected for analysis., Results: A total of 2613 participants completed the TH-JSQ-P, with 1207 completing it twice to assess test-retest reliability. The TH-JSQ-P had good internal consistency reliability and test-retest ability with Cronbach's alpha value of 0.898 and intraclass correlation coefficient of 0.814. The content validity was acceptable. The ESS had correlation with sleep problems in almost all subscales except for sleep habit., Conclusions: The TH-JSQ-P is a valid and reliable instrument for evaluating sleep problems in preschool children in Thailand. It has the potential to be extensively utilized to screen for sleep problems, thereby enabling healthcare professionals to identify them early and implement prompt management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Failure-free survival (FFS) rates of low-risk patients with rhabdomyosarcoma improved in Intergroup Rhabdomyosarcoma Study IV after the escalation of cyclophosphamide total dose to 26.4 g/m 2 . However, this dose may increase the risk of adverse events, including infertility, in some patients. The JRS-I LRA0401 and LRB0402 protocols aimed to reduce the cyclophosphamide dose to 9.6 g/m 2 and 17.6 g/m 2 , respectively, without decreasing the FFS rates., Methods: Subgroup-A patients received eight cycles (24 weeks) of vincristine, actinomycin D, and 1.2 g/m 2 /cycle cyclophosphamide. Subgroup-B patients received eight cycles (24 weeks) of vincristine, actinomycin D, and 2.2 g/m 2 /cycle cyclophosphamide, followed by six cycles (24 weeks) of vincristine and actinomycin D. Group II/III patients in both subgroups received radiotherapy., Results: In subgroup A (n = 12), the 3-year FFS rate was 83% (95% confidence interval [CI], 48-96), and the 3-year overall survival (OS) rate was 100%. Only one isolated local recurrence was observed (8.3%). There were no unexpected grade-4 toxicities and no deaths. In subgroup B (n = 16), the 3-year FFS and OS rates were 88% (95% CI, 59-97) and 94% (95% CI, 63-99), respectively. There were no unexpected grade 4 toxicities and no deaths., Conclusions: Shorter duration therapy using vincristine, actinomycin D, and lower dose cyclophosphamide with or without radiotherapy for patients with low-risk subgroup A rhabdomyosarcoma (JRS-I LRA0401 protocol) and moderate reduction of cyclophosphamide dose for patients with low-risk subgroup B rhabdomyosarcoma (JRS-I LRB0402 protocol) did not compromise FFS., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is increasingly utilized in pediatric patients. Failure to recognize membrane oxygenator failure can lead to critical complications due to rapid deterioration of membrane oxygenator function. Therefore, identifying the predictors for membrane oxygenator exchange is crucial. However, risk factors for membrane oxygenator exchange in pediatric V-A ECMO remain unclear; therefore, this study aimed to evaluate these risk factors., Methods: This retrospective cohort study enrolled all pediatric patients aged <18 years who received V-A ECMO between August 2018 and July 2023 at a tertiary-care pediatric hospital in Japan. The Cox proportional hazards model was used to evaluate the predictors of membrane oxygenator failure within 72 h after initiation., Results: During the study period, membrane oxygenator failure occurred in 18/55 (32.7%) children within 72 h; membrane oxygenator failure within 72 h occurred in 4/29 (13.8%) and 14/26 (53.8%) in the groups with ratio of blood flow divided by the blood flow limit of the membrane oxygenator (B/L) of <0.5 and ≥0.5, respectively (adjusted hazards ratio, 4.97 [95% confidence interval, 1.33-18.5]; p = 0.017). After adjusting for delta pressure of the oxygenator, an increase in body weight and aspartate aminotransferase levels were associated with an increase in early membrane oxygenator failure., Conclusions: This retrospective study demonstrated that a B/L ratio >0.5, an increase in body weight, and elevated aspartate aminotransferase were independent risk factors for early membrane oxygenator failure in pediatric V-A ECMO. However, a prospective multicenter study with an appropriate sample size is warranted to mitigate potential bias, and enhance generalizability for further investigation of the association between a B/L ratio and early membrane oxygenator failure., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Vici syndrome (VICIS) is a congenital disorder characterized by agenesis of the corpus callosum, cataracts, hypopigmentation, cardiomyopathy, combined immunodeficiency, microcephaly, and failure to thrive. This study aimed to elucidate the number of patients with VICIS, its clinical characteristics and relevant genetic information in Japan., Methods: After developing diagnostic criteria for VICIS, we conducted a nationwide questionnaire-based survey of VICIS in Japan. In the initial survey, we investigated the number of VICIS patients who fulfilled definite or probable criteria. The second survey was used to obtain detailed clinical and genetic information of VICIS from institutions that responded to the initial survey., Results: Clinical information was available for 15 patients (12 definite, three probable). As of October 2023, nine patients (60%) were alive and six (40%) had died. All patients presented with developmental delay, agenesis of the corpus callosum, elevated serum aspartate/alanine aminotransferase, hypopigmentation and hypotonia. Developmental delay was profound. Most patients developed recurrent infection, high-arched palate, epilepsy, failure to thrive, and microcephaly. Cardiomyopathy and cataracts, both initially described as principal features in VICIS, were notably uncommon in our study. Based on the information collected, all 14 patients for whom information was available received home medical care: 11 (79%) received tube feeding, three (21%) required noninvasive ventilation, four (29%) required tracheostomy, and four (29%) required home subcutaneous immunoglobulin administration., Conclusion: This study revealed for the first time the nationwide status of patients with VICIS in Japan. The mortality rate of patients with VICIS is as high as 40%, and almost all VICIS patients require various forms of home medical care, necessitating comprehensive management. Additionally, we identified one adult patient, underscoring the need for comprehensive medical management extending into adulthood for patients with VICIS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Urinary tract infections caused by Aerococcus urinae have rarely been reported in children, and the clinical characteristics remain unclear. We reviewed medical records of children whose urine cultures grew A. urinae (≥10 4  CFU/mL) at a tertiary children's hospital in Tokyo, Japan. We found 17 pediatric patients in a review of 22,769 urine cultures between June 2006 and May 2022. The median age of 17 patients was 10.7 years (IQR 8-13 years), and males represented 76.5 % of the patients. Sixteen patients (94.1 %) had underlying urological conditions (neurogenic bladder, vesicoureteral reflux, urethral stenosis, bladder exstrophy, or urinary catheterization). The chief symptoms were fever (35.3 %), malodorous urine (23.5 %), nausea (11.8 %), and back pain (5.9 %). Ten patients were asymptomatic. Pyelonephritis was diagnosed in five male patients. All of them had underlying abnormal conditions of the bladder, and two had malodorous urine. All patients had favorable outcomes after 10-14 days of ampicillin/amoxicillin-based antimicrobial therapy., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Cholesteryl esters (CE) are sterols comprising various fatty acyl chains attached to a cholesterol hydroxyl moiety. CEs are often considered plasma biomarkers of liver function; however, their absolute concentrations in the plasma of Japanese preadolescents have not been well explored. This study aimed to determine the plasma CE levels in Japanese preadolescents of different sexes, ages, and body weights living in Hokkaido, Japan using targeted liquid chromatography/tandem mass spectrometry. The analysis was performed on the non-fasting plasma of preadolescents aged 9-12 years (n = 339 healthy volunteers; 178 boys and 161 girls) from Sapporo, Hokkaido, Japan. The analysis results showed that the total CE levels in boys and girls were 871 ± 153 and 862 ± 96 pmol/μL, respectively. CE 18:2 (41 ± 2.9 %) was found to be the most abundant species followed by CE 18:1 (16 ± 1.5 %) and CE 16:0 (13 ± 1.1 %). The ω-3 fatty acid-containing CEs such as CE 18:3 and CE 20:5 were significantly lower in girls than in boys. Despite the different ages, CEs were tightly regulated in the plasma of children's, and the total CEs ranged between 844 and 906 pmol/μL in boys and 824 and 875 pmol/μL in girls. The participants were further classified into three groups based on their body mass index underweight (n = 237), normal weight (n = 94), and overweight (n = 8). Most of the quantified CEs were accumulated in the overweight group. Interestingly, CE 18:3 was significantly upregulated in the overweight group compared to that in the normal range, and the area under the receiver operating characteristic curve was 0.73, suggesting that it could be a possible marker for obesity. This study marks the initial investigation of absolute CE levels in the plasma of children and can help elucidate the relationship between CEs and childhood obesity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Forgiveness plays an important role in restoring and maintaining cooperative relationships. Previous studies have demonstrated that young children could forgive transgressors both as a third party and as a victim. However, the research on young children's understanding of forgiveness is scant. This study focused on the two main functions of forgiveness-the restoration of a damaged relationship between the victim and the transgressor and the positive emotional change in the victim toward the transgressor. In this study, 48 4-year-olds (25 girls), 50 5-year-olds (21 girls), and 50 6-year-olds (21 girls) in Japan heard stories in which a victim either did or did not forgive a transgressor. They answered questions about the relationship between the victim and the transgressor and the victim's feelings toward the transgressor. Regarding the restoration of a damaged relationship, 4- to 6-year-olds understood that the restoration could occur in the presence of forgiveness. Yet, 6-year-olds showed more distinctive belief than 4- and 5-year-olds that the damaged relationship remains unrestored without forgiveness from the victim. For emotional changes, 6-year-olds understood that the forgiving victim would experience positive emotional changes, whereas the unforgiving victim would not. However, 4- and 5-year-olds expected positive emotional changes even without forgiveness, although they anticipated greater changes after forgiveness. The results show that the understanding of the important functions of forgiveness is present at 4 years of age and matures by 6 years of age. Children may develop a sophisticated understanding of the functions of forgiveness later than the actual forgiving behavior., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aims to determine the incidence of pure orbital fractures with concomitant lacrimal drainage system injuries., Methods: A retrospective observational study involving 956 sides from 940 pure orbital blowout fracture patients was conducted in our institution. Patients with concomitant orbital rim fracture and those with old orbital fractures were excluded., Results: A total of 13 sides (1.4%) from 13 patients were included in the study. Canalicular laceration, bony nasolacrimal canal fracture, and lacrimal sac wall laceration were found in 9, 4, and 1 patients, respectively (one overlapping). Majority of the injuries resulted from either sports or falls. Inferomedial orbital strut fracture (23.1% vs. 7.6%; p  = .075) and orbital floor fracture occurring lateral to the infraorbital groove (30.8% vs. 9.9%; p  = .035) tended to be higher in patients with lacrimal drainage system injuries., Conclusion: There is a 1.4% incidence rate of pure orbital fractures with concomitant lacrimal drainage system injuries among the Japanese population included in this study. Inferomedial orbital strut fractures and orbital floor fracture lateral to the infraorbital groove were found to have higher association with lacrimal drainage system injuries.

Background: This study evaluated the level of burden in pediatric and adolescent atopic dermatitis (AD) patients in Japan, the associated burden on caregivers/families, and whether this burden varied with age., Methods: Data were drawn from the Adelphi Pediatric AD Disease Specific Programme (DSP)™, a cross-sectional survey of physicians and their patients conducted in Japan between July and December 2022. Physicians reported patient demographics, clinical characteristics, disease burden, and current/previous therapies. Patients and/or caregivers reported perceived disease severity and impact of AD, including the Children's Dermatology Life Quality Index (CDLQI) and Dermatitis Family Impact questionnaire (DFI)., Results: Overall, 55 physicians provided data for 537 AD patients aged ≤17. Mean (SD) overall scores for CDLQI, POEM, and DFI were 9.3 (6.3), 8.3 (6.8), and 11.7 (7.2), respectively. Age was associated with higher patient and/or caregiver-reported CDLQI scores, which increased by 0.543 points per year of age (P = 0.01). Patients with severe disease reported a more significant impact on quality of life factors compared with mild patients (P < 0.001). Age was associated with higher caregiver-reported burden, with DFI scores increasing by 0.325 per year (P = 0.01). Physician-reported impact on caregivers showed that age was significantly associated with increased burden on sleep, daily activities, work, and mood (P < 0.05), with disease severity associated with impact across all factors (P < 0.01)., Conclusions: Both increasing age and disease severity were associated with the increased impact of AD on patients and their caregivers. Disease control/modification through appropriate therapeutic intervention at a younger age may relieve the burden of pediatric AD on patients and their families., (© 2024 The Author(s). International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

The Japan Children's Cancer Group Relapsed Acute Lymphoblastic Leukemia (ALL) Committee conducted a prospective observational study (ALL-R14) to explore promising reinduction therapy regimens for relapsed ALL to investigate in future trials. In Japan, clofarabine- and bortezomib-based regimens were of interest since they were newly introduced for ALL in the study period (2015-2018). Seventy-five pediatric patients were enrolled in total. The 2-year event-free/overall survival rates in patients with first (n = 59) or second (n = 11) relapse were 40.1% (95% confidence interval [CI]: 25.5-52.3%)/66.3% (95% CI 52.3-77.0%) and 34.1% (95% CI 9.1-61.6%)/62.3% (95% CI 27.7-84.0%), respectively. Clofarabine- or bortezomib-based regimens were used only in patients with high-risk disease. The first reinduction therapy used in the 41 patients with early or multiple relapsed B-cell precursor ALL was clofarabine in 7 patients and bortezomib in 9 patients. The odds ratio for reinduction failure risk with a clofarabine- or bortezomib-based regimen compared with other regimens was 9.0 (95% CI 0.9-86.4, P = 0.057) or 1.9 (95% CI 0.4-8.7, P = 0.42), respectively. Thus, clofarabine- or bortezomib-based regimens had no obvious advantage as reinduction therapy for relapsed ALL in children., (© 2024. Japanese Society of Hematology.)

Purpose: To investigate the incidence and prognostic factors of ocular sequelae in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) cases arising between 2016 and 2018 in Japan, and compare the findings with those presented in the previous 2005-2007 survey., Design: Retrospective, national trend survey., Methods: Dermatologic case report forms (CRFs) (d-CRFs) were sent to 257 institutions that treated at least 1 SJS/TEN case, and 508 CRFs were collected from 160 institutions. Ophthalmologic CRFs (o-CRFs) regarding patient demographic data, onset date, ocular findings (first appearance, day of worst severity, and final follow-up), topical treatment (betamethasone), outcome (survival or death), and ocular sequelae (visual disturbance, eye dryness) were sent to the ophthalmologists in those 160 institutions. The results of this survey were then compared with that of the previous 2005-2007 survey., Results: A total of 240 cases (SJS/TEN: 132/108) were included. The incidence of ocular sequelae incidence was 14.0%, a significant decrease from the 39.2% in the previous survey (SJS/TEN: 87/48). In 197 (82.1%) of the cases, systemic treatment was initiated within 3 days after admission, an increase compared to the previous survey (ie, treatment initiated in 82 [60.7%] of 135 cases). Of the 85 cases with an Acute Ocular Severity Score of 2 and 3, 62 (72.9%) received corticosteroid pulse therapy and 73 (85.9%) received 0.1% betamethasone therapy; an increase compared to the 60.0% and 70.8%, respectively, in the previous survey. Ocular-sequelae-associated risk factors included Acute Ocular Severity Score (P < .001) and specific year in the survey (P < .001)., Conclusions: The ophthalmologic prognosis of SJS/TEN has dramatically improved via early diagnosis, rapid assessment of acute ocular severity, and early treatment., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Comprehensive evidence about the burden of infectious diseases in the Western Pacific Region is scarce. We thus examined the disease burden of infectious diseases in Japan in terms of disability-adjusted life years (DALYs)., Methods: We extracted national claims data from Japan's universal health insurance system to estimate the burden of disease for selected infections between 2015 and 2020 using DALYs. The mortality rate, disability duration and severity weight of each disease were estimated based on national data and literature reviews., Results: Disease burden per 100,000 population was 1307.0 in 2015 and 972.1 in 2020 for bloodstream infections (BSI), 796.5 DALYs in 2015 and 498.9 DALYs in 2020 for pneumonia, 171.5 in 2015 and 149.4 in 2020 for meningitis and 11.6 in 2015 and 11.4 in 2020 for urinary tract infections (UTI). Only surgical site infections (SSI) showed a slightly increasing trend over the 5-year period, from 2.2 in 2015 to 2.8 in 2020., Conclusions: Our results showed that the disease burden of the five major infectious diseases was higher in Japan than in other countries. However, while the burden of SSI increased, the burden of pneumonia, meningitis, BSI and UTI gradually decreased year on year. The possible causes of the decreased morbidity should be examined in future work., Competing Interests: Declaration of competing interest All authors have nothing to disclose., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)