Association between use of antipyretics and antibody titers after two doses of the BNT162b2 SARS-CoV-2 vaccine in adolescents and young adults with underlying diseases.

There are few reports on the association between antipyretic use and antibody titers in adolescents and young adults following SARS-CoV-2 vaccination. Multivariable linear regression analyses were performed to examine the association between antipyretic use and antibody titers. The use of antipyretics was not associated with antibody titers (ß coefficient [95% CI] = -0.107 [-0.438 to 0.224]).

Safety and antibody response of the BNT162b2 SARS-CoV-2 vaccine in children aged 5-11 years with underlying diseases: A prospective observational study.

BACKGROUND: Data on the safety and antibody response of the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in children aged 5-11 years with underlying diseases are limited. Thus, our study aimed to address this gap. METHODS: This prospective observational study investigated the antibody titers for SARS-CoV-2 spike protein receptor-binding domain (S-IgG) and nucleocapsid protein (N-IgG) in patients aged 5-11 years with chronic underlying diseases following two doses of BNT162b2. Additionally, a questionnaire was used to assess adverse events (AEs) arising within 7 days after each dose. Data on severe AEs arising within 28 days after each dose were extracted from the patients' electronic medical records. RESULTS: Among 122 patients, 24.6% (30/122) were immunocompromised. Furthermore, 79 patients experienced at least one AE following vaccination, but all recovered without sequelae, including one severe case after the first dose. The seropositivity rate after the second dose was 99.1% (116/117). Excluding 19 N-IgG-positive patients, the geometric mean antibody titer (GMT) was significantly higher in immunocompetent patients than in immunocompromised patients (1496 U/mL [95% confidence interval 1199-1862] vs. 472 U/mL [200-1119], p = 0.035). Additionally, the GMT of S-IgG was higher in N-IgG-positive patients than in N-IgG-negative patients (8203 [5847-11482] U/mL vs. 1127 [855-1486] U/mL, p < 0.001). CONCLUSIONS: BNT162b2 is acceptably safe and immunogenic for children aged 5-11 years with underlying diseases. Although seroconversion was satisfactory in immunocompromised patients, the titers were lower than in immunocompetent patients.

Safety of and antibody response to the BNT162b2 COVID-19 vaccine in adolescents and young adults with underlying disease.

BACKGROUND: Data are limited regarding the safety of and antibody response to the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid vaccine in adolescents and young adults with underlying disease. METHODS: This prospective observational study enrolled patients age 12-25 years with chronic underlying disease who received 2 doses of BNT162b2. A 18-item questionnaire was used to assess adverse events within 7 days post-vaccination, and data regarding severe adverse events were collected from electronic medical records. An antibody titer for the receptor-binding domain of the spike protein in SARS-CoV-2 was used to assess antibody response after the second vaccine dose. RESULTS: Study participants were 429 patients (241 [56.2%] age 12-15 years; 188 [43.8%] age 16-25 years). The most common underlying diseases were genetic or chromosomal abnormalities and/or congenital anomalies, followed by endocrine or metabolic diseases; 32% of participants were immunocompromised. Severe adverse events were observed after the second dose in 1 (0.4%) patient age 12-15 years and in 2 (1.1%) patients age 16-25 years; all patients recovered. Seropositivity after the second vaccine dose was 99.0%. The geometric mean antibody titer was higher in patients age 12-15 years versus 16-25 years (1603.3 [1321.8-1944.7] U/mL vs. 949.4 [744.2-1211.0] U/mL). Compared with immunocompetent patients, immunocompromised patients had a lower antibody titer (2106.8 [1917.5-2314.7] U/mL vs. 467.9 [324.4-674.8] U/mL). CONCLUSIONS: Vaccination with BNT162b2 was acceptably safe and immunogenic for adolescents and young adults with underlying disease.

Epidemiologic study of patients after Fontan operation based on Medical Aid Program for Chronic Pediatric Diseases of Specified Categories cohort.

Nationwide registry data of patients with single-ventricle physiology have been rarely reported. The Medical Aid Program for Chronic Pediatric Diseases of Specified Categories (Japan) has contributed to the financial support of medical expense for patients younger than 20 years with chronic paediatric disease, and almost all children in Japan who require disease-specific treatment voluntarily apply to this programme. The epidemiology and medium- to long-term outcome of patients following a Fontan procedure were investigated using the database. The usefulness of this epidemiologic investigation in identifying real-world objectives and clinical applications was also examined. A total of 2862 patients who underwent a Fontan operation were identified from 18,589 patients with chronic heart disease registered to the medical aid programme. The details of symptoms, treatment, and somatic growth were evaluated, from which we were able to clarify the nationwide data regarding the current status of post-Fontan patients younger than 20 years. This study elucidated the current status of post-Fontan patients under 20 years of age in Japan. Data analysis of the Medical Aid Program for Chronic Pediatric Diseases of Specified Categories cohort provided useful information towards understanding the comprehensive status of patients with chronic heart disease and contributed to improved disease management.

The pilot study of group robot intervention on pediatric inpatients and their caregivers, using 'new aibo'.

The study on robot-assisted therapy in a pediatric field has not been applied sufficiently in clinical settings. The purpose of this pilot study is to explore the potential therapeutic effects of a group robot intervention (GRI), using dog-like social robot (SR) 'aibo' in pediatric ward. GRI by aibo was conducted for those children with chronic illness (127 in total) who are hospitalized in National Centre for Child Health and Development (NCCHD), and their caregivers (116 in total), from March to April 2018. The observer made structured behavioural observation records, based on which qualitative research on the features of their words and conducts, were carried out. As a result, first, during the GRI, about 2/3 of total expression by children were positive, while about 1/4 were negative or inappropriate. On the other hand, as seen in the 'change' group, those children who had originally responded with negative expression eventually came to express positive expression, while getting involved in a ternary relationship or participating in a session more than once. Secondly, as for the expression from the caregivers during the GRI, active expressions such as 'participation' and 'exploration' accounted for the 2/3, while 1/3 turned out to be rather placid expressions such as 'watch over' or 'encourage.'Conclusion: There has not been any precedent study on the features of words and conducts expressed by patients and their caregivers during the GRI by aibo. The outcome suggests that aibo could possibly be used as a tool for group robot-assisted therapy in the pediatric treatment setting. What is Known: • The study on robot-assisted therapy in a pediatric field has only just begun. • Though many kinds of social robot have been reportedly used so far, none has yet to be applied in clinical settings What is New: • Our study revealed the features of words and behaviour expressed by the patients and their caregivers, when dog-like social robot 'aibo' was used for a group robot intervention in the pediatric ward. • The outcome suggests that aibo could possibly be used as a tool for group robot-assisted therapy in the pediatric treatment setting.

Outcomes of hypertrophic cardiomyopathy in Japanese children: a retrospective cohort study.

There has been no multicenter study on the prognosis of pediatric hypertrophic cardiomyopathy (HCM) in Japan. Therefore, we conducted a retrospective multicenter observational study on the long-term survival rate in patients diagnosed with HCM under the age of 18 between 1990 and 2014. Twenty institutions participated. A total of 180 patients were identified. The median age at diagnosis was 5.8 years old and median duration of observation was 8.3 years. Although six patients (3%) deteriorated into the dilated phase of HCM, no patient received heart transplantation. Freedom from death at 1, 5, 10, and 20 years were 97%, 92%, 84%, and 80%, respectively. There were 26 deaths. Among them, 11 patients died suddenly, presumably due to arrhythmia, and 15 patients died of heart failure. The presence of heart failure symptoms and a greater cardiothoracic ratio were significant risk factors for heart failure-related death. There were no significant risk factors identified for arrhythmia-related death. In conclusion, the prognosis of pediatric HCM in Japan is good and similar to those reported in population-based studies in the United States and Australia. Significant risk factors for heart failure-related death were identified in pediatric patients with HCM in Japan.

Outcomes of Dilated Cardiomyopathy in Japanese Children　- A Retrospective Cohort Study.

BACKGROUND: There has been no nationwide survey on the prognosis of pediatric dilated cardiomyopathy (DCM) in Japan. Therefore, we designed this retrospective multicenter study to investigate the long-term survival rate in pediatric patients with DCM in Japan.Methods and Results:In this multicenter retrospective observational study, data were reviewed for 106 patients aged <18 years who had been diagnosed with DCM at any 1 of 18 Japanese institutions between 1990 and 2014. The median age at diagnosis was 2.0 years and the median duration of observation was 3.3 years. Most DCM patients were diagnosed because of symptoms of heart failure. On echocardiography, the median left ventricular end-diastolic dimension z score was 5.4 and fractional shortening was 0.10. Freedom from death or transplantation rates at 1, 3, 5, 10, and 20 years after diagnosis were 76%, 66%, 64%, 58%, and 43%, respectively. Freedom from death rates at 1, 5, 10, and 20 years after diagnosis were 81%, 75%, 72%, and 53%, respectively. The incidence of heart transplantation at 1, 5, 10, and 20 years after diagnosis was 6%, 15%, 20%, and 20%, respectively, suggesting that only 15% of patients in Japan underwent heart transplantation within 5 years of diagnosis. CONCLUSIONS: In Japan, the prognosis of pediatric DCM is poor and the rate of heart transplantation is low.

Clinical trial of the CP stent for pulmonary artery stenosis: the first investigator-initiated clinical trial for pediatric interventional cardiology in Japan.

Stenting is an important treatment option for pulmonary artery stenosis (PS) associated with congenital heart disease (CHD). However, no stent has been approved for this indication in Japan, despite negotiation between academia and the regulatory bodies for longer than 20 years. To evaluate efficacy and safety of the CP stent, we performed the first investigator-initiated clinical trial for pediatric interventional cardiology in Japan. This trial was designed as a single-arm, prospective, clinical trial. Patients who had postoperative PS associated with CHD were included. Stenting was attempted in 24 cases and succeeded in 22 cases. The median age of the patients was 11 years (3-36 years) and weight was 38 kg (12-69 kg), while follow-up for 12 months was completed. In all 22 cases, stenting was successful, with a 50% increase in the minimum lumen diameter (MLD) in 86.4% of patients (90% confidence interval, 68.4-96.2%). The mean percent change in MLD was 119.3 ± 52.5%. In two-ventricle repair, the mean percent change in systolic right ventricular/aortic pressure was - 8.5 ± 16.1%, while that of pressure gradient was - 55.9 ± 41.7%. In single-ventricle repair, the percent change in the mean pressure gradient was - 100.0 ± 0%, while that of SaO2 was 1.4 ± 1.7%. No serious adverse events or significant restenosis was reported. The CP stent is highly effective and safe for PS associated with CHD. This study has significant importance in not only scientific but also social considerations.

Pregnancy and Delivery in Patients With Repaired Congenital Heart Disease　- A Retrospective Japanese Multicenter Study.

BACKGROUND: Although advances in cardiac surgery have led to an increased number of survivors with congenital heart disease (CHD), epidemiological data regarding the pregnancies and deliveries of patients with repaired CHD are scarce.Methods and Results:In this study, we retrospectively reviewed the clinical outcomes of pregnancies and deliveries of women with repaired CHD. Overall, 131 women with repaired CHD were enrolled and there were 269 gestations. All patients were classified as New York Heart Association (NYHA) Class I or II. The prevalence of cesarean sections was higher in patients with (CyCHD) than without (AcyCHD) a past history of cyanosis (51% vs. 19%, respectively; P<0.01). There were 228 offspring from 269 gestations and the most prevalent neonatal complication was premature birth (10%), which was more frequent in the CyCHD than AcyCHD group (15.7% vs. 5.6%, respectively; P<0.01). Five maternal cardiac complications during delivery were observed only in the CyCHD group (8%); these were classified as NYHA Class II and none was fatal. CONCLUSIONS: Delivery was successful in most women with repaired CHD who were classified as NYHA Class I or II, although some with CyCHD and NYHA Class II required more attention. Cesarean sections were more common in the CyCHD than AcyCHD group, and CyCHD may be a potential risk for preterm deliveries.

Using the upper buttocks as a subcutaneous site for treprostinil infusion in children with pulmonary artery hypertension.

A 14-year-old boy was receiving subcutaneous infusions of treprostinil for pulmonary artery hypertension. Because he had severe infusion site pain in the lower abdomen, we changed his infusion site to the upper buttocks, adding some analgesics. His pain improved gradually. This change may be an effective method for reducing infusion site pain in subcutaneous treprostinil therapy, particularly in children.

Preferences Regarding Transfer of Patients With Congenital Heart Disease Who Attend Children's Hospital.

BACKGROUND: The aim of this study was to determine preferences regarding transfer of patients with congenital heart disease (CHD) attending a children's hospital in Japan and related factors. Methods and Results: We conducted a self-administered questionnaire survey with CHD patients >15 years of age treated at the pediatric cardiology outpatient clinic of a children's hospital. Logistic regression analysis was used to identify factors related to patient preferences regarding the transfer. One hundred and eleven of the 122 patients given a questionnaire provided valid responses (valid response rate, 91.0%). Sixty-six subjects (64.9%) reported "not being told anything specific" by their physicians about the transfer from the children's hospital, and 72 (59.5%) stated that they "wished to continue attending the children's hospital". Visiting outpatient clinic with parents (OR, 11.00; 95% CI: 2.01-60.97), having low uncertainty about continuing to attend the children's hospital (OR, 0.95; 95% CI: 0.92-0.98), and having high uncertainty about leaving the current physician (OR, 1.04; 95% CI: 1.01-1.07) were significantly related to the patient's wish to continue to attend the children's hospital. CONCLUSIONS: There is a need to improve patient education regarding the opportunities for transfer, and to develop a systematic transition program for children's hospitals and aligned specialized adult CHD centers.

Nationwide Survey of Patients With Giant Coronary Aneurysm Secondary to Kawasaki Disease 1999-2010 in Japan.

BACKGROUND: Giant coronary aneurysm is the most severe sequela in Kawasaki disease, occurring in approximately 0.2% of patients in Japan. Regression is rare, while myocardial infarction (MI) and sudden death are relatively common. Herein, we reviewed patients with giant coronary aneurysm in a 10-year period.Methods and Results:A nationwide questionnaire survey was conducted based on a national epidemiological database from 1999 to 2010. We identified 355 giant coronary aneurysm patients, of whom 209 were analyzed. The 5- and 10-year total cardiac event-free rates were 0.72 and 0.68, respectively. Twelve patients died, and MI was observed in 32 patients (18.1%). Five and 6 deaths were due to coronary rupture and MI, respectively. All ruptures occurred within 1 month of onset, while most MI occurred within 18 months. There was no death beyond 2 years. Aneurysm size was significantly related to the occurrence of MI in both the right and left coronary arteries. At the time of writing, 55% of patients had no exercise limitations. And including patients who cannot perform strenuous exercises, 81% of patients were leading ordinary lives. CONCLUSIONS: Severe cardiac events are likely to occur within 2 years from onset of Kawasaki disease, while no deaths occurred beyond this time. Hence, careful monitoring is needed especially for the first 2 years. Most patients with giant coronary aneurysms can lead ordinary lives with appropriate management.

Echocardiographic assessment of prosthetic mitral valves in children.

AIMS: We studied how Doppler-derived hemodynamic parameters in children change as the relative prosthetic mitral valve (PMV) size decreases with somatic growth and evaluated the diagnostic utility of the parameters for detecting PMV obstruction in children. METHODS AND RESULTS: We reviewed 26 echocardiographic examination results of 15 mechanical bileaflet PMVs in 12 children. The median age at echocardiographic examination was 6.6 (0.6-18.1) years. The PMV functioned normally in 24 examinations but was obstructed due to thrombosis in two cases. PMV sizes ranged between 16 and 25 mm, which were standardized to body surface area (BSA) at the examination with z-score calculations. We assessed the peak E velocity, mean pressure gradient (PG), and pressure half time (PHT) of the transprosthetic flow, the velocity-time integral (VTI) ratio of the PMV inflow to the left ventricular outflow, and the BSA-indexed effective orifice area (iEOA) of the PMV calculated with the continuity equation. Linear regression analysis revealed statistically significant correlations between all parameters of normally functioning PMVs and the PMV size z-scores (Pearson correlation coefficients: peak E velocity, -0.68; mean PG, -0.71; PHT, -0.82; VTI ratio, -0.76; iEOA, 0.79). Compared with the predictive values derived from the regression equations, the VTI ratio and iEOA exceeded ± 2 standard errors in both patients with obstructive PMVs. CONCLUSION: To assess PMV function in children, Doppler-derived hemodynamic parameters should be compared with their predictive values based on relative PMV sizes. The deviation of the VTI ratio and iEOA from their predictive values may indicate prosthetic obstruction.

Social independence of adult congenital heart disease patients in Japan.

BACKGROUND: As treatment outcomes for congenital heart disease (CHD) have improved, the social independence of adult CHD patients has become a key goal. The aims of this study were therefore to (i) determine the relationship between social independence and psychological profile, and (ii) identify patient anxieties, difficulties, and demands related to life in society. METHODS: A total of 143 patients aged ≥15 years with physical disability certificates were selected using a questionnaire distributed by a patients' association. Each participant was asked about employment status, income, and receipt of disability pension as a social independence index, and about financial and psychological distress as a psychological status index. Furthermore, each participant was asked to freely describe his or her difficulties, anxieties, and needs pertaining to life in society. RESULTS: The subjects were 15-73 years old. Seventy-one (50%) were female, and 94 (66%) had a grade 1 physical disability certificate. Fifty-nine subjects (41%) were employed, 37 (26%) were unemployed, and 45 (31%) were students. Of those employed, 34 subjects (58%) reported annual individual income ≤2 million yen. Frequent hospital visits, low total household income, low individual annual income, work dissatisfaction, and receipt of a disability pension were associated with poorer psychological profile. In an open description section, subjects expressed desires for better pension systems, support for medical fees, and employment support. CONCLUSIONS: Because financial issues can adversely affect the psychological profiles of adult CHD patients, enhancement of social welfare and employment support may improve their social independence.

Needs assessment for collaborative network in pediatric clinical research and education.

BACKGROUND: A collaborative network for pediatric research has not been fully established in Japan. To identify the network infrastructure, we conducted a survey on the support and education for clinical research currently available in children's hospitals. METHODS: In November 2014, a 27-question survey was distributed to 31 hospitals belonging to the Japanese Association of Children's Hospitals and Related Institutions (JACHRI) to assess clinical research support, research education, research achievements, and their expectations. RESULTS: All the hospitals responded to the survey. Overall, 74.2% of hospitals had clinical research support divisions. Although all hospitals had ethics committees, <30% of the hospitals had a data manager, intellectual property management unit, biostatistician, and English-language editor. Seven hospitals had education programs for clinical research. The number of seminars and workshops for clinical research had significant correlations with the number of physicians (r = 0.927), pediatricians (r = 0.922), and clinical trial management physicians (r = 0.962). There was a significant difference in the number of clinical trials initiated by physicians between hospitals with research education programs and those without (P < 0.01). The number of education programs was significantly correlated with the number of original articles and case reports in English (r = 0.788), and the number of publications in Japanese (r = 0.648). All hospitals recognized the need for a leader to establish a collaborative network for clinical research. CONCLUSIONS: Important factors for creating a collaborative system for pediatric research in Japan were identified. Human resources to support clinical research are a key factor to improve clinical research education and research achievements.

Genetic mutation analysis in Japanese patients with non-syndromic congenital heart disease.

Congenital heart disease (CHD) is the most common birth defect occurring in humans and some transcriptional factors have been identified as causative. However, additional mutation analysis of these genes is necessary to develop effective diagnostic and medical treatment methods. We conducted sequence analysis of the coding regions of NKX2.5, GATA4, TBX1, TBX5, TBX20, CFC1 and ZIC3 in 111 Japanese patients with non-syndromic CHD and 9 of their relatives. All patient samples were also analyzed by multiplex ligation-dependent probe amplification using probes involved in chromosome deletion related to CHD. Five novel variations of TBX5, GATA4 and TBX20 were detected in 6 of the patients, whereas none were found in 200 controls. The TBX5 variation p.Pro108Thr, located in the T-box domain, was identified in a patient with tricuspid atresia, an exon-intron boundary variation of GATA4 (IVS4+5G>A) was detected in a Tetralogy of Fallot patient and an 8p23 microdeletion was detected in one patient with atrioventricular septal defect and psychomotor delay. A total of seven non-synonymous polymorphisms were found in the patients and controls. Accumulation of novel variations of genes involving the cardiac development may be required for better understanding of CHD.

Nationwide Survey of the Transfer of Adults With Congenital Heart Disease From Pediatric Cardiology Departments to Adult Congenital Heart Disease Centers in Japan.

BACKGROUND: Current Japanese transfer practices for adult congenital heart disease (ACHD) patients in pediatric departments are elucidated in this study. The focus was on 149 facilities (from the Japanese Society of Pediatric Cardiology and Cardiac Surgery Subspecialty Board and the Japanese Association of Children's Hospitals and Related Institutions). One hundred and thirteen facilities were surveyed and the response rate was 75.8%. METHODS AND RESULTS: Twenty-six facilities (23.0%) treated ≥200 outpatients annually; 48 facilities (42.9%) treated <50 outpatients. Only eight facilities admitted ≥50 inpatients; 61 facilities (54.0%) admitted <10 inpatients. Nine facilities fulfilled international regional ACHD center criteria. The estimated median number of patients receiving outpatient pediatric department follow up was 33,806. Sixty facilities (53.6%) treated patients in pediatric departments after they reached adulthood. Of 49 facilities that transferred patients, the transfer was most commonly to another department in the same facility (20 facilities; 40.8%), typically the adult cardiology department (29 facilities; 59.2%). In future, 55 facilities (48.7%) desired the transfer of patients to regional ACHD centers, while 34 facilities (30.1%) preferred to continue treating patients in the pediatric department. CONCLUSIONS: The number of regional ACHD centers offering sufficient outpatient and inpatient care is limited; transfer from pediatric departments is not standard in Japan. Role division clarification between regional ACHD centers and other facilities and cooperative network establishment including transitional care programs is necessary. (Circ J 2016; 80: 1242-1250).