Pediatric Patients In Japan Research Articles

Causes of death in critically ill paediatric patients in Japan: a retrospective multicentre cohort study

ObjectivesThe primary objective is to clarify the clinical profiles of paediatric patients who died in intensive care units (ICUs) or paediatric intensive care units (PICUs), and the secondary objective is...

Genotypic characterization of Haemophilus influenzae isolates from paediatric patients in Japan.

Purpose. β-lactamase-negative ampicillin-resistant (BLNAR) Haemophilus influenzae is frequently isolated from respiratory samples and is particularly problematic in Japan. The aim of this study was to characterize circulating isolates of H. influenzae genotypically by BLNAR-PCR and multilocus sequence typing (MLST), and to determine any associations between them.Methods. H. influenzae isolates (n=191) were collected from paediatric patients (1 month to 12 years old) between 2000 and 2011 for three types of infections: pneumonia (n=61), acute otitis media (AOM) (n=68) and meningitis (n=62). All were characterized for capsular type by agglutination tests, and for β-lactam resistance by real-time PCR. The sequence types (STs) determined by MLST were analysed using eburst v3.Results. Eighty-eight out of 191 (46.1 %) H. influenzae isolates were BLNAR by PCR; 37 of 61 (60.7 %) from pneumonia; 33 of 68 (48.5 %) from AOM and 18 of 62 (29.0 %) from meningitis cases. MLST identified 40 and 44 STs among isolates from pneumonia and AOM, respectively. BLNAR were found in singletons such as ST156 in pneumonia, and ST161 and ST396 in AOM. In contrast, eight STs were identified in meningitis, of which seven were genotypically closely related, while ST54 was the most frequent (62.9 %), unlike in the MLST database registrations, where ST6 predominated.Conclusion. Non-typeable H. influenzae (NTHi), mostly derived from pneumonia and AOM, were genetically diverse, in contrast to the predominance of H. influenzae type b (Hib) among meningitis cases. The associations between certain STs and β-lactam resistance among NTHi were confirmed.

Proton beam therapy for pediatric malignancies: aretrospective observational multicenter study in Japan.

Recent progress in the treatment for pediatric malignancies using a combination of surgery, chemotherapy, and radiotherapy has improved survival. However, late toxicities of radiotherapy are a concern in long‐term survivors. A recent study suggested reduced secondary cancer and other late toxicities after proton beam therapy (PBT) due to dosimetric advantages. In this study, we evaluated the safety and efficacy of PBT for pediatric patients treated in Japan. A retrospective observational study in pediatric patients who received PBT was performed. All patients aged <20 years old who underwent PBT from January 1983 to August 2014 at four sites in Japan were enrolled in the study. There were 343 patients in the study. The median follow‐up periods were 22.6 months (0.4–374.3 months) for all patients and 30.6 months (0.6–374.3 months) for survivors. The estimated 1‐, 3‐, 5‐, and 10‐year survival rates were 82.7% (95% CI: 78.5–87.0%), 67.4% (61.7–73.2%), 61.4% (54.8–67.9%), and 58.7% (51.5–65.9%), respectively. Fifty‐two events of toxicity ≥ grade 2 occurred in 43 patients. Grade 4 toxicities of myelitis, visual loss (two cases), cerebral vascular disease, and tissue necrosis occurred in five patients. This study provides preliminary results for PBT in pediatric patients in Japan. More experience and follow‐up with this technique are required to establish the efficacy of PBT in this patient population.

Targeted age, device deployment, and problems associated with pediatric defibrillation in pediatric prehospital emergency medical care settings in Japan.

The use of automated external defibrillators was expanded to include infants according to the 2010 cardiopulmonary resuscitation guidelines in Japan. However, deployment has been slower for pediatric patients in Japan, because there are fewer appropriate pediatric patients for automated external defibrillators than adults. This study aimed to investigate the targeted age range for pediatric defibrillation and device deployment of defibrillators for pediatric patients in prehospital emergency medical care settings in Japan, and present the issues associated with automated external defibrillators. We administered a web-based survey to the fire defense headquarters in Japan regarding prehospital emergency medical care for pediatric patients in June 2013. We extracted and analyzed some parts of the data related to pediatric defibrillation. Eighty-eight percent of the fire defense headquarters responded to the survey. Sixty-two percent of the fire defense headquarters applied the expanded indication protocol for pediatric defibrillation, which included infants. Forty-three percent of the fire defense headquarters replied that their emergency medical service personnel were using semi-automatic defibrillators without a pediatric mode, whereas 21% of them were using automated external defibrillators that were not equipped with pediatric attenuators. Moreover, many of the semi-automatic defibrillators are not designed for pediatric defibrillation in patients aged <8 years. Pediatric prehospital emergency medical care in Japan is inadequately equipped for pediatric defibrillation. It will be necessary to use age-appropriate defibrillators as the targeted age range for automated external defibrillators rapidly expands to include infants.

Brain Death in Pediatric Patients in Japan: Diagnosis and Unresolved Issues.

Brain death (BD) is a physiological state defined as complete and irreversible loss of brain function. Organ transplantation from a patient with BD is controversial in Japan because there are two classifications of BD: legal BD in which the organs can be donated and general BD in which the organs cannot be donated. The significance of BD in the terminal phase remains in the realm of scientific debate. As indicated by the increasing number of organ transplants from brain-dead donors, certain clinical diagnosis for determining BD in adults is becoming established. However, regardless of whether or not organ transplantation is involved, there are many unresolved issues regarding BD in children. Here, we will discuss the historical background of BD determination in children, pediatric emergencies and BD, and unresolved issues related to pediatric BD.

Epidemiology of gastroenteritis viruses in Japan: Prevalence, seasonality, and outbreak

Acute gastroenteritis has been recognized as one of the most common diseases in humans and continues to be a major public health problem worldwide. Several groups of viruses have been reported as the causative agents of acute gastroenteritis, including rotavirus, norovirus, sapovirus, human astrovirus, adenovirus, and an increasing number of others which have been reported more recently. The epidemiology, prevalence, seasonality, and outbreaks of these viruses have been reviewed in a number of studies conducted in Japan over three decades. Rotavirus and norovirus were the two most common viruses detected almost equally in children under 5 years of age who were suffering from acute gastroenteritis. Like many other countries, the main rotavirus strains circulating in pediatric patients in Japan are G1P[8], G2P[4], G3P[8], and G9P[8]. Norovirus GII.4 was involved in most outbreaks in Japan and found to be associated with the emergence of new variants Sydney_2012. The classic human astrovirus, MLB, and VA clades astroviruses were also commonly found in pediatric patients with acute diarrhea. The sapovirus and adenovirus have been identified as the minor viral causative agents for acute gastroenteritis in Japan.

Rapid Decrease of 7-Valent Conjugate Vaccine Coverage for Invasive Pneumococcal Diseases in Pediatric Patients in Japan

In Japan, the heptavalent pneumococcal conjugate vaccine (PCV7) has been introduced on a voluntary basis since February 2010, and official financial support for children under 5 years started in November 2010. The impact of PCV7 on invasive pneumococcal diseases (IPD) in children is unknown. There are 340 medical institutions that actively participated in our surveillance project throughout Japan. We collected 252 strains from patients with IPD in 2006 (pre-PCV7), 280 strains in 2010 (under 10% immunization achieved), and 128 strains in 2011 (50% to 60% immunization). Serotypes and penicillin-resistance genotypes (g) were compared between these years. Multilocus sequence typing was also carried out on these strains. Due to the official promotion, IPD significantly decreased in 2011 (p<0.001). In particular, meningitis and sepsis caused by vaccine type (VT) strains declined (p=0.033, p<0.001). In less than 2 years, among nonvaccine types (NVT), 15A and 22F increased in 2011 (p=0.015, p=0.015). Coverage by PCV7 decreased from 71.8% in 2006 to 51.6% in 2011. Sequence-type diversities accompanied by evolution to gPRSP occurred in both VT and NVT strains. Reduction of IPD caused by VT strains was accomplished, but a rapid increase of NVT raises concern about a future decrease in the efficacy of PCV7.

Clinical guideline for Use of Parenteral and Enteral Nutrition in Pediatric Patients in Japan

Clinical guideline for Use of Parenteral and Enteral Nutrition in Pediatric Patients in Japan

Emotional and Psychological Support of Living Lung Donors Who Failed to Donate to their Child: A Case Report

Objectives: Living-donor lung transplantation (LDLT) is a real therapeutic option for pediatric patients in Japan. However, not all families with sick children can take advantages of a LDLT because of luck of suitable donors. Mental care for such a family becomes important when the parents cannot be donor candidates due to their own illness. The aim of this report is to describe the emotional and psychological status of donor candidates who could not be a lung donor due to malignancy. Methods: A semi-structured interview was performed with a donor candidate who was unable to donate due to whose own malignancy. The recipient was a 12 year- old girl, and the donor candidates were her parents. Results were obtained by a qualitative inductive analysis. Results: Donor assessment revealed that the recipient’s mother had malignancy. She was excluded from being a donor candidate and the planned living donor transplant for her daughter was cancelled. The mother’s emotional responses when she failed to donate to her sick daughter were the major theme extracted from the data. In this context, nine codes were obtained and this theme was detected across three main categories including mood disturbances, anxiety symptoms, and affective reactions. A transplant team supported the donor’s and recipient’s emotional health. The donor developed a more positive attitude at overcoming her own disease and began to expect brain-dead donor could save her daughter’s life. Three years later, the recipient underwent a successful lung transplant from a brain-dead donor. Conclusion: These findings have the potential to help transplant nurses develop interventions to improve the emotional health of living donors who failed to have the ability to donate their organs. Mental health promotion, assessment, and treatment must become priorities to improve the overall domestic mental environment of having a sick child waiting for lung transplant.

Prevalence of bacteriophage-associated super-antigen genes in Streptococcus pyogenes isolated from pediatric patients in Japan

Prevalence of bacteriophage-associated super-antigen genes in Streptococcus pyogenes isolated from pediatric patients in Japan

Clinical efficacy of macrolide antibiotics against genetically determined macrolide‐resistant Mycoplasma pneumoniae pneumonia in paediatric patients

Since 2000, the prevalence of macrolide-resistant (MR) Mycoplasma pneumoniae has increased among paediatric patients in Japan. To determine the efficacy of macrolides against MR M. pneumoniae pneumonia, microbiological and clinical efficacies were compared during the antibiotic treatment. Samples from a total of 30 children with M. pneumoniae pneumonia, as confirmed by PCR and serology, were analyzed. Primers for domain V of 23S rRNA were used, and DNA sequences of the PCR products were compared with the sequence of an M. pneumoniae reference strain. Isolates from 21 patients demonstrated point mutations, and these patients were defined as MR. The remaining nine patients, whose isolates showed no point mutations, were categorized as control (macrolide-sensitive) patients. The number of M. pneumoniae in nasopharyngeal samples from the control group decreased rapidly 48 h after initiation of macrolide treatment and showed a close relationship with clinical outcome. In contrast, the number of M. pneumoniae 48 h after initiation of macrolide treatment were significantly higher in samples from MR patients than in samples from macrolide-sensitive patients. In 15 of 21 MR patients, fever persisted for more than 48 h after the initiation of macrolide treatment. When treatment was changed to minocycline, fever disappeared within 48 h in all these MR patients. There were no differences between MR patients who demonstrated a reduction in fever and those in whom fever persisted after 48 h of macrolide treatment. The microbiological and clinical efficacies of macrolides for treating patients with MR M. pneumoniae pneumonia were low. These results show that macrolides are clearly less effective in patients with MR M. pneumoniae pneumonia.

Optimal Dosage Regimen of Meropenem for Pediatric Patients Based on Pharmacokinetic/Pharmacodynamic Considerations

A population pharmacokinetic (PK) model for meropenem in Japanese pediatric patients with various infectious diseases was developed based on 116 plasma concentrations from 50 pediatric patients. The population PK parameters developed in this analysis are useful for calculation of the percent time above minimum inhibitory concentration (%T>MIC) and for optimal dosing of meropenem in pediatric patients. After dosing at 20 mg/kg t.i.d. by 0.5-h infusion (approved standard dose for pediatric patients in Japan), the target value of 50%T>MIC was achieved, indicating that 20 mg/kg t.i.d. by 0.5-h infusion is effective for susceptible bacteria. In contrast, for bacteria with higher MICs such as Pseudomonas aeruginosa (MIC ≥ 2 µg/mL), the probability of target attainment of 50%T>MIC was 60.7% at a dose of 40 mg/kg t.i.d. by 0.5-h infusion (highest dose approved for pediatric patients in Japan). The simulations described in this article indicated that 40 mg/kg t.i.d. with a longer infusion duration (e.g., 4 h) is more effective against bacteria with a MIC higher than 2 µg/mL. The predicted probability of target attainment for 50%T>MIC (97.0%) was well correlated not only to the microbiological efficacy rate (97.0%) but also to the clinical efficacy rate (95.9%) in the present phase 3 study.

Retrospective analysis of non‐anaplastic peripheral T‐cell lymphoma in pediatric patients in Japan

Reports of non-anaplastic peripheral T-cell lymphoma (PTCL) in pediatric patients are relatively rare. We performed a retrospective analysis in patients with PTCL over an 18-year period (1991-2008). We could analyze clinical data in 21 patients with non-anaplastic PTCL; 10 were female and 10 male. Median age of onset was 11 years (range: 1-21 years). There were nine patients with PTCL, not otherwise specified (PTCL-NOS); ten with extranodal NK/T-cell lymphoma, nasal type; one with angioimmunoblastic T-cell lymphoma; and one with subcutaneous panniculitis-like T-cell lymphoma. Initial lesions involved cervical lymph nodes in five patients, and the skin in five patients. In five patients, hemophagocytic syndrome (HPS) was the initial clinical feature. There were 12 patients with advanced stage disease (stages III and IV). Chemotherapy and radiation was administered in 18 and 2 patients, respectively. Among the two patients who did not receive chemotherapy and radiation, one patient died while being treated for HPS but another improved spontaneously. Although 5 patients relapsed, 18 of 21 patients remained alive without disease at last follow-up. Five-year overall survival rate was 85.2%. Generally, the outcome results of conventional chemotherapy for high-risk PTCL are poor in adult patients. However, the excellent results in our study suggest that PTCL of childhood is quite different from that of adulthood. Although this study is first report about PTCL of Asian children, the number of patients was small in this study. Larger studies are needed to confirm these findings.

Antifungal activity of micafungin againstCandidaandAspergillusspp. isolated from pediatric patients in Japan

The in vitro antifungal activities of micafungin in comparison to caspofungin, fluconazole, itraconazole, voriconazole, and amphotericin B were evaluated against 93 Candida and 23 Aspergillus isolates recovered from pediatric patients with fungal infections. MICs were determined by the CLSI M27-A2 and M38-A for Candida and Aspergillus species, respectively. Micafungin showed potent activity against Candida albicans, Candida tropicalis, and Candida glabrata with a MIC range of <= 0.002 to 0.015mug/ml. In contrast, micafungin demonstrated higher MIC levels against Candida parapsilosis with a MIC range of 0.12 to 2 mug/ml. Micafungin showed potent antifungal activity against Aspergillus species tested with a MIC range of 0.004 to 0.015 mug/ml. Overall, micafungin had excellent in vitro antifungal activities against Candida and Aspergillus species recovered from pediatric patients with fungal infections.

Mechanisms, molecular and sero-epidemiology of antimicrobial resistance in bacterial respiratory pathogens isolated from Japanese children

BackgroundThe clinical management of community-acquired respiratory tract infections (RTIs) is complicated by the increasing worldwide prevalence of antibacterial resistance, in particular, β-lactam and macrolide resistance, among the most common causative bacterial pathogens. This study aimed to determine the mechanisms and molecular- and sero-epidemiology of antibacterial resistance among the key paediatric respiratory pathogens in Japan.MethodsIsolates were collected at 18 centres in Japan during 2002 and 2003 from children with RTIs as part of the PROTEKT surveillance programme. A proportion of Haemophilus influenzae isolates was subjected to sequencing analysis of the ftsI gene; phylogenetic relatedness was assessed using multilocus sequence typing. Streptococcus pneumoniae isolates were screened for macrolide-resistance genotype by polymerase chain reaction and serotyped using the capsular swelling method. Susceptibility of isolates to selected antibacterials was performed using CLSI methodology.Results and DiscussionOf the 557 H. influenzae isolates collected, 30 (5.4%) were β-lactamase-positive [BL+], 115 (20.6%) were BL-nonproducing ampicillin-resistant (BLNAR; MIC ≥ 4 mg/L) and 79 (14.2%) were BL-nonproducing ampicillin-intermediate (BLNAI; MIC 2 mg/L). Dabernat Group III penicillin binding protein 3 (PBP3) amino acid substitutions in the ftsI gene were closely correlated with BLNAR status but phylogenetic analysis indicated marked clonal diversity. PBP mutations were also found among BL+ and BL-nonproducing ampicillin-sensitive isolates. Of the antibacterials tested, azithromycin and telithromycin were the most active against H. influenzae (100% and 99.3% susceptibility, respectively). A large proportion (75.2%) of the 468 S. pneumoniae isolates exhibited macrolide resistance (erythromycin MIC ≥ 1 mg/L); erm(B) was the most common macrolide resistance genotype (58.8%), followed by mef(A) (37.2%). The most common pneumococcal serotypes were 6B (19.7%), 19F (13.7%), 23F (13.5%) and 6A (12.8%). Telithromycin and amoxicillin-clavulanate were the most active antibacterials against S. pneumoniae (99.8% and 99.6% susceptibility, respectively).ConclusionApproximately one-third of H. influenzae isolates from paediatric patients in Japan are BLNAI/BLNAR, mainly as a result of clonally diverse PBP3 mutations. Together with the continued high prevalence of pneumococcal macrolide resistance, these results may have implications for the clinical management of paediatric RTIs in Japan.

Nippon Boehringer Ingelheim has received approval for 1% epinastine [Alesion] dry syrup for use in paediatric patients in Japan.

Nippon Boehringer Ingelheim has received approval for 1% epinastine [Alesion] dry syrup for use in paediatric patients in Japan.

In vitro antimicrobial activity of meropenem against clinical isolates of various bacterial species from pediatric patients in Japan

<I>In vitro</I> antimicrobial activity of meropenem against clinical isolates of various bacterial species from pediatric patients in Japan

In vitro susceptibilities to 23 antimicrobial agents of Haemophilus influenzae from pediatric patients in Japan.

One hundred eighty-six clinical isolates of Haemophilus influenzae (H. influenzae) collected from January 1996 through December 1997 from 182 pediatric patients and 16 isolates from blood or cerebrospinal fluid (CSF) of 13 patients with bacteremia and purulent meningitis collected during the last ten years were examined for in vitro susceptibilities to 23 antibiotic agents, including 3 penicillins, 9 cephalosporins, 4 carbapenems and others, as well as for their encapsulated types and beta-lactamase production. Ceftriaxone (a third generation cephalosporin) had the highest activity against the strains in this study (minimal inhibitory concentration, MIC90 of 0.025 microgram/ml) and cefditoren (a new oral cephalosporin) was the most active oral antimicrobial agent (MIC90 of 0.05 microgram/ml). Meropenem had a much higher activity against H. influenzae (MIC90 of 0.2 microgram/ml) than the other carbapenems (imipenem, MIC90 of 1.56 micrograms/ml, panipenem, MIC90 of 1.56 micrograms/ml, and biapenem, MIC90 of 3.13 micrograms/ml). Regarding the serotyping of the encapsulated strains, 172 strains (85.1%) were nontypeable and 30 (14.9%) were serotyped (24 strains of type b, 4 strains of type e, one each of type a and c). Fifteen of the strains isolated from blood and CSF were type b and one was nontypeable. Sixteen of 202 strains (7.9%) produced beta-lactamase and all of them produced both penicillinase and cephalosporinase. The production of beta-lactamase in this study was lower than that reported in previous studies [1-3]. In this study, some strains were found against which the MICs of carbapenems were very high (highest MIC of imipenem was 12.5 micrograms/ml, of panipenem was 6.25 micrograms/ml and of biapenem was 25 micrograms/ml). Therefore, we assayed the binding affinities of imipenem for each of penicillin-binding proteins (PBPs) about one of these resistant strains. In resistant strains, inhibitory concentrations (IC50) of imipenem for PBP4 and 5 were much higher than those in susceptible strains. Thus, the results demonstrate the decrease of the affinity of imipenem for PBP4 and 5. It seems, therefore, that the major factor in the resistance to imipenem of H. influenzae was the low affinity of PBP4 and 5 for the drug.

Clinical and pharmacokinetic study of parenteral administration of cefsulodin in pediatric patients in Japan.

A multicenter study of cefsulodin was carried out with pediatric patients having infections caused by Pseudomonas aeruginosa. Clinical responses were evaluated in 78 of 84 cases, and bacteriologic responses were evaluated in 77 cases. Peak serum levels, urinary excretion rates, and biologic half-lives were determined for some patients. Daily dosage of cefsulodin was usually 60-100 mg/kg of body weight given in three to four divided doses. Infections were mainly septicemia (12 cases), respiratory tract infections (23), and urinary tract infections (26); clinical responses in these cases were excellent or good in 75.0% of the cases (nine of 12), 78.3% (18 of 23), and 84.6% (22 of 26), respectively. P. aeruginosa was eradicated in 67.5% of patients (52 of 77) and was replaced in an additional 5.2% (four of 77). No adverse reactions were observed except for four cases of eosinophilia and one case in which serum transaminase levels were elevated. These results indicate that cefsulodin is a safe and useful drug for the treatment of pseudomonal infections in pediatric patients.