Trend in antibiotic prescription at pediatric primary emergency medical centers in Japan: A multi-center, cross-sectional study.

INTRODUCTION: Antimicrobial resistance is a global issue, and implementation of antimicrobial stewardship programs in outpatient settings is crucial. Japan has also focused on outpatient oral antimicrobial stewardship programs and difficulties in standardizing prescriptions have led to overprescription in primary emergency medical centers. There is a lack of research investigating the antibiotic prescription status of pediatric primary emergency medical centers and the benchmark prescription rates in pediatric outpatient settings. METHODS: We conducted a multi-center, cross-sectional study of seven pediatric primary emergency medical centers located in five prefectures of Japan. We retrospectively extracted data from health claims or directly obtained them from charts at each institution and evaluated trends in the antibiotic prescription rate based on the AWaRe classification between April 2016 and December 2019. RESULTS: Our study included 383,525 encounters, with the most common infectious disease diagnosis being acute upper respiratory tract infection in 93,449 cases (24.4 %). The antibiotic prescription rate during the study period was 7.4 %, representing a decrease of 46 %, from 10.2 % in 2016 to 5.5 % in 2019. The percentage of prescriptions in the Access group increased at all institutions; however, it exceeded 60 % in only three facilities in 2019. The percentage of third-generation cephalosporins varied among facilities, ranging from 1.7 % to 59.4 %, as of 2019. CONCLUSIONS: For pediatric primary emergency medical centers where antimicrobial stewardship programs are implemented, we suggest 5 % as a reasonable benchmark level for the antibiotic prescription rate. Prescribing the antibiotics in the Access groups less frequently remains a domestic challenge in Japan.

Trend of oral antimicrobial use after removal of broad-spectrum antimicrobials from the formulary at a pediatric primary emergency medical center.

INTRODUCTION: While the effects of the Japanese action plan formulated in 2016 have gradually appeared, the appropriate use of antimicrobials in outpatient settings is still important. We conducted a previous study to recommend appropriate antimicrobial use via monthly newsletters at a pediatric primary emergency medical center (PEC). As a result, the rate of inappropriate prescription of oral third-generation cephalosporins (3GCs) decreased by 67.2%. This decrease prompted our institution to change the antimicrobials adopted from 3GCs to first-generation cephalosporins. There have been no reports on the prescribing trend of narrow-spectrum antimicrobials after the discontinuation of 3GCs in pediatric PECs. METHODS: We conducted a single-center, observational study at one pediatric PEC between April 2020 and March 2022. We recorded the total number of patients and oral antimicrobial prescriptions, diagnoses, and descriptions of the electronic health records and evaluated the prescription trends and appropriateness of antimicrobial use after removal of cefditoren-pivoxil and fosfomycin from the formulary. RESULTS: The total number of patients was 22,744 during the study period, and antimicrobials were prescribed to 496 (2.2%) patients. The proportion of amoxicillin prescriptions among total antimicrobials was high (53.4%). For each prescription, 85 of 259 prescriptions (32.8%) for amoxicillin, 161 of 185 prescriptions (87.0%) for cephalexin, and 17 of 43 prescriptions (39.5%) for clarithromycin were judged to be appropriate. CONCLUSION: We suggest that after the removal of broad-spectrum antimicrobials and achieving a reduction in the prescription rate of oral antimicrobials, it is necessary to evaluate whether narrow-spectrum antimicrobials are used properly in pediatric PECs.

Comparing the effects of antimicrobial stewardship at primary emergency centers.

BACKGROUND: Antimicrobial prescription rates tend to be high in outpatient settings and Primary Emergency Medical Centers (PECs) in Japan encounter difficulties in implementing antimicrobial stewardship programs (ASPs). While a nudge-based ASP publishing monthly newsletters reduces inappropriate prescription of oral third-generation cephalosporins (3GCs), which requires considerable effort. Therefore, developing more preferable ASP models in PECs is essential. METHODS: We conducted a three-center, retrospective observational study. Himeji City Emergency Medical Center (Site A) introduced a facility-specific guideline for antimicrobial stewardship with reference to national guidelines. The Kobe Children's Primary Emergency Medical Center (Site B) provided the results of monitoring antibiotics prescription in a monthly newsletter. The Hanshin-Kita Children's First-Aid Center (Site C) did not perform a specific ASP. Prescription rates for 3GCs were categorized into pre- and post-intervention and compared using Poisson regression analysis. The difference-in-difference method was used to assess the effect of these interventions. RESULTS: The numbers of patients pre- and post- intervention were 177,126 and 91,251, respectively. The 3GCs prescription rate at Site A, Site B, and Site C decreased from 6.7%, 4.2%, and 6.1% in 2016 to 2.3%, 1.0%, and 2.0% in 2019, respectively. Site B had a greater reduction than Site A and Site C (relative risk [RR] 0.71 [95% confidence interval (CI): 0.62-0.82]; p < 0.001, RR 0.71, [95% CI: 0.62-0.81]; p < 0.001). There was no significant difference between Site A and Site C (RR 1.00 [95% CI 0.88-1.13]; p = 0.963). CONCLUSION: A facility-specific guideline was less effective than a nudge-based ASP for decreasing oral 3GC prescriptions in PECs.

Epidemiological impact of universal varicella vaccination on consecutive emergency department visits for varicella and its economic impact among children in Kobe City, Japan.

INTRODUCTION: Previous studies reported a dramatic decline in the incidence of varicella and varicella-related deaths after implementing universal varicella vaccination (VarV). Although previous studies reported the effectiveness and economic impact of VarV, they were unknown in the emergency department (ED) setting. METHODS: To determine the effectiveness and economic impact of VarV in the ED, Kobe, Japan, we retrospectively reviewed the clinical database of consecutive patients younger than 16 years presenting to our primary ED from 2011 to 2019. RESULTS: Of the 265,191 children presenting to our ED, 3,092 patients were clinically diagnosed with varicella. The number of patients with varicella was approximately 500 annually, before introducing the universal two-dose VarV for children aged 1 to <3 years in October 2014, in the Japanese national immunization program, and decreased to approximately 200 in 2019. The number of patients with varicella younger than 1 year (ineligible for the vaccination) also decreased. Regarding the economic impact, the medical cost in our ED reduced after the introduction of VarV was JPY 4.1 million (US$ 40,049) annually. From the central data, approximately 95% of children were vaccinated after October 2014; however, a relatively large percentage of infected unvaccinated children (59.0%) presented to ED in this study. After the implementation of the universal VarV, infection was mainly observed in older children (i.e., the unvaccinated generation). CONCLUSIONS: Our data showed the effectiveness and economic impact of VarV in the ED setting. Additionally, our data suggested that the public vaccination program should include older unvaccinated children and other unvaccinated individuals.

Multivariate analysis of the impact of weather and air pollution on emergency department visits for unprovoked seizure among children: A retrospective clinical observational study.

BACKGROUND: An unprovoked seizure is a seizure or a cluster of seizures occurring within 24 h in a patient older than 1 month of age without precipitating factors. Recent studies have reported that extrinsic factors, such as meteorological conditions and air pollutants, may be important in seizure occurrence. Thus, this study aimed to examine the association between the number of visits to the emergency department (ED) by children for nighttime unprovoked seizures and exposure to multi-faceted factors, such as meteorological conditions and air pollution. METHODS: We conducted a clinical observational analysis and reviewed consecutive patients younger than 16 years of age who visited the primary ED center in Kobe City, Japan, during nighttime (7:30 p.m.-7:00 a.m.) between January 1, 2011 and December 31, 2015. We investigated the effects of meteorological factors and air pollutants on the number of patients with unprovoked seizures using multivariate analysis of Poisson regression estimates. RESULTS: In total, 151,119 children visited the ED, out of which 97 patients presented with unprovoked seizures. The mean age of the patients was 4.7 years (range, 1 month to 15.3 years), and 54.6% of them were boys. The total number of patients with unprovoked seizures showed no significant changes with the seasons; however, there were dominant peaks during the fall and fewer visits during the summer. The multivariate analysis of Poisson regression estimates revealed a significant positive relationship between the number of patients presenting with unprovoked seizures and precipitation (+1 patient/87 mm; p = 0.03) and methane (+1 patient/0.14 ppm; p = 0.03) levels and a negative relationship between the number of patients presenting with unprovoked seizures and nitrogen dioxide level (-1 patient/0.02 ppm; p = 0.04). CONCLUSIONS: The present study is the first to evaluate the association between the number of children who presented to the ED with nighttime unprovoked seizures and environmental factors after controlling for confounding factors.

Effects of a nudge-based antimicrobial stewardship program in a pediatric primary emergency medical center.

Outpatient medical facilities tend to have high antimicrobial prescription rates and are therefore major targets for antimicrobial stewardship programs (ASPs). Pediatric primary emergency medical centers in Japan have difficulties in implementing conventional ASPs due to the low continuity of stewardship. Accordingly, there is a need to develop effective ASP models for these facilities. We conducted a single-center, quasi-experimental study to evaluate the effects of a nudge-based ASP in reducing unnecessary third-generation cephalosporin (3GC) prescriptions in a pediatric primary emergency care center (PEC). The implemented ASP utilizes monthly newsletters that report current antimicrobial use patterns and prescribing targets. We compared the monthly 3GC prescription numbers and proportions of unnecessary prescriptions before and after the ASP was implemented. The trends in 3GC prescriptions were examined using an interrupted time-series analysis. The numbers of patients before and after ASP implementation were 129,156 and 28,834, respectively. The number of unnecessary 3GC prescriptions decreased by 67.2% in the year after ASP implementation. The interrupted time-series analysis showed that the ASP was significantly associated with a reduction in 3GC prescriptions (regression coefficient - 0.58, P < 0.001).Conclusion: The nudge-based ASP was effective in reducing 3GC use in a Japanese PEC. This simple and inexpensive approach may have applications in other outpatient facilities. What is Known: • Outpatient medical facilities tend to have high antimicrobial prescription rates. Despite the development of several strategies for outpatient antimicrobial stewardship programs, these approaches have not sufficiently reduced antimicrobial use. What is New • Our nudge-based antimicrobial stewardship program using newsletters was shown to be a simple, inexpensive, and feasible method for reducing unnecessary antimicrobial use in a pediatric primary emergency care center. This may represent an effective antimicrobial stewardship strategy in Japanese outpatient facilities.

Current Situation of Treatment for Anaphylaxis in a Japanese Pediatric Emergency Center.

OBJECTIVE: Anaphylaxis is a systemic allergic reaction that sometimes requires prompt treatment with intramuscular adrenaline. The aim of the study was to investigate the current situation regarding anaphylaxis treatment in a representative pediatric primary emergency facility in Japan. METHODS: We retrospectively examined the medical records dating from April 2011 through March 2014 from Kobe Children's Primary Emergency Medical Center, where general pediatricians work on a part-time basis. Clinical characteristics and current treatments for patients with anaphylaxis who presented to the facility were investigated. Furthermore, we compared the clinical characteristics between anaphylaxis patients given intramuscular adrenaline and those not given it. RESULTS: During the study period, 217 patients were diagnosed with anaphylaxis. The median Sampson grade at the time of visit was 2, and 90 patients (41%) were grade 4 or higher. No patients received self-intramuscular injected adrenaline before arrival at our emergency medical center because none of the patients had been prescribed it. Further treatment during the visit was provided to 128 patients (59%), with only 17 (8%) receiving intramuscular adrenaline. Patients given intramuscular adrenaline had significantly lower peripheral saturation of oxygen at the visit (P = 0.025) and more frequent transfer to a referral hospital (P < 0.001) than those not given intramuscular adrenaline. CONCLUSIONS: Education for Japanese pediatric practitioners and patients is warranted, because no patients used self-intramuscular injected adrenaline as a prehospital treatment for anaphylaxis, and only severely affected patients who needed oxygen therapy or hospitalization received intramuscular adrenaline in a pediatric primary emergency setting.

Clinical factors associated with prehospital exacerbation of anaphylaxis in children.

BACKGROUND: The severity of anaphylaxis often varies with time. Because prehospital intervention and initial treatment at hospital are affected by changing symptoms, the aim of this study was to determine the clinical factors associated with prehospital remission and exacerbation in the course of anaphylaxis in children. METHODS: Data from medical records on anaphylactic children who were treated for 3 years at Kobe Children's Primary Emergency Medical Center were retrospectively analyzed. Severity of symptoms was evaluated using Sampson's grade (S-G). Patients with increased S-G at the hospital visit from disease onset (worsened group) were compared with those with decreased S-G at the visit (improved group). Uni- and multivariate analyses were performed to identify clinical differences between the groups, with P<0.05 considered statistically significant. RESULTS: Among 115 anaphylactic children who showed S-G changes from onset to hospital visit, 43 were assigned to the worsened group and 72 to the improved group. Univariate analysis showed no significant differences in age, sex, history of asthma, prehospital treatment, type of antigen, or period from symptom onset to hospital visit between the groups. However, the time from antigen exposure to symptom onset was significantly longer, and S-G at onset was significantly lower in the worsened group than in the improved group. Multivariate analysis identified time from antigen exposure to symptom onset (odds ratio: 3.89, P<0.01) and S-G at onset (odds ratio: 0.06, P<0.001) as independent predictors of exacerbation. CONCLUSIONS: Anaphylactic children with slower and milder symptoms at onset are more likely to show deterioration.

Changes in the numbers of patients with acute gastroenteritis after voluntary introduction of the rotavirus vaccine in a Japanese children's primary emergency medical center.

BACKGROUND: Acute gastroenteritis (AGE) is a major reason for presentation to pediatric primary emergency medical centers. Because rotavirus vaccines were introduced in November 2011 for voluntary vaccination in Japan, we analyzed the changes in the numbers of AGE patients. METHODS: The number and proportion of patients visiting Kobe children's primary emergency medical center from January 2011 to February 2015 due to AGE, out of all visiting children, were investigated retrospectively. The rotavirus and norovirus epidemic periods were defined as the periods from March to June and from November to February, respectively, based on their disease prevalence. RESULTS: In patients ≤2 years of age, the numbers and proportions of patients with AGE were significantly decreased from 2464/14098 (17%) in 2011 to 1888/12321 (15%) in 2014 (p < 0.01). In patients ≤2 and 3-5 years of age, significant decreases in AGE patients between 2011 and 2014 were observed during the rotavirus season (from 20% [1090/5329] to 14% [642/4482] in patients aged ≤2 years and from 23% [704/3047] to 20% [572/2807] in patients aged 3-5 years, p < 0.01 and p < 0.05, respectively), but not during the norovirus season (from 19% [834/4436] to 19% [797/4160] in patients aged ≤2 years and from 20% [679/3334] to 25% [710/2852] in patients aged 3-5 years). CONCLUSIONS: The estimated rotavirus vaccine coverage in our area increased from 1% in 2011 to 49% in 2014; this coverage may have resulted in a reduction in AGE patients, both directly and indirectly, in our Japanese children's primary emergency medical center.

Comprehensive analysis of serum cytokines/chemokines in febrile children with primary human herpes virus-6B infection.

Cytokines and chemokines induced by primary human herpes virus (HHV)-6B infection may play a critical role in the clinical manifestations of infection. In this study, we analyzed 40 cytokines/chemokines in febrile children with primary HHV-6B infection. Blood samples from 233 febrile and 36 afebrile patients 0-3 years of age were used for this study. In febrile patients, primary HHV-6B infection was determined by detection of HHV-6B DNA without anti-HHV-6 immunoglobulin G in the blood (HHV-6B group). Infection by other pathogens was assumed when HHV-6B DNA was not detected in the blood (non-HHV-6B group). Of the 233 febrile patients, 30 patients (13%) were diagnosed with primary HHV-6B infection. To analyze serum cytokines/chemokines, patients were randomly chosen from the HHV-6B (n = 25) and non-HHV-6B groups (n = 8). Sera from 25 afebrile patients were used as a control. When comparing the levels of 40 cytokines/chemokines between the HHV-6B and control groups, we found that four chemokines (chemokine [C-X-C motif] ligand [CXCL] 11, CXCL10, CXCL16, and chemokine [C-C motif] ligand [CCL] 2) were significantly upregulated in the HHV-6B group compared with those in the control. Of these, only CXCL11 levels were significantly higher in the HHV-6B group than in the non-HHV-6B group. Because the induction of CCL2 was already reported in an early study, we found, for the first time, the induction of three new chemokines, i.e., CXCL11, CXCL10, and CXCL16 in patients with primary HHV-6B infection. Importantly, we demonstrated that serum CXCL11 levels increased specifically in patients with HHV-6B infection.

A pediatric patient with interstitial pneumonia due to enterovirus D68.

Enterovirus D68 (EV-D68) infection is associated with upper and lower respiratory tract symptoms such as fever, cough, and wheezing. Pediatric patients with EV-D68 infection easily develop more severe respiratory complications compared to patients infected with other species of enterovirus, and consequently, have a higher rate of hospitalization and admission to intensive care units. Therefore, the clinical picture of respiratory complications associated with EV-D68 infection needs to be elucidated. Here, we report a 4-year-old girl of EV-D68 infection that required artificial respiration management within 24 h from the onset of cold symptoms. The patient was diagnosed with interstitial pneumonia on the basis of chest imaging findings with patchy, funicular and frosted glassy shadows, increased blood markers of surfactant protein-A, surfactant protein-D and sialylated carbohydrate antigen KL-6, and increased neutrophils and lymphocytes in the bronchoalveolar lavage. Steroids showed a remarkable effect in her treatment. Further investigations are needed to confirm the efficacy of steroids for interstitial pneumonia due to EV-D68 infection. As rapid deterioration of respiratory status is observed in EV-D68 infection, the possibility of interstitial pneumonia may be considered.

Serial assessment of left-ventricular function using tissue Doppler imaging in premature infants within 7 days of life.

Although many echocardiographic parameters can assess cardiac function noninvasively in preterm infants, it has not been determined what indices are the best. We assessed left-ventricular performance in 101 very low-birth weight (VLBW) infants using tissue Doppler imaging (TDI) echocardiography. Echocardiographic examinations, including TDI, were performed serially within 7 days of life. Pulsed-Doppler TDI waveforms were recorded at the mitral valve annulus, and peak systolic velocities (Sa), early diastolic velocities (Ea), and late diastolic velocities (Aa) were measured. Sa and Aa velocities were both decreased significantly from 3 to 12 h and then gradually increased. Ea velocities showed no significant, longitudinal changes, but Ea values in premature groups appeared to be significantly lower than those in mature groups. The ratio of E to Ea (E/Ea) of VLBW infants seemed to be almost stable from birth to day 7, and this also showed no significant differences between different gestational age groups. E/Ea values in infants with patent ductus arteriosus (PDA) appeared to be greater than those in non-PDA infants. Our present findings suggest that TDI assessment in the early neonatal period might be useful in detecting latent systolic/diastolic failure of critically ill preterm infants.

Impact after the Change from Voluntary to Universal Oral Rotavirus Vaccination on Consecutive Emergency Department Visits for Acute Gastroenteritis among Children in Kobe City, Japan (2016-2022).

Rotavirus (RV) is the leading cause of acute gastroenteritis (AGE), particularly in infants. In 2006, the high efficacy of oral RV vaccines (RVVs, RotarixTM and RotaTeqTM) was demonstrated. Voluntary RVV started in Japan in 2011, and in October 2020 were launched as universal oral RVVs in Japan. However, the impact of changes from voluntary to universal RVVs has not been studied in a primary emergency medical center in Japan. We investigated changes in the number of pediatric patients with AGE after introducing universal RVVs in our center. A clinical database of consecutive patients aged <16 who presented to Kobe Children's Primary Emergency Medical Center between 1 April 2016 and 30 June 2022 was reviewed. After implementing universal RVVs, fewer children presented with RV-associated AGE (the reduction of proportion of the patients in 2022 was −61.7% (all ages), −57.9% (<1 years), −67.8% (1−<3 years), and −61.4% (3−<5 years) compared to 2019). A similar decrease in those of age who were not covered by the universal RVV was observed. There was a significant decline in the number of patients with AGE during the RV season who presented to the emergency department after implementing universal RVVs.

Familial cases of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome.

We report three familial cases of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome, including a pair of monozygotic twins and their mother. It suggests that periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome may have a certain monogenetic background.

Multivariate analysis of the impact of weather and air pollution on emergency department visits for night-time headaches among children: retrospective, clinical observational study.

OBJECTIVES: To examine the association between the number of visits to the emergency department (ED) by children for night-time headaches and exposure to multifaceted factors, such as meteorological conditions and air pollution. DESIGN: We conducted a clinical observational time-series analysis study. SETTING: We reviewed consecutive patients younger than 16 years of age at the primary ED centre in Kobe city, Japan, during the night shift (19:30-7:00 hours) between 1 January 2011 and 31 December 2019. PARTICIPANTS: In total, 265 191 children visited the ED; 822 presented with headache during the study period. PRIMARY OUTCOME MEASURES: We investigated the effects of meteorological factors and air pollutants by multivariate analysis of Poisson regression estimates. A subanalysis included the relationship between the number of patients with night-time headaches and the above factors by sex. Furthermore, the effect of typhoon landing on patient visits for headache was also analysed. Headache was not classified because examinations were performed by general paediatricians (non-specialists). RESULTS: The number of patients with night-time headaches displayed distinct seasonal changes, with peaks during the summer. Multivariate analysis of Poisson regression estimates revealed a significant positive relationship between the number of patients for headache and mean temperature. Subanalysis by sex indicated a positive relationship between the number of patients with headache and mean temperature in both sexes; however, it was significant only for females. No relationship was found between the number of patients with headache and air pollution. There was no change in the number of patients for night-time headaches 3 days before and after typhoon landing. CONCLUSIONS: High temperature is the main factor for visiting ED for night-time headaches among children in Kobe city. Our results suggest that preventive measures against night-time headaches may be possible by reducing time spent outside during summer.

Impact of the State of Emergency during the COVID-19 Pandemic in 2020 on Asthma Exacerbations among Children in Kobe City, Japan.

The coronavirus disease (COVID-19) pandemic altered environmental factors. We studied the impact of these changes on asthma exacerbation (AE) by comparing the AE-related environmental factors between COVID-19 (2020) and pre-COVID-19 (2011-2019) eras. Between 2011 and 2020, 278,465 children (<16 years old) visited our emergency department, and 7476 were diagnosed with AE. The number of patients showed spring and fall peaks in 2011-2019. Multivariate analyses showed significant positive relationships of the number of AE patients with the average temperature among all patients and 0-5-year-olds and with sulfur dioxide (SO2) levels in 2011-2019 among 0-5-year-olds. Although the spring peak in the number of patients was not observed in 2020 after declaration of a state of emergency, the fall peak was again observed after the state of emergency was lifted. No changes in average temperature were detected, but SO2 was significantly reduced following declaration of the state of emergency in 2020. Therefore, SO2 reduction might have contributed to the disappearance of the peak of AE. However, a fall peak was observed again in 2020, although SO2 levels continued to be low. These data suggest that person to person interaction seems to be associated with AE, presumably due to unknown viral infections.

Current management for foreign body and toxic agent ingestion in a paediatric primary emergency centre.

OBJECTIVES: Accidental foreign body ingestion (FBI) and toxic agent ingestion (TAI) are commonly encountered among children in primary emergency settings. Early detection and appropriate medical intervention are crucial to improve outcomes. Although many reports from tertiary institutions have shown improvements in therapy, data are still lacking from primary emergency facilities. METHODS: We performed a retrospective analysis based on medical records of FBI/TAI over 4 years at the Kobe Children's Primary Emergency Medical Center. We collected patient information, including age, sex, time between FBI/TAI occurrence and centre visit, provision of first aid, symptoms, type of FBI/TAI, examinations, treatments, and outcomes. RESULTS: A total of 580 children were enrolled. The median age was 1.3 years, and patients under 2 years old accounted for 70% of total cases. Cigarettes (17.5%) were the most common ingested foreign body, followed by medicines (15.3%), detergents (8.1%), in TAI, plastics (14.1%), metal (13.4%), batteries (9.0%) in FBI, and others (22.6%). A total of 42 patients were transferred to advanced hospitals; among these, 22 patients were hospitalised but the foreign body was removed in only 3 (0.9%) patients. Transferred patients were significantly older (P<0.05) in FBI and had a higher rate of any of symptoms (P<0.05) in FBI/TAI. CONCLUSIONS: This large-scale retrospective study of accidental FBI/TAI conducted at a primary emergency facility clarified current management, including treatment at a primary facility. Very few cases of FBI/TAI were treated, even when they were transferred to an advanced treatment hospital. Unified protocols should be established, to improve the management of FBI/TAI.

[Efficacy of topiramate in childhood epilepsies].

To evaluate the efficacy of topiramate (TPM) for the treatment of children with epilepsies, we introduced TPM to 45 patients whose epilepsy began in childhood and whose ages ranged from 4 months to 30 years old (mean age: 11 years 7 months). Thirteen of these patients had been diagnosed with generalized epilepsy (GE) (1 cryptogenic, 12 symptomatic), 30 with localization-related epilepsy (LRE) (7 idiopathic, 23 symptomatic), and 2 with unclassified epilepsy [1 case of severe myoclonic epilepsy in infancy (SMEI), 1 case of epilepsy with continuous spikes and waves during slow sleep (CSWS)]. The initial dose of TPM was 1.97 +/- 0.45 mg/kg/day, followed by a slow titration to the maximum dose of 7.32 +/- 1.32 mg/kg/day. After a mean treatment period of 13.5 months (range 4-20 months), the rate of reduction in seizure frequency by more than 50% [50% responder rate (50% RR)] and the rate of complete remission (seizure-free) were 53.8% and 23.1%, respectively, in patients with GE, and 73.3% and 23.3%, respectively, in patients with LRE. TPM was significantly effective against many seizure types including tonic, clonic, complex partial, myoclonic, and atypical absence seizures. Adverse effects included sleepiness in 13 cases (28.9%), weight loss in 6 cases (13.3%), and metabolic acidosis in 2 cases (4.4%); all of these effects were both mild and transient. In conclusion, TPM is effective and safe for the treatment of pediatric epilepsies.

Left and right ventricular myocardial performance index (Tei index) in very-low-birth-weight infants.

This study presents a report of serial assessment of ventricular myocardial performance index (Tei index) in very-low-birth-weight (VLBW) infants. One hundred ninety-five VLBW infants, weighing <1,500 g, who were admitted to the neonatal intensive care units at Kakogawa Municipal Hospital between September 2000 and August 2004. Left ventricular (LV) and right ventricular (RV) Tei indexes were assessed consecutively from birth to day 28 in all VLBW infants using pulsed-Doppler echocardiography. The mean values of the LV Tei index rose rapidly from 3 to 12 h after birth and then fell significantly after 24 h. Those of the RV Tei index increased slightly from 3 to 12 h, then decreased drastically after 24 h. The LV Tei index was found to correlate inversely with LV output and LV ejection fraction in the early neonatal period, while the relationship between the LV Tei index and the LV E/A velocity ratio was not significant. The RV Tei index was inversely correlated with RV output. In conclusion, both of the ventricular Tei indexes in VLBW infants showed drastic and significant changes on the first to second day after birth.

Blood asymmetric dimethylarginine and nitrite/nitrate concentrations in short-stature children born small for gestational age with and without growth hormone therapy.

Objective To investigate the basal amino acid metabolism and impact of growth hormone (GH) therapy in short-stature children born small for gestational age (short SGA children). Methods In this age-matched case-control study, the basal blood levels of amino acids, asymmetric dimethylarginine (ADMA), and nitrite/nitrate (NOx) were compared between 24 short SGA children and 25 age-matched normal children. Changes in these parameters were assessed for 12 months in 12 short SGA children initiating GH therapy (Group A) and 12 age-matched short SGA children without GH therapy (Group B). Results The arginine levels were significantly lower in the short SGA than in normal children. The ADMA levels were significantly higher and NOx levels were significantly lower in the short SGA than normal children. In Group A, the ADMA level was significantly lower and NOx level was significantly higher at 6 months than at baseline. At 12 months, the ADMA level in Group A began to increase, but the NOx level remained the same. Group B showed no significant changes. Conclusions This study is the first to show that ADMA is promoted and nitric oxide is suppressed in short SGA children and that GH therapy affects the production of ADMA and nitric oxide.