Once-Weekly Exenatide in Youth With Type 2 Diabetes.

OBJECTIVE: Approved treatments for type 2 diabetes in pediatric patients include metformin, liraglutide, and insulin. However, approximately one-half of the youth fail metformin monotherapy within 1 year, insulin therapy is associated with challenges, and liraglutide requires daily injections. Consequently, the efficacy and safety of once-weekly injections of exenatide for the treatment of youth with type 2 diabetes was evaluated. RESEARCH DESIGN AND METHODS: Participants (aged 10 to <18 years) were randomized (5:2) to once-weekly exenatide 2 mg or placebo, respectively. The primary efficacy end point was change in glycated hemoglobin from baseline to week 24. Secondary efficacy end points were also evaluated, and the frequency of adverse events (AEs) was assessed. RESULTS: A total of 83 participants were randomized (exenatide, 59; placebo, 24) and 72 completed 24-week treatment (exenatide, 49; placebo, 23). At 24 weeks, the least squares mean change in glycated hemoglobin was -0.36% for the exenatide and +0.49% for the placebo groups (between-group difference, -0.85%; 95% CI -1.51, -0.19; P = 0.012). Nonsignificant least squares mean differences from baseline to 24 weeks favoring exenatide were observed: fasting glucose -21.6 mg/dL (-49.0, 5.7; P = 0.119), systolic blood pressure -2.8 mmHg (-8.0, 2.4; P = 0.284), and body weight -1.22 kg (-3.59, 1.15; P = 0.307). AEs occurred in 36 (61.0%) and 17 (73.9%) participants in the exenatide and placebo groups, respectively. CONCLUSIONS: In youth with type 2 diabetes suboptimally controlled with current treatments, once-weekly exenatide reduced glycated hemoglobin at 24 weeks and was well tolerated.

A Phase 3, Randomized, Investigator-blinded Trial Comparing Ceftobiprole With a Standard-of-care Cephalosporin, With or Without Vancomycin, for the Treatment of Pneumonia in Pediatric Patients.

BACKGROUND: The advanced-generation, broad-spectrum, intravenous (IV) cephalosporin, ceftobiprole, is an effective and well-tolerated treatment for adults with hospital-acquired pneumonia (HAP) or community-acquired pneumonia (CAP), but its effects in pediatric patients have not been established. METHODS: In this multicenter, investigator-blinded, active-controlled, phase 3 study, patients 3 months to <18 years old with HAP or CAP requiring hospitalization were randomized (2:1) to ceftobiprole versus standard-of-care (SoC) IV cephalosporin treatments (ceftazidime or ceftriaxone), with or without vancomycin. After at least 3 days' IV treatment, patients demonstrating clinical improvement could be switched to an oral antibiotic, to complete a minimum of 7 days' treatment. RESULTS: Overall, 138 patients were randomized to ceftobiprole (n = 94) or a SoC cephalosporin (n = 44). Median time to oral switch was 6.0 days in the ceftobiprole group and 8.0 days in the SoC cephalosporin group. While on IV therapy, adverse events and treatment-related adverse events were reported by 20.2% and 8.5% of ceftobiprole-treated patients and 18.2% and 0% of SoC cephalosporin-treated patients. Early clinical response rates at day 4 in the intention-to-treat population were 95.7% and 93.2% (between-group difference, 2.6%; 95% confidence interval, -5.5% to 14.7%) in the ceftobiprole and comparator groups, and clinical cure rates at the test-of-cure visit were 90.4% and 97.7% (between-group difference, -7.3%; 95% confidence interval, -15.7% to 3.6%), respectively. CONCLUSIONS: Ceftobiprole was well tolerated and, in this small phase 3 study, demonstrated similar efficacy to SoC cephalosporins in pediatric patients with HAP or CAP requiring hospitalization.

A cluster of salivirus A1 (Picornaviridae) infections in newborn babies with acute gastroenteritis in a neonatal hospital unit in Hungary.

Salivirus (family Picornaviridae) may be associated with acute gastroenteritis in humans, but there have been no reports of salivirus outbreaks. Salivirus A1 infection with faecal virus concentrations of 2.1-2.6 × 10(9)/g were identified retrospectively in newborn babies, between the ages of 1.5 and 5 days, with apparent clinical symptoms of diarrhea (100 %), fever (40 %), vomiting (40 %), and loss of appetite (40 %) in a neonatal hospital unit in Hungary in July 2013. The complete genome sequence of the salivirus (including the 5'-terminal end) was determined. Salivirus mono-infection may be associated with gastroenteritis in babies who are a few days old. Salivirus testing should be done in public health laboratories in gastroenteritis outbreaks with unknown etiology.

Blood pressure reference tables for Hungarian adolescents aged 11-16 years.

BACKGROUND/AIMS: Blood pressure (BP) during childhood is an established predictor of adult BP, which in turn predicts mortality in the event of cardiovascular disease. Reference data for systolic (SBP) and diastolic (DBP) BP are not available for Hungarian children (aged 11-14 years). The aim was to make up for this deficit. METHODS: Analyses were performed on 14,504 Hungarian children aged 11-16 years. All measurements were made with a validated, automated device. Criteria described by international guidelines were used. RESULTS: The 50th, 90th and 95th percentile BP values were defined by dividing the participating population into age-, gender- and height-specific subgroups. The SBP increased linearly with age to an apparent plateau at around the age of 15-16 years in both girls and boys, and there were similar increases in DBP and mean arterial pressure. Both the SBP and DBP revealed highly significant correlations in both genders with weight (SBP: r = 0.452, p < 0.01; DBP: r = 0.340, p < 0.01), height (SBP: r = 0.314, p < 0.01; DBP: r = 0.245, p < 0.01) and body mass index (SBP: r = 0.407, p < 0.01; DBP: r = 0.294, p < 0.01). CONCLUSION: The present study provides reference data on SBP and DBP, facilitating the diagnosis of essential hypertension in the 11- to 16-year age group.

Heat shock protein 72 (HSPA1B) gene polymorphism and Toll-like receptor (TLR) 4 mutation are associated with increased risk of urinary tract infection in children.

Innate immunity and urinary tract response play a central role in the development of urinary tract infection (UTI). Heat shock protein (HSP) 72 and Toll-like receptor (TLR) 4 are among the key elements of innate defence mechanisms. This study assesses the role of HSPA1B A(1267)G and TLR4 A(896)G polymorphisms using allele-specific polymerase chain reaction in 103 patients treated with recurrent UTI. Allelic prevalence was compared with reference values of 235 healthy controls. Clinical data were also statistically evaluated. TLR4 (896)AG genotype and TLR4 (896)G allele had also higher prevalence in UTI patients versus controls (p = 0.031 and 0.041, respectively). Our data indicates a relationship between the carrier status of HSPA1B (1267)G and TLR4 (896)G alleles and the development of recurrent UTI in childhood independently of other renal abnormalities, while raising further questions about the clinical and therapeutic relevance of these polymorphisms in everyday pediatric nephrology.

ACE gene polymorphism and renal scarring in primary vesicoureteric reflux.

The objective of this study was to investigate whether mutations of the renin-angiotensin system genes are involved in primary vesicoureteric reflux (VUR) and VUR-associated renal scarring. The M235T polymorphism of the angiotensinogen ( ATG) gene, the I/D polymorphism of the angiotensin converting enzyme ( ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor ( AT1) gene were identified in 77 patients with primary VUR (aged 6.9+/-3.2 years, mean+/-SD) and 80 healthy controls (aged 33+/-7 years). Thirty-eight of the 77 VUR patients had low-grade VUR (grade I-III) and 39 had high-grade VUR (grade IV and V). Renal scarring was found in 43 VUR patients, while 34 patients had normal kidneys on dimercaptosuccinic acid scan. The ACE gene polymorphism was determined by polymerase chain reaction and the ATG and AT1 gene polymorphisms were determined by single-step LightCycler technology. We found significant over-representation of the DD genotype in patients with renal scarring (44 %) compared with normal controls (23%, P<0.05) and patients with no scar formation (21%, P<0.05). Significantly higher D and significantly lower I allele frequencies were present in VUR patients with scarred kidneys (D allele 0.64 and I allele 0.36) compared with controls (D allele 0.53 and I allele 0.47, P<0.05) and patients with unscarred kidneys (D allele 0.4 and I allele 0.6, P<0.05). No differences in the ATG and AT1 genotype distributions and allele frequencies were observed in VUR patients compared with the normal population. The DD genotype and D allele of ACE may be a genetic susceptibility factor contributing to scar formation in VUR. We detected no linkage of genetic polymorphisms of ATG and AT1 to VUR and VUR-associated renal scarring.