Discordant antibiotic therapy and length of stay in children hospitalized for urinary tract infection

BACKGROUND: Urinary tract infections (UTIs) are a common reason for pediatric hospitalizations. OBJECTIVE: To determine the effect of discordant antibiotic therapy (in vitro nonsusceptibility of the uropathogen to initial antibiotic) on clinical outcomes for children hospitalized for UTI. DESIGN/SETTING: Multicenter retrospective cohort study in children aged 3 days to 18 years, hospitalized at 5 children's hospitals with a laboratory‐confirmed UTI. Data were obtained from medical records and the Pediatric Hospital Information System (PHIS) database. PARTICIPANTS: Patients with laboratory‐confirmed UTI. MAIN EXPOSURE: Discordant antibiotic therapy. MEASUREMENTS: Length of stay and fever duration. Covariates included age, sex, insurance, race, vesicoureteral reflux, antibiotic prophylaxis, genitourinary abnormality, and chronic care conditions. RESULTS: The median age of the 216 patients was 2.46 years (interquartile range [IQR]: 0.27, 8.89) and 25% were male. The most common causative organisms were E. coli and Klebsiella species. Discordant therapy occurred in 10% of cases and most commonly in cultures positive for Klebsiella species, Enterobacter species, and mixed organisms. In adjusted analyses, discordant therapy was associated with a 1.8 day (95% confidence interval [CI]: 1.5, 2.1) longer length of stay [LOS], but not with fever duration. CONCLUSIONS: Discordant antibiotic therapy for UTI is common and associated with longer hospitalizations. Further research is needed to understand the clinical factors contributing to the increased LOS and to inform decisions for empiric antibiotic selection in children with UTIs. Journal of Hospital Medicine 2012; © 2012 Society of Hospital MedicinePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94298/1/1960_ftp.pd

DMP1 C-Terminal Mutant Mice Recapture the Human ARHR Tooth Phenotype

DMP1 mutations in autosomal recessive hypophosphatemic rickets (ARHR) patients and mice lacking Dmp1 display an overlapping pathophysiology, such as hypophosphatemia. However, subtle differences exist between the mouse model and human ARHR patients. These differences could be due to a species specificity of human versus mouse, or it may be that the mutant DMP1 in humans maintains partial function of DMP1. In this study we report a deformed tooth phenotype in a human DMP1 deletion mutation case. Unexpectedly, the deletion of nucleotides 1484 to 1490 (c.1484_1490delCTATCAC, delMut, resulting in replacement of the last 18 residues with 33 random amino acids) showed a severe dentin and enamel defect similar to a dentinogenesis imperfecta (DI) III–like phenotype. To address the molecular mechanism behind this phenotype, we generated delMut transgenic mice with the endogenous Dmp1 gene removed. These mutant mice did not recapture the abnormal phenotype observed in the human patient but displayed a mild rachitic tooth phenotype in comparison with that in the Dmp1-null mice, suggesting that the DI III–like phenotype may be due to an as-yet-undetermined acquired gene modifier. The mechanism studies showed that the mutant fragment maintains partial function of DMP1 such as stimulating MAP kinase signaling in vitro. Last, the in vitro and in vivo data support a role of odontoblasts in the control of fibroblast growth factor 23 (FGF-23) regulation during early postnatal development, although this regulation on Pi homeostasis is likely limited. © 2010 American Society for Bone and Mineral Research

Oral Ondansetron Administration in Emergency Departments to Children with Gastroenteritis: An Economic Analysis

Stephen Freedman and colleagues performed a cost analysis of the routine administration of ondansetron in both the United States and Canada and show that its routine administration to eligible children in such settings could provide substantial benefit

Genetic causes of hypercalciuric nephrolithiasis

Renal stone disease (nephrolithiasis) affects 3–5% of the population and is often associated with hypercalciuria. Hypercalciuric nephrolithiasis is a familial disorder in over 35% of patients and may occur as a monogenic disorder that is more likely to manifest itself in childhood. Studies of these monogenic forms of hypercalciuric nephrolithiasis in humans, e.g. Bartter syndrome, Dent’s disease, autosomal dominant hypocalcemic hypercalciuria (ADHH), hypercalciuric nephrolithiasis with hypophosphatemia, and familial hypomagnesemia with hypercalciuria have helped to identify a number of transporters, channels and receptors that are involved in regulating the renal tubular reabsorption of calcium. Thus, Bartter syndrome, an autosomal disease, is caused by mutations of the bumetanide-sensitive Na–K–Cl (NKCC2) co-transporter, the renal outer-medullary potassium (ROMK) channel, the voltage-gated chloride channel, CLC-Kb, the CLC-Kb beta subunit, barttin, or the calcium-sensing receptor (CaSR). Dent’s disease, an X-linked disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, is due to mutations of the chloride/proton antiporter 5, CLC-5; ADHH is associated with activating mutations of the CaSR, which is a G-protein-coupled receptor; hypophosphatemic hypercalciuric nephrolithiasis associated with rickets is due to mutations in the type 2c sodium–phosphate co-transporter (NPT2c); and familial hypomagnesemia with hypercalciuria is due to mutations of paracellin-1, which is a member of the claudin family of membrane proteins that form the intercellular tight junction barrier in a variety of epithelia. These studies have provided valuable insights into the renal tubular pathways that regulate calcium reabsorption and predispose to hypercalciuria and nephrolithiasis