NTIBIOTICS ARE THE MOST COMmon prescription drugs given to children. 1 Although hospitalized children frequently receive antibiotics, 2 the vast majority of antibiotic use occurs in the outpatient setting, roughly 75% of which is for acute respiratory tract infections (ARTIs). 3 Unnecessary prescribing for viral AR-TIs is well documented 3-8 and has been declining. 7-9 However, inappropriate prescribing also occurs for bacterial ARTIs, particularly when broadspectrum antibiotics are used to treat infections for which narrow-spectrum antibiotics are indicated and recommended. 1,3,6,8,9 The American Academy of Pediatrics (AAP) recommends penicillin or amoxicillin as first-line agents for streptococcal pharyngitis, acute sinusitis, and pneumonia 10,11 ; however, roughly 50% of children receive broader-spectrum antibiotics for these common infections. 3 Antimicro-Author Affiliations are listed at the end of this article.

The inflammatory bowel diseases (IBD) Crohn’s disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD1. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 × 10−9), 22q12 (rs2412973, P = 1.55 × 10−9), 10q22 (rs1250550, P = 5.63 × 10−9), 2q37 (rs4676410, P = 3.64 × 10−8) and 19q13.11 (rs10500264, P = 4.26 × 10−10). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn’s disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

We present a database of copy number variations (CNVs) detected in 2026 disease-free individuals, using high-density, SNP-based oligonucleotide microarrays. This large cohort, comprised mainly of Caucasians (65.2%) and AfricanAmericans (34.2%), was analyzed for CNVs in a single study using a uniform array platform and computational process. We have catalogued and characterized 54,462 individual CNVs, 77.8% of which were identified in multiple unrelated individuals. These nonunique CNVs mapped to 3272 distinct regions of genomic variation spanning 5.9% of the genome; 51.5% of these were previously unreported, and >85% are rare. Our annotation and analysis confirmed and extended previously reported correlations between CNVs and several genomic features such as repetitive DNA elements, segmental duplications, and genes. We demonstrate the utility of this data set in distinguishing CNVs with pathologic significance from normal variants. Together, this analysis and annotation provides a useful resource to assist with the assessment of CNVs in the contexts of human variation, disease susceptibility, and clinical molecular diagnostics.

Objectives Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock. Design Retrospective observational study. Setting PICU at an academic medical center. Patients One hundred thirty patients treated for severe sepsis or septic shock. Interventions None. Measurements and Main Results We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure–free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74–277 min) and to first appropriate antimicrobial was 177 minutes (90–550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27–12.06) and 3.59 (95% CI, 1.09–11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45–16.2) and 4.92 (95% CI, 1.30–18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure–free days (16 [interquartile range, 1–23] vs 20 [interquartile range, 6–26]; p = 0.04). Conclusions Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis.

We have identified a locus containing DENND1B on chromosome 1q31.3 that is associated with susceptibility to asthma.

BACKGROUND: Electronic health record (EHR)-linked patient portals are a promising approach to facilitate shared decision-making between families of children with chronic conditions and pediatricians. This study evaluated the feasibility, acceptability, and impact of MyAsthma, an EHR-linked patient portal supporting shared decision-making for pediatric asthma.

Inflammatory bowel disease (IBD) is a common inflammatory disorder with complex etiology that involves both genetic and environmental triggers, including but not limited to defects in bacterial clearance, defective mucosal barrier and persistent dysregulation of the immune response to commensal intestinal bacteria. IBD is characterized by two distinct phenotypes: Crohn’s disease (CD) and ulcerative colitis (UC). Previously reported GWA studies have identified genetic variation accounting for a small portion of the overall genetic susceptibility to CD and an even smaller contribution to UC pathogenesis. We hypothesized that stratification of IBD by age of onset might identify additional genes associated with IBD. To that end, we carried out a GWA analysis in a cohort of 1,011 individuals with pediatric-onset IBD and 4,250 matched controls. We identified and replicated significantly associated, previously unreported loci on chromosomes 20q13 (rs2315008[T] and rs4809330[A]; P = 6.30 × 10−8 and 6.95 × 10−8, respectively; odds ratio (OR) = 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 × 10−8; OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively.

WHAT'S KNOWN ON THIS SUBJECT: Despite proven health benefits, human papillomavirus (HPV) vaccination rates are among the lowest of all routine immunizations. No previous largescale trial has compared the benefit of automated decision support directed at clinicians, families, or both in any context. WHAT THIS STUDY ADDS:We found that a clinician-focused intervention was most effective for initiating the HPV vaccine series, whereas a family-focused intervention supported completion. Decision support directed at both clinicians and families most effectively promotes HPV vaccine series receipt. abstract OBJECTIVE: To improve human papillomavirus (HPV) vaccination rates, we studied the effectiveness of targeting automated decision support to families, clinicians, or both.METHODS: Twenty-two primary care practices were cluster-randomized to receive a 3-part clinician-focused intervention (education, electronic health record-based alerts, and audit and feedback) or none. Overall, 22 486 girls aged 11 to 17 years due for HPV vaccine dose 1, 2, or 3 were randomly assigned within each practice to receive family-focused decision support with educational telephone calls. Randomization established 4 groups: family-focused, clinician-focused, combined, and no intervention. We measured decision support effectiveness by final vaccination rates and time to vaccine receipt, standardized for covariates and limited to those having received the previous dose for HPV #2 and 3. The 1-year study began in May 2010. RESULTS:Final vaccination rates for HPV #1, 2, and 3 were 16%, 65%, and 63% among controls. The combined intervention increased vaccination rates by 9, 8, and 13 percentage points, respectively. The control group achieved 15% vaccination for HPV #1 and 50% vaccination for HPV #2 and 3 after 318, 178, and 215 days. The combined intervention significantly accelerated vaccination by 151, 68, and 93 days. The clinician-focused intervention was more effective than the familyfocused intervention for HPV #1, but less effective for HPV #2 and 3.CONCLUSIONS: A clinician-focused intervention was most effective for initiating the HPV vaccination series, whereas a family-focused intervention promoted completion. Decision support directed at both clinicians and families most effectively promotes HPV vaccine series receipt.