Key Points Question How have US mortality rates for pediatric opioid poisonings changed over the past 2 decades? Findings In this cross-sectional study, 8986 children and adolescents died between 1999 and 2016 from prescription and illicit opioid poisonings. During this time, the mortality rate increased 268.2%. Meaning Pediatric-specific and family-centered interventions are needed to address pediatric opioid poisonings, a growing public health problem in the United States.

Objectives To evaluate data for the period 2004–2013 to identify changes in demographics, pathogens, and outcomes in a single, level IV neonatal intensive care unit (NICU). Study design Sepsis episodes were identified prospectively and additional information obtained retrospectively from infants with sepsis while in the NICU from 2004–2013. Demographics, hospital course, and outcome data were collected and analyzed. Sepsis was categorized as early (≤3 days of life) or late-onset (>3 days of life). Results Four hundred and fifty two organisms were identified from 410 episodes of sepsis in 340 infants. Ninety percent of cases were late-onset. Rates of early-onset sepsis remained relatively static throughout the study period (0.9 per 1000 live births). The majority (60%) of infants with early-onset sepsis were very low birth weight for the first time in decades, and E. coli (45%) replaced GBS (36%) as the most common organism associated with early-onset sepsis. Rates of late-onset sepsis, particularly due to coagulase-negative staphylococci (CoNS), decreased significantly after implementation of several infection prevention initiatives. CoNS was responsible for 31% of all cases from 2004–2009 but accounted for no cases of late-onset sepsis after 2011. Conclusions The epidemiology and microbiology of early- and late-onset sepsis continue to change, impacted by targeted infection prevention efforts. We believe the decrease in sepsis indicates that these interventions have been successful, but additional surveillance and strategies based on evolving trends are necessary.

OBJECTIVES: To derive and internally validate a prediction model for the identification of febrile infants #60 days old at low probability of invasive bacterial infection (IBI). METHODS: We conducted a case-control study of febrile infants #60 days old who presented to the emergency departments of 11 hospitals between July 1, 2011 and June 30, 2016. Infants with IBI, defined by growth of a pathogen in blood (bacteremia) and/or cerebrospinal fluid (bacterial meningitis), were matched by hospital and date of visit to 2 control patients without IBI. Ill-appearing infants and those with complex chronic conditions were excluded. Predictors of IBI were identified with multiple logistic regression and internally validated with 10-fold cross-validation, and an IBI score was calculated. RESULTS: We included 181 infants with IBI (155 [85.6%] with bacteremia without meningitis and 26 [14.4%] with bacterial meningitis) and 362 control patients. Twenty-three infants with IBI (12.7%) and 138 control patients (38.1%) had fever by history only. Four predictors of IBI were identified (area under the curve 0.83 [95% confidence interval (CI): 0.79-0.86]) and incorporated into an IBI score: age ,21 days (1 point), highest temperature recorded in the emergency department 38.0-38.4°C (2 points) or $38.5°C (4 points), absolute neutrophil count $5185 cells per mL (2 points), and abnormal urinalysis results (3 points). The sensitivity and specificity of a score $2 were 98.8% (95% CI: 95.7%-99.9%) and 31.3% (95% CI: 26.3%-36.6%), respectively. All 26 infants with meningitis had scores $2. CONCLUSIONS: Infants #60 days old with fever by history only, a normal urinalysis result, and an absolute neutrophil count ,5185 cells per mL have a low probability of IBI. WHAT'S KNOWN ON THIS SUBJECT: Commonly used risk-stratification criteria for febrile infants were either developed .2 decades ago in studies that included relatively few infants with bacteremia and/or bacterial meningitis or include procalcitonin, which is not readily available in some hospitals. WHAT THIS STUDY ADDS: A newly derived score is highly sensitive for the identification of non-ill-appearing febrile infants #60 days old with invasive bacterial infection. Infants with fever by history only, normal urinalysis results, and an absolute neutrophil count ,5185 cells per mL had a low probability of infection.

No abstract

OBJECTIVES: We obtained preliminary evidence on the efficacy of early prophylaxis on the risk of central venous catheter-associated deep venous thrombosis and its effect on thrombin generation in critically ill children. DESIGN: Bayesian phase 2b randomized clinical trial. SETTING: Seven PICUs. PATIENTS: Children less than 18 years old with a newly inserted central venous catheter and at low risk of bleeding. Intervention: Enoxaparin adjusted to anti-Xa level of 0.2–0.5 international units/mL started at less than 24 hours after insertion of central venous catheter (enoxaparin arm) versus usual care without placebo (usual care arm). MEASUREMENTS AND MAIN RESULTS: At the interim analysis, the proportion of central venous catheter-associated deep venous thrombosis on ultrasonography in the usual care arm, which was 54.2% of 24 children, was significantly higher than that previously reported. This resulted in misspecification of the preapproved Bayesian analysis, reversal of direction of treatment effect, and early termination of the randomized clinical trial. Nevertheless, with 30.4% of 23 children with central venous catheter-associated deep venous thrombosis on ultrasonography in the enoxaparin arm, risk ratio of central venous catheter-associated deep venous thrombosis was 0.55 (95% credible interval, 0.24–1.11). Including children without ultrasonography, clinically relevant central venous catheter-associated deep venous thrombosis developed in one of 27 children (3.7%) in the enoxaparin arm and seven of 24 (29.2%) in the usual care arm (p = 0.02). Clinically relevant bleeding developed in one child randomized to the enoxaparin arm. Response profile of endogenous thrombin potential, a measure of thrombin generation, was not statistically different between trial arms. CONCLUSIONS: These findings suggest the efficacy and safety of early prophylaxis that should be validated in a pivotal randomized clinical trial.

Eunice Kennedy Shriver National Institute of Child Health and Human Development.

ABSTRACT Background Recent literature suggests that the Western diet's imbalance between high ω-6 (n–6) and low ω-3 (n–3) PUFA intake contributes to fatty liver disease in obese youth. Objectives We tested whether 12 wk of a low n–6:n–3 PUFA ratio (4:1) normocaloric diet mitigates fatty liver and whether the patatin-like containing domain phospholipase 3 (PNPLA3) rs738409 variant affects the response. Methods In a single-arm unblinded study, obese youth 9–19 y of age with nonalcoholic fatty liver disease were treated with a normocaloric low n–6:n–3 PUFA ratio diet for 12 wk. The primary outcome was change in hepatic fat fraction (HFF%), measured by abdominal MRI. Metabolic parameters included alanine aminotransferase (ALT), lipids, measures of insulin sensitivity, and plasma oxidized linoleic acid metabolites (OXLAMs). Outcomes were also analyzed by PNPLA3 rs738409 genotype. Wilcoxon's signed rank test, the Mann–Whitney U test, and covariance pattern modeling were used. Results Twenty obese adolescents (median age: 13.3 y; IQR: 10.5–16.4 y) were enrolled and 17 completed the study. After 12 wk of dietary intervention, HFF% decreased by 25.8% (P = 0.009) despite stable weight. We observed a 34.4% reduction in ALT (P = 0.001), 21.9% reduction in triglycerides (P = 0.046), 3.28% reduction in LDL cholesterol (P = 0.071), and a 26.3% improvement in whole body insulin sensitivity (P = 0.032). The OXLAMs 9-hydroxy-octadecandienoic acid (9-HODE) (P = 0.011), 13-HODE (P = 0.007), and 9-oxo-octadecadienoic acid (9-oxoODE) (P = 0.024) decreased after 12 wk. HFF% declined in both the not-at-risk (CC/CG) and at-risk (GG) PNPLA3 rs738409 genotype groups, with significant (P = 0.016) HFF% reduction in the GG group. Changes in 9-HODE (P = 0.023), 9-oxoODE (P = 0.009), and 13-oxoODE (P = 0.003) differed between the 2 genotype groups over time. Conclusions These data suggest that, independently of weight loss, a low n–6:n–3 PUFA diet ameliorates the metabolic phenotype of adolescents with fatty liver disease and that response to this diet is modulated by the PNPLA3 rs738409 genotype. This trial was registered at clinicaltrials.gov as NCT01556113.

Background: Antiretroviral therapy (ART) scale-up in resource-limited countries, with limited capacity for CD4 and HIV viral load monitoring, presents a unique challenge. We determined the effectiveness of first-line ART in a real world pediatric HIV clinic and explored associations between readily obtainable patient data and the trajectories of change in CD4 count and HIV viral load. Methods: We performed a longitudinal study of a cohort of HIV-infected children initiating ART at the Korle-Bu Teaching Hospital Pediatric HIV clinic in Accra, Ghana, aged 0-13 years from 2009-2012. CD4 and viral load testing were done every 4 to 6 months and genotypic resistance testing was performed for children failing therapy. A mixed linear modeling approach, combining fixed and random subject effects, was employed for data analysis.