Objective The international scope of critical neurological insults in children is unknown. Our objective was to assess the prevalence and outcomes of children admitted to pediatric intensive care units (PICUs) with acute neurological insults. Design Prospective study. Setting Multicenter (n=107 PICUs) and multinational (23 countries, 79% in North America and Europe). Patients Children aged 7d–17y admitted to the ICU with new traumatic brain injury, stroke, cardiac arrest, central nervous system infection or inflammation, status epilepticus, spinal cord injury, hydrocephalus, or brain mass. Interventions None. Measurements and main results We evaluated the prevalence and outcomes of children with pre-determined acute neurological insults. Child and center characteristics were recorded. Unfavorable outcome was defined as change in pre-post insult Pediatric Cerebral Performance Category (PCPC) score ≥ 2 or death at hospital discharge or 3 months, whichever came first. Screening data yielded overall prevalence of 16.2%. Of 924 children with acute neurological insults, cardiac arrest (23%) and traumatic brain injury (19%) were the most common. All-cause mortality at hospital discharge was 12%. Cardiac arrest subjects had highest mortality (24%), and TBI subjects had the most unfavorable outcomes (49%). The most common neurological insult was infection/inflammation in South America, Asia, and the single African site but cardiac arrest in the remaining regions. Conclusions Neurological insults are a significant pediatric international health issue. They are frequent and contribute substantial morbidity and mortality. These data suggest a need for an increased focus on acute critical neurological diseases in infants and children including additional research, enhanced availability of clinical resources, and the development of new therapies.

No abstract

Objective: Legitimate opioid prescriptions have been identified as a risk factor for opioid misuse in pediatric patients. In 2014, Pennsylvania legislation expanded a prescription drug monitoring program (PDMP) to curb inappropriate controlled substance prescriptions. The authors’ objective was to describe recent opioid prescribing trends at a large, pediatric health system situated in a region with one of the highest opioid-related death rates in the United States and examine the impact of the PDMP on prescribing trends.Design: Quasi-experimental assessment of trends of opioid e-prescriptions, from 2012 to 2017. Multivariable Poisson segmented regression examined the effect of the PDMP. Period prevalence comparison of opioid e-prescriptions across the care continuum in 2016.Results: There were 62,661 opioid e-prescriptions identified during the study period. Combination opioid/non-opioid prescriptions decreased, while oxycodone prescriptions increased. Seasonal variation was evident. Of 110,884 inpatient encounters, multivariable regression demonstrated lower odds of an opioid being prescribed at discharge per month of the study period (p 0.001) and a significant interaction between passage of the PDMP legislation and time (p = 0.03). Black patients had lower odds of receiving an opioid at discharge compared to white patients. Inpatients had significantly greater odds of receiving an opioid compared to emergency department (Prevalence Odds Ratio 7.1 [95% confidence interval: 6.9-7.3]; p 0.001) and outpatient (398.9 [355.5-447.5]; p 0.001) encounters.Conclusion: In a large pediatric health system, oxycodone has emerged as the most commonly prescribed opioid in recent years. Early evidence indicates that a state-run drug monitoring program is associated with reduced opioid prescribing. Additional study is necessary to examine the relationship between opioid prescriptions and race.

Introduction Autophagy is well known as one of the biogenic responses against various stresses, which possesses the benefi cial roles for survival, but little is known about the dynamics and its signifi cance during the septic condition. We hypothesized that autophagy is induced during the septic condition, and contributes to protect from tissue damage which subsequently leads to organ dysfunction. We confi rm whether the autophagic process is accelerated or sustained in an acute phase of sepsis and we also determine its physiological role. Methods Sepsis was induced by cecal ligation and puncture (CLP) in mice. We examined the kinetics of autophagosome and auto lysosome formation which may explain the status of autophagy by western blotting, immunohistochemistry, and electron microscopy. To investigate a precise role of autophagy in CLP-induced sepsis, chloroquine, an autophagy inhibitor, was administered to the CLP-operated mice, and blood chemistry, pathology of the liver and survival were evaluated. Results Autophagy demonstrated by the ratio of LC3-II/LC3-I was induced over the time course up to 24 hours after CLP. The ratio was particularly increased in the liver, heart and spleen. Autophagosome formation became maximal at 6 hours and declined by 24 hours after CLP. Autolysosome formation as evaluated by both fusion of GFP-LC3 dots with LAMP1 immunohistochemistry and electron microscopy was also increased after the procedure. Furthermore, inhibition of autophagy by chloroquine during the CLP procedure resulted in elevation of serum AST levels, and signifi cantly increased mortality in mice. Conclusion Autophagy was induced in several organs over the time course of the CLP sepsis model and then the process was gradually completed to degradation of the components. Our data suggest autophagy plays a protective role in organ dysfunction in sepsis. P2Reversible depressive eff ect of TNFα on a model of isolated perfused rat heart BV Nguyen Introduction Acute myocardial depression in septic shock is common [1]. Myocardial depression is mediated by circulating depressant substances, which until now have been incompletely characterized [2].The aim of our study was to observe the eff ects of TNFα on the model of perfused rat heart. Methods After profound anesthesia with pentothal, the Wistar rats were killed by exsanguination. After sternotomy, the heart was taken and connected to the Langendorf column. The apex of the heart was hooked to a strength sensor. Biopac student laboratory software was used to record and analyse heart contractions. Contractions were recorded every 5 minutes during periods of 20 minutes. Control measurements were fi rst recorded. We measured four parameters: heart rate, contraction force, speeds of contraction and relaxation for control, during TNFα (20 ng/ml) exposure and after removal of TNFα. We express the variations of parameters as percentage of the control ± SEM. A paired t test was used to compare heart rate, contraction amplitude, speeds of contraction and relaxation with TNFα and ...

No abstract