Prevalence and Characteristics of Diagnostic Error in Pediatric Critical Care: A Multicenter Study.

OBJECTIVES: Effective interventions to prevent diagnostic error among critically ill children should be informed by diagnostic error prevalence and etiologies. We aimed to determine the prevalence and characteristics of diagnostic errors and identify factors associated with error in patients admitted to the PICU. DESIGN: Multicenter retrospective cohort study using structured medical record review by trained clinicians using the Revised Safer Dx instrument to identify diagnostic error (defined as missed opportunities in diagnosis). Cases with potential errors were further reviewed by four pediatric intensivists who made final consensus determinations of diagnostic error occurrence. Demographic, clinical, clinician, and encounter data were also collected. SETTING: Four academic tertiary-referral PICUs. PATIENTS: Eight hundred eighty-two randomly selected patients 0-18 years old who were nonelectively admitted to participating PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 882 patient admissions, 13 (1.5%) had a diagnostic error up to 7 days after PICU admission. Infections (46%) and respiratory conditions (23%) were the most common missed diagnoses. One diagnostic error caused harm with a prolonged hospital stay. Common missed diagnostic opportunities included failure to consider the diagnosis despite a suggestive history (69%) and failure to broaden diagnostic testing (69%). Unadjusted analysis identified more diagnostic errors in patients with atypical presentations (23.1% vs 3.6%, p = 0.011), neurologic chief complaints (46.2% vs 18.8%, p = 0.024), admitting intensivists greater than or equal to 45 years old (92.3% vs 65.1%, p = 0.042), admitting intensivists with more service weeks/year (mean 12.8 vs 10.9 wk, p = 0.031), and diagnostic uncertainty on admission (77% vs 25.1%, p < 0.001). Generalized linear mixed models determined that atypical presentation (odds ratio [OR] 4.58; 95% CI, 0.94-17.1) and diagnostic uncertainty on admission (OR 9.67; 95% CI, 2.86-44.0) were significantly associated with diagnostic error. CONCLUSIONS: Among critically ill children, 1.5% had a diagnostic error up to 7 days after PICU admission. Diagnostic errors were associated with atypical presentations and diagnostic uncertainty on admission, suggesting possible targets for intervention.

Evaluation of an ex-vivo neonatal extracorporeal membrane oxygenation circuit on antiepileptic drug sequestration.

Antiepileptic dosing information used to manage neonatal patients receiving extracorporeal membrane oxygenation (ECMO) is limited. The objective of this study is to quantify the extent of sequestration of various antiepileptic drugs using an ex-vivo neonatal ECMO circuit. Two neonatal closed-loop ECMO circuits were prepared using a Rotaflow centrifugal pump, custom polyvinylchloride tubing and a Quadrox-i Neonatal membrane oxygenator. After 5 minutes of circuit priming and stabilization with normal saline/albumin or expired human whole blood, single boluses of levetiracetam (200 mg), lacosamide (20 mg), and phenytoin (200 mg) were injected into the circuit. To account for spontaneous drug degradation, two polyvinylchloride beakers were filled with normal saline/albumin or expired human whole blood and equivalent antiepileptic drug doses were prepared. Simultaneous pharmacokinetic samples were collected from the control solution and the pre-centrifugal pump, pre-oxygenator, and post-oxygenator sampling ports from each circuit. Similar drug recovery profiles were observed among the three sampling sites investigated. Percent drug sequestration after a 24-hour circuit flow period was relatively similar between the two different circuits and ranged between 5.5%-13.2% for levetiracetam, 18.4%-22.3% for lacosamide, and 24.5%-30.2% for phenytoin. A comparison at 12 and 24 hours demonstrated similar percent drug sequestration across all three drugs in each circuit. Percent drug sequestrations for levetiracetam and lacosamide were less than 20% and for phenytoin were as high as 30% based on the sampling following single bolus dose administration into a neonatal ECMO circuit. Careful consideration of patient clinical status should be taken in consideration when optimizing antiepileptic therapy in neonates receiving ECMO.

Outcomes of Pediatric Patients With Sepsis Related to Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus Infections Requiring Extracorporeal Life Support: An ELSO Database Study.

Background: Extracorporeal membrane oxygenation (ECMO) is increasingly utilized for pediatric sepsis unresponsive to steroids and inotropic support. Outcomes of children with sepsis are influenced by the type of pathogen causing their illness. Objective: To determine if the outcomes of children with Staphylococcus aureus sepsis receiving ECMO differed according to microbial sensitivity (Methicillin-resistant Staphylococcus aureus [MRSA] vs. Methicillin-sensitive Staphylococcus aureus [MSSA]). Methods: Retrospective case-matched cohort study of children (0-<18 years) with Staphylococcus aureus sepsis reported to the ELSO registry from more than 995 centers. Inclusion criteria were age 0-18 years, laboratory diagnosis of Staphylococcal infection, clinical diagnosis of sepsis, and ECMO deployment. Exclusion criteria were no laboratory diagnosis of Staphylococcal infection. We compared patient demographics, pre-ECMO management and outcomes of those with MRSA vs. MSSA using Chi-Square test, with independent samples t-test used to test to compare continuous variables. Results: In our study cohort of 308 patients, 160 (52%) had MSSA and 148 (48%) MRSA with an overall survival rate of 41.5%. There were no differences in the age group (p = 0.76), gender distribution (p = 0.1) or racial distribution (p = 0.58) between the two groups. P value for racial distribution should be 0.058. There were 91 (56.8%) deaths in the MSSA group and 89 (60.1%) deaths (p = 0.56) in the MRSA group. Duration on ECMO (p = 0.085) and the time from intubation to ECMO (p = 0.37) were also similar in the two groups. Survival with MSSA sepsis and MRSA sepsis did not improve significantly over the 20 years evaluated despite an increase in ECMO utilization. Conclusion: In this multi-center retrospective study, there were no differences in outcomes for children receiving ECMO support with Staphylococcus aureus sepsis according to microbial methicillin sensitivity. There was no significant increase in survival among patients with MRSA and MSSA infections receiving ECMO in the last 20 years.

The Impact of Dedicated Cardiac Intensive Care Units on Outcomes in Pediatric Cardiac Surgery: A Virtual Pediatric Systems Database Analysis.

Care of children undergoing cardiac surgery occurs in dedicated cardiac intensive care units (CICU) or mixed intensive care units. In this article, we analyzed data from Virtual Pediatric Systems (VPS, LLC) database (2009-2014) for children < 18 years of age undergoing cardiac surgery, classified according to Society of Thoracic Surgery-European Association of Cardiothoracic Surgery (STS-EACTS) risk category. We had 25,052 (52%) patients in 53 mixed units (mortality rate, 2.99%), and 22,762 (48%) patients in 19 dedicated CICUs (mortality rate, 2.62%). There was a direct relationship between STS-EACTS risk category and death rate in both units. By multivariable logistic and linear regression, there was no difference in mortality between mixed unit and CICU death rates within STS-EACTS risk categories. We found no difference in outcomes for children undergoing cardiac surgery based on the unit type (dedicated CICU or mixed unit).

Outcomes of Children With Firearm Injuries Admitted to the PICU in the United States.

OBJECTIVES: Firearm-related injury is the second leading cause of injury and death for children 1-18 years old in United States. The objective of our study was to analyze the outcomes of children admitted to the PICU with firearm injuries. DESIGN: Retrospective study. SETTING: PICUs in United States contributing data to Virtual Pediatric Systems, LLC, from January 2009 to December 2017. PATIENTS: Children age 1 month to 18 years old admitted to the PICU with firearm injury, identified by external cause of injury E-codes and International Classification of Diseases, 9th Edition, and International Classification of Diseases, 10th Edition, codes were identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 1,447 cases identified of which 175 (12%) died in the PICU. Unintentional firearm injury (67.7%) and assault with a firearm injury (20%) comprised 90% of the cases. Males comprised 78% of the cohort (1,122) and race distribution included 45% Black (646), 27% White (390), and 12% Hispanic (178). Among the children who died in the PICU, 55% were 13-18 years old. Children attempting suicide with a firearm were more likely to die in the PICU as compared to the other causes of firearm injury. Based on their Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores at discharge, there is high morbidity in children with firearm injuries. CONCLUSIONS: Mortality rate of children with firearm injury admitted to the PICU is high. Children admitted to the PICU with suicide attempt with a firearm carried the highest mortality. Further studies may help further define the epidemiology of firearm injuries in children and plan interventions to minimize these unnecessary deaths.

Botulism in the Pediatric Intensive Care Units in the United States: Interrogating a National Database.

Botulism in children can have severe complications necessitating intensive care. The current literature lacks data of children with botulism requiring critical care. We aim to describe the outcomes of pediatric botulism in the pediatric intensive care unit (PICU). Retrospective cohort data from Virtual Pediatric Systems (VPS, LLC, Los Angeles, California), from 2009 to 2016 including all PICU admissions among children with botulism, were analyzed. Characteristics and outcomes were compared with similar studies. A total of 380 children were identified over 8 years. Our cohort had the shortest length of stay (median 4.6 days), the smallest percent requiring mechanical ventilation (40%), and the highest median age (120 days) amongst comparable studies. Length of mechanical ventilation and PICU stay has decreased among children with botulism. Advances in PICU care may have contributed to these improved outcomes.

Characteristics and outcomes of children with congenital heart disease needing diaphragm plication.

BACKGROUND: Diaphragm dysfunction following surgery for congenital heart disease is a known complication leading to delays in recovery and increased post-operative morbidity and mortality. We aimed to determine the incidence of and risk factors associated with diaphragm plication in children undergoing cardiac surgery and evaluate timing to repair and effects on hospital cost and length of stay. METHODS: We conducted a multi-institutional retrospective observational cohort study. Forty-three hospitals from the Pediatric Health Information System database were included, and a total of 112,110 patients admitted between January 2004 and December 2014 were analysed. RESULTS: Patients less than 18 years of age who underwent cardiac surgery were included. Risk Adjustment for Congenital Heart Surgery was utilized to determine procedure complexity. The overall incidence of diaphragm dysfunction was 2.2% (n = 2513 out of 112,110). Of these, 24.0% (603 patients) underwent diaphragm plication. Higher complexity cardiac surgery (Risk Adjustment for Congenital Heart Surgery 5-6) and age less than 4 weeks were associated with a higher likelihood of diaphragm plication (p-value < 0.01). Diaphragmatic plication was associated with increased hospital length of stay (p-value < 0.01) and increased medical cost. CONCLUSIONS: Diaphragm plication after surgery for congenital heart disease is associated with longer hospital length of stay and increased cost. There is a strong correlation of prolonged time to plication with increased length of stay and medical cost. The likelihood of plication increases with younger age and higher procedure complexity. Methods to improve early recognition and treatment of diaphragm dysfunction should be developed.

The utility of guaiac stool testing in the detection of gastrointestinal complications in infants with critical congenital heart disease.

BACKGROUND: Guaiac stool testing has been routinely used as a method to detect gastrointestinal complications in infants with critical congenital heart disease (CHD); however, the sensitivity and specificity have not been established. METHODS: A retrospective chart review was performed investigating the presence of heme-positive stools and subsequent gastrointestinal complications as well as time to goal caloric intake and radiograph exposure. RESULTS: The presence of heme-positive stools was not a statistically significant factor in patients with critical CHD that experienced gastrointestinal complications. Additionally, patients with heme-positive stools did undergo more abdominal X-rays than those with heme-negative stools. CONCLUSIONS: The routine use of guaiac stool testing in infants with critical CHD is not a predictor of possible gastrointestinal complications and leads to more radiograph exposure for the patient. Close clinical monitoring can be used to evaluate feeding tolerance in infants with critical CHD.

Short-Term Adverse Outcomes Associated With Hypoglycemia in Critically Ill Children.

OBJECTIVES: Previous studies report worse short-term outcomes with hypoglycemia in critically ill children. These studies relied on intermittent blood glucose measurements, which may have introduced detection bias. We analyzed data from the Heart And Lung Failure-Pediatric INsulin Titration trial to determine the association of hypoglycemia with adverse short-term outcomes in critically ill children. DESIGN: Nested case-control study. SETTING: Thirty-five PICUs. A computerized algorithm that guided the timing of blood glucose measurements and titration of insulin infusion, continuous glucose monitors, and standardized glucose infusion rates were used to minimize hypoglycemia. PATIENTS: Nondiabetic children with cardiovascular and/or respiratory failure and hyperglycemia. Cases were children with any hypoglycemia (blood glucose < 60 mg/dL), whereas controls were children without hypoglycemia. Each case was matched with up to four unique controls according to age group, study day, and severity of illness. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 112 (16.0%) of 698 children who received the Heart And Lung Failure-Pediatric INsulin Titration protocol developed hypoglycemia, including 25 (3.6%) who developed severe hypoglycemia (blood glucose < 40 mg/dL). Of these, 110 cases were matched to 427 controls. Hypoglycemia was associated with fewer ICU-free days (median, 15.3 vs 20.2 d; p = 0.04) and fewer hospital-free days (0 vs 7 d; p = 0.01) through day 28. Ventilator-free days through day 28 and mortality at 28 and 90 days did not differ between groups. More children with insulin-induced versus noninsulin-induced hypoglycemia had zero ICU-free days (35.8% vs 20.9%; p = 0.008). Outcomes did not differ between children with severe versus nonsevere hypoglycemia or those with recurrent versus isolated hypoglycemia. CONCLUSIONS: When a computerized algorithm, continuous glucose monitors and standardized glucose infusion rates were used to manage hyperglycemia in critically ill children with cardiovascular and/or respiratory failure, severe hypoglycemia (blood glucose < 40 mg/dL) was uncommon, but any hypoglycemia (blood glucose < 60 mg/dL) remained common and was associated with worse short-term outcomes.

Minimally invasive technique for measuring transdermal glucose with a fluorescent biosensor.

There is a need for blood glucose monitoring techniques that eliminate the painful and invasive nature of current methods, while maintaining the reliability and accuracy of established medical technology. This research aims to ultimately address these shortcomings in critically ill pediatric patients. Presented in this work is an alternative, minimally invasive technique that uses microneedles (MN) for the collection of transdermal glucose (TG). Due to their comparable skin properties, diffusion studies were performed on full thickness Yucatan miniature pig skin mounted to an in-line diffusion flow cell and on different skin sites of human subjects. Collected TG samples were measured with a L255C mutant of the E. coli glucose-binding protein (GBP) with an attached fluorescent probe. The binding constant (Kd = 0.67 µM) revealed the micromolar sensitivity and high selectivity of the his-tagged GBP biosensor for glucose, making it suitable for TG measurements. In both the animal and human models, skin permeability and TG diffusion across the skin increased with MN application. For intact and MN-treated human skin, a significant positive linear correlation (r > 0.95, p < 0.01) existed between TG and BG. The micromolar sensitivity of GBP minimized the volume required for interstitial fluid glucose analysis allowing MN application time (30 s) to be shortened compared to other studies. This time reduction can help in eliminating skin irritation issues and improving practical use of the technique by caregivers in the hospital. In addition, the his-tagged optical biosensor used in this work can be immobilized and used with a portable sensing fluorometer device at the point of care (POC) making this minimally invasive technology more ideal for use in the pediatric intensive care unit. Graphical abstract ᅟ.

Pediatric Anti-N-Methyl-d-Aspartate Receptor Encephalitis: A Review with Pooled Analysis and Critical Care Emphasis.

PURPOSE: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is being recognized with increasing frequency among children. Given the paucity of evidence to guide the critical care management of these complex patients, we provide a comprehensive review of the literature with pooled analysis of published case reports and case series. METHODS: We performed a comprehensive literature search using PubMed, Scopus, EMBASE, and Web of Science for relevant published studies. The literature search was conducted using the terms NMDA, anti-NMDA, Anti-N-methyl-d-aspartate, pediatric encephalitis, and anti-NMDAR and included articles published between 2005 and May 1, 2016. RESULTS: Forty-eight references met inclusion criteria accounting for 373 cases. For first-line treatments, 335 (89.8%) received high-dose corticosteroids, 296 received intravenous immunoglobulin (79.3%), and 116 (31%) received therapeutic plasma exchange. In these, 187 children (50.1%) had a full recovery with only minor deficits, 174 patients (46.7%) had partial recovery with major deficits, and 12 children died. In addition, 14 patients were reported to require mechanical ventilation. CONCLUSION: Anti-NMDA encephalitis is a formidable disease with great variation in clinical presentation and response to treatment. With early recognition of this second most common cause of pediatric encephalitis, a multidisciplinary approach by physicians may provide earlier access to first- and second-line therapies. Future studies are needed to examine the efficacy of these current therapeutic strategies on long-term morbidity.

High-Flow Nasal Cannula Utilization in Pediatric Critical Care.

BACKGROUND: High-flow nasal cannula (HFNC) is increasingly utilized in pediatrics, delivering humidified air and oxygen for respiratory conditions causing hypoxia and distress. In the neonatal ICU, it has been associated with better tolerance, lower complications, and lower cost. Few data exist regarding indications for use and the epidemiology of disease/pathology that warrants HFNC in the pediatric ICU. METHODS: This study is a retrospective cohort study of patients admitted to a tertiary children's hospital pediatric ICU and placed on HFNC from October 1, 2011 to October 31, 2013. Descriptive statistics were used to describe demographics and utilization data. t test comparisons were used for comparison data. RESULTS: Over the enrollment study period, 620 subjects with HFNC were managed, which represented 27% of total ICU admissions. The average age was 3.74 y (range 0-18.1 y), and subjects were 44% female and 65% African American. Reported primary indications for the utilization of HFNC were status asthmaticus (24%), status asthmaticus with pneumonia (17%), and bronchiolitis (16%). Of the subjects admitted with a primary diagnosis of status asthmaticus, 41% required management with terbutaline. Respiratory viral infections were detected by polymerase chain reaction in 334 subjects managed with HFNC (53.8%) and included 260 subjects testing positive for rhinovirus/enterovirus. When compared with all other respiratory viral illness, subjects with rhinovirus/enterovirus required a higher peak flow (14.9 L vs 13.1 L, P = .01); however, this was an older population, and peak oxygen concentration did not differ between the 2 groups (49.8% vs 47.1%, P = .25). HFNC was used as postextubation support in 16% of the subjects. Of the 63 subjects with congenital heart disease, 92% of the utilization was postextubation. CONCLUSIONS: HFNC was utilized in 27% of all pediatric ICU admissions for a wide range of indications. Development of protocols for the initiation, escalation, and weaning of HFNC would optimize the utilization.

Extracorporeal Membrane Oxygenation for Neonates with Congenital Renal and Urological Anomalies and Pulmonary Hypoplasia: A Case Report and Review of the Extracorporeal Life Support Organization Registry.

Objective Congenital anomalies of the kidney and urinary tract constitute up to 30% of anomalies identified in the neonatal period. In utero oligohydramnios is often associated with pulmonary hypoplasia and respiratory failure in the neonate who may not be responsive to mechanical ventilation. Placement of these neonates on extracorporeal membrane oxygenation (ECMO) remains controversial and is considered in most centers to be a relative contraindication. The objective of this study is to use the Extracorporeal Life Support Organization (ELSO) database to describe the outcomes and complications of patients with congenital renal and urogenital anomalies with pulmonary hypoplasia who underwent ECMO in the neonatal period. Data Sources Data from the ELSO registry were retrospectively reviewed for all patients with congenital renal and urogenital anomalies with pulmonary hypoplasia treated with ECMO support between 1990 and November 2014 using ICD-9 diagnosis codes. Data Synthesis We identified 45 patients. The average age of the patient at the time of ECMO was 1.7 days (range: 0-14 days) and weight was 3.1 kg (interquartile range [IQR]: 2.5-3.3). Patients spent an average of 162 hours on ECMO (IQR: 81-207). The majority of patients were managed with venoarterial ECMO (60%), and the overall survival of this cohort was 42%. Survivors had higher weights (3.4 vs. 2.8 kg; p < 0.019) and were more likely to be male (90 vs. 44%; p < 0.002). Patients with obstructive urogenital lesions had an overall survival of 71 versus 16.6% in patients with a primary intrinsic renal diagnosis ( p = 0.004). Renal replacement therapy was required in 51% of the patients during their ECMO support. Conclusion Neonates with renal or urogenital disease and pulmonary hypoplasia have an overall survival rate of 42%. Patients with a diagnosis of urogenital obstruction have much more favorable outcomes when compared with those with intrinsic renal disease such as polycystic kidney disease.

Enterovirus D68 in Critically Ill Children: A Comparison With Pandemic H1N1 Influenza.

OBJECTIVE: In 2014, the Unites States experienced an outbreak of enterovirus D68 associated with severe respiratory illness. The clinical characteristics associated with severe illness from enterovirus D68 during this outbreak compared with those associated with the 2009 H1N1 influenza virus outbreak are unknown. DESIGN AND SETTING: In this retrospective cohort study, we characterized the clinical features of children with enterovirus D68 admitted to the PICU between August 1, 2014, and November 1, 2014, and compared them with critically ill children infected with H1N1 influenza during the pandemic admitted between May 1, 2009, and January 31, 2010. PATIENTS: PICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ninety-seven severely ill children with enterovirus D68 infections were compared with 68 children infected with H1N1 influenza during the 2009 pandemic. Children with enterovirus D68 were more likely to have asthma (62% vs 23%; p < 0.001) and present with reactive airway disease exacerbations, with greater receipt of albuterol (94% vs 49%) and steroids (89% vs 40%; p < 0.0001 for both). Although more children with enterovirus D68 were admitted to the ICU compared with those with H1N1 influenza, they had a shorter hospital length of stay (4 vs 7 d; p < 0.0001), with lower intubation rates (7% vs 44%), vasopressor use (3% vs 32%), acute respiratory distress syndrome (3% vs 24%), shock (0% vs 16%), and death (0% vs 12%; p < 0.05 for all). Compared with children with other enteroviruses and rhinoviruses, children with enterovirus D68 were more likely to have a history of asthma (64% vs 45%) or multiple prior wheezing episodes (54% vs 34%; p < 0.01 for both). CONCLUSIONS: Critically ill children with enterovirus D68 were more likely to present with reactive airway disease exacerbations, whereas children with H1N1 influenza were more likely to present with pneumonia. Compared with the pandemic H1N1 influenza outbreak, the enterovirus D68 outbreak resulted in more children requiring admission to the ICU, but was associated with less severe outcomes.

Optimizing Team Dynamics: An Assessment of Physician Trainees and Advanced Practice Providers Collaborative Practice.

OBJECTIVES: The presence of advanced practice providers has become increasingly common in many ICUs. The ideal staffing model for units that contain both advanced practice providers and physician trainees has not been described. The objectives of this study were to evaluate ICU staffing models that include physician trainees and advanced practice providers and their effects on patient outcomes, resident and fellow education, and training experience. A second aim was to assess strategies to promote collaboration between team members. DATA SOURCES: PubMed, CINAHL, OVID MEDLINE, and Cochrane Review from 2002 to 2015. STUDY SELECTION: Experimental study designs conducted in an ICU setting. DATA EXTRACTION: Two reviewers screened articles for eligibility and independently abstracted data using the identified search terms. DATA SYNTHESIS: We found 21 articles describing ICU team structure and outcomes. Four articles were found describing the impact of advanced practice providers on resident or fellow education. Two articles were found discussing strategies to promote collaboration between advanced practice providers and critical care fellows or residents. CONCLUSIONS: Several articles were identified describing the utilization of advanced practice providers in the ICU and the impact of models of care on patient outcomes. Limited data exist describing the impact of advanced practice providers on resident and fellow education and training experience. In addition, there are minimal data describing methods to enhance collaboration between providers. Future research should focus on determining the optimal ICU team structure to improve patient outcomes, education of trainees, and job satisfaction of team members and methods to promote collaboration between advanced practice providers and physicians in training.

Hospitalized Children With Encephalitis in the United States: A Pediatric Health Information System Database Study.

OBJECTIVES: Given the paucity of data on resource utilization among children with encephalitis, the objective of this study was to describe the epidemiology and evaluate resource utilization and discharge data of children with encephalitis admitted to US hospitals from 2004 to 2013. METHODS: We conducted a retrospective cohort study utilizing the Pediatric Health Information System database of children aged 0 to 18 years with the International Classification of Diseases, Ninth Revision codes for encephalitis from 2004 to 2013. Only the initial admissions were included, and the age group analyzed was 0 to 18 years. RESULTS: Among 7298 children with encephalitis, 2933 (40%) were admitted to a pediatric intensive care unit. The median age was nine years, the overall median length of stay was 16 days, and children requiring critical care had a median length of stay of 25 days. Children in the pediatric intensive care unit were more likely to have seizures (P <0.001) and head magnetic resonance imaging (P <0.001) than children on the floor. Similarly, children requiring critical care were more likely to have a broad diagnostic evaluation sent including cerebrospinal fluid cultures, blood bacterial and fungal cultures, western equine encephalitis antibody, St. Louis equine encephalitis antibody, varicella-zoster serology, human immunodeficiency virus 1 antibody, human immunodeficiency virus DNA polymerase chain reaction, acid-fast stain, and Lyme disease serology. Seventeen percent of children were treated with intravenous immunoglobulin, and 4% underwent plasmapheresis. There was a trend of increasing use of intravenous immunoglobulin and plasmapheresis in children with encephalitis over the study period. A total of 5944 (81%) children were discharged home, and the mortality in this cohort was 3% (230). The mean charges for hospitalization for a child with encephalitis was $64,604 and for those requiring critical care was $260,012. CONCLUSIONS: Encephalitis is a significant cause of morbidity and mortality in children. Children with encephalitis admitted to the pediatric intensive care unit are more likely to have seizures and to undergo a more extensive evaluation to determine the cause of encephalitis. Use of plasmapheresis and intravenous immunoglobulin is on the rise in hospitalized children. Prospective studies are necessary to better understand treatment and intervention strategies for children with encephalitis and their impact on outcomes.

Enhanced allergic responsiveness after early childhood infection with respiratory viruses: Are long-lived alternatively activated macrophages the missing link?

Early childhood infection with respiratory viruses, including human rhinovirus, respiratory syncytial virus (RSV) and influenza, is associated with an increased risk of allergic asthma and severe exacerbation of ongoing disease. Despite the long recognition of this relationship, the mechanism linking viral infection and later susceptibility to allergic lung inflammation is still poorly understood. We discuss the literature and provide new evidence demonstrating that these viruses induce the alternative activation of macrophages. Alternatively activated macrophages (AAM) induced by RSV or influenza infection persisted in the lungs of mice up to 90 days after initial viral infection. Several studies suggest that AAM contribute to allergic inflammatory responses, although their mechanism of action is unclear. In this commentary, we propose that virus-induced AAM provide a link between viral infection and enhanced responses to inhaled allergens.

Anaphylaxis to scorpion antivenin and its management following envenomation by Indian red scorpion, Mesobuthus tamulus.

Mesobuthus tamulus is an Indian red scorpion that is responsible for numerous cases of scorpion stings in the Indian subcontinent. Antivenin, vasodilators, and benzodiazepines are medications of choice in the treatment of scorpion bites. Adverse reactions such as anaphylaxis to antivenin have been infrequently described in the literature. We, herein, present a case of a 42-year-old man stung by Indian red scorpion while gardening at home in India, who presented with extreme pain at the sting site and signs of cardio-toxicity. He was treated with scorpion antivenin and vasodilators but developed anaphylaxis to antivenin. We discuss management strategies. Anaphylaxis to antivenin should be on the differential during management of scorpion bites because classical signs of anaphylaxis may be absent.

A comparison of H1N1 influenza among pediatric inpatients in the pandemic and post pandemic era.

BACKGROUND: The novel influenza A H1N1 (A[H1N1]pdm09) strain emerged in 2009, contributing to significant morbidity and mortality. It is not known whether illness associated with A(H1N1) pdm09 in the post-pandemic era exhibits a similar disease profile. OBJECTIVE: The objectives of this study were to compare the burden of disease of A(H1N1) pdm09 influenza from the 2009 pandemic year to the post-pandemic years (2010-2014), and to explore potential reasons for any differences. STUDY DESIGN: We conducted a retrospective cohort study of inpatients admitted to Children's Hospital Colorado with a positive respiratory specimen for influenza from May-December, 2009 and December, 2010-April, 2014. Univariate and multivariate analyses were conducted to compare the demographics and clinical characteristics of patients with H1N1 during the two periods. RESULTS: There were 388 inpatients with influenza A(H1N1) pdm09 in 2009, and 117 during the post-pandemic years. Ninety-four percent of all H1N1 during the post-pandemic era was observed during the 2013-2014 influenza season. Patients with A(H1N1) pdm09 during the post-pandemic year were less likely to have an underlying medical condition (P<0.01). Patients admitted to the ICU during the post-pandemic year had a lower median age (5 vs 8 years, P=0.01) and a lower proportion of patients were intubated, had mental status changes, and ARDS compared with the pandemic years, (P<0.01 for all), with decreased mortality (P=0.02). CONCLUSION: Patients with influenza A(H1N1) pdm09 during the post-pandemic years appeared to have less severe disease than patients with A(H1N1) pdm09 during the pandemic year. The reasons for this difference are likely multifactorial.