OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin.

The linear ubiquitin (Ub) chain assembly complex (LUBAC) is an E3 ligase that specifically assembles Met1-linked (also known as linear) Ub chains that regulate nuclear factor κB (NF-κB) signaling. Deubiquitinases (DUBs) are key regulators of Ub signaling, but a dedicated DUB for Met1 linkages has not been identified. Here, we reveal a previously unannotated human DUB, OTULIN (also known as FAM105B), which is exquisitely specific for Met1 linkages. Crystal structures of the OTULIN catalytic domain in complex with diubiquitin reveal Met1-specific Ub-binding sites and a mechanism of substrate-assisted catalysis in which the proximal Ub activates the catalytic triad of the protease. Mutation of Ub Glu16 inhibits OTULIN activity by reducing kcat 240-fold. OTULIN overexpression or knockdown affects NF-κB responses to LUBAC, TNFα, and poly(I:C) and sensitizes cells to TNFα-induced cell death. We show that OTULIN binds LUBAC and that overexpression of OTULIN prevents TNFα-induced NEMO association with ubiquitinated RIPK1. Our data suggest that OTULIN regulates Met1-polyUb signaling.

The Management of Children and Youth With Pediatric Mental and Behavioral Health Emergencies.

Mental and behavioral health (MBH) emergencies in children and youth continue to increasingly affect not only the emergency department (ED), but the entire spectrum of emergency medical services for children, from prehospital services to the community. Inadequate community and institutional infrastructure to care for children and youth with MBH conditions makes the ED an essential part of the health care safety net for these patients. As a result, an increasing number of children and youth are referred to the ED for evaluation of a broad spectrum of MBH emergencies, from depression and suicidality to disruptive and aggressive behavior. However, challenges in providing optimal care to these patients include lack of personnel, capacity, and infrastructure, challenges with timely access to a mental health professional, the nature of a busy ED environment, and paucity of outpatient post-ED discharge resources. These factors contribute to prolonged ED stays and boarding, which negatively affects patient care and ED operations. Strategies to improve care for MBH emergencies, including systems level coordination of care, is therefore essential. The goal of this policy statement and its companion technical report is to highlight strategies, resources, and recommendations for improving emergency care delivery for pediatric MBH.

Parent Intent and Willingness to Immunize Children Against Influenza in the Pediatric Emergency Department.

OBJECTIVES: To determine rates of influenza immunization among children treated in a pediatric emergency department (ED) and to ascertain parent willingness for children to receive influenza vaccine (IV) in the ED. METHODS: Interviews were conducted with parents of children 6 months or older evaluated in the ED for minor illness or injury. Demographic data, IV history, and intent and willingness to receive future IV were recorded during the summer of 2013. Participants were contacted in March 2014 to assess IV status, barriers to obtaining IV, and willingness to obtain IV in the ED. Chart review determined number of patients who were at high risk. RESULTS: Of 457 families approached, 285 (62%) were enrolled. Two hundred forty-two (85%) intended to vaccinate; 83% reported willingness to receive IV at a future ED visit. Common reasons for not receiving IV were concerns about adverse effects (31%) and lack of time or interest (24%). Of the 224 participants (79%) reached in follow-up, 112 (50%) had received IV in the prior season. Among those who did not receive IV, 65 (66%) had intended to vaccinate, and 54 (55%) indicated they would have accepted IV in the ED. Fifty-three (54%) of unvaccinated patients at follow-up had high risk of influenza complications. CONCLUSIONS: Our data support an IV program in the pediatric ED as a means of increasing vaccination rates, particularly among high-risk patients. Parents are often concerned about adverse effects of IV, and providers should target education in this area.

Bedside ultrasound diagnosis of nonangulated distal forearm fractures in the pediatric emergency department.

OBJECTIVES: Ultrasound (US) may be a useful tool for rapidly diagnosing fractures. Our objective was to determine the accuracy of US as compared with radiographs in the detection of nonangulated distal forearm fractures. METHODS: Distal forearm US was performed and interpreted at the bedside by a pediatric emergency medicine physician before radiography in a prospective sample of children with possible nonangulated distal forearm fractures. A second pediatric emergency medicine physician with extensive US experience gave a final interpretation of the images. This second reviewer was blinded to both clinical and radiographic findings. The primary outcome was accuracy in the detection of fracture via the blinded reviewer's US interpretation when compared with the radiologist's clinical radiography results. Patient-reported FACES pain scores (range, 0-5) associated with both US and radiography were compared. RESULTS: Of 101 enrolled patients, 46 had a fracture detected by the radiologist. When compared with radiographs, the blinded US interpretation had an overall accuracy of 94% (95% confidence interval [CI], 88%-99%). Sensitivity and specificity were 96% (95% CI, 85%-99%) and 93% (95% CI, 82%-98%), respectively. Positive predictive value was 92%, and negative predictive value was 96%. Mean FACES pain scores were higher following radiography than US (1.7 vs 1.2, respectively; P = 0.004). CONCLUSIONS: For the diagnosis of nonangulated distal forearm fractures in children, bedside US holds promise as a diagnostic modality, particularly with appropriate training. Ultrasound is at least no more painful that traditional radiographs. Pediatric emergency medicine physicians should consider becoming proficient in this application.

Single-dose dexamethasone for mild-to-moderate asthma exacerbations: effective, easy, and acceptable.

QUESTION: I prescribe oral steroids for children in my community when they suffer asthma exacerbation. How many doses of steroids are recommended? Do all children need to take steroids for 5 days? ANSWER: Traditionally, mild-to-moderate pediatric asthma exacerbations have been treated with a short course of oral steroids-often 5 days of prednisone or prednisolone. However, recent evidence suggests a similar outcome can be acheived with a single dose of dexamethasone, which has a longer half-life and powerful anti-inflammatory effects, along with easier administration and compliance. Single-dose dexamethasone offers a simple and reliable treatment for these patients in office, urgent care, and emergency department settings.

Randomized clinical trial of docusate, triethanolamine polypeptide, and irrigation in cerumen removal in children.

BACKGROUND: Cerumen obstructing visualization of the tympanic membrane in children is a common and frustrating problem. Docusate sodium, triethanolamine polypeptide, and saline were compared to determine their effectiveness in relieving cerumen obstruction in children. METHODS: A randomized, controlled, double-blind trial was performed on pediatric patients aged 6 months through 5 years with cerumen obstruction. The enrolling physician determined whether the cerumen completely or partially obstructed visualization of the tympanic membrane. One milliliter of docusate sodium, triethanolamine polypeptide, or normal saline as control was placed into the patient's ear canal. If the tympanic membrane was not completely visualized after 15 minutes, the ear was irrigated with 50 mL of tepid water. Irrigation was repeated a second time if needed. The main outcome was the proportion of tympanic membranes that were completely visualized after cerumeno-eblytic agents or control saline, alone or with irrigation if needed. RESULTS: Of 92 patients enrolled, 34 received docusate sodium; 30, triethanolamine polypeptide; and 28, saline. Mean +/- SD patient age was 34.7 +/- 18.1 months, and 50 (54%) of the patients were girls. Groups were similar in age, race, sex, ear enrolled, wax consistency, and degree of obstruction. There was no significant difference in the proportion of tympanic membranes completely visualized after treatment with docusate (18/34; 53%), triethanolamine polypeptide (13/30; 43%), or saline (19/28; 68%) (P =.17). CONCLUSION: Application of docusate sodium or triethanolamine polypeptide did not significantly improve the proportion of tympanic membranes that were completely visualized vs application of the saline control.

Bedside ultrasound diagnosis of clavicle fractures in the pediatric emergency department.

OBJECTIVES: Clavicle fractures are among the most common orthopedic injuries in children. Diagnosis typically involves radiographs, which expose children to radiation and may consume significant time and resources. Our objective was to determine if bedside emergency department (ED) ultrasound (US) is an accurate alternative to radiography. METHODS: This was a prospective study of bedside US for diagnosing clavicle fractures. A convenience sample of children ages 1-18 years with shoulder injuries requiring radiographs was enrolled. Bedside US imaging and an unblinded interpretation were completed by a pediatric emergency physician (EP) prior to radiographs. A second interpreter, a pediatric EP attending physician with extensive US experience, determined a final interpretation of the US images at a later date. This final interpretation was blinded to both clinical and radiography outcomes. The reference standard was an attending radiologist's interpretation of radiographs. The primary outcome was the accuracy of the blinded US interpretation for detecting clavicle fractures compared to the reference standard. Secondary outcome measures included the interrater reliability of the unblinded bedside and the blinded physicians' interpretations and the FACES pain scores (range, 0-5) for US and radiograph imaging. RESULTS: One-hundred patients were included in the study, of whom 43 had clavicle fractures by radiography. The final US interpretation had 95% sensitivity (95% confidence interval [CI] = 83% to 99%) and 96% specificity (95% CI = 87% to 99%), and overall accuracy was 96%, with 96 congruent readings. Positive and negative predictive values (PPVs and NPVs, respectively) were 95% (95% CI = 83% to 99%) and 96% (95% CI = 87% to 99%), respectively. Interrater reliability (kappa) was 0.74 (95% CI = 0.60 to 0.88). FACES pain scores were available for the 86 subjects who were at least 5 years old. Pain scores were similar during US and radiography. CONCLUSIONS: Compared to radiographs, bedside US can accurately diagnose pediatric clavicle fractures. US causes no more discomfort than radiography when detecting clavicle fractures. Given US's advantage of no radiation, pediatric EPs should consider this application.