An update on the safety of prescribing opioids in pediatrics.

INTRODUCTION: The opioid abuse epidemic and its toll on the adolescent population have heightened awareness for safer opioid prescribing practices in pediatric pain management. Opioids remain the mainstay of therapy for severe pain, although there is an emphasis on multimodal therapy. Areas covered: In this update, the authors present information on parenteral/oral opioids commonly used in pediatrics. Recommendations for opioid use in special circumstances including neonates and developmental pharmacokinetic concerns are discussed. Due to noticeable interindividual variability, pharmacogenomics may be important for tailoring pain regimens. In particular, the role of CYP2D6 phenotypes on opioid selection/dosing and clinical implications are discussed. A summary of adverse effects and opioid safety data, and the role of regulations, risk assessment, Centers for Disease Control and Prevention guidelines, follow-up, and monitoring for compliance in opioid prescribing, are detailed. Expert opinion: 'One size does not fit all' describes the need for public policies focused on pediatric pain and opioid use, as children are not 'little adults.' Clinical trials to evaluate pharmacokinetics-pharmacodynamics of opioids are currently lacking. Development of novel biased opioid agonists, clinical integration of genetics in informed decision-making, and emphasis on top-down approaches to pain management will be key to decrease opioid reliance.

Role for a novel Usher protein complex in hair cell synaptic maturation.

The molecular mechanisms underlying hair cell synaptic maturation are not well understood. Cadherin-23 (CDH23), protocadherin-15 (PCDH15) and the very large G-protein coupled receptor 1 (VLGR1) have been implicated in the development of cochlear hair cell stereocilia, while clarin-1 has been suggested to also play a role in synaptogenesis. Mutations in CDH23, PCDH15, VLGR1 and clarin-1 cause Usher syndrome, characterized by congenital deafness, vestibular dysfunction and retinitis pigmentosa. Here we show developmental expression of these Usher proteins in afferent spiral ganglion neurons and hair cell synapses. We identify a novel synaptic Usher complex comprised of clarin-1 and specific isoforms of CDH23, PCDH15 and VLGR1. To establish the in vivo relevance of this complex, we performed morphological and quantitative analysis of the neuronal fibers and their synapses in the Clrn1-/- mouse, which was generated by incomplete deletion of the gene. These mice showed a delay in neuronal/synaptic maturation by both immunostaining and electron microscopy. Analysis of the ribbon synapses in Ames waltzer(av3J) mice also suggests a delay in hair cell synaptogenesis. Collectively, these results show that, in addition to the well documented role for Usher proteins in stereocilia development, Usher protein complexes comprised of specific protein isoforms likely function in synaptic maturation as well.

The comparative usefulness of orthostatic testing and tilt table testing in the evaluation of autonomic-associated dizziness.

OBJECTIVE: To elucidate the usefulness of clinical orthostatic blood pressure testing (COBP) as a screening tool for autonomic dysfunction. STUDY DESIGN: In this retrospective case review, the records of 156 consecutive patients with nonotologic dizziness as the primary complaint seen in an academic neurotology clinic between 2005 and 2009 were reviewed. The objective of this study was accomplished by comparing the diagnostic yield of COBP with that of head-upright tilt table testing (HUT) and assessing the sensitivity and specificity of COBP in predicting an abnormal HUT in patients with nonotologic dizziness. SETTING: Ambulatory tertiary referral center. PATIENTS: Patients presenting to the clinic with dizziness without otologic cause. INTERVENTION(S): Clinical evaluation, orthostatic blood pressure testing, and HUT. MAIN OUTCOME MEASURE(S): The primary outcome assessed in this study was patient blood pressure. Blood pressures were measured in the clinic in the following order: supine, sitting, and standing. Positive COBP was defined as a reduction in systolic or diastolic blood pressure greater than 20 or 10 mm Hg, respectively, or both, within 3 minutes of sitting from supine or standing from sitting. For comparison, HUT was used as the gold standard. A positive HUT was defined as a reduction in systolic or diastolic blood pressure greater than 20 or 10 mm Hg, respectively, or both, relative to baseline at any point after initiation of HUT. RESULTS: Forty patients were referred for HUT. Twenty-four (61.5%) of these patients were deemed to have a positive response. Thirty-three patients (85%) referred to HUT were initially evaluated with COBP, which revealed orthostatic hypotension (OH) in 8 patients (24%). COBP was calculated to have sensitivity and specificity of 21% and 71%, respectively, when asymptomatic OH was included in the positivity criteria. When asymptomatic OH was excluded from the positivity criteria, the sensitivity and specificity remained similar at 25% and 76%, respectively. However, the exclusion of asymptomatic OH from the positivity criteria resulted in a decrease in the positive predictive value from 50% to 25% and an increase in the negative predictive value from 40% to 76%. Overall, HUT detected 16 patients with an abnormal result that were missed by COBP testing. CONCLUSION: Evaluation for autonomic dysfunction should be part of the comprehensive evaluation of a dizzy patient, involving, at a minimum, orthostatic testing of blood pressure and heart rate. Patients with nonotologic dizziness and light-headedness with a normal neurotologic evaluation can reasonably be referred for HUT, even in the presence of normal in-office orthostatic testing.

Ectopic glioneuronal tissue in the middle cranial fossa region. Report of four cases.

The growth of ectopic glioneuronal tissue in the middle cranial fossa region is an uncommon event, with very few cases reported in the literature. In this paper the authors document 4 cases of ectopic glioneuronal tissue in the middle cranial fossa in children and briefly describe the clinical course and pathology. All of the children presented within the first 6 months of life. Two children presented with facial masses, 1 with airway obstruction, and another with proptosis of the right eye. Each child underwent a customized surgery dependent on the location and characteristics of the harbored lesion. Ectopic glioneuronal masses in the middle cranial fossa are rare and benign congenital tumors, and affected newborns can present with airway obstruction, feeding difficulties, and facial deformity depending on the lesion location. Determining an appropriate surgical approach and strategy is a significant challenge and may involve a multidisciplinary team of craniofacial plastic surgeons, otolaryngologists, and neurosurgeons. Although these lesions share clinical and anatomical similarities, because of their histopathological heterogeneity, it is unlikely that they represent a single pathological entity. The long-term outcome in these children is still unknown and is an area for future study. The pathogenesis of these lesions also remains unknown and may be revealed in future research.

Surgical management and outcome of scalp subcutaneous granuloma annulare in children: case report.

OBJECTIVE: Subcutaneous granuloma annulare (SGA) is a benign inflammatory disorder that rarely affects the scalp. We report 5 cases of children with SGA scalp lesions and discuss our clinical experience and the characteristic findings, diagnostic evaluation, method of treatment, and course of the disease. CLINICAL PRESENTATION: Five patients presented with multiple subcutaneous nodules at single or multiple sites overlying the scalp. A retrospective review of the medical, surgical, and pathology records of the 5 patients was conducted. INTERVENTION: All scalp lesions were excised and were confirmed histologically to be SGA nodules. In 4 of the 5 patients, the nodules were nontender and nonmobile. The mean number of lesions was 4.2. The mean age of patients at presentation was 3.8 years. Of the 5 patients, 4 experienced at least 1 recurrence of a solitary lesion at either the same site or a different site. In the 80% of patients who experienced a recurrence, all lesions recurred less than 1 year postoperatively, except in the case of 1 patient who continued to experience a disappearance and reappearance of lesions at 72 months. The ultimate diagnosis of all lesions was established through biopsy and subsequent microscopic evaluation. No postoperative complications were noted. CONCLUSION: Granuloma annulare should be included in the differential diagnosis whenever a scalp subcutaneous superficial nodule is observed. Although many modalities of treatment for SGA nodules are used, recurrence is common, even with surgical excision.