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Importance: Prior publications have reported the sporadic development of sensorineural hearing loss (SNHL) after intravenous or high-dose macrolide therapy for adults with comorbid conditions, but investigations of the auditory effect of oral outpatient dosing for children, adolescents, and young adults have been limited., Objective: To determine whether broad-based outpatient use of oral macrolide therapy is associated with increased risk of pediatric SNHL through nationally representative analyses., Design, Setting, and Participants: A retrospective case-control study of 875 matched pairs of children, adolescents, and young adults was performed, matching on age, sex, and the time elapsed since prescription date. All eligible pediatric patients were included, with matched control participants from the TRICARE US military health insurance system who were evaluated between October 1, 2009, and September 30, 2014., Exposures: Oral outpatient macrolide treatment compared with penicillin use among pediatric patients., Main Outcomes and Measures: The clinical outcome of interest was SNHL in children, adolescents, and young adults. Multivariable conditional logistic regression was used to compare the risk of prior macrolide exposure with penicillin exposure, adjusted for other risk factors and potential confounders. Four time frames between exposure and diagnosis were additionally assessed., Results: There were 875 eligible matched pairs of children, adolescents, and young adults included. The mean (SD) age of the participants was 5.7 (4.9) years; 1082 participants were male (62%), 58 were Asian (3%), 254 were Black (15%), 1152 were White (66%), and 286 were of Native American and other (no further breakdown was available in the TRICARE database) race and ethnicity (16%). In multivariable analysis, participants who had SNHL had increased odds of having received a macrolide prescription compared with a penicillin prescription when all time frames from exposure were included (adjusted odds ratio, 1.31; 95% CI, 1.05-1.64). There were significantly higher odds of macrolide exposure than penicillin exposure when diagnosis and testing occurred more than 180 days after antibiotic exposure (adjusted odds ratio, 1.79; 95% CI, 1.23-2.60)., Conclusions and Relevance: In this case-control study of a nationally representative patient population, findings suggest that children, adolescents, and young adults with SNHL had increased odds of outpatient oral macrolide use compared with penicillin use, particularly when having received a diagnosis more than 180 days after exposure. Further study of the association of macrolides with SNHL in children, adolescents, and young adults is warranted.

The coronavirus 2019 pandemic has increased the use of powered air-purifying respirator (PAPR) devices, which produce appreciable noise levels during filtration. Our objective was to determine if active PAPR usage significantly impairs auditory communication in health care providers. We additionally sought to assess what volume of speech presentation was required for adequate communication with providers wearing a PAPR. In subjects with normal hearing at baseline, audiometric data demonstrated a 93% (95% CI, 86%-99%) decrease in word recognition scores during active PAPR usage. Presentation at 85 to 90 dB was needed to obtain word recognition scores similar to baseline in subjects with normal hearing without a PAPR. Pure tone averages also significantly decreased with PAPR usage, by 54 dB (95% CI, 46-62). Active PAPR usage has a substantial impact on auditory perception when utilized by health care providers. The potential longer-term effect of these devices on providers with regular active usage is of interest for future study.

Hypothesis: Computed tomography (CT) density measurement can be used to objectively distinguish otosclerosis from normal bone and to determine histologic grades of otosclerosis., Background: Otosclerosis can be seen on CT as subtle radiolucent areas. An objective radiologic measurement that corresponds to known otosclerosis pathology may improve diagnostic accuracy, and could be used as a radiologic biomarker for otosclerosis grade., Methods: A blinded, randomized evaluation of both histologic grade on histopathology slides and CT density measurement was performed on 78 human temporal bone specimens (31 with otosclerosis and 47 controls) that had undergone high-resolution multi-detector CT before histologic processing. Assessments were performed at 11 regions of interest (ROIs) in the otic capsule for each specimen., Results: The CT density measurement mean (Hounsfield Units) ± standard deviation for all ROIs (Nos. 1-9) was 2245 ± 854 for grade 0 (no otosclerosis, n = 711), 1896 ± 317 for grade 1 (inactive otosclerosis, n = 109), and 1632 ± 255 for grades 2 and 3 combined (mixed/active otosclerosis, n 35). There was a strong inverse correlation of CT density to histologic grade at ROIs Nos. 1-5 (ANOVA, p < 0.0001). The inter-rater reliability for CT density was very good (correlation coefficient 0.87, p < 0.05). ROC curves suggested a cut-off of 2,150HU to distinguish otosclerosis from normal bone, and 1,811HU to distinguish low grade from mixed/high grade otosclerosis., Conclusions: In human temporal bone specimens, CT density may be used to distinguish normal bone from bone involved by otosclerosis. A higher histologic grade (i.e., indicating a more active otosclerotic focus) correlated with lower density., Competing Interests: Conflicts of Interest: A.M.Q. had sponsored research agreements and consulting with Frequency Therapeutics, consulting with Alcon Corp., sponsored research agreement and licensing of a patent with Grace Medical, research study participant for Akouos., (Copyright © 2022, Otology & Neurotology, Inc.)

Background: The development of systemic treatment options leveraging the molecular landscape of advanced thyroid cancer is a burgeoning field. This is a multidisciplinary evidence-based statement on the definition of advanced thyroid cancer and its targeted systemic treatment., Methods: An expert panel was assembled, a literature review was conducted, and best practice statements were developed. The modified Delphi method was applied to assess the degree of consensus for the statements developed by the author panel., Results: A review of the current understanding of thyroid oncogenesis at a molecular level is presented and characteristics of advanced thyroid cancer are defined. Twenty statements in topics including the multidisciplinary management, molecular evaluation, and targeted systemic treatment of advanced thyroid cancer are provided., Conclusions: With the growth in targeted treatment options for thyroid cancer, a consensus definition of advanced disease and statements regarding the utility of molecular testing and available targeted systemic therapy is warranted., (© 2022 Wiley Periodicals LLC.)

Children are more likely to experience recurrent laryngeal nerve (RLN) injury during thyroid surgery. Intraoperative nerve monitoring (IONM) may assist in nerve identification and surgical decision making. A literature review of pediatric IONM was performed and used to inform a monitoring technique guide and expert opinion statements. Pediatric IONM is achieved using a variety of methods. When age-appropriate endotracheal tubes with integrated surface electrodes are not available, an alternative method should be used. Patient age and surgeon experience with laryngoscopy influence technique selection; four techniques are described in detail. Surgeons must be familiar with the nuances of monitoring technique and interpretation; opinion statements address optimizing this technology in children. Adult IONM guidelines may offer strategies for surgical decision making in children. In some cases, delay of second-sided surgery may reduce bilateral RLN injury risk., (© 2022 Wiley Periodicals LLC.)

Background: The noninvasive subtype of encapsulated follicular variant of papillary thyroid carcinoma (eFVPTC) has been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reflect the indolent behavior and favorable prognosis of this type of tumor. This terminology change has also de-escalated its management approach from cancer treatment to a more conservative treatment strategy befitting a benign thyroid neoplasm. Objective: To characterize the reduced health care costs and improved quality of life (QOL) from management of NIFTP as a nonmalignant tumor compared with the previous management as eFVPTC. Methods: A cost-effectiveness analysis was performed by creating Markov models to simulate two management strategies for NIFTP: (i) de-escalated management of the tumor as NIFTP involving lobectomy with reduced follow-up, (ii) management of the tumor as eFVPTC involving completion thyroidectomy/radioactive iodine ablation for some patients, and follow-up recommended for carcinoma. The model was simulated for 5 and 20 years following diagnosis of NIFTP. Aggregate costs and quality-life years were measured. One-way sensitivity analysis was performed for all variables. Results: Over a five-year simulation period, de-escalated management of NIFTP had a total cost of $12,380.99 per patient while the more aggressive management of the tumor as eFVPTC had a total cost of $16,264.03 per patient (saving $3883.05 over five years). Management of NIFTP provided 5.00 quality-adjusted life years, whereas management as eFVPTC provided 4.97 quality-adjusted life years. Sensitivity analyses showed that management of NIFTP always resulted in lower costs and greater quality-adjusted life years (QALYs) over the sensitivity ranges for individual variables. De-escalated management for NIFTP is expected to produce ∼$6-42 million in cost savings over a five-year period for these patients, and incremental 54-370 QALYs of increased utility in the United States. Conclusion: The degree of cost savings and improved patient utility of de-escalated NIFTP management compared with traditional management was estimated to be $3883.05 and 0.03 QALYs per patient. We demonstrate that these findings persisted in sensitivity analysis to account for variability in recurrence rate, surveillance approaches, and other model inputs. These findings allow for greater understanding of the economic and QOL impact of the NIFTP reclassification.

Background: The recurrent laryngeal nerve (RLN) can be injured during thyroid surgery, which can negatively affect a patient's quality of life. The impact of intraoperative anatomic variations of the RLN on nerve injury remains unclear. Objectives of this study were to (1) better understand the detailed surgical anatomic variability of the RLN with a worldwide perspective; (2) establish potential correlates between intraoperative RLN anatomy and electrophysiologic responses; and (3) use the information to minimize complications and assure accurate and safe intraoperative neuromonitoring (IONM). Methods: A large international registry database study with prospectively collected data was conducted through the International Neural Monitoring Study Group (INMSG) evaluating 1000 RLNs at risk during thyroid surgery using a specially designed online data repository. Monitored thyroid surgeries following standardized IONM guidelines were included. Cases with bulky lymphadenopathy, IONM failure, and failed RLN visualization were excluded. Systematic evaluation of the surgical anatomy of the RLN was performed using the International RLN Anatomic Classification System. In cases of loss of signal (LOS), the mechanism of neural injury was identified, and functional evaluation of the vocal cord was performed. Results: A total of 1000 nerves at risk (NARs) were evaluated from 574 patients undergoing thyroid surgery at 17 centers from 12 countries and 5 continents. A higher than expected percentage of nerves followed an abnormal intraoperative trajectory (23%). LOS was identified in 3.5% of NARs, with 34% of LOS nerves following an abnormal intraoperative trajectory. LOS was more likely in cases of abnormal nerve trajectory, fixed splayed or entrapped nerves (including at the ligament of Berry), extensive neural dissection, cases of cancer invasion, or when lateral lymph node dissection was needed. Traction injury was found to be the most common form of RLN injury and to be less recoverable than previous reports. Conclusions: Multicenter international studies enrolling diverse patient populations can help reshape our understanding of surgical anatomy during thyroid surgery. There can be significant variability in the anatomic and intraoperative characteristics of the RLN, which can impact the risk of neural injury.

Background: This American Head and Neck Society (AHNS) consensus statement focuses on evidence-based comprehensive pain management practices for thyroid and parathyroid surgery. Overutilization of opioids for postoperative pain management is a major contributing factor to the opioid addiction epidemic however evidence-based guidelines for pain management after routine head and neck endocrine procedures are lacking., Methods: An expert panel was convened from the membership of the AHNS, its Endocrine Surgical Section, and ThyCa. An extensive literature review was performed, and recommendations addressing several pain management subtopics were constructed based on best available evidence. A modified Delphi survey was then utilized to evaluate group consensus of these statements., Conclusions: This expert consensus provides evidence-based recommendations for effective postoperative pain management following head and neck endocrine procedures with a focus on limiting unnecessary use of opioid analgesics., (© 2021 Wiley Periodicals LLC.)

Objective: The overall discriminatory ability of validated instrument scores for computed tomography (CT) findings of chronic rhinosinusitis has limitations and may be modified by multiple factors. To support optimal methods for assessment, we studied which factors could influence this relationship, including the concurrent impact of multiple discrete CT scoring mechanisms, colocalized imaging findings, and nasal comorbid conditions., Study Design: Observational outcomes study., Setting: Academic medical center., Methods: Patients with sinonasal complaints who completed the 22-item Sinonasal Outcome Test (SNOT-22) and underwent CT were included. Multivariate ordinal regression was utilized to assess associations. CT data were quantified with the Lund-Mackay system, Zinreich system, and a direct measure of maximal mucosal thickness. The impact of incidental findings (mucous retention cysts, periapical dental disease) and nasal comorbid conditions was also assessed., Results: A total of 233 patients were included. SNOT-22 nasal scores were significantly associated with CT results when those with incidental findings were excluded, regardless of the radiologic scoring mechanism utilized: Lund-Mackay regression coefficient, 0.321 ( P = .046); Zinreich, 0.340 ( P = .033); and maximum mucosal thickness, 0.316 ( P = .040). This relationship subsided when incidental findings were present. SNOT-22 overall scores, sleep scores, and psychological domain scores had no significant association with imaging results, regardless of radiologic scoring system utilized. Nasal comorbid conditions had inconsistent associations., Conclusions: SNOT-22 nasal domain scores were associated with all 3 radiologic scoring systems when incidental findings were absent but not when they were present. Delineating the presence or absence of these colocalized findings affected the relationship between SNOT-22 scores and radiological results, beyond other concurrent factors.

Objectives: To determine the ability of the reflux symptom index (RSI) to predict objective impedance and pH-probe testing, and to examine the relationship between disease-specific and general health status in patients diagnosed with laryngopharyngeal reflux (LPR)., Methods: Adults presenting to a tertiary care academic center with a primary voice complaint completed the RSI and the Patient-Reported Outcomes Measurement Information System 10-item global health instrument (PROMIS). An RSI score ≥13 was considered abnormal. Objective testing for LPR was performed using hypopharyngeal-esophageal multichannel intraluminal impedance catheter with dual pH (HEMII-pH) testing; a positive test was defined as more than one pharyngeal impedance events over 24 hours. Spearman rho analyses were applied, and the sensitivity and specificity of the RSI to detect HEMII-pH findings were determined., Results: One hundred four patients underwent HEMII-pH testing. Mean scores were 16.7 (95%CI 15.1-18.3) for RSI. Sixty-three (60.6%) patients were diagnosed with LPR by HEMII-pH testing. RSI scores were moderately correlated with PROMIS physical (Spearman rho 0.43, P < 0.0001), social (Spearman rho 0.33, P < 0.0001) and mental health (Spearman rho 0.33, P < 0.0001) scores. The RSI has a sensitivity and specificity of 66.7% and 31.7%, respectively, for detecting pharyngeal events on HEMII-pH testing., Conclusions: There is moderate sensitivity and lack of specificity of the RSI for detecting increased pharyngeal reflux events. Reflux-specific and general health status instruments are correlated. Further investigation could assess the diagnostic ability of RSI compared proximal reflux events on HEMII-pH, as well as whether health status instruments can be used to detect clinically meaningful change in the LPR population., (Copyright © 2019 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To provide a clinical disease state review of recent relevant literature and to generate expert consensus statements regarding the breadth of pediatric thyroid cancer diagnosis and care, with an emphasis on thyroid surgery. To generate expert statements to educate pediatric practitioners on the state-of-the-art practices and the value of surgical experience in the management of this unusual and challenging disease in children., Methods: A literature search was conducted and statements were constructed and subjected to a modified Delphi process to measure the consensus of the expert author panel. The wording of statements, voting tabulation, and statistical analysis were overseen by a Delphi expert (J.J.S.)., Results: Twenty-five consensus statements were created and subjected to a modified Delphi analysis to measure the strength of consensus of the expert author panel. All statements reached a level of consensus, and the majority of statements reached the highest level of consensus., Conclusion: Pediatric thyroid cancer has many unique nuances, such as bulky cervical adenopathy on presentation, an increased incidence of diffuse sclerosing variant, and a longer potential lifespan to endure potential complications from treatment. Complications can be a burden to parents and patients alike. We suggest that optimal outcomes and decreased morbidity will come from the use of advanced imaging, diagnostic testing, and neural monitoring of patients treated at high-volume centers by high-volume surgeons., (© AACE published by Elsevier Inc. as a dual publication under license from Wiley Periodicals, LLC.)

Objective: To provide a contemporary resource to update clinicians and researchers on the current state of assessment of patient preferences., Data Sources: Published studies and literature regarding patient preferences, evidence-based practice, and patient-centered management in otolaryngology., Review Methods: Patients make choices based on both physician input and their own preferences. These preferences are informed by personal values and attitudes, and they ideally result from a deliberative evaluation of the risks, benefits, and other outcomes pertaining to medical care. To date, rigorous evaluation of patient preferences for otolaryngologic conditions has not been integrated into clinical practice or research. This installment of the "Evidence-Based Medicine in Otolaryngology" series focuses on formal assessment of patient preferences and the optimal methods to determine them., Conclusions: Methods have been developed to optimize our understanding of patient preferences., Implications for Practice: Understanding these patient preferences may help promote an evidence-based approach to the care of individual patients.

Objectives: To provide a clinical disease state review of recent relevant literature and to generate expert consensus statements regarding the breadth of pediatric thyroid cancer diagnosis and care, with an emphasis on thyroid surgery. To generate expert statements to educate pediatric practitioners on the state-of-the-art practices and the value of surgical experience in the management of this unusual and challenging disease in children., Methods: A literature search was conducted and statements were constructed and subjected to a modified Delphi process to measure the consensus of the expert author panel. The wording of statements, voting tabulation, and statistical analysis were overseen by a Delphi expert (J.J.S.)., Results: Twenty-five consensus statements were created and subjected to a modified Delphi analysis to measure the strength of consensus of the expert author panel. All statements reached a level of consensus, and the majority of statements reached the highest level of consensus., Conclusion: Pediatric thyroid cancer has many unique nuances, such as bulky cervical adenopathy on presentation, an increased incidence of diffuse sclerosing variant, and a longer potential lifespan to endure potential complications from treatment. Complications can be a burden to parents and patients alike. We suggest that optimal outcomes and decreased morbidity will come from the use of advanced imaging, diagnostic testing, and neural monitoring of patients treated at high-volume centers by high-volume surgeons., (Copyright © 2020 AACE. All rights reserved.)

Objective: To determine whether psychological status is an effect modifier of the previously observed low discriminatory capacity of Sinonasal Outcome Test-22 (SNOT-22) scores for Lund-Mackay computed tomography (CT) results., Study Design: Observational outcomes study., Setting: Tertiary care center., Subjects and Methods: We assessed patients presenting with chronic sinonasal complaints who underwent CT of the sinuses within 1 month of completing the SNOT-22 instrument. SNOT-22 overall and domain scores were calculated, as were Lund-Mackay CT scores. The discriminatory capacity of SNOT-22 scores for CT results was determined using the receiver-operator characteristic area under the curve (ROC-AUC). Patient-Reported Outcome Measurement Information System (PROMIS) mental health T-scores were assessed, and stratified analyses were used to test for effect modification by psychological status., Results: In stratified analyses, patients with better PROMIS mental health scores had SNOT-22 overall (ROC-AUC 0.96) and nasal domain scores (ROC-AUC 0.97-0.98) that were highly discriminatory for Lund-Mackay scores, while those with worse mental health scores did not (ROC-AUC 0.42-0.55, P < .007). Patients with better SNOT-22 psychological domain scores also had nasal scores that discriminated among CT results significantly better than those with worse psychological domain scores (ROC-AUC 0.65-0.69 and 0.34-0.35, respectively, P < .013)., Conclusions: Psychological status is an effect modifier of the relationship between SNOT-22 and Lund-Mackay scores. SNOT-22 scores were discriminatory for Lund-Mackay CT results in patients with better psychological status, while they were nondiscriminatory in those with worse psychological status. When assessing the relationship between subjective and objective measures of chronic rhinosinusitis, accounting for effect modification may have practical utility.

Objective: Eustachian tube dysfunction (ETD) is a common diagnosis among adults presenting for outpatient care. We sought to determine national utilization and the associated cost of invasive procedures for adult ETD., Study Design: Cross-sectional study., Setting: National health care database., Subjects and Methods: The Truven Health MarketScan Databases (2010-2014) analytic cohort included health care encounters of patients ≥18 years of age with a diagnosis of ETD or related conditions of otitis media with effusion (OME) or tympanic membrane retraction (TMR). Visits associated with recent diagnoses of acute upper respiratory infection, head and neck cancer, or radiation therapy were excluded. Invasive procedure usage was subdivided into nasal and otologic procedures., Results: ETD, OME, or TMR was diagnosed in 1,298,987 patients, 11.1% of which were chronic. The most common procedure was diagnostic endoscopy (including nasal endoscopy and laryngopharyngoscopy), which was used most frequently in the first 3 months after diagnosis, during which it was performed in 120,971 (9.3%) patients. The most frequent therapeutic nasal procedure was eustachian tube inflation without catheterization, performed in 11,412 patients over 5 years at a total cost of $1,210,939 ($106 per person annually). The most common therapeutic otologic procedure was myringotomy with tympanostomy, performed on 56,137 patients over 5 years at a total cost of $47,713,708 ($810 per person annually)., Conclusion: Several nasal and otologic procedures are associated with a diagnosis of adult ETD at substantial cost. Development of therapeutic alternatives should be sought to mitigate the need for invasive procedures to treat this condition.

Objectives: To determine whether the Voice Handicap Index-10 (VHI-10) predicts diagnoses made via laryngoscopy/stroboscopy, as compared to common clinical inquiries about vocal characteristics., Methods: We prospectively collected data from a cohort of 204 consecutive patients newly presenting for ambulatory laryngology evaluation. Each patient completed the VHI-10 and 16 concurrent mainstream queries about vocal characteristics such as weakness, breathiness, fatiguability, or inability to shout. Using the objective diagnoses made by laryngoscopy/stroboscopy as a gold standard, the area under the receiver operating characteristic curves (AUC), sensitivity, and specificity were determined., Results: For unilateral vocal fold paralysis, VHI-10 scores had an AUC of 0.78 (95% CI, 0.68-0.88) and had better discrimination than 12 common clinical queries. At a threshold score of ≥11, VHI-10 sensitivity was 0.94; at a threshold of ≥31, specificity was 0.91. For laryngeal stenosis, the VHI-10 score demonstrated moderate discrimination, with an AUC of 0.79 (95% CI, 0.56-1.00) and higher discrimination than three common clinical queries. At a threshold score of ≥11, VHI-10 sensitivity was 1.00; at a threshold of ≥31, specificity was 0.89. Both VHI-10 scores and common clinical queries had low diagnostic ability for vocal fold paresis, laryngopharyngeal reflux (LPR), paradoxical vocal fold motion, and vocal fold scar or atrophy., Conclusions: The VHI-10 score is an effective diagnostic indicator of laryngoscopy/stroboscopy findings of vocal fold paralysis and laryngeal stenosis, performing better than multiple mainstream queries about vocal characteristics. VHI-10 scores and common clinical queries are limited in their ability to indicate paresis, reflux, paradoxical motion, and vocal fold scar or atrophy., Level of Evidence: 2c Laryngoscope, 130:992-999, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose of Review: To examine the role of allergy medications in the treatment of otitis media with effusion (OME), focusing on use of intranasal steroids and antihistamines., Recent Findings: There has been ongoing controversy regarding the role of allergy in the development of OME. Treatment of OME with medications commonly used for allergic symptomatology has been studied. Proposed treatment options include decongestants, mucolytics, oral steroids, topical steroids, antihistamines, and antibiotics. We begin by evaluating the proposed association between allergy and OME, and then evaluate intranasal steroids and oral antihistamine therapy in the treatment of OME. The role of the adenoid and concurrent nasal symptomatology is also addressed. The preponderance of data suggests that neither intranasal steroids nor antihistamines improve the long-term clearance of isolated OME and are therefore not recommended. However, data are notably limited with regard to improvement rates in OME in patients specifically with concurrent allergy and/or adenoid hypertrophy. Future studies of medications for OME would ideally incorporate study designs controlling for both allergic rhinitis and adenoid hypertrophy, to better understand the impact of these medications on OME in these subgroups of patients.

Clinicians seek to pursue the most clinically effective treatment strategies, but costs have also become a key determinant in contemporary health care. Economic analyses have thus emerged as a valuable resource to both quantify and qualify the value of existing and emerging interventions and programs. Cost-effectiveness analyses estimate the benefits gained per monetary unit, providing insights to guide resource allocation. Herein, we delineate the related concepts and considerations to facilitate understanding and appraisal of these analyses, so as to better inform the stakeholders in our otolaryngology community.

Objective: Eustachian tube dysfunction (ETD) prompts >2 million adult visits in the United States annually. While disease prevalence and health care utilization are established for children, practice patterns for adults remain unknown. Our objective was to determine national resource utilization for adult ETD., Study Design: Cross-sectional study., Setting: National database sample., Subjects and Methods: The Truven Health MarketScan Databases (2010-2014) analytic cohort included health care encounters of patients ≥18 years of age with a diagnosis of ETD, otitis media with effusion, or tympanic membrane retraction. Visits associated with recent diagnoses of acute upper respiratory infection, head and neck cancer, or radiation therapy were excluded. Acute ETD (<3 months) and chronic ETD (≥3 months) were subgroups. Medication usage was quantified by class., Results: ETD was diagnosed for 1,298,987 patients, 11% of which was chronic. Over 92% of patients were seen in outpatient clinics, most often by otolaryngology (57%) for chronic ETD and by general medicine (49%) for acute ETD. Medications were frequently utilized, as 530,146 (53.7%) patients received ≥1 prescription. Top prescriptions for chronic ETD included intranasal corticosteroids (22%), antibiotics (22%), oral corticosteroids (13%), and analgesics (6%). The overall annual cost of prescribed medications associated with visits in which either acute or chronic ETD was diagnosed exceeded $8.5 million for a mean of $80.78 per patient who filled a prescription., Conclusion: Adult ETD is frequently treated with several medication classes by a variety of provider types. Understanding the potential adverse effects and cost associated with these practices should be a priority.

For the preponderance of patients with unilateral idiopathic sudden sensorineural hearing loss (SSNHL), the etiology is unknown. The pathogenesis of disease and a definitive mechanism for this abrupt hearing loss has not yet been elucidated. We hypothesize that there is a time-clustered presentation for idiopathic SSNHL; from an epidemiological standpoint, this suggests an environmental or infectious etiology. At a tertiary referral center in the northeast United States, we have observed that adult patients with SSNHL present in clusters with interspersed intervals of time with no presentations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose of Review: To examine the relationship between otitis media, allergic rhinitis, and age., Recent Findings: Otitis media and allergic rhinitis are prevalent conditions with a controversial relationship. Some data suggest that these entities are significantly associated, either through allergic rhinitis inducing Eustachian tube dysfunction or through allergic pathophysiology simultaneously occurring intranasally and in the ear. Other studies, however, have refuted this relationship. For example, treatment with antihistamines does not reliably improve OME, making causation and association challenging to establish. Age may have an effect on the nature of the relationship between allergic rhinitis and otitis media, by impacting both the individual conditions and their association. Epidemiological, immunological, and adenoidal studies have suggested that differences occur with age, and this review encapsulates the related data and publications. We begin by evaluating how allergic rhinitis and otitis media each are affected by age, then evaluate the role that age may have in the relationship between the two conditions. Adult and pediatric literature are evaluated so as to include the full impact of age across patients' lifespan. Age induces changes in immunity, patterns of inflammation, and susceptibility to both allergic rhinitis and otitis media with effusion. Age may also be an effect modifier which impacts the nature of the relationship between these two conditions. The influence of age on the association between these highly prevalent conditions remains a topic of active study.

Objective: Given ongoing debate about the suggested association, the primary objective was to determine if idiopathic sudden sensorineural hearing loss (ISSNHL) was a sentinel event for acute myocardial infarction (AMI) in adults., Study Design: Case-control study., Setting: United States MarketScan administrative health claims database., Patients: Aged 18 years or older, had a diagnosis of ISSNHL on or after January 1st, 2011 and had sufficient follow-up data available to assess for AMI occurrence., Intervention: N/A., Main Outcome Measures: Incidence rates (per 1,000 patient years) of AMI for cases and controls were computed. Adjusted and unadjusted Cox proportional hazards models were created to explore possible associations between ISSNHL and initial AMI., Results: A total of 10,749 ISSNHL cases and 10,749 matched controls were included. There were no significant differences in the incidence rate of AMI between ISSNHL cases (8.29 events/1,000 person-years) and controls (9.25 events/1,000 person-years), nor were there differences within age groups, sex, or comorbidity status (overall incidence rate ratio 0.90; 95% confidence interval [CI] 0.70-1.15 p = 0.39). The unadjusted and adjusted Cox proportional hazards models did not demonstrate an association between ISSNHL and initial AMI (hazard ratio [HR]: 0.90, 95% CI: 0.70-1.15; HR: 0.86, 95% CI: 0.67-1.10, respectively)., Conclusions: ISSNHL is not a predictor of an initial AMI in adult patients from the United States. Considerable inconsistencies in associations between cardiovascular risk factors and ISSNHL exist in the literature. Further work is needed to confirm or refute direct associations between cardiovascular disease risk factors and ISSNHL before definitive mechanistic conclusions can be made.

The assessment of patient-reported outcome measures (PROMs) in the outpatient setting is gaining momentum in clinical and research venues. Implementing this data capture into one's practice, however, is not a one-size-fits-all venture, and it is critical to determine when, how, and where to include these patient-centered assessments. This installment of the "Evidence-Based Medicine in Otolaryngology" series provides insight into the implementation process and experiences with successful incorporation of PROMs into clinical practice. Specifically, 4 differing clinical scenarios and collection techniques are described, including data acquisition protocols, formats for clinician data usage, and applications of PROM results in clinical and research scenarios.

Objectives Pediatric chronic rhinosinusitis has a substantial impact, but its epidemiology has yet to be elucidated. Our objectives were (1) to determine the associated national visit burden and (2) to assess its frequency relative to other frequent childhood otolaryngological illnesses. Study Design Analysis of national survey databases. Setting Ambulatory care settings in the United States, 2005 to 2012. Subjects and Methods Cases with a diagnosis of chronic rhinosinusitis were assessed in total and as a proportion of all visits reported in National Ambulatory Medical Care Surveys. To place these data into context, results for acute rhinosinusitis, allergic rhinitis, upper respiratory tract infection, and otitis media were also extracted and compared. Data specific to individual age group and calendar year were assessed. Results Chronic rhinosinusitis accounted for 5.6 million visits per annum (range, 3.7-7.5 million) among patients 0 to 20 years of age. Children in the >5- to 10-year-old and >10- to 15-year-old age groups were more likely to be affected ( P < .001). Among all visits, chronic rhinosinusitis was diagnosed in 2.1% (95% confidence interval [CI], 1.9%-2.4%), acute rhinosinusitis in 0.6% (95% CI, 0.5%-0.7%), allergic rhinitis in 2.6% (95% CI, 2.3%-2.8%), upper respiratory tract infection in 8.0% (95% CI, 7.5%-8.4%), and otitis media in 6.7% (95% CI, 6.5%-7.1%). Chronic rhinosinusitis visits were significantly more prevalent than for acute rhinosinusitis (relative risk, 3.40; 95% CI, 2.70-4.10; P < .0001). Among those >15 to 20 years of age, chronic rhinosinusitis was 2.18-fold (95% CI, 1.65-2.70) more frequently diagnosed than otitis media. Conclusions The visit burden from pediatric chronic rhinosinusitis exceeds that of acute rhinosinusitis and equals the burden from allergic rhinitis.

Hypothesis testing using a frequentist approach is the mainstay of biostatistics and forms the foundation for assessing the significance of study results. This classical method has well-understood advantages as it determines whether data are statistically improbable and provides a threshold (ie, the P value) for delineating significance. Alternative statistical approaches have been proposed, including Bayesian analysis. This technique incorporates a prior probability as to what is already known clinically with the observed data. It is important for otolaryngologists to understand the advantages and disadvantages of these 2 approaches to conduct the most appropriate analyses.

Objectives Pediatric eustachian tube dysfunction (ETD), otitis media with effusion (OME), and tympanic membrane retraction (TMR) have been well studied, but no large analyses have described the associated burden beyond childhood. The potential impact and feasibility of prospective trials designed to optimize management of affected adults are thus unclear. Our objectives were therefore (1) to determine the national visit burden associated with ETD/OME/TMR beyond childhood and (2) to examine risk factors specific to adults, highlighting differences in comparison with children. Study Design Cross-sectional analysis of a national database. Setting Ambulatory visits in the United States. Methods Epidemiologic analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (2005-2012) included data from 761,291 observations representing 9,369,388,092 visits. Chi-square test with Bonferroni adjustment for multiple comparisons was utilized for hypothesis testing. Results Visits related to ETD/OME/TMR exceeded 2 million per annum in patients 0 to 20 years of age (mean 2,625,965; range 2,239,288-3,329,858). Among those >20 years old, visits also exceeded 2 million (mean, 2,025,050; range, 1,550,669-2,353,799). Characteristics differed according to age: whereas ETD/OME/TMR affected more males <20 years, females were more frequently diagnosed in the older age group ( P < .0001). Patients >20 to 40 years of age were the most likely to visit the emergency department ( P = .0022). There were no statistically significant differences per season or region. The related diagnoses of cholesteatoma and chronic otitis media prompted additional visits. Conclusions ETD/OME/TMR is associated with a visit burden for adults that extends beyond childhood. Among adults, there may also be age-related differences in patient characteristics.

Objectives Adherence to the allergic rhinitis clinical practice guideline is being considered as a potential focus for national performance metrics. To help inform this discussion, we assessed patient- and clinician-reported medication administration among nationally representative populations of patients with allergic rhinitis. Study Design Cross-sectional analyses. Setting and Subjects Home health assessments, ambulatory visits. Methods Participants in the National Health and Nutrition Examination Survey and the National Ambulatory Medical Care Survey / National Hospital Ambulatory Medical Care Survey were assessed. The primary outcomes were the percentage of patients reporting receipt of antihistamines and/or nasal steroids among those with allergy-related symptoms and the percentage for whom a clinician administered these medications when diagnosing allergic rhinitis. Secondary outcomes included assessments of those with worse quality of life, confirmatory allergy testing, and leukotriene receptor antagonist use. Results Within the National Health and Nutrition Examination Survey, an estimated 29.2 million patients were diagnosed with "hay fever," while 92.2 million were diagnosed with "allergies." Patients with symptoms of allergic rhinitis reported that antihistamines or nasal steroids were prescribed in 21.1% to 24.0% of cases. Leukotriene receptor antagonists were given to 1.7% of those without asthma or use of other allergy medications. Within the National Ambulatory Medical Care Survey / National Hospital Ambulatory Medical Care Survey, observations representing 149.5 million visits for allergic rhinitis demonstrated that nasal steroids were administered in 29.6% of cases, while nonsedating and sedating antihistamines were given in 22.4% and 17.2%, respectively. Conclusions Despite a high prevalence of allergic rhinitis, per patient report and clinician entry, a substantial number of affected patients do not receive antihistamines and nasal steroids.

Importance: Antireflux medication has been endorsed as a useful adjunctive therapy for chronic rhinosinusitis, but its use remains controversial., Objectives: To determine whether chronic rhinosinusitis is associated with administration of proton pump inhibitors, histamine2-receptor antagonists, antacids, or prokinetic agents; whether practice patterns vary according to visit setting; and whether those patterns vary according to the presence or absence of potentially confounding conditions., Design, Setting, and Participants: A cross-sectional analysis was performed of data from January 1, 2005, to December 31, 2010, from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, which included 590 772 observations representing 7 191 711 480 ambulatory care visits. Univariate, multivariate, and stratified analyses were performed from January 1, 2005, to December 31, 2010., Exposures: Chronic rhinosinusitis., Main Outcomes and Measures: The probability of receiving antireflux medications was the main measured outcome., Results: Of 7 191 711 480 ambulatory care visits, those for chronic rhinosinusitis were not more likely to result in the administration of proton pump inhibitors (odds ratio, 1.00; 95% CI, 0.62-1.63; P = .99) or antacids and prokinetic agents (odds ratio, 1.24; 95% CI, 0.30-5.10; P = .77). In addition, patients with chronic rhinosinusitis were less likely to receive histamine2-receptor antagonists than were those without chronic rhinosinusitis, even when adjusted for age, sex, race/ethnicity, visit setting, other antireflux agents, and presence or absence of gastroesophageal reflux, laryngopharyngeal reflux, or allergy diagnoses (odds ratio, 0.25; 95% CI, 0.12-0.57; P = .001)., Conclusions and Relevance: National practice patterns observed thus far have not favored the use of proton pump inhibitors, histamine2-receptor antagonists, antacids, or prokinetic agents for chronic rhinosinusitis.

This American Head and Neck Society (AHNS) consensus statement discusses the techniques of laryngeal examination for patients undergoing thyroidectomy and parathyroidectomy. It is intended to help guide all clinicians who diagnose or manage adult patients with thyroid disease for whom surgery is indicated, contemplated, or has been performed. This consensus statement concludes that flexible transnasal laryngoscopy is the optimal laryngeal examination technique, with other techniques including laryngeal ultrasound and stroboscopy being useful in selected scenarios. © 2016 Wiley Periodicals, Inc. Head Neck 38: 811-819, 2016., (© 2016 Wiley Periodicals, Inc.)

Importance: Surgical competency requires sound clinical judgment, a systematic diagnostic approach, and integration of a wide variety of nontechnical skills. This more complex aspect of clinician development has traditionally been difficult to measure through standard assessment methods., Objective: This study was conducted to use the Clinical Practice Instrument (CPI) to measure nontechnical diagnostic and management skills during otolaryngology residency training; to determine whether there is demonstrable change in these skills between residents who are in postgraduate years (PGYs) 2, 4, and 5; and to evaluate whether results vary according to subspecialty topic or method of administration., Design, Setting, and Participants: Prospective study using the CPI, an instrument with previously established internal consistency, reproducibility, interrater reliability, discriminant validity, and responsiveness to change, in an otolaryngology residency training program. The CPI was used to evaluate progression in residents' ability to evaluate, diagnose, and manage case-based clinical scenarios. A total of 248 evaluations were performed in 45 otolaryngology resident trainees at regular intervals. Analysis of variance with nesting and postestimation pairwise comparisons were used to evaluate total and domain scores according to training level, subspecialty topic, and method of administration., Interventions: Longitudinal residency educational initiative., Main Outcomes and Measures: Assessment with the CPI during PGYs 2, 4, and 5 of residency., Results: Among the 45 otolaryngology residents (248 CPI administrations), there were a mean (SD) of 5 (3) administrations (range, 1-4) during their training. Total scores were significantly different among PGY levels of training, with lower scores seen in the PGY-2 level (44 [16]) compared with the PGY-4 (64 [13]) or PGY-5 level (69 [13]) (P < .001). Domain scores related to information gathering and organizational skills were acquired earlier in training, while knowledge base and clinical judgment improved later in residency. Trainees scored higher in general otolaryngology (mean [SD], 72 [14]) than in subspecialties (range, 55 [12], P = .003, to 56 [19], P < .001). Neither administering the examination with an electronic scoring system, rather than a paper-based scoring system, nor the calendar year of administration affected these results., Conclusions and Relevance: Standardized interval evaluation with the CPI demonstrates improvement in qualitative diagnostic and management capabilities as PGY levels advance.

Objective: This plain language summary serves as an overview in explaining otitis media with effusion (pronounced Oh-TIE-tis ME-dee-uh with Ef-YOO-zhun), abbreviated "OME" and often called "ear fluid." The summary applies to children aged 2 months through 12 years with OME and is based on the 2015 "Clinical Practice Guideline: Otitis Media with Effusion (Update)." The evidence-based guideline includes research to support more effective diagnosis and treatment of OME in children. The guideline was developed as a quality improvement opportunity for managing OME by creating clear recommendations to use in medical practice., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Importance: While propranolol is touted as superior to prednisolone for treating infantile hemangiomas (IH), a randomized clinical trial (RCT) comparing the outcome and tolerability of these medications for symptomatic, proliferating IH has not been reported., Objectives: To determine if oral propranolol is more efficacious and better tolerated than prednisolone in treating symptomatic, proliferating IH and to determine the feasibility of conducting a multi-institutional, RCT comparing efficacy and tolerability of both medications., Design, Setting, and Participants: Phase 2, investigator-blinded, multi-institutional RCT conducted in 3 academic vascular anomalies clinics on 19 of 44 eligible infants aged between 2 weeks and 6 months. All participating patients had symptomatic proliferating IH treated between September 1, 2010, and August 1, 2012., Interventions: Treatment with oral propranolol vs prednisolone (2.0 mg/kg/d) until halted owing to toxic effects or clinical response., Main Outcomes and Measures: Primary outcome was change in IH size after 4 months of therapy. Secondary outcomes were response rate and frequency and severity of adverse events (AEs)., Results: The primary outcome showed no difference in lesion size or affected skin area after 4 months of therapy: 41% and 1.32 mm2 for prednisolone vs 64% and 0.55 mm2 for propranolol (P = .12 for lesion size, and P = .56 for affected skin area). Longitudinal analyses showed a faster response in total lesion outer dimension with prednisolone (P = .03), but this advantage over time was not noted when central clearing and outer dimension were included in the analysis (P = .91). The overall frequency of AEs was similar (44 for prednisolone vs 32 for propranolol) (P = .84), but prednisolone-treated participants had more grade 3 severe AEs (11 vs 1) (P = .01), particularly growth retardation resulting in size and weight below the fifth percentile. Early study withdrawal owing to AEs occurred in 6 (75%) of 8 patients in the prednisolone group but 0 of 11 propranolol-treated participants. The mean duration of therapy was shorter for prednisolone (141 vs 265 days), reflecting the higher rate of early withdrawals., Conclusions and Relevance: Both medications show similar efficacy for reducing the area of symptomatic, proliferating IH. Although prednisolone showed a faster response rate, propranolol was better tolerated with significantly fewer severe AEs. Propranolol should be the first line of therapy for symptomatic IH unless contraindicated or unless future studies demonstrate severe AEs from propranolol. Recruiting participants for a phase 3 RCT would be difficult owing to safety profiles measured here and emerging trends favoring propranolol. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00967226.

Objective: To characterize factors that surgeons perceive as affecting selection of procedures designed to treat hypopharyngeal obstruction in adults with obstructive sleep apnea (OSA) and to compare those factors among 2 groups of American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) member surgeons., Study Design: Cross-sectional online survey., Subjects and Methods: AAO-HNS members with a self-identified subspecialty interest either in sleep medicine or general otolaryngology were asked to complete an online survey, each respondent rated (5-point Likert scale) the perceived quality of their education and training and the role of specific factors in selection, both for procedure categories (eg, all hypopharyngeal) and individual procedures. Responses were examined for the entire group and for subgroups., Results: Response rate was 27% (163/610). Sixty-five percent of respondents rated their surgical OSA education and training during postgraduate continuing medical education (CME) courses as of high quality, compared with 39% for residency/fellowship and 4% for medical school (P < 0.01). For individual hypopharyngeal procedures, over 40% of respondents reported limited training (except for tongue radiofrequency), and over 30% raised concerns about scientific evidence and reimbursement. Surgeon personal experience suggested treatment benefits without clearly favoring individual procedures. Respondents noted that patients were reluctant to undergo procedures, despite treatment recommendations, particularly maxillomandibular advancement. The sleep medicine subgroup reported higher ratings for education and training quality, research evidence, and personal experience with hypopharyngeal procedures. Concerns about adequate education and training, the quality of research evidence, and reimbursement issues were major factors in procedure selection., Conclusion: Multiple factors affect procedure selection. Surgeons identify concerns regarding education and training and research evidence.

Recent studies have demonstrated that the majority of physicians cannot accurately determine the predictive values of diagnostic tests. Physicians must understand the predictive probabilities associated with diagnostic testing in order to convey accurate information to patients, a key aspect of evidence-based practice. While sensitivity and specificity are widely understood, predictive values require a further understanding of conditional probabilities, pretest probabilities, and the prevalence of disease. Therefore, this third installment of the series "Evidence-Based Medicine in Otolaryngology" focuses on understanding the probabilities needed to accurately convey the results of dichotomous diagnostic tests in everyday practice.

Background: Hearing loss associated with congenital cytomegalovirus (CMV) infection occurs in 0.2 to 0.6 per 1000 neonates., Objective: The primary goal of this systemic review was to test the following null hypotheses: (1) antiviral therapy has no impact on congenital CMV-related sensorineural hearing loss and (2) surgical therapy has no impact on congenital CMV-related sensorineural hearing loss., Data Sources: Computerized searches of MEDLINE and EMBASE databases through September 2010 were performed, supplemented with manual searches and inquiries to topic experts., Review Methods: Studies were included based on review of 387 studies according to criteria developed a priori. Data extraction was performed by independent reviewers and focused on relevant audiologic measurements, study designs, and potential confounders., Results: Criterion-meeting studies (n = 19) included a total of 446 participants. The largest randomized controlled trial (RCT) suggested a significant protective effect of intravenous ganciclovir against deterioration of hearing in neonates with central nervous system manifestations of CMV infection. It also, however, suggested a 3-fold increase in neutropenia. The second RCT suggested that there may be no significant benefit of intravenous ganciclovir for normal-hearing infants with asymptomatic congenital CMV. Additional prospective and retrospective data evaluated the impact of oral therapy and cochlear implantation in affected patients., Conclusion: Although results are mixed, the highest level of evidence suggests that antiviral therapy confers a protective benefit on neonates with hearing loss and symptomatic CMV. Cochlear implantation can result in advancement of speech and language skills, but there are mixed results compared with non–CMV-infected patients.

Evidence-based medicine, with its capacity to improve patient outcomes, has grown prominent throughout the medical field. Otolaryngology is at a crucial stage in the expansion of evidence-based medicine, with its impact seen in many arenas. As the evidence continues to shape our field, we hope to serve our otolaryngology community through this invited series, which is dedicated to the exposition of evidence-based medicine and its applications. This first installment examines evidence-based medicine itself and its multiple interpretations, including a purist view, a population-based view, and a view centered on the individual. Strengths and weaknesses of each are discussed, as well the potential for unification and evolution of these concepts. We also place evidence-based medicine in the context of the mindset of traditional medicine and anticipate future developments., (Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.)

Objective: To develop and validate an instrument to measure the progression of clinical practice ability among surgical trainees., Study Design: Prospective validation study., Setting: Three academic training institutions: Massachusetts Eye and Ear Infirmary, Brigham and Women's Hospital, Harvard School of Public Health., Subjects and Methods: A clinical practice instrument (CPI) was created and prospectively validated in otolaryngology trainees at three institutional sites. The instrument is completed during an oral examination of a trainee who is presented with a patient scenario; the scenario yields one clinical diagnosis, one therapeutic intervention, and one interventional complication. On the basis of the trainee's responses, 21 item scores are calculated focusing on key areas within the diagnostic and management paradigm. Internal consistency, reproducibility, inter-rater reliability, discriminant and criterion validity, and responsiveness to change over time were evaluated., Results: There were 87 administrations of the instrument over a period of 22 months. The subjects (n = 32) spanned the range of training from medical student to clinical fellow. There was strong internal consistency within each domain (Cronbach's alpha 0.85-0.94, one-sided 95% confidence interval > 0.81). Inter-rater reliability was high (kappa 0.66, absolute agreement 72%). Reproducibility of item scores was excellent (intraclass correlation coefficient [ICC] final summary score 0.78, global item score 0.83). Discriminant validity (P < 0.0001), criterion validity (P = 0.03), and responsiveness to change (P = 0.0055) were also established., Conclusion: The CPI serves as a reliable, reproducible, and valid means to measure the progression of clinical practice ability in trainees as they transition from "novice" to "attending equivalent" surgeons., (Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.)

Background: The risk of postoperative venous thromboembolic disease is as high as 30%, with an associated fatality risk of 1%. Therefore, prophylaxis is essential, but the optimal regimen remains controversial. This study was designed to systematically review and quantitatively summarize the impact of mechanical compression versus subcutaneous heparin on venous thromboembolic disease and posttreatment bleeding in postsurgical and posttrauma patients., Methods: Computerized searches of the MEDLINE and EMBASE databases through November 2008 were performed and supplemented with manual searches. We included studies that had: (1) a patient population undergoing surgery or admitted immediately posttrauma, (2) a randomized comparison of prophylaxis with mechanical compression versus subcutaneous heparin, (3) outcome measured in terms of deep vein thrombosis (DVT), pulmonary embolism (PE), or bleeding., Results: Two reviewers independently extracted data from the original articles, which represented 16 studies, including a total of 3,887 subjects. Meta-analysis was performed using a random effects model. The pooled relative risk for mechanical compression compared with subcutaneous heparin was 1.07 (95% confidence interval [CI] 0.72, 1.61) for DVT and 1.03 (95% CI 0.48, 2.22) for PE. Mechanical compression was associated with a significantly reduced risk of postoperative bleeding compared with subcutaneous heparin (risk ratio 0.47; 95% CI 0.31, 0.70). Subgroup analyses by heparin type suggested that low molecular weight heparin may reduce risk of DVT compared with compression (relative risk 1.80; 95% CI 1.16, 2.79) but remains similarly associated with an increased risk of bleeding., Conclusions: These results suggest that the overall bleeding risk profile favors the use of compression over heparin, with the benefits in term of venous thromboembolic disease prophylaxis being similar between groups. Subgroup analyses suggest that low molecular weight heparin may have a differential effect; this observation should be further evaluated in future studies.

Objectives: To determine the range and prevalence of otologic disorders in patients with ectodermal dysplasia (ED) and provide a general review of its multiple otolaryngological manifestations., Design: Case series., Setting: Ectodermal dysplasia family conference., Patients: Sixty-nine individuals with ED were evaluated. The average age was 11 years (range, 1-56 years). Most were male patients (44 [64%]), and most had Christ-Siemens-Touraine syndrome/hypohidrotic ED (42 [61%]), with the remaining having Hay-Wells, Clouston, and ectrodactyly ED clefting syndromes and unclassified types of ED., Interventions: Questionnaire including a quality-of-life assessment modeled after the Otitis Media 6 instrument, physical examination, screening audiogram, and tympanometry., Results: Of the 69 patients, 15 (22%) had a known history of hearing loss, and over half reported some level of difficulty processing verbal information (30 patients [43%] reported speech problems and 4 patients [6%] required hearing aids). A history of otitis media was common, with 15 patients (21%) presenting with tympanostomy tubes in place. The mean +/- SD quality-of-life rating was 2.0 +/- 1.1 (range 1-7), with lower scores suggesting less of a problem. On physical examination, 18 patients (26%) had pinna anomalies. One case of advanced cholesteatoma and 2 cases of external auditory canal stenosis were identified. Of the 24 patients who received 4-tone screening audiogram, 2 (8%) had a highest pure-tone average threshold of 50 to 65 dB, whereas 5 patients (21%) had a 30- to 45-dB threshold, with the remaining having a 0- to 25-dB threshold., Conclusion: In our study, which is, to our knowledge, the largest reported collection of ED patients evaluated for otologic disease, most patients were found to have 1 or more otologic abnormalities, ranging from auricular anomaly to complications of otitis media to profound hearing loss.

Objective: To develop short hairpin RNA (shRNA) vectors and virions to trigger RNA interference against human p16., Design and Interventions: A modular vector-based shRNA system was used to construct multiple distinct shRNA vectors against the unique exon 1alphaof p16. Target sequences were designed using rigid criteria for length and GC content, along with basic local alignment search tool (BLAST) evaluation to ensure targeting specificity. Individual shRNA-p16 cassettes were then cotransfected with a p16 expression vector and evaluated by Western blot. Cassettes showing a high level of p16 repression were used to construct shRNA-p16 expressing adenoviral and retroviral vectors and tested in a human head and neck squamous cell carcinoma line expressing endogenous and exogenous p16., Results: Adenoviral and retroviral transfer of shRNA-p16 significantly reduced p16 protein levels, while control constructs left p16 expression unchanged., Conclusions: Although p16 is a common target of inactivation in head and neck cancer, its biological role remains ill defined. RNA interference is rapidly becoming the standard to target selected genes of interest for inactivation. We have successfully inhibited p16 expression using shRNA cassettes with strong activity against human p16 and integrated these constructs into adenoviral and retroviral vectors for transient and integrated expression in human cells. Application of this novel modular system to primary human cells will allow the biological consequences of p16 loss to be examined both in vitro and in vivo.