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Introduction: Osteogenesis imperfecta (OI) is a common heritable disorder affecting type 1 collagen. The sequelae of OI vary, but hearing loss is a significant complication with 46-58 % of patients having some degree of hearing loss. Previous studies have suggested patients with OI may have conductive, sensorineural, or mixed hearing loss. Majority of these studies focus on the adult population., Objectives: Identify a relationship between OI and hearing loss in the pediatric population., Methods: The TriNetx Analytics Network, a federated health research network that aggregates the de-identified electronic health record data of over 78 million patients across the United States, was queried for patients 18 years old or younger with a diagnosis of OI. Patients in this group with diagnosis of sensorineural, conductive, or mixed hearing loss were recorded. Patients with diagnoses of congenital cytomegalovirus, congenital inner ear malformations, and noise-induced hearing loss were excluded from analysis., Results: Out of 3256 patients 18 years old or younger with OI, 10.07 % (95 % CI: 9.06-11.16) had a history of any form of hearing loss, 5.71 % (95 % CI: 4.94-6.57) had conductive hearing loss, 3.01 % (95 % CI: 2.45-3.66) had sensorineural hearing loss, and 1.35 % (95 % CI: 0.98-1.81) had mixed hearing loss. Relative risks for diagnosis of any type of hearing loss, conductive hearing loss, sensorineural hearing loss, and mixed hearing loss were calculated: 5.90 (95 % CI 5.32-6.53), 5.08 (95 % CI 4.42-5.84), 6.18 (95 % CI 5.09-7.51), and 13.86 (95 % CI 10.33-18.59) respectively., Discussion: This study is the largest to date that describes a relationship between OI and conductive, sensorineural, and mixed hearing loss. Pediatric patients with OI are almost five times as likely to have any type of hearing loss. There was a significant increased risk in each subgroup, but conductive hearing loss was the most common for hearing loss in children with OI. The highest risk subtype when compared to controls was mixed hearing loss., Competing Interests: Declaration of competing interest Authors Chelsea Cleveland, Jamil Hayden, Tekin Baglam, and Todd Otteson have no disclosures to report., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hearing loss is the cause of significant morbidity throughout the United States and the world. Because of numerous factors, such as ongoing noise exposure, poorly controlled chronic disease, and an aging population, the burden of hearing loss is expected to continue to increase. Hearing loss commonly is categorized as conductive, sensorineural, or mixed. The type of hearing loss can be determined through a combination of patient history and physical examination, and then confirmed with audiometry and tympanometry. Advanced imaging is not typically necessary, but it may be helpful in specific instances. The presentation of sudden sensorineural hearing loss should prompt urgent referral to an otolaryngologist and audiologist. Management of this condition is selective but may initially include oral corticosteroids. Management for chronic hearing loss involves the use of hearing aids, which can offer a large benefit to users but historically have been expensive and not covered by many insurance plans. Recent US legislation has made hearing aids more accessible and affordable by allowing direct-to-consumer marketing and offering over-the-counter hearing aids without a clinical evaluation., (Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.)

Background: The association between the sensorineural hearing loss (SNHL) and triglyceride-glucose (TyG) index remains inadequately understood. This investigation seeks to elucidate the connection between the TyG index and SNHL., Methods: In this cross-sectional study, we utilized datasets sourced from the National Health and Nutrition Examination Survey (NHANES). A comprehensive analysis was conducted on 1,851 participants aged 20 to 69, utilizing complete audiometry data from the NHANES database spanning from 2007 to 2018. All enrolled participants had accessible hearing data, and the average thresholds were measured and calculated as both low-frequency pure-tone average and high-frequency pure-tone average. Sensorineural hearing loss (SNHL) was defined as an average pure tone of 20 dB or higher in at least one better ear. Our analysis involved the application of multivariate linear regression models to examine the linear relationship between the TyG index and SNHL. To delineate any non-linear associations, we utilized fitted smoothing curves and conducted threshold effect analysis. Furthermore, we conducted a two-sample Mendelian randomization (MR) study, leveraging genetic data from genome-wide association studies (GWAS) on circulating lipids, blood glucose, and SNHL. The primary analytical method for the MR study was the application of the inverse-variance-weighted (IVW) approach., Results: In our multivariate linear regression analysis, a substantial positive correlation emerged between the TyG index and SNHL [2.10 (1.80-2.44), p < 0.0001]. Furthermore, using a two-segment linear regression model, we found an L-shaped relationship between TyG index, fasting blood glucose and SNHL with an inflection point of 9.07 and 94 mg/dL, respectively. Specifically, TyG index [3.60, (1.42-9.14)] and blood glucose [1.01, (1.00-1.01)] concentration higher than the threshold values was positively associated with SNHL risk. Genetically determined triglyceride levels demonstrated a causal impact on SNHL (OR = 1.092, p = 8.006 × 10 -4 ). In addition, blood glucose was found to have a protective effect on SNHL (OR = 0.886, p = 1.012 × 10 -2 )., Conclusions: An L-shaped association was identified among the TyG index, fasting blood glucose, and SNHL in the American population. TyG index of more than 9.07 and blood glucose of more than 94 mg/dL were significantly and positively associated with SNHL risk, respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Liu, Nie, Lu, Yan, Wang and Zhao.)

Over a century of research has focused on improving our understanding of congenital cytomegalovirus (cCMV), yet it remains the most common congenital infection in the United States, affecting 3 to 6 per 1000 live born infants each year. Pregnancies affected by cCMV are at a heightened risk of spontaneous abortion and intrauterine fetal demise. Neonates born with cCMV are also at substantial risk for long-term neurodevelopmental sequelae and disability, including sensorineural hearing loss, even those born without clinically apparent disease. Considerable progress has been made in recent years in study of the epidemiology and transmission of cCMV, developing better diagnostic strategies, implementing newborn screening programs, improving therapeutics, and launching vaccine trials. In this article, we review recent developments in the understanding of the virology and immunobiology of cytomegalovirus. We further discuss how this knowledge informs our understanding of the pathophysiology of cCMV and directs strategies aimed at improving outcomes and quality of life for congenitally infected children. We also provide an update on the epidemiology of cCMV in the United States, evolving scientific understanding of maternal-fetal transmission, enhanced screening approaches, and recognition of neonatal and long-term sequelae. Finally, we review the current landscape of pediatric cCMV research and provide recommendations for novel and high-priority areas for future investigation., (Copyright © 2022 by the American Academy of Pediatrics.)

Understanding racial and ethnic disparities in diagnostic rates of genetic testing is critical for health equity. We sought to understand the extent and cause of racial and ethnic disparities in diagnostic efficacy of comprehensive genetic testing (CGT) for sensorineural hearing loss (SNHL). We performed a retrospective cohort study at two tertiary children's hospitals on a diverse cohort of 240 consecutive pediatric patients (76% publicly insured, 82% non-White) with SNHL of unknown etiology who underwent CGT. Definite and possible genetic diagnoses were assigned for each patient, representing the likelihood of a genetic cause of hearing loss. Associations between diagnostic rates were examined. 3.8 ± 2.1 variants were detected per patient; this frequency did not vary between White/Asian and Hispanic/Black cohorts. Overall, 82% of variants were variants of uncertain significance (VUS). Compared with White and Asian subjects, variants identified among Hispanic and Black children were less likely to be classified as pathogenic/likely pathogenic (15% vs. 24%, p < 0.001), and Hispanic and Black children were less likely to have a definite genetic diagnosis (10% vs. 37%, p < 0.001). The adjusted odds ratio for definite genetic diagnosis in Black and Hispanic children compared with White and Asian children was 0.19. Expanding genetic diagnostic criteria to include predicted deleterious VUSs reduced these disparities between White/Asian and Hispanic/Black children, with comparable molecular diagnostic rates (41% vs. 38%, p = 0.72). However, in silico predictions are insufficiently valid for clinical use. Increased inclusion of underrepresented groups in genetic hearing-loss studies to clinically validate these variants is necessary to reduce racial and ethnic disparities in diagnostic efficacy of comprehensive genetic testing., (© 2021. The Author(s).)

Importance: Early detection and intervention of pediatric hearing loss is critical for language development and academic achievement. However, variations in the diagnostic workup and management of pediatric sensorineural hearing loss (SNHL) exist., Objective: To identify patient and clinician factors that are associated with variation in practice on a national level., Design, Setting, and Participants: This cross-sectional study used the Optum claims database to identify 53 711 unique children with SNHL between January 1, 2008, and December 31, 2018., Main Outcomes and Measures: National use rates and mean costs for diagnostic modalities (electrocardiogram, cytomegalovirus testing, magnetic resonance imaging, computed tomography, and genetic testing) and interventions (speech-language pathology, billed hearing aid services, and cochlear implant surgery) were reported. The associations of age, sex, SNHL laterality, clinician type, race/ethnicity, and household income with diagnostic workup and intervention use were measured in multivariable analyses., Results: Of 53 711 patients, 23 735 (44.2%) were girls, 2934 (5.5%) were Asian, 3797 (7.1%) were Black, 5626 (10.5%) were Hispanic, 33 441 (62.3%) were White, and the mean (SD) age was 7.3 (5.3) years. Of all patients, 32 200 (60.0%) were seen by general otolaryngologists, while 7573 (14.10%) were seen by pediatric otolaryngologists. Diagnostic workup was received by 14 647 patients (27.3%), while 13 482 (25.1%) received intervention. Use of genetic testing increased (odds ratio, 1.22 per year; 95% CI, 1.20-1.24), whereas use of computed tomography decreased (odds ratio, 0.93 per year; 95% CI, 0.92-0.94) during the study period. After adjusting for relevant covariables, children who were seen by pediatric otolaryngologists and geneticists had the highest odds of receiving workup and intervention. Additionally, racial/ethnic and economic disparities were observed in the use of most modalities of diagnostic workup and intervention for pediatric SNHL., Conclusions and Relevance: This cross-sectional study identified factors associated with disparities in the diagnostic workup and intervention of pediatric SNHL, thus highlighting the need for increased education and standardization in the management of this common sensory disorder.

We present detailed comparative analyses to assess population-level differences in patterns of genetic deafness between European/American and Japanese cohorts with non-syndromic hearing loss. One thousand eighty-three audiometric test results (921 European/American and 162 Japanese) from members of 168 families (48 European/American and 120 Japanese) with non-syndromic hearing loss secondary to pathogenic variants in one of three genes (KCNQ4, TECTA, WFS1) were studied. Audioprofile characteristics, specific mutation types, and protein domains were considered in the comparative analyses. Our findings support differences in audioprofiles driven by both mutation type (non-truncating vs. truncating) and ethnic background. The former finding confirms data that ascribe a phenotypic consequence to different mutation types in KCNQ4; the latter finding suggests that there are ethnic-specific effects (genetic and/or environmental) that impact gene-specific audioprofiles for TECTA and WFS1. Identifying the drivers of ethnic differences will refine our understanding of phenotype-genotype relationships and the biology of hearing and deafness.

Objective: To assess quality of life (QOL) in pediatric patients with sensorineural hearing loss (SNHL) with the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) and the Hearing Environments and Reflection on Quality of Life 26 (HEAR-QL-26) and HEAR-QL-28 surveys., Study Design: Prospective longitudinal study., Setting: Tertiary care center., Subjects and Methods: Surveys were administered to patients with SNHL (ages 2-18 years) from July 2016 to December 2018 at a multidisciplinary hearing loss clinic. Patients aged >7 years completed the HEAR-QL-26, HEAR-QL-28, and PedsQL 4.0 self-report tool, while parents completed the PedsQL 4.0 parent proxy report for children aged ≤7 years. Previously published data from children with normal hearing were used for controls. The independent t test was used for analysis., Results: In our cohort of 100 patients, the mean age was 7.7 years (SD, 4.5): 62 participants had bilateral SNHL; 63 had mild to moderate SNHL; and 37 had severe to profound SNHL. Sixty-eight patients used a hearing device. Mean (SD) total survey scores for the PedsQL 4.0 (ages 2-7 and 8-18 years), HEAR-QL-26 (ages 7-12 years), and HEAR-QL-28 (ages 13-18 years) were 83.9 (14.0), 79.2 (11.1), 81.2 (9.8), and 77.5 (11.3), respectively. Mean QOL scores for patients with SNHL were significantly lower than those for controls on the basis of previously published normative data ( P < .0001). There was no significant difference in QOL between children with unilateral and bilateral SNHL or between children with SNHL who did and did not require a hearing device. Low statistical power due to small subgroup sizes limited our analysis., Conclusion: It is feasible to collect QOL data from children with SNHL in a hearing loss clinic. Children with SNHL had significantly lower scores on validated QOL instruments when compared with peers with normal hearing.

Objective: To investigate the current practice of intratympanic steroid (ITS) injection for sudden sensorineural hearing loss (SSNHL) in the United Kingdom and link the data with data from the United States and continental Europe., Methods: A survey of 21 questions was distributed to members of the British Society of Otology using an online survey platform via ENT UK. Data obtained from UK otolaryngologists (n = 171) were integrated with previously published data from other countries, including the United States (n = 63) and continental Europe (n = 908)., Results: In the United Kingdom, 62% of responding otolaryngologists use ITS injection for SSNHL, while 38% do not. Of those using ITS, 59% use it as first-line treatment, either using it in conjunction with oral steroids (51%) or using it as monotherapy (8%). Of those that use ITS, a majority (83%) use it as salvage therapy when primary treatment with systemic steroids has failed, and similar results are found in the continental Europe and US surveys. The most commonly used preparation is dexamethasone. Responses to questions regarding treatment regimes used are enlightening and show considerable variation in the treatment regimes used within and between countries., Conclusions: There is a wide variation in practice with regards to ITS for SSNHL hearing loss in the United Kingdom, United States, and continental Europe. In the absence of protocols or definitive guidance from published literature, knowledge of contemporary practice may help guide or encourage reevaluation of clinical practice and will help guide the design of future clinical trials.

Background: The hearing in noise test (HINT) is the most popular adaptive test used to evaluate speech in noise performance, especially in context of hearing aid features. However, the number of conditions that can be tested on the HINT is limited by a small speech corpus. The American English Matrix test (AEMT) is a new alternative adaptive speech in noise test with a larger speech corpus. The study examined the relationships between the performance of hearing aid wearers on the HINT and the AEMT., Purpose: To examine whether there was a difference in performance of hearing aid wearers on the HINT and the AEMT. A secondary purpose, given the AEMT's steep performance-intensity function, was to determine whether the AEMT is more sensitive to changes in speech recognition resulting from directional (DIR) microphone processing in hearing aids., Research Design: A repeated measures design was used in this study. Multiple measurements were made on each subject. Each measurement involved a different experimental condition., Study Sample: Ten adults with hearing loss participated in this study., Data Collection and Analysis: All participants completed the AEMT and HINT, using adaptive and fixed test formats while wearing hearing aids. Speech recognition was assessed in two hearing aid microphone settings-omnidirectional and fixed DIR. All testing was conducted via sound field presentation. Performance on HINT and AEMT were systematically compared across all test conditions using a linear model with repeated measures., Results: The results of this study revealed that adult hearing aid users perform differently on the HINT and AEMT, with adaptive AEMT testing yielding significantly better (more negative) thresholds than the HINT. Slopes of performance intensity functions obtained by testing at multiple fixed signal-to-noise ratios, revealed a somewhat steeper slope for the HINT compared with the AEMT. Despite this steeper slope, the benefit provided by DIR microphones was not significantly different between the two speech tests., Conclusions: The observation of similar DIR benefits of the HINT and AEMT suggests that the HINT and AEMT are equally sensitive to changes in speech recognition thresholds following intervention. Therefore, the decision to use the AEMT or the HINT will depend on the purpose of the study and/or the technology being investigated. Other test related factors such as available sentence corpus, learning effects and test time will also influence test selection., (American Academy of Audiology.)

Objective The American Academy of Otolaryngology-Head and Neck Surgery Foundation clinical practice guideline (CPG) proposes recommendations regarding sudden sensorineural hearing loss (SSNHL). SSNHL is managed by primary care, emergency medicine, and otolaryngology providers in the Department of Defense (DoD). However, their adherence to this CPG is unknown. We sought to determine provider compliance and identify areas for improvement. Study Design Case series with chart review. Setting DoD's electronic medical record. Subjects and Methods Patients with SSNHL (N = 204) were treated between March 1, 2012, and September 30, 2015. Time from onset of symptoms to evaluation by primary care, emergency department, audiology, and otolaryngology providers and treatments were analyzed. Results The average interval from onset of symptoms to evaluation by a primary care or emergency department provider was 4.86 days (95% CI, 3.46-6.26). Time from presentation to ear, nose, and throat and audiologic evaluation was 15.26 days (95% CI, 12.34-18.20) and 14.16 days (95% CI, 11.31-17.01), respectively. Diagnostic workup included magnetic resonance imaging (n = 150, 73.5%), computed tomography (n = 28, 13.7%), and laboratory testing (n = 50, 24.5%). Oral steroids were used in 137 (67.2%) patients, with 78.8% treated with the recommended dose. Intratympanic steroids were utilized in 65 (31.9%) patients, with variable dosing. Conclusion The DoD is uniquely positioned to evaluate adherence to CPGs on national and international levels given the robust and standardized electronic medical record. Areas of improvement include timely identification of SSNHL with rapid referral to ear, nose, and throat and audiology providers; minimizing unnecessary imaging, laboratory testing, and medications; and correct dosing of oral and intratympanic steroids.

Objective: To examine the possible speech recognition and health related quality of life (HRQoL) benefits of cochlear implantation among adults with asymmetric sensorineural hearing loss., Study Design: Retrospective chart review, single-subject design., Methods: A total of 45 adult cochlear implant recipients with asymmetric sensorineural hearing loss where performance for the best-aided condition exceeded 60% correct open set sentence recognition in quiet, and the implanted ear met traditional candidacy criteria. End point testing of the implanted ear was evaluated with use of the Consonant-Vowel Nucleus-Consonant (CNC) word test and AzBio sentence test materials in quiet, and bimodally with the AzBio sentence test materials in noise at +5 dB signal-to-noise ratio (SNR). HRQoL was measured using the Nijmegen Cochlear Implant Questionnaire (NCIQ)., Results: Measured in quiet, with the non-implanted ear plugged, the average CNC word scores increased from 9.1% preoperatively to 55.7% (p < 0.01) at the 6-month post-activation test interval. Similarly, average AzBio sentence scores in quiet, with the non-implanted ear plugged, increased from 13.9% preoperatively to 73.4% (p < 0.01) at the 6-month post-activation test interval. Finally, in the bilateral/bimodal condition, the AzBio sentence score in +5 dB SNR improved from an average of 26.8% preoperatively to 52.4% (p < 0.01) at the 6-month test interval. Results of the NCIQ showed improved scores on all six subdomains., Conclusions: These data demonstrate significant benefit of cochlear implantation among a group of postlingually deafened adults whose preoperative hearing and aided speech recognition fell outside of the currently specified Food and Drug Administration candidacy guidelines. Results of this study support the evaluation of a candidate's speech recognition in noise in the best-aided condition to adequately assess candidacy for a cochlear implant.

Objective To reevaluate asymmetric sensorineural hearing loss (ASNHL) criteria used to justify magnetic resonance imaging (MRI) in the evaluation of retrocochlear tumors in a military population. Study Design Retrospective case-control study. Setting Tertiary care military medical center. Subjects and Methods Patients with military service and a history of ASNHL prompting referral for MRI, with or without retrocochlear tumors, were compared between 2005 and 2016. Predictor variables included pure tone ASNHL, speech audiometry, and a history of noise exposure. Logistic regression models for hearing asymmetries were performed, and receiver operator curves were used to calculate sensitivity and specificity. Results Thirty-eight retrocochlear tumors were identified. The MRI diagnosis rate for patients with ASHNL was 0.85%. Patients with tumors were slightly older (42 vs 37 years, P = .021) and had less noise exposure (47% vs 85%, P < .001). A sensitivity of 0.83 and a specificity of 0.58 were calculated for asymmetries ≥10 dB at 2000 Hz without adjusting for noise exposure. Instituting this imaging threshold would have reduced the number of MRI scans by half while missing 16% of tumors. Conclusion The tumor diagnosis rate among those undergoing MRI for ASNHL is low in the military population, likely because service-related noise exposure commonly causes ASNHL. Optimal MRI referral criteria should conserve resources while balancing the risks of over- and underdiagnosis. For those with a history of military service, an asymmetry ≥10 dB at 2000 Hz among patients meeting current ANSHL referral criteria is most predictive of a retrocochlear tumor.

Purpose: Patients treated with cranial radiation therapy (RT) are at risk for sensorineural hearing loss (SNHL). Although SNHL is often characterized as a delayed consequence of anticancer therapy, longitudinal reports of SNHL in childhood cancer survivors treated with contemporary RT are limited. We report the incidence, onset, severity, and long-term trajectory of SNHL among children receiving RT. Potential risk factors for SNHL were also identified., Patients and Methods: Serial audiologic testing was conducted on 235 pediatric patients who were treated with conformal or intensity-modulated RT as part of an institutional phase II trial for localized primary brain tumors, including craniopharyngioma, ependymoma, and juvenile pilocytic astrocytoma. All but one patient had measurable cochlear radiation dose (CRD) greater than 0 Gy. The median follow-up from RT initiation to latest audiogram was 9 years with a median of 11 post-RT audiograms per patient. Audiograms were classified by the Chang Ototoxicity Grading Scale. Progression was defined by an increase in Chang grade from SNHL onset to the most recent evaluation., Results: At last evaluation, SNHL was prevalent in 14% of patients: 2.1% had mild and 11.9% had significant SNHL requiring hearing aids. Median time from RT to SNHL onset was 3.6 years (range, 0.4 to 13.2 years). Among 29 patients with follow-up evaluations after SNHL onset, 65.5% experienced continued decline in hearing sensitivity in either ear and 34.5% had no change. Younger age at RT initiation (hazard ratio [HR], 2.32; 95% CI, 1.21 to 4.46), higher CRD (HR, 1.07; 95% CI, 1.03 to 1.11), and cerebrospinal fluid shunting (HR, 2.02; 95% CI, 1.07 to 3.78) were associated with SNHL., Conclusion: SNHL is a late effect of RT that likely worsens over time. Long-term audiologic follow-up for a minimum of 10 years post-RT is recommended., (© 2016 by American Society of Clinical Oncology.)

Infant hearing loss is common. Screening is performed in more than 98% of US infants. Otolaryngologists play an important role in identification and management of infants and children who are deaf and hard of hearing. Otolaryngologists should routinely assess for hearing screening results and intervene for screens not passed. Long-term follow-up and reassessment of patients with hearing loss is an ongoing component of otolaryngology practice. This article reviews the otolaryngologist's role in the management of infants and children who are deaf or hard of hearing from screening to intervention and management., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Universal newborn hearing screening has significantly improved the ability to identify patients with congenital sensorineural hearing loss (SNHL), which results in earlier treatment and better hearing and development outcomes. It is recommended that patients born with SNHL who meet criteria receive cochlear implants (CIs) by a target age of 12 months, however many children are being implanted at an older age. This study aims to describe populations of pre-lingual patients with SNHL that are at risk for delayed implantation and to identify and analyze barriers that cause this delay., Methods: Charts of patients receiving a CI between January 2008 and June 2012 at a tertiary care cochlear implant center were reviewed retrospectively. We looked at patient demographics, age at hearing loss diagnosis, age at implantation, and etiology of hearing loss. Barriers to implantation were identified through surveys completed by team members., Results: Fifty-seven CI recipients were identified of which 42 were in patients with pre-lingual SNHL. SNHL etiology included: cochlear dysplasia (18%), GJB2/GJB6 (17%), acquired (10%) extreme prematurity (9%), and idiopathic (46%). The median age of SNHL diagnosis for pre-lingual patients was 15 months. Compared to private insurance, public insurance status was associated with SNHL diagnosis at a significantly later median age (20.0 vs. 4.0 months, p=0.024), and with a significantly longer median interval from diagnosis to implantation (25.5 vs. 11.0 months, p=0.029). While cochlear implant team members identified delayed insurance approval and medical comorbidities as reasons for delayed implantation, the most significant factor identified was parental, with delayed/missed appointments or reluctance for evaluations or surgery., Conclusion: 52% of patients with pre-lingual SNHL that met criteria for CI were implanted more than 12 months after diagnosis. Having public or no insurance was significantly associated with delayed implantation. Parental barriers were most common factors cited for delays in implantation. Overcoming these delays necessitates appropriate identification of at risk patients and creating a system to educate families and chaperone them through the process., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To characterize mitochondrial sequence variants present in a nationwide hereditary deafness DNA repository of samples from deaf subjects and to define the clinical presentation and audiometric characteristics of individuals with a mitochondrial sequence variant., Study Design: Retrospective review of results for select mitochondrial mutations performed on DNA samples from subjects compiled from 1997 to 2009., Setting: National hereditary deafness DNA repository., Subjects and Methods: Available samples from subjects in the repository were screened to identify those with mitochondrial sequence variants. Clinical data on the nature of mutation, type and severity of the hearing loss, and sex, age at diagnosis, family history of hearing loss, and ethnicity were analyzed., Results: Eighty-six patients were identified with mitochondrial mutations or 3.5% of the subjects studied. Among those with mitochondrial mutations, 21 (24.4%) had the m.7445A>G substitution, 18 (20.9%) had the m.1555A>G substitution, 18 (20.9%) had the m.961T>G substitution, and 29 (33.7%) had a m.961delT+C(n) complex deletion. The majority of patients had bilateral severe to profound hearing loss. Fifty-three (62%) patients were female, and a family history of hearing loss was documented in 66 (76.7%) patients. The deafness was recognized prior to 3 years of age in 26 patients., Conclusion: Mitochondrial deafness in this sample was associated with a variety of genetic mutations and a wide spectrum of clinical presentations. Because of increased aminoglycoside susceptibility associated with some forms of mitochondrial deafness, matrilineal relatives may be at risk in those cases, highlighting the importance of making an accurate diagnosis prior to exposure.

Objective: To evaluate the performance of a next-generation sequencing (NGS)-based targeted resequencing genetic test, OtoSeq, to identify the sequence variants in the genes causing sensorineural hearing loss (SNHL)., Study Design: Retrospective study., Setting: Tertiary children's hospital., Subjects and Methods: A total of 8 individuals presenting with prelingual hearing loss were used in this study. The coding and flanking intronic regions of 24 well-studied SNHL genes were enriched using microdroplet polymerase chain reaction and sequenced on an Illumina HiSeq 2000 sequencer. The filtered high-quality sequence reads were mapped to reference sequence, and variants were detected using NextGENe software., Results: A total of 1148 sequence variants were detected in 8 samples in 24 genes. Using in-house developed NGS data analysis criteria, we classified 810 (~71%) of these variants as potential true variants that include previously detected pathogenic mutations in 5 patients. To validate our strategy, we Sanger sequenced the target regions of 5 of the 24 genes, accounting for about 29.2% of all target sequence. Our results showed >99.99% concordance between NGS and Sanger sequencing in these 5 genes, resulting in an analytical sensitivity and specificity of 100% and 99.997%, respectively. We were able to successfully detect single base substitutions, small deletions, and insertions of up to 22 nucleotides., Conclusion: This study demonstrated that our NGS-based mutation screening strategy is highly sensitive and specific in detecting sequence variants in the SNHL genes. Therefore, we propose that this NGS-based targeted sequencing method would be an alternative to current technologies for identifying the multiple genetic causes of SNHL.

Objective: This study examined specific spoken language abilities of 160 children with severe-to-profound sensorineural hearing loss followed prospectively 4, 5, or 6 years after cochlear implantation., Study Sample: Ninety-eight children received implants before 2.5 years, and 62 children received implants between 2.5 and 5 years of age., Design: Language was assessed using four subtests of the Comprehensive Assessment of Spoken Language (CASL). Standard scores were evaluated by contrasting age of implantation and follow-up test time., Results: Children implanted under 2.5 years of age achieved higher standard scores than children with older ages of implantation for expressive vocabulary, expressive syntax, and pragmatic judgments. However, in both groups, some children performed more than two standard deviations below the standardization group mean, while some scored at or well above the mean., Conclusions: Younger ages of implantation are associated with higher levels of performance, while later ages of implantation are associated with higher probabilities of continued language delays, particularly within subdomains of grammar and pragmatics. Longitudinal data from this cohort study demonstrate that after 6 years of implant experience, there is large variability in language outcomes associated with modifiers of rates of language learning that differ as children with implants age.

Introduction: Hearing loss is common and, in young persons, can compromise social development and educational achievement. Exposure to heavy metals has been proposed as an important risk factor for hearing loss., Methods: We evaluated the cross-sectional associations between blood lead, blood mercury, and urinary cadmium and arsenic levels and audiometrically determined hearing loss in participants aged 12 to 19 years in the 2005-2008 National Health and Nutrition Examination Survey after accounting for the complex survey design. There were 2535 individuals available for analysis of blood lead and mercury levels, 878 for urinary cadmium levels, and 875 for urinary arsenic levels. Multivariate logistic regression was used to calculate adjusted odds ratios (ORs) and 95% CIs., Results: A blood lead level greater than or equal to 2 μg/dL (to convert to micromoles per liter, multiply by 0.0483) compared with less than 1 μg/dL was associated with increased odds of high-frequency hearing loss (OR, 2.22; 95% CI, 1.39-3.56). Individuals in the highest quartile of urinary cadmium levels had significantly higher odds of low-frequency hearing loss than those in the lowest quartile (OR, 3.08; 95% CI, 1.02-9.25). There was no overall association between quartiles of blood mercury or urinary arsenic levels and hearing loss., Conclusion: Blood lead levels well below the current recommended action level are associated with substantially increased odds of high-frequency hearing loss.

Objectives: To evaluate current trends in the management of idiopathic sudden sensorineural hearing loss (ISSNHL), determine if variance in diagnostic and treatment protocols exists, and compare diagnostic and treatment strategies of ISSNHL between nonotologists/neurotologists (NONs) and otologists/neurotologists (ONs)., Study Design: Cross-sectional survey of practicing otolaryngologists., Setting: Otolaryngology practices within the United States., Subjects and Methods: In January 2010, a survey was mailed to 500 NONs and 500 ONs. Data were collected and analyzed using χ(2), standard deviations, and variance., Results: A variety and distribution of responses were seen in the definition of ISSNHL, including dB loss necessary for diagnosis, number of consecutive frequencies involved, and maximum duration of hearing loss. Differences in diagnostic tools were also seen, with 50.4% of respondents (NON 34.2%, ON 66.7%; P = .0001) always using magnetic resonance imaging in their workup. Of the total respondents, 26.7% (NON 35.0%, ON 18.3%; P < .0001) preferred oral steroids alone; 22.1% (NON 11.7%, ON 32.5%; P < .0001) preferred a combination of oral and intratympanic steroids. Of the respondents, 68.6% (NON 57.5%, ON 80.0%; P = .0003) would continue with additional treatment after partial response; 20.8% (NON 33.3%, ON 8.3%; P < .005) would retreat with oral steroids alone and 46.6% (NON 35.8%, ON 57.3%; P < .05) with intratympanic injections. Overall, 69.2% (NON 45.8%, ON 92.5%; P = .0001) were very comfortable managing ISSNHL., Conclusion: Significant differences exist in the diagnosis and treatment of ISSNHL. Such lack of uniformity highlights the need for strong evidence-based research-ultimately leading to formalized practice guidelines and educational outreach.

Objectives: To describe clinical findings from a multidisciplinary program for children with permanent hearing loss (PHL)., Methods: Retrospective chart review at a tertiary care children's hospital., Patients: Two hundred patients charts were selected from the population of 260 children with permanent hearing loss presenting between July 2005 and December 2006., Main Outcome Measures: PHL etiology; radiographic findings; clinical findings by genetics, ophthalmology, developmental pediatrics, speech pathology, and aural rehabilitation., Results: Etiology of hearing loss was determined in 60% of subjects. Genetic causes of hearing loss were identified or presumed (positive history of first degree relative with hearing loss) in 27% of the children. Structural ear anomalies were found in 20% of children. Among the 36% of children with CNS imaging, abnormal findings were noted in 32%. There were a high rate of ophthalmological findings (53%) among children seen by ophthalmology (n = 105). Neurodevelopmental evaluations were completed in 58% of subjects and clinically significant findings were noted in 68%. Of the 61% of children who receiving received speech/language evaluations, 77% required intervention. Over half of the 40% of subjects who had an aural rehabilitation evaluation needed therapy. There were not significant differences in rates of findings for children with mild or unilateral hearing loss as compared to children with more severe degrees of hearing loss., Conclusions: Interdisciplinary medical evaluation of children with PHL allows for the identification and treatment of clinically significant ophthalmologic, neurodevelopmental, genetic, and speech/language disorders. A high rate of CNS and temporal bone abnormalities were identified. These findings provide an understanding of the importance of considering thorough medical and developmental evaluations among children who are deaf/hard of hearing., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate the hypothesis that second-hand smoke (SHS) exposure is associated with sensorineural hearing loss (SNHL) in adolescents., Design: A complex, multistage, stratified geographic area design for collecting representative data from the noninstitutionalized US population., Participants: Cross-sectional data from National Health and Nutrition Examination Survey (2005-2006) were available for 1533 participants 12 to 19 years of age who underwent audiometric testing, had serum cotinine levels available, and were not actively smoking., Main Outcome Measures: SNHL was defined as an average pure-tone level greater than 15 dB for 0.5, 1, and 2 kHz (low frequency) and 3, 4, 6, and 8 kHz (high frequency)., Results: Secondhand smoke exposure, as assessed by serum cotinine levels, was associated with elevated pure-tone hearing thresholds at 2, 3, and 4 kHz, a higher rate of unilateral low-frequency SNHL (11.8% vs 7.5%; P < .04), and a 1.83-fold increased risk of unilateral low-frequency SNHL in multivariate analyses (95% confidence interval, 1.08-3.41). The prevalence of SNHL was directly related to level of SHS exposure as reflected by serum cotinine levels. In addition, nearly 82% of adolescents with SNHL did not recognize hearing difficulties., Conclusions: Secondhand smoke is associated with elevated pure-tone thresholds and an increased prevalence of low-frequency SNHL that is directly related to level of exposure, and most affected individuals are unaware of the hearing loss. Thus, adolescents exposed to SHS may need to be closely monitored for early hearing loss with periodic audiologic testing.

Objectives/hypothesis: To determine the cause of autosomal dominant hearing loss segregating in an American family., Study Design: Family study., Methods: Otologic and audiometric examination was performed on affected family members. Genome wide parametric multipoint linkage mapping using a dominant model was performed with Affymetrix 50K GeneChip data. Direct sequencing was used to confirm the causative mutation., Results: In American family 467, segregating autosomal dominant nonsyndromic hearing loss, a novel heterozygous missense mutation (c.362T>C; p.F121S) was identified in the COCH gene. This mutation was also associated with vestibular dysfunction typical of other DFNA9 families. However, affected family members also exhibited memory loss and night blindness., Conclusions: The novel COCH mutation affects the functionally important limulus factor C, Coch-5b2 and Lgl1 domain where most DFNA9 mutations have been localized. The onset of the hearing loss, in the 2nd or 3rd decade of life, is earlier than in most DFNA9 families. The progression of hearing loss and vestibular dysfunction in the American family is typical of other DFNA9 families with mutations in this domain. Memory loss and night blindness have not been previously reported in DFNA9 families.

Objectives: (1) To analyze if socioeconomic status influences access to cochlear implantation in an environment with adequate Medicaid reimbursement. (2) To determine the impact of socioeconomic status on outcomes after unilateral cochlear implantation., Design: Retrospective cohort study., Setting: University Hospitals Case Medical Center and Rainbow Babies and Children's Hospital (tertiary referral center), Cleveland, Ohio., Participants: Pediatric patients (age range, newborn to 18 years) who received unilateral cochlear implantation during the period 1996 to 2008., Main Outcome Measures: Access to cochlear implantation after referral to a cochlear implant center, postoperative complications, compliance with follow-up appointments, and access to sequential bilateral cochlear implantation., Results: A total of 133 pediatric patients were included in this study; 64 were Medicaid-insured patients and 69 were privately insured patients. There was no statistical difference in the odds of initial cochlear implantation, age at referral, or age at implantation between the 2 groups. The odds of prelingual Medicaid-insured patients receiving sequential bilateral cochlear implantation was less than half that of the privately insured group (odds ratio [OR], 0.43; P = .03). The odds of complications in Medicaid-insured children were almost 5-fold greater than the odds for privately insured children (OR, 4.6; P = .03). There were 10 complications in 51 Medicaid-insured patients (19.6%) as opposed to 3 in 61 privately insured patients (4.9%). Medicaid-insured patients missed substantially more follow-up appointments overall (35% vs 23%) and more consecutive visits (1.9 vs 1.1) compared with privately insured patients., Conclusions: In an environment with adequate Medicaid reimbursement, eligible children have equal access to cochlear implantation, regardless of socioeconomic background. However, lower socioeconomic background is associated with higher rates of postoperative complications, worse follow-up compliance, and lower rates of sequential bilateral implantation, observed herein in Medicaid-insured patients. These findings present opportunities for cochlear implant centers to create programs to address such downstream disparities.

Objective: The purpose of the study is to determine whether Caribbean Hispanic and African admixture populations have a paucity of mutations in GJB2, encoding connexin 26., Methods: We reported the paucity of mutations in GJB2 and deletions in GJB6 in Caribbean Hispanic and African admixture populations in the Bronx, NY, in 2007 [1]. We have now collected 102 additional probands with non-syndromic sensorineural hearing impairment (NSHI), for a total of 209. We describe here a presentation of the combined data., Results: Of the 209 probands, 36% have affected family members with NSHI and the rest have sporadic occurrence. Of the familial cases, 43% had a first-degree relative affected, and the remainder a more distant relative. The hearing impairment ranged from unilateral mild to bilateral profound, with 76% exhibiting bilateral NSHI (BLNSHI). The single coding exon of the GJB2 gene was sequenced in 209 probands, PCR screening for del(GJB6-D13S1830) and sequencing of the non-coding exon of GJB2 to look for the known splice site mutation was performed in 32 NSHI patients with a heterozygous variation in GJB2, and multiplex ligation-dependent probe amplification (MLPA) testing of GJB2 and GJB6 exon deletions or amplifications (P163 GJB-WFS1 kit) was done in 70 probands. Eight unrelated individuals had biallelic GJB2 mutations, representing 4% of our entire cohort, or 5% of our probands with BLNSHI. Of 127 probands of Hispanic or African descent with BLNSHI, six (4.7%) had biallelic pathogenic mutations, three (2.3%) had monoallelic mutations and 118 (93%) had no disease-causing mutations in GJB2. At the same time, no major deletions were identified either by PCR screening (del(GJB6-D13S1830)) or by MLPA analysis (GJB2 or GJB6), and no subjects had the known splice site mutation in GJB2., Conclusion: These results demonstrate that GJB2 is not the major contributor to the genetic basis of NSHI for the Bronx minority admixture populations., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Current protocols presumably use criteria that are chosen on the basis of the sensitivity and specificity rates they produce. Such an approach emphasizes test performance but does not include societal implications of the benefit of early identification. The purpose of the present analysis was to evaluate an approach to selecting criteria for use in Universal Newborn Hearing Screening (UNHS) programs that uses benefit-cost ratio (BCR) to demonstrate an alternative method to audiologists, administrators, and others involved in UNHS protocol decisions., Design: Existing data from more than 1200 ears were used to analyze BCR as a function of Distortion Product Otoacoustic Emission (DPOAE) level. These data were selected because both audiometric and DPOAE data were available on every ear. Although these data were not obtained in newborns, this compromise was necessary because audiometric outcomes (especially in infants with congenital hearing loss) in neonates are either lacking or limited in number. As such, it is important to note that the characteristics of responses from the group of subjects that formed the bases of the present analyses are different from those for neonates. This limits the extent to which actual criterion levels can be selected but should not affect the general approach of using BCR as a framework for considering UNHS criteria. Estimates of the prevalence of congenital hearing loss identified through UNHS in 37 states and U.S. territories in 2004 were used to calculate BCR. A range of estimates for the lifetime monetary benefits and yearly costs for UNHS were used, based on data available in the literature. Still, exact benefits and costs are difficult to know. Both one-step (DPOAE alone) and two-step (DPOAE followed by automated auditory brainstem response, AABR) screening paradigms were considered in the calculation of BCR. The influence of middle ear effusion was simulated by incorporating a range of expected DPOAE level reductions into an additional BCR analyses, Results: Our calculations indicate that for a range of proposed benefit and cost estimates, the monetary benefits of both one-step (DPOAE alone) and two-step (DPOAE followed by AABR) NHS programs outweigh programmatic costs. Our calculations indicate that BCR is robust in that it can be applied regardless of the values that are assigned to benefit and cost. Maximum BCR was identified and remained stable regardless of these values; however, it was recognized that the use of maximum BCR could result in reduced test sensitivity and may not be optimal for use in UNHS programs. The inclusion of secondary AABR screening increases BCR but does not alter the DPOAE criterion level at which maximum BCR occurs. The model of middle ear effusion reduces overall DPOAE level, subsequently lowering the DPOAE criterion level at which maximum BCR was obtained, Conclusion: BCR is one of several alternative methods for choosing UNHS criteria, in which the evaluation of costs and benefits allows clinical and societal considerations to be incorporated into the pass/refer decision in a meaningful way. Although some of the benefits of early identification of hearing impairment cannot be estimated through a monetary analysis, such as improved psychosocial development and quality of life, this article provides an alternative to audiologists and administrators for selecting UNHS protocols that includes consideration of societal implications of UNHS screening criteria. BCR suggests that UNHS is a worthwhile investment for society as benefits always outweigh costs, at least for the estimations included in this article. Although the use of screening criteria that maximize BCR results in lower test sensitivity compared with other criteria, BCR may be used to select criteria that result in increased test sensitivity and still provide a high, although not maximal, BCR. Using BCR analysis provides a framework in which the societal implications of NHS protocols are considered and emphasizes the value of UNHS.

Conclusions: T2-weighted fast-spin echo magnetic resonance imaging (MRI) can be an economically beneficial protocol for screening patients with asymmetric sensorineural hearing loss without other neurologic findings in a public hospital population., Objective: The goal of this study was to determine if fast spin echo T2 MRI is similar to gadolinium-enhanced MRI in evaluating asymmetric sensorineural hearing loss in a county hospital population., Patients and Methods: This was a retrospective chart review of all outpatients seen at a public hospital, comprising patients with no other cranial nerve findings who underwent gadolinium-enhanced MRI of the internal auditory canal and brain between January 2002 and September 2003. Patients with >15 dB difference in hearing at one frequency or 10 dB hearing difference at two frequencies underwent gadolinium-enhanced MRI scan with FSE T2 sequence as part of the examination protocol., Results: A total of 146 patients were identified who met all the inclusion criteria for the study. Of the 146 MRI scans performed, abnormalities were seen on 71 of them, the majority of which were inconsequential. No acoustic neuromas were identified in our study population. Cost savings of over 100,000 dollars would have been realized if only T2 FSE protocols had been used.

Given the rapidly growing area of molecular genetic laboratory testing, we sought to assess changing issues over a 2-year period of time pertaining to the availability of testing for GJB2 mutations associated with non-syndromic hearing loss. Laboratory assessments carried out by telephone interviews with directors or other key personnel revealed variations among laboratories in informed consent practices, evaluation of test requests for appropriateness, and the reporting of results. From 1999 to 2000, referral patterns shifted as did sources for reimbursement, policies regarding evaluation of incoming test requests, and reporting procedures. We propose that these results reflect changes occurring as a result of a new test moving from the research to the clinical phase.

Objective: To analyze the phenotype in a 5-generation DFNA13 family with a missense mutation in the COL11A2 gene that causes autosomal dominant, presumably prelingual, nonsyndromic sensorineural hearing impairment., Design: Family study., Setting: University hospital department., Patients: Twenty mutation carriers from a large American kindred., Methods: Cross-sectional analysis using pure-tone threshold measurements at 0.25, 0.5, 1, 2, 4, and 8 kHz. The audiometric configuration was evaluated according to an existing consensus protocol. The significance of features relating to audiometric configuration was tested using 1-way analysis of variance. Progression was evaluated with linear regression analyses of threshold-on-age., Results: Most individuals showed midfrequency (U-shaped) characteristics. The mean threshold in generations IV and V was 44 dB at 1, 2, and 4 kHz (midfrequencies); it was 29 dB at the other frequencies (0.25, 0.5, and 8 kHz). There was no significant progression beyond presbyacusis., Conclusion: The trait in this family can be characterized as autosomal dominant, nonprogressive, presumably prelingual, midfrequency sensorineural hearing impairment.

This study compared two approaches for measuring speech-recognition thresholds (SRTs): the ASHA (1979) and ASHA (1988) guidelines. The subjects were 30 veterans with impaired hearing. Contrary to prior reports, the ASHA (1979) approach was found to be slightly less time consuming than the ASHA (1988) approach. The ASHA (1979) approach also yielded slightly better pure tone average (PTA)-SRT agreement than the ASHA (1988) approach for two of three generally accepted measures for comparing these tests; the third measure yielded equivalent results. Although statistically significant, the differences between these guidelines in test time and PTA-SRT agreement were small and are considered to be clinically insignificant.

The authors emphasize the importance of early identification and early intervention concerning the management of children with Sensorineural Hearing Loss. The pediatrician plays a critical role in initiating the necessary clinical and audiological evaluations. Guidelines and treatment options are reviewed.