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Hearing Disorders: HELP
Articles from Toronto
Based on 260 articles published since 2010
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These are the 260 published articles about Hearing Disorders that originated from Toronto during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11
26 Review Asymmetric Hearing During Development: The Aural Preference Syndrome and Treatment Options. 2015

Gordon, Karen / Henkin, Yael / Kral, Andrej. ·Archie's Cochlear Implant Laboratory, The Hospital for Sick Children, Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Canada; karen.gordon@utoronto.ca. · Hearing, Speech, and Language Center, Sheba Medical Center, Tel Hashomer, Department of Communication Disorders, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and. · Cluster of Excellence Hearing4all, Institute of AudioNeuroTechnology, Hannover, Germany; Department of Experimental Otology, ENT Clinics, School of Medicine, Hannover Medical University, Hannover, Germany; and School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, Texas. ·Pediatrics · Pubmed #26055845.

ABSTRACT: Deafness affects ∼2 in 1000 children and is one of the most common congenital impairments. Permanent hearing loss can be treated by fitting hearing aids. More severe to profound deafness is an indication for cochlear implantation. Although newborn hearing screening programs have increased the identification of asymmetric hearing loss, parents and caregivers of children with single-sided deafness are often hesitant to pursue therapy for the deaf ear. Delayed intervention has consequences for recovery of hearing. It has long been reported that asymmetric hearing loss/single-sided deafness compromises speech and language development and educational outcomes in children. Recent studies in animal models of deafness and in children consistently show evidence of an "aural preference syndrome" in which single-sided deafness in early childhood reorganizes the developing auditory pathways toward the hearing ear, with weaker central representation of the deaf ear. Delayed therapy consequently compromises benefit for the deaf ear, with slow rates of improvement measured over time. Therefore, asymmetric hearing needs early identification and intervention. Providing early effective stimulation in both ears through appropriate fitting of auditory prostheses, including hearing aids and cochlear implants, within a sensitive period in development has a cardinal role for securing the function of the impaired ear and for restoring binaural/spatial hearing. The impacts of asymmetric hearing loss on the developing auditory system and on spoken language development have often been underestimated. Thus, the traditional minimalist approach to clinical management aimed at 1 functional ear should be modified on the basis of current evidence.

27 Review Review of weapon noise measurement and damage risk criteria: considerations for auditory protection and performance. 2015

Nakashima, Ann / Farinaccio, Rocco. ·Defence Research and Development Canada, Toronto Research Centre 1133 Sheppard Avenue West, Toronto, Ontario, Canada M3K 2C9. · Defence Research and Development Canada, Valcartier Research Centre 2459 Pie-XI Blvd North, Val-Bélair, Québec, Canada G3J 1X5. ·Mil Med · Pubmed #25826345.

ABSTRACT: Noise-induced hearing loss resulting from weapon noise exposure has been studied for decades. A summary of recent work in weapon noise signal analysis, current knowledge of hearing damage risk criteria, and auditory performance in impulse noise is presented. Most of the currently used damage risk criteria are based on data that cannot be replicated or verified. There is a need to address the effects of combined noise exposures, from similar or different weapons and continuous background noise, in future noise exposure regulations. Advancements in hearing protection technology have expanded the options available to soldiers. Individual selection of hearing protection devices that are best suited to the type of exposure, the auditory task requirements, and hearing status of the user could help to facilitate their use. However, hearing protection devices affect auditory performance, which in turn affects situational awareness in the field. This includes communication capability and the localization and identification of threats. Laboratory training using high-fidelity weapon noise recordings has the potential to improve the auditory performance of soldiers in the field, providing a low-cost tool to enhance readiness for combat.

28 Review Aminoglycoside-induced ototoxicity. 2015

Leis, Jerome A / Rutka, John A / Gold, Wayne L. ·Division of Infectious Diseases (Leis, Gold), Department of Medicine · Centre for Quality Improvement and Patient Safety (Leis) · Department of Otolaryngology - Head and Neck Surgery (Rutka), University of Toronto, Toronto, Ont. ·CMAJ · Pubmed #25225217.

ABSTRACT: -- No abstract --

29 Review Turning down the noise: the benefit of musical training on the aging auditory brain. 2014

Alain, Claude / Zendel, Benjamin Rich / Hutka, Stefanie / Bidelman, Gavin M. ·Rotman Research Institute, Baycrest Centre for Geriatric Care, Canada; Department of Psychology, University of Toronto, Canada. Electronic address: calain@research.baycrest.org. · International Laboratory for Brain, Music and Sound Research (BRAMS), Département de Psychologie, Université de Montréal, Québec, Canada; Centre de Recherche, Institut Universitaire de Gériatrie de Montréal, Québec, Canada. · Rotman Research Institute, Baycrest Centre for Geriatric Care, Canada; Department of Psychology, University of Toronto, Canada. · Institute for Intelligent Systems & School of Communication Sciences and Disorders, University of Memphis, USA. ·Hear Res · Pubmed #23831039.

ABSTRACT: Age-related decline in hearing abilities is a ubiquitous part of aging, and commonly impacts speech understanding, especially when there are competing sound sources. While such age effects are partially due to changes within the cochlea, difficulties typically exist beyond measurable hearing loss, suggesting that central brain processes, as opposed to simple peripheral mechanisms (e.g., hearing sensitivity), play a critical role in governing hearing abilities late into life. Current training regimens aimed to improve central auditory processing abilities have experienced limited success in promoting listening benefits. Interestingly, recent studies suggest that in young adults, musical training positively modifies neural mechanisms, providing robust, long-lasting improvements to hearing abilities as well as to non-auditory tasks that engage cognitive control. These results offer the encouraging possibility that musical training might be used to counteract age-related changes in auditory cognition commonly observed in older adults. Here, we reviewed studies that have examined the effects of age and musical experience on auditory cognition with an emphasis on auditory scene analysis. We infer that musical training may offer potential benefits to complex listening and might be utilized as a means to delay or even attenuate declines in auditory perception and cognition that often emerge later in life.

30 Review Hearing in time: evoked potential studies of temporal processing. 2013

Picton, Terence. ·University of Toronto, Toronto, Ontario, Canada. terry.picton@gmail.com ·Ear Hear · Pubmed #24005840.

ABSTRACT: This article reviews the temporal aspects of human hearing as measured using the auditory evoked potentials. Interaural timing cues are essential to the detection and localization of sound sources. The temporal envelope of a sound--how it changes in amplitude over time--is crucially important for speech perception. Time is taken to integrate, identify, and dissolve auditory streams. These temporal aspects of human hearing can be examined using the auditory evoked potentials, which measure the millisecond-by-millisecond activity of populations of neurons as they form an auditory percept. Important measurements are the time taken to localize sounds on the basis of their interaural time differences as measured by the cortical N1 wave, the contribution of the vocal cord frequency and phonemic frequency to the perception of speech sounds as indicated by the envelope-following responses, the temporal integration of sound as assessed using the steady state responses, and the duration of auditory memory as shown in the refractory periods of the slow auditory evoked potentials. Disorders of temporal processing are a characteristic feature of auditory neuropathy, a significant component of the hearing problems that occur in the elderly, and a possible etiological factor in developmental dyslexia and central auditory processing disorders. Auditory evoked potentials may help in the diagnosis and monitoring of these disorders.

31 Review Speech comprehension training and auditory and cognitive processing in older adults. 2012

Pichora-Fuller, M Kathleen / Levitt, Harry. ·University of Toronto, Mississauga, Ontario, Canada. k.pichora.fuller@utoronto.ca ·Am J Audiol · Pubmed #23233521.

ABSTRACT: PURPOSE: To provide a brief history of speech comprehension training systems and an overview of research on auditory and cognitive aging as background to recommendations for future directions for rehabilitation. METHOD: Two distinct domains were reviewed: one concerning technological and the other concerning psychological aspects of training. Historical trends and advances in these 2 domains were interrelated to highlight converging trends and directions for future practice. RESULTS: Over the last century, technological advances have influenced both the design of hearing aids and training systems. Initially, training focused on children and those with severe loss for whom amplification was insufficient. Now the focus has shifted to older adults with relatively little loss but difficulties listening in noise. Evidence of brain plasticity from auditory and cognitive neuroscience provides new insights into how to facilitate perceptual (re-)learning by older adults. CONCLUSIONS: There is a new imperative to complement training to increase bottom-up processing of the signal with more ecologically valid training to boost top-down information processing based on knowledge of language and the world. Advances in digital technologies enable the development of increasingly sophisticated training systems incorporating complex meaningful materials such as music, audiovisual interactive displays, and conversation.

32 Review The role of high-frequency oscillatory ventilation in the treatment of acute respiratory failure in adults. 2012

Ip, Terence / Mehta, Sangeeta. ·Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada. ·Curr Opin Crit Care · Pubmed #22157255.

ABSTRACT: PURPOSE OF REVIEW: High-frequency oscillatory ventilation (HFOV) is increasingly used in adults with the acute respiratory distress syndrome (ARDS), who remain hypoxemic during conventional mechanical ventilation. In this review, we will summarize the trials evaluating HFOV in adults with ARDS and discuss issues relevant to the clinician regarding the use of HFOV. RECENT FINDINGS: Several observational and randomized trials support the safety of HFOV and improvements in oxygenation in adult patients with severe ARDS, who remain hypoxemic during conventional mechanical ventilation. SUMMARY: HFOV theoretically meets the goals of lung-protective ventilation. On the basis of the current evidence, HFOV is associated with improvements in oxygenation in severe, adult ARDS. However, whether HFOV influences mortality, length of ICU stay, ventilator-free days, quality-of-life factors and is cost-effective remains to be determined. Large, prospective, randomized controlled trials such as the ongoing OSCAR and OSCILLATE trials will help further define the role of HFOV in adult ARDS.

33 Review Chlorhexidine ototoxicity in ear surgery, part 1: review of the literature. 2011

Lai, Philip / Coulson, Chris / Pothier, David D / Rutka, John. ·Department of Otolaryngology, Head and Neck Surgery, University of Toronto, Toronto, ON. ·J Otolaryngol Head Neck Surg · Pubmed #22420428.

ABSTRACT: OBJECTIVE: Chlorhexidine is a common antiseptic used to prevent surgical infection. However, its exposure to the middle ear may lead to deafness. The mechanisms of the ototoxicity of chlorhexidine are reviewed. The importance of recognizing its toxicity cannot be overstated in preventing injury to patients undergoing ear surgery. METHODS: A systematic literature search was performed looking at data from human and animal studies. Search engines included MEDLINE, EMBASE, The Cochrane Library, CENTRAL, CINAHL, and Web of Science to November 1, 2010, for relevant studies published in all languages. Two independent reviewers (P.L. and D.D.P.) screened the references from published articles for additional relevant studies. Medical Subject Headings and key words including intervention (chlorhexidine, antiseptic), exposure (myringoplasty, intratympanic), and adverse effects (sensorineural hearing loss, ototoxicity, vestibular toxicity) were used. RESULTS: Twelve studies were identified, two of which were non-English and were excluded. Only 2 articles on human subjects and 12 articles on animal models concerning chlorhexidine ototoxicity were identified. CONCLUSIONS: Chlorhexidine in both human studies and animal models demonstrates ototoxicity if it reaches the inner ear. The toxicity of chlorhexidine appears to be related to its concentration and probable contact time with the round window membrane intraoperatively. It is conceivable that the incidence of chlorhexidine toxicity may be higher than stated if unrecognized or has resulted in subsequent medicolegal actions. From the evidence available, safer preparation solutions are available without clinical risks for ototoxicity should surgeons continue with this practice.

34 Review What is the optimal timing for bilateral cochlear implantation in children? 2011

Gordon, K A / Jiwani, S / Papsin, B C. ·Archie's Cochlear Implant Laboratory, The Hospital for Sick Children, Toronto, ON, Canada. karen.gordon@utoronto.ca ·Cochlear Implants Int · Pubmed #21917210.

ABSTRACT: Bilateral cochlear implants (CIs) have been provided to children who are deaf in both ears with intent to promote binaural hearing. If it is possible to establish binaural hearing with two CIs, these children would be able to make use of interaural level and timing differences to localize sound and to distinguish between sounds separated in space. These skills are central to the ability to attend to one particular sound amidst a number of sound sources. This may be particularly important for children because they are typically learning and interacting in groups. However, the development of binaural processing could be disrupted by effects of bilateral deafness, effects of unilateral CI use, or issues related to the child's age at onset of deafness and age at the time of the first and second cochlear implantation. This research aims to determine whether binaural auditory processing is affected by these variables in an effort to determine the optimal timing for bilateral cochlear implantation in children. It is now clear that the duration of bilateral deafness should be limited in children to restrict reorganization in the auditory thalamo-cortical pathways. It has also been shown that unilateral CI use can halt such reorganization to some extent and promote auditory development. At the same time, however, unilateral input might compromise the development of binaural processing if CIs are provided sequentially. Mismatches in responses from the auditory brainstem and cortex evoked by the first and second CI after a long period of unilateral CI use suggest asymmetry in the bilateral auditory pathways which is significantly more pronounced than in children receiving bilateral implants simultaneously. Moreover, behavioural responses to level and timing differences between implants suggest that these important binaural cues are not being processed normally by children who received a second CI after a long period of unilateral CI use and at older ages. In sum, there may be multiple sensitive periods in the developing auditory system, which must be considered when determining the optimal timing for bilateral cochlear implantation.

35 Review Use it or lose it? Lessons learned from the developing brains of children who are deaf and use cochlear implants to hear. 2011

Gordon, K A / Wong, D D E / Valero, J / Jewell, S F / Yoo, P / Papsin, B C. ·Archie's Cochlear Implant Laboratory, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada. karen.gordon@utoronto.ca ·Brain Topogr · Pubmed #21479928.

ABSTRACT: In the present paper, we review what is currently known about the effects of deafness on the developing human auditory system and ask: Without use, does the immature auditory system lose the ability to normally function and mature? Any change to the structure or function of the auditory pathways resulting from a lack of activity will have important implications for future use through an auditory prosthesis such as a cochlear implant. Data to date show that deafness in children arrests and disrupts normal auditory development. Multiple changes to the auditory pathways occur during the period of deafness with the extent and type of change being dependent upon the age and stage of auditory development at onset of deafness, the cause or type of deafness, and the length of time the immature auditory pathways are left without significant input. Structural changes to the auditory nerve, brainstem, and cortex have been described in animal models of deafness as well in humans who are deaf. Functional changes in deaf auditory pathways have been evaluated by using a cochlear implant to stimulate the auditory nerve with electrical pulses. Studies of electrically evoked activity in the immature deaf auditory system have demonstrated that auditory brainstem development is arrested and that thalamo-cortical areas are vulnerable to being taken over by other competitive inputs (cross-modal plasticity). Indeed, enhanced peripheral sight and detection of visual movement in congenitally deaf cats and adults have been linked to activity in specific areas of what would normally be auditory cortex. Cochlear implants can stimulate developmental plasticity in the auditory brainstem even after many years of deafness in childhood but changes in the auditory cortex are limited, at least in part, by the degree of reorganization which occurred during the period of deafness. Consequently, we must identify hearing loss rapidly (i.e., at birth for congenital deficits) and provide cochlear implants to appropriate candidates as soon as possible. Doing so has facilitated auditory development in the thalamo-cortex and allowed children who are deaf to perceive and use spoken language.

36 Review Medical and noninvasive therapy for Meniere's disease. 2010

Greenberg, Simon L / Nedzelski, Julian M. ·Department of Otolaryngology-Head and Neck Surgery, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Room M1 102, Toronto, Ontario M4N3M5, Canada. ·Otolaryngol Clin North Am · Pubmed #20713246.

ABSTRACT: Nonoperative therapy continues to be the mainstay of treatment of patients suffering from Meniere disease. Despite extensive research, the exact pathogenesis of Meniere disease remains elusive. The poorly understood nature of this condition has made it nearly impossible to develop treatments that are curative. Most modern treatments are aimed at controlling symptoms. This article reviews the various nonoperative treatments that have been used to treat Meniere disease historically as well as outlining the authors' clinical treatment paradigm.

37 Review Disability associated with alcohol abuse and dependence. 2010

Samokhvalov, Andriy V / Popova, Svetlana / Room, Robin / Ramonas, Milita / Rehm, Jürgen. ·Centre for Addiction and Mental Health (CAMH), Public Health and Regulatory Policy, 33 Russell Street, Room 2035, Toronto, ON M5S2S1, Canada. avsamokhvalov@yahoo.ca ·Alcohol Clin Exp Res · Pubmed #20662803.

ABSTRACT: BACKGROUND:  Alcohol use disorders (AUD), i.e., alcohol dependence and abuse, are major contributors to burden of disease. A large part of this burden is because of disability. However, there is still controversy about the best disability weighting for AUD. The objective of this study was to provide an overview of alcohol-related disabilities. METHODS: Systematic literature review and expert interviews. RESULTS: There is heterogeneity in experts' descriptions of disabilities related to AUD. The major core attributes of disability related to AUD are changes of emotional state, social relationships, memory and thinking. The most important supplementary attributes are anxiety, impairments of speech and hearing. CONCLUSIONS: This review identified the main patterns of disability associated with AUD. However, there was considerable variability, and data on less prominent patterns were fragmented. Further and systematic research is required for increasing the knowledge on disability related to AUD and for application of interventions for reducing the associated burden.

38 Clinical Trial Clinical and genetic associations for carboplatin-related ototoxicity in children treated for retinoblastoma: A retrospective noncomparative single-institute experience. 2018

Soliman, Sameh E / D'Silva, Crystal N / Dimaras, Helen / Dzneladze, Irakli / Chan, Helen / Gallie, Brenda L. ·Faculty of Medicine, Department of Ophthalmology, University of Alexandria, Alexandria, Egypt. · Department of Ophthalmology and Vision Science, Hospital for Sick Children, Toronto, Canada. · Department of Medical Biophysics, University of Toronto, Toronto, Canada. · Department of Ophthalmology and Vision Science, University of Toronto, Toronto, Canada. · Child Health Evaluative Sciences Program, SickKids Research Institute, Toronto, Canada. · Division of Clinical Public Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. · Division of Haematology/Oncology, Hospital for Sick Children, Toronto, Canada. ·Pediatr Blood Cancer · Pubmed #29350448.

ABSTRACT: BACKGROUND: Children with retinoblastoma treated with carboplatin chemotherapy risk moderate to severe, irreversible hearing loss. Based on published evidence, we hypothesized that ototoxicity risk is associated with clinical parameters and variants in candidate genes in drug metabolism pathways (methyltransferases [thiopurine S-methyltransferase, TPMT] and [catechol-O-methyltransferase, COMT], and drug transporter ABCC3). PROCEDURE: We retrospectively reviewed clinical records of patients with retinoblastoma treated with carboplatin chemotherapy regarding age (at diagnosis and chemotherapy initiation), chemotherapy sessions (cycles number, drug doses, and cumulative carboplatin dose), and hearing loss (defined as ototoxicity ≥grade 2 by at least one classification system). Blood samples were genotyped for genetic variants in TPMT (rs12201199, rs1800460), COMT (rs4646316, rs9332377), and ABCC3 (rs1051640) by quantitative PCR and confirmed by allele-specific PCR. Univariate statistical tests, receiver-operating characteristic analysis, and Kaplan-Meier curves were used to examine the association between hearing loss, clinical factors, and variants in candidate genes. RESULTS: Audiometric data and stored DNA were available for 71 patients with retinoblastoma (88% carried an RB1 pathogenic variant allele). Median carboplatin cumulative dose was 1,400 mg/m CONCLUSIONS: We observed a 25% prevalence of ototoxicity in patients with retinoblastoma treated with carboplatin, higher than previously published. Age at chemotherapy initiation was associated with carboplatin-induced ototoxicity, with children <4.25 months of age at highest risk.

39 Clinical Trial Musical Rehabilitation in Adult Cochlear Implant Recipients With a Self-administered Software. 2017

Smith, Leah / Bartel, Lee / Joglekar, Samidha / Chen, Joseph. ·*Department of Otolaryngology-Head and Neck Surgery, Sunnybrook Health Sciences Centre †Department of Music ‡Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada. ·Otol Neurotol · Pubmed #28806336.

ABSTRACT: OBJECTIVE: The goal of this study was to determine if a self-administered computer-based rehabilitation program could improve music appreciation and speech understanding in adults who have a cochlear implant (CI). STUDY DESIGN: Prospective study. SETTING: Tertiary adult CI program. PATIENTS: Twenty-one postlingually deafened cochlear implant users between the ages of 27 and 79 years were recruited. INTERVENTIONS(S): A self-administered music rehabilitative software was designed to help improve the perception of musical patterns of increasing complexity, as well as pitch and timbre perception, premised on focused and divided attention. All participants completed a diagnostic music test before and after rehabilitative training, including tests of pitch and timbre perception and pattern identification with increasing levels of difficulty. Speech data in quiet and noise was also collected both pre- and post-training. Participants trained for a minimum of 3.5 hours a week, for 4 weeks. MAIN OUTCOME MEASURE(S): Mean changes in music perception and enjoyment as well as speech perception (IEEE sentence test in quiet and noise). RESULTS: Post-training diagnostic test scores, as compared with pretraining scores, indicated significant improvements in musical pattern perception. Tests of speech perception in quiet and in noise were significantly improved in a subset of this cohort. All of the training participants thought that the training helped to improve their recognition skills, and found the program to be beneficial. CONCLUSION: Despite the limitations of current CI technology, the results of this study suggest that auditory training can improve music perception skills, and possibly speech intelligibility, lending further support to rehabilitation being an integral part of the postimplantation paradigm.

40 Clinical Trial Preliminary experience using a cochlear implant with a novel linear pedestal design. 2017

Parkes, William J / Gnanasegaram, Joshua J / Cushing, Sharon L / James, Adrian L / Gordon, Karen A / Papsin, Blake C. ·Archie's Cochlear Implant Laboratory, Department of Otolaryngology, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Otolaryngology - Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada. Electronic address: wjparkes@gmail.com. · Archie's Cochlear Implant Laboratory, Department of Otolaryngology, The Hospital for Sick Children, Toronto, Ontario, Canada; The Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. · Archie's Cochlear Implant Laboratory, Department of Otolaryngology, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Otolaryngology - Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada. · Archie's Cochlear Implant Laboratory, Department of Otolaryngology, The Hospital for Sick Children, Toronto, Ontario, Canada; The Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Otolaryngology - Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada. ·Int J Pediatr Otorhinolaryngol · Pubmed #28109496.

ABSTRACT: OBJECTIVE: To assess the safety and efficiency of cochlear implantation using a novel device with a linear silastic pedestal (2 mm wide, 2 mm deep, 10 mm long) on the flat undersurface. METHODS: Operative times required to drill a linear groove (LG) for the new linear pedestal design were prospectively accrued for 46 implantations in 30 children (median age 3). Intra-operative safety was assessed during each case. Instances of dural exposure in the base of the LG were noted. Length of stay was also recorded as a secondary measure of efficiency. RESULTS: Across all surgeons, the mean time needed to create the LG was 1.9 ± 1.5 min (±SD) with a median time of 1.5 min (95% Cl: 1-2 min). The range in time was 1-10 min. No intraoperative complications occurred. Intended device positioning was confirmed with on-table post-operative x-rays in all cases. 43% of patients were discharged on the day of surgery. CONCLUSIONS: The novel linear pedestal design allows for deliberate device placement while adding little additional operative time and complexity, an improvement on our current standard of care.

41 Clinical Trial Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial. 2017

Freyer, David R / Chen, Lu / Krailo, Mark D / Knight, Kristin / Villaluna, Doojduen / Bliss, Bonnie / Pollock, Brad H / Ramdas, Jagadeesh / Lange, Beverly / Van Hoff, David / VanSoelen, Michele L / Wiernikowski, John / Neuwelt, Edward A / Sung, Lillian. ·Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA; Departments of Pediatrics and Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: dfreyer@chla.usc.edu. · Children's Oncology Group, Monrovia, CA, USA. · Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Children's Oncology Group, Monrovia, CA, USA. · Doernbecher Children's Hospital, Oregon Health and Science University, Portland, OR, USA. · Department of Public Health Sciences, University of California Davis, Davis, CA, USA. · Pediatric Hematology/Oncology, Geisinger Medical Center, Danville, PA, USA. · Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. · Helen DeVos Children's Hospital, Grand Rapids, MI, USA. · Pharmaceutical Services, McMaster University, Hamilton, ON, Canada. · Hematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada. ·Lancet Oncol · Pubmed #27914822.

ABSTRACT: BACKGROUND: Sodium thiosulfate is an antioxidant shown in preclinical studies in animals to prevent cisplatin-induced hearing loss with timed administration after cisplatin without compromising the antitumour efficacy of cisplatin. The primary aim of this study was to assess sodium thiosulfate for prevention of cisplatin-induced hearing loss in children and adolescents. METHODS: ACCL0431 was a multicentre, randomised, open-label, phase 3 trial that enrolled participants at 38 participating Children's Oncology Group hospitals in the USA and Canada. Eligible participants aged 1-18 years with newly diagnosed cancer and normal audiometry were randomly assigned (1:1) to receive sodium thiosulfate or observation (control group) in addition to their planned cisplatin-containing chemotherapy regimen, using permuted blocks of four. Randomisation was initially stratified by age and duration of cisplatin infusion. Stratification by previous cranial irradiation was added later as a protocol amendment. The allocation sequence was computer-generated centrally and concealed to all personnel. Participants received sodium thiosulfate 16 g/m FINDINGS: Between June 23, 2008, and Sept 28, 2012, 125 eligible participants were randomly assigned to either sodium thiosulfate (n=61) or observation (n=64). Of these, 104 participants were assessable for the primary endpoint (sodium thiosulfate, n=49; control, n=55). Hearing loss was identified in 14 (28·6%; 95% CI 16·6-43·3) participants in the sodium thiosulfate group compared with 31 (56·4%; 42·3-69·7) in the control group (p=0·00022). Adjusted for stratification variables, the likelihood of hearing loss was significantly lower in the sodium thiosulfate group compared with the control group (odds ratio 0·31, 95% CI 0·13-0·73; p=0·0036). The most common grade 3-4 haematological adverse events reported, irrespective of attribution, were neutropenia (117 [66%] of 177 participant cycles in the sodium thiosulfate group vs 145 [65%] of 223 in the control group), whereas the most common non-haematological adverse event was hypokalaemia (25 [17%] of 147 vs 22 [12%] of 187). Of 194 serious adverse events reported in 26 participants who had received sodium thiosulfate, none were deemed probably or definitely related to sodium thiosulfate; the most common serious adverse event was decreased neutrophil count: 26 episodes in 14 participants. INTERPRETATION: Sodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use. Further research is needed to define the appropriate role for sodium thiosulfate among emerging otoprotection strategies. FUNDING: US National Cancer Institute.

42 Clinical Trial Evaluation of amifostine for protection against cisplatin-induced serious hearing loss in children treated for average-risk or high-risk medulloblastoma. 2014

Gurney, James G / Bass, Johnnie K / Onar-Thomas, Arzu / Huang, Jie / Chintagumpala, Murali / Bouffet, Eric / Hassall, Tim / Gururangan, Sridharan / Heath, John A / Kellie, Stewart / Cohn, Richard / Fisher, Michael J / Panandiker, Atmaram Pai / Merchant, Thomas E / Srinivasan, Ashok / Wetmore, Cynthia / Qaddoumi, Ibrahim / Stewart, Clinton F / Armstrong, Gregory T / Broniscer, Alberto / Gajjar, Amar. ·Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis Tenneessee (J.G.G., G.T.A.) · Department of Rehabilitation Service, St. Jude Children's Research Hospital, Memphis Tenneessee (J.K.B.) · Department of Biostatistics, St. Jude Children's Research Hospital, Memphis Tenneessee (A.O.-T., J.H.) · Department of Oncology, St. Jude Children's Research Hospital, Memphis Tenneessee (C.W., I.Q., G.T.A., A.B., A.G.) · Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis Tenneessee, (A.P.P., T.E.M.) · Department of Bone Marrow Transplantation, St. Jude Children's Research Hospital, Memphis, Tenneessee (A.S.) · Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis Tenneessee (C.F.S.) · Department of Pediatrics, Texas Children's Cancer Center, Houston, Texas (M.C.) · Hospital for Sick Children, Toronto, Ontario, Canada (E.B.) · Royal Children's Hospital Brisbane, Herston, Australia (T.H.) · The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina (S.G.) · The Royal Children's Hospital Melbourne, Victoria, Australia (J.A.H.) · Children's Hospital at Westmead, Sydney, Australia (S.K.) · Sydney Children's Hospital, Sydney, Australia (R.C.) · Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (M.J.F.) · School of Public Health, University of Memphis, Memphis, Tenneessee (J.G.G.). ·Neuro Oncol · Pubmed #24414535.

ABSTRACT: BACKGROUND: The purpose of this study was to evaluate amifostine for protection from cisplatin-induced serious hearing loss in patients with average-risk medulloblastoma by extending a previous analysis to a much larger sample size. In addition, this study aimed to assess amifostine with serious hearing loss in patients with high-risk medulloblastoma treated with cisplatin. METHODS: Newly diagnosed medulloblastoma patients (n = 379; ages 3-21 years), enrolled on one of 2 sequential St. Jude clinical protocols that included 4 courses of 75 mg/m(2) cisplatin, were compared for hearing loss by whether or not they received 600 mg/m(2) of amifostine immediately before and 3 hours into each cisplatin infusion. Amifostine administration was not randomized. The last audiological evaluation between 5.5 and 24.5 months following protocol treatment initiation was graded using the Chang Ototoxicity Scale. A grade of ≥ 2b (loss requiring a hearing aid or deafness) was considered a serious event. RESULTS: Among average-risk patients (n = 263), amifostine was associated with protection from serious hearing loss (adjusted OR, 0.30; 95% CI, 0.14-0.64). For high-risk patients (n = 116), however, there was not sufficient evidence to conclude that amifostine prevented serious hearing loss (OR, 0.89; 95% CI, 0.31-2.54). CONCLUSIONS: Although patients in this study were not randomly assigned to amifostine treatment, we found evidence in favor of amifostine administration for protection against cisplatin-induced serious hearing loss in average-risk but not in high-risk, medulloblastoma patients.

43 Article Detection of vision and /or hearing loss using the interRAI Community Health Assessment aligns well with common behavioral vision/hearing measurements. 2019

Urqueta Alfaro, Andrea / Guthrie, Dawn M / Phillips, Natalie A / Pichora-Fuller, M Kathleen / Mick, Paul / McGraw, Cathy / Wittich, Walter. ·School of Optometry, University of Montréal, Montréal, Quebec, Canada. · Centre de Recherche Interdisciplinaire en Réadaptation du Montréal Métropolitain, Montréal, Quebec, Canada. · Department of Kinesiology & Physical Education, Wilfrid Laurier University, Waterloo, Ontario, Canada. · Department of Health Sciences, Wilfrid Laurier University, Waterloo, Ontario, Canada. · Department of Psychology, Concordia University, Montréal, Quebec, Canada. · Department of Psychology, University of Toronto, Mississauga, Ontario, Canada. · Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. · CRIR/Lethbridge-Layton-Mackay Rehabilitation Centre of West-Central Montreal,Montréal, Quebec, Canada. · CRIR/Institut Nazareth et Louis-Braille du CISSS de la Montérégie-Centre, Montréal, Quebec, Canada. ·PLoS One · Pubmed #31581243.

ABSTRACT: This study's main objective was to assess the sensitivity and specificity of the interRAI Community Health Assessment (CHA) for detecting the presence of vision loss (VL), hearing loss (HL) or both (Dual Sensory Loss, DSL) when compared against performance-based measures of vision and hearing. The interRAI CHA and the Montreal Cognitive Assessment (MoCA) were administered to 200 adults (61+ years of age) who had VL, HL or DSL. We calculated the sensitivity and specificity of the interRAI CHA for detecting sensory impairments using as the gold standard performance based measurements of hearing (pure-tone audiogram) and vision (distance acuity) as determined from the rehabilitation centre record. Results were divided according to participants' cognitive status, as measured by the MoCA and the Cognitive Performance Scale (CPS, embedded within the interRAI CHA). Overall, sensitivity was 100% for VL, 97.1% for HL, and 96.9% for DSL. Specificity was at least 93% in all three groups. In participants who failed the MoCA (i.e., at risk of mild cognitive impairment), the sensitivity was 100% for VL, 96.8% for HL and 96.2% for DSL; in those who were not at risk, the sensitivity was 100% for VL, and 97.4% for HL and DSL. In participants classified by the CPS as borderline intact or mild cognitively impaired, sensitivity was 100% in all groups; in those classified as cognitively intact, sensitivity was 100% for VL, 97.0% for HL, and 96.8% for DSL. These results suggest that the interRAI CHA detects VL, HL, and DSL in high agreement with performance-based measurements of vision and hearing. The interRAI CHA shows high accuracy even in participants with mild cognitive difficulties. Since results were found in a specific population of older rehabilitation clients who all had sensory difficulties, further research is needed to understand its role in screening in other more diverse groups.

44 Article A systematic review and network meta-analysis of existing pharmacologic therapies in patients with idiopathic sudden sensorineural hearing loss. 2019

Ahmadzai, Nadera / Kilty, Shaun / Cheng, Wei / Esmaeilisaraji, Leila / Wolfe, Dianna / Bonaparte, James P / Schramm, David / Fitzpatrick, Elizabeth / Lin, Vincent / Skidmore, Becky / Moher, David / Hutton, Brian. ·Ottawa Hospital Research Institute, Ottawa, Canada. · Department of ENT, the Ottawa Hospital, Ottawa, Canada. · Dr. S. Kilty Medicine Prof. Corp, Ottawa, Canada. · Faculty of Health Sciences, University of Ottawa, Ottawa, Canada. · Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada. · Department of Otolaryngology - Head & Neck Surgery, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Canada. · Faculty of Medicine, University of Toronto, Toronto, Canada. · University of Ottawa School of Epidemiology, Public Health and Preventive Medicine, Ottawa, Canada. ·PLoS One · Pubmed #31498809.

ABSTRACT: BACKGROUND: Hearing loss is one of the leading causes of disability worldwide. Patients with hearing loss experience impaired quality of life, as well as emotional and financial consequences that affect both themselves and their families. Idiopathic sudden sensorineural hearing loss (ISSNHL) is a common but difficult to treat condition that has a sudden onset of ≤ 72 hour associated with various etiologies, with the majority of cases being idiopathic. There exists a wide range of therapeutic options, however, the uncertainty surrounding their comparative efficacy and safety makes selection of treatment difficult. This systematic review and network meta-analysis (NMA) assessed the relative effects of competing treatments for management of ISSNHL. METHODS: A protocol for this review was registered with PROSPERO (CRD42017073756). A detailed search of MEDLINE, Embase and the Cochrane Library from inception to February 8th, 2018 was carried out by an experienced information specialist. Grey literature was also searched. Screening full-text records, and risk of bias assessment were carried out independently by two reviewers, and disagreements were resolved through consensus or third party adjudication, while data was collected by one reviewer and verified by a second reviewer. Bayesian network meta-analyses (NMA) were performed to inform comparisons between interventions for a priori specified outcomes that included pure tone average (PTA) improvement and hearing recovery. RESULTS: The search identified a total of 1,138 citations, of which 613 remained for review after removal of duplicates. Of these, 23 publications describing 19 unique studies (total sample size of 1,527) met our a priori eligibility criteria, that were assessed to be at unclear or high risk of bias on several domains. We identified data on several interventions for ISSNHL therapy and were able to construct treatment networks consisting of six intervention groups that included placebo; intratympanic (IT) steroid; IT plus systemic steroid; per oral (PO) steroid; intravenous (IV) steroid; and IV plus PO steroid for our NMAs. IT plus systemic steroids demonstrated the largest difference in PTA improvement compared to placebo (25.85 dB, 95% CrI 7.18-40.58), followed by IV plus PO steroids (22.06 dB, 95% CrI 1.24-39.17), IT steroids (18.24 dB, 95% CrI 3.00-29.81). We observed that the difference of PTA improvement between each intervention and placebo diminished over time, attributed to spontaneous recovery. The binary outcomes of hearing recovery demonstrated similar relative ordering of interventions but were less sensitive than PTA improvement to capture the significant differences between interventions and placebo. CONCLUSION: Unclear to high risk of bias trials rated IT plus systemic steroid treatment as the best among the six interventions compared, and all active treatments were better than placebo in improving PTA. However, it should be noted that certain comparisons were based on indirect evidence only or few studies of small sample size, and analyses were unable to control for steroid type and dosage. Given these limitations, further data originating from methodologically sound and rigorous trials with adequate reporting are needed to confirm our findings.

45 Article Etiology and therapy indication for cochlear implantation in children with single-sided deafness : Retrospective analysis. 2019

Cushing, S L / Gordon, K A / Sokolov, M / Papaioannou, V / Polonenko, M / Papsin, B C. ·Department of Otolaryngology, Head and Neck Surgery, Hospital for Sick Children, Room 6103C Burton Wing, 555 University Avenue, M5G 1X8, Toronto, ON, Canada. sharon.cushing@sickkids.ca. · Department of Otolaryngology, Head and Neck Surgery, University of Toronto, Toronto, ON, Canada. sharon.cushing@sickkids.ca. · Archie's Cochlear Implant Laboratory, Hospital for Sick Children, Toronto, ON, Canada. sharon.cushing@sickkids.ca. · Department of Otolaryngology, Head and Neck Surgery, University of Toronto, Toronto, ON, Canada. · Archie's Cochlear Implant Laboratory, Hospital for Sick Children, Toronto, ON, Canada. · Department of Communication Disorders, Hospital for Sick Children, Toronto, ON, Canada. · Department of Otolaryngology, Head and Neck Surgery, Hospital for Sick Children, Room 6103C Burton Wing, 555 University Avenue, M5G 1X8, Toronto, ON, Canada. · Department of Neurosciences & Mental Health, Hospital for Sick Children, Toronto, ON, Canada. · Institute of Medical Science, University of Toronto, Toronto, ON, Canada. ·HNO · Pubmed #31478064.

ABSTRACT: OBJECTIVE: The characteristics of children with single-sided deafness (SSD) who become candidates for unilateral cochlear implantation (uCI) were identified. STUDY DESIGN: In all, 118 children with SSD presenting from 2013-2019 to a tertiary pediatric children's hospital were retrospectively assessed regarding candidacy for uCI. RESULTS: Of the 118 children, 103 had completed uCI candidacy assessment, while 15 were undergoing this assessment at the time of review. More than half of children did not go on to implantation (63/103, 61%), with the 2 main reasons being (1) half (31/63) did not meet candidacy criteria for implantation, most commonly due to cochlear nerve aplasia/hypoplasia (31/82 who were assessed with MRI, 38%) and (2) families (30/103; 29%) declined participation in the surgical arm of the trial. The most common etiologies of SSD in the 37/103 (36%) children who both met candidacy and consented to implantation were congenital cytomegalovirus (cCMV; 16/37, 43%), unknown (6/37, 16%), cochleovestibular anomaly and trauma (each 5/37, 14%). CONCLUSIONS: Many children with SSD who present for implant candidacy assessment do not ultimately receive uCI. Major factors contributing to noncandidacy are cochlear nerve aplasia and parental acceptance of the intervention. While approximately half of children with SSD in our cohort were candidates for implantation, only 1/3 of the total cohort proceeded with implantation with the main predictors of acceptability of this intervention being an etiology (i.e., cCMV) that carries risk of progressive deterioration in the better hearing ear or SSD that was sudden in onset. These findings provide important insight into this new population of cochlear implant users and the emerging acceptance of intervention in children with SSD.

46 Article Age-related hearing loss increases full-brain connectivity while reversing directed signaling within the dorsal-ventral pathway for speech. 2019

Bidelman, Gavin M / Mahmud, Md Sultan / Yeasin, Mohammed / Shen, Dawei / Arnott, Stephen R / Alain, Claude. ·Institute for Intelligent Systems, University of Memphis, Memphis, TN, USA. gmbdlman@memphis.edu. · School of Communication Sciences and Disorders, University of Memphis, 4055 North Park Loop, Memphis, TN, 38152, USA. gmbdlman@memphis.edu. · Department of Anatomy and Neurobiology, University of Tennessee Health Sciences Center, Memphis, TN, USA. gmbdlman@memphis.edu. · Department of Electrical and Computer Engineering, University of Memphis, Memphis, TN, USA. · Rotman Research Institute-Baycrest Centre for Geriatric Care, Toronto, ON, Canada. · Department of Psychology, University of Toronto, Toronto, ON, Canada. · Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada. ·Brain Struct Funct · Pubmed #31346715.

ABSTRACT: Speech comprehension difficulties are ubiquitous to aging and hearing loss, particularly in noisy environments. Older adults' poorer speech-in-noise (SIN) comprehension has been related to abnormal neural representations within various nodes (regions) of the speech network, but how senescent changes in hearing alter the transmission of brain signals remains unspecified. We measured electroencephalograms in older adults with and without mild hearing loss during a SIN identification task. Using functional connectivity and graph-theoretic analyses, we show that hearing-impaired (HI) listeners have more extended (less integrated) communication pathways and less efficient information exchange among widespread brain regions (larger network eccentricity) than their normal-hearing (NH) peers. Parameter optimized support vector machine classifiers applied to EEG connectivity data showed hearing status could be decoded (> 85% accuracy) solely using network-level descriptions of brain activity, but classification was particularly robust using left hemisphere connections. Notably, we found a reversal in directed neural signaling in left hemisphere dependent on hearing status among specific connections within the dorsal-ventral speech pathways. NH listeners showed an overall net "bottom-up" signaling directed from auditory cortex (A1) to inferior frontal gyrus (IFG; Broca's area), whereas the HI group showed the reverse signal (i.e., "top-down" Broca's → A1). A similar flow reversal was noted between left IFG and motor cortex. Our full-brain connectivity results demonstrate that even mild forms of hearing loss alter how the brain routes information within the auditory-linguistic-motor loop.

47 Article Evidence-Based Medicine in Otolaryngology Part 10: Cost-Effectiveness Analyses in Otolaryngology. 2019

Caulley, Lisa / Rodin, Danielle / Kilty, Shaun / Randolph, Gregory / Hunink, Myriam G / Shin, Jennifer J. ·1 Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. · 2 The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. · 3 Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. · 4 Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. · 5 Department of Otolaryngology-Head and Neck Surgery, University of Ottawa, Ottawa, Ontario, Canada. · 6 Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, USA. · 7 Department of Epidemiology and Department of Radiology, Erasmus MC, Rotterdam, the Netherlands. · 8 Center for Health Decision Sciences, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA. ·Otolaryngol Head Neck Surg · Pubmed #31184254.

ABSTRACT: 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.

48 Article Novel Statistical Analyses to Assess Hearing Outcomes After ABI Implantation in NF2 Patients: Systematic Review and Individualized Patient Data Analysis. 2019

Taslimi, Shervin / Zuccato, Jeffrey A / Mansouri, Alireza / Hachem, Laureen D / Badhiwala, Jetan / Kuchta, Johannes / Chen, Joseph / Pirouzmand, Farhad. ·Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. · Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. Electronic address: jeff.zuccato@mail.utoronto.ca. · Department of Neurosurgery, University of Cologne, Köln, Germany. · Department of Otolaryngology, Sunnybrook Health Science Centre, Toronto, Ontario, Canada. · Division of Neurosurgery, Department of Surgery, Sunnybrook Health Science Centre, Toronto, Ontario, Canada. ·World Neurosurg · Pubmed #31059859.

ABSTRACT: BACKGROUND: Patients with neurofibromatosis type 2 develop bilateral vestibular schwannomas with progressive hearing loss. Auditory brainstem implants (ABIs) stimulate hearing in the cochlear nuclei and show promise in improving hearing. Here, we assess the impact of ABI on hearing over time by systematically reviewing the literature and re-analyzing available individual patient data. METHODS: A multidatabase search identified 3 studies with individual patient data of longitudinal hearing outcomes after ABI insertion in adults. Data were collected on hearing outcomes of different sound complexities from sound to speech using an ABI ± lip reading ability plus demographic data. Because of heterogeneity each study was analyzed separately using random effects multilevel mixed linear modeling. RESULTS: Across all 3 studies (n = 111 total) there were significant improvements in hearing over time from ABI placement (P < 0.000 in all). Improvements in comprehension of sounds, words, sentences, and speech occurred over time with ABI use + lip reading but lip reading ability did not improve over time. All categories of hearing complexity had over 50% comprehension after over 1 year of ABI use and some subsets had over 75% or near 100% comprehension. Vowel comprehension was greater than consonant, and word comprehension was greater than sentence comprehension (P < 0.0001 in both). Age and sex did not predict outcomes. CONCLUSIONS: ABIs improve hearing beyond lip reading alone, which represents baseline patient function prior to treatment, and the benefits continue to improve with time. These findings may be used to guide patient counseling regarding ABI insertion, rehabilitation course after insertion, and future studies.

49 Article Novel Usher syndrome pathogenic variants identified in cases with hearing and vision loss. 2019

Pater, Justin A / Green, Jane / O'Rielly, Darren D / Griffin, Anne / Squires, Jessica / Burt, Taylor / Fernandez, Sara / Fernandez, Bridget / Houston, Jim / Zhou, Jiayi / Roslin, Nicole M / Young, Terry-Lynn. ·Craig L. Dobbin Research Centre, Discipline of Genetics, Faculty of Medicine, Memorial University, St. John's, Newfoundland & Labrador, AIB 3V6, Canada. · Molecular Diagnostic Laboratory, Eastern Health, Craig L. Dobbin Genetics Research Centre, Faculty of Medicine, Memorial University, 300 Prince Phillip Drive, St. John's, Newfoundland and Labrador, A1B 3V6, Canada. · Provincial Medical Genetics, Craig L. Dobbin Research Centre, Eastern Health, 300 Prince Phillip Drive, St. John's, Newfoundland and Labrador, A1B 3V6, Canada. · The Centre for Applied Genomics, The Hospital for Sick Children, 686 Bay Street, Toronto, Ontario, M5G 0A4, Canada. · Craig L. Dobbin Research Centre, Discipline of Genetics, Faculty of Medicine, Memorial University, St. John's, Newfoundland & Labrador, AIB 3V6, Canada. tlyoung@mun.ca. · Molecular Diagnostic Laboratory, Eastern Health, Craig L. Dobbin Genetics Research Centre, Faculty of Medicine, Memorial University, 300 Prince Phillip Drive, St. John's, Newfoundland and Labrador, A1B 3V6, Canada. tlyoung@mun.ca. ·BMC Med Genet · Pubmed #31046701.

ABSTRACT: BACKGROUND: Usher syndrome, the most common form of inherited deaf-blindness, is unlike many other forms of syndromic hereditary hearing loss in that the extra aural clinical manifestations are also detrimental to communication. Usher syndrome patients with early onset deafness also experience vision loss due to progressive retinitis pigmentosa that can lead to legal blindness in their third or fourth decade. METHODS: Using a multi-omic approach, we identified three novel pathogenic variants in two Usher syndrome genes (USH2A and ADGRV1) in cases initially referred for isolated vision or hearing loss. RESULTS: In a multiplex hearing loss family, two affected sisters, the product of a second cousin union, are homozygous for a novel nonsense pathogenic variant in ADGRV1 (c.17062C > T, p.Arg5688*), predicted to create a premature stop codon near the N-terminus of ADGRV1. Ophthalmological examination of the sisters confirmed typical retinitis pigmentosa and prompted a corrected Usher syndrome diagnosis. In an unrelated clinical case, a child with hearing loss tested positive for two novel USH2A splicing variants (c.5777-1G > A, p. Glu1926_Ala1952del and c.10388-2A > G, p.Asp3463Alafs*6) and RNA studies confirmed that both pathogenic variants cause splicing errors. Interestingly, these same USH2A variants are also identified in another family with vision loss where subsequent clinical follow-up confirmed pre-existing hearing loss since early childhood, eventually resulting in a reassigned diagnosis of Usher syndrome. CONCLUSION: These findings provide empirical evidence to increase Usher syndrome surveillance of at-risk children. Given that novel antisense oligonucleotide therapies have been shown to rescue retinal degeneration caused by USH2A splicing pathogenic variants, these solved USH2A patients may now be eligible to be enrolled in therapeutic trials.

50 Article Surfer's ear in a 29-year-old man. 2019

McParland, Aidan / Elffers-Tan, Frederique / Ackery, Alun. ·Faculty of Medicine (McParland), University of Toronto, Toronto, Ont. · University Medical Center Utrecht (Elffers-Tan), Utrecht, The Netherlands · Emergency Department (Ackery), St. Michael's Hospital, Toronto, Ont. ·CMAJ · Pubmed #30962199.

ABSTRACT: -- No abstract --

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