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Purpose: In rodents and nonhuman primates with bilateral vestibular hypofunction, we previously demonstrated that motion-modulated current pulses delivered via electrodes in the ampullae can partially restore the 3D angular vestibulo-ocular reflex (VOR) while partially preserving hearing. Based on those studies, we initiated a first-in-human clinical trial of continuous motion-modulated prosthetic stimulation using the MVI™ Multichannel Vestibular Implant system developed by Labyrinth Devices LLC and MedEl GmbH. Methods: Four subjects underwent unilateral implantation; two were observed overnight and two were discharged the same day. VOR responses to 0.5-5 Hz passive head or whole-body rotation and prosthetic stimulation; pure tone and speech audiometry; and metrics of posture, gait, dynamic visual acuity and quality of life were assessed during 2-14 months of continuous MVI™ use. Results: Electrically-evoked VOR responses typically ranged from 5-40°/s and aligned approximately with the stimulated canal for ≥1 electrode in each of 3 canals in each implanted ear. VOR responses were typically smaller than those for similar currents in animals, but significantly greater with motion-modulated stimulation than without. Motion perception thresholds are below VOR thresholds. Hearing sufficient for unaided communication was preserved in all subjects. At >12 months postop, subjects 1-3 have preserved hearing except for high-frequency SNHL; as of 3 months post-op, subject 4 has a high frequency SNHL and 25dB speech reception threshold change. Conclusions: The MVI™ system can be implanted in outpatient surgery with preservation of useful hearing, and it generates motion perception and 3D binocular VOR responses consistent with selective stimulation of 3 implanted canals. Funding: Research reported in this publication was supported by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health under R01DC013536 and R01DC9255. The use of the MVI™ Multichannel Vestibular Implant is permitted under an investigational device exemption (US FDA IDE Case #130248). All research was conducted under a protocol approved by the Johns Hopkins University Institutional Review Board (IRB Study Number NA_00051349). This trial is registered as ClinicalTrials.gov #NCT02725463. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. PJB was supported by NIDCD 2T32DC000023-31 through the Johns Hopkins Center for Hearing and Balance. CCDS holds an equity interest in Labyrinth Devices LLC. The terms of this arrangement are managed in accordance with university policies. [ABSTRACT FROM AUTHOR] more...

Background: Bilateral vestibular hypofunction is associated with chronic disequilibrium, postural instability, and unsteady gait owing to failure of vestibular reflexes that stabilize the eyes, head, and body. A vestibular implant may be effective in alleviating symptoms.Methods: Persons who had had ototoxic (7 participants) or idiopathic (1 participant) bilateral vestibular hypofunction for 2 to 23 years underwent unilateral implantation of a prosthesis that electrically stimulates the three semicircular canal branches of the vestibular nerve. Clinical outcomes included the score on the Bruininks-Oseretsky Test of Motor Proficiency balance subtest (range, 0 to 36, with higher scores indicating better balance), time to failure on the modified Romberg test (range, 0 to 30 seconds), score on the Dynamic Gait Index (range, 0 to 24, with higher scores indicating better gait performance), time needed to complete the Timed Up and Go test, gait speed, pure-tone auditory detection thresholds, speech discrimination scores, and quality of life. We compared participants' results at baseline (before implantation) with those at 6 months (8 participants) and at 1 year (6 participants) with the device set in its usual treatment mode (varying stimulus pulse rate and amplitude to represent rotational head motion) and in a placebo mode (holding pulse rate and amplitude constant).Results: The median scores at baseline and at 6 months on the Bruininks-Oseretsky test were 17.5 and 21.0, respectively (median within-participant difference, 5.5 points; 95% confidence interval [CI], 0 to 10.0); the median times on the modified Romberg test were 3.6 seconds and 8.3 seconds (difference, 5.1; 95% CI, 1.5 to 27.6); the median scores on the Dynamic Gait Index were 12.5 and 22.5 (difference, 10.5 points; 95% CI, 1.5 to 12.0); the median times on the Timed Up and Go test were 11.0 seconds and 8.7 seconds (difference, 2.3; 95% CI, -1.7 to 5.0); and the median speeds on the gait-speed test were 1.03 m per second and 1.10 m per second (difference, 0.13; 95% CI, -0.25 to 0.30). Placebo-mode testing confirmed that improvements were due to treatment-mode stimulation. Among the 6 participants who were also assessed at 1 year, the median within-participant changes from baseline to 1 year were generally consistent with results at 6 months. Implantation caused ipsilateral hearing loss, with the air-conducted pure-tone average detection threshold at 6 months increasing by 3 to 16 dB in 5 participants and by 74 to 104 dB in 3 participants. Changes in participant-reported disability and quality of life paralleled changes in posture and gait.Conclusions: Six months and 1 year after unilateral implantation of a vestibular prosthesis for bilateral vestibular hypofunction, measures of posture, gait, and quality of life were generally in the direction of improvement from baseline, but hearing was reduced in the ear with the implant in all but 1 participant. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT02725463.). [ABSTRACT FROM AUTHOR] more...

Background: Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are severe, treatment-refractory, epileptic encephalopathies that often develop in infancy or early childhood. Since December 1, 2022, plant-derived highly purified cannabidiol (CBD) medicine (Epidyolex®; 100 mg/mL oral solution) has been reimbursed in the Netherlands for the adjunctive treatment of seizures associated with LGS or DS. Objective: To estimate the cost-effectiveness of CBD plus usual care vs usual care alone in patients with LGS or DS in the Netherlands. Methods: A cohort-based Markov model from a Dutch societal perspective, based on seizure frequency and seizure-free days, was developed for patients receiving CBD plus usual care (antiseizure medications, including clobazam) or usual care alone. Population characteristics, clinical inputs, and utility values were sourced from CBD clinical trials and quality-of-life studies. Drug acquisition, disease management, adverse events, and societal costs from published literature were included. A 2019/2020 price year in euros was used. The model used a mean dosage of 12 mg/kg/day, a lifetime (90-year) horizon, and a 3-month cycle length. Discount rates of 4.0% and 1.5% per annum were applied to costs and outcomes, respectively. Uncertainty was explored through deterministic and probabilistic sensitivity analyses. Results: In patients with LGS, CBD plus usual care led to additional costs of €28 338 and increased quality-adjusted life-years (QALYs) of 1.318 compared with usual care alone. The incremental cost-effectiveness ratio of €21 493/QALY in LGS is below the willingness-to-pay threshold of €80 000/QALY in the Netherlands. In patients with DS, CBD plus usual care dominated usual care alone, with cost savings of €23 642 and increased QALYs of 0.868. The probability that CBD plus usual care is cost-effective in the Netherlands compared with usual care alone is 96% and 99% in patients with LGS and DS, respectively. Discussion: Elicitation methods were used to address data gaps in model inputs (eg, healthcare resource utilization and utilities); Dutch clinical experts, sensitivity, and scenario analyses validated this approach. Conclusions: Based on a willingness-to-pay threshold of €80 000, the base case cost-utility analysis demonstrated the cost-effectiveness of CBD plus usual care in patients with treatment-refractory LGS or DS aged 2 years or older in the Netherlands., Competing Interests: J.S. was employed by FIECON at the time of the study and received grant/research support from Jazz Pharmaceuticals, Inc.; J.S. is now an employee of Jazz Pharmaceuticals UK Ltd. and holds stock and/or stock options in Jazz Pharmaceuticals, plc. S.B. is an employee of Jazz Pharmaceuticals UK Ltd. and holds stock and/or stock options in Jazz Pharmaceuticals, plc. more...

Tuberous sclerosis complex (TSC)-associated seizures result in a significant burden for caregivers. To quantify time spent and describe activities undertaken by caregivers of individuals with TSC-associated seizures in Sweden, primary caregivers participated in a cross-sectional, non-interventional online survey. Questions comprised patient/caregiver characteristics, care provision, time, and activities associated with generalized seizures or non-seizure-related care. Twenty-three primary caregivers participated; 96 % parents, 100 % female. Median number of caregivers per individual was three. In the last month, median (interquartile range [IQR]) hours for caregiving per week was 52.0 (25.7-100.0; n = 21); median (IQR) hours for non-seizure-related care was 46.7 (20.0-93.3; n = 21) and for generalized seizure-related care was 4.7 (1.7-15.8; n = 12). Beyond the last month, hours/week of generalized seizure-related care varied from 1.9 (0-8.8) to 14.0 (0.5-77.0). Professional/paid carers contributed 99.2 (73.5-127.5) hours/week of care. Non-seizure-related care activities included assisting with routine medical care (n = 22, 96 %) and daily activities (n = 22, 96 %). Activities relating to generalized seizures included assessing the need for (n = 16, 84 %) and giving (n = 17, 89 %) rescue medication, providing physical support (n = 16, 84 %), and clearing the individual's environment during generalized seizures (n = 13, 68 %). During generalized seizure recovery, activities included taking the individual to bed (n = 18, 95 %), emotional support (n = 14, 74 %), and managing behavioral issues (n = 14, 74 %). In Sweden, despite contributions of paid caregivers, individuals with TSC-associated seizures require substantial time from unpaid primary caregivers, including seizure- and non-seizure-related care. Generalized seizures have a considerable impact on time spent caregiving and the care activities undertaken., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SHL and HS are employees of Acaster Lloyd Consulting Ltd, which received payment from GW Pharmaceuticals, now a part of Jazz Pharmaceuticals, Inc., in the conduct of this study. MH, JS, and SB are employees of Jazz Pharmaceuticals UK Ltd and hold stock and/or stock options in Jazz Pharmaceuticals, plc., (© 2024 The Authors.) more...

Introduction: Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are rare, childhood-onset conditions associated with severe, treatment-resistant epilepsy and developmental issues, including motor and cognitive impairment. Tuberous sclerosis complex (TSC) is a rare genetic disease commonly associated with epilepsy and other neuropsychiatric disorders. This cross-sectional, interview-based study examined the qualitative impact of caring for patients with LGS, DS, and TSC-associated epilepsy on caregivers in Japan, from the perspective of both caregivers and physicians., Methods: The survey included a pre-interview worksheet to describe caregivers' emotional journeys, followed by a ≤ 60-minute one-on-one interview. Eligible participants were Japanese caregivers of patients with LGS, DS, or TSC treated for epilepsy symptoms, and Japan-residing pediatricians or neurologists treating ≥ 3 patients with LGS, DS, and/or TSC. Interview question responses were subjected to content analysis to identify the most common response tendencies and themes., Results: Twenty-six caregivers responded (mean [standard deviation (SD)] age, 45.9 [9.5] years; age range 29-68; 92 % female), caring for patients with LGS (n = 5), DS (n = 10), and TSC (n = 11); patient mean (SD) age, 13.6 (10.0) years; age range 2-44; 27 % adults; 50 % female. Nineteen physicians, treating patients with LGS (n = 9), DS (n = 7), and TSC (n = 10), participated. Caregivers and physicians generally aligned on the factors affecting caregivers' emotional states / quality of life (QoL). The most frequently reported caregiver emotions at the time of diagnosis were shock and discouragement, anxiety for the future, and relief at receiving a diagnosis. Negative emotions throughout disease progression up until the time of survey were mainly caused by worsening of seizures, burden of constant caregiving / lack of free time, and patient's developmental issues. Positive emotions were linked to effective treatment / reduced seizures; more free time owing to the use of facilities, services, or other caregiving support; and developmental progress. Physicians acknowledged that caregivers required consultation services to support their emotional needs. In terms of unmet needs, caregiver and physician responses were aligned on the insufficient availability of services/facilities, the lack of effective treatments, and the uncertainties of adult patient care., Conclusions: Caregivers of patients with LGS, DS, or TSC-associated epilepsy in Japan reported a high degree of emotional burden related to frequent seizures, developmental issues, and constant caregiving. The burden of suboptimal treatment effectiveness, limited access to support services, and uncertainties in long-term care emphasize important unmet treatment needs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [All authors met the International Committee of Medical Journal Editors (ICMJE) authorship criteria and had full access to relevant data. Neither honoraria nor payments were made for authorship. M. LoPresti and Y. Sonohara are employees of INTAGE Healthcare Inc., which received funding from Jazz Pharmaceuticals, Inc. to conduct the fieldwork and data analysis. A. Igarashi has no conflicts of interest. S. Bowditch is an employee of Jazz Pharmaceuticals UK Ltd., and holds stocks/stock options with Jazz Pharmaceuticals UK Ltd.]., (Copyright © 2024 Jazz Pharmaceuticals, Inc. Published by Elsevier Inc. All rights reserved.) more...

Objectives: The aim of this study was to evaluate the cost effectiveness of plant-derived highly purified cannabidiol (Epidyolex ® in the UK; 100 mg/mL oral solution) as an add-on treatment to usual care for the management of treatment-refractory seizures associated with tuberous sclerosis complex (TSC) in patients aged ≥ 2 years., Methods: A cohort-based model was developed using a National Health Service perspective and lifetime horizon. Health states were based on weekly seizure frequency and seizure-free days, utilizing patient-level data from the GWPCARE6 trial (ClinicalTrials.gov identifier: NCT02544763). Two independent regression models were applied to individual patient-level data to predict seizure-free days and seizure frequency. Healthcare resource utilization data were sourced from a Delphi panel, and patient and caregiver health-related quality of life values were elicited using vignettes valued by the general public. Outcomes relating to TSC-associated neuropsychiatric disorders were modeled with costs and quality-adjusted life-years sourced from published literature., Results: In the base case, compared with usual care alone, 12 mg/kg/day cannabidiol was associated with an incremental cost-effectiveness ratio (ICER) of £23,797. The National Institute for Health and Care Excellence disease severity modifier reduced the ICER to £19,831. Probabilities of cost effectiveness at willingness-to-pay thresholds of £20,000 and £30,000 were 30% and 52%, respectively, for the base case and 39% and 66%, respectively, for the disease severity modifier. Results were robust to sensitivity and scenario analyses., Conclusions: At 12 mg/kg/day and an ICER threshold of £20,000-£30,000, we provide evidence for the cost effectiveness of add-on cannabidiol treatment for patients with TSC-associated seizures aged ≥ 2 years who are refractory to current treatment., (© 2024. The Author(s).) more...

Introduction: Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC)-associated epilepsy are rare conditions associated with severe childhood-onset epilepsy. Caregivers play a critical role in the patients' care and may experience significant psychosocial and socioeconomic burden. This cross-sectional study determined the burden of caring for patients with these rare epilepsy conditions in Japan., Methods: A quantitative online survey was used to assess patients' and caregivers' characteristics and the caregivers' emotional state, among others. Several validated questionnaires were used: the Hospital Anxiety and Depression Scale (HADS; 0-21 score) assessed the caregivers' emotional wellbeing, the Pediatric Quality of Life Inventory Family Impact Module (PedsQL FIM; 0-100 score) assessed the health-related quality of life (HRQoL) of the caregivers and their families, and the Work Productivity and Activity Impairment General Health (WPAI:GH; 0-100 % score) questionnaire assessed work productivity., Results: A total of 36 caregivers responded (median [interquartile range (IQR)] age 43.5 [39.5, 48.3] years; 33/36 [92 %] female; 13/36 [36 %] working part-time and 13/36 [36 %] not working). Participants cared for 7/36 (19 %), 19/36 (53 %), and 10/36 (28 %) patients with LGS, DS, and TSC, respectively (median [IQR] age, 11.0 [6.8, 16.3] years; age at first seizure, 0 [0, 0] years). Patients received a median (IQR) of 4 (3, 5) treatment drug types. Patients experienced median (IQR) 3.0 (0, 21.0) epileptic seizures in the previous week; 28/36 (78 %) had severe intellectual disabilities, and 34/36 (94 %) had developmental delays. Caregivers reported stress (17/36 [47 %]), sleep problems (13/36 [36 %]), and anxiety (12/36 [33 %]). They spent a median (IQR) of 50.0 (17.5, 70.0) hours caregiving in the previous week, with 3.0 (1.0, 11.0) hours of seizure-specific care. Caregivers reported that their lives would be easier with a median (IQR) of 1.5 (0, 5.0) hours fewer per week caring for patients during/following seizures. Median HADS scores were 9.5 ('suspected anxiety diagnosis') and 7.5 ('no depression') for caregivers, and PedsQL FIM Total median score was 60.1, indicating HRQoL impairment for the caregiver and their family. WPAI:GH scores for paid workers indicated important work impairment. Higher caregiving hours (≥ 21 h vs. < 21 h in the previous week) resulted in higher caregiver burden as indicated by the HADS Total score (p = 0.0062) and PedsQL FIM Total score (p = 0.0007)., Conclusions: Caregivers of patients with LGS, DS, or TSC in Japan experience a significant time burden, reduced HRQoL, and high level of work/activity impairment. Caregivers provide round-the-clock care to patients and rely on family and specialized caring services to help manage the increased caregiving time, which tends to be associated with greater emotional burden and HRQoL impact., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘All authors met the International Committee of Medical Journal Editors (ICMJE) authorship criteria and had full access to relevant data. Neither honoraria nor payments were made for authorship. ML and YS are employees of INTAGE Healthcare Inc., which received funding from Jazz Pharmaceuticals, Inc. to conduct the fieldwork and data analysis. AI has no conflicts of interest. SB is an employee of Jazz Pharmaceuticals UK Ltd., and holds stock/stock options with Jazz Pharmaceuticals UK Ltd.’., (Copyright © 2024 Jazz Pharmaceuticals, Inc. Published by Elsevier Inc. All rights reserved.) more...

Objective: This study aimed to estimate the size of the United States candidacy pool meeting expanded Center for Medicare Services criteria for cochlear implantation., Study Design: Retrospective cross-sectional., Setting: Tertiary care center., Methods: Preimplantation audiometric data from 486 patients seen at a single academic medical center were collected retrospectively and used to generate a predictive model of AzBio score based on audiometric pure tone thresholds. This model was then used to estimate nationally representative cochlear implantation (CI)-candidacy using pure tone averages included in the National Health and Nutrition Examination Survey. Qualitative and quantitative analyses were performed., Results: We find that the estimated prevalence of CI candidacy in individuals 65 years of age or older is expected to more than double with a change in the CI candidacy criteria from ≤40% to ≤60% (from 1.42%, 95% confidence interval [1.33, 1.63] to 3.73% [2.71, 6.56]) on speech testing. We also found the greatest absolute increase in candidacy in the 80+ age group, increasing from 4.14% [3.72, 5.1] of the population meeting the ≤40% criteria to 12.12% [9.19, 18.35] meeting the ≤60% criteria., Conclusion: The United States population size meeting expanded CMS audiologic criteria for cochlear implantation is estimated to be 2.5 million adults and 2.1 million age 65 or older. Changing the CI candidacy criteria from ≤40% to ≤60% on CI testing has the greatest effect on the eligible patient population in the >65-year-old age group. The determination of utilization rates in newly eligible patients will require further study., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.) more...

Introduction: Single sided deafness (SSD) results in profound cortical reorganization that presents clinically with a significant impact on sound localization and speech comprehension. Cochlear implantation (CI) has been approved for two manufacturers' devices in the United States to restore bilateral function in SSD patients with up to 10 years of auditory deprivation. However, there is great variability in auditory performance and it remains unclear how auditory deprivation affects CI benefits within this 10-year window. This prospective study explores how measured auditory performance relates to real-world experience and device use in a cohort of SSD-CI subjects who have between 0 and 10 years of auditory deprivation., Methods: Subjects were assessed before implantation and 3-, 6-, and 12-months post-CI activation via Consonant-Nucleus-Consonant (CNC) word recognition and Arizona Biomedical Institute (AzBio) sentence recognition in varying spatial speech and noise presentations that simulate head shadow, squelch, and summation effects (S 0 N 0 , S SSD N NH , S NH N SSD ; 0 = front, SSD = impacted ear, NH = normal hearing ear). Patient-centered assessments were performed using Tinnitus Handicap Inventory (THI), Spatial Hearing Questionnaire (SHQ), and Health Utility Index Mark 3 (HUI3). Device use data was acquired from manufacturer software. Further subgroup analysis was performed on data stratified by <5 years and 5-10 years duration of deafness., Results: In the SSD ear, median (IQR) CNC word scores pre-implant and at 3-, 6-, and 12-months post-implant were 0% (0-0%), 24% (8-44%), 28% (4-44%), and 18% (7-33%), respectively. At 6 months post-activation, AzBio scores in S 0 N 0 and S SSD N NH configurations ( n  = 25) demonstrated statistically significant increases in performance by 5% ( p  = 0.03) and 20% ( p  = 0.005), respectively. The median HUI3 score was 0.56 pre-implant, lower than scores for common conditions such as anxiety (0.68) and diabetes (0.77), and comparable to stroke (0.58). Scores improved to 0.83 (0.71-0.91) by 3  months post-activation. These audiologic and subjective benefits were observed even in patients with longer durations of deafness., Discussion: By merging CI-associated changes in objective and patient-centered measures of auditory function, our findings implicate central mechanisms of auditory compensation and adaptation critical in auditory performance after SSD-CI and quantify the extent to which they affect the real-world experience reported by individuals., 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 © 2023 Ullah, Cevallos, Shen, Carver, Dunham, Marsiglia, Yeagle, Della Santina, Bowditch and Sun.) more...

Objective: To examine the effect of patient age on longitudinal speech understanding outcomes after cochlear implantation (CI) in bilateral hearing loss., Study Design: Retrospective cohort study., Setting: Tertiary academic center., Patients: One thousand one hundred five adult patients with bilateral hearing loss receiving a unilateral CI between 1987 and 2022InterventionsNone., Main Outcome Measures: Postoperative speech recognition outcomes, including AzBio sentences, consonant-nucleus-consonant word, and Hearing in Noise Test in quiet were analyzed at short-term (<2 yr), medium-term (2-8 y), and long-term (>8 yr) term postoperative intervals., Results: Eighty-six very elderly (>80 yr), 409 elderly (65-80 yr), and 709 nonelderly (18-65 yr) patients were included. Short-term postoperative AzBio scores demonstrated similar magnitude of improvement relative to preoperative scores in the very elderly (47.6, 95% confidence interval [CI], 28.9-66.4), elderly (49.0; 95% CI, 39.2-58.8), and nonelderly (47.9; 95% CI, 35.4-60.4). Scores for those older than 80 years remained stable after 2 years after implant, but in those 80 years or younger, scores continued to improve for up to 8 years (elderly: 6.2 [95% CI, 1.5-12.4]; nonelderly: 9.9 [95% CI, 2.1-17.7]) after implantation. Similar patterns were observed for consonant-nucleus-consonant word scores. Across all age cohorts, patients with preoperative Hearing in Noise Test scores between 40 and 60% had similar scores to those with preoperative scores of less than 40%, at short-term (82.4, 78.9; 95% CI, -23.1 to 10.0), medium-term (77.2, 83.9; 95% CI, -15.4 to 8.2), or long-term (73.4, 71.2; 95% CI, -18.2 to 12.2) follow-up., Conclusions: Patients older than 80 years gain significant and sustained auditory benefit after CI, including those meeting expanded Centers for Medicare & Medicaid Service criteria for implantation. Patients younger than 80 years demonstrated continued improvement over longer periods than older patients, suggesting a role of central plasticity in mediating CI outcomes as a function of age., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.) more...

Objective: To increase understanding of the impact of cannabidiol (CBD) on outcomes beyond seizure control among individuals with Dravet syndrome or Lennox-Gastaut syndrome., Methods: Qualitative interviews were conducted with caregivers of individuals with Dravet syndrome or Lennox-Gastaut syndrome treated with plant-derived, highly purified CBD medicine (Epidiolex in the USA; Epidyolex in Europe; 100 mg/mL oral solution). Symptoms and impacts of Dravet syndrome and Lennox-Gastaut syndrome on individuals were explored, as were the effects of CBD. Data were analyzed using thematic analysis., Results: Twenty-one caregivers of individuals with Dravet syndrome (n = 14) and Lennox-Gastaut syndrome (n = 7) aged 4-22 years participated. Health-related quality of life improvements associated with CBD included cognitive function, communication, behavior, mobility, and participation in daily activities. Seizure frequency reduction was commonly reported (n = 12), resulting in caregivers having greater freedom and family life being less disrupted. Adverse events were reported by 10 caregivers., Conclusion: In addition to reduced seizure frequency, CBD may have a wide range of beneficial effects beyond seizure control that warrant further investigation. more...

Background: Tuberous sclerosis complex (TSC) is a rare genetic condition commonly accompanied by neurological and neuropsychological disorders, resulting in a high burden of illness for individuals and a substantial impact on their caregivers. Due to the diversity and complexity of clinical manifestations, patients with TSC need aligned multidisciplinary healthcare services starting in childhood through to adulthood. However, patients and caregivers are sometimes dissatisfied with the care provided, for which one of the most common reasons is a lack of involvement in clinical decision-making. Shared decision-making, whereby clinicians make clinical management decisions together with patients and their caregivers, is advocated for in the management of epilepsy, but evidence of its benefit in managing TSC is currently lacking. In this cross-sectional, UK-based analysis we used an online survey to capture the experiences of primary caregivers for individuals with TSC, including the impact on work productivity, clinical shared decision-making, satisfaction with care, and the impact of the coronavirus disease 2019 (COVID-19) pandemic., Results: In total, 73 eligible caregivers provided consent (analysis set), with 14 completing the survey partially and 59 completing the full survey. Many caregivers (72%) reported receiving recommendations about new treatments from their doctor and discussing the treatment together, with a high proportion (89%) preferring that treatment was initiated at a low dose. Most caregivers (69%) were satisfied or extremely satisfied with pediatric TSC healthcare services, but only 25% were satisfied or extremely satisfied with the transition to adult TSC healthcare services. Several (n = 30) caregivers specified the impact of caring on their work productivity and career in optional open-ended survey responses. Finally, 80% of caregivers indicated that the COVID-19 pandemic had a "large" or "very large" impact on their caring activities, negatively affecting the emotional wellbeing and behavior of individuals with TSC, and caregivers' ability to work and arrange medical appointments., Conclusions: Caregivers largely feel involved in treatment decisions, and the majority were satisfied with healthcare services for children with TSC. However, many highlighted the need for an improved transition from pediatric to adult healthcare services. The survey also showed that COVID-19 has considerably affected caregivers and individuals with TSC., (© 2023. The Author(s).) more...

Introduction: Tuberous sclerosis complex (TSC) is a rare multisystem genetic condition characterised by benign tumours; prevalent manifestations include epilepsy and neuropsychiatric disorders. This study examined the burden of TSC for primary caregivers and families, exploring the impact of characteristics such as seizures., Methods: Primary caregivers of individuals with TSC in the United Kingdom participated in an online survey, comprising the Pediatric Quality of Life Inventory™ Family Impact Module, Hospital Anxiety and Depression Scale (HADS), and TSC-specific items. Responses were analysed using descriptive and regression analysis statistics (closed-ended) or qualitative content analysis (open-ended)., Results: Seventy-three participants partially completed and 59 fully completed the survey; 95% were female, and 90% were parents of an individual with TSC. A median (range) of 2 (1-11) household members were carers. Primary caregivers spent a mean (standard deviation [SD]) of 104.3 (51.7) hours caring in the previous week, reporting high mean (SD) HADS scores of 11.2 (4.8) (anxiety) and 7.9 (4.4) (depression) and considerable family burden. Increased seizure frequency increased hours spent caring by primary caregivers (p = 0.01) and was associated with a decreased mean (SD) family functioning score of 46.2 (23.0) and parent health-related quality of life (HRQL) score of 45.4 (20.3) (both p = 0.03). Multivariable models predicted intellectual disability increased hours spent caring by primary caregivers (p = 0.01-0.04), and neuropsychiatric comorbidities decreased family functioning (p = 0.02) and caregiver HRQL (p < 0.01)., Conclusion: These findings highlight the role of epileptic seizures and neuropsychiatric disorders in the considerable burden of TSC on primary caregivers and families., (© 2023. The Author(s).) more...

Objectives: Cochlear implants (CI) are reliable implantable devices that are highly cost-effective in reducing the burden of hearing loss at an individual and societal scale. However, only 10% of CI candidates are aware of their candidacy and receive a CI. A web-based screening tool to assess CI candidacy may make many more individuals aware of their candidacy for cochlear implantation. The objective of this study was to validate and optimize the online Cochlear Implant Candidacy Calculator against in-clinic audiometric testing., Methods: Audiogram data and word discrimination scores for 132 patients who underwent initial CI consultation at the Johns Hopkins Cochlear Implant Center in 2020 were inputted into the calculator. Candidacy results from the calculator were compared against formal clinical diagnoses provided by the audiologist at the time of visit. Receiver Operating Characteristic (ROC) and Area Under the Curve (AUC) analyses were performed to identify optimal diagnostic thresholds., Results: Of the resulting 132 patients, 54 presented with single-sided deafness (SSD), and 114 were clinically determined to be CI candidates. ROC AUC analyses identified optimal thresholds of high-frequency PTA ≥65 dB and word discrimination score ≤ 50%. To maximize sensitivity at the expense of specificity, diagnostic thresholds of high-frequency PTA ≥ 65 dB and word discrimination score ≤ 70% were chosen, which yielded accuracy, sensitivity, specificity, and ROC AUC of 0.90, 0.94, 0.82, and 0.88, respectively., Conclusion: The novel online CI Candidacy Calculator exhibits high sensitivity and accuracy, and moderate specificity. The calculator may thereby be useful in increasing awareness of potential CI candidacy, increasing prevalence of CIs, and decreasing the burden of hearing loss., Competing Interests: The authors have no conflicts of interest to declare., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC. on behalf of The Triological Society.) more...

Purpose: The purpose of this study is to establish if obstructive sleep apnoea (OSA) predicted by the STOP-BANG questionnaire would be associated with higher rates of post-operative cardiac, respiratory or neurological complications among a selected high-risk population with established major comorbidities undergoing major surgery. We hypothesise that a cohort selected for major comorbidities will show a higher post-operative complication rate that may power any potential association with co-existent OSA and identify an important target group for OSA screening and treatment pathways in preparation for major surgery., Methods: Patients attending a high-risk preadmission clinic prior to major surgery from May 2015 to November 2015 were prospectively screened for OSA using the STOP-BANG questionnaire. Patients with treated OSA were excluded. Patient data and complications were attained from the pre-admission clinic and subsequent inpatient medical record at discharge., Results: Three-hundred-and-ten patients were included in the study (age 68.6 ± 13.1 years, body mass index [BMI] 30.6 ± 7.4 kg/m 2 ; 52.9% female). Sixty-four patients (20.6%) experienced 82 post-operative complications. Seventy-five percent of the cohort had a STOP-BANG ≥ 3. There was no association between the STOP-BANG score (unadjusted and adjusted for comorbidity) with the development of post-operative complications., Conclusions: OSA predicted by the STOP-BANG score was not associated with higher rates of post-operative complications in patients with major comorbidities undergoing high-risk surgery. As the findings from this cohort contrast with other observational studies, more definitive studies are required to establish a causative link between OSA and post-operative complications and determine whether treating OSA reduces this complication rate. more...

Objective: To compare postoperative hearing outcomes between transmastoid and middle fossa craniotomy (MFC) approaches for surgical repair of superior semicircular canal dehiscence syndrome (SCDS) in a tertiary referral center., Study Design: Historical cohort study., Setting: Tertiary referral center., Patients: Twelve consecutive SCDS cases who underwent transmastoid plugging of the superior canal; "controls" were 18 audiogram-matched patients who underwent MFC plugging and resurfacing., Main Outcome Measures: Differences between preoperative, 7-day postoperative, and long-term (>6 wk) postoperative air and bone conduction, speech discrimination scores (SDS), and pure-tone averages (PTA) in TM cases versus MFC controls., Methods: MFC controls were selected by matching preoperative bone conduction (BC) pure-tone thresholds from the TM cases within 10-dBs NHL in ≥80% of recorded frequencies. Wilcoxon signed-rank tests were performed to compare primary outcomes between matches, with a Bonferroni corrected p value of 0.004 (n = 13 variables measured at each time period)., Results: No statistically significant differences were found in long-term postoperative air conduction and BC thresholds at any frequency both during the immediate postoperative period as well as at long-term follow-up (p > 0.004). Similarly, there were no differences in long-term SDS or PTA (p > 0.004)., Conclusions: In this pilot study, there were no long-term significant differences in hearing outcomes between the two repair techniques for SCDS. We recommend continuing with the established practice for recommending surgical repair based on individual patient characteristics and preferences in managing both vestibular and auditory function. more...

Objective: Cochlear implants are generally considered a contraindication for any procedure requiring electrical stimulation near the implant. We present a case of a patient undergoing intraoperative transcranial electrical motor-evoked potential monitoring with a cochlear implant without adverse outcomes., Patient: A 12-year-old girl with a history of VACTERL presented with worsening congenital kyphosis and bilateral severe-to-profound hearing loss. Since age 7 the patient used a cochlear implant in the right ear and hearing aid in the left ear. Physical examination and magnetic resonance imaging in 2016 revealed a left-sided 66-degree thoracolumbar kyphosis at T11 making the patient a candidate for surgical correction., Interventions: She underwent a posterior spinal fusion surgery, performed with intraoperative transcranial electrical motor-evoked potential monitoring. Steps were taken to mitigate electrical stimulation of the patient's cochlear implant., Main Outcome Measures: Postoperative impedance of individual channels, audiometry, and neural response testing were compared with preoperative measurements., Results: Significant (>10%) impedance changes were observed postoperatively in channels 1, 2, 4, and 6; however, the net variation across all the channels was low (3%). The patient reported no hearing changes, and no significant changes in hearing threshold were seen in postoperative audiometric testing or neural response testing., Conclusion: We present a case of successful posterior spinal fusion with intraoperative neurophysiological monitoring via transcranial electrical stimulation, in a patient with a cochlear implant. With proper precautions, motor-evoked potential monitoring can be safely performed in a patient with a cochlear implant. more...

Background: Persistence with antimuscarinic therapy in overactive bladder (OAB) is poor, but may be different for mirabegron, a β 3 -adrenoceptor agonist with a different adverse event profile., Objective: To compare persistence and adherence with mirabegron versus tolterodine extended release (ER) and other antimuscarinics in routine clinical practice over a 12-mo period., Design, Setting, and Participants: Retrospective, longitudinal, observational study of anonymised data from the UK Clinical Practice Research Datalink GOLD database. Eligibility: age ≥18 yr, ≥1 prescription for target OAB drug (between May 1, 2013 and June 29, 2014), and 12-mo continuous enrolment before and after the index prescription date., Interventions: Mirabegron, darifenacin, fesoterodine, flavoxate, oxybutynin ER or immediate-release (IR), propiverine, solifenacin, tolterodine ER or IR, and trospium chloride., Outcome Measurements and Statistical Analysis: The primary endpoint was persistence (time to discontinuation). Secondary endpoints included 12-mo persistence rates and adherence (assessed using medication possession ratio, MPR). Cox proportional-hazards regression models and logistic regression models adjusted for potential confounding factors were used to compare cohorts. Analyses were repeated after 1:1 matching., Results and Limitations: The study population included 21996 eligible patients. In the unmatched analysis, the median time-to-discontinuation was significantly longer for mirabegron (169 d, interquartile range [IQR] 41-not reached) compared to tolterodine ER (56 d, IQR 28-254; adjusted hazard ratio [HR] 1.55, 95% confidence interval 1.41-1.71; p<0.0001) and other antimuscarinics (range 30-78 d; adjusted HR range 1.24-2.26, p<0.0001 for all comparisons). The 12-mo persistence rates and MPR were also significantly greater with mirabegron than with all the antimuscarinics. Limitations include the retrospective design, use of prescription records to estimate outcomes, and inability to capture reasons for discontinuation., Conclusions: Persistence and adherence were statistically significantly greater with mirabegron than with tolterodine ER and other antimuscarinics prescribed for OAB in the UK., Patient Summary: This study assessed persistence and adherence (or compliance) with medications prescribed for OAB in a large UK population. We found that patients prescribed mirabegron remained on treatment for longer and showed greater adherence than those prescribed traditional antimuscarinics., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.) more...

Background: To assess treatment persistence and adherence in men ≥45 years of age with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), using prescription records from the Netherlands IMS Lifelink™ LRx database., Methods: In this retrospective, observational cohort study, we identified men who received combination therapy with an α-blocker plus an antimuscarinic (e.g. solifenacin or tolterodine) between 1 November 2013 and 31 October 2014. Treatment could be received as a fixed-dose combination (FDC) tablet or as two drugs administered together (concomitant therapy), if both combination drugs were prescribed within 30 days. The primary objective was to assess treatment persistence, defined as the time from initiation of combination therapy until first discontinuation of the FDC or at least one of the drugs given concomitantly (i.e. ≥30 days without prescription renewal). Subgroup and sensitivity analyses were conducted to assess persistence by antimuscarinic agent, and with different gap lengths used to define discontinuation (45, 60 and 90 days), respectively., Results: A total of 1891 men received an α-blocker plus an antimuscarinic (FDC, N = 665; concomitant therapy, N = 1226). Median time to discontinuation was significantly longer with FDC versus concomitant therapy (414 vs. 112 days; adjusted hazard ratio [HR] 2.04, 95% confidence interval 1.77, 2.35; p < 0.0001). Persistence at 12 months (51.3% vs. 29.9%) was also significantly greater with FDC compared with concomitant therapy. Assessment of antimuscarinic subgroups showed that median time to discontinuation was longest with solifenacin combinations (214 days) compared with other antimuscarinic combinations (range, 47-164 days; adjusted HR range, 1.27-1.77, p = 0.037). No observable impact on treatment persistence was found by adjusting the gaps used to define discontinuation., Discussion: This study of real-world evidence of men with LUTS/BPH treated with α-blocker plus antimuscarinic combination therapy in the Netherlands showed that treatment persistence was significantly greater in those who received a FDC tablet compared with combination therapy given concomitantly. The study also shows that treatment persistence was extended in men who received combination therapy containing solifenacin compared with other antimuscarinics., Conclusions: Overall, these findings may be useful for prescribers, as improved persistence on-treatment may translate into improved outcomes for men with LUTS/BPH. Further study is warranted to establish the key drivers of persistence in men receiving combination therapy for LUTS/BPH. more...

Purpose: Our objective was to estimate the economic outcomes of using mirabegron versus antimuscarinics in the treatment of patients with overactive bladder (OAB) from a societal perspective in the UK., Materials and Methods: A Markov model was developed using Microsoft Excel ® . The time horizon and cycle length are 12 and 1 months, respectively; and the hypothetical cohort size 100 patients. Antimuscarinic comparators are fesoterodine, oxybutynin extended release (ER) and immediate release (IR), solifenacin, tolterodine ER/IR, trospium ER/IR, darifenacin and flavoxate. Model inputs included real-world treatment patterns data, healthcare resource use (e.g. clinic visits) and direct and indirect costs (e.g. drug acquisition and productivity loss). Model outputs included patient disposition, healthcare resource use, drug acquisition costs and other treatment-related costs over a 1-year time horizon. A one-way sensitivity analysis was performed to determine the key drivers of the model., Results: In a hypothetical cohort of 100 patients, total annual costs per patient were lower with mirabegron than with all antimuscarinics (£1270.84 vs. 1321.71-1607.48). Healthcare resource use was lower with mirabegron than with all antimuscarinics (115 vs. 119-123 general practitioner visits; 173 vs. 178-185 specialist visits and 0.0042 vs. 0.0050-0.0060 surgical operations) and fewer work hours were lost (4017 vs. 5114-6990 [all per 100 patients]). Sensitivity analysis showed the model was sensitive to persistence and switching rates, although the impact on the overall results was minimal., Conclusions: In the UK, using mirabegron to treat OAB may improve persistence and lead to reductions in switching treatment, healthcare resource utilization, productivity costs, and overall treatment costs versus antimuscarinics. more...

Importance: To our knowledge, this is the first study to assess the potential to pharmacologically improve auditory function in adults with age-related sensorineural hearing loss., Objective: To explore the potential for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid potentiator mechanism to affect auditory function in individuals with mild to moderate age-related sensorineural hearing loss., Design, Setting, and Participants: A randomized, double-blind, placebo-controlled, single-dose, 3-way crossover study was conducted in 3 academic ear, nose, and throat clinics and 2 private clinical research centers between December 22, 2011, and February 26, 2013. Participants were 50- to 75-year-old men and women of nonchildbearing potential with mild to moderate sensorineural hearing loss., Interventions: Three single doses of PF-04958242, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate-positive allosteric modulator, and placebo., Main Outcomes and Measures: Pure-tone average, speech discrimination score, and speech in noise testing change from baseline at 1 and 5 hours after a single dose of PF-04958242., Results: The treatment was safe and well tolerated. The estimates for the primary end point change from baseline in pure-tone average compared with placebo at 1 hour were -0.77 (95% CI, -2.14 to 0.59) and 0.37 (95% CI, -0.97 to 1.72) for 0.27 and 0.35 mg, respectively. At 5 hours the estimates were -0.57 (95% CI, -2.43 to 1.29) and -0.56 (95% CI, -2.45 to 1.33) for 0.27 and 0.35 mg, respectively. No significant change from baseline was demonstrated compared with placebo in the primary or secondary study end points at 1 or 5 hours after receiving treatment., Conclusions and Relevance: To our knowledge, this clinical trial is the first study of a pharmacologic treatment for age-related sensorineural hearing loss and provides information with regard to study design, end points, variability, data characteristics, and operational feasibility to guide the design of future hearing loss trials., Trial Registration: clinicaltrials.gov Identifier: NCT01518920. more...

Objectives: To confirm an increased susceptibility to informational masking among individuals with single-sided deafness (SSD). To demonstrate a reduction in informational masking when SSD is treated with an integrated bone conduction hearing aid (IBC). To identify the acoustic cues that contribute to IBC-aided masking release. To determine the effects of device experience on the IBC advantage., Design: Informational masking was evaluated with the coordinate-response measure. Participants performed the task by reporting color and number coordinates that changed randomly within target sentences. The target sentences were presented in free field accompanied by zero to three distracting sentences. Target and distracting sentences were spoken by different talkers and originated from different source locations, creating two sources of information for auditory streaming. Susceptibility to informational masking was inferred from the error rates of unaided SSD patients relative to normal controls. These baseline measures were derived by testing inexperienced IBC users without the device on the day of their initial fitting. The benefits of IBC-aided listening were assessed by measuring the aided performance of users who had at least 3 months' device experience. The acoustic basis of the listening advantage was isolated by correlating response errors with the voice pitch and location of distracting sentences. The effects of learning on cue effectiveness were evaluated by comparing the error rates of experienced and inexperienced users., Results: Unaided SSD participants (inexperienced users) performed as well as normal controls when tested without distracting sentences but produced significantly higher error rates when tested with distracting sentences. Most errors involved responding with coordinates that were contained in distracting sentences. This increased susceptibility to informational masking was significantly reduced when experienced IBC users were tested with the device. The listening advantage was most strongly correlated with the availability of voice pitch cues, although performance was also influenced by the location of distracting sentences. Directional asymmetries appear to be dictated by location-dependent cues that are derived from the distinctive transmission characteristics of IBC stimulation. Experienced users made better use of these cues than inexperienced users., Conclusions: These results suggest that informational masking is a significant source of communication impairment among individuals with SSD. Despite the lateralization of auditory function, unaided SSD subjects experience informational masking when distractors occur in either the deaf or normal spatial hemifield. Restoration of aural sensitivity in the deaf hemifield with an IBC enhances speech intelligibility under complex listening conditions, presumably by providing additional sound-segregation cues that are derived from voice pitch and spatial location. The optimal use of these cues is not immediate, but a significant listening advantage is observed after 3 months of unstructured use. more...

Objective: Vibromechanical stimulation with a semi-implantable bone conductor (Entific BAHA device) overcomes some of the head-shadow effects in unilateral deafness. What specific rehabilitative benefits are observed when the functional ear exhibits normal hearing versus moderate sensorineural hearing loss (SNHL)?, Design: The authors conducted a prospective trial of subjects with unilateral deafness in a tertiary care center., Patients: This study comprised adults with unilateral deafness (pure-tone average [PTA] > 90 dB; Sp.D. < 20%) and either normal monaural hearing (n = 18) or moderate SNHL (PTA = 25-50 dB: Sp.D. > 75%) in the contralateral functional ear (n = 5)., Interventions: Subjects were fit with contralateral routing of signal (CROS) devices for 1 month and tested before (mastoid) implantation, fitting, and testing with a bone-anchored hearing aid (BAHA)., Outcome Measures: Outcome measures were: 1) subjective benefit; 2) source localization tests (Source Azimuth Identification in Noise Test [SAINT]); 3) speech discrimination in quiet and in noise assessed with Hearing In Noise Test (HINT) protocols., Results: There was consistent satisfaction with BAHA amplification and poor acceptance of CROS amplification. General directional hearing decreased with CROS use and was unchanged by BAHA and directional microphone aids. Relative to baseline and CROS, BAHA produced significantly better speech recognition in noise. Twenty-two of 23 subjects followed up in this study continue to use their BAHA device over an average follow-up period of 30.24 months (range, 51-12 months)., Conclusion: BAHA amplification on the side of a deaf ear yields greater benefit in subjects with monaural hearing than does CROS amplification. Advantages likely related to averting the interference of speech signals delivered to the better ear, as occurs with conventional CROS amplification, while alleviating the negative head-shadow effects of unilateral deafness. The advantages of head-shadow reduction in enhancing speech recognition with noise in the hearing ear outweigh disadvantages inherent in head-shadow reduction that can occur by introducing noise from the deaf side. The level of hearing impairment correlates with incremental benefit provided by the BAHA. Patients with a moderate SNHL in the functioning ear perceived greater increments in benefit, especially in background noise, and demonstrated greater improvements in speech understanding with BAHA amplification. more...

Objective: An aging American population carries a high prevalence of profound sensorineural hearing loss. We examined the performance of multichannel cochlear implant recipients in a large database of adult subjects., Design: Nonconcurrent prospective study of a national cohort with multivariate regression analysis of preoperative and postoperative performance variables in multichannel cochlear implant recipients. We applied models of prediction established in previous studies to the observed results., Setting: Referral centers with active cochlear implant programs., Patients: Adolescents and adults with profound hearing loss (N = 749; age range, 14-91 years)., Main Outcome Measure: Postoperative monosyllabic word recognition., Results: The population 65 years and older demonstrated a clinically insignificant 4.6%-smaller postoperative word score compared with the population younger than 65 years. When duration of deafness exceeded 25 years, elderly recipients demonstrated higher word scores than their younger counterparts. A more significant factor affecting outcomes is the ratio of duration of deafness to age at implantation., Conclusions: Age at implantation carried relatively little predictive value for postoperative performance in subjects 65 years and older. Although a small decrement in mean speech recognition scores was evident, the clinical significance of this difference is questionable when all of the results observed in elderly patients are considered. A shorter percentage of life spent in severe-to-profound sensorineural hearing loss suggests a foundation of acoustic/auditory processing in the elderly cohort that may mitigate potential physiological effects associated with advanced age. This study confirms and extends previous observations that duration of profound deafness and residual speech recognition carry higher predictive value than the age at which an individual receives an implant. more...

Objective: We analyzed pure-tone and speech audiometric results from a prospective trial of anti-inflammatory treatment of subjects with active autoimmune inner ear disease (AIED). We sought to characterize the pattern and size of the treatment effect as reflected in clinical audiometry and to identify audiometric predictors of response to steroid treatment of AIED., Subjects: Adult participants demonstrated clinically established criteria for AIED (n = 116). Eligibility required audiometric evidence of active AIED as indicated by idiopathic sensorineural hearing loss with threshold elevations within 3 months of enrollment., Methods: We evaluated audiometric changes after 4 weeks of treatment with pharmacologic doses (60 mg/day) of prednisone. We examined the relationship between audiometric pure-tone thresholds at baseline and changes in word intelligibility score (WIS) using parametric and nonparametric analyses. Magnitudes of change were assessed using independent or paired t-tests. Separate analyses were performed on subgroups that did or did not show improved WIS score with steroid treatment., Results: Overall mean pure-tone averages improved from baseline to closeout of prednisone treatment in better hearing ears from 52.4 to 48.3 dB (p < .0001). Mean WIS improved in the better ear from 71.4% to 78.1% (p < .0001). Of pure-tone measures, only the six-tone average showed significant correlation with both the absolute improvements in WIS and with the percentage change in WIS after treatment. Individual frequencies at baseline showed no significant relationship with changes in WIS score after treatment. In 69 (59.5%) of 116 subjects, WIS improved (range, 2-80%) in the better ear. In these subjects, the baseline pure-tone thresholds and pure-tone averages correlated significantly and positively with improvement in WIS., Conclusions: Steroid treatment in AIED-mediated hearing loss produce variable but significant hearing gains. Neither a focal, cochleotopic region of greatest vulnerability to AIED nor frequency-specific amenability to treatment were evident. We did observe that analysis of predictors and the degree of treatment effect vary with different approaches to measuring change in the WIS. Depending on the approach adopted, the size of the treatment effect may be greatest across intermediate hearing levels at baseline. These observations offer an audiometric database that may enable greater precision in judging clinically meaningful parameters for future studies of AIED treatment and other interventions for sensorineural hearing loss. more...