Extended High-Frequency Thresholds: Associations With Demographic and Risk Factors, Cognitive Ability, and Hearing Outcomes in Middle-Aged and Older Adults.

OBJECTIVES: This study had two objectives: to examine associations between extended high-frequency (EHF) thresholds, demographic factors (age, sex, race/ethnicity), risk factors (cardiovascular, smoking, noise exposure, occupation), and cognitive abilities; and to determine variance explained by EHF thresholds for speech perception in noise, self-rated workload/effort, and self-reported hearing difficulties. DESIGN: This study was a retrospective analysis of a data set from the MUSC Longitudinal Cohort Study of Age-related Hearing Loss. Data from 347 middle-aged adults (45 to 64 years) and 694 older adults (≥ 65 years) were analyzed for this study. Speech perception was quantified using low-context Speech Perception In Noise (SPIN) sentences. Self-rated workload/effort was measured using the effort prompt from the National Aeronautics and Space Administration-Task Load Index. Self-reported hearing difficulty was assessed using the Hearing Handicap Inventory for the Elderly/Adults. The Wisconsin Card Sorting Task and the Stroop Neuropsychological Screening Test were used to assess selected cognitive abilities. Pure-tone averages representing conventional and EHF thresholds between 9 and 12 kHz (PTA(9 - 12 kHz)) were utilized in simple linear regression analyses to examine relationships between thresholds and demographic and risk factors or in linear regression models to assess the contributions of PTA(9 - 12 kHz) to the variance among the three outcomes of interest. Further analyses were performed on a subset of individuals with thresholds ≤ 25 dB HL at all conventional frequencies to control for the influence of hearing loss on the association between PTA(9 - 12 kHz) and outcome measures. RESULTS: PTA(9 - 12 kHz) was higher in males than females, and was higher in White participants than in racial Minority participants. Linear regression models showed the associations between cardiovascular risk factors and PTA(9 - 12 kHz) were not statistically significant. Older adults who reported a history of noise exposure had higher PTA(9 - 12 kHz) than those without a history, while associations between noise history and PTA(9 - 12 kHz) did not reach statistical significance for middle-aged participants. Linear models adjusting for age, sex, race and noise history showed that higher PTA(9 - 12 kHz) was associated with greater self-perceived hearing difficulty and poorer speech recognition scores in noise for both middle-aged and older participants. Workload/effort was significantly related to PTA(9 - 12 kHz) for middle-aged, but not older, participants, while cognitive task performance was correlated with PTA(9 - 12 kHz) only for older participants. In general, PTA(9 - 12 kHz)did not account for additional variance in outcome measures as compared to conventional pure-tone thresholds, with the exception of self-reported hearing difficulties in older participants. Linear models adjusting for age and accounting for subject-level correlations in the subset analyses revealed no association between PTA(9 - 12 kHz)and outcomes of interest. CONCLUSIONS: EHF thresholds show age-, sex-, and race-related patterns of elevation that are similar to what is observed for conventional thresholds. The current results support the need for more research to determine the utility of adding EHF thresholds to routine audiometric assessment with middle-aged and older adults.

Gray matter and episodic memory associations with olfaction in middle-aged to older adults.

BACKGROUND: Age-related declines in olfaction contribute to low quality of life and appear to occur with declines in cognitive function, including diminished episodic memory. We tested the hypothesis that low gray matter volume within cortical regions that support olfaction and episodic memory can explain age-related differences in olfactory and episodic memory functions. METHODS: T1-weighted images, Sniffin' Sticks olfactory measures, and the NIH Toolbox-Cognition Battery were administered to 131 middle-aged to older adults (50-86 years; 66% female). Correlation was used to examine the associations between these measures. A network-based image processing approach was then used to examine the degree to which spatial patterns of gray matter variance were related to the olfactory and cognitive measures. Structural equation modeling was used to characterize the relative specificity of olfactory, cognitive, gray matter, and aging associations. RESULTS: Olfactory threshold, discrimination, and identification exhibited small to medium effect size associations with episodic memory performance (rs = 0.27-0.42, ps < 0.002). Gray matter volume within medial temporal and orbitofrontal cortex was also related to olfactory (discrimination and identification) and episodic memory function (rs = 0.21-0.36, ps < 0.019). Age and episodic memory explained the same variance in olfaction that was explained by the medial temporal and orbitofrontal pattern of gray matter volume. CONCLUSIONS: The results of this cross-sectional study suggest that identifying mechanisms contributing to differences in medial temporal and orbitofrontal cortex will advance our understanding of co-morbid olfactory and cognitive declines.

Conditional Minimal Detectable Change for the Cochlear Implant Quality of Life-35 Profile Associated With Improved Functional Abilities 12 Months After Cochlear Implantation.

Importance: It is essential to measure an individual patient's baseline and follow-up abilities to demonstrate changes in clinical outcomes over time. Inherent in this strategy is interpreting whether the measured change is clinically significant and beyond measurement error. Conditional minimal detectable change (cMDC) values are widely used in many disciplines but have rarely been established for outcome measures in otolaryngology or hearing research, and never in cochlear implantation. Objective: To determine cMDC values for the Cochlear Implant Quality of Life-35 (CIQOL-35) Profile instrument to enhance our understanding of the initial and ongoing changes in functional abilities from cochlear implants (CIs). Design, Setting, and Participants: Item response theory analyses of responses from a multi-institutional cohort of 705 CI users at a tertiary CI center were used to derive standard error (SE) values for each possible CIQOL-35 domain score. Using an iterative approach, these SE values were used to calculate cMDC values for every possible pre-CI and post-CI domain score combination. We then compared pre-CI to 12-month post-CI CIQOL-35 domains scores in an independent cohort of 65 adult CI users to determine whether the measured change exceeded error to be clinically significant. The analysis took place on December 14, 2022. Interventions: The CIQOL-35 Profile instrument and cochlear implantation. Results: The cMDC values were smaller for the communication domain, and global measure and cMDC values for all domains were larger at the extremes of the measurement scale. Overall, 60 CI users (92.3%) demonstrated improvement beyond cMDC at 12 months post-CI for at least 1 CIQOL-35 domain, and no patients' scores declined beyond cMDC for any domain. The percentage of CI users demonstrating improvement beyond cMDC varied by domain, with communication (53 [81.5%]) showing the largest number of CI users improving, followed by global (42 [64.6%]) and entertainment (40 [60.9%]). In general, CI users who demonstrated improvement in CIQOL-35 domains had greater improvement in speech recognition scores than patients who did not, but the strength and significance of these associations greatly varied by domain and speech material. Conclusions and Relevance: This multistep cohort study found that cMDC values for the CIQOL-35 Profile provided personalized thresholds for detecting real changes in patient self-reported functional abilities over time across multiple domains, which may inform clinical decision-making. Moreover, these longitudinal results reveal the domains with more or less improvement, which may aid in patient counseling.

The Stria Vascularis in Mice and Humans Is an Early Site of Age-Related Cochlear Degeneration, Macrophage Dysfunction, and Inflammation.

Age-related hearing loss, or presbyacusis, is a common degenerative disorder affecting communication and quality of life for millions of older adults. Multiple pathophysiologic manifestations, along with many cellular and molecular alterations, have been linked to presbyacusis; however, the initial events and causal factors have not been clearly established. Comparisons of the transcriptome in the lateral wall (LW) with other cochlear regions in a mouse model (of both sexes) of "normal" age-related hearing loss revealed that early pathophysiological alterations in the stria vascularis (SV) are associated with increased macrophage activation and a molecular signature indicative of inflammaging, a common form of immune dysfunction. Structure-function correlation analyses in mice across the lifespan showed that the age-dependent increase in macrophage activation in the stria vascularis is associated with a decline in auditory sensitivity. High-resolution imaging analysis of macrophage activation in middle-aged and aged mouse and human cochleas, along with transcriptomic analysis of age-dependent changes in mouse cochlear macrophage gene expression, support the hypothesis that aberrant macrophage activity is an important contributor to age-dependent strial dysfunction, cochlear pathology, and hearing loss. Thus, this study highlights the SV as a primary site of age-related cochlear degeneration and aberrant macrophage activity and dysregulation of the immune system as early indicators of age-related cochlear pathology and hearing loss. Importantly, novel new imaging methods described here now provide a means to analyze human temporal bones in a way that had not previously been feasible and thereby represent a significant new tool for otopathological evaluation.SIGNIFICANCE STATEMENT Age-related hearing loss is a common neurodegenerative disorder affecting communication and quality of life. Current interventions (primarily hearing aids and cochlear implants) offer imperfect and often unsuccessful therapeutic outcomes. Identification of early pathology and causal factors is crucial for the development of new treatments and early diagnostic tests. Here, we find that the SV, a nonsensory component of the cochlea, is an early site of structural and functional pathology in mice and humans that is characterized by aberrant immune cell activity. We also establish a new technique for evaluating cochleas from human temporal bones, an important but understudied area of research because of a lack of well-preserved human specimens and difficult tissue preparation and processing approaches.

Potential Clinical and Economic Outcomes of Over-the-Counter Hearing Aids in the US.

Importance: Over-the-counter (OTC) hearing aids are now available in the US; however, their clinical and economic outcomes are unknown. Objective: To project the clinical and economic outcomes of traditional hearing aid provision compared with OTC hearing aid provision. Design, Setting, and Participants: This cost-effectiveness analysis used a previously validated decision model of hearing loss (HL) to simulate US adults aged 40 years and older across their lifetime in US primary care offices who experienced yearly probabilities of acquiring HL (0.1%-10.4%), worsening of their HL, and traditional hearing aid uptake (0.5%-8.1%/y at a fixed uptake cost of $3690) and utility benefits (0.11 additional utils/y). For OTC hearing aid provision, persons with perceived mild to moderate HL experienced increased OTC hearing aid uptake (1%-16%/y) based on estimates of time to first HL diagnosis. In the base case, OTC hearing aid utility benefits ranged from 0.05 to 0.11 additional utils/y (45%-100% of traditional hearing aids), and costs were $200 to $1400 (5%-38% of traditional hearing aids). Distributions were assigned to parameters to conduct probabilistic uncertainty analysis. Intervention: Provision of OTC hearing aids, at increased uptake rates, across a range of effectiveness and costs. Main Outcomes and Measures: Lifetime undiscounted and discounted (3%/y) costs and quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Results: Traditional hearing aid provision resulted in 18.162 QALYs, compared with 18.162 to 18.186 for OTC hearing aids varying with OTC hearing aid utility benefit (45%-100% that of traditional hearing aids). Provision of OTC hearing aids was associated with greater lifetime discounted costs by $70 to $200 along with OTC device cost ($200-$1000/pair; 5%-38% traditional hearing aid cost) due to increased hearing aid uptake. Provision of OTC hearing aids was considered cost-effective (ICER<$100 000/QALY) if the OTC utility benefit was 0.06 or greater (55% of the traditional hearing aid effectiveness). In probabilistic uncertainty analysis, OTC hearing aid provision was cost-effective in 53% of simulations. Conclusions and Relevance: In this cost-effectiveness analysis, provision of OTC hearing aids was associated with greater uptake of hearing intervention and was cost-effective over a range of prices so long as OTC hearing aids were greater than 55% as beneficial to patient quality of life as traditional hearing aids.

Why Do Candidates Forgo Cochlear Implantation?

OBJECTIVE: Identify barriers and facilitating factors in cochlear implant (CI) utilization by comparing functional measures between CI candidates who undergo or forgo implantation. METHODS: Forty-three participants were separated into two groups: (1) 28 participants who underwent CI and (2) 15 participants who elected not to proceed with CI despite meeting eligibility criteria (no-CI). Prior to implantation, all participants completed the CI Quality of Life (CIQOL)-35 Profile and CIQOL-Expectations instrument. They were also surveyed on factors contributing to their decision to either undergo or forgo CI. Word and speech recognition were determined using the Consonant-Nucleus-Consonant (CNC) and the AzBio tests, respectively. RESULTS: CIQOL-Expectations scores were indistinguishable between groups, but there were substantial differences in baseline CIQOL-35 Profile scores. Compared to the CI group, the no-CI group exhibited higher pre-CI scores in the Emotional (Cohen's d [95% CI] = 0.8 [0.1, 1.5]) and Entertainment (Cohen's d [95% CI] = 0.8 [0.1, 1.5]) domains. Survey data revealed that the most commonly reported barriers to pursuing CI in the no-CI cohort were fear of surgical complications (85%), cost associated with implantation (85%), and perception that hearing was not poor enough for CI surgery (85%). CONCLUSIONS AND RELEVANCE: The results of this study indicate that functional outcome expectations are similar between candidates who elect to receive or forgo CI, yet those who forgo CI have higher baseline CI-specific QOL abilities. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:3548-3553, 2023.

Model-Projected Cost-Effectiveness of Adult Hearing Screening in the USA.

BACKGROUND: While 60% of older adults have hearing loss (HL), the majority have never had their hearing tested. OBJECTIVE: We sought to estimate long-term clinical and economic effects of alternative adult hearing screening schedules in the USA. DESIGN: Model-based cost-effectiveness analysis simulating Current Detection (CD) and linkage of persons with HL to hearing healthcare, compared to alternative screening schedules varying by age at first screen (45 to 75 years) and screening frequency (every 1 or 5 years). Simulated persons experience yearly age- and sex-specific probabilities of acquiring HL, and subsequent hearing aid uptake (0.5-8%/year) and discontinuation (13-4%). Quality-adjusted life-years (QALYs) were estimated according to hearing level and treatment status. Costs from a health system perspective include screening ($30-120; 2020 USD), HL diagnosis ($300), and hearing aid devices ($3690 year 1, $910/subsequent year). Data sources were published estimates from NHANES and clinical trials of adult hearing screening. PARTICIPANTS: Forty-year-old persons in US primary care across their lifetime. INTERVENTION: Alternative screening schedules that increase baseline probabilities of hearing aid uptake (base-case 1.62-fold; range 1.05-2.25-fold). MAIN MEASURES: Lifetime undiscounted and discounted (3%/year) costs and QALYs and incremental cost-effectiveness ratios (ICERs). KEY RESULTS: CD resulted in 1.20 average person-years of hearing aid use compared to 1.27-1.68 with the screening schedules. Lifetime total per-person undiscounted costs were $3300 for CD and ranged from $3630 for 5-yearly screening beginning at age 75 to $6490 for yearly screening beginning at age 45. In cost-effectiveness analysis, yearly screening beginning at ages 75, 65, and 55 years had ICERs of $39,100/QALY, $48,900/QALY, and $96,900/QALY, respectively. Results were most sensitive to variations in hearing aid utility benefit and screening effectiveness. LIMITATION: Input uncertainty around screening effectiveness. CONCLUSIONS: We project that yearly hearing screening beginning at age 55+ is cost-effective by US standards.

Understanding Patient Expectations Before Implantation Using the Cochlear Implant Quality of Life-Expectations Instrument.

Importance: Previous research suggests that clinicians view realistic patient expectations as the most important nonaudiological factor in the decision to proceed with a cochlear implant (CI). However, clinicians have few data to determine whether patients' outcome expectations are realistic. Objective: To address this unmet clinical need through the development and psychometric analysis of a new patient-reported outcome measure, the CI Quality of Life (CIQOL) Expectations. Design, Setting, and Participants: This cross-sectional study was conducted at a tertiary CI center from February 26, 2020, to August 31, 2021. First, a team comprising 2 CI audiologists, a CI surgeon, a hearing scientist, and 2 psychometricians with experience in instrument development converted all items from the CIQOL-35 Profile instrument into statements reflecting expected outcomes. Then, cognitive interviews with 20 potential CI users assessed the clarity and comprehensiveness of the new instrument. Next, responses to the CIQOL-Expectations instrument for 131 potential adult CI candidates were psychometrically analyzed using confirmatory factor analysis and item response theory. Finally, degree to which patient expectations changed from before to after and their CI evaluation appointments was measured. Intervention: The CIQOL-Expectations instrument. Results: Of 178 participants, 85 (47.8%) were female, and there was 1 (0.6%) Asian, 26 (14.6%) Black or African American, 1 (0.6%) Latinx, and 150 (84.3%) White individuals. No major content or grammar changes were identified during the cognitive interviews. Overall, all CIQOL domains demonstrated adequate to strong psychometric properties. Several domains did not meet all a priori established indicators of model fit or ability to separate CI users based on response patterns, but all met most indicators. Potential CI users demonstrated the highest mean (SD) expectation scores for the environment (70.2 [20.8]) and social (68.4 [18.0]) domains. In addition, the entertainment (20 [15.3%]) and environment (31 [24.4%]) domains had the highest percentage of patients with expectation scores of 100. Yet, normative CIQOL-35 Profile data from experienced CI users suggested few patients obtain this high degree of functional benefit after implant. Conclusions and Relevance: The results of this cross-sectional study suggest that the CIQOL-Expectations instrument may provide an opportunity to assess potential CI users' expected outcomes using modification of an established CIQOL instrument and a patient-centered framework. The included items and domains reflect real-world functional abilities valued by CI users and may provide opportunities for an evidence-based shared decision-making approach to the CI evaluation process. With this instrument, clinicians can compare individual patients' pre-CI outcome expectations with established normative data and provide appropriate counseling.

Unsupervised Clustering of Olfactory Phenotypes.

BACKGROUND: Current clinical classifications of olfactory function are based primarily upon a percentage of correct answers in olfactory identification testing. This simple classification provides little insight into etiologies of olfactory loss, associated comorbidities, or impact on the quality of life (QOL). METHODS: Community-based subjects underwent olfactory psychophysical testing using Sniffin Sticks to measure threshold (T), discrimination (D), and identification (I). The cognitive screening was performed using Mini-Mental Status Examination (MMSE). Unsupervised clustering was performed based upon T, D, I, and MMSE. Post hoc differences in demographics, comorbidities, and QOL measures were assessed. RESULTS: Clustering of 219 subjects, mean age 51 years (range 20-93 years) resulted in 4 unique clusters. Cluster 1 was the largest and predominantly younger normosmics. Cluster 2 had the worst olfaction with impairment in nearly all aspects of olfaction and decreased MMSE scores. This cluster had higher rates of smoking, heart disease, and cancer and had the worst olfactory-specific QOL. Cluster 3 had normal MMSE with relative preservation of D and I, but severely impaired T. This cluster had higher rates of smoking and heart disease with moderately impaired QOL. Cluster 4 was notable for the worst MMSE scores, but general preservation of D and I with moderate loss of T. This cluster had higher rates of Black subjects, diabetes, and viral/traumatic olfactory loss. CONCLUSION: Unsupervised clustering based upon detailed olfactory testing and cognitive testing results in clinical phenotypes with unique risk factors and QOL impacts. These clusters may provide additional information regarding etiologies and subsequent therapies to treat olfactory loss.

Individual Differences in Speech Recognition Changes After Cochlear Implantation.

Importance: Cochlear implantation is highly effective at improving hearing outcomes, but results have been limited to groupwise analysis. That is, limited data are available for individual patients that report comparisons of preoperative aided speech recognition and postimplantation speech recognition. Objective: To assess changes in preoperative aided vs postoperative speech recognition scores for individual patients receiving cochlear implants when considering the measurement error for each speech recognition test. Design, Setting, and Participants: This cross-sectional study used a prospectively maintained database of patients who received cochlear implants between January 1, 2012, and December 31, 2017, at a tertiary, university-based referral center. Adults with bilateral sensorineural hearing loss undergoing cochlear implantation with 6- or 12-month postoperative measures using 1 or more speech recognition tests were studied. Exposures: Cochlear implantation. Main Outcomes and Measures: Postoperative word recognition (consonant-nucleus-consonant word test), sentence recognition (AzBio sentences in quiet), and sentence recognition in noise (AzBio sentences in +10-dB signal-to-noise ratio) scores, and association of each speech recognition score change with aided preoperative score to each test's measurement error. Results: Analysis of data from a total of 470 implants from 323 patients included 253 male (53.8%) patients; the mean (SD) age was 61.2 (18.3) years. Most patients had statistically significant improvement in all speech recognition tests postoperatively beyond measurement error, including 262 (84.8%) for word recognition, 226 (87.6%) for sentence recognition, and 33 (78.6%) for sentence recognition in noise. A small number of patients had equivalent preoperative and postoperative scores, including 45 (14.5%) for word recognition, 28 (10.9%) for sentence recognition, and 9 (21.4%) for sentence recognition in noise. Four patients (1.6%) had significantly poorer scores in sentence recognition after implantation. The associations between age at implantation and change in speech recognition scores were -0.12 (95% CI, -0.23 to -0.01) for word recognition, -0.22 (95% CI, -0.34 to -0.10) for sentence recognition, and -0.10 (95% CI, -0.39 to 0.21) for sentence recognition in noise. Patients with no significant improvement were similarly distributed between all preoperative aided speech scores for word recognition (range, 0%-58%) and sentence recognition (range, 0%-56%) testing. Conclusions and Relevance: In this cross-sectional study, with respect to preoperative aided speech recognition, postoperative cochlear implant outcomes for individual patients were largely encouraging. However, improvements in scores for individual patients remained highly variable, which may not be adequately represented in groupwise analyses and reporting of mean scores. Presenting individual patient data from a large sample of individuals with cochlear implants provides a better understanding of individual differences in speech recognition outcomes and contributes to more complete interpretations of successful outcomes after cochlear implantation.

Atorvastatin is associated with reduced cisplatin-induced hearing loss.

BACKGROUNDCisplatin is widely used to treat adult and pediatric cancers. It is the most ototoxic drug in clinical use, resulting in permanent hearing loss in approximately 50% of treated patients. There is a major need for therapies that prevent cisplatin-induced hearing loss. Studies in mice suggest that concurrent use of statins reduces cisplatin-induced hearing loss.METHODSWe examined hearing thresholds from 277 adults treated with cisplatin for head and neck cancer. Pretreatment and posttreatment audiograms were collected within 90 days of initiation and completion of cisplatin therapy. The primary outcome measure was a change in hearing as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).RESULTSAmong patients on concurrent atorvastatin, 9.7% experienced a CTCAE grade 2 or higher cisplatin-induced hearing loss compared with 29.4% in nonstatin users (P < 0.0001). A mixed-effect model analysis showed that atorvastatin use was significantly associated with reduced cisplatin-induced hearing loss (P ≤ 0.01). An adjusted odds ratio (OR) analysis indicated that an atorvastatin user is 53% less likely to acquire a cisplatin-induced hearing loss than a nonstatin user (OR = 0.47; 95% CI, 0.30-0.78). Three-year survival rates were not different between atorvastatin users and nonstatin users (P > 0.05).CONCLUSIONSOur data indicate that atorvastatin use is associated with reduced incidence and severity of cisplatin-induced hearing loss in adults being treated for head and neck cancer.TRIAL REGISTRATIONClinicalTrials.gov identifier NCT03225157.FUNDINGFunding was provided by the Division of Intramural Research at the National Institute on Deafness and Other Communication Disorders (1 ZIA DC000079, ZIA DC000090).

Comparative implementation-effectiveness of three strategies to perform hearing screening among older adults in primary care clinics: study design and protocol.

BACKGROUND: The burden of hearing loss among older adults could be mitigated with appropriate care. This study compares implementation of three hearing screening strategies in primary care, and examines the reliability and validity of patient self-assessment, primary care providers (PCP) and diagnostic audiologists in the identification of 'red flag' conditions (those conditions that may require medical consultation and/or intervention). METHODS: Six primary care practices will implement one of three screening strategies (2 practices per strategy) with 660 patients (220 per strategy) ages 65-75 years with no history of hearing aid use or diagnosis of hearing loss. Strategies differ on the location and use of PCP encouragement to complete a telephone-based hearing screen (tele-HS). Group 1: instructions for tele-HS to complete at home and educational materials on warning signs and consequences of hearing loss. Group 2: PCP counseling/encouragement on importance of hearing screening, instructions to take the tele-HS from home, educational materials. Group 3: PCP counseling/encouragement, in-office tele-HS, and educational materials. Patients from all groups who fail the tele-HS will be referred for diagnostic audiological testing and medical evaluation, and complete a self-assessment of red flag conditions at this follow-up appointment. Due to the expected low incidence of ear disease in the PCP cohort, we will enroll a complementary population of patients (N = 500) from selected otolaryngology head and neck surgery clinics in a national practice-based research network to increase the likelihood of occurrence of medical conditions that might contraindicate hearing aid fitting. The primary outcome is the proportion of patients who complete the tele-HS within 2 months of the PCP appointment comparing Group 3 (PCP encouragement, in-office tele-HS, education) versus Groups 2 and 1 (education and tele-HS at home, with and without PCP encouragement, respectively). The several secondary outcomes include direct and indirect costs, patient, family and provider attitudes of hearing healthcare, and accuracy of red flag condition evaluations compared with expert medical assessment by an otolaryngology provider. DISCUSSION: Determining the relative effectiveness of three different strategies for hearing screening in primary care and the assessment accuracy of red flag conditions can each lead to practice and policy changes that will reduce individual, family and societal burden from hearing loss among older adults. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02928107; 10/10/2016 protocol version 1.

Association of Patient-Related Factors With Adult Cochlear Implant Speech Recognition Outcomes: A Meta-analysis.

Importance: Multiple studies have evaluated associations between post-cochlear implant (CI) speech recognition outcomes and patient-related factors. Current literature often appears equivocal or contradictory, so little is known about the factors that contribute to successful speech recognition outcomes with CIs. Objective: To use a meta-analysis to pool data from the extant literature and provide an objective summary of existing evidence on associations of patient-related factors and CI speech recognition outcomes. Data Sources: A literature search was performed using PubMed, Scopus, and CINAHL databases in January 2019 using the following search terms: cochlear implant or cochlear implants or cochlear implantation and speech recognition or word recognition or sentence recognition. Studies of postlingually deafened adult CI recipients that reported word or sentence recognition scores were included. Study Selection: Inclusion criteria were postlingual adult CI recipients 18 years or older with word or sentence recognition scores at minimum 6-month postimplantation. Studies that included patients undergoing revision or reimplantation surgery were excluded. Data Extraction and Synthesis: Following the Preferred Reporting Items for Systemic Reviews and Meta-analyses (PRISMA) guidelines, 1809 unique articles underwent review by abstract, and 121 articles underwent full-text review, resulting in 13 articles of 1095 patients for a meta-analysis of correlations. Random-effects model was used when the heterogeneity test yielded a low P value (P < .05). Main Outcomes and Measures: The planned primary outcome was the pooled correlation values between postimplant speech recognition scores and patient-related factors. Results: Of the 1095 patients included from the 13 studies, the mean age at implantation ranged from 51.2 to 63.7 years and the mean duration of hearing loss ranged from 9.5 to 31.8 years; for the 825 patients for whom sex was reported, 421 (51.0%) were women. A weak negative correlation was observed between age at implantation and postimplant sentence recognition in quiet (r = -0.31 [95% CI, -0.41 to -0.20]). Other correlations between patient-related factors and postimplant word or sentence recognition were statistically significant, but all correlations were absent to negligible (r = 0.02-0.27). Conclusions and Relevance: Given that most associations were weak, negligible, or absent, patient-related factors often thought to affect CI speech recognition ability offer limited assistance in clinical decision-making in cochlear implantation. Additional research is needed to identify patient-related and other factors that predict CI outcomes, including speech recognition and other important variables related to success with CIs.

Association of Demographic and Hearing-Related Factors With Cochlear Implant-Related Quality of Life.

Importance: Only limited evidence is available describing the contribution of patient-related factors to quality of life in adults with cochlear implants. Objective: Assess the association between demographic, hearing-related, and cochlear implant-related factors and quality of life by using a new Cochlear Implant Quality of Life (CIQOL) item bank, which was developed to meet rigorous psychometric standards. Design, Setting, and Participants: Multicenter cross-sectional study of adults 18 to 89 years of age who had at least 1 year of cochlear implant use and who were recruited through a consortium of 20 cochlear implant centers in the United States. Using an online format, questionnaires were sent to the first 500 participants who contacted the research team. Of these participants, 371 (74.2%) completed the questionnaire. Demographic, hearing-related, and cochlear implant-related data were obtained along with responses to each of the 81 items in the CIQOL item bank. Multivariable linear regression was used to examine demographic, hearing-related, and cochlear implant-related factors associated with scores in each of the 6 CIQOL domains (communication, emotional, entertainment, environment, listening effort, and social). Main Outcomes and Measures: Association among demographic, hearing-related, and cochlear implant-related factors and CIQOL scores for each of 6 domains. Results: Of the 371 participants who completed the questionnaire, 222 (59.8%) were women, and the mean (SD) age was 59.5 (14.9) years. The CIQOL scores were normally distributed across the 6 domains. Being employed, having higher household income, longer duration of hearing loss prior to cochlear implantation, and having bilateral rather than unilateral cochlear implantation were associated with higher CIQOL scores in 1 or more domains, but the effect size varied widely (ß, 0.1-6.9). Better sentence recognition ability (using AzBio to measure speech recognition) was associated with only a small positive effect size for the communication (ß, 0.0 [95% CI, 0.0-0.1]), entertainment (ß, 0.0 [95% CI, 0.0-0.1]), and environmental (ß, 0.0 [95% CI, 0.0-0.0]) domains. Increased age was associated with lower CIQOL in the entertainment domain (ß, -0.3 [95% CI, -1.5 to -0.4]). The demographic, hearing-related, and cochlear implant-related factors included in the multivariable regression models accounted for only a small percentage of the variance in CIQOL domain scores (R2, 0.08-0.17). Conclusions and Relevance: Several factors were found to predict higher or lower CIQOL scores in specific domains, with speech-recognition ability having only a minimal association. Despite evaluating a large number of demographic, hearing-related, and cochlear implant-related factors, the multivariable models accounted for only a small amount of CIQOL variance. This suggests that patient or other characteristics that contribute to cochlear implant-related quality of life remain largely unknown.

Use of Adult Patient Focus Groups to Develop the Initial Item Bank for a Cochlear Implant Quality-of-Life Instrument.

Importance: No instrument exists to assess quality of life (QOL) in adult cochlear implant (CI) users that has been developed and validated using accepted scientific standards. Objective: To develop a CI-specific QOL instrument for adults in accordance with the Patient Reported Outcomes Measurement Information System (PROMIS) guidelines. Design, Setting, and Participants: As required in the PROMIS guidelines, patient focus groups participated in creation of the initial item bank. Twenty-three adult CI users were divided into 1 of 3 focus groups stratified by word recognition ability. Three moderator-led focus groups were conducted based on grounded theory on December 3, 2016. Two reviewers independently analyzed focus group recordings and transcripts, with a third reviewer available to resolve discrepancies. All data were reviewed and reported according to the Consolidated Criteria for Reporting Qualitative Research. The setting was a tertiary referral center. Main Outcomes and Measures: Coded focus group data. Results: The 23 focus group participants (10 [43%] female; mean [range] age, 68.1 [46.2-84.2] years) represented a wide range of income levels, education levels, listening modalities, CI device manufacturers, duration of CI use, and age at implantation. Data saturation was determined to be reached before the conclusion of each of the focus groups. After analysis of the transcripts, the central themes identified were communication, emotion, environmental sounds, independence and work function, listening effort, social isolation and ability to socialize, and sound clarity. Cognitive interviews were carried out on 20 adult CI patients who did not participate in the focus groups to ensure item clarity. Based on these results, the initial QOL item bank and prototype were developed. Conclusions and Relevance: Patient focus groups drawn from the target population are the preferred method of identifying content areas and domains for developing the item bank for a CI-specific QOL instrument. Compared with previously used methods, the use of patient-centered item development for a CI-specific QOL instrument will more accurately reflect patient experience and increase our understanding of how CI use affects QOL.

Sox10 expressing cells in the lateral wall of the aged mouse and human cochlea.

Age-related hearing loss (presbycusis) is a common human disorder, affecting one in three Americans aged 60 and over. Previous studies have shown that presbyacusis is associated with a loss of non-sensory cells in the cochlear lateral wall. Sox10 is a transcription factor crucial to the development and maintenance of neural crest-derived cells including some non-sensory cell types in the cochlea. Mutations of the Sox10 gene are known to cause various combinations of hearing loss and pigmentation defects in humans. This study investigated the potential relationship between Sox10 gene expression and pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human temporal bones from older donors. Cochlear tissues prepared from young adult (1-3 month-old) and aged (2-2.5 year-old) mice, and human temporal bone donors were examined using quantitative immunohistochemical analysis and transmission electron microscopy. Cells expressing Sox10 were present in the stria vascularis, outer sulcus and spiral prominence in mouse and human cochleas. The Sox10(+) cell types included marginal and intermediate cells and outer sulcus cells, including those that border the scala media and those extending into root processes (root cells) in the spiral ligament. Quantitative analysis of immunostaining revealed a significant decrease in the number of Sox10(+) marginal cells and outer sulcus cells in aged mice. Electron microscopic evaluation revealed degenerative alterations in the surviving Sox10(+) cells in aged mice. Strial marginal cells in human cochleas from donors aged 87 and older showed only weak immunostaining for Sox10. Decreases in Sox10 expression levels and a loss of Sox10(+) cells in both mouse and human aged ears suggests an important role of Sox10 in the maintenance of structural and functional integrity of the lateral wall. A loss of Sox10(+) cells may also be associated with a decline in the repair capabilities of non-sensory cells in the aged ear.

Heptanol application to the mouse round window: a model for studying cochlear lateral wall regeneration.

OBJECTIVE: Identify cells supporting cochlear lateral wall regeneration. STUDY DESIGN: Prospective controlled trial. SETTING: Laboratory. Human presbyacusis occurs, in part, secondary to age-related degeneration of cochlear lateral wall structures such as the stria vascularis and spiral ligament fibrocytes. This degeneration is likely linked to the diminished regenerative capacity of lateral wall cells with age. While lateral wall regeneration is known to occur after an acute insult, this process remains poorly understood and the cells capable of self-replication unidentified. We hypothesized that spiral ligament fibrocytes constitute these proliferative cells. SUBJECTS AND METHODS: To test the hypothesis, an acute ototoxic insult was created in 65 normal-hearing, young adult mice via cochlear exposure to heptanol. Sacrifice occurred at 1 to 60 days posttreatment. Auditory brainstem responses, 5-ethynyl-2'-deoxyuridine assay, and immunostaining were used to assess regeneration. RESULTS: Posttreatment hearing thresholds were elevated in nearly all treated mice. Selective fibrocyte apoptosis and strial injury were observed at the time of peak hearing loss around 1 to 7 days posttreatment. Cellular proliferation was detected in the region of type II fibrocytes during this time. Hearing thresholds plateaued at 7 days posttreatment followed by a significant recovery of both hearing and morphologic appearance. Permanent outer hair cell degeneration was observed. CONCLUSIONS: Heptanol application to the round window of young adult mice is a rapid, selective, and reliable technique for investigating proliferation in the cochlear lateral wall. The data indirectly showed that spiral ligament fibrocytes may be the proliferative cells of the cochlear lateral wall. Further studies of this process are needed.

Lipid and C-reactive protein levels as risk factors for hearing loss in older adults.

OBJECTIVE: To determine the role of cardiovascular disease (CVD) markers, lipids and C-reactive protein, in age-related hearing loss over time. STUDY DESIGN: Prospective cohort study. SETTING: Research laboratories at an academic medical center. SUBJECTS AND METHODS: In total, 837 older adults (mean age 67.5 years) were included. Primary dependent variables were pure-tone thresholds (pure-tone average [PTA]), including "narrow" PTA (0.5, 1, 2, 4 kHz), "broad" PTA (0.5, 1, 2, 3, 4, 6, 8 kHz), low-frequency PTA (0.25, 0.5, 1 kHz), and high-frequency PTA (2, 3, 4, 6, 8 kHz). Repeated-measures mixed regression modeling was used to assess the relationship between C-reactive protein (CRP) and lipid levels with PTAs over time. RESULTS: In a cross-sectional sample of 837 subjects, modest associations were found between triglycerides and all PTAs. Weak associations were observed between the ratio of total cholesterol and high-density lipoprotein and narrow PTA, broad PTA, and high-frequency PTA. However, when assessing changes in hearing and lipids over time in a longitudinal analysis, no significant associations between hearing and lipids remained. PTAs and CRP were not statistically associated when controlling for age and sex. CONCLUSION: Associations between hearing and blood lipids have been the focus of scientific inquiry for more than 50 years. The current results suggest that the association is either spurious or too small to be of consequence in the assessment and treatment of hearing loss in older adults. Inquiry into other potential risk factors for age-related hearing loss and associations with CVD may prove more fruitful.