Various prognostic factors for idiopathic sudden sensorineural hearing loss (SSNHL) have been reported. Hearing loss directly derived from idiopathic SSNHL is important for understanding underlying pathogenesis and outcomes. We assessed the usefulness of evaluating hearing loss and recovery of idiopathic SSNHL on the basis of estimated hearing loss. The study included 115 patients whose characteristics and outcomes of hearing loss were investigated. The effects of vertigo/dizziness and age on hearing thresholds before/after treatment, nonaffected ear threshold, estimated hearing loss, improvement of hearing loss, and estimated remaining hearing loss were investigated. Vertigo/dizziness was a significant prognostic factor for hearing. In vertigo/dizziness patients, significantly more severe hearing loss and poorer improvement of hearing loss were observed above 500 Hz and below 1000 Hz, respectively. Severe hearing disorder remained at all frequencies. Conversely, post-treatment thresholds were significantly higher in the older population (≥65 years), although no differences in pretreatment thresholds were observed between the younger (≤64 years) and older populations. However, on the basis of nonaffected ear thresholds, previously existing hearing loss could have influenced the outcome. Thus, comparison of hearing outcomes between affected and nonaffected ears is essential for understanding hearing loss and outcomes in idiopathic SSNHL cases with existing hearing disorder. Idiopathic sudden sensorineural hearing loss (SSNHL) is one of the major emergency diseases in otolaryngology. The frequency is not rare , and it The outcomes of idiopathic SSNHL are usually evaluated according to the hearing thresholds before and after treatment ,5,6,7. AIn this study, we investigated the effects of prognostic factors according to hearing thresholds before treatment and improvement after treatment similar to previous studies ,5,6. In Patients who visited our department for the treatment of idiopathic SSNHL from 2009 to 2017 were registered for this study. The criteria for enrollment into this study were as follows: (1) no ear diseases in both ears before the onset of idiopathic SSNHL; (2) no hearing disorder except presbycusis; (3) a time from onset of idiopathic SSNHL to treatment initiation within 14 days; (4) no radical treatment performed before visiting our department. The diagnosis of idiopathic SSNHL was performed according to the criteria defined by the Research Committee of the Ministry of Health and Welfare in Japan . OccasioConventional pure tone audiometry was performed using an audiometer , and hearing thresholds were obtained at frequencies of 125, 250, 500, 1000, 2000, 4000, and 8000 Hz. The severity of hearing loss was evaluated according to the grading system established by the Research Committee of the Ministry of Health and Welfare in Japan. It was classified into four grades according to the audiometric mean of the five frequencies . The criteria of the audiometric means for Grades 1, 2, 3, and 4 were <40, 40–59, 60–89, and ≥90 dB, respectively [Hearing ability was monitored until participants recovered from the hearing loss. When the thresholds recovered to within 20 dB of the hearing level (HL) at all frequencies or reached the same level as the nonaffected ear, the hearing loss was considered completely recovered, and no further follow-up was performed. In the other cases, when the threshold remained stable for 1 month, the hearing loss was considered fixed. These final thresholds were regarded as the post-treatment thresholds. The treatment outcome of the hearing loss was diagnosed by calculating the audiometric mean of the five frequencies  according to the hearing improvement criteria defined by the Research Committee of the Ministry of Health and Welfare in Japan [The effect of age (≤64 or ≥65 years), sex, time from onset of idiopathic SSNHL to treatment initiation (within or after 7 days), and vertigo/dizziness on hearing loss grade were investigated. According to a previous study [In addition, we investigated the effects of vertigo/dizziness and age on the threshold at each frequency. For the statistical analysis, the threshold was regarded as the maxi-mum output level plus 5 dB when the participant could not hear the stimulus at the maximum output level. The respective maximum output levels at 125, 250, and 8000 Hz were set at 70, 90, and 100 dB HLs. The others were set at 110 dB HLs. In addition, assuming that the thresholds in the nonaffected ear were almost equal to those in the affected ear before the onset, the hearing loss directly derived from idiopathic SSNHL was estimated by subtracting the nonaffected ear threshold from the pretreatment threshold. The remaining hearing loss was also estimated by subtracting the nonaffected ear threshold from the post-treatment threshold. The improvement of the hearing loss was calculated by subtracting the post-treatment threshold from the pretreatment threshold. The effects of vertigo/dizziness (with or without) and age (≤64 or ≥65 years) on hearing disorder, improvement, and remaining hearing loss were also investigated at frequencies of 125–8000 Hz. The data were statistically analyzed by two-way analysis of variance (ANOVA) using SPSS ver. 22  at a 0.05 significance level. The Bonferroni method was used for post hoc comparisons.The participants’ characteristics are presented in The estimated hearing loss directly derived from the idiopathic SSNHL ear was significantly higher for patients with vertigo/dizziness at frequencies of 500–8000 Hz. In contrast, the improvements of hearing loss for patients with vertigo/dizziness were significantly lower at 125–1000 Hz. Notably, patients with vertigo/dizziness had significantly higher estimated remaining hearing loss at all frequencies.The hearing loss grade and treatment outcome in this study were evaluated according to the criteria defined by the Ministry of Health and Welfare in Japan and were compared to the results of a previous nationwide epidemiological survey that used the same criteria . The heaThe treatment outcomes in the present study  are similar to those in the previous study . RegardiNo differences were found in the thresholds of the nonaffected ear at all frequencies between patients with and without vertigo/dizziness, which suggests that hearing threshold before disease onset does not influence the symptom of vertigo/dizziness. In the affected ear, the thresholds before and after treatment for the patients with vertigo/dizziness were significantly higher than those for the patients without it at frequencies ≥ 500 Hz and all frequencies, respectively. These results suggest severe hearing loss and poor outcomes in patients with vertigo/dizziness, which agrees with the findings of previous studies ,7,8,9. IThe estimated hearing loss directly derived from idiopathic SSNHL was significantly larger in patients with vertigo/dizziness, particularly by ≥20 dB at frequencies ≥ 2000 Hz. In contrast, regarding hearing improvement, no significant difference was found at high frequency between patients with and without vertigo/dizziness. This finding suggests that the initial hearing loss at disease onset rather than poor improvement determines the remaining hearing disorder after treatment. Vertigo/dizziness is one of the poor prognostic factors for idiopathic SSNHL. Severe hearing loss at disease onset may result in poor outcomes in patients with vertigo/dizziness. The hearing threshold after treatment was higher in the older population (≥65), while no difference in pretreatment threshold was observed between the two age groups ≤64 and ≥65). This result suggests a poorer outcome in the older population, which is consistent with previous findings that age may significantly influence prognosis ,3,4. How and ≥65.The findings of the present study suggest the usefulness of estimated hearing loss in evaluating idiopathic SSNHL and its recovery. However, quality data on hearing loss directly derived from idiopathic SSNHL are currently missing, thus warranting further research. Vertigo/dizziness is a significant poor prognostic factor for hearing loss directly derived from idiopathic SSNHL. The improvement of the initial hearing loss does not significantly differ between patients with and without vertigo/dizziness. Substantial hearing loss occurs at disease onset and leads to poor treatment outcome. The treatment outcome is also poorer in the older population. Notably, the previously existing hearing loss may influence the treatment outcome of idiopathic SSNHL. The comparison of hearing outcomes between the affected and nonaffected ears is essential for understanding the hearing loss and outcomes in idiopathic SSNHL cases with existing hearing disorder.


Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss. The number of people with mild-to-complete hearing impairment is projected to increase to an estimated 2.45 billion worldwide by 2050, principally driven by age-related hearing impairment (ARHI).,Hearing thresholds tend to deteriorate gradually with age and ARHI is typically more pronounced in the higher frequencies. Knowledge of the pathophysiological mechanisms of hearing loss derives primarily from animal studies , the Danish Twin Registry , the Estonian Genome Center at the University of Tartu , FinnGen , Framingham Heart Study , Health Aging and Body Composition , Italian Network of Genetic Isolates - Friuli Venezia Giulia , the Rotterdam Study , the Salus in Apulia study , Screening Across the Lifespan Twin , Screening Twin Adults: Genes and Environment , TwinsUK , UK Biobank , and the Women’s Genome Health Study . All participants provided written informed consent; ethical approval was obtained locally. The declaration of Helsinki was adhered to. Phenotype was based on ICD9 & 10 diagnoses of hearing loss (EGCUT and FinnGen) or questions on hearing loss . Mean age overall was 59.6. A detailed description of phenotype definition case control distribution and age range for each study can be found in GWASs have been carried out for each cohort locally and summary statistics were collected for each study. Standardized quality control was performed using EasyQC software,−8. Conditional and joint association analysis (COJO) was carried out to reveal independent lead SNPs for genome-wide significant loci using GCTA software.Meta-analysis of GWAS summary statistics was conducted using an inverse-variance-weighted fixed-effect model in METAL.−6) implemented in FUMAhttps://vegas2.qimrberghofer.edu.au/glist-hg19) and included 26,056 genes. Given that the number of genes in the output would depend on the analysis parameters, we chose to correct for multiple testing assuming 20,000 independent tests by Bonferroni approach.For gene prioritization in the genome-wide significant loci, we used MAGMAwww.mousephenotype.org) were consulted.Genes within 500 Mb from the top SNP were checked for any known association with hearing loss in either humans or mice. For that purpose, existing literature and the website of the International Mouse Phenotyping Consortium (https://vegas2.qimrberghofer.edu.au/biosystems20160324.vegas2pathSYM).We used VEGAS2 for pathway analysis based on the results of gene prioritization as described above and the list of pathways provided as part of VEGAS2 distribution (2ZW3) and the structural consequences of GJB2 variants were modeled using PyMOL v..1.1.All variants identified in genes of interest in the gnomAD v.2.1.1 were downloaded, and minor allele frequencies (MAFs) were filtered to select for variants that were common (MAF ≥1%) in the non-Finnish European (EUR) population. Transcripts were selected based on consensus with the Deafness Variation Database transcript catalog,https://github.com/mulinlab/CAUSALdb-finemapping-pip). We analyzed 1 Mb regions surrounding lead SNPs in each genome-wide significant locus. The output includes credible sets and posterior probabilities for SNPs to be causal as per PAINTOR, CAVIARBF, and FINEMAP algorithms.Fine-mapping was carried out using CAUSALdb-finemapping-pip pipeline  collated by the Psychiatric Genomics Consortium, we used LDSC to get SNP-based genetic correlation between hearing loss and psychiatric and anthropometric traits.We obtained expression specificity data in 37 GTEx v8We processed and calculated the expression specificity as previously described.Specificity ranges from 0 to 1; a higher value indicates that the gene is more specific to the corresponding cell types compared to its expression profiles across all included cell types. We selected genes with the top 10% specificity values in each cell type as the gene list for the cell type that was used for the heritability enrichment analyses.2 of hearing loss.We used MAGMA (v.1.08),MAGMA evaluated whether the cell-type-specific genes were enriched in hearing loss gene-level associations in two steps. In the first step , we filtered out SNPs with minor allele frequency <1% and poor imputation quality (INFO < 0.6) from the ARHI summary statistics and calculated the p value for per gene association with hearing loss using SNP p values (35 kb upstream and 10 kb downstream window per gene).Z score coefficient for tissue/cell-type-specific genes.We then applied partitioned LDSC adjusting for the baseline annotations.−8). There was no evidence of residual population stratification in the results of meta-analysis . LD score regression intercept is 1.0039 (0.0095), indicating that the inflation of the GWAS test statistics was due to polygenicity (2) on the observed scale was h2 = 0.0252 (SE = 0.0013) and on the liability scale was estimated to be between 0.033 (SE = 0.002) and 0.061 (SE = 0.003) given the case/control ratio in our sample (20%) and populational prevalence in the range of 5%–40%. Next, we employed conditional and joint analysis (COJO) to identify lead independent signals in the loci  and 575,269 controls (79.5%). Affected individuals were defined by either clinical diagnosis of hearing loss  or self-reported hearing impairment . We completed a genome-wide meta-analysis of 8,244,938 imputed SNPs that passed quality control (QC) and identified 48 significant loci . Four of the identified genes have an established connection to deafness: EYA4 , CDH23 (DFNB12 [MIM: 601543]), GJB2 (DFNA3A [MIM 601544] and DFNB1A [MIM: 220290]), and TRIOBP (DFNB28 [MIM: 609823]).FSCN2,ANKRD24, and KLHDC7B (https://www.mousephenotype.org/about-impc/). Mutations in COL9A3 cause autosomal-recessive Stickler syndrome,ANKRD24 [CADD score = 0.241]), CADD scores of the missense SNPs (18.45 to 31) were among the top ∼1%–0.1% of deleterious variants in the human genome. We conducted an additional in silico functional analysis on these 8 missense variants and the results provide strong evidence that variants in FSCN2 and COL9A3 are highly deleterious and likely impact gene function  (Eight SNPs encoded missense mutations . The profunction . High-re5887622) A. The GJ5887622) A. The am5887622) B.Table 2A significant positive genetic correlation was found between hearing loss and insomnia, depressive symptoms, neuroticism, and obesity LD Hub, . A signi2 in GTEx tissues  influencing hearing loss with the greatest probability, while the whole iceberg is pictured by the contribution of all GWAS signals, pointing to genes expressed in cells from the lateral wall, namely basal cells and spindle cells of the stria vascularis and root cells in the outer sulcus . These three cell types are primarily involved in endolymph ion homeostasis.,Fifth, although lead association SNPs are related to sensory hair cell function and their involvement in hearing loss is well established, our cell-specific enrichment analysis revealed hearing loss being also driven, at least in part, by basal cells and spindle cells in the stria vascularis and root cells in the outer sulcus. Indeed, the lead SNPs mainly related to hair cell and auditory neuron function represent the tip of the iceberg . For instance, using 1,100 proprioceptive neurons and Smart-seq2, Wu et al. detected 11,000 genes per cell and identified 8 cell types,Hearing loss is a heterogeneous disorder with many contributing factors during life. A potential implication for future genetic studies is the elucidation of the bulk of common variants using a cost-effective shortcut involving on-line self-reports combined with auditory tests, such as automated speech and noise test.This study of hearing loss identified 48 associated loci, including 10 novel associations and 8 missense SNPs. Our work highlights the role of the cochlear lateral wall including the stria vascularis and the outer sulcus as a contributor to hearing loss. The results provide a valuable resource for the selection of promising genes for further functional validation in pre-clinical models and define targets for screening purposes, drug development, gene therapy, or stratification approaches. We believe such experiments will serve as a solid foundation for ultimately improving therapies against hearing loss.The Estonian Biobank Research Team is composed of Andres Metspalu, Mari Nelis, Reedik Mägi, and Tõnu Esko.


A variety of outcome domains are currently measured for the assessment of hearing rehabilitation. To date, there is no consensus about which outcome domains should be measured, when they should be measured, and how they should be measured. In addition, most studies seeking to develop core outcome sets and measures for hearing rehabilitation services have primarily focussed on the opinions and expertise of researchers, and, to a lesser extent, clinicians, rather than also involving clients of those services. The principles of experience-based co-design suggest that health services, researchers, and policymakers should come together with clients and their families to design health services and define what metrics should be used for their success.This study aimed to seek views and consensus from a range of key stakeholders to define which client-centred self-report outcome domains should be measured, when they should be measured, and how they should be measured, in a national publicly funded hearing rehabilitation scheme. In addition, the study aimed to identify current and future potential mechanisms and systems to standardise the collection of data and reporting of outcomes, to enable comparison across clients and hearing service providers.Two stakeholder groups participated in a three-round online Delphi process: (1) 79 professional stakeholders involved in the delivery of hearing services in Australia, and (2) 64 hearing rehabilitation services’ clients identified by not-for-profit consumer organisations. An initial set of in-person workshops scoped the key issues upon which to develop the initial open-ended questions and subsequent Likert-scale statements addressing these issues. These statements were then distributed to both groups in an online survey. The respondent ratings were summarised, and the summary was returned to respondents along with a second round of the survey. This process was then repeated once more. The five most important outcome domains from both groups were then combined, and a consensus workshop of seven professionals and three client advocates agreed on the top four ranked domains.A range of potential outcome domains were identified as relevant indicators of successful hearing rehabilitation. Communication ability, personal relationships, wellbeing, and participation restrictions were identified as a core outcome domain set that should be measured as a minimum for patients receiving hearing rehabilitation. There was little agreement on the preferred timepoints for collection of outcome measures, with respondents expressing the view that this should be established by research once a set of outcome measures has been selected. However, there was broad agreement that measurements of these domains should be collected at baseline (before the provision of hearing rehabilitation) and no earlier than 3 months following the completion of rehabilitation. Potential benefits and issues with the development of a national outcomes database/collection system were also identified and prioritised, with participants highlighting the importance of valid, high-quality, trustworthy, and comprehensive data collection.These results provide a Core Outcome Domain Set for the self-reported evaluation of hearing rehabilitation and provide important background information for the design of methods to implement them across hearing healthcare systems. However, the wide range of outcome domains identified as potentially providing important additional information and the lack of specific measures to address these domains strongly suggest that there is still more research to be done. Ongoing stakeholder engagement will continue to be vital for future implementation. In addition, further research is required to determine the optimal time following hearing rehabilitation to utilise any particular outcome measure. Hearing loss is a chronic condition that affects around four million adults in Australia, which represents one in six of the population . In addiAuditory rehabilitation aims to address the negative impact of hearing loss and includes a range of interventions. The primary intervention is hearing aids, which have been shown to be clinically effective in terms of listening ability, hearing-related quality of life  and health-related quality of life . There aIn order to assess the effectiveness of interventions for adults with hearing loss, irrespective of the intervention type, it is essential to have appropriate and sensitive outcome measures that are relevant to the outcome domains targeted for improvement by auditory rehabilitation . These aOne of the major problems with measuring outcomes within auditory rehabilitation is the large number of tools and instruments, including behavioural and self-report measures . In partMany of these measures measure similar underlying constructs, such as hearing device use, benefit, satisfaction, and social participation. In the context of hearing outcomes, these underlying constructs are known as outcome domains. However, even among outcome domains that are in widespread use and seen to be important indicators of successful rehabilitation, such as hearing aid use, there is little consensus around which outcome measures should be used . FurtherThe evidence is clear that both auditory rehabilitation clinical practice and research lack a single (or even a few) outcome measure that is used widely and consistently and accepted as a “gold standard” instrument. Furthermore, even though there is a large number and variety of measures within the field, clinical trials of adult auditory rehabilitation interventions have overlooked outcomes such as adverse effects and quality of care that may be important to key stakeholders, especially patients, hearing healthcare professionals and commissioners of hearing healthcare . The invA major consequence of an non-standardised approach to outcome measurement is that comparison across different patient cohorts and services is almost impossible. Similarly, within research, it is very difficult to compare and combine the results of different trials that use different measures , which results in reduced relevance of the results and increased risk of outcome reporting bias .Within the Australian hearing healthcare context, hearing services are provided free of charge to over one million people each year through the Hearing Services Program (HSP), primarily through the Voucher Scheme, at a cost of $590 million per annum . The VouA Government-commissioned review of the HSP published in 2017 found that the majority of key healthcare stakeholders  who were consulted agreed that client outcomes were important, however there was no consensus on how they should be measured . Four tywhat outcome domains should be measured, and then how this should be measured using an outcomes tool : a set of outcome domains that should be used as a minimum standard for the assessment of a health condition , as wellmes tool . The firThe specific aims of this study were to:1.Seek views and consensus from a range of key stakeholders to define which client-centred outcome domains should be used, when they should be measured, and how they should be measured, for the assessment of hearing rehabilitation delivered within a national publicly funded hearing rehabilitation scheme.2.Identify current and future potential mechanisms and systems to standardise the collection of data and reporting of outcomes, to enable comparison across clients and hearing service providers.This study was approved by the Hearing Australia Human Research Ethics Committee. Informed consent was obtained from all participants.Outcome Domains, Time of Collection, Methods of Collection, Parties Responsible for Collection, Reason for Collection, and National Outcomes Database. Where information from a previous stage was used to inform or develop a subsequent stage, this is denoted by an arrow.The overall structure of this research study is shown in Outcome Domains section of the Delphi reviews. Three workshops were conducted with the Professionals group, one each in Sydney, Melbourne, and Brisbane. One workshop was conducted in Sydney with Consumers from around Australia, with travel costs covered by the research team.Four in-person scoping workshops were used to establish the initial statements for the At these workshops, structured brainstorming exercises were used to assist participants to identify a comprehensive long list of domains in which outcomes of hearing rehabilitation might be observed.For the workshops conducted with the Professional group, the New South Wales Government Human Services Outcomes Framework was used to guide brainstorming . This frFor the workshop conducted with the Consumer group, participants were asked to define “personas” for people involved in hearing services, including people with hearing loss, their family members, clinicians, and policymakers. For each of these personas, participants then brainstormed markers of successful hearing rehabilitation  and markers of unsuccessful hearing rehabilitation .The lists of identified outcome domains from the workshops were then combined by the research team, and duplicates were removed.via an online survey.A Delphi review is an iterative process in which respondents are asked to complete a series of surveys (rounds), with subsequent rounds including summary information about the responses to the previous round, allowing participants to re-evaluate their previous rating of a statement based on any emerging group consensus . The DelTwo Delphi reviews, each of three rounds, were conducted with the Professional and Consumer groups separately. These reviews utilised different surveys and slightly different questions, targeted to the two different populations. Where the same question was asked of both groups, summary information from both groups was presented, allowing respondents to use information from both groups of stakeholders in their re-evaluation see .Outcome Domains, Methods of Collection, and National Outcomes Database) were asked of both groups, and three  were asked only of the Professionals group, as it was felt by the research team that these would likely be out of the scope of understanding of non-professionals.The Delphi reviews covered six sections. Three of these  that need to be checked grows superfactorially (due to ties) with the number of items to be ranked : while tOutcome Domains, Time of Collection, and Methods of Collection sections of the Delphi Reviews was distributed to workshop participants prior to the workshop.A summary of results from the At the online workshop, the top five outcome domains as determined by the Consumer group and the top five outcome domains as determined by the Professional group were discussed. Due to similarities between outcome domains across the groups, seven were identified as separate constructs. These were then presented to the workshop and discussed in detail, to ensure that participants had a coherent shared understanding of each domain.Participants then separated into two groups to discuss the domains and their importance. Project team staff attended these groups but did not participate in the discussion beyond answering questions about the methodology and the results.Participants then individually and anonymously ranked the domains from most important to least important. The summary of the individual rankings was presented to the group and discussed until unanimous agreement was reached on a short list of domains that should be recommended for collection from all people receiving hearing services in Australia.Some discussion was also had regarding methods and time of collection of outcome measures, which was synthesised qualitatively and is summarised below.The research team met to synthesise the results from all phases of the work, primarily the Consensus Workshop and literature review of potentially applicable outcome measures, into specific interim recommendations for the assessment of hearing rehabilitation in clinical and research practice. Discussion continued until unanimous agreement was reached.This group comprised Professionals involved in the hearing industry in Australia. Potential participants were identified by the research team by brainstorming within each of the categories of hearing researchers, representatives of professional organisations, hearing service organisations, industry organisations such as hearing device manufacturers, and hearing consumer advocacy organisations. This resulted in a list of 59 people who were invited to take part in the study, with 43 (73%) consenting to take part.n = 6), Melbourne (n = 7), and Sydney (n = 7). Following these scoping workshops, several other potential participants were identified by workshop participants as being people who would be interested in contributing to the Delphi review, and were added to the list, giving a total of 79 potential participants for the Delphi review, of whom 50 (63%) completed at least one round of the Delphi review. Of these, 19 (38%) completed only one round, 16 (32%) completed only two rounds, and 15 (30%) completed all three. Participation in a future round was not contingent on completion of all previous rounds.Participants were invited to join in one of three initial scoping workshops, which were conducted in Brisbane  and invited to nominate one or more representatives who identified as people with hearing loss. Seven representatives across all these groups took part in the initial scoping workshop.n = 64) were then invited to participate in rounds 2 and 3. Of these, 55 (86%) completed all three rounds, 6 (9%) completed only two rounds, and 3 (5%) completed only round one. There was higher engagement with the review process in this group that in the Professional group, potentially due to the self-selected nature of the participants.Following the workshop, the organisations were invited to share a link to the first round of the Delphi review with their members, and all did so. Participants who responded to round 1 of the Delphi Review (n = 18) was selected by the research team from those in the Professional group who had responded to at least 2 rounds of the Delphi Review (n = 32). In the selection of these potential participants, the categories used at the potential participant identification stage were considered to ensure broad coverage of the Australian hearing industry. One potential participant from each consumer organisation was then added. The resulting 22 potential participants were then invited to take part in an online workshop (due to COVID-19), with 10 attending.A group of potential participants  for each section of each survey can be seen in In round 1, participants were asked open-ended questions about the topics, which were then synthesised into statements for rating in subsequent rounds.Methods of Collection and National Outcomes Database sections, questions asked were similar between the two groups, and so summary information for both groups was presented.In rounds 2 and 3, statements were presented for rating using one of the standard items or ranking, along with summary information about responses to any previous rounds of ratings or rankings. In the Outcome Domains section, statements were rated using the standard importance item. As statements had already been determined during the scoping workshops, in Round 1 they were presented for rating, along with an open-ended question to allow participants to add any outcome domains that they felt were missing. In Round 3 participants were also asked to select, in ranked order, the top five domains, which were used to generate a consensus ranking. Due to the large number of outcome domains that reached consensus in Round 1 among Consumer participants, in Round 2 Consumers were presented with only the top 10 outcome domains from the previous round (as determined by the Kemeny-Young method), as well as five additional domains synthesised from open-ended responses. All of these reached consensus as being important, and so in Round 3 Consumer participants were not asked to rate, but only to rank the domains.In the Time of Collection section, Professional participants were asked about the different time points at which outcomes could be collected, and why. Responses were synthesised into four major time points and a set of statements regarding the potential reasons why these time points might be useful. In Rounds 2 and 3, Professional participants were asked to rank the four time points in order of importance, and to rate their agreement with the statements using the standard agreement rating item. The ranked time points were used to generate a consensus ranking.In the Methods of Collection section, Professional participants were asked about potential methods that could be used to collect outcomes, and the benefits and drawbacks that might be associated with each method. Professional participants were asked to rank the top five most important methods of collection in both Rounds 2 and 3 to facilitate the recommendation of a single method of collection at the close of the study. Consumer respondents were asked to rate the comfortableness of each method in Round 2, and to rank the top five most important methods in Round 3.In the Parties responsible for collection section, Professional participants were asked about different parties  who could be responsible for the collection of outcome measures in the Hearing Services Program, and the potential benefits and drawbacks of each these parties undertaking outcomes collection. Statements were rated by Professional participants using the standard agreement rating item in subsequent rounds.In the Reasons for Collection section, Professional participants were asked about reasons why different stakeholders might find it important for outcomes to be measured. Statements were rated by Professional participants using the standard agreement rating item in subsequent rounds.In the National Outcomes Database section, Professional participants were asked about the potential beneficiaries, benefits, and drawbacks of the development of a national database of outcomes for hearing rehabilitation. The beneficiaries and benefits were synthesised into potential purposes for such a system. The potential purposes and drawbacks were then presented to both groups, and participants were asked to rate them using the standard importance rating item. In Round 2, Consumer participants were also asked how comfortable they would feel with a range of different stakeholders running a national outcomes database.In the Questions asked in each section are available as Results for this section are shown in The primary question for this section was “What outcome domains should be measured as markers of success of hearing rehabilitation?”Results from the Professional group are shown in Most domains that were identified through this process were psychosocial. Notably, the consensus criterion was not reached for the domain “Increased use of hearing aids.”Results from the Consumer group are shown in The primary question for this section was “At what time point(s) should outcome measures be collected, and why?” It was conducted in two parts: by presenting respondents with four specific time points for ranking, and then by presenting a set of statements.The four specific post-fitting time points identified were, in ranked order from most to least preferred, at 3 months following the fitting, at 6 months following the fitting, at 12 months following the fitting, and at the follow-up appointment .The statements and consensus percentages for this section are shown in The primary question for this section was “What different methods could be used to collect outcome measures?”Consensus rankings for this section are shown in The primary question for this section was “Thinking of patients being seen for hearing rehabilitation, who could potentially collect outcome measures?”Statements and consensus percentages for this section are shown in The primary question for this section was “Why might it be important to clinicians providing hearing services/hearing service providers/Government that outcomes are measured?”The statements and consensus percentages are shown in The primary questions for this section were: “Are there any people who you think might benefit from a national outcomes database? What are the potential benefits of a national outcomes database? What are the potential drawbacks associated with having a national outcomes database?” Detailed results of this section, including consensus percentages and rankings, are available in Both groups agreed that a database should be designed to promote person-centred care, to help determine best practice, and to provide a national standard for hearing care. Both groups also agreed that such a database should be designed to measure the impacts of hearing loss beyond the person themselves, on their partners, family members, and friends. The Consumer group, but not the Professional group, agreed that a database should support clients to choose hearing services and providers and help identify poorly performing clinicians and services.Both groups were agreed that the accuracy and relevance of measures and the integrity of the data was highly important, with misuse of data by professionals or organisations a significant concern. Professional participants were also concerned with the potential for data breaches and use of the data to justify funding cuts.Consumer participants felt more comfortable with organisations that might be considered independent from both the hearing industry and Government running a national outcomes database, including independent research organisations, professional associations, and universities.The synthesised domains as presented to the consensus workshop are available in During initial discussion to ensure that participants understood the domains as presented, participants decided that “Improved participation in activities” should instead refer to reduction of “participation restrictions,” as it was felt that it was unreasonable to expect that the provision of hearing rehabilitation alone would result in increased participation by patients in social activities. Rather, participants felt that while hearing rehabilitation could reduce the barriers to participation caused by the hearing loss, the social and psychological effects of long-standing hearing difficulty may result in some continued persistence of patterns of reduced participation for a period of time following any reduction in participation restrictions.Following this discussion, participants separated into groups to further discuss the domains, and anonymously ranked the domains individually. A summary of the results of individual prioritisation for both groups are shown in After prioritisation, group discussion was undertaken to identify which outcome domains were considered core for assessment of hearing services. Discussion focussed on the importance of capturing the full breadth of outcomes experienced by patients, the importance of domains that were clearly articulable and comprehensible by patients and clinicians, and on selecting domains that would be directly modifiable by rehabilitation efforts.Following the discussion, the group decided unanimously that four outcome domains should be recommended as part of a CODS for self-report in hearing rehabilitation in Australia. These were, in order of importance: (1) communication ability, (2) personal relationships, (3) well-being, and (4) participation restrictions. The group stressed that all seven domains presented to the group were important and should be considered for settings where the collection of additional outcomes is possible.Following the discussion of which outcome domains should be measured following hearing rehabilitation, additional discussion was had regarding the time points at which outcomes should be measured, and which outcome measures should be used. There was no decision made regarding a positive answer to either question, with participants agreeing that these questions should be answered with reference to the research literature. Participants felt that the time of collection may differ between particular outcome measures and should therefore be determined with reference to research relevant to each particular outcome measure.Three overarching recommendations were made as a primary output of this project. It should be noted that these recommendations were made specifically for the Australian publicly funded hearing rehabilitation context, and with the assumption that outcomes would be collected to facilitate their tracking and improvement over time.1)Target the outcome domains “communication ability,” “personal relationships,” “well-being,” and “participation restrictions” when assessing hearing rehabilitation.2)Measure within these domains at baseline and then following the conclusion of the rehabilitation, with a delay of at least 3 months being recommended.3)Establish an independent body to develop a standardised outcomes instrument and mechanism for outcomes collection.The detailed recommendations from this project are available in This study identified four primary outcome domains that are recommended as part of a core outcome domain set for the self-report evaluation of individual hearing rehabilitation programmes: communication ability, personal relationships, well-being, and participation restrictions.Many currently available outcome measures used as measures of the success of hearing rehabilitation focus on improvements in communication ability, including the Glasgow Hearing Aid Benefit Profile GHABP; , the AbbThe most specific measure of hearing-related participation restriction currently available, the Social Participation Restrictions Questionnaire (SPaRQ), focuses primarily on social participation ,b. PartiThere currently are no measures validated in hearing rehabilitation for the assessment of personal relationships or general well-being, although general measures of well-being such as the Warwick-Edinburg Mental Well-Being Scale (WEMWBS) are available . ApplicaWith respect to the time points at which outcomes should be collected, there was disagreement between professional stakeholders in the Australian hearing industry, reflecting the lack of research into the optimal time to collect outcomes measurements. While there is good evidence that auditory ability stabilises quickly after hearing aid fitting , the perWhile both Consumer and Professional groups agreed that outcomes could be appropriately collected by hearing care professionals face-to-face with a patient, the difference in preference for online delivery of questionnaires—Consumer respondents ranking it second only to face-to-face collection by a hearing care professional while Professional respondents ranking it as least preferred—suggest that a range of methods are likely to be useful in practice. The principles of experience-based co-design suggest that health services, policymakers, and consumers should be involved in the design of services and the selection of appropriate metrics for their assessment , and theThere was substantial overlap in the identified reasons for collecting outcomes and the purposes of establishing a national database of patient outcomes. Both Consumer and Professional groups highlighted the importance of promoting patient-centred care beyond solely the provision of hearing aids, the comparison of professional practice and outcomes to national benchmarks, the value of outcomes to Government and other funders in developing policy, and potential enhancements in the development of evidence-based hearing care. This overlap suggests that to the participants in this study these two ideas—that outcome measurements should be collected and that outcome measurements should be combined and analysed across health systems—may be conceptually inseparable. Indeed, several of the reasons identified for collecting outcomes, such as the targeting by Government of auditing activities, are likely to only be possible through a centralised outcomes storage and analysis system.Respondents were clear that centralised outcomes collection systems should be designed to maximise their benefits for various parts of the hearing health system, including hearing healthcare organisations and professionals, other healthcare providers, the public, and policymakers. When designing and implementing these systems, a broad base of stakeholders should be involved in the design and implementation of data products, ensuring their applicability across the health system. Consumers, perhaps unsurprisingly, felt that such a system could and should provide important information to consumers to support their hearing rehabilitation decision-making. The provision of information to consumers alone, however, is not sufficient to ensure that they can use that information to support healthcare decision-making; careful design of the consumer-accessible outputs of these systems will be necessary to ensure that outcomes information can be useful to consumers .In addition to the benefits of aggregating outcome measurements across patients for services and systems evaluation, the results of the present study also highlight the immediate utility of outcome measurements to clinicians as a basis for decisions about the future progress of individual rehabilitation programmes. Making patient outcome measurements available to clinicians and health services may therefore provide an immediate and direct benefit to the care of the patient whose outcomes are being measured. In addition to the use of baseline measurements to support rehabilitation programme planning , outcome measurements may identify patients whose progress has been less than might be expected, prompting additional intervention from the clinician. Providing those results that are available to hearing care professionals and organisations to the patient, both in aggregate and individualised format, may provide significant benefits to clinical practice, improve engagement and uptake by hearing care professionals and service delivery organisations, and smooth the implementation of outcome measurement within hearing health systems.Concerns relating to the development of a national outcomes database largely related to the validity, quality, trustworthiness, and comprehensiveness of the data stored within it. Both groups expressed concerns that there could be significant potential for interested parties  to modify or misrepresent data in an attempt to appear more favourably in any aggregate results. This concern has implications for the ways in which data may be collected, as methods of data collection that directly involve hearing care professionals or organisations may be viewed as more susceptible to misuse than those that bypass hearing services entirely.Interestingly, the potential impacts on professionals and organisations of receiving poor outcomes results were not considered important by either Consumer or Professional participants. Publication of health quality data can prompt quality improvement within health systems , with syWhile the results of the present study do provide important guidance for researchers, clinicians, and policymakers in the selection of outcome domains for the assessment of hearing rehabilitation, the decision in the early stages of the Delphi Review conducted with the Consumer group to restrict to a manageable number of outcome domains does mean that this list should not be considered a comprehensive description of the areas in which consumers of hearing services might experience or seek benefit from hearing rehabilitation. Indeed, several items that reached consensus in the Professional group, including reductions in social isolation and the ability to communicate in groups, were filtered out of consideration by Consumer participants at this stage. In addition, a number of items that might be considered valuable by researchers or clinicians—including feelings of empowerment, improved access to paid and volunteer work, and confidence in the effectiveness of hearing services—were also excluded from further consideration by Consumer participants. As a result, this work does not preclude the usefulness of other domains that have not been listed above, or of measures that assess other aspects of benefit. For example, where a comprehensive assessment of benefit of hearing rehabilitation is desired, the use of a general measure of improvement such as the Clinical Global Impression, which has been adapted for use in hearing rehabilitation , may capThis study includes consumers of hearing services as primary participants in the development of recommendations for the assessment of hearing rehabilitation, which has not previously been done in this field. In addition to providing a possible example to future researchers seeking to include consumers as domain experts in their research, we believe that direct involvement of consumers in research is vital to the principles of patient- and family-centred care. It is also the first in the hearing literature to make use of the Kemeny-Young method for consensus ranking, a data-driven method with useful properties including satisfaction of the Condorcet criterion  and the ready availability of “off-the-shelf” algorithms for both its exact computation and heuristic approximation.The recommendations from this study define a minimum patient-centred core outcome domain set that should be considered for the assessment of hearing rehabilitation in research and clinical practice. However, there is still significant research required to establish a set of outcome measures suitable for the measurement of each of these outcome domains. The selection of measurement instruments to be associated with a COS is a multi-stage process that will require considerable additional work, particularly given the identified lack of appropriate, validated measures for the identified domains . As partIn general, these results have identified, through a consensus approach, a core outcome domain set that might be considered for the self-report evaluation of hearing rehabilitation and provide important background information for the design of methods to implement them across hearing healthcare systems. A broader set of self-report outcome domains that researchers and clinicians may also choose to collect in their particular context has also been identified. Furthermore, other outcome areas in addition to self-report, such as behavioural  and physiological  tests, need to be considered before there is a full COS for auditory rehabilitation. For self-report, which was the focus of this study, the range of suggested outcome domains, potential purposes for outcomes collection, and potential concerns with the establishment of centralised national outcomes collection and analysis systems strongly suggest that ongoing stakeholder engagement will be vital for the operationalisation of these results into any hearing healthcare system. In addition, significant further research is required on any selected or developed outcomes measurement instruments to determine the optimal time of outcomes collection following hearing rehabilitation.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Hearing Australia Human Research Ethics Committee. The patients/participants provided their written informed consent to participate in this study.MF designed the study. MF and DA designed the Delphi review with subject matter advice from LH. DA managed the data collection, analysed the data, and wrote the manuscript. All authors interpreted the data, reviewed the manuscript and provided critical revision, and approved the submitted version.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Hearing aids are effective at improving listening ability and health-related quality of life. Recently, we observed that there are many hearing aids-related videos published on TikTok. However, the quality of the information they offer remains unstudied. This study aimed to evaluate the information quality of hearing aids videos on TikTok. We collected a sample of 155 hearing aids-related videos in Chinese and extracted the basic information. First, we identified the source of each video. Two independent raters assessed the quality of the information in the videos, using the PEMAT-A/V tool and DISCERN instrument. Regarding content, the results showed that the video contents on TikTok mainly about features, functionalities, and suggestions of purchase or fitting of hearing aids, while the information about the disadvantages and complications of hearing aids was limited. The overall quality of the hearing aids-related videos was acceptable on average, although the quality varies greatly depending on the type of source. Patients should be cautious in obtaining information about hearing aids on TikTok. Acquired hearing loss is common and increased significantly with age . People With the popularity of social media, access to information has become more and more diverse, which have an unprecedented influence on people's daily life. People who watch online videos account for 85% of Internet users in the USA, while it is as high as 92% in China .Song et al. found that hedonic social applications such as TikTok are an important channel for users to access health information . TikTok Despite the benefits of social media, its use for health communication has some shortcomings . InformaWe observed that there are many hearing aids-related videos on TikTok. However, the quality of the information they offer remains unstudied. Therefore, to fill this gap, this study aimed to evaluate the information quality of hearing aids videos on TikTok.Videos were searched on TikTok on March 16, 2022, using the keyword “助听器” (“hearing aids” in Chinese). TikTok search was conducted on a newly installed app on an iPhone 13 (v.15.3) with a cleared cache and without any login. TikTok provides three ways to sort items: “overall ranking”, “most recent”, and “most likes”. Given that most users employ the overall ranking mode, the default mode of sorting recommended by TikTok, we used this mode to retrieve the first 250 videos. We included videos directly related to hearing aids, excluding commercial videos and duplicate videos. After screening, we obtained 155 videos for data extraction and analysis, representing 62% . We extrWe measured 2 aspects of hearing aids-related videos on TikTok: their understandability, actionability, and reliability. First, to rate the understandability and actionability of the videos, we adopted the Patient Education Materials Assessment Tool for Audio-Visual Materials (PEMAT-A/V) tool . PEMAT iWe adopted the DISCERN instrument to rate the reliability of eligible videos . DISCERNTwo independent researchers (KC and LZ) evaluated and rated the videos. A third researcher (YT) helped to resolve the discrepancies between the two reviewers.P < 0.001). These results indicated that the rating process had satisfactory interrater reliability. Medians and interquartile ranges (IQRs) were used to analyze as the DISCERN and PEMAT-A/V scores data failed the Shapiro–Wilk normality tests. Any analyses of scores based on video sources were performed using the Kruskal-Wallis H test. A two-tailed p-value of <0.05 was considered to be statistically significant.SPSS 21.0 statistical software  was used for data analyses. Shapiro-Wilk test was used to assess the normality of data. The interrater reliability (Cohen κ) for each item ranged from 0.902 to 0.942 . Among individual users, health professionals created the most videos , followed by science communicators  and general users . meanwhile, the hearing aid fitters division accounts for 77.6% of the health professionals. Among organizational users, for-profit organizations published the most videos , followed by non-profit organizations  and news agencies . The characteristics of the videos were shown in The hearing aids videos on TikTok came mainly from two types of sources: individual users and organizational users. Individual users published most of the videos  and suggestion of purchase or fitting of hearing aids (35.4%). Then comes hearing aids type or brand (8.3%) and hearing aids maintenance (7.7%). The content category of the videos was shown in Regarding reliability, videos released by non-profit organizations  had the highest scores, while those from general users  were lowest. Our results showed that news agencies  and health professionals  also contributed videos with relatively high reliability. For-profit organizations  and science communicators  contributed videos with relatively low reliability. The differences in reliability across the different video sources were statistically significant .Videos published by non-profit organizations  had the highest understandability, whereas the videos contributed by general users  had the lowest reliability. News agencies , science communicators , and health professionals  also contributed videos with relatively high reliability. For-profit organizations  contributed videos with relatively low reliability. The differences in understandability across the different video sources were statistically significant .Regarding actionability, videos released by the health professionals  had the highest scores, while those from the general users  were lowest. Our results showed that the for-profit organizations  and the non-profit organizations  also contributed videos with relatively high reliability. The differences in reliability across the different video sources were statistically significant .With regard to the last item concerning the total PEMAT-A/V scores, the highest-quality videos were created by non-profit organizations  and the lowest-quality videos were generated by general users . The differences were statistically significant .This study systematically evaluated the information quality of hearing aids-related videos on TikTok. With the development of the Internet, various social media channels provide convenient means for patients to seek medical knowledge. Our research found that TikTok is an important platform for information-related hearing aids. The 155 videos we studied received 52,568 “likes” and 4,143 comments, which indicates that TikTok is a promising channel for health communication.In the present study, we use the classification of previous research to divide the uploaders into individual users and organizational users . IndividIn terms of video content, the study found that most of the videos were about the features and functionalities, and purchase or fitting suggestions, while few videos introduced the disadvantages or complications of hearing aids. These results are consistent with a previous study, whose content categories with over 50% of all videos commenting on general information about hearing aids, hearing aid types, and handling and maintenance of hearing aids . SecondlOur research found that the information quality of videos was mixed. Overall, the videos published by non-profit organizations and health professions had a high quality, while those from the for-profit organizations had the lowest quality. Given the uneven quality of videos, we recommend that patients be cautious in obtaining information about hearing aids on TikTok, avoiding unnecessary hearing loss caused by wrong information.This research should be viewed in light of several limitations. Firstly, we only include hearing aids-related videos in our study in Chinese. We hope that more studies in the future to evaluate the information quality of hearing aids-related videos in other languages on TikTok. Furthermore, our study does not discuss the misinformation of videos, and future research needs to discuss the influence of misinformation on patients.This study evaluated the information quality of 155 hearing aids-related videos on TikTok. The results show that the video contents on TikTok mainly about features, functionalities, and suggestions of purchase or fitting of hearing aids, while the information about other aspects was limited, such as the disadvantages and complications of hearing aids. The overall quality of the hearing aids-related videos was found to be acceptable on average, although the quality varies greatly depending on the type of source. Patients should be cautious in obtaining information about hearing aids on TikTok.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.KC: design, conduct, analyzed data, and drafting. LZ: conduct and analyzed data. RZ: conduct. YT: design of the study, revised article, final approval, and accountable for all aspects. All authors contributed to the article and approved the submitted version.The work was funded by the Science and Technology of Department of Sichuan Province (No.: 2021YJ0183).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The amplitude modulated (AM) neural oscillation is an essential feature of neural dynamics to coordinate distant brain areas. The AM transcranial alternating current stimulation (tACS) has recently been adopted to examine various cognitive functions, but its neural mechanism remains unclear. The current study utilized the phosphene phenomenon to investigate whether, in an AM‐tACS, the AM frequency could modulate or even override the carrier frequency in phosphene percept. We measured the phosphene threshold and the perceived flash rate/pattern from 12 human subjects  under tACS that paired carrier waves  with different envelope conditions  over the mid‐occipital and left facial areas. We also examined the phosphene source by adopting a high‐density stimulation montage. Our results revealed that (1) phosphene threshold was higher for AM‐tACS than sinusoidal tACS and demonstrated different carrier frequency functions in two stimulation montages. (2) AM‐tACS slowed down the phosphene flashing and abolished the relation between the carrier frequency and flash percept in sinusoidal tACS. This effect was independent of the intensity change of the stimulation. (3) Left facial stimulation elicited phosphene in the upper‐left visual field, while occipital stimulation elicited equally distributed phosphene. (4) The near‐eye electrodermal activity (EDA) measured under the threshold‐level occipital tACS was greater than the lowest power sufficient to elicit retinal phosphene. Our results show that AM frequency may override the carrier frequency and determine the perceived flashing frequency of AM‐tACS‐induced phosphene. The current study examined the effect of amplitude‐modulated tACS on phosphene perception. The results showed that the amplitude‐modulating frequency increased the phosphene threshold and overrode the carrier frequency by changing the frequency function of flashing perception. This study, therefore, suggests amplitude modulation as a critical neural cross‐frequency‐coupling format in visual perception. The current study, therefore, adopts carrier frequencies within the visible range (10–22 Hz) based on previous studies  as an index of the epidermis potential change. We collected the near‐eye EDA and calculated the power of applied frequency under each participant's phosphene threshold (PT) intensities. We compared the power between occipital and forehead/upper‐cheek stimulations. The EDA under facial PT stimulation is defined as the “threshold EDA” of eliciting phosphene from the retina. If the EDA recorded during occipital PT stimulation was higher than the “threshold EDA”, it indicates that the leaked current from the weakest occipital montage was enough to elicit a retinal response, and the retina may also contribute to phosphene generation. In contrast, if the EDA under occipital PT stimulation is lower than the threshold EDA, the phosphene is more likely to generate from the visual cortex.The current study aims to delineate the neural mechanism of amplitude‐modulated tACS and hopes to bridge the neural activation with visual perception by examining the relation between AM‐tACS properties and phosphene perception. To verify the source of the AM‐tACS phosphene, we adopt focal stimulation montages to overcome the problem of mixing contributions from the retina and visual cortex in previous studies.22.1α error = 0.05, medium effect size partial η2 = 0.06, number of measurements = 24, correlation among repeated measure = 0.5, Nonsphericity correction = 1). All subjects had normal or corrected‐to normal vision and no history of neuronal diseases. The mean age of subjects was 27 years old (range from 20 to 44), and four were female. All subjects were informed of the experiment's procedure, and they agreed to and signed the consent form approved by the Institutional Review Board of the Chang‐Gung Memorial Hospital.Twelve subjects were recruited from the National Central University, Taiwan. The subject number is based on calculation of G*Power , carrier frequency , and AM frequency . The frequency selection was based on previous studies  Planning Module  through 128‐channel elastic cap. Ten electrodes  with the ROAST software  with the following equation:2.3Before the formal experiment, participants were informed about the phenomenon of phosphene as well as the individual difference in phosphene sensitivity to minimize the possibility of guessing and expectation. Participants first received the highest intensity (1000 uA) stimulation to see if he/she could perceive phosphene and get familiar with the possible tactile sensation caused by the stimulation. Participants who could not perceive phosphene with 1 mA stimulation on the occipital area were excluded from the experiment. In the formal experiment, participants came for two experimental sessions with at least a one‐week gap. In each session, participants were stimulated with either occipital or left facial montage. The order of occipital and left facial sessions was counterbalanced across participants. During each montage session, participants were tested with 12 stimulation waveforms in random order to find the phosphene threshold. Each condition took about 6–7 trials to find the threshold intensity. Each session took 70–80 stimulation trials to finish. For more detailed information about the threshold measurement method please refer to Appendix 2). Observation distance was fixed with a chin rest at 60 cm from a 24‐inch, 120 Hz refresh rate LCD monitor. The task was programmed in Matlab (R2015b) using Psychtoolbox‐3 (PTB‐3)  at a 1000 Hz sampling rate. Signals were recorded with 3 Ag/CL electrodes contacted on the left side, supra‐eyebrow, and lower side around the left eye , AM frequency , and carrier frequency  was conducted to the phosphene thresholds, flashing frequency ratings, and mean coordinates of phosphene drawing. The normalized EDA power of each stimulation condition was calculated based on the HHSA methods described in Appendix 3t‐test were conducted in the analysis. The results are summarized below in Table Three sets of repeated measured ANOVA and one paired 3.1F = 169.39, p < 0.001, ηp2 = 0.94), indicating higher PT for occipital  than left facial montage (82.29 ± 15.63). As illustrated in Figure F = 12.55, p < 0.001, ηp2 = 0.53). Paired comparisons with Bonferroni correction showed higher PT for 4 Hz AM (399.27 ± 60.41) than both 2 Hz AM  and 0 Hz AM . The main effect of carrier frequency was significant . Following comparisons showed that PT for 14 Hz (343.33 ± 55.93) was significantly lower than 10 Hz (373.89 ± 56.81) and 22 Hz (395.21 ± 41.29), and the PT for 18 Hz (352.43 ± 51.45) was lower than 22 Hz. The contrast analysis on the carrier frequencies showed a significant quadratic trend .The three‐way ANOVA on the phosphene threshold (PT) shows significant main effect of montage  and a significant three‐way interaction among montage, AM frequency, and carrier frequency . Further analyses showed unequal AM effect in two montages. In the facial montage, AM frequency effect was significant in all carrier frequencies  = 7.45, p = 0.01, ηp2 = 0.6; 14 Hz: F = 6.54, p = 0.015, ηp2 = 0.57; 18 Hz: F = 13.77, p = 0.001, ηp2 = 0.73; 22 Hz: F = 4.66, p = 0.037, ηp2 = 0.48), while for the occipital montage, the AM frequency effect was only found in the 10 Hz  = 4.36, p = 0.04, ηp2 = 0.47) and 22 Hz  = 5.9, p = 0.02, ηp2 = 0.54) carrier frequencies.The results also revealed a two‐way interaction between montage and AM frequency . Subsequent comparisons showed that flash was perceived faster for 0 Hz AM (13.76 ± 5.4) than 2 Hz  and 4 Hz  AM. Main effect of carrier frequency was also significant . Subsequent comparisons showed faster ratings for 22 Hz (11.5 ± 5.8) and 18 Hz (10.85 ± 5.59) than 10 Hz (6.35 ± 3.25), but not for 14 Hz (8.5 ± 4.87). Contrast analysis showed a linear trend of carrier frequency  that the ratings increased as a function of carrier frequency. We also found a marginal interaction between AM frequency and carrier frequency . Subsequent analysis showed that the carrier frequency effect was significant only in the 0 Hz AM condition  = 9.9, p = 0.02, ηp2 = 0.86 for 0 Hz AM; F = 1.2, p = 0.4, ηp2 = 0.42 for 2 Hz AM; F = 1.9, p = 0.24, ηp2 = 0.5 for 4 Hz AM). No montage effect or interactions with other factors were found in this analysis.The mean flash ratings of each stimulation condition are illustrated in Figure y=x, where x indicates the given carrier frequency and y indicates the participants' rating. The results showed that participants' ratings in the 0 Hz AM fitted well to the model , but the model could not explained performance in 2 Hz AM  and 4 Hz AM  conditions.Based on the linear trend found in the carrier frequency main effect, we examined whether the subjective ratings of phosphene flashing reflected the real stimulated frequencies in each of the AM frequencies. Data were pooled across two montages and fitted to a simple linear regression model 3.3D = 0.85, p < 0.001) that the phosphene distribution differed between facial and occipital montages. We also conducted the three‐way ANOVA on the x and y values of the mean coordinates. Both examinations revealed significant montage effect  = 58.37, p < 0.001, ηp2 = 0.89; y‐values: F = 19.96, p = 0.003, ηp2 = 0.74). Compared to the phosphene perceived in occipital stimulation montage , phosphene in facial stimulation  was more left‐lateralized and focused on the upper screen. None of the main effects of AM frequency, carrier frequency, and interactions were significant, showing that the stimulation condition did not affect the phosphene pattern except for the montage.Figure 3.4t‐test contrasting between occipital and left facial montages revealed that the carrier frequency power was significantly higher for the occipital  than facial (0.046 ± 0.003) stimulation , while similar result was found in AM frequency . Please see Figure The EDA data from one participant were excluded from the analysis due to serious channel noise. Results of the HHSA   and we found the EDA recorded during occipital‐PT stimulation  was higher than the threshold EDA. This result implies that the leaking current to the eye during occipital stimulation with its least intensity was strong enough to elicit a retinal response, which is in line with previous findings  stimulation with high‐definition electrodes is usually arranged in a ring‐shape montage to limit the current distribution. However, we found it difficult to elicit phosphene with a ring‐shaped montage in the pilot study. Moreover, to the best of our knowledge, no study has ever elicited phosphene with a ring‐shaped montage. We, therefore, adopted the electric pad‐like montage that two groups of electrodes being the positive and negative polarities. To better limit the current distribution, we arranged both positive and negative electrodes on the occipital area. According to model simulation results  usually does not induce phosphene, but participants may perceive phosphene in the form of 2 Hz AMtACS or vice versa. Finally, our study may provide further insight for visual prostheses applications such as the hand‐free support system for blind people (Kanamaru et al., Che‐Yi Hsu, Tzu‐Ling Liu, Yan‐Hsun Chen, and Chi‐Hung Juan designed the experiment. Dong‐Han Lee and Yan‐Hsun Chen programmed the experiment. Che‐Yi Hsu and Ding‐Ruey Yeh acquired the data which Che‐Yi Hsu, Tzu‐Ling Liu, and Wei‐Kuang Liang analyzed. Che‐Yi Hsu, Tzu‐Ling Liu, and Chi‐Hung Juan wrote the article.The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.The studies involving human participants were reviewed and approved by the Research Ethics Committee of Chang‐Gung Memorial Hospital. Furthermore, the patients/participants provided their written informed consent to participate in this study.Appendix S1:Click here for additional data file.


Hearing loss is a risk factor for dementia; whether this association differs by race is unknown. Although hearing loss is less prevalent in Blacks than Whites, we hypothesized the hearing loss-dementia relationship is stronger in Blacks. All-cause dementia and mild cognitive impairment (MCI) were adjudicated using longitudinal cognitive data. Hearing was measured using pure tone better-ear thresholds (0.5-4 kHz). Cox proportional hazards models adjusted for demographic and clinical covariates and included an interaction term between hearing and race. In 3,605 participants from a population-based cohort , estimates for 7-year dementia risk per 10 decibels increase in hearing loss were stronger in Blacks :1.07,1.43) than Whites . Hearing loss is a risk factor for dementia in Black Americans. These findings emphasize the need to address existing racial disparities in hearing healthcare.


Electrically Evoked Compound Action Potential is a measure of synchronous cochlear nerve fibers activity elicited by electrical stimulation of the cochlear implant. The electrophysiological nerve responses may contribute to explain the variability in individual performance of cochlear implant recipients.To compare speech perception tests’ performances of cochlear implant users according to the presence or absence of intraoperative neural telemetry responses.Prospective study design with 100 “Nucleus 24” cochlear implant users divided in two groups according to the presence or absence of intraoperative neural telemetry responses. Speech perception tests were performed after 6 months of continuous use of the device and compared among groups.Intraoperative action potentials were observed in 72 % of individuals. Open-set sentence test results were better in implant users who had neural telemetry responses when compared to implant users in whom this potential was absent . There was a strong association between post meningitis-related deafness and absence of intraoperative potentials.The absence of intraoperative neural telemetry responses was associated with worse performances in speech perception tests and meningitis as etiology of deafness. On the other hand, the presence of these potentials suggests excellent prognosis. Individuals with severe to profound sensorineural hearing loss suffer deep damage or reduction in the number of hair cells, and many do not have any benefit from sound amplification through a conventional hearing aid, thus becoming candidates to cochlear implant (CI)In this type of device, each electrode directly stimulates the auditory nerve when the electrical current necessary to trigger a hearing sensation passes; and the quantity of electrical current necessary to trigger an auditory sensation is different for each individual and for each stimulation canal. Therefore, the speech processor of each user must be individually adjusted together with each stimulation canal and such process is called “programming” or “mapping”. In adults, power levels must be determined through psychophysical measures . With the progressive increase in energy intensity in each one of the channels, the individual reports on the least intensity at which he/she detects the stimulus , as well as the maximum intensity allowed without discomfort. In babies, small children or individuals with multiple disorders, such procedure requires techniques that may be inconsistent and non-systematic, because of hearing inexperience or the child’s age. Thus, the use of measures obtained only from the behavioral method to program the speech processor may extend the implant adaptation process because of the difficulty in establishing proper stimulation levelsObjective measures used in order to obtain stimulation thresholds and the maximum level of discomfort are being studied and used in an attempt to predict the most adequate stimulation methods for mapping, especially for babies and toddlersThe Evoked Compound Action Potential - ECAP, reflects the auditory nerve neural activity and may be recorded during surgery, directly from the cochlea by using the implant electrodes as stimulus generator and response recorders, by means of using the specific softwareWith this method, the speech processor programming became faster and safer, even for babies, toddlers or individuals with multiple disorders since it is not always that conditioned or behavioral responses were consistent and systematic. The programming software allows one to import the threshold levels obtained by NRT and automatically combine them with the psychoacoustic levels obtained through the behavioral test in at least one of the electrodes. Practically all programming methods available and recommended by the manufacturer currently use NRT measures for mapping. They may be adjusted with totally objective methods, or combined with those of correction factor programmingMoreover, the potential testing during surgery is advantageous, since it allows to check the integrity of electrode bundles right after their insertion, and also to investigate neural responses in different cochlear regions. Obtaining data related to the cochlear nerve’s permeability towards electrical stimulation and the way through which some electrical stimulation parameters interact with remaining neural structures still constitutes a challenge. Early determination of exciting neural elements present in the different cochlear pathological processes would also be very useful, since it is supposed that the survival of ganglion cells and other neural elements may constitute one of the causes for variability in relation to speech recognition performance found in implanted individualsNonetheless, clinical observation shows that in some patients it is not possible to observe the action potential during surgery, not even in the first months of follow up after activation. In these cases, mapping becomes dependent on the behavioral responses of the individual in order to refer the auditory threshold and the maximum comfort threshold for electrical stimulation in at least three of the 22 electrodes. The more uniform and reliable the answers, the better are the chances of a proper stimulation without discomfort, and this could result in good speech perception.This study aims at comparing the speech perception performance after 6 months of CI use among patients that have and do not have action potentials found by NRT during surgery, in order to assess the repercussion of response absence in the auditory nerve from the electrical stimulation.The study was approved by the Research Ethics Committee of our institution, under protocol # 633/04.Between March of 2003 and March of 2005, 102 patients underwent surgery to receive the Nucleus® 24 multichannel cochlear implant. Eighty four patients received models CI24M and CI24K (straight electrodes chain), 7 got the CI24 Contour model (pre-curved electrodes chain for peri-modiolar insertion) and 11 patients that had cochlear ossification proved by tridimensional MRI reconstruction of the cochlear lumen, were implanted with the CI24 Double Array (with two electrodes bundle) model.Two individuals implanted with model CI24 Double Array were taken off the study later on because they presented inadequate insertion of the electrodes array. Data related to gender, age and time of hearing privation in the patients, as well as etiology, type  and modus of hearing loss installation  of the 100 patients studied were collected and are presented in ECAP investigation was carried out in all individuals during surgery, right after inserting the electrode bundle in the cochlea. We used the NRT 3.1  software in a microcomputer coupled to the portable programming interface and a SPrint® model speech processor. Recording technique and the subtraction method used to separate the artifact were described by Dillier et al.Interpulse interval was fixed in 500µs. Stimulation speed was of 80 Hz with series of 25µs of pulse width. The number of presentations varied between 100 and 200 pulses per second for amplifier gains in 60 and 40db, respectively. Recording window varied from 50 to 150µs according to the optimization of each electrode. The current level of the masking noise was fixed in 10 units above the stimulation level.The action potential was initially studied in electrodes 20 , 15, 10 , 5 e 3  as active electrodes, we used distant electrodes + 2 or + 3 as a reference. In case the action potential could not be observed in any of these electrodes, other adjacent pairs were used as active and reference electrodes for the optimization series, until some positive response could be observed. We considered it absence of intraoperative NRT when we did not observe ECAP in any of the tested electrode pairs, considering as bases the characteristics described by Abbas et al.On the day we activate the CI, usually 30 days after surgery, all children who presented NRT responses were mapped according to the action potential thresholds obtained through the linear regression of the amplitude growth curve, carried out by the NRT software (extrapolated threshold) in at least 3 electrodes, Stimulation levels were also stipulated by the programming software, automatically, according to the pre-adjusted progressive maps techniqueIn order to program the implant of those children that did not have NRT responses, we used behavioral observation in order to obtain the electric threshold. The audiologist was progressively increasing electrical stimulation levels until the child showed some response . In the case of older children, the threshold was obtained through conditioning by fitting parts. Afterwards, power levels were progressively increased until detecting the intensity at which there were signs of discomfort or adverse reaction from the child in relation to the sound stimulus. Thus, the maximum comfort level was stipulated to be 5 current units below this value. Such procedures were carried out in 4 or 5 channels; the remaining were calculated through the interpolation techniqueIn adults, energy levels were always obtained through the psychoacoustic method, in which the individual responds to stimuli, in each channel, following a loudness scale. By the same token, after initial mapping, the parameters were globally adjusted at live voice.The remaining stimulation parameters were fixed and identical in both groups: ACE® speech coding strategy at 900 pulses per second per channel and 8 maximum, with pulse width of 25µs. In all children, we activated the ADRO® signal processing to enhance the signal to noise ratio, since they all used the SPrint®Tests to assess speech perception were carried out after six months of continuous cochlear implant use (at least eight hours per day) and without orofacial reading or support from signs and gestures. The tests are part of the pre and post-operative assessment protocol and the details of each procedure application were described by Gomez et al.In order to assess speech perception of the children with pre-lingual hearing impairment, we employed the TACAM test - Hearing Capacity Assessment Test, and the adaptation of the GASP - Glendonald Auditory Screening Procedure test, according to each patient’s ageThe mean values of speech perception tests in adults and children were compared among the groups that presented and did not present responses during intra-operative telemetry using the non-parametric Mann-Whitney U test. P values below 0.05 were considered statistically significant.Data were analyzed with the Statistical Package for Social Sciences  software.Intra-operative NRT was observed in 72 (72%) patients.Auditory Results in Adults: The results from the 40 adults who completed 6 months of CI use are presented on Hearing results in Children: We did not find statistically significant differences in speech performance results among children who had and those who did not have intra-operative NRT -Many authors have analyzed ECAP characteristics and its relation with the current psychoacoustics levels used in electrode mapping. Nonetheless, they failed to find relations between thresholds and potential characteristics and the auditory results from speech perception tests in implanted individualsThe hypothesis that ECAP measures could provide some indication as to hearing performance was confirmed in this study, despite we having seen that meningitis was an important factor associated with the absence of potential and the bad results.No potential found, when isolated from other factors, showed a significant relation with the worst performances in adult speech perception tests, and the absolute speech recognition average was much higher in the group that showed intra-operative NRT responses . Results close to 100% provide excellent speech perception capacity and a good chance of the patient being able to talk on the phone, thanks to the possibility of auditory recognition without the use of orofacial reading or the need for prior knowledge of the context. Individuals that did not respond to the intra-operative NRT test had the most difficulties to understand the day-to-day speech, however they showed an important gain in relation to pre-operative perception .ECAP represents the synchronic activity of a certain group of neurons and the response amplitude must be proportional to the number of neurons activated by the stimulus. Consequently, the very presence of ECAP may be able to reveal some association with post-operative performanceAs to the worst performance in open format phrases tests, shown by the group of students in the sample with post-meningitis hearing loss, the findings coincide with those from Blamey et al.It is important to highlight that most individuals with meningitis-related hearing loss presented results in the phrases test below 40%, that is, still below CI indication criterion. In our series, individuals with post-meningitis hearing loss had worse results, even when the potential found by NRT was present. In these patients, the ECAP was not enough to guarantee, by itself, a good performance in speech perception tests. Thus, the triggering of ganglionary cells does not necessarily mean that there will be stimulus recognition in more central levels, because NRT potential recording does not assure that the cognitive mechanisms involved in auditory perception be activated3. For a better assessment of the aspects that may be involved in post-implant and auditory information processing performance, it is necessary, for example, to look for late potentials, such as P300.In children, we did not observe performance differences between the NRT present and NRT absent groups during surgery. Such fact may be related to the short hearing experience span (6 months), since they all had pre-lingual hearing loss. Moreover, performance in these cases is directly dependent on the therapeutic rehabilitation method employed, as well as its effectiveness. The children implanted in our service come from different Brazilian States, many of them under rehabilitation therapy with local professionals. Although there is a guideline as to the stimulation method and the effective number of therapy sessions, in practice this is heterogeneous, making up an important confusion factor to be considered during the results analysis. Nonetheless, it is possible that after a long term follow up there may be differences in results between the two groups of children.We did not find data in the literature relating hearing performance in children and the results from the neural telemetry tests. Bevilacqua et al.As far as mapping is concerned, we noticed that the children who did not respond to the NRT and that, therefore, could not be mapped by means of objective or combined techniques require a greater number of returns and a longer time during program. However, since speech perception test results were similar in both groups, we can suggest that the psychoacoustic thresholds study is also valid for babies and small children. It is important to highlight that for the technique to be successful, it is fundamental for the examiners to have experience in childhood audiology and in behavioral observation techniques.-ECAP seen at NRT in adult patients who did not have meningitis, was associated with better results in speech perception tests after 6 months of continuous use of CI, suggesting an excellent short term prognosis.-Hearing impaired patients with meningitis were associated with higher indices of lack of intraoperative NRT response, and also the worst performances of adult individuals in speech perception tests.-In children there were no significant differences in speech perception tests between the groups. The marked heterogeneity among the therapies is a confounding factor to be considered, and it is possible that with more time and CI use we may see differences in results.