Unlocking the human inner ear for therapeutic intervention.

The human inner ear contains minute three-dimensional neurosensory structures that are deeply embedded within the skull base, rendering them relatively inaccessible to regenerative therapies for hearing loss. Here we provide a detailed characterisation of the functional architecture of the space that hosts the cell bodies of the auditory nerve to make them safely accessible for the first time for therapeutic intervention. We used synchrotron phase-contrast imaging which offers the required microscopic soft-tissue contrast definition while simultaneously displaying precise bony anatomic detail. Using volume-rendering software we constructed highly accurate 3-dimensional representations of the inner ear. The cell bodies are arranged in a bony helical canal that spirals from the base of the cochlea to its apex; the canal volume is 1.6 µL but with a diffusion potential of 15 µL. Modelling data from 10 temporal bones enabled definition of a safe trajectory for therapeutic access while preserving the cochlea's internal architecture. We validated the approach through surgical simulation, anatomical dissection and micro-radiographic analysis. These findings will facilitate future clinical trials of novel therapeutic interventions to restore hearing.

Development and validation of DeciBHAL-US: A novel microsimulation model of hearing loss across the lifespan in the United States.

BACKGROUND: Hearing loss affects over 50% of people in the US across their lifespan and there is a lack of decision modeling frameworks to inform optimal hearing healthcare delivery. Our objective was to develop and validate a microsimulation model of hearing loss across the lifespan in the US. METHODS: We collaborated with the Lancet Commission on Hearing Loss to outline model structure, identify input data sources, and calibrate/validate DeciBHAL-US (Decision model of the Burden of Hearing loss Across the Lifespan). We populated the model with literature-based estimates and validated the conceptual model with key informants. We validated key model endpoints to the published literature, including: 1) natural history of sensorineural hearing loss (SNHL), 2) natural history of conductive hearing loss (CHL), and 3) the hearing loss cascade of care. We reported the coefficient of variance root mean square error (CV-RMSE), considering values ≤15% to indicate adequate fit. FINDINGS: For SNHL prevalence, the CV-RMSE for model projected male and female age-specific prevalence compared to sex-adjusted National Health and Nutrition Examination Survey (NHANES) data was 4.9 and 5.7%, respectively. Incorporating literature-based age-related decline in SNHL, we validated mean four-frequency average hearing loss in the better ear (dB) among all persons to longitudinal data (CV-RMSE=11.3%). We validated the age-stratified prevalence of CHL to adjusted NHANES data (CV-RMSE=10.9%). We incorporated age- and severity-stratified time to first hearing aid (HA) use data and HA discontinuation data (adjusted for time-period of use) and validated to NHANES estimates on the prevalence of adult HA use (CV-RMSE=10.3%). INTERPRETATION: Our results indicate adequate model fit to internal and external validation data. Future incorporation of cost and severity-stratified utility data will allow for cost-effectiveness analysis of US hearing healthcare interventions across the lifespan. Further research might expand the modeling framework to international settings. FUNDING: This study was funded by the National Institute on Deafness and Other Communication Disorders and the National Institute on Aging (3UL1-TR002553-03S3 and F30 DC019846).

Global hearing health care: new findings and perspectives.

In 2015, approximately half a billion people had disabling hearing loss, about 6·8% of the world's population. These numbers are substantially higher than estimates published before 2013, and point to the growing importance of hearing loss and global hearing health care. In this Review, we describe the burden of hearing loss and offer our and others' recommendations for halting and then reversing the continuing increases in this burden. Low-cost possibilities exist for prevention of hearing loss, as do unprecedented opportunities to reduce the generally high treatment costs. These possibilities and opportunities could and should be exploited. Additionally, a comprehensive worldwide initiative like VISION 2020 but for hearing could provide a focus for support and also enable and facilitate the increased efforts that are needed to reduce the burden. Success would produce major personal and societal gains, including gains that would help to fulfil the "healthy lives" and "disability inclusive" goals in the UN's new 2030 Agenda for Sustainable Development.

An Assessment of the Clinical Acceptability of Direct Acoustic Cochlear Implantation for Adults With Advanced Otosclerosis in the United Kingdom.

HYPOTHESIS: Assess the clinical acceptability of direct acoustic cochlear implantation for patients with advanced otosclerosis and the support for conducting a controlled trial of its effectiveness in the United Kingdom. BACKGROUND: Emerging evidence supports the efficacy of direct acoustic cochlear implantation in patients with advanced otosclerosis whose needs cannot be managed using the combination of stapes surgery and hearing aids. A controlled trial would provide evidence for its effectiveness and cost-effectiveness to healthcare commissioners. METHODS: An online survey of clinical professionals was constructed to characterize current standard of care for patients with advanced otosclerosis and to assess whether clinicians would be willing to refer patients into a trial to evaluate direct acoustic cochlear implantation. A consensus process was conducted to define inclusion criteria for the future trial. RESULTS: No survey respondent considered direct acoustic cochlear implantation to be inappropriate with a majority indicating that they would refer patients into a future trial. The consensus was that there is a lack of available treatment options for those patients with bone conduction thresholds worse than 55 dB HL and who did not meet current criteria for cochlear implantation. CONCLUSION: The present study confirms that a controlled trial to evaluate the effectiveness of direct acoustic cochlear implantation would have the support of clinicians in the United Kingdom. A feasibility study would be required to determine whether patients who meet the inclusion criteria could be recruited in a timely manner and in sufficient numbers to conduct a formal evaluation of effectiveness.

Neurocognitive factors in sensory restoration of early deafness: a connectome model.

Progress in biomedical technology (cochlear, vestibular, and retinal implants) has led to remarkable success in neurosensory restoration, particularly in the auditory system. However, outcomes vary considerably, even after accounting for comorbidity-for example, after cochlear implantation, some deaf children develop spoken language skills approaching those of their hearing peers, whereas other children fail to do so. Here, we review evidence that auditory deprivation has widespread effects on brain development, affecting the capacity to process information beyond the auditory system. After sensory loss and deafness, the brain's effective connectivity is altered within the auditory system, between sensory systems, and between the auditory system and centres serving higher order neurocognitive functions. As a result, congenital sensory loss could be thought of as a connectome disease, with interindividual variability in the brain's adaptation to sensory loss underpinning much of the observed variation in outcome of cochlear implantation. Different executive functions, sequential processing, and concept formation are at particular risk in deaf children. A battery of clinical tests can allow early identification of neurocognitive risk factors. Intervention strategies that address these impairments with a personalised approach, taking interindividual variations into account, will further improve outcomes.

Self-reported symptoms and patient experience: A British Acoustic Neuroma Association survey.

OBJECTIVE: To assess patient-reported outcomes and experience of vestibular schwannoma (VS) management. STUDY DESIGN: Survey of members of the British Acoustic Neuroma Association (BANA). METHODS: Members of the BANA were invited to complete an online survey. Questions were divided into five areas: Demographic details; symptoms at diagnosis; level of information received; treatment after-effects; and overall experience of diagnosis and/or treatment. DEMOGRAPHICS: 598 (58%) BANA members completed the survey. 77.1% of respondents were aged between 41 and 70 years. Symptoms at diagnosis: hearing loss (84%), unilateral tinnitus (40%) and imbalance (51%) were commonest. Isolated tinnitus and imbalance occurred in 2% and 6%, respectively. Information received: 39% stated they were given 'just the right amount of information about all management options', and 32% 'not enough information'. Treatment after-effects: Overall quality of life was classified as 'a lot better' (11%), 'a little better' (7%), 'unchanged' (25%), 'a little worse' (38%) and 'a lot worse' (19%). 61% respondents continued in the same job. Return to social life, hobbies and sports was impaired in 65%. Overall experience: Experience of treatment was graded as 'much better than expected' (20%), 'a little better' (15%), 'about the same' (27%), 'a little worse' (22%) and 'much worse' (16%). CONCLUSION: Quality of life measures are important in assessing VS management outcomes, and will increasingly inform clinical decision-making. Further examination of how patients with VS perceive their disease, cope with illness and use social support networks may also help to inform future practice and the creation of decision analytical models.

Comparison of the benefits of cochlear implantation versus contra-lateral routing of signal hearing aids in adult patients with single-sided deafness: study protocol for a prospective within-subject longitudinal trial.

BACKGROUND: Individuals with a unilateral severe-to-profound hearing loss, or single-sided deafness, report difficulty with listening in many everyday situations despite having access to well-preserved acoustic hearing in one ear. The standard of care for single-sided deafness available on the UK National Health Service is a contra-lateral routing of signals hearing aid which transfers sounds from the impaired ear to the non-impaired ear. This hearing aid has been found to improve speech understanding in noise when the signal-to-noise ratio is more favourable at the impaired ear than the non-impaired ear. However, the indiscriminate routing of signals to a single ear can have detrimental effects when interfering sounds are located on the side of the impaired ear. Recent published evidence has suggested that cochlear implantation in individuals with a single-sided deafness can restore access to the binaural cues which underpin the ability to localise sounds and segregate speech from other interfering sounds. METHODS/DESIGN: The current trial was designed to assess the efficacy of cochlear implantation compared to a contra-lateral routing of signals hearing aid in restoring binaural hearing in adults with acquired single-sided deafness. Patients are assessed at baseline and after receiving a contra-lateral routing of signals hearing aid. A cochlear implant is then provided to those patients who do not receive sufficient benefit from the hearing aid. This within-subject longitudinal design reflects the expected care pathway should cochlear implantation be provided for single-sided deafness on the UK National Health Service. The primary endpoints are measures of binaural hearing at baseline, after provision of a contra-lateral routing of signals hearing aid, and after cochlear implantation. Binaural hearing is assessed in terms of the accuracy with which sounds are localised and speech is perceived in background noise. The trial is also designed to measure the impact of the interventions on hearing- and health-related quality of life. DISCUSSION: This multi-centre trial was designed to provide evidence for the efficacy of cochlear implantation compared to the contra-lateral routing of signals. A purpose-built sound presentation system and established measurement techniques will provide reliable and precise measures of binaural hearing. TRIAL REGISTRATION: Current Controlled Trials http://www.controlled-trials.com/ISRCTN33301739 (05/JUL/2013).

Results of a prospective surgical audit of bilateral paediatric cochlear implantation in the UK.

OBJECTIVES: Since being approved in 2009, bilateral simultaneous cochlear implantation (CI) has been the standard treatment for children in the UK who meet the criteria for CI. The aim was to report surgical outcomes of bilateral CI in the UK. METHODS: Between January 2010 and December 2011, 14 UK CI centres collected data prospectively: demographics, aetiology, use of imaging, device type, surgery duration, use of intra-operative electrophysiology, length of stay, and post-operative complications. RESULTS: 1397 CI procedures in 961 CI recipients were included; 436 bilateral simultaneous, 394 bilateral sequential, and 131 unilateral. The majority (85%) were congenitally deaf. The commonest causes of acquired deafness were meningitis and cytomegalovirus infection. The median age for congenitally deaf bilateral simultaneous CI was 2.2 years, mean surgical duration 4.5 hours. 6.3% surgeries were day case procedures. Eight cases (2.0%) of planned bilateral CI had unilateral surgery. The overall major complication rate was 1.6% (0.9% excluding device failures), including explantation due to infection (0.2%), cerebrospinal fluid leak (0.2%), and meningitis (0.1%). There were no permanent facial nerve palsies and no deaths. Sixty-two (6.5%) immediate minor complications included 12 (1.3%) children with significant vestibular impairment. The complication rate was similar following bilateral CI compared to sequential and unilateral CI, and is comparable to other published series. CONCLUSION: This prospective multi-centre audit provides evidence that bilateral paediatric CI is a safe procedure in the UK, thus endorsing its role as a major therapeutic intervention in childhood deafness.

Spatial hearing of normally hearing and cochlear implanted children.

OBJECTIVE: Spatial hearing uses both monaural and binaural mechanisms that require sensitive hearing for normal function. Deaf children using either bilateral (BCI) or unilateral (UCI) cochlear implants would thus be expected to have poorer spatial hearing than normally hearing (NH) children. However, the relationship between spatial hearing in these various listener groups has not previously been extensively tested under ecologically valid conditions using a homogeneous group of children who are UCI users. We predicted that NH listeners would outperform BCI listeners who would, in turn, outperform UCI listeners. METHODS: We tested two methods of spatial hearing to provide norms for NH and UCI using children and preliminary data for BCI users. NH children (n=40) were age matched (6-15 years) to UCI (n=12) and BCI (n=6) listeners. Testing used a horizontal ring of loudspeakers within a booth in a hospital outpatient clinic. In a 'lateral release' task, single nouns were presented frontally, and masking noises were presented frontally, or 90° left or right. In a 'localization' task, allowing head movements, nouns were presented from loudspeakers separated by 30°, 60° or 120° about the midline. RESULTS: Normally hearing children improved with age in speech detection in noise, but not in quiet or in lateral release. Implant users performed more poorly on all tasks. For frontal signals and noise, UCI and BCI listeners did not differ. For lateral noise, BCI listeners performed better on both sides (within ~2 dB of NH), whereas UCI listeners benefited only when the noise was opposite the unimplanted ear. Both the BCI and, surprisingly, the UCI listeners performed better than chance at all loudspeaker separations on the ecologically valid, localization task. However, the BCI listeners performed about twice as well and, in two cases, approached the performance of NH children. CONCLUSION: Children using either UCI or BCI have useful spatial hearing. BCI listeners gain benefits on both sides, and localize better, but not as well as NH listeners.

International classification of reliability for implanted cochlear implant receiver stimulators.

OBJECTIVE: To design an international standard to be used when reporting reliability of the implanted components of cochlear implant systems to appropriate governmental authorities, cochlear implant (CI) centers, and for journal editors in evaluating manuscripts involving cochlear implant reliability. STUDY DESIGN: The International Consensus Group for Cochlear Implant Reliability Reporting was assembled to unify ongoing efforts in the United States, Europe, Asia, and Australia to create a consistent and comprehensive classification system for the implanted components of CI systems across manufacturers. SETTING: All members of the consensus group are from tertiary referral cochlear implant centers. INTERVENTIONS: None. MAIN OUTCOME MEASURE: A clinically relevant classification scheme adapted from principles of ISO standard 5841-2:2000 originally designed for reporting reliability of cardiac pacemakers, pulse generators, or leads. RESULTS: Standard definitions for device failure, survival time, clinical benefit, reduced clinical benefit, and specification were generated. Time intervals for reporting back to implant centers for devices tested to be "out of specification," categorization of explanted devices, the method of cumulative survival reporting, and content of reliability reports to be issued by manufacturers was agreed upon by all members. The methodology for calculating Cumulative survival was adapted from ISO standard 5841-2:2000. CONCLUSION: The International Consensus Group on Cochlear Implant Device Reliability Reporting recommends compliance to this new standard in reporting reliability of implanted CI components by all manufacturers of CIs and the adoption of this standard as a minimal reporting guideline for editors of journals publishing cochlear implant research results.

Effectiveness of computer-based auditory training for adult users of cochlear implants.

Cochlear implantation is effective at restoring partial hearing to profoundly deaf adults, but not all patients receive equal benefit. The present study evaluated the effectiveness of a computer-based self-administered training package that was designed to improve speech perception among adults who had used cochlear implants for more than three years. Eleven adults were asked to complete an hour of auditory training each day, five days a week, for a period of three weeks. Two training tasks were included, one based around discriminating isolated words, and the other around discriminating words in sentences. Compliance with the protocol was good, with eight out of eleven participants completing approximately 15 hours of training, as instructed. A significant improvement of eight percentage points was found on a test of consonant discrimination, but there were no significant improvements on sentence tests or on a test of vowel discrimination. Self-reported benefits were variable and generally small. Further research is needed to establish whether auditory training is particularly effective for identifiable sub-groups of cochlear-implant users.

Disproportionate language impairment in children using cochlear implants.

OBJECTIVES: To examine the nature of previously unexplained, severe language impairments in some children using a cochlear implant (CI). DESIGN: Six prelingually deaf children with unexplained, "disproportionate" language problems (DLI group) were matched to Control children on etiology, age at implantation, and CI experience. All children completed a test battery used to identify specific language impairment in normally hearing children. RESULTS: Despite equivalent performance IQ, significant differences were found between the DLI and Control children on all five language tests. CONCLUSIONS: Language difficulties experienced by some children using a CI seem to be additional to those produced by their deafness and may reflect the same, predominantly inherited basis as specific language impairment.

Spatial hearing disability after acoustic neuroma removal.

OBJECTIVES/HYPOTHESIS: Previous studies on hearing loss (HL) after acoustic neuroma removal concentrate mainly on pure-tone hearing results rather than hearing disability. Our objectives were to use the Speech, Spatial and Qualities of Hearing scale (SSQ), a comprehensively validated questionnaire, to characterize and quantify the auditory disabilities that patients experience with a profound unilateral HL after acoustic neuroma removal. STUDY DESIGN: Forty-four patients with profound unilateral HL after acoustic neuroma surgery completed the SSQ. Their findings were compared with those of a control population sample matched for age, sex, and hearing level in the better hearing ear. RESULTS: In comparison with controls, with use of analysis of variance, acoustic neuroma patients scored poorly on all items except for the identification of sounds and objects (P = .123). The greatest difficulties involved speech in the presence of noise, situations of multiple speech-streams and switching (such as listening to someone speaking and the television at the same time), the location of unseen objects, and increased listening effort (P < .05). CONCLUSION: This study demonstrates that, compared with a control population, these patients experience a significant range of auditory disabilities. It is important that clinicians be aware of the impact of such a profound unilateral HL and its potential to affect daily life. Patient counseling prior to surgery is essential, especially in patients whose loss of binaural hearing could constitute a major disability.

Ensuring the long-term use of cochlear implants in children: the importance of engaging local resources and expertise.

Cochlear implantation for children is now a mature service, recognized as being safe and effective. Early identification is enabling implantation to be undertaken in the first years of life, with the likelihood of better outcomes. Traditional models of service delivery provided excellent clinic-based services, with intensive early habilitation. However, the current challenges extend beyond this time frame, and clinic-based services are overstretched with the growing numbers of children with implants. Needs analyses of parents and teachers in Europe provide evidence that they are keen to have regular links between implant center and home and school and that for both parents and teachers a major concern is the long-term management of the technology. There are major challenges, not in the implant clinic, but at home and school where implant systems are used. Implementing complex technology in the child's community in the long term is only possible by engaging parents and the local professionals, particularly teachers, from the outset, and using their expertise. This calls for a critical appraisal of the traditional approach to service delivery. Such engagement of local professionals does not happen automatically but can be achieved by educational programs for parents and local professionals that are adapted to local needs and cultures. Communication between implant center and home and school is essential, ensuring that the technology of implantation is used effectively at all times and is accessible to all wherever they live. This article recommends ways in which parents, teachers, and local professionals can play a central role in the management of children with implants to ensure the successful long-term use of their implant systems. Engaging and using the skills and expertise of those who know the child best, parents and teachers, will not only ensure that implantation is sustainable in the long term in diverse cultures, but is also cost-effective.