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Although animal models show a clear link between noise exposure and damage to afferent cochlear synapses, the relationship between noise exposure and efferent function appears to be more complex. Animal studies indicate that high intensity noise exposure reduces efferent medial olivocochlear (MOC) reflex strength, whereas chronic moderate noise exposure is associated with a conditioning effect that enhances the MOC reflex. The MOC reflex is predicted to improve speech-in-noise perception and protects against noise-induced auditory damage by reducing cochlear gain. In humans, MOC reflex strength can be estimated by measuring contralateral inhibition of distortion product otoacoustic emissions (DPOAEs). The objective of this study was to determine the impact of military noise exposure on efferent auditory function by measuring DPOAE contralateral inhibition in young Veterans and non-Veterans with normal audiograms. Compared with non-Veteran controls, Veterans with high levels of reported noise exposure demonstrated a trend of reduced contralateral inhibition across a broad frequency range, suggesting efferent damage. Veterans with moderate noise exposure showed trends of reduced inhibition from 3 to 4 kHz but greater inhibition from 1 to 1.5 kHz, consistent with conditioning. These findings suggest that, in humans, the impact of noise exposure on the MOC reflex differs depending on the noise intensity and duration.

Purpose The engagement of patients as key stakeholders in their experience of care processes is a critical component of quality improvement efforts for both clinical care and translational research. Increasingly, health care systems are soliciting input from patients on care processes and experiences through surveys, patient interviews, and patient video narratives. The purpose of this viewpoint article is twofold: (a) to describe the increasing role of patient narratives about their experiences with adverse health conditions to inform patient-centered research and quality improvement efforts and (b) to present three patient narratives that highlight the real-world impacts of hearing loss and tinnitus, the life enhancing impacts of aural rehabilitation, and the importance of prospective ototoxicity monitoring in individuals with complex health conditions. Conclusion Patient narratives provide individual patient perspectives that can be used to build awareness of the range of experiences and impact of hearing disorders, and to explore patient preferences for when and how to implement hearing-related clinical services.

Purpose Several military occupations, particularly those within the U.S. Air Force, require working with or around jet fuels. Jet fuels contain components that are known to affect central nervous function, yet effects of these fuels on auditory function, specifically auditory processing of sound, are not well understood at this time. Animal studies have demonstrated that exposure to jet fuels prior to noise exposure can exacerbate the noise exposure's effects, and service members exposed to jet fuels are at risk of noise exposure within their work environments. The purpose of this article was to give a brief synopsis of the evidence on the ototoxic effects due to jet fuel exposure to aid audiologists in their decision making when providing care for populations who are occupationally exposed to fuels or while during military service. Conclusions Exposure to jet fuels impacts central nervous function and, in combination with noise exposure, may have detrimental auditory effects that research has yet to fully explain. Additional longitudinal research is needed to explain the relationships, which have clinical implications for service members and others exposed to jet fuels. In the meantime, audiologists can gain useful information by screening for chemical exposures when obtaining patient case histories. If jet fuel exposure is suspected, the Lifetime Exposure to Noise and Solvents Questionnaire can be used to estimate a noise exposure ranking and identify other potentiating agents such as jet fuel and industrial chemicals. A history of jet fuel exposure should inform the selection of hearing tests in the audiometric evaluation and when devising the treatment plan.

Purpose Determine the efficacy of ototoxicity monitoring (OM) administered as automated protocols with the Oto-ID mobile audiometer (automated ototoxicity monitoring [A-OM]), compared with usual care (UC) OM in cancer patients receiving cisplatin. Method Participants were patients ( n = 46, mean age 64.7 years; range: 30–78 years) receiving cisplatin-based chemotherapy at the Department of Veterans Affairs Portland Health Care System. A randomized controlled trial contrasted A-OM and UC at up to three program evaluations (PEs) conducted by the study audiologist who was blinded to arm through PE1. PE1 occurred before randomization or oncology treatment; PE2 and PE3 occurred during and/or after treatment at 35 and 365 days postrandomization. The A-OM group ( n = 24) used Oto-ID to screen their hearing before each cisplatin dose. Oto-ID results were sent to the study audiologist for interpretation, follow-up, and care coordination. The UC group ( n = 22) received a consult for OM services through the audiology clinic. Outcomes included hearing shift near each patient's high-frequency hearing limit, revised hearing-handicap inventory score, and survival time from the start of treatment. Adherence to OM protocols, patients' use of aural rehabilitation services, and oncologists' treatment decisions were also examined. Results Ototoxicity was identified at a high overall rate (46% and 76% at 35 and 365 days, respectively, postrandomization). Adherence to monitoring prior to each cisplatin dose was 83.3% for those randomized to A-OM compared with 4.5% for UC. Randomization to A-OM was not associated with reduced ototoxic hearing shifts or self-reported hearing handicap relative to UC; neither did it compromise participants' survival. Half of participants in each arm accessed aural rehabilitation services. One in each arm had a documented ototoxicity-related cisplatin dose reduction. Conclusions Auditory impairment was an actionable concern for the participants and their oncology providers. A dedicated surveillance program using the Oto-ID's automated protocols improved adherence to OM recommendations over a traditional UC service delivery model. Supplemental Material https://doi.org/10.23641/asha.16649602

Measures of signal-in-noise neural encoding may improve understanding of the hearing-in-noise difficulties experienced by many individuals in everyday life. Usually noise results in weaker envelope following responses (EFRs); however, some studies demonstrate EFR enhancements. This experiment tested whether noise-induced enhancements in EFRs are demonstrated with simple 500- and 1000-Hz pure tones amplitude modulated at 110 Hz. Most of the 12 young normal-hearing participants demonstrated enhanced encoding of the 110-Hz fundamental in a noise background compared to quiet; in contrast, responses at the harmonics were decreased in noise relative to quiet conditions. Possible mechanisms of such an enhancement are discussed.

Purpose: Type 2 diabetes mellitus (DM2) is associated with impaired hearing. However, the evidence is less clear if DM2 can lead to difficulty understanding speech in complex acoustic environments, independently of age and hearing loss effects. The purpose of this study was to estimate the magnitude of DM2-related effects on speech understanding in the presence of competing speech after adjusting for age and hearing. Method: A cross-sectional study design was used to investigate the relationship between DM2 and speech understanding in 190 Veterans ( M age = 47 years, range: 25–76). Participants were classified as having no diabetes ( n = 74), prediabetes ( n = 19), or DM2 that was well controlled ( n = 24) or poorly controlled ( n = 73). A test of spatial release from masking (SRM) was presented in a virtual acoustical simulation over insert earphones with multiple talkers using sentences from the coordinate response measure corpus to determine the target-to-masker ratio (TMR) required for 50% correct identification of target speech. A linear mixed model of the TMR results was used to estimate SRM and separate effects of diabetes group, age, and low-frequency pure-tone average (PTA-low) and high-frequency pure-tone average. A separate model estimated the effects of DM2 on PTA-low. Results: After adjusting for hearing and age, diabetes-related effects remained among those whose DM2 was well controlled, showing an SRM loss of approximately 0.5 dB. Results also showed effects of hearing loss and age, consistent with the literature on people without DM2. Low-frequency hearing loss was greater among those with DM2. Conclusions: In a large cohort of Veterans, low-frequency hearing loss and older age negatively impact speech understanding. Compared with nondiabetics, individuals with controlled DM2 have additional auditory deficits beyond those associated with hearing loss or aging. These results provide a potential explanation for why individuals who have diabetes and/or are older often report difficulty understanding speech in real-world listening environments. Supplemental Material: https://doi.org/10.23641/asha.16746475

Purpose Specific classes of antibiotics, such as aminoglycosides, have well-established adverse events producing permanent hearing loss, tinnitus, and balance and/or vestibular problems (i.e., ototoxicity). Although these antibiotics are frequently used to treat pseudomonas and other bacterial infections in patients with cystic fibrosis (CF), there are no formalized recommendations describing approaches to implementation of guideline adherent ototoxicity monitoring as part of CF clinical care. Method This consensus statement was developed by the International Ototoxicity Management Working Group (IOMG) Ad Hoc Committee on Aminoglycoside Antibiotics to address the clinical need for ototoxicity management in CF patients treated with known ototoxic medications. These clinical protocol considerations were created using consensus opinion from a community of international experts and available evidence specific to patients with CF, as well as published national and international guidelines on ototoxicity monitoring. Results The IOMG advocates four clinical recommendations for implementing routine and guideline adherent ototoxicity management in patients with CF. These are (a) including questions about hearing, tinnitus, and balance/vestibular problems as part of the routine CF case history for all patients; (b) utilizing timely point-of-care measures; (c) establishing a baseline and conducting posttreatment evaluations for each course of intravenous ototoxic drug treatment; and (d) repeating annual hearing and vestibular evaluations for all patients with a history of ototoxic antibiotic exposure. Conclusion Increased efforts for implementation of an ototoxicity management program in the CF care team model will improve identification of ototoxicity signs and symptoms, allow for timely therapeutic follow-up, and provide the clinician and patient an opportunity to make an informed decision about potential treatment modifications to minimize adverse events. Supplemental Material https://doi.org/10.23641/asha.16624366

Objectives The objective of this study was to develop a framework for investigating the roles of neural coding and cognition in speech perception. Design N1 and P3 auditory evoked potentials, QuickSIN speech understanding scores, and the Digit Symbol Coding cognitive test results were used to test the accuracy of either a compensatory processing model or serial processing model. Results The current dataset demonstrated that neither the compensatory nor the serial processing model were well supported. An additive processing model may best represent the relationships in these data. Conclusions With the outcome measures used in this study, it is apparent that an additive processing model, where exogenous neural coding and higher order cognition contribute independently, best describes the effects of neural coding and cognition on speech perception. Further testing with additional outcome measures and a larger number of subjects is needed to confirm and further clarify the relationships between these processing domains.

Objectives: Integrating audiological management into the care pathways of clinical specialties that prescribe ototoxic medications for essential, often life-preserving medical care that is critical for early hearing loss identification and remediation. Research shows that successful implementation of a new health service or intervention requires alignment of goals among provider groups, institutional leadership and patients. Thoughtful consideration of the physician’s viewpoints about ototoxicity and its implications for treatment planning is, therefore, important for the implementation and enduring success of an ototoxicity monitoring programme (OMP). Design: This discussion paper uses qualitative methods to explore the perspectives of four physicians on OMP provision in their patient populations. Study sample: Three pulmonologists and one oncologist completed the written survey or survey-based interview described in this report. Results: Each physician indicated that (i) ototoxicity is a potential problem for their patients; (ii) monitoring hearing is important to ensure good quality of life among their patients and (iii) treatment modification would be considered if an alternative treatment option were available. The physicians differed in their approaches to ototoxicity monitoring, from routine referrals to audiology, to relying on patient self-referral. Conclusion: Physician provider input is needed to optimise monitoring schedules and OMP care coordination with audiology.

Tinnitus is commonly experienced by military Service Members and Veterans, especially by the newest generation who served in Iraq and Afghanistan. When patients seek health care for tinnitus, it is important to determine its type, check for comorbid conditions that might be triggering or exacerbating the condition, and to address its functional and psychosocial effects. Otolaryngologists are usually the first health care professional to evaluate a patient with tinnitus, and it is essential to provide appropriate referrals for this high-burden condition. Noise-induced tinnitus is multifaceted; by performing a thorough assessment, appropriate action can be taken to best meet the needs of patients.

Objectives To determine whether auditory brainstem response (ABR) wave I amplitude is associated with measures of auditory perception in young people with normal distortion product otoacoustic emissions (DPOAEs) and varying levels of noise exposure history. Design Tinnitus, loudness tolerance, and speech perception ability were measured in 31 young military Veterans and 43 non-Veterans (19 to 35 years of age) with normal pure-tone thresholds and DPOAEs. Speech perception was evaluated in quiet using Northwestern University Auditory Test (NU-6) word lists and in background noise using the words in noise (WIN) test. Loudness discomfort levels were measured using 1-, 3-, 4-, and 6-kHz pulsed pure tones. DPOAEs and ABRs were collected in each participant to assess outer hair cell and auditory nerve function. Results The probability of reporting tinnitus in this sample increased by a factor of 2.0 per 0.1 µV decrease in ABR wave I amplitude (95% Bayesian confidence interval, 1.1 to 5.0) for males and by a factor of 2.2 (95% confidence interval, 1.0 to 6.4) for females after adjusting for sex and DPOAE levels. Similar results were obtained in an alternate model adjusted for pure-tone thresholds in addition to sex and DPOAE levels. No apparent relationship was found between wave I amplitude and either loudness tolerance or speech perception in quiet or noise. Conclusions Reduced ABR wave I amplitude was associated with an increased risk of tinnitus, even after adjusting for DPOAEs and sex. In contrast, wave III and V amplitudes had little effect on tinnitus risk. This suggests that changes in peripheral input at the level of the inner hair cell or auditory nerve may lead to increases in central gain that give rise to the perception of tinnitus. Although the extent of synaptopathy in the study participants cannot be measured directly, these findings are consistent with the prediction that tinnitus may be a perceptual consequence of cochlear synaptopathy.

The goal of this article is to highlight mobile technology that is not yet standard of care but could be considered for use in an ototoxicity monitoring programme (OMP) as an adjunct to traditional audiometric testing. Current guidelines for ototoxicity monitoring include extensive test protocols performed by an audiologist in an audiometric booth. This approach is comprehensive, but it may be taxing for patients suffering from life-threatening illnesses and cost prohibitive if it requires serial clinical appointments. With the use of mobile technology, testing outside of the confines of the audiometric booth may be possible, which could create more efficient and less burdensome OMPs.A non-systematic review of new OMP technology was performed. Experts were canvassed regarding the impact of new technology on OMPs.OMP devices and technologies that are commercially available and discussed in the literature.The benefits and limitations of portable, tablet-based technology that can be deployed for efficient ototoxicity monitoring are discussed.New mobile technology has the potential to influence the development and implementation of OMPs and lower barriers to patient access by providing time efficient, portable and self-administered testing options for use in the clinic and in the patient's home.

Objectives Recent animal studies demonstrated that cochlear synaptopathy, a partial loss of inner hair cell-auditory nerve fiber synapses, can occur in response to noise exposure without any permanent auditory threshold shift. In animal models, this synaptopathy is associated with a reduction in the amplitude of wave I of the auditory brainstem response (ABR). The goal of this study was to determine whether higher lifetime noise exposure histories in young people with clinically normal pure-tone thresholds are associated with lower ABR wave I amplitudes. Design Twenty-nine young military Veterans and 35 non Veterans (19 to 35 years of age) with normal pure-tone thresholds were assigned to 1 of 4 groups based on their self-reported lifetime noise exposure history and Veteran status. Suprathreshold ABR measurements in response to alternating polarity tone bursts were obtained at 1, 3, 4, and 6 kHz with gold foil tiptrode electrodes placed in the ear canal. Wave I amplitude was calculated from the difference in voltage at the positive peak and the voltage at the following negative trough. Distortion product otoacoustic emission input/output functions were collected in each participant at the same four frequencies to assess outer hair cell function. Results After controlling for individual differences in sex and distortion product otoacoustic emission amplitude, the groups containing participants with higher reported histories of noise exposure had smaller ABR wave I amplitudes at suprathreshold levels across all four frequencies compared with the groups with less history of noise exposure. Conclusions Suprathreshold ABR wave I amplitudes were reduced in Veterans reporting high levels of military noise exposure and in non Veterans reporting any history of firearm use as compared with Veterans and non Veterans with lower levels of reported noise exposure history. The reduction in ABR wave I amplitude in the groups with higher levels of noise exposure cannot be accounted for by sex or variability in outer hair cell function. This change is similar to the decreased ABR wave I amplitudes observed in animal models of noise-induced cochlear synaptopathy. However, without post mortem examination of the temporal bone, no direct conclusions can be drawn concerning the presence of synaptopathy in the study groups with higher noise exposure histories.

The purpose of this report is to provide guidance on the use of otoacoustic emissions (OAEs) as a clinical trial outcome measure for pharmaceutical interventions developed to prevent acquired hearing loss secondary to cochlear insult. OAEs are a rapid, noninvasive measure that can be used to monitor cochlear outer hair cell function. Serial monitoring of OAEs is most clearly established for use in hearing conservation and ototoxicity monitoring programs in which they exhibit more frequent and earlier changes compared with pure-tone audiometry. They also show promise in recent human trials of otoprotectants. Questions remain, however, concerning the most appropriate OAE protocols to use and what constitutes a "significant" OAE response change. Measurement system capabilities are expanding and test efficacy will vary across locations and patient populations. Yet, standardizing minimal measurement criteria and reporting of results is needed including documentation of test-retest variability so that useful comparisons can be made across trials. It is also clear that protocols must be theoretically sound based on known patterns of damage, generate valid results in most individuals tested, be accurate, repeatable, and involve minimal time. Based on the potential value added, OAEs should be included in clinical trials when measurement conditions and time permit.

Objectives: (1) To characterize the influence of type 2 diabetes mellitus (DM) on cortical auditory-evoked potentials (CAEPs) separate from the effects of normal aging, and (2) to determine whether the disease-related effects are modified by insulin dependence. Design: A cross-sectional study was conducted in a large cohort of Veterans to investigate the relationships among type 2 DM, age, and CAEPs in randomly selected participants with (N = 108) and without (N = 114) the disease and who had no more than a moderate hearing loss. Participants with DM were classified as insulin-dependent (IDDM, N = 47) or noninsulin-dependent (NIDDM, N = 61). Other DM measures included concurrent serum glucose, HbA1c, and duration of disease. CAEPs were evoked using a passive homogeneous paradigm (single repeating stimulus) by suprathreshold tones presented to the right ear, left ear, or both ears. Outcome measures were adjusted for the pure-tone threshold average for frequencies of 0.5, 1, and 2 kHz and analyzed for differences in age effects between participant groups using multiple regression. Results: There is little variation across test ear conditions (left, right, binaural) on any CAEP peak in any of the groups. Among no-DM controls, P2 latency increases about 9 msec per decade of life. DM is associated with an additional delay in the P2 latency of 7 and 9 msec for the IDDM and NIDDM groups, respectively. Moreover, the slope of the function relating P2 latency with age is similar across participant groups and thus the DM effect appears constant across age. Effects on N1 latency are considerably weaker, with age effects of less than 4 msec per decade across all groups, and DM effects of only 2 (IDDM) or 3 msec (NIDDM). In the NIDDM group, the slope relating N1 latency to age is steeper relative to that observed for the no-DM group, providing some evidence of accelerated “aging” for this CAEP peak. DM does not substantially reduce N1–P2 amplitude and age relationships with N1–P2 amplitude are effectively absent. There is no association between pure-tone average at 0.5, 1, and 2 kHz and any aspect of CAEPs in this cohort. Conclusions: In a large cohort of Veterans, we found that type 2 DM is associated with prolonged N1 and P2 latencies regardless of whether insulin is required to manage the disease and independent of peripheral hearing thresholds. The DM-related effects on CAEP latencies are threefold greater for P2 compared with N1, and there is little support that at the cortical level, IDDM participants had poorer responses compared with NIDDM participants, although their responses were more variable. Overall, these results indicate that DM is associated with slowed preattentive neural conduction. Moreover, the observed 7 to 9 msec P2 latency delay due to DM is substantial compared with normal age changes in P2, which are 9 msec per decade of life in this cohort. Results also suggest that whereas N1 latency changes with age are more pronounced among individuals with DM versus without DM, there was no evidence for more rapid aging of P2 among patients with DM. Thus, the damage responsible for the major DM-related differences may occur early in the DM disease process. These cross-sectional results should be verified using a longitudinal study design.

OBJECTIVES: To promote establishment of more uniformly effective ototoxicity monitoring programs (OMPs), this report reviews the U.S. national audiology guidelines in relation to “real world” OMP application. A secondary aim is to review the mechanisms, risk and clinical presentation of hearing loss associated with major classes of ototoxic medications. DESIGN: This is a non-systematic review using PubMed, national and international agency websites, personal communications between ototoxicity experts, and results of unpublished research. Examples are provided of OMPs in various healthcare settings within the U.S. civilian sector, Department of Defense (DoD), and Department of Veterans Affairs (VA). STUDY SAMPLE: The five OMPs compared in this report represent a convenience sample of the programs with which the authors are affiliated. Their opinions were elicited via two semi-structured teleconferences on barriers and facilitators of OMP, followed by a self-administered questionnaire on OMP characteristics and practices, with responses synthesized and tabulated herein. Preliminary results are provided from an ongoing VA clinical trial at one of these OMP sites. Participants were 40 VA patients who received cisplatin chemotherapy in 2014-2017. The study arms contrast access to care for OMP delivered on the treatment unit versus usual care as provided in the audiology clinic. RESULTS: Protocols of the OMPs examined vary, reflecting the diverse settings in which they exist. Service delivery concerns included baseline tests missed or completed after the initial treatment, and monitoring tests done infrequently or only after cessation of treatment. Perceived barriers involved logistics related to accessing and testing patients, such as a lack of processes to help patients enter programs, patients’ time and scheduling constraints, and inconvenient audiology clinic locations. Most sites routinely used abbreviated or screening methods to facilitate monitoring. CONCLUSIONS: The most effective OMPs integrated audiological management into the care pathways of the clinical specialties that prescribe ototoxic medications. More OMP guidance is needed to inform evaluation schedules, outcome reporting, and determination of an actionable ototoxic change. Guidance is also lacking on the potential use of hearing conservation approaches suitable for the mass testing needed to support large-scale OMP efforts. Guideline adherence might improve with formal endorsement from the organizations governing medical specialty stakeholders in OMP such as medical oncologists, pulmonologists, infectious disease specialists, and ototolaryngologists.

Objective: Distortion product otoacoustic emissions (DPOAEs) have long been heralded as a means to objectively monitor cochlear function and increasingly are becoming a key component in hearing surveillance programs for individuals at risk for ototoxic- and occupational noise-related hearing loss. Yet clinicians are unsure how to define clinically meaningful shifts in DPOAE level. In this study, a meta-analysis approach is used to synthesize the DPOAE level test–retest literature to construct a set of DPOAE level shift reference limits that can be used clinically to define a statistically significant emission change. Design: The authors reviewed all published articles identified through a Medline search using the terms “Otoacoustic Emission Variability,” “Otoacoustic Emission Reliability,” “Otoacoustic Emission Repeatability,” and “Otoacoustic Emission Test Retest” restricted to DPOAEs, adults, and English language. Articles with DPOAE level data elicited by moderate stimulus levels for f 2 frequencies of 1000, 2000, 4000, or 6000 Hz were selected because these stimulus parameters were relatively well represented in the literature. The authors only included articles that reported the standard error of the measurement (SEM) or from which the SEM could be calculated. Meta-analysis was used to estimate the population mean SEM over the included studies. Models were fit separately for each f 2 primary and included days since baseline and study-specific random effects. Results: Ten DPOAE test–retest studies met inclusion criteria for this meta-analysis. The SEM values varied widely across published studies (0.57 to 3.9 dB) and were provided for relatively short time intervals (less than 15 days on average). Time, or days since baseline, was statistically significant at higher f 2 frequencies (4000 and 6000 Hz). From the model results, 90% reference limits specific to the f 2 and elapsed time between baseline and follow-up measurements were established. Reference limits provided correspond to negative (emission decrement) and positive (emission enhancement) shifts indicative of the amount of measurement variability that, using this approach, must be tolerated as “normal” fluctuations over time. Changes larger than the reference limits are considered significant and warrant follow-up testing. Conclusions: The meta-analysis presented provides reference limits that are appropriate for a set of specific f 2 frequencies and time intervals. The meta-analysis concerns the SEM statistic directly, so that any preferred reference limit can be computed from the results and should be predicated upon the screening application. The presumed advantage of this meta-analytic approach is increased precision relative to limits suggested by any of the individual studies included in the analysis.

Background: Nonbehavioral methods for identifying cisplatin ototoxicity are important for testing patients with cancer who become too tired or sick to provide a reliable response. The auditory brainstem response (ABR) is a nonbehavioral test that is sensitive to ototoxicity but can be time consuming to implement over a range of frequencies and/or levels. To address this issue, trains of stimuli were developed that offer reliable ABR testing over a range of tone-burst frequencies and levels at a time savings of 77% relative to tone-burst stimuli presented individually. The clinical accuracy of this new method has yet to be determined on a clinical population. Purpose: This project was designed to determine the test performance of a time-effective ABR methodology aimed at identifying hearing shifts from cisplatin among veterans. A secondary goal was to determine whether improved test performance could be achieved by including our previously developed ototoxicity risk assessment model in the ABR prediction algorithm. Research Design: A set of discriminant functions were derived using logistic regression to model the risk for cisplatin-induced hearing change. Independent variables were one of several ABR metrics alone and combined with an ototoxicity risk assessment model that includes pre-exposure hearing and cisplatin dose. Receiver operating characteristic curve analysis was used to evaluate the test performance of these discriminant functions. Study Sample: Twenty-two male veterans treated with cisplatin for various cancers provided data from a total of 71 monitoring appointments. Data Collection and Analysis: Data were collected prospectively from one ear of each participant as designated below. Hearing shift was determined for frequencies within an octave of each patient's high-frequency hearing limit, tested in 1/6th-octave steps. ABRs were monitored using a set of two intensity trains from the highest two multiple frequency tone-burst center frequencies (up to 11.3 kHz) that yielded a robust response at baseline. Each intensity train was presented at 65–105 dB peSPL in 10 dB steps. Scorable ABRs were generally limited to the highest two intensities; therefore, analyses concern those levels. Results: The ABR measurement failure was high, up to 52% for some frequencies and levels. Furthermore, the ABR was not frequently obtained at levels below 85 dB peSPL, consistent with previous studies that suggest a stimulus level of greater than 80 dB peSPL is required to obtain a reliable response to trained stimuli. Using multivariate metrics that included the dose-ototoxicity model, the most accurate scoring function was change in amplitude at lowest half-octave frequency obtained at 105 dB (change in wave V amplitude at frequency 2/105). However, absence of wave V at a monitor patient visit of the ABR response at levels 105 or 95 dB peSPL was deemed the preferred scoring function, because it had lower measurement failure and was within one standard error of the most accurate function. Conclusions: Because of the large number of responses that could not be measured at baseline, this technique as implemented holds limited value as an ototoxicity-monitoring method.

Stimulus-frequency (SF) otoacoustic emission (OAE) amplitude and the amplitude of medial olivocochlear (MOC) inhibition of SF OAEs for ipsilateral, contralateral and bilateral MOC reflex elicitors were recorded in six subjects with type 2 diabetes during a glucose tolerance test (GTT). Five of the six subjects were tested twice for a total of 11 trials and three subjects were tested in a control experiment. During the GTT experiment, the subjects’ blood glucose was elevated from a euglycemic level below 150 mg/dL to a hyperglycemic level above 160 mg/dL following the consumption of a bolus of 80 g of sugar. A subset of three subjects were tested in a control experiment during which SF OAE and MOC reflex measurements were made while blood sugar levels remained constant within the euglycemic region. Mean SF OAE amplitudes were elevated following glucose consumption. A statistically significant increase in MOC inhibition amplitude was observed during elevated sugar levels for the 11 GTT trials. Maximum inhibition occurred about an hour after glucose consumption when blood glucose levels peaked. Results indicate that acute hyperglycemia influences efferent control of the cochlea in people with type 2 diabetes.

Distortion-product otoacoustic emissions (DPOAEs) provide a window into real-time cochlear mechanical function. Yet, relationships between the changes in DPOAE metrics and auditory sensitivity are still poorly understood. Explicating these relationships might support the use of DPOAEs in hearing conservation programs (HCPs) for detecting early damage leading to noise-induced hearing loss (NIHL) so that mitigating steps might be taken to limit any lasting damage. This report describes the development of DPOAE-based statistical models to assess the risk of hearing loss from cisplatin treatment among cancer patients. Ototoxicity risk assessment (ORA) models were constructed using a machine learning paradigm in which partial least squares and leave-one-out cross-validation were applied, yielding optimal screening algorithms from a set of known risk factors for ototoxicity and DPOAE changes from pre-exposure baseline measures. Single DPOAE metrics alone were poorer indicators of the risk of ototoxic hearing shifts than the best performing multivariate models. This finding suggests that multivariate approaches applied to the use of DPOAEs in a HCP, will improve the ability of DPOAE measures to identify ears with noise-induced mechanical damage and/or hearing loss at each monitoring interval. This prediction must be empirically assessed in noise-exposed subjects.

Purpose: This cross-sectional study had two goals: (1) Identify and quantify the effects of aging on the auditory brainstem response (ABR); (2) Describe how click rate and hearing impairment modify effects of aging. Research Design and Analysis: ABR measures were obtained from 131 predominately male Veteran participants aged 26 to 71 yr. Metrics analyzed include amplitude and latency for waves I, III, and V, and the I–V interpeak latency interval (IPI) at three repetition rates (11, 51, and 71 clicks/sec) using both polarities. In order to avoid confounding from missing data due to hearing impairment, participants had hearing thresholds Results: Aging substantially diminished amplitudes of all of the principal ABR peaks, largely independent of any threshold differences within the group. For waves I and III, age-related amplitude decrements were greatest at a low (11/sec) click rate. At the 11/sec rate, the model-based mean wave III amplitude was significantly smaller in older compared with younger subjects even after adjusting for wave I amplitude. Aging also increased ABR peak latencies, with significant shifts limited to early waves. The I–V IPI did not change with age. For both younger and older subjects, increasing click presentation rate significantly decreased amplitudes of early peaks and prolonged latencies of later peaks, resulting in increased IPIs. Advanced age did not enhance effects of rate. Instead, the rate effect on wave I and III amplitudes was attenuated for the older subjects due to reduced peak amplitudes at lower click rates. Compared with model predictions from the sample of better hearing subjects, mean ABR amplitudes were diminished in the group with poorer hearing, and wave V latencies were prolonged. Conclusions: In a sample of veterans, aging substantially reduced amplitudes of all principal ABR peaks, with significant latency shifts limited to waves I and III. Aging did not influence the I–V IPI even at high click rates, suggesting that the observed absolute latency changes associated with aging can be attributed to changes in auditory nerve input. In contrast, ABR amplitude changes with age are not adequately explained by changes in wave I. Results suggest that aging reduces the numbers and/or synchrony of contributing auditory nerve units. Results also support the concept that aging reduces the numbers, though perhaps not the synchrony, of central ABR generators.

Background: Tele-audiology improves access, controls cost, and improves efficiency of many aspects within health care. We have developed and validated a device, the ototoxicity identification device (OtoID), which enables remote hearing monitoring by a patient during chemotherapy treatment. Aspects of the design such as patient self-testing and texting of results to the audiology clinic are important features of this device. Purpose: The purpose of this article is to present the efficacy and effectiveness of the OtoID hearing screener. Research Design: A repeated measures design was used in this study. Study Sample: Twenty-one veterans undergoing cisplatin chemotherapy were recruited in this study. Data Collection and Analysis: Participants were tested using the OtoID at each cisplatin treatment by an audiologist using the manual mode of test and the participant using the automated mode of test. Test sensitivity and specificity were developed from the detection (yes/no) of an American Speech-Language-Hearing Association (ASHA) change in hearing. Results: The OtoID had a test sensitivity of 80.6% and specificity of 85.3%. A logistic regression model analysis of the probability of an ASHA shift identified by the automated OtoID was conducted. Separate models were fit to establish effects of age, average baseline thresholds in the sensitive range for ototoxicity (SRO), and dose of cisplatin on the probability of a positive hearing change result. Interactions were also included to evaluate these effects on the sensitivity and false-positive rates of the automated test. Results indicated no statistically significant effects of age, of baseline hearing in the SRO frequencies, or of cisplatin dose. Conclusions: The OtoID automated test can be recommended for use. The automated test provides significant personnel efficiencies. The modem with simple text messaging function recently added to the device improves on these efficiencies.

Objective Type 2 diabetes is epidemic among veterans, approaching three times the prevalence of the general population. Diabetes leads to devastating complications of vascular and neurologic malfunction and appears to impair auditory function. Hearing loss prevention is a major health-related initiative in the Veterans Health Administration. Thus, this research sought to identify, and quantify with effect sizes, differences in hearing, speech recognition, and hearing-related quality of life (QOL) measures associated with diabetes and to determine whether well-controlled diabetes diminishes the differences. Design The authors examined selected cross-sectional data from the baseline (initial) visit of a longitudinal study of Veterans with and without type 2 diabetes designed to assess the possible differences in age-related trajectories of peripheral and central auditory function between the two groups. In addition, the diabetes group was divided into subgroups on the basis of medical diagnosis of diabetes and current glycated hemoglobin (HbA1c) as a metric of disease severity and control. Outcome measures were pure-tone thresholds, word recognition using sentences presented in noise or time-compressed, and an inventory assessing the self-perceived impact of hearing loss on QOL. Data were analyzed from 130 Veterans ages 24 to 73 (mean 48) years with well-controlled (controlled) diabetes, poorly controlled (uncontrolled) diabetes, prediabetes, and no diabetes. Regression was used to identify any group differences in age, noise exposure history, and other sociodemographic factors, and multiple regression was used to model each outcome variable, adjusting for potential confounders. Results were evaluated in relation to diabetes duration, use of insulin (yes, no), and presence of selected diabetes complications (neuropathy and retinopathy). Results Compared with nondiabetics, Veterans with uncontrolled diabetes had significant differences in hearing at speech frequencies, including poorer hearing by 3 to 3.5 dB for thresholds at 250 Hz and in a clinical pure-tone average, respectively. Compared with nondiabetic controls, individuals with uncontrolled diabetes also significantly more frequently reported that their hearing adversely impacted QOL on one of the three subscales (ability to adapt). Despite this, although they also had slightly poorer mean scores on both word recognition tasks performed, these differences did not reach statistical significance and all subjects performed well on these tasks. Compared with Veterans with controlled diabetes, those with uncontrolled disease tended to have had diabetes longer, be insulin-dependent, and have a greater prevalence of diabetic retinopathy. Results are generally comparable with the literature with regard to the magnitude of threshold differences and the prevalence of hearing impairment but extend prior work by providing threshold difference and hearing loss prevalence effect sizes by category of diabetes control and by including additional functional measures. Conclusions In a cohort of Veterans with type 2 diabetes and relatively good hearing, significant effects of disease severity were found for hearing thresholds at a subset of frequencies and for one of the three QOL subscales. Significant differences were concentrated among those with poorly controlled diabetes based on current HbA1c. Results provide evidence that the observed hearing dysfunction in type 2 diabetes might be prevented or delayed through tight metabolic control. Findings need to be corroborated using longitudinal assessments.

Transient-evoked stimulus-frequency otoacoustic emissions (SFOAEs), recorded using a nonlinear differential technique, and distortion-product otoacoustic emissions (DPOAEs) were measured in 17 normal-hearing and 10 hearing-impaired subjects using pairs of tone pips (pp), gated tones (gg), and for DPOAEs, continuous and gated tones (cg). Temporal envelopes of stimulus and OAE waveforms were obtained by narrow-band filtering at the stimulus or DP frequency. Mean SFOAE latencies in normal ears at 2.7 and 4.0 kHz decreased with increasing stimulus level and were larger at 4.0 kHz than latencies in impaired ears. Equivalent auditory filter bandwidths were calculated as a function of stimulus level from SFOAE latencies by assuming that cochlear transmission is minimum phase. DPOAE latencies varied less with level than SFOAE latencies. The ppDPOAEs often had two (or more) peaks separated in time with latencies consistent with model predictions for distortion and reflection components. Changes in ppDPOAE latency with level were sometimes explained by a shift in relative amplitudes of distortion and reflection components. The pp SFOAE SPL within the main spectral lobe of the pip stimulus was higher for normal ears in the higher-frequency half of the pip than the lower-frequency half, which is likely an effect of basilar membrane two-tone suppression.

Primary and secondary sources combine to produce the 2f1-f2 distortion product otoacoustic emission (DPOAE) measured in the ear canals of humans. DPOAEs were obtained in nine normal-hearing subjects using a fixed-f2 paradigm in which f1 was varied. The f2 was 2 or 4 kHz, and absolute and relative primary levels were varied. Data were obtained with and without a third tone (f3) placed 15.6 Hz below 2f1-f2. The level of f3 was varied in order to suppress the stimulus frequency otoacoustic emission (SFOAE) coming from the 2f1-f2 place. These data were converted from the complex frequency domain into an equivalent time representation using an inverse fast Fourier transform (IFFT). IFFTs of unsuppressed DPOAE data were characterized by two or more peaks. Relative amplitudes of these peaks depended on overall primary level and on primary-level differences. The suppressor eliminated later peaks, but early peaks remained relatively unaltered. Results are interpreted to mean that the DPOAE measured in humans includes components from the f2 place (intermodulation distortion) and DP place (in the form of a SFOAE). These findings build on previous work by providing evidence that multiple peaks in the IFFT are due to a secondary source at the DP place.

Prevention and rehabilitation of hearing loss and tinnitus, the two most commonly awarded service-connected disabilities, are high priority initiatives in the Department of Veterans Affairs (VA). At least 4,000 Veterans, most with significant hearing loss, will receive cisplatin this year, with more than half sustaining permanent hearing shift and nearly 40% developing new tinnitus. With improved survivability following cancer treatment, Veterans treated with cisplatin are approached with the dual goals of effective treatment and preserved quality of life. This article describes COMP-VA, a comprehensive ototoxicity monitoring program developed for VA patients receiving cisplatin. The program includes an individualized pretreatment prediction model that identifies the likelihood of hearing shift given cisplatin dose and patient factors. It supports both manual and automated hearing testing with a newly developed portable audiometer capable of performing the recommended procedures on the chemotherapy unit during treatment. It also includes objective methods for identifying outer hair cell changes and predicting audiogram changes using distortion-product otoacoustic emissions. We describe this program of evidence-based ototoxicity monitoring protocols using a case example to give the reader an understanding of how this program would be applied, along with a plan for future work to accomplish the final stages of program development.

A cisplatin ototoxicity monitoring protocol was recently proposed using distortion-product otoacoustic emissions (DPOAEs) measured in 1/48th octave steps over the highest obtainable quarter octave ( Dille et al, 2010 ). This protocol can take up to 40 minutes to complete in both ears among seriously ill patients in a potentially noisy test environment. The goal of the current study was to contrast the diagnostic accuracy of ototoxicity monitoring protocols based on changes in DPOAE levels at wider, more rapidly tested, primary frequency step sizes.Measure DPOAE levels in 1/48th octave steps over the highest half-octave of obtainable DPOAEs prior to treatment and at each ototoxicity monitoring session during the course of treatment with cisplatin.Nineteen cancer patients being treated with cisplatin at the Portland Veterans Affairs Medical Center were observed over 56 monitoring appointments. Hearing thresholds in the sensitive region for ototoxicity (SRO) were measured concurrently with DPOAE levels.DPOAE levels measured in 1/24th octave steps provided comparable accuracy, and half the testing time, to the 1/48th octave step protocol previously described.DPOAE level shifts measured in 1/24th octave steps may provide a basis for rapid ototoxicity monitoring among adult cancer patients treated with cisplatin.

Background: Cisplatin is effective in the treatment of several cancers but is a known ototoxin resulting in shifts to hearing sensitivity in up to 50–60% of patients. Cisplatin-induced hearing shifts tend to occur first within an octave of a patient’s high frequency hearing limit, termed the sensitive range for ototoxicity (SRO), and progress to lower frequencies. While it is currently not possible to know which patients will experience ototoxicity without testing their hearing directly, monitoring the SRO provides an early indication of damage. A tool to help forecast susceptibility to ototoxic-induced changes in the SRO in advance of each chemotherapy treatment visit may prove useful for ototoxicity monitoring efforts, patient counseling, and therapeutic planning. Purpose: This project was designed to (1) establish pretreatment risk curves that quantify the probability that a new patient will suffer hearing loss within the SRO during treatment with cisplatin and (2) evaluate the accuracy of these predictions in an independent sample of Veterans receiving cisplatin for the treatment of cancer. Study Sample: Two study samples were used. The Developmental sample contained 23 subjects while the Validation sample consisted of 12 subjects. Data Collection and Analysis: Risk curve predictions for SRO threshold shifts following cisplatin exposure were developed using a Developmental sample comprised of data from a total of 155 treatment visits obtained in 45 ears of 23 Veterans. Pure-tone thresholds were obtained within each subject’s SRO at each treatment visit and compared with baseline measures. The risk of incurring an SRO shift was statistically modeled as a function of factors related to chemotherapy treatment (cisplatin dose, radiation treatment, doublet medication) and patient status (age, pre-exposure hearing, cancer location and stage). The model was reduced so that only statistically significant variables were included. Receiver-operating characteristic (ROC) curve analyses were then used to determine the accuracy of the risk curve predictions in an independent Validation sample of observations from over 62 treatment visits obtained in 24 ears of 12 Veterans. Results: Only cumulative cisplatin dose and pre-exposure hearing were found to be significantly related to the risk for hearing shift. The dose-ototoxicity risk curve predictions developed from the Developmental sample yielded area under the ROC curve accuracy estimates of 0.85 when applied to an independent Validation sample. Conclusions: Cumulative cisplatin dose in combination with pre-exposure hearing provides an indication of whether hearing will shift in the SRO in advance of cisplatin administration. The validated dose-ototoxicity risk curves described herein can be used before and during treatment to anticipate hearing loss. While having such a tool would not replace serial hearing testing, it would be of great benefit to an ototoxicity monitoring program. It would promote relevant pretreatment counseling. Furthermore, for those found to be at risk of SRO shifts within the speech frequencies, the oncology treatment plan could incorporate anticipated dosing adjustments that could stave off the impact that ototoxicity might bring.

Introduction: A nonbehavioral method for monitoring ototoxicity in patients treated with cisplatin is needed because patients enduring chemotherapy may not be well or cooperative enough to undergo repeated hearing tests. Distortion-product otoacoustic emissions (DPOAEs) provide a nonbehavioral measure of auditory function that is sensitive to cisplatin exposure. However, interpreting DPOAE findings in the context of ototoxicity monitoring requires that their accuracy be determined in relation to a clinically accepted gold standard test. Objectives: Among patients receiving cisplatin for the treatment of cancer, we sought to (1) identify the combination of DPOAE metrics and ototoxicity risk factors that best classified ears with and without ototoxic-induced hearing changes; and (2) evaluate the test performance achieved by the composite measure as well as by DPOAEs alone. Design: Odds of experiencing hearing changes at a given patient visit were determined using data collected prospectively from 24 Veterans receiving cisplatin. Pure-tone thresholds were examined within an octave of each subject's high-frequency hearing limit. DPOAE were collected as a set of four response growth (input/output) functions near the highest f 2 frequency that yielded a robust response at L 2 = L 1 = 65 dB SPL. Logistic regression modeled the risk of hearing change using several DPOAE metrics, drug treatment factors, and other patient factors as independent variables. An optimal discriminant function was derived by reducing the model so that only statistically significant variables were included. Receiver operating characteristic curve analyses were used to evaluate test performance. Results: At higher cisplatin doses, ears with better hearing at baseline were more likely to exhibit ototoxic hearing changes than those with poorer hearing. Measures of pre-exposure hearing, cumulative drug dose, and DPOAEs generated a highly accurate discriminant function with a cross-validated area under the receiver operating characteristic curve of 0.9. DPOAEs alone also provided an indication of ototoxic hearing change when measured at the highest DPOAE test frequency that yielded a robust response. Conclusions: DPOAEs alone and especially in combination with pre-exposure hearing and cisplatin dose provide an indication of whether or not hearing has changed as a result of cisplatin administration. These promising results need to be validated in a separate sample.

Background and Purpose: To report on the incidence and relative risk of tinnitus onset from a variety of drug therapies known to be ototoxic. Two main questions were asked: (1) What is the prevalence and incidence of tinnitus among patients treated with cisplatin, carboplatin, or ototoxic antibiotic therapies? (2) Do commonly reported treatment or subject factors confound or modify the incidence of tinnitus onset? Data Collection and Analysis: A prospective observational study design was used to evaluate occurrence of significant otologic changes in 488 veterans (962 ears) receiving chemotherapeutic agents (cisplatin, carboplatin), ototoxic antibiotics (primarily aminoglycoside), or nonototoxic drugs (control medications). A subset of 260 veterans lacking tinnitus prior to drug exposure was used to compare rates of tinnitus onset. Subjects were tested prior to, during, and following their treatment. Planned comparisons using logistic regression, analysis of variance (ANOVA), and χ2 statistics were made among groups by the type of medication taken, age, presence of preexisting hearing loss, days on drug, and cumulative dose of drug. Results: Baseline tinnitus rates were high (nearly 47%) relative to the general population of a similar age. Subjects with exposure to ototoxic medications had significantly increased risk for developing tinnitus. Those on chemotherapeutic agents were found to have the greatest risk. Cisplatin elevated the risk by 5.53 times while carboplatin increased the risk by 3.75 over nonototoxic control medications. Ototoxic antibiotics resulted in borderline risk (2.81) for new tinnitus. Contrary to other reports, we did not find that subject factors (increased age or pre-existing hearing loss) or treatment factors (days on drug or cumulative dose) contributed to rates of tinnitus onset during treatment. Conclusions: This large prospective study confirms that new tinnitus during treatment is associated with chemotherapy and with certain ototoxic antibiotic treatment. Cisplatin and carboplatin were found to be the most potent ototoxic agents causing tinnitus at much greater numbers than the other drugs studied. Implications for counseling and audiological resource allocation are discussed.

Background: There is disagreement about ototoxicity monitoring methods. Controversy exists about what audiometric threshold shift criteria should be used, which frequencies should be tested, and with what step size. An evaluation of the test performance achieved using various criteria and methods for ototoxicity monitoring may help resolve these issues. Purpose: (1) Evaluate test performance achieved using various significant threshold shift (STS) definitions for ototoxicity monitoring in a predominately veteran population; and (2) determine whether testing in ⅙- or ⅓-octave steps improves test performance compared to ½-octave steps. Research Design: A prospective, observational study design was used in which STSs were evaluated at frequencies within an octave of each subject's high-frequency hearing limit at two time points, an early monitoring test and the final monitoring test. Study Sample: Data were analyzed from 78 ears of 41 patients receiving cisplatin and from 53 ears of 28 hospitalized patients receiving nonototoxic antibiotics. Cisplatin-treated subjects received a cumulative dosage ≥350 mg by the final monitoring test. Testing schedule, age, and pre-exposure hearing characteristics were similar between the subject groups. Data Collection and Analysis: Threshold shifts relative to baseline were examined to determine whether they met criteria based on magnitudes of positive STS (shifts of ≥5, 10, 15, or 20 dB) and numbers of frequencies affected (shifts at ≥1, 2, or 3 adjacent frequencies) for data collected using approximately ⅙-, ⅓-, or ½-octave steps. Thresholds were confirmed during monitoring sessions in which shifts were identified. Test performance was evaluated with receiver operating characteristic (ROC) curves developed using a surrogate “gold standard”; true positive (TP) rates were derived from the cisplatin-exposed group and false positive (FP) rates from the nonexposed, control group. Best STS definitions were identified that achieved the greatest areas under ROC curves or resulted in the highest TP rates for a fixed FP rate near 5%, chosen to minimize the number of patients incorrectly diagnosed with ototoxic hearing loss. Results: At the early monitoring test, average threshold shifts differed only slightly across groups. Test-frequency step size did not affect performance, and changes at one or more frequencies yielded the best test performance. At the final monitoring test, average threshold shifts were +10.5 dB for the cisplatin group, compared with −0.2 dB for the control group. Compared with the ½-octave step size used clinically, use of smaller frequency steps improved test performance for threshold shifts at ≥2 or ≥3 adjacent frequencies. Best overall test performance was achieved using a criterion cutoff of ≥10 dB threshold shift at ≥2 adjacent frequencies tested in ⅙-octave steps. Best test performance for the ½-octave step size was achieved for shifts ≥15 dB at one or more frequencies. Conclusions: An ototoxicity monitoring protocol that uses an individualized, one-octave range of frequencies tested in ⅙-octave steps is quick to administer and has an acceptable FP rate. Similar test performance can be achieved using ⅓-octave test frequencies, which further reduces monitoring test time.

Determine the effects on hearing of diabetes mellitus (DM) severity.We conducted a cross-sectional study among Veterans to investigate the relationship of diabetes severity and hearing in randomly selected subjects with (165) and without (137) DM and who had no more than a moderate hearing loss.Subjects were classified by three age tertiles (50, 50-56, and 57+ years). Diabetes severity was classified as insulin-dependent (IDDM), noninsulin-dependent (NIDDM), or no DM. Other DM measures included concurrent serum glucose, serum HbA(1c), duration of disease, and several measures of DM-related complications. Pure-tone thresholds were measured in both ears of each subject at frequencies from 250 Hz through 14,000 Hz. Outcome measures were adjusted for age and frequency and analyzed for differences between subject groups using analysis of variance. Contrasts of the mean NIDDM and IDDM thresholds at each frequency to the DM group, and controlled for the effects of frequency, age, and interactions were modeled.There was greater hearing loss in younger tertile DM subjects compared to those without DM. Significant hearing differences were at all frequencies for NIDDM subjects, but for IDDM subjects, differences were at 1,000 Hz and below, and 10,000 Hz and above. Over age 50 years, there were significant associations between hearing at low frequencies and IDDM only. Self-report of prior noise exposure did not explain observed differences.Diabetes is associated with an increased risk of hearing loss, and this difference is manifest particularly in adults50 years old.

Objectives: (1) To determine the ototoxicity detection rate (sensitivity) for distortion-product otoacoustic emissions (DPOAEs) testing in adults who received ototoxic medications and experienced pure-tone threshold changes during the course of treatment; (2) to determine the extent to which DPOAE sensitivity to ototoxicity depends on the type of drug administered (platinum or antibiotic), magnitude of ototoxic threshold shifts, pre-exposure pure-tone threshold, and DPOAE data; and (3) to build a model to predict DPOAE sensitivity. Design: DPOAE and audiometric data were obtained as part of a prospective Veterans Affairs study investigating methods of ototoxicity monitoring. Data were analyzed from 90 ears of 53 subjects receiving ototoxic medications and showing significant hearing changes in at least one ear. Pure-tone threshold data were obtained at frequencies from 0.5 to 20 kHz, using 1/6-octave precision near the upper frequency limit of hearing. DPOAE data are reported for f2’s from 0.8 to 8.0 kHz in 1/6-octave increments using primary levels (L1/L2) of 65/59 dB SPL and a primary frequency ratio (f2/f1) of 1.2. Test results were evaluated at various times during drug treatment to determine whether DPOAE level changes were associated with behavioral hearing changes. Univariate and multivariate analysis techniques were used to determine factors that affected DPOAE sensitivity to ototoxic damage. Results: Of the 90 ears examined, 82 (91%) had DPOAEs that could be monitored for changes. Sixty-four of these 82 ears (78%) had DPOAEs that were reduced or absent following drug treatment. DPOAE sensitivity to ototoxicity was unrelated to the type of ototoxic drug administered. Rather, DPOAE sensitivity depended on the magnitude of postexposure hearing changes and on variables related to pre-exposure audiogram and DPOAE measurements. Behavioral hearing changes not detected by DPOAEs were small on average (

The long term objective of this research is to develop a new means for diabetic patients to painlessly and non-invasively monitor their blood glucose levels. We propose a novel method for noninvasive glucose monitoring based on measurement and analysis of otoacoustic emissions (OAEs). OAEs are low-intensity sounds generated by the cochlea in response to acoustic stimuli. Evoking and measuring OAEs is done using a tiny speaker and microphone that fit snugly inside the ear canal. The OAE response can be partially masked or reduced in amplitude by presenting competing acoustic stimuli contralaterally (opposite ear), ipsilaterally (same ear), or both. This masking effect is caused by activation of neural efferent pathways from the brain. Neural effects, including evoked responses such as auditory brainstem responses and axonal transmission latencies, are known to correlate with glucose. This suggests that masked OAEs may correlate with glucose since masking is a result of neural activity, and neural activity is affected by glucose levels. Prior to our research, no studies have investigated the correlation of masked OAEs with blood glucose. In this paper we present our preliminary findings, including experimental results that suggest a correlation with blood glucose levels.

Hearing loss affects 31 million Americans, particularly veterans who were exposed to harmful levels of noise during military functions. Many veterans also receive treatment with ototoxic medications, which may exacerbate preexisting hearing loss. Thus, hearing loss is the most common and tinnitus the third most common service-connected disability among veterans. Poor implementation of hearing protection programs and a lack of audiometric testing during medical treatment leave veterans vulnerable to unrecognized and untreated hearing loss until speech communication is impaired. Individualized audiometric testing techniques, including assessment of high frequencies, can be used in clinical and occupational settings to detect early hearing loss. Antioxidants also may alleviate cochlear damage caused by noise and ototoxicity. Ultimately, hearing loss prevention requires education on reducing occupational and recreational noise exposure and counseling on the risks and options available to patients. Technological advances will improve monitoring, allow better noise engineering controls, and lead to more effective hearing protection.

Ototoxic hearing loss is usually detected earliest through monitoring of the highest audible frequencies in individuals administered ototoxic medications. Conducting ototoxicity monitoring may require testing patients in the hospital room. This study evaluated the use of insert earphones for obtaining reliable threshold responses at bedside. Twenty adult subjects were tested during two different sessions in the sound booth and on the ward. Thresholds were obtained for frequencies from 5 to 16 kHz and at 2 kHz with the use of the KOSS Pro/4X Plus earphones and Etymotic ER-4B MicroPro insert earphones. Results indicate that ER-4B insert earphones are as reliable as KOSS earphones for testing on the ward for high-frequency ototoxicity monitoring.

Time-frequency representations (TFRs) of otoacoustic emissions (OAEs) provide information simultaneously in time and frequency that may be obscured in waveform or spectral analyses. TFRs were applied to transient-evoked stimulus-frequency (SF) and distortion-product (DP) OAEs to test cochlear model predictions. SFOAEs and DPOAEs were elicited in 18 normal-hearing subjects using gated tones and tone pips. Synchronous spontaneous (SS) OAEs were measured to assess their contributions to SFOAEs and DPOAEs. A common form of TFR of measured OAEs was a collection of frequency-specific components often aligned with SSOAE sites, with each component characterized by one or more brief segments or a single long-duration segment. The spectral envelope of evoked OAEs differed from that of the evoking stimulus. Strong emission regions or cochlear "hot spots" were detected, and sometimes accounted for OAE energy observed outside the stimulus bandwidth. Contributions of hot spots and multiple internal reflections to the OAE, and differences between measured and predicted OAE spectra, increased as stimulus level decreased, consistent with level-dependent changes in the estimated cochlear reflectance. Suppression and frequency-pulling effects between components were observed. A recursive formulation was described for the linear coherent reflection emission theory [Zweig and Shera, J. Acoust. Soc. Am. 98, 2018-2047 (1995)] that is well suited for time-domain calculations.

DPOAE sources are modeled by intermodulation distortion generated near the f2 place and a reflection of this distortion near the DP place. In a previous paper, inverse fast Fourier transforms (IFFTs) of DPOAE filter functions in normal ears were consistent with this model [Konrad-Martin et al., J. Acoust. Soc. Am. 109, 2862-2879 (2001)]. In the present article, similar measurements were made in ears with specific hearing-loss configurations. It was hypothesized that hearing loss at f2 or DP frequencies would influence the relative contributions to the DPOAE from the corresponding basilar membrane places, and would affect the relative magnitudes of SFOAEs at frequencies equal to f2 and fDP. DPOAEs were measured with f2 = 4 kHz, f1 varied, and a suppressor near fDP. L2 was 25-55 dB SPL (L1 = L2 + 10 dB). SFOAEs were measured at f2 and at 2.7 kHz (the average fDP produced by the f1 sweep) for stimulus levels of 20-60 dB SPL. SFOAE results supported predictions of the pattern of amplitude differences between SFOAEs at 4 and 2.7 kHz for sloping losses, but did not support predictions for the rising- and flat-loss categories. Unsuppressed IFFTs for rising losses typically had one peak. IFFTs for flat or sloping losses typically have two or more peaks; later peaks were more prominent in ears with sloping losses compared to normal ears. Specific predictions were unambiguously supported by the results for only four of ten cases, and were generally supported in two additional cases. Therefore, the relative contributions of the two DPOAE sources often were abnormal in impaired ears, but not always in the predicted manner.

DPOAE input/output (I/O) functions were measured at 7f2 frequencies (1 to 8 kHz; f2/f1 = 1.22) over a range of levels (-5 to 95 dB SPL) in normal-hearing and hearing-impaired human ears. L1-L2 was level dependent in order to produce the largest 2f1-f2 responses in normal ears. System distortion was determined by collecting DP data in six different acoustic cavities. These data were used to derive a multiple linear regression model to predict system distortion levels. The model was tested on cochlear-implant users and used to estimate system distortion in all other ears. At most but not all f2's, measurements in cochlear implant ears were consistent with model predictions. At all f2 frequencies, the ears with normal auditory thresholds produced I/O functions characterized by compressive nonlinear regions at moderate levels, with more rapid growth at low and high stimulus levels. As auditory threshold increased, DPOAE threshold increased, accompanied by DPOAE amplitude reductions, notably over the range of levels where normal ears showed compression. The slope of the I/O function was steeper in impaired ears. The data from normal-hearing ears resembled direct measurements of basilar membrane displacement in lower animals. Data from ears with hearing loss showed that the compressive region was affected by cochlear damage; however, responses at high levels of stimulation resembled those observed in normal ears.

An objective method for identifying ototoxic hearing loss among patients receiving cisplatin is necessary since the ability of patients to take a behavioral test may change over the course of treatment. Data from 56 monitoring visits by 19 Veterans taking cisplatin were used to identify combinations of distortion-product otoacoustic emission DPOAE metrics and ototoxicity risk factors that best identified ototoxic hearing loss. Models were tested that incorporated DPOAE metrics generated statistically using partial least-squares analysis. Models were also tested that incorporated a priori DPOAE change criteria, such as a minimum DPOAE level shift of 6 dB. Receiver Operating Characteristic analysis was used to compare the accuracy of these models. The best performing model incorporated weighted combinations of pre-treatment hearing, cumulative cisplatin dose and DPOAE metrics that were determined using partial least-squares and evaluated over a quarter octave range near each subjects’ high frequency DPOAE limit. Using this model and the DPOAE recording methods described herein, the chance of ototoxic hearing change can be determined at any given observed change in DPOAE level. This approach appears to provide an accurate and rapid ototoxicity risk assessment ORA that once validated can be used clinically. DOI: 10.1121/1.3473693