Fundamental Concepts for Assessment and Interpretation of Wideband Acoustic Immittance Measurements.

Assessment of middle ear impedance using noninvasive electroacoustic measurements has undergone successive developments since its first clinical application in the 1940s, and gained widespread adoption since the 1970s in the form of 226-Hz tympanometry, and applications in multifrequency tympanometry. More recently, wideband acoustic immittance (WAI) is allowing unprecedented assessments of the middle ear acoustic mechanics thanks to the ability to record responses over a wide range of frequencies. The purpose of this article is to present fundamental concepts for the assessment and interpretation of wideband measures, including a review of acoustic impedance and its relation to the mass, stiffness, and resistance components of the middle ear. Additionally, an understanding of the middle ear transfer function reveals the relationship between impedance and middle-ear gain as a function of frequency. Wideband power absorbance, a WAI measure, quantifies the efficiency of sound conduction through the middle ear over a wide range of frequencies, and can serve as an analogous clinical measure to the transfer function. The interpretation of absorbance measures in ears with or without a conductive condition using absorbance measured at ambient pressure and pressurized conditions (wideband tympanometry) is described using clinical case examples. This article serves as an introduction to the fundamental principles of WAI measurements.

Wideband Acoustic Reflex Measurement.

Acoustic reflex thresholds (ART) obtained using pure-tone probe stimuli as part of a traditional immittance test battery can be used to evaluate site of lesion and provide a cross-check with behavioral results. ARTs obtained as part of a wideband acoustic immittance (WAI) test battery using a click as the probe stimulus can be used in the same way with the added benefit that they may provide lower ARTs than those obtained using a pure-tone probe. Another benefit of the WAI ART test is that it can be completed without requiring a hermetic seal or pressurizing the ear canal. A new adaptive method of obtaining ARTs using WAI techniques may cut test time in half, thus making this an attractive option for future clinical use. More advanced uses of WAI ART tests include the measurement of AR growth functions. These may be used to investigate the possible effects of synaptopathy related to high levels of noise exposure and possible auditory deficits related to ototoxicity.

Automated Adaptive Wideband Acoustic Stapedius Reflex Thresholds in Adults With Normal Hearing and Sensorineural Hearing Loss.

OBJECTIVES: This study compared the measurement of the acoustic stapedius reflex threshold (ART) obtained using a traditional method with that obtained using an automated adaptive wideband (AAW) method. Participants included three groups of adults with normal hearing (NH), mild sensorineural hearing loss (SNHL), or moderate SNHL. The purpose of the study was to compare ARTs for the three groups and to determine which method had the best performance in detecting SNHL. DESIGN: Ipsilateral and contralateral ARTs were obtained using 0.5, 1, and 2 kHz tonal activators, and broadband noise (BBN) activators on a traditional admittance system (Clinical) at tympanometric peak pressures (TPP) and on an experimental wideband system using an AAW method at both ambient pressure and TPP. ART data previously reported for 39 NH adults with a mean age of 47.7 years were compared with data for 25 participants with mild SNHL with a mean age of 63.8 years, and 20 participants with moderate SNHL with a mean age of 65.7 years. Differences in ARTs between the normal-hearing and SNHL groups for the three methods were examined using a General Linear Model Repeated-Measures test. A receiver operating characteristic curve (ROC) analysis was also used to determine the ability of an ART test to detect SNHL. RESULTS: For the 0.5 kHz activator condition, there were no significant group mean differences in ART between NH and SNHL groups for either ipsilateral or contralateral activator presentation modes for the Clinical or AAW methods. There were significant group mean differences for the 1 and 2 kHz tonal activators and BBN activator for both ipsilateral and contralateral modes with greater differences in ART between groups for the AAW method than the Clinical method. In these conditions, the mean ART was lower for the AAW tests relative to the Clinical test. The greatest difference between groups was for the ipsilateral AAW tests for the comparison of NH with moderate SNHL for the BBN activator. This difference was approximately 20 dB for the AAW tests and 8 dB for the Clinical test. The ROC analysis showed that the area under the ROC curve (AUC) increased with the frequency of the activator stimulus and with the degree of hearing loss and was maximal for the BBN activator for both the AAW and Clinical methods for both ipsilateral and contralateral presentations. CONCLUSIONS: For ipsilateral and contralateral ART tests for activator frequencies above 0.5 kHz and BBN, listeners with SNHL generally had elevated ARTs compared with those with NH. The AAW method resulted in greater differences between SNHL groups and NH than the Clinical method. The AUC for detecting SNHL also increased with activator frequency and degree of hearing loss and was greatest for the BBN activator for the AAW method in both the ambient and TPP conditions. The results are encouraging for the use of an AAW ART method for the assessment of individuals with SNHL.

The Impacts of Noise Exposure on the Middle Ear Muscle Reflex in a Veteran Population.

PURPOSE: Human studies of noise-induced cochlear synaptopathy using physiological indicators identified in animal models (auditory brainstem response [ABR] Wave I amplitude, envelope following response [EFR], and middle ear muscle reflex [MEMR]) have yielded mixed findings. Differences in the population studied may have contributed to the differing results. For example, due to differences in the intensity level of the noise exposure, noise-induced synaptopathy may be easier to detect in a military Veteran population than in populations with recreational noise exposure. We previously demonstrated a reduction in ABR Wave I amplitude and EFR magnitude for young Veterans with normal audiograms reporting high levels of noise exposure compared to non-Veteran controls. In this article, we expand on the previous analysis in the same population to determine if MEMR magnitude is similarly reduced. METHOD: Contralateral MEMR growth functions were obtained in 92 young Veterans and non-Veterans with normal audiograms, and the relationship between noise exposure history and MEMR magnitude was assessed. Associations between MEMR magnitude and distortion product otoacoustic emission, EFR, and ABR measurements collected in the same sample were also evaluated. RESULTS: The results of the statistical analysis, although not conventionally statistically significant, suggest a reduction in mean MEMR magnitude for Veterans reporting high noise exposure compared with non-Veteran controls. In addition, the MEMR appears relatively insensitive to subclinical outer hair cell dysfunction, as measured by distortion product otoacoustic emissions, and is not well correlated with ABR and EFR measurements. CONCLUSIONS: When combined with our previous ABR and EFR findings in the same population, these results suggest that noise-induced synaptopathy occurs in humans. In addition, the findings indicate that the MEMR may be a good candidate for noninvasive diagnosis of cochlear synaptopathy/deafferentation and that the MEMR may reflect the integrity of different neural populations than the ABR and EFR. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.18665645.

Automated Adaptive Wideband Acoustic Reflex Threshold Estimation in Normal-hearing Adults.

OBJECTIVES: Acoustic stapedius reflex threshold (ART) tests are included in a standard clinical acoustic immittance test battery as an objective cross-check with behavioral results and to help identify site of lesion. In traditional clinical test batteries, middle-ear admittance of a 226 Hz probe is estimated using ear-canal measurements in the presence of a reflex-activating stimulus. In the wideband (WB) acoustic immittance ART test used in this study, the pure-tone probe is replaced by a WB probe stimulus and changes in absorbed power are estimated using ear-canal measurements in the presence of the activator. The ART is defined as the lowest level at which a criterion change in admittance (clinical) or absorbed power (WB) is observed in the presence of the activator. In the present study, ARTs were obtained in adults with normal hearing using the clinical, manual method and with a new WB automated adaptive threshold detection method. It was hypothesized that the WB test would result in lower ARTs than the clinical test because reflex-related changes in power absorbance could be observed across multiple frequency bands in the WB test compared with a single frequency in the traditional test. DESIGN: Data were collected in a prospective research design. ARTs were obtained in ipsilateral and contralateral conditions using 500, 1000, 2000 Hz, and broadband noise (BBN) activators on a clinical system and on an experimental WB system. The bandwidth of the BBN activator was 125 to 4000 Hz on the clinical system and 200 to 8000 Hz on the wideband system. ARTs were estimated at both tympanometric peak pressure (TPP) and ambient pressure on the WB system. Data were collected in both ears of 39 adults (21 males) of mean age 47.7 years (range 23-72 years). Differences in ARTs among the three threshold estimation methods (clinical, WB at TPP, WB at ambient) were examined using the general linear model repeated measures test in SPSS. Post-hoc pairwise comparisons were completed with Bonferroni correction for multiple comparisons. Statistical significance was defined as p < 0.05 for all analyses. RESULTS: ARTs obtained on the WB system at TPP and ambient pressure were significantly lower than obtained on the clinical system. ARTs obtained on the WB system at TPP were significantly higher than at ambient pressure in the 500 and 2000 Hz ipsilateral conditions. CONCLUSIONS: WB automated adaptive ARTs in normal-hearing adults were lower than for clinical methods when measured at TPP and ambient pressure. Lower presentation levels required to estimate ART in the WB test may be more tolerable to patients. Patients with ARTs that are not present at the maximum level of a traditional reflex test may have present ARTs with a WB ART test, which may reduce the need to refer for additional testing for possible retrocochlear involvement. Automation of the test may allow clinicians more time to attend to the other requisite tasks of a hearing evaluation and make the system useful for telehealth applications.

Hearing Health Care Utilization Following Automated Hearing Screening.

BACKGROUND: The study examined follow-up rates for pursuing hearing health care (HHC) 6 to 8 months after participants self-administered one of three hearing screening methods: an automated method for testing of auditory sensitivity (AMTAS), a four-frequency pure-tone screener (FFS), or a digits-in-noise test (DIN), with and without the presentation of a 2-minute educational video about hearing. PURPOSE: The study aims to determine if the type of self-administered hearing screening method (with or without an educational video) affects HHC follow-up rates. RESEARCH DESIGN: The study is a randomized controlled trial of three automated hearing screening methods, plus control group, with and without an educational video. The control group completed questionnaires and provided follow-up data but did not undergo a hearing screening test. STUDY SAMPLE: The study sample includes 1,665 participants (mean age 50.8 years; 935 males) at two VA Medical Centers and at university and community centers in Portland, OR; Bay Pines, FL; Minneapolis, MN; Mauston, WI; and Columbus, OH. DATA COLLECTION AND ANALYSIS: HHC follow-up data at 6 to 8 months were obtained by contacting participants by phone or mail. Screening methods and participant characteristics were compared in relation to the probability of participants pursuing HHC during the follow-up period. RESULTS: The 2-minute educational video did not have a significant effect on HHC follow-up rates. When all participants who provided follow-up data are considered (n = 1012), the FFS was the only test that resulted in a significantly greater percentage of HHC follow-up (24.6%) compared with the control group (16.8%); p = 0.03. However, for participants who failed a hearing screening (n = 467), follow-up results for all screening methods were significantly greater than for controls. The FFS resulted in a greater probability for HHC follow-up overall than the other two screening methods. Moreover, veterans had higher follow-up rates for all screening methods than non-veterans. CONCLUSION: The FFS resulted in a greater HHC follow-up rate compared with the other screening methods. This self-administered test may be more motivational for HHC follow-up because participants who fail the screening are aware of sounds they could not hear which does not occur with adaptive assessments like AMTAS or the DIN test. It is likely that access to and reduced personal cost of audiological services for veterans contributed to higher HHC follow-up rates in this group compared with non-veteran participants.

Wideband Acoustic Reflex Growth in Adults With Cystic Fibrosis.

Purpose Individuals with cystic fibrosis (CF) are often treated with intravenous (IV) aminoglycoside (AG) antibiotics to manage life-threatening bacterial infections. Preclinical animal data suggest that, in addition to damaging cochlear hair cells, this class of antibiotics may cause cochlear synaptopathy and/or damage to higher auditory structures. The acoustic reflex growth function (ARGF) is a noninvasive, objective measure of neural function in the auditory system. A shallow ARGF (small reflex-induced changes in middle ear function with increasing elicitor level) has been associated with synaptopathy due to noise exposure in rodent and human studies. In this study, the ARGF was obtained in CF patients with normal hearing, some of whom have been treated with IV AGs, and a control group without CF. The hypothesis was that patients with IV-AG exposure would have a shallow ARGF due to cochlear synaptopathy caused by ototoxicity. Method Wideband ARGFs were examined in four groups of normal-hearing participants: a control group of 29 individuals without CF; and in 57 individuals with CF grouped by lifetime IV-AG exposure: 15 participants with no exposure, 21 with low exposure, and 21 with high exposure. Procedures included pure-tone audiometry, clinical immittance, wideband acoustic immittance battery, including ARGFs, and transient evoked otoacoustic emissions. Results CF subjects with normal pure-tone thresholds and either high or low lifetime IV-AG exposure had enhanced ARGFs compared to controls and CF participants without IV-AG exposure. The groups did not differ in transient evoked otoacoustic emission signal-to-noise ratio. Conclusion These results diverge from the shallow ARGF pattern observed in studies of noise-induced cochlear synaptopathy and are suggestive of a central mechanism of auditory dysfunction in patients with AG-induced ototoxicity.

Functional Impacts of Aminoglycoside Treatment on Speech Perception and Extended High-Frequency Hearing Loss in a Pediatric Cystic Fibrosis Cohort.

Purpose The purpose of this study is to better understand the prevalence of ototoxicity-related hearing loss and its functional impact on communication in a pediatric and young adult cohort with cystic fibrosis (CF) and individuals without CF (controls). Method We did an observational, cross-sectional investigation of hearing function in children, teens, and young adults with CF (n = 57, M = 15.0 years) who received intravenous aminoglycoside antibiotics and age- and gender-matched controls (n = 61, M = 14.6 years). Participants completed standard and extended high-frequency audiometry, middle ear measures, speech perception tests, and a hearing and balance questionnaire. Results Individuals with CF were 3-4 times more likely to report issues with hearing, balance, and tinnitus and performed significantly poorer on speech perception tasks compared to controls. A higher prevalence of hearing loss was observed in individuals with CF (57%) compared to controls (37%). CF and control groups had similar proportions of slight and mild hearing losses; however, individuals with CF were 7.6 times more likely to have moderate and greater degrees of hearing loss. Older participants displayed higher average extended high-frequency thresholds, with no effect of age on average standard frequency thresholds. Although middle ear dysfunction has not previously been reported to be more prevalent in CF, this study showed that 16% had conductive or mixed hearing loss and higher rates of previous otitis media and pressure equalization tube surgeries compared to controls. Conclusions Individuals with CF have a higher prevalence of conductive, mixed, and sensorineural hearing loss; poorer speech-in-noise performance; and higher rates of multiple symptoms associated with otologic disorders (tinnitus, hearing difficulty, dizziness, imbalance, and otitis media) compared to controls. Accordingly, children with CF should be asked about these symptoms and receive baseline hearing assessment(s) prior to treatment with potentially ototoxic medications and at regular intervals thereafter in order to provide otologic and audiologic treatment for hearing- and ear-related problems to improve communication functioning.

Effects of Otosclerosis on Middle Ear Function Assessed With Wideband Absorbance and Absorbed Power.

OBJECTIVE: Wideband absorbance and absorbed power were evaluated in a group of subjects with surgically confirmed otosclerosis (Oto group), mean age 51.6 years. This is the first use of absorbed power in the assessment of middle ear disorders. Results were compared with control data from two groups of adults, one with normal hearing (NH group) mean age of 31 years, and one that was age- and sex-matched with the Oto group and had sensorineural hearing loss (SNHL group). The goal was to assess group differences using absorbance and absorbed power, to determine test performance in detecting otosclerosis, and to evaluate preoperative and postoperative test results. DESIGN: Audiometric and wideband tests were performed over frequencies up to 8 kHz. The three groups were compared on wideband tests using analysis of variance to assess group mean differences. Receiver operating characteristic (ROC) curve analysis was also used to assess test accuracy at classifying ears as belonging to the Oto or control groups using the area under the ROC curve (AUC). A longitudinal design was used to compare preoperative and postoperative results at 3 and 6 months. RESULTS: There were significant mean differences in the wideband parameters between the Oto and control groups with generally lower absorbance and absorbed power for the Oto group at ambient and tympanometric peak pressure (TPP) depending on frequency. The SNHL group had more significant differences with the Oto group than did the NH group in the high frequencies for absorbed power at ambient pressure and tympanometric absorbed power at TPP, as well as for the tympanometric tails. The greatest accuracy for classifying ears as being in the Oto group or a control group was for absorbed power at ambient pressure at 0.71 kHz with an AUC of 0.81 comparing the Oto and NH groups. The greatest accuracy for an absorbance measure was for the comparison between the Oto and NH groups for the peak-to-negative tail condition with an AUC of 0.78. In contrast, the accuracy for classifying ears into the control or Oto groups for static acoustic admittance at 226 Hz was near chance performance, which is consistent with previous findings. There were significant mean differences between preoperative and postoperative tests for absorbance and absorbed power. CONCLUSIONS: Consistent with previous studies, wideband absorbance showed better sensitivity for detecting the effects of otosclerosis on middle ear function than static acoustic admittance at 226 Hz. This study showed that wideband absorbed power is similarly sensitive and may perform even better in some instances than absorbance at classifying ears as having otosclerosis. The use of a group that was age- and sex-matched to the Oto group generally resulted in greater differences between groups in the high frequencies for absorbed power, suggesting that age-related norms in adults may be useful for the wideband clinical applications. Absorbance and absorbed power appear useful for monitoring changes in middle ear function following surgery for otosclerosis.

The role of the oncostatin M/OSM receptor ß axis in activating dermal microvascular endothelial cells in systemic sclerosis.

BACKGROUND: Scleroderma (SSc) is a rare autoimmune disease characterized by vascular impairment and progressive fibrosis of the skin and other organs. Oncostatin M, a member of the IL-6 family, is elevated in SSc serum and was recognized as a significant player in various stages of fibrosis. The goal of this study was to assess the contribution of the OSM/OSMRß pathway to endothelial cell (EC) injury and activation in SSc. METHODS: IHC and IF were used to assess the distribution of OSM and OSMRß in SSc (n = 14) and healthy control (n = 7) skin biopsies. Cell culture experiments were performed in human dermal microvascular endothelial cells (HDMECs) and included mRNA and protein analysis, and cell migration and proliferation assays. Ex vivo skin organoid culture was used to evaluate the effect of OSM on perivascular fibrosis. RESULTS: OSMRß protein was elevated in dermal ECs and in fibroblasts of SSc patients. Treatments of HDMECs with OSM or IL-6+sIL-6R have demonstrated that both cytokines similarly stimulated proinflammatory genes and genes related to endothelial to mesenchymal transition (EndMT). OSM was more effective than IL-6+sIL-6R in inducing cell migration, while both treatments similarly induced cell proliferation. The effects of OSM were mediated via OSMRß and STAT3, while the LIFR did not contribute to these responses. Both OSM and IL-6+sIL-6R induced profibrotic gene expression in HDMECs, as well as expansion of the perivascular PDGFRß+ cells in the ex vivo human skin culture system. Additional studies in HDMECs showed that siRNA-mediated downregulation of FLI1 and its close homolog ERG resulted in increased expression of OSMRß in HDMECs. CONCLUSIONS: This work provides new insights into the role of the OSM/OSMRß axis in activation/injury of dermal ECs and supports the involvement of this pathway in SSc vascular disease.

Expert-Based Consensus on the Principles of Pavlik Harness Management of Developmental Dysplasia of the Hip.

Developmental dysplasia of the hip (DDH) is the most common orthopaedic disorder in newborns. While the Pavlik harness is one of the most frequently used treatments for DDH, there is immense variability in treatment parameters reported in the literature and in clinical practice, leading to difficulties in standardizing teaching and comparing outcomes. In the absence of definitive quantitative evidence for the optimal Pavlik harness management strategy for DDH, we addressed this problem by obtaining international expert-based consensus on the subject. METHODS: An initial list of items relevant to Pavlik harness treatment was derived by a review of the literature. Delphi methodology was used to guide serial rounds of surveying and obtaining feedback from content matter experts from the International Hip Dysplasia Institute (IHDI), which continued in the same manner until consensus based on standard statistical analysis was reached. This was followed by a corroboration of face validity to derive the final set of management principles. RESULTS: Four rounds of structured surveying were required to reach consensus. Following 2 rounds of peer review, and from an initial list of 66 items in 8 categories, we were able to derive 2 simplified, yet comprehensive, print-friendly tables consisting of 28 items in 8 categories to assist clinicians in managing DDH with a Pavlik harness. The tables contain principles of treatment initiation, application and follow-up of the harness, complications, weaning, and end-of-treatment decision-making as well as specific criteria based on the severity of the DDH. Furthermore, highly contentious items were identified as important areas of future study. CONCLUSIONS: We developed a comprehensive set of principles based on expert consensus to assist clinicians in the management of DDH using the Pavlik harness. This study also generated a list of the most controversial areas in the nonoperative management of DDH, which should be considered high priority for future study to further refine and optimize outcomes. LEVEL OF EVIDENCE: Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.

Enhancing Screening Systems to Facilitate Hearing-Healthcare Access: A Qualitative Study.

BACKGROUND: Although hearing loss is a common health issue, hearing healthcare (HHC) is poorly accessed. Screening to identify hearing loss is an important part of HHC access, specifically for those who screen positive for hearing loss and would benefit from seeing a HHC provider. New technologies can be automated to provide information and recommendations that are tailored to the needs of individual users, potentially enhancing rates of HHC access after positive screens. A greater understanding of the facilitators of postscreening HHC access that could be leveraged in such systems is needed. PURPOSE: The purpose of this project was to identify facilitators of postscreening HHC access that can be used in automated screening systems. RESEARCH DESIGN: This qualitative study used focus groups (FGs) to understand perceived barriers, perceived benefits, and potential cues to action, as informed by the Health Belief Model, for accessing HHC after use of automated hearing screening systems. STUDY SAMPLE: Fifty individuals participated in one of seven FGs. FGs were conducted separately with three types of stakeholders: four FGs included adults who reported some degree of perceived hearing loss and had recently completed a hearing screening; two FGs included adults who had recently sought HHC for the first time because of hearing loss; and one FG involved significant others/family members of individuals with hearing loss. DATA COLLECTION AND ANALYSIS: FGs were 60-90 minutes in length and were led by a trained facilitator following a discussion guide. A research audiologist was present at each FG and served as a notetaker. FGs were recorded and transcribed by research team members, and transcripts were then coded in an iterative process by multiple team members. Qualitative content analysis was used to reduce data and to identify salient themes and subthemes, following an inductive approach. We focused on identifying themes that were related to facilitators of HHC access after positive screens for hearing loss and, separately, potential enhancements to automated hearing screening systems that would leverage these facilitators to improve HHC access. RESULTS: We identified five key themes related to HHC access after a positive screen for hearing loss, along with ideas for enhancing automated hearing screening systems based on these themes. The themes included knowledge, trust, access, quality of life, and interpersonal influence. CONCLUSIONS: The results of our work help inform the development of innovative hearing screening systems that can be automated to leverage individual facilitators of HHC access.

High frequency transient-evoked otoacoustic emission measurements using chirp and click stimuli.

Transient-evoked otoacoustic emissions (TEOAEs) at high frequencies are a non-invasive physiological test of basilar membrane mechanics at the basal end, and have clinical potential to detect risk of hearing loss related to outer-hair-cell dysfunction. Using stimuli with constant incident pressure across frequency, TEOAEs were measured in experiment 1 at low frequencies (0.7-8 kHz) and high frequencies (7.1-14.7 kHz) in adults with normal hearing up to 8 kHz and varying hearing levels from 9 to 16 kHz. In combination with click stimuli, chirp stimuli were used with slow, medium and fast sweep rates for which the local frequency increased or decreased with time. Chirp TEOAEs were transformed into equivalent click TEOAEs by inverse filtering out chirp stimulus phase, and analyzed similarly to click TEOAEs. To improve detection above 8 kHz, TEOAEs were measured in experiment 2 with higher-level stimuli and longer averaging times. These changes increased the TEOAE signal-to-noise ratio (SNR) by 10 dB. Slower sweep rates were investigated but the elicited TEOAEs were detected in fewer ears compared to faster rates. Data were acquired in adults and children (age 11-17 y), including children with cystic fibrosis (CF) treated with ototoxic antibiotics. Test-retest measurements revealed satisfactory repeatability of high-frequency TEOAE SNR (median of 1.3 dB) and coherence synchrony measure, despite small test-retest differences related to changes in forward and reverse transmission in the ear canal. The results suggest the potential use of such tests to screen for sensorineural hearing loss, including ototoxic loss. Experiment 2 was a feasibility study to explore TEOAE test parameters that might be used in a full-scale study to screen CF patients for risk of ototoxic hearing loss.

Cochlear Microphonic and Summating Potential Responses from Click-Evoked Auditory Brain Stem Responses in High-Risk and Normal Infants.

BACKGROUND: Examination of cochlear and neural potentials is necessary to assess sensory and neural status in infants, especially those cared for in neonatal intensive care units (NICU) who have high rates of hyperbilirubinemia and thus are at risk for auditory neuropathy (AN). PURPOSE: The purpose of this study was to determine whether recording parameters commonly used in click-evoked auditory brain stem response (ABR) are useful for recording cochlear microphonic (CM) and Wave I in infants at risk for AN. Specifically, we analyzed CM, summating potential (SP), and Waves I, III, and V. The overall aim was to compare latencies and amplitudes of evoked responses in infants cared for in NICUs with infants in a well-baby nursery (WBN), both of which passed newborn hearing screening. RESEARCH DESIGN: This is a prospective study in which infants who passed ABR newborn hearing screening were grouped based on their birth history (WBN and NICU). All infants had normal hearing status when tested with diagnostic ABR at about one month of age, corrected for prematurity. STUDY SAMPLE: Thirty infants (53 ears) from the WBN [mean corrected age at test = 5.0 weeks (wks.)] and thirty-two infants (59 ears) from the NICU (mean corrected age at test = 5.7 wks.) with normal hearing were included in this study. In addition, two infants were included as comparative case studies, one that was diagnosed with AN and another case that was diagnosed with bilateral sensorineural hearing loss (SNHL). DATA COLLECTION AND ANALYSIS: Diagnostic ABR, including click and tone-burst air- and bone-conduction stimuli were recorded. Peak Waves I, III, and V; SP; and CM latency and amplitude (peak to trough) were measured to determine if there were differences in ABR and electrocochleography (ECochG) variables between WBN and NICU infants. RESULTS: No significant group differences were found between WBN and NICU groups for ABR waveforms, CM, or SP, including amplitude and latency values. The majority (75%) of the NICU group had hyperbilirubinemia, but overall, they did not show evidence of effects in their ECochG or ABR responses when tested at about one-month corrected age. These data may serve as a normative sample for NICU and well infant ECochG and ABR latencies at one-month corrected age. Two infant case studies, one diagnosed with AN and another with SNHL demonstrated the complexity of using ECochG and otoacoustic emissions to assess the risk of AN in individual cases. CONCLUSIONS: CM and SPs can be readily measured using standard click stimuli in both well and NICU infants. Normative ranges for latency and amplitude are useful for interpreting ECochG and ABR components. Inclusion of ECochG and ABR tests in a test battery that also includes otoacoustic emission and acoustic reflex tests may provide a more refined assessment of the risks of AN and SNHL in infants.

Optimizing Clinical Interpretation of Distortion Product Otoacoustic Emissions in Infants.

OBJECTIVES: The purpose of this study was to analyze distortion product otoacoustic emission (DPOAE) level and signal to noise ratio in a group of infants from birth to 4 months of age to optimize prediction of hearing status. DPOAEs from infants with normal hearing (NH) and hearing loss (HL) were used to predict the presence of conductive HL (CHL), sensorineural HL (SNHL), and mixed HL (MHL). Wideband ambient absorbance was also measured and compared among the HL types. DESIGN: This is a prospective, longitudinal study of 279 infants with verified NH and HL, including conductive, sensorineural, and mixed types that were enrolled from a well-baby nursery and two neonatal intensive care units in Cincinnati, Ohio. At approximately 1 month of age, DPOAEs (1-8 kHz), wideband absorbance (0.25-8 kHz), and air and bone conduction diagnostic tone burst auditory brainstem response (0.5-4 kHz) thresholds were measured. Hearing status was verified at approximately 9 months of age with visual reinforcement audiometry (0.5-4 kHz). Auditory brainstem response air conduction thresholds were used to assign infants to an NH or HL group, and the efficacy of DPOAE data to classify ears as NH or HL was analyzed using receiver operating characteristic (ROC) curves. Two summary statistics of the ROC curve were calculated: the area under the ROC curve and the point of symmetry on the curve at which the sensitivity and specificity were equal. DPOAE level and signal to noise ratio cutoff values were defined at each frequency as the symmetry point on their respective ROC curve, and DPOAE results were combined across frequency in a multifrequency analysis to predict the presence of HL. RESULTS: Single-frequency test performance of DPOAEs was best at mid to high frequencies (3-8 kHz) with intermediate performance at 1.5 and 2 kHz and chance performance at 1 kHz. Infants with a conductive component to their HL (CHL and MHL combined) displayed significantly lower ambient absorbance values than the NH group. No differences in ambient absorbance were found between the NH and SNHL groups. Multifrequency analysis resulted in the best prediction of HL for the SNHL/MHL group with poorer sensitivity values when infants with CHL were included. CONCLUSIONS: Clinical interpretation of DPOAEs in infants can be improved by using age-appropriate normative ranges and optimized cutoff values. DPOAE interpretation is most predictive at higher F2 test frequencies in young infants (2-8 kHz) due to poor test performance at 1 to 1.5 kHz. Multifrequency rules can be used to improve sensitivity while balancing specificity. Last, a sensitive middle ear measure such as wideband absorbance should be included in the test battery to assess possibility of a conductive component to the HL.

Pressurized transient otoacoustic emissions measured using click and chirp stimuli.

Transient-evoked otoacoustic emission (TEOAE) responses were measured in normal-hearing adult ears over frequencies from 0.7 to 8 kHz, and analyzed with reflectance/admittance data to measure absorbed sound power and the tympanometric peak pressure (TPP). The mean TPP was close to ambient. TEOAEs were measured in the ear canal at ambient pressure, TPP, and fixed air pressures from 150 to -200 daPa. Both click and chirp stimuli were used to elicit TEOAEs, in which the incident sound pressure level was constant across frequency. TEOAE levels were similar at ambient and TPP, and for frequencies from 0.7 to 2.8 kHz decreased with increasing positive and negative pressures. At 4-8 kHz, TEOAE levels were larger at positive pressures. This asymmetry is possibly related to changes in mechanical transmission through the ossicular chain. The mean TEOAE group delay did not change with pressure, although small changes were observed in the mean instantaneous frequency and group spread. Chirp TEOAEs measured in an adult ear with Eustachian tube dysfunction and TPP of -165 daPa were more robust at TPP than at ambient. Overall, results demonstrate the feasibility and clinical potential of measuring TEOAEs at fixed pressures in the ear canal, which provide additional information relative to TEOAEs measured at ambient pressure.

Home Hearing Test: Within-Subjects Threshold Variability.

BACKGROUND: The Home Hearing Test (HHT) is an automated pure-tone threshold test that obtains an air conduction audiogram at five test frequencies. It was developed to provide increased access to hearing testing and support home telehealth programs. PURPOSE: Test and retest thresholds for 1000-Hz stimuli were analyzed to determine intrasubject variability from two independent data sets. RESEARCH DESIGN: Prospective, repeated measures. STUDY SAMPLE: In the Veterans Affairs (VA) study, results from 26 subjects 44 to 88 years of age (mean = 65) recruited from the Nashville VA audiology clinic were analyzed. Subjects were required to have a Windows PC in the home and were self-reported to be comfortable with using computers. Two subjects had normal hearing, and 24 had hearing losses of various severities and configurations. The National Center for Rehabilitative Auditory Research (NCRAR) sample included 100 subjects (68 males; 32 females) with a complaint of hearing difficulty recruited from the local community and Veteran population. Subjects ranged in age from 32 to 87 years (mean = 63.7 years). They were tested in a quiet room at the NCRAR. DATA COLLECTION AND ANALYSIS: Subjects in the VA study were provided kits for installing HHT on their home computers. HHT was installed on a computer at NCRAR to test subjects in the NCRAR study. HHT obtains a five-frequency air conduction audiogram with a retest of 1000 Hz in both ears. Only the 1000-Hz test-retest results are analyzed in this report. Six statistical measures of test-retest variability are reported. RESULTS: Test and retest thresholds were highly correlated in both studies (r ≥ 0.96). Test-retest differences were within ±5 dB ≥92% of the time in the two studies. Standard deviations of absolute test-retest difference were ≤3.5 dB in the two studies. CONCLUSIONS: Intrasubject variability is comparable to that obtained with manual testing by audiologists in sound-treated test rooms.

Longitudinal Development of Distortion Product Otoacoustic Emissions in Infants With Normal Hearing.

OBJECTIVES: The purpose of this study was to describe normal characteristics of distortion product otoacoustic emission (DPOAE) signal and noise level in a group of newborns and infants with normal hearing followed longitudinally from birth to 15 months of age. DESIGN: This is a prospective, longitudinal study of 231 infants who passed newborn hearing screening and were verified to have normal hearing. Infants were enrolled from a well-baby nursery and two neonatal intensive care units (NICUs) in Cincinnati, OH. Normal hearing was confirmed with threshold auditory brainstem response and visual reinforcement audiometry. DPOAEs were measured in up to four study visits over the first year after birth. Stimulus frequencies f1 and f2 were used with f2/f1 = 1.22, and the DPOAE was recorded at frequency 2f1-f2. A longitudinal repeated-measure linear mixed model design was used to study changes in DPOAE level and noise level as related to age, middle ear transfer, race, and NICU history. RESULTS: Significant changes in the DPOAE and noise levels occurred from birth to 12 months of age. DPOAE levels were the highest at 1 month of age. The largest decrease in DPOAE level occurred between 1 and 5 months of age in the mid to high frequencies (2 to 8 kHz) with minimal changes occurring between 6, 9, and 12 months of age. The decrease in DPOAE level was significantly related to a decrease in wideband absorbance at the same f2 frequencies. DPOAE noise level increased only slightly with age over the first year with the highest noise levels in the 12-month-old age range. Minor, nonsystematic effects for NICU history, race, and gestational age at birth were found, thus these results were generalizable to commonly seen clinical populations. CONCLUSIONS: DPOAE levels were related to wideband middle ear absorbance changes in this large sample of infants confirmed to have normal hearing at auditory brainstem response and visual reinforcement audiometry testing. This normative database can be used to evaluate clinical results from birth to 1 year of age. The distributions of DPOAE level and signal to noise ratio data reported herein across frequency and age in normal-hearing infants who were healthy or had NICU histories may be helpful to detect the presence of hearing loss in infants.

OV21/PETROC: a randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer.

Background: The purpose of this multistage, adaptively, designed randomized phase II study was to evaluate the role of intraperitoneal (i.p.) chemotherapy following neoadjuvant chemotherapy (NACT) and optimal debulking surgery in women with epithelial ovarian cancer (EOC). Patients and methods: We carried out a multicenter, two-stage, phase II trial. Eligible patients with stage IIB-IVA EOC treated with platinum-based intravenous (i.v.) NACT followed by optimal (<1 cm) debulking surgery were randomized to one of the three treatment arms: (i) i.v. carboplatin/paclitaxel, (ii) i.p. cisplatin plus i.v./i.p. paclitaxel, or (iii) i.p. carboplatin plus i.v./i.p. paclitaxel. The primary end point was 9-month progressive disease rate (PD9). Secondary end points included progression-free survival (PFS), overall survival (OS), toxicity, and quality of life (QOL). Results: Between 2009 and 2015, 275 patients were randomized; i.p. cisplatin containing arm did not progress beyond the first stage of the study after failing to meet the pre-set superiority rule. The final analysis compared i.v. carboplatin/paclitaxel (n = 101) with i.p. carboplatin, i.v./i.p. paclitaxel (n = 102). The intention to treat PD9 was lower in the i.p. carboplatin arm compared with the i.v. carboplatin arm: 24.5% (95% CI 16.2% to 32.9%) versus 38.6% (95% CI 29.1% to 48.1%) P = 0.065. The study was underpowered to detect differences in PFS: HR PFS 0.82 (95% CI 0.57-1.17); P = 0.27 and OS HR 0.80 (95% CI 0.47-1.35) P = 0.40. The i.p. carboplatin-based regimen was well tolerated with no reduction in QOL or increase in toxicity compared with i.v. administration alone. Conclusion: In women with stage IIIC or IVA EOC treated with NACT and optimal debulking surgery, i.p. carboplatin-based chemotherapy is well tolerated and associated with an improved PD9 compared with i.v. carboplatin-based chemotherapy. Clinical trial number: clinicaltrials.gov, NCT01622543.

Chirp-Evoked Otoacoustic Emissions and Middle Ear Absorbance for Monitoring Ototoxicity in Cystic Fibrosis Patients.

OBJECTIVES: The goal of this study was to investigate the use of transient-evoked otoacoustic emissions (TEOAEs) and middle ear absorbance measurements to monitor auditory function in patients with cystic fibrosis (CF) receiving ototoxic medications. TEOAEs were elicited with a chirp stimulus using an extended bandwidth (0.71 to 8 kHz) to measure cochlear function at higher frequencies than traditional TEOAEs. Absorbance over a wide bandwidth (0.25 to 8 kHz) provides information on middle ear function. The combination of these time-efficient measurements has the potential to identify early signs of ototoxic hearing loss. DESIGN: A longitudinal study design was used to monitor the hearing of 91 patients with CF (median age = 25 years; age range = 15 to 63 years) who received known ototoxic medications (e.g., tobramycin) to prevent or treat bacterial lung infections. Results were compared to 37 normally hearing young adults (median age = 32.5 years; age range = 18 to 65 years) without a history of CF or similar treatments. Clinical testing included 226-Hz tympanometry, pure-tone air-conduction threshold testing from 0.25 to 16 kHz and bone conduction from 0.25 to 4 kHz. Experimental testing included wideband absorbance at ambient and tympanometric peak pressure and TEOAEs in three stimulus conditions: at ambient pressure and at tympanometric peak pressure using a chirp stimulus with constant incident pressure level across frequency and at ambient pressure using a chirp stimulus with constant absorbed sound power across frequency. RESULTS: At the initial visit, behavioral audiometric results indicated that 76 of the 157 ears (48%) from patients with CF had normal hearing, whereas 81 of these ears (52%) had sensorineural hearing loss for at least one frequency. Seven ears from four patients had a confirmed behavioral change in hearing threshold for ≥3 visits during study participation. Receiver operating characteristic curve analyses demonstrated that all three TEOAE conditions were useful for distinguishing CF ears with normal hearing from ears with sensorineural hearing loss, with an area under the receiver operating characteristic curve values ranging from 0.78 to 0.92 across methods for frequency bands from 2.8 to 8 kHz. Case studies are presented to illustrate the relationship between changes in audiometric thresholds, TEOAEs, and absorbance across study visits. Absorbance measures permitted identification of potential middle ear dysfunction at 5.7 kHz in an ear that exhibited a temporary hearing loss. CONCLUSIONS: The joint use of TEOAEs and absorbance has the potential to explain fluctuations in audiometric thresholds due to changes in cochlear function, middle ear function, or both. These findings are encouraging for the joint use of TEOAE and wideband absorbance objective tests for monitoring ototoxicity, particularly, in patients who may be too ill for behavioral hearing tests. Additional longitudinal studies are needed in a larger number of CF patients receiving ototoxic drugs to further evaluate the clinical utility of these measures in an ototoxic monitoring program.