To evaluate the efficacy and safety of AM-111, a c-Jun N-terminal Kinase (JNK) ligand, in patients with acute sensorineural hearing loss (ASNHL). Prospective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 3, 7, 30, and 90. Twenty-five European sites (academic tertiary referral centers, private ENT practices). Approximately 210 patients aged 18 to 61 years presenting within 48 hours after acute acoustic trauma or idiopathic sudden sensorineural hearing loss with mean hearing loss of 30 dB or greater at the 3 most affected contiguous test frequencies. Single-dose intratympanic injection of AM-111 (0.4 or 2.0 mg/ml) or placebo; optionally, oral prednisolone if hearing improvement was less than 10 dB at Day 7. Efficacy was assessed by absolute hearing improvement (primary end point, Day 7), percentage hearing improvement, complete hearing recovery, speech discrimination improvement, and complete tinnitus remission. Safety was evaluated by the frequency of clinically relevant hearing deterioration and adverse events. The study failed to demonstrate a treatment benefit for the entire study population because mild-to-moderate ASNHL cases showed unexpectedly strong spontaneous recovery. In severe-to-profound ASNHL patients (threshold ≥60 dB), AM-111 0.4 mg/ml showed statistically significant, clinically relevant, and persistent improvements in hearing and speech discrimination and higher tinnitus remission compared with placebo. The study drug and the intratympanic injections were well tolerated. The study established proof of concept for AM-111 in the treatment of severe-to-profound ASNHL. Control for spontaneous hearing recovery is essential for ASNHL studies.

Objective The aim of this study was to evaluate the cochlear micromechanics and central auditory function in patients with type 1 diabetes mellitus and to identify the site of possible dysfunction. Methods Cochlear activity was evaluated by recording distortion product otoacoustic emissions (DPOAEs). DPOAEs were performed using an ILO 92 Otodynamics Analyser. Functional changes in the retrocochlear auditory pathway were evaluated by auditory brainstem responses (ABRs). DPOAEs and ABRs were measured in 42 normally hearing patients with type 1 diabetes mellitus aged 21 to 42 years, and 33 age-and sex-matched nondiabetic control subjects. Results Both of the groups (diabetic and control) had normal and undifferentiated results in tonal and impedance audiometry. ABR peripheral transmission time (wave I) and central transmission time (interpeak latencies I–V) were significantly delayed in the diabetic compared with normal subjects, and the mean amplitudes of various DPOAEs were significantly reduced in the diabetic patients compared with the control subjects. Conclusions Combined use of different procedures for monitoring central and peripheral portions of the auditory pathway in diabetic patients showed alterations in cochlear micromechanics and the retrocochlear auditory pathway. Hearing impairment in diabetic patients is usually mild and subclinical, and can be detected early by accurate and objective audiometric methods.

To evaluate the efficacy and safety of intratympanic AM-101 in patients with persistent acute inner ear tinnitus after acute acoustic trauma, idiopathic sudden sensorineural hearing loss (ISSNHL), or acute otitis media. Prospective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 7, 30, and 90. Twenty-eight European sites (academic tertiary referral centers and private ENT practices). 248 patients aged 16 to 65 years. Three intratympanic injections of AM-101 (0.27 or 0.81 mg/ml) or placebo over 3 consecutive days. Efficacy was assessed by changes in minimum masking level (MML; primary end point), loudness match, tinnitus loudness, tinnitus annoyance, and sleep difficulties on a 0 to 100 numerical rating scale, THI-12 questionnaire, and patient global impression of change. Safety was evaluated using the frequency of clinically relevant hearing deterioration and adverse events. The study overall failed to demonstrate a treatment benefit based on the change in MML. However, AM-101 0.81 mg/ml showed statistically significantly better improvement for tinnitus loudness, annoyance, sleep difficulties, and tinnitus impact in patients with tinnitus after noise trauma or otitis media. The subgroup of ISSNHL-related tinnitus patients did not show conclusive results. The study drug and I.T. injections were well tolerated. The study established proof of concept for AM-101 in the treatment of tinnitus arising from cochlear glutamate excitotoxicity. Patient-reported outcomes seem to be more relevant and reliable efficacy measures for assessing treatment-related changes in tinnitus than psychoacoustic tests.

Objective: To investigate the use of transtympanic electrocochleography (TT-ECochG) analyzed on-line by a detector strategy software that made possible automatic extraction of TT-ECochG components intraoperatively in real-time domain. Patients: Fifteen patients with cerebellopontine angle tumor among 50 patients were included in this study. Intervention: All subjects were operated on via middle fossa or retrosigmoid approach. Pure-tone average (PTA) was measured at 0.5, 1.0, and 2.0 kHz, and calculations were performed before and after surgery. Auditory function was monitored intraoperatively via TT-ECochG, and analyzed data were displayed on-line. Main Outcome Measures: TT-ECochG changes in morphology were described. Postoperative PTA elevation level correlated with TT-ECochG morphology changes occurring intraoperatively. Results: Analyzed on-line, TT-ECochG data were displayed as first negative peak of compound action potential amplitude and latency in time domain every 3 to 5 seconds. A good correlation between postoperative PTA elevation and TT-ECochG morphology changes was showed (Spearman rank test, R = +0.93; t_(N-2) = 9.00; p < 0.0001). Conclusion: TT-EcochG seemed to effectively mirror even minimal changes in auditory function during intraoperative monitoring in real-time domain. Developed strategy of on-line analysis makes the intraoperative hearing status assessment faster and easier.

In order to test the frequency specificity of the efferent suppressive effect on otoacoustic emissions, changes in the 2f1-f2 distortion product otoacoustic emission (DPOAE) levels induced by contralateral stimuli of different spectra were measured in 10 normally hearing adults. Three types of contralateral stimuli were used: (i) a set of 6 pairs of pure tones with the same frequencies as used for DPOAE stimulation; (ii) 6 narrow-band noise signals with cut-off frequencies equal to the frequencies of the primary tones used for DPOAE stimulation; and (iii) broad-band noise with a bandwidth of 840-6,000 Hz. A small suppressive effect was observed mainly in the mid-frequency region. Broad-band noise was more effective at suppressing DPOAEs than narrow-band noises and two-tone complexes. Occasionally, small enhancements in DPOAE amplitudes were observed. Based on the results of this study, it is concluded that DPOAE changes induced by contralateral stimuli are not frequency-specific, and are too small to have routine clinical value.

Background: In addition to the aging process, risk factors for hearing loss in adults include, among others, exposure to noise, use of ototoxic drugs, genetics, and limited access to medical care. Differences in exposure to these factors are bound to be reflected in the prevalence of hearing loss. Assessment of hearing loss can easily be carried out on a large scale and at low cost using mobile apps. Objective: This study aimed to conduct a worldwide assessment of the differences in hearing loss prevalence between countries in a group of mobile device users. Methods: Hearing tests were conducted using the open-access Android-based mobile app Hearing Test. The app is available free of charge in the Google Play store, provided that consent to the use of the results for scientific purposes is given. This study included hearing tests carried out on device models supported by the app with bundled headphones in the set. Calibration factors for supported models were determined using the biological method. The tests consisted of self-determining the quietest audible tone in the frequency range from 250 Hz to 8 kHz by adjusting its intensity using the buttons. The ambient noise level was optionally monitored using a built-in microphone. Following the test, the user could compare his hearing threshold against age norms by providing his or her age. The user's location was identified based on the phone’s IP address. Results: From November 23, 2016 to November 22, 2019, 733,716 hearing tests were conducted on 236,716 mobile devices across 212 countries. After rejecting the tests that were incomplete, performed with disconnected headphones, not meeting the time criterion, repeated by the same user, or carried out regularly on one device, 116,733 of 733,716 tests (15.9%) were qualified for further analysis. The prevalence of hearing loss, defined as the average threshold at frequencies 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz above 25 dB HL in the better ear, was calculated at 15.6% (95% CI 15.4-15.8). Statistically significant differences were found between countries (P<.001), with the highest prevalences for Bangladesh, Pakistan, and India (>28%) and the lowest prevalences for Taiwan, Finland, and South Korea (<11%). Conclusions: Hearing thresholds measured by means of mobile devices were congruent with the literature data on worldwide hearing loss prevalence. Uniform recruitment criteria simplify the comparison of the hearing loss prevalence across countries. Hearing testing on mobile devices may be a valid tool in epidemiological studies carried out on a large scale.