Intratympanic gentamicin treatment for Ménière's disease: A randomized, double-blind, placebo-controlled trial on dose efficacy - results of a prematurely ended study

Background: Gentamicin is used as a therapeutic agent for Ménière's disease because of its vestibulotoxicity causing chemo-ablation of the vestibular sensory epithelia. Its use has increased in recent years. However, there is still no consensus about the dose regimen of gentamicin in the treatment of Ménière's disease. In this study two different dose regimen treatment protocols are compared in a placebo controlled study design. The primary objective is to quantify the treatment effect on dizziness, the secondary objective is hearing evaluation.Methods: We performed a randomized, double-blind, placebo-controlled study in adults with unilateral Ménière's disease according to the AAO-HNS guidelines resistant to conservative medication. Three groups received four injections, administered weekly (four intratympanic injections with 40 mg/mL gentamicin solution, two injections gentamicin solution and two injections of placebo in random order, or four injections with placebo). Outcome measures were the score on the Dizziness Handicap Inventory and pure tone audiometry (PTA). Intended follow-up was 2 years.Results: During follow-up one patient exceeded the accepted amount of hearing loss. Further, enrollment was very slow (until 12 months between two patients) and new insights showed an apparent benefit of intratympanic gentamicin treatment (ITG). Therefore we performed an unscheduled interim analysis which showed that PTA threshold shifts reached the stopping criteria in two more patients. Because of this, this study was ended. Of the three patients with the significant PTA threshold shift two were enrolled in the gentamicin group.Conclusion: No conclusions can be drawn concerning doses regimens. Now that new publications have shown that ITG treatment can be an effective and safe treatment, a placebo-controlled randomized controlled trial may not pass the ethical committee because of these recent reports in literature. Still, a dose regimen study (without placebo) on ITG treatment needs to be performed.Trial registration: This trial was registered in The University Medical Center Utrecht/ Gelre hospital Apeldoorn. Protocol ID: 07/343, EudraCT number 2006-005913-37

Short-term outcomes of cochlear implantation for single-sided deafness compared to bone conduction devices and contralateral routing of sound hearing aids—Results of a Randomised controlled trial (CINGLE-trial)

Single-sided deafness (SSD) leads to difficulties with speech perception in noise, sound localisation, and sometimes tinnitus. Current treatments (Contralateral Routing of Sound hearing aids (CROS) and Bone Conduction Devices (BCD)) do not sufficiently overcome these problems. Cochlear implants (CIs) may help. Our aim was to evaluate these treatments in a Randomised Controlled Trial (RCT). Adult SSD patients were randomised using a web-based randomisation tool into one of three groups: CI; trial period of ‘first BCD, then CROS’; trial period of ‘first CROS, then BCD’. After these trial periods, patients opted for BCD, CROS, or No treatment. The primary outcome was speech perception in noise (directed from the front (S0N0)). Secondary outcomes were speech perception in noise with speech directed to the poor ear and noise to the better ear (SpeNbe) and vice versa (SbeNpe), sound localisation, tinnitus burden, and disease-specific quality of life (QoL). We described results at baseline (unaided situation) and 3 and 6 months after device activation. 120 patients were randomised. Seven patients did not receive the allocated intervention. The number of patients per group after allocation was: CI (n = 28), BCD (n = 25), CROS (n = 34), and No treatment (n = 26). In S0N0, the CI group performed significantly better when compared to baseline, and when compared to the other groups. In SpeNbe, there was an advantage for all treatment groups compared to baseline. However, in SbeNpe, BCD and CROS groups performed worse compared to baseline, whereas the CI group improved. Only in the CI group sound localisation improved and tinnitus burden decreased. In general, all treatment groups improved on disease-specific QoL compared to baseline. This RCT demonstrates that cochlear implantation for SSD leads to improved speech perception in noise, sound localisation, tinnitus burden, and QoL after 3 and 6 months of follow-up. For most outcome measures, CI outperformed BCD and CROS. Trial registration: Netherlands Trial Register (www.trialregister.nl): NTR4580, CINGLE-trial

Tinnitus reduction in patients with single-sided deafness: the effect of cochlear implantation, bone conduction devices, and contralateral routing of sound hearing aids investigated in a randomized controlled trial

Objectives: Single-sided deafness (SSD) is often accompanied by tinnitus, resulting in a decreased quality of life. Currently, there is a lack of high level of evidence studies comparing different treatment options for SSD regarding tinnitus reduction. This randomized controlled trial (RCT) evaluated the effect of a cochlear implant (CI), bone conduction device (BCD), contralateral routing of sound (CROS), and no treatment on tinnitus outcomes in SSD patients, with follow-up extending to 24 months. Methods: A total of 120 adult SSD patients were randomized to three groups: CI, a trial period with first a BCD on a headband, then a CROS, or vice versa. After the trial periods, patients opted for a BCD, CROS, or no treatment. At the start of follow-up, 28 patients were implanted with a CI, 25 patients with a BCD, 34 patients had a CROS, and 26 patients chose no treatment. The Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), the Visual Analog Scale (VAS), and the Hospital Anxiety and Depression Scale (HADS) were completed at baseline and at 3, 6, 12, and 24 months of follow-up. Results: The CI and BCD groups showed significantly decreased tinnitus impact scores. The CI group showed the largest decrease, which was already observed at 3 months of follow-up. Compared to the baseline, the median THI score decreased by 23 points, the TQ score by 17 points, and the VAS score by 60 points at 24 months. In the BCD group, the TQ score decreased by 9 points, and the VAS decreased by 25 points at 24 months. The HADS anxiety and depression subscale showed no indication for anxiety or depression at baseline, nor at 24 months, for all groups. Conclusion: In this RCT, SSD patients treated with a CI or BCD showed an overall decrease in tinnitus impact scores up to 24 months compared to baseline. The CI group reported a stable and the largest reduction. Cochlear implants appear to be superior to BCD and CROS, and no treatment for achieving partial or complete resolution of tinnitus in patients with SSD. Clinical trial registration: Netherlands Trial Register, www.onderzoekmetmensen.nl/nl/trial/26952, NTR4457, CINGLE trial

Oorzaak en gevolg

In de komende drie kwartier ga ik met u enkele onderwerpen bespreken die gaan over het gehoor, gehoorverlies en de revalidatie van ernstige slechthorendheid. Ik zal mijn visie geven op waar wij in de toekomst het onderzoek betreffende het gehoor op zullen richten. Kortom, ik ga het hebben over oorzaak en gevolg. Tevens wil ik met u bespreken hoe de afdeling Keel-, Neus- en Oorheelkunde van het UMC Utrecht telemedicine gebruikt om de oorchirurgie aan (toekomstige) collega’s uit te leggen en hoe deze multimediatechnieken het onderwijs zullen gaan veranderen. Voor mij is dit een onderwerp dat door mijn recente aanstelling door de Raad van Bestuur van het UMC Utrecht als manager onderzoek en onderwijs van de Divisie Heelkundige Specialismen (DHS) nog actueler is geworden

First experience with a new stapes clip piston in stapedotomy

Objective: Hearing results after 23 implantations of a newly designed titanium-clip stapes piston prosthesis (the aWengen Clip Piston prosthesis) in patients with otosclerosis were evaluated. This new type of stapes piston was designed to avoid the crimping onto the incus in stapedotomy. This one clip fits all designs and enables solid fixation by clicking the prosthesis onto the long process of the incus without crimping. Study Design: A retrospective pilot study was carried out by microcomputer of the preoperative and postoperative audiological results of patients in whom the titanium-clip stapes piston prosthesis was implanted. Setting: Ear, nose and throat department of Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Patients: 23 Patients underwent a stapedotomy for hearing improvement suffering from otosclerosis. implantations of a newly designed titanium-clip stapes piston prosthesis (the aWengen Clip Piston prosthesis) in patients with otosclerosis were evaluated. Intervention(s): The stapedotomy was performed with the aWengen Clip Piston prosthesis. Main Outcome Measure(s): Pre and postoperative audiograms were used to evaluate the hearing gain improvement with the new stapes piston. Especially we looked at the airbone gap Closure and the sensorineural hearing after the surgical procedure and compared these with the ones before surgery. Results: The hearing results showed a closure of the pure-tone average air-bone gap to within 10 dB in 56.6% of cases (10 of 23 implantations) and to within 20 dB in 100% (23 of 23 implantations). A residual air-bone gap of greater than 20 dB was seen in the present pilot study. Postoperative overclosure of bone-conduction thresholds was discovered only for the frequency of 2 kHz. Sensorineural hearing loss greater than 10% did not occur, and there was no decline in the speech discrimination. Conclusions: The use of a newly designed titanium-clip stapes piston prosthesis with a diameter of 0.4 mm gives good results in cases of stapedotomy for otosclerosis. The titanium-clip design is a new development in the evolution of stapes piston prostheses. Surgical introduction, placement, and fixation are not always easy, depending on the anatomy of the middle ear and the thickness of the fixation area on the long process of the incu

Development and realization of an artificial patient with hearing impairment

The paper proposes a narrowband stochastic system model for auditory signal processing. The parameters are ipsilateral, contralateral and interaural hearing losses, false positive and false negative responses, and patient response time. The auditory model is then used to realize a patient simulator (artificial patient), comprising out of two microphones, a skull simulator, sound cards and a noiseless personal computer. A locally stored database contains the simulated and the recorded patient data. First field trials in an audiometric test room at the University Medical Center, Utrecht, The Netherlands, indicate that the artificial patient resembles the behavior of a real patient within a band of 10 dB-HL over the entire audiometric frequency range