The multilingual digits-in-noise (DIN) test: development and evaluation.

OBJECTIVE: To develop a methodologically uniform digits-in-noise (DIN) test in 17 different languages. DESIGN: The DIN test was developed for Android devices as an extension to the open-access Hearing Test™ app, available on the Google Play store. It utilised professionally recorded female speech, speech-shaped noise, a digit scoring method and a variable step size. The test was adaptively optimised and evaluated as the results of tests taken online by users of the app became available. STUDY SAMPLE: Optimisation using 35,534 ears, evaluation using 6012 ears. RESULTS: Optimisation improved the slopes of the psychometric functions for all languages by an average of 6.8%/dB. Evaluation included calculation of normative speech reception thresholds (SRTs) and estimation of test-retest standard deviations. Normative values for SRTs ranged from -14.2 dB SNR (95% CI -14.3 to -14.0) for Chinese to -11.2 dB SNR (95% CI -11.3 to -11.1) for Japanese, with reliability estimates ranging from 0.48 dB (95% CI 0.36-0.64) for Portuguese to 0.91 dB (95% CI 0.73-1.21) for Romanian. CONCLUSIONS: The optimisation of each language version was confirmed by the improvement in the slopes of the psychometric functions. The normative values obtained from the test evaluation were in agreement with literature data. TRIAL REGISTRATION: Science Support Centre of Wroclaw Medical University BW-59/2020.

Intraoperative Hearing Monitoring Using ABR and TT-ECochG and Hearing Preservation during Vestibular Schwannoma Resection.

Background: Quick and appropriate diagnostics and the use of intraoperative monitoring (IM) of hearing during vestibular schwannoma (VS) resection increase the likelihood of hearing preservation. During surgery, various methods of IM can be used, i.e., auditory brainstem responses (ABRs), transtympanic electrocochleography (TT-ECochG), and direct cochlear nerve action potentials. The aim of the study was to evaluate the prognostic values of IM of hearing using ABR and TT-ECochG in predicting postoperative hearing preservation and to evaluate relationships between them during various stages of surgery. Methods: This retrospective study presents the pre- and postoperative audiological test results and IM of hearing records (TT-ECochG and ABR) in 75 (43 women, 32 men, aged 18-69) patients with diagnosed VS. Results: The preoperative pure tone average hearing threshold was 25.02 dB HL, while after VS resection, it worsened on average by 30.03 dB HL. According to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Hearing Classification, before and after (pre/post) surgery, there were 47/24 patients in hearing class A, 9/8 in B, 2/1 in C, and 17/42 in D. In speech audiometry, the average preoperative speech discrimination score at an intensity of 60 dB SPL was 70.93%, and after VS resection, it worsened to 38.93%. The analysis of electrophysiological tests showed that before the tumor removal the I-V ABR interlatencies was 5.06 ms, and after VS resection, it was 6.43 ms. Conclusions: The study revealed correlations between worse postoperative hearing and changes in intraoperatively measured ABR and TT-ECochG. IM of hearing is very useful in predicting postoperative hearing in VS patients and increases the chance of postoperative hearing preservation in these patients.

Handheld laser-fiber vibrometry probe for assessing auditory ossicles displacement (Erratum).

The erratum corrects an author affiliation.

Handheld laser-fiber vibrometry probe for assessing auditory ossicles displacement.

SIGNIFICANCE: Measurements of auditory ossicles displacement are commonly carried out by means of laser-Doppler vibrometry (LDV), which is considered to be a gold standard. The limitation of the LDV method, especially for in vivo measurements, is the necessity to expose an object in a straight line to a laser beam operating from a distance. An alternative to this approach is the use of a handheld laser-fiber vibrometry probe (HLFVP) with a curved tip. AIM: We evaluate the feasibility of an HLFVP with a curved tip for measuring sound-induced displacement of the auditory ossicles. APPROACH: A handheld vibrometer probe guiding the laser beam with a fiber-optic cable was used for displacement measurements of the incus body and the posterior crus of the stapes. Tonal stimuli at frequencies of 0.5, 1, 2, and 4 kHz were presented by means of an insert earphone positioned in the outer ear canal. The probe was fixed at the measurement site using a tripod or hand-held by one of the two surgeons. RESULTS: The measurements were carried out on six fresh temporal bones. Multivariate analysis of variance showed statistically significant differences for stimulus frequency (F3,143 = 29.37, p < 0.001, and η2 = 0.35), bone (F5,143 = 4.61, p = 0.001, and η2 = 0.01), and measurement site (F1,143 = 4.74, p = 0.03, and η2 = 0.02) in the absence of statistically significant differences for the probe fixation method (F2,143 = 0.15, p = 0.862, and η2 = 0.001). Standard deviations of the means were 6.9, 2.6, 1.9, and 0.6 nm / Pa for frequency, bone, site, and fixation, respectively. Ear transfer functions were found to be consistent with literature data. CONCLUSIONS: The feasibility of applying HLFVP to measure the displacement of auditory ossicles has been confirmed. HLFVP offers the possibility of carrying out measurements at various angles; however, this needs to be standardized taking into account anatomical limitations and surgical convenience.

Optimization of the Speech Test Material in a Group of Hearing Impaired Subjects: A Feasibility Study for Multilingual Digit Triplet Test Development.

BACKGROUND: The development of the global digit-in-noise test requires optimization of each language version on a group of normal-hearing native-speakers. An alternative solution may be an adaptive optimization during ongoing tests in a group of subjects with unknown hearing impairments. The objective of the research was to compare the optimization results between these groups. METHODS: Digit triplets consisting of three pseudo-randomly selected digits were presented in speech-shaped noise at various signal-to-noise ratios (SNRs), according to the protocol of the final speech test. Digit-specific and position-specific speech reception thresholds (SRTs) were determined and compared between groups. RESULTS: The study sample consisted of 82 subjects, 26 normal-hearing subjects and 56 patients with diverse hearing disorders. Statistically significant differences in digit-specific SRTs between the control and the investigated group were obtained for three digits in continuous noise (digits 0, 4, 6; p-value of 0.04, 0.03, 0.05) and two in modulated noise (digits 1 and 6; p-value of 0.05 and 0.01). An analysis including only ears with SRTs within the range of the normal hearing control group showed no statistically significant differences between digits. CONCLUSION: Optimization of speech material can be carried out in a group of subjects with unknown hearing impairments, provided the ears with scores outside normal range are rejected.

Worldwide Prevalence of Hearing Loss Among Smartphone Users: Cross-Sectional Study Using a Mobile-Based App.

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.

[A case of rare laryngeal neurogenic tumor].

Laryngeal schwannoma is a rare benign tumour of the larynx. Schwannomas derive from the Schwann cells. Magnetic resonance imaging (MRI) is the best imaging tool for suggesting the diagnosis. We report case of laryngeal schwannoma. The case was a 61-year-old man with a 1-year history of dysphonia and stridor. Laryngoscopy revealed a submucosal mass of the glottic area. A computed tomography scan of the larynx showed an 26(CC) x 18 (TR) x 24 (AP)mm expansile mass in the glottic area. Histopathological examination diagnosed a schwannoma of the larynx. External surgeries were successfully performed. Diagnosis and specific treatment are discussed.

Serum levels of interleukin-32 and interleukin-6 in granulomatosis with polyangiitis and microscopic polyangiitis: association with clinical and biochemical findings.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder of unknown etiology with dysregulated cytokines levels. OBJECTIVES: The main aim of this study was to assess the clinical correlation between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, granulomatosis with polyangiitis (GPA) serum levels of the microscopic polyangiitis (MPA), serum levels of the proinflammatory cytokines, interleukin (IL)-32 and interleukin-6. METHODS: Study included 71 patients, 47 with GPA and 24 with MPA. Serum IL-32 and IL-6 concentrations were analyzed in all patients, and compared with levels observed in 10 controls. IL-32 and IL-6 were evaluated using DuoSet and Quantikine HS ELISA, respectively. IL-32 and IL-6 concentrations were correlated with disease-related clinical and laboratory findings. RESULTS: IL-32 and IL-6 levels were significantly higher in GPA and MPA than in controls, especially IL-32 levels in GPA were elevated. IL-32 concentrations correlated positively with anti-proteinase 3 - ANCA (PR3-ANCA) levels in GPA (P < 0.0001), and with anti-myeloperoxidase ANCA (MPO-ANCA) in MPA (P = 0.049). IL-32 levels correlated positively with disease activity in GPA and MPA (P < 0.0001). GPA patients with pulmonary, cutaneous, and musculoskeletal involvement presented the highest IL-6 serum levels. Cutaneous manifestations correlated positively with IL-6 levels in MPA patients (P = 0.05). ANCA-positive patients with GPA expressed significantly high IL-6 levels (P = 0.036). No significant difference in IL-32 values was observed between ANCA-positive and ANCA-negative patients. CONCLUSIONS: Patients with GPA and MPA present higher serum IL-32 and IL-6 levels than controls. IL-32 levels correlate positively with disease activity.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY TO DETERMINE THE RECOVERY OF RETINAL LAYERS AFTER INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR MACULAR HOLE: Correlation With Visual Acuity Improvement.

PURPOSE: To analyze the recovery of retinal lines using swept-source optical coherence tomography after inverted internal limiting membrane flap technique to treat full-thickness macular hole, and the relationship between best-corrected visual acuity and retinal line repair. METHODS: Thirty-eight eyes were evaluated for recovery of the external limiting membrane, photoreceptor inner segment/outer segment junction line, and cone outer segment tips (COST) line. Correlation between the recovery of retinal lines and best-corrected visual acuity improvement was analyzed 6 months after surgery. RESULTS: The closure rate of full-thickness macular hole was 97%. The best recovery rates were associated with external limiting membrane line recovery (25 eyes, 65.8%), followed by inner segment/outer segment line recovery (22 eyes, 57.9%), and less frequently, COST line recovery (9 eyes, 23.7%); moreover, recovery of the COST line was apparent only in eyes with recovered external limiting membrane and inner segment/outer segment lines. Mean postoperative visual acuity in the COST line recovery group (COST+) was 20/42 (0.48, 0.33 logarithm of the minimum angle of resolution), compared with 20/95 (0.21, 0.68 logarithm of the minimum angle of resolution) without COST line recovery (COST-). Final visual acuity was significantly better in the COST+ group compared with the COST- group (P = 0.002). CONCLUSION: Cone outer segment tips line recovery is correlated with best-corrected visual acuity improvement for eyes treated with inverted internal limiting membrane flap technique for full-thickness macular hole.

Evaluation of the Sensory Organization Test to differentiate non-fallers from single- and multi-fallers.

BACKGROUND: Among the elderly, instability leading to falls (and consequences of them) is one of the most important problems. The etiology of falls is usually complex, but balance, posture and gait problems are considered to be the most important risk factors. OBJECTIVES: The objective of this study was to assess the usefulness of the Sensory Organization Test (SOT) in differentiating multi-fallers from single-fallers. MATERIAL AND METHODS: The studied group included 92 patients aged >60 years with balance disorders and falls in their history. The patients were divided into 2 groups: multi-fallers and single-fallers. The control group (non-fallers) included 21 individuals. The SOT was performed on the 1st day (SOT1) and on the last day (SOT2) of rehabilitation. Mean equilibrium score (ES) of 1-3 and 4-6 sensory conditions and composite score (CS) of the SOT1 and SOT2 were analyzed. The falls were analyzed as a total number of falls while performing SOT and a number of falls in all 3 repetitions of both conditions 5 and 6 separately. In SOT conditions 1-4 there were no falls observed. RESULTS: The importance of SOT to differentiate fallers from non-fallers and single-fallers from multi-fallers is ambiguous. CONCLUSIONS: The SOT may or may not indicate the differences between the groups - it does not fully explain those differences. It shows only postural dysfunction without indicating any localization in particular part of vestibular organ. The basic diagnostic evaluation in the elderly with a proneness to falls should include clinical examination and the Dix-Hallpike maneuver, supplemented with a videonystagmography (VNG), which would assess the structure of damage in vestibular organ. Posturography is of less validity in the differentiation of fallers from non-fallers.

Hearing Restoration with Cochlear Implantation in Patients Deafened after Blunt Head Trauma.

OBJECTIVES: The objective of the study was to assess the outcomes of cochlear implantation in patients deafened following blunt head trauma. MATERIAL AND METHODS: Retrospective case series review of seven patients post-lingually deafened following blunt head trauma and aided with cochlear implants. The following data were analyzed: Cause of injury, computed tomography results, surgical information, intra- and post-implantation complications, audiometric and speech perception assessment, processor mapping, and data from follow-up appointments. RESULTS: The median age of patients at the time of cochlear implantation was 29 years. The median time elapsed between head trauma and cochlear implantation was 5.77 months (minimum 0.8 and maximum 6.73 months). The median post-implantation follow-up time was 11.97 years. No facial nerve stimulation was observed in any case. All patients significantly improved their audiology and speech perception performances within a short time following cochlear implantation and CI performance did not decrease with long-term follow-up in any case. CONCLUSION: The results of this study showed that cochlear implantation is an effective treatment method for patients deafened following blunt head trauma.

Extremophilic proteases as novel and efficient tools in short peptide synthesis.

The objective of this review is to outline the crucial role that peptides play in various sectors, including medicine. Different ways of producing these compounds are discussed with an emphasis on the benefits offered by industrial enzyme biotechnology. This paper describes mechanisms of peptide bond formation using a range of proteases with different active site structures. Importantly, these enzymes may be further improved chemically and/or genetically to make them better suited for their various applications and process conditions. The focus is on extremophilic proteases, whose potential does not seem to have been fully appreciated to date. The structure of these proteins is somewhat different from that of the common commercially available enzymes, making them effective at high salinity and high or low temperatures, which are often favorable to peptide synthesis. Examples of such enzymes include halophilic, thermophilic, and psychrophilic proteases; this paper also mentions some promising catalytic proteins which require further study in this respect.

Intraoperative endoscopy of the anterior epitympanum recess through the posterior tympanotomy.

INTRODUCTION: The anterior epitympanum recess (AER) is a common place of the development of the cholesteatoma, which is why removal of the matrix from this area plays a key role in the surgical treatment of chronic otitis media. AIM: To evaluate the intraoperative visibility of AER in endoscopic optics in comparison to microscopic optics and to determine the prevalence of cholesteatoma in various types of construction of the AER. Study design: retrospective analysis of intraoperative search. MATERIAL AND METHODS: The study included 55 patients treated in the Department of Otolaryngology, Medical University of Warsaw within the years 2009-2011, who underwent endoscopy-assisted canal wall up tympanoplasty with posterior tympanotomy. The type of construction of the AER - cellular or dome-shaped - was determined. RESULTS: Cellular type of recess was found intraoperatively in 32% of ears and dome-shaped in 68% of the study group. The population with chronic otitis media does not differ significantly compared to the general population in terms of the construction of the anterior epitympanum recess (p = 0.668108; χ2 = 0.1838235, df = 1). Among the ears with cholesteatoma a cellular AER was found in 48.3% of cases and a dome-shaped AER was found in 51.7%. CONCLUSIONS: The cellular type of AER was significantly more frequent in ears with cholesteatoma (p < 0.01, χ2 = 29.86492, df = 1). Level of evidence: 1b.

THE ANALYSIS OF SPONTANEOUS CLOSURE MECHANISMS AND REGENERATION OF RETINAL LAYERS OF A FULL-THICKNESS MACULAR HOLE: Relationship with Visual Acuity Improvement.

PURPOSE: To analyze the spontaneous closure mechanisms, retinal layer regeneration, and best corrected visual acuity (BCVA) in the full-thickness macular hole (FMTH). METHODS: Ten eyes of 10 patients were studied. The measured outcomes included the time of persisting clinical symptoms and spontaneous closure of FTMH, BCVA, and spectral domain optical coherence tomography (SD-OCT) of vitreomacular interface. RESULTS: In a follow-up period, all eyes showed closure of FTMH (closure range: 3-64 weeks). The "bridging" phenomenon was a main mechanism of a spontaneous FMTH closure. Additionally, posterior vitreous detachment with the release of vitreomacular traction was observed in 4 eyes (40%). The statistical analysis showed that shorter the duration of symptoms, shorter the duration of the spontaneous FTMH closure (r = 0 673, P < 0 05). No significant association was observed between the time of spontaneous closure FTMH, the age of patients, and BCVA. The regeneration of the outer nuclear layer (ONL) and external limiting membrane (ELM) was confirmed in 10 and 9 eyes, respectively. In six eyes, connections between inner and outer segments of photoreceptors were rebuilt; in these cases, the final BCVA was the best. None of the eyes showed the regeneration of the connections between the outer segments of photoreceptor and retinal pigment epithelium (RPE). CONCLUSION: The main mechanism leading to a spontaneous closure of FTMH is the "bridging" phenomenon. Vitreous detachment and vitreomacular traction release are not necessary conditions promoting the closure of FTMH. Shorter duration of symptoms and regeneration of photoreceptors IS/OS interface provide a better final BCVA.

Retinoblastoma in Patients with 13q deletion syndrome - case series.

Deletion of the long arm of chromosome 13 (13q deletion syndrome) is very rare chromosomal aberration which causes mental retardation and multiple congenital malformations. Furthermore, it is associated with the increased risk of retinoblastoma. The aim of the paper was to present two cases of retinoblastomna in children with 13q deletion syndrome, discussing the diagnostic and therapeutic management, clinical manifestation and the importance of genetic testing which helps to determine the type of retinoblastoma and may also contribute to the diagnosis of other congenital abnormalities associated with intraocular tumors.

Autologous internal limiting membrane flap graft as a modification of the inverted flap technique in the treatment of full thickness macular holes ­ case report. / Autologiczny przeszczep platka blony granicznej wewnetrznej jako modyfikacja techniki odwróconego platka w leczeniu otworów w plamce ­ opis przypadku.

The aim of this paper is to present the autologous internal limiting membrane flap graft as a modification of the inverted flap technique in the surgical management of the full thickness macular hole. The 50-year old male admitted as an inpatient due to the full thickness macular hole was treated with 23G vitrectomy (Constellation). During the follow-up period his best corrected visual acuity improved significantly from 0.05 to 0.5. The optical coherence tomography confirmed the regeneration of the inner and outer retinal segments as well as of the internal limiting membrane. Autologous internal limiting membrane flap graft may be an alternative for cases of complicated full thickness macular holes and those patients in whom the conventional inverted flap technique cannot be used for various reasons.

[Endophthalmitis as a complication of intravitreal anti-VEGF therapy in patients with exudative age-related macular degeneration and degenerative myopia]. / Zapalenie wnetrza galki ocznej jako powiklanie doszklistkowych iniekcji czynnika anty-VEGF u chorych na wysiekowq postac zwyrodnienia plamki zwiazanego z wiekiem i ze zwyrodnieniowa krotkowzrocznoscia.

Anti-vascular endothelial growth factor agents, injected intravitreally, became a standard therapy for choroidal neovascularization in a course of wet age-related macular degeneration and degenerative myopia. Endophthalmitis is a very rare but the most serious complication associated with this procedure. The purpose of this paper is to present three patients with endophthalmitis following intravitreal injections of anti-VEGF agents. In the analysed material, the authors confirmed endophthalmitis in 2 of 4176 patients with exudative age-related macular degeneration and choroidal neovascularization associated with degenerative myopia (0.048%). The third reported case is a patient with endophthalmitis following the injection of bevacizumab performed in another center. The time interval between the injection and the onset of endophthalmitis was 2-5 days. In two patients who underwent pars plana vitrectomy--one patient regained best corrected visual acuity, while another showed no improvement and developed eye atrophy. In one case the microbiological examination showed a growth of Staphylococcus epidermidis, while in another a negative culture result was present. Endopthalmitis is a rare complication following the intravitreal injections of anti-VEGF agents. The proper selection of therapy depends on presenting best corrected visual acuity and severity of intraocular inflammation. The time of commencing treatment is a crucial prognostic factor, however, our observations showed that prompt and repeated surgical procedures cannot prevent irreversible vision loss in all cases.

[Available approaches to retinoblastoma therapy--literature review]. / Dostepne metody leczenia siatkówczaka--przeglad pismiennictwa.

Retinoblastoma is a malignant tumor and treatment should be started as soon as possible. Currently, the most common approach combines local therapy with chemotherapy. Chemoreduction represents a significant advance in the treatment of retinoblastoma. This paper presents treatment approaches including local chemotherapy, intraarterial and intravitreous chemiotheraphy. retinoblastoma, chemotherapy chemoreduction, brachytherapy, thermotherapy, laser photocoagulation, proton radiotherapy, teleradiotherapy, intraarterial chemotherapy.

Strategy for the surgical treatment of vestibular schwannomas in patients with neurofibromatosis type 2.

OBJECTIVE: Guidelines for appropriate management of vestibular schwannomas in NF2 patients are controversial. In this paper we reviewed our experience with patients with NF2 for the results of surgical treatment with particular reference to hearing and facial nerve preservation. METHODS: We included in the study 30 patients (16 women and 14 men) with the diagnosis of NF2 treated in our department between 1998 and 2014 who underwent surgery for vestibular schwannoma removal with a follow-up for at least 1 year. In 3 cases, the vestibular schwannomas were unilateral. Six patients with bilateral vestibular schwannomas underwent unilateral procedure. Therefore, 51 acoustic tumors were studied in 30 patients. RESULTS: No operative death we noted. Significant deterioration to the non-functional level occurred in 19 out of 22 cases with well-preserved preoperative hearing. Only three ears maintained their preoperative good hearing. Hearing was preserved in cases of small schwannoma not exceeding 2 cm. Among 21 patients who underwent bilateral operations hearing was preserved in 3 out of 7 cases when smaller tumor or better hearing level side was attempted at first surgery. In contrary none of the 14 patients retained hearing when the first operation concerned the worse-hearing ear. Among 14 tumors up to 2 cm there was only one case of moderately severe facial nerve dysfunction (House-Brackmann Grade IV) in the long follow-up. CONCLUSION: Early surgical intervention for vestibular schwannoma in NF2 patient is a viable management strategy to maintain hearing function and preserve facial nerve function.

Selecting appropriate dose regimens for AM-101 in the intratympanic treatment of acute inner ear tinnitus.

Inhibition of cochlear N-methyl-D-aspartate (NMDA) receptors with AM-101, a small molecule antagonist delivered by intratympanic injection, represents a novel approach to treat acute tinnitus triggered by glutamate excitotoxicity. An earlier double-blind, randomized, placebo-controlled phase II clinical trial (TACTT0) had demonstrated a significant and dose-dependent improvement in tinnitus triggered by acute acoustic trauma or otitis media from baseline to day 90. A second phase II trial (TACTT1) now sought to evaluate the most appropriate dose regimen for this treatment. Outcomes from the TACTT1 trial showed no significant difference in tinnitus improvement between a single-dose treatment and a dose regimen comprising three doses over 2 weeks. Taken together, three injections over 3 consecutive days showed the best results in the two phase II trials, suggesting that repeated and concentrated inhibition of cochlear NMDA receptors provides best treatment effects, while keeping the procedural impact on patients short.