Pharmacokinetics and safety of tobramycin nebulization with the I-neb and PARI-LC Plus in children with cystic fibrosis: A randomized, crossover study.

AIMS: We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I-neb device to the standard PARI-LC Plus nebulizer in children with cystic fibrosis. METHODS: A randomized, open-label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I-neb (75 mg) and PARI-LC Plus (300 mg). Study visits were separated by 1 month, in which 1 of the study nebulizers was used twice daily. Tobramycin PK for both nebulizers was established using measured tobramycin concentrations and Bayesian PK modelling software. Hearing and renal function tests were performed to test for aminoglycoside associated toxicity. In addition to standard estimated glomerular filtration rate values, biomarkers for tubular injury (KIM-1 and NAG) were measured. Patient and nebulizer satisfaction were assessed. RESULTS: Inhalations were well tolerated and serum trough concentrations below the predefined toxic limit were reached with no significant differences in PK parameters between nebulizers. Results of audiometry and estimated glomerular filtration rate revealed no abnormalities. However, increased urinary NAG/creatinine ratios at visit 2 for both nebulizers suggest TIS-induced subclinical tubular kidney injury. Nebulization time was 50% shorter and patient satisfaction was significantly higher with the I-neb. CONCLUSIONS: Nebulization of 75 mg TIS with the I-neb in children with cystic fibrosis resulted in comparable systemic exposure to 300 mg TIS with the PARI-LC Plus and was well tolerated and preferred over the PARI-LC Plus. Long-term safety of TIS nebulization should be monitored clinically, especially regarding the effects on tubular kidney injury.

Comparison of Place-versus-Pitch Mismatch between a Perimodiolar and Lateral Wall Cochlear Implant Electrode Array in Patients with Single-Sided Deafness and a Cochlear Implant.

BACKGROUND: In electric-acoustic pitch matching experiments in patients with single-sided deafness and a cochlear implant, the observed "mismatch" between perceived pitch and predicted pitch, based on the amended Greenwood frequency map, ranges from -1 to -2 octaves. It is unknown if and how this mismatch differs for perimodiolar versus lateral wall electrode arrays. OBJECTIVES: We aimed to investigate if the type of electrode array design is of influence on the electric-acoustic pitch match. METHOD: Fourteen patients (n = 8 with CI422 + lateral wall electrode array, n = 6 with CI512 + perimodiolar electrode array; Cochlear Ltd.) compared the pitch of acoustic stimuli to the pitch of electric stimuli at two test sessions (average interval 4.3 months). We plotted these "pitch matches" per electrode contact against insertion angle, calculated from high-resolution computed tomography scans. The difference between these pitch matches and two references (the spiral ganglion map and the default frequency allocation by Cochlear Ltd.) was defined as "mismatch." RESULTS: We found average mismatches of -2.2 octaves for the CI422 group and -1.3 octaves for the CI512 group. For any given electrode contact, the mismatch was smaller for the CI512 electrode array than for the CI422 electrode array. For all electrode contacts together, there was a significant difference between the mismatches of the two groups (p < 0.05). Results remained stable over time, with no significant difference between the two test sessions considering all electrode contacts. Neither group showed a significant correlation between the mismatch and phoneme recognition scores. CONCLUSION: The pitch mismatch was smaller for the perimodiolar electrode array than for the lateral wall electrode array.

Assessing auditory nerve condition by tone decay in deaf subjects with a cochlear implant.

The condition of the auditory nerve is a factor determining hearing performance of cochlear implant (CI) recipients. Abnormal loudness adaptation is associated with poor auditory nerve survival. We examined which stimulus conditions are suitable for tone decay measurements to differentiate between CI recipients with respect to their speech perception. Tone decay was defined here as occurring when the percept disappears before the stimulus stops. We measured the duration of the percept of a 60-s pulse train. Current levels ranged from below threshold up to maximum acceptable loudness, pulse rates from 250 to 5000 pulses/s, and duty cycles (percentages of time the burst of pulses is on) from 10% to 100%. Ten adult CI recipients were included: seven with good and three with poor speech perception. Largest differences among the subjects were found at 5000 pulses/s and 100% duty cycle. The well performing subjects had a continuous percept of the 60-s stimulus within 3 dB above threshold. Two poorly performing subjects showed abnormal loudness adaptation, that is, no continuous percept even at levels greater than 6 dB above threshold. We conclude that abnormal loudness adaptation can be detected via an electric tone decay test using a high pulse rate and 100% duty cycle.

Automatic Localization of Cochlear Implant Electrode Contacts in CT.

OBJECTIVES: Determining the exact location of cochlear implant (CI) electrode contacts after implantation is important, as it helps quantifying the relation between CI positioning and hearing outcome. Unfortunately, localization of individual contacts can be difficult, because the spacing between the electrode contacts is near the spatial resolution limit of high-resolution clinical computed tomography (CT) scanners. This study introduces and examines a simple, automatic method for the localization of intracochlear electrode contacts. CI geometric specifications may provide the prior knowledge that is essential to accurately estimate contact positions, even though individual contacts may not be visibly resolved. DESIGN: The prior knowledge in CI geometry is used to accurately estimate intracochlear electrode contact positions in high-resolution CT scans of seven adult patients implanted with a CI (Cochlear Ltd.). The automatically detected electrode contact locations were verified against locations marked by two experienced observers. The interobserver errors and the errors between the averaged locations and the automatically detected locations were calculated. The estimated contact positions were transformed to a cylindrical cochlear coordinate system, according to an international consensus, in which the insertion angles and the radius and elevation were measured. RESULTS: The linear correlation of the automatically detected electrode contact positions with the manually detected locations was high (R = 0.98 for the radius, and R = 1.00 for the insertion angle). The errors in radius and in insertion angle between the automatically detected locations and the manually detected locations were 0.12 mm and 1.7°. These errors were comparable to the interobserver errors. Geometrical measurements were in line with what is usually found in human cochleae. The mean insertion angle of the most apical electrode was 410° (range: 316° to 503°). The mean radius of the electrode contacts in the first turn of the cochlear spiral was 3.0 mm, and the mean radius of the remainder in the second turn was 1.7 mm. CONCLUSIONS: With implant geometry as prior knowledge, automatic analysis of high-resolution CT scans enables accurate localization of CI electrode contacts. The output of this method can be used to study the effect of CI positioning on hearing outcomes in more detail.

Correlation between subjective and objective hearing tests after unilateral and bilateral cochlear implantation.

BACKGROUND: There are many methods for assessing hearing performance after cochlear implantation. Standard evaluations often encompass objective hearing tests only, while patients' subjective experiences gain importance in today's healthcare. The aim of the current study was to analyze the correlation between subjective (self-reported questionnaires) and objective (speech perception and localization) hearing test results in adult cochlear implant (CI) users. Secondary, the correlation between subjective and objective hearing tests was compared between bilateral and unilateral CI patients. METHODS: Data for this study were prospectively collected as part of a multicentre randomized controlled trial. Thirty-eight postlingually deafened adult patients were randomly allocated to receive either unilateral (n = 19) or bilateral (n = 19) cochlear implantation. We used data gathered after one year of follow-up. We studied the correlation between objectively measured speech perception and localization skills on the one hand and related domains of the Speech, Spatial and Qualities of Hearing Scale (SSQ) and Nijmegen Cochlear Implant Questionnaire (NCIQ) on the other hand. We also compared these correlations between unilateral and bilateral CI users. RESULTS: We found significant weak to moderate negative correlations between the subjective test results (speech domain of the SSQ and the advanced speech perception domain of the NCIQ) and the related objective speech perception in noise test results (r = -0.33 to -0.48). A significant moderate correlation was found between the subjective test results (spatial domain of the SSQ) and the related objective localization test results (r = 0.59). The correlations in the group of bilateral CI patients (r = -0.28 to -0.54) did not differ significantly from the correlations in the group of unilateral CI patients (r = 0.15 to -0.40). CONCLUSIONS: Current objective tests do not fully reflect subjective everyday listening situations. This study elucidates the importance and necessity of questionnaires in the evaluation of cochlear implantation. Therefore, it is advised to evaluate both objective and subjective tests in CI patients on a regular basis. TRIAL REGISTRATION: This trial was registered on March 11, 2009 in the Dutch Trial Register. Trial registration number: NTR1722.

CINGLE-trial: cochlear implantation for siNGLE-sided deafness, a randomised controlled trial and economic evaluation.

BACKGROUND: Individuals with single-sided deafness (SSD) have problems with speech perception in noise, localisation of sounds and with communication and social interaction in their daily life. Current treatment modalities (Contralateral Routing of Sound systems [CROS] and Bone Conduction Devices [BCD]) do not restore binaural hearing. Based on low level of evidence studies, CROS and BCD do not improve speech perception in noise or sound localisation. In contrast, cochlear implantation (CI) may overcome the limitations of CROS and BCD, as binaural input can be restored. Promising results have previously been achieved on speech perception in noise, sound localisation, tinnitus and quality of life. METHODS AND DESIGN: A single-center Randomised Controlled Trial (RCT) was designed to compare all treatment strategies for SSD. One hundred and twenty adult single-sided deaf patients (duration of deafness >3 months and maximum 10 years; pure tone average at 0.5, 1, 2, 4 kHz, deaf ear: threshold equal to or more than 70 dB, better ear: threshold of maximum 30 dB) will be included in this trial and randomised to CI, 'first BCD, then CROS' or 'first CROS, then BCD'-groups. After the trial period, patients in the two latter groups may choose with which treatment option they continue. Outcomes of interest are speech perception in noise, sound localization, tinnitus and quality of life. These outcomes will be measured during a baseline visit and at follow up visits, which will take place at 6, 12, 18, 24, 36, 48 and 60 months after onset of treatment. Furthermore, an economic evaluation will be performed and adverse events will be monitored. DISCUSSION: This RCT allows for a comparison between the two current treatment modalities for single-sided deafness and a new promising treatment strategy, CI, on a range of health outcomes: speech perception in noise, sound localization, tinnitus and quality of life. Additionally, we will be able to answer the question if the additional costs of CI are justified by increased benefits, when compared to current treatment strategies. This study will inform health policy makers with regard to reimbursement of CI. TRIAL REGISTRATION: Netherlands Trial Register (www.trialregister.nl): NTR4580.

Socio-demographic, health, and tinnitus related variables affecting tinnitus severity.

OBJECTIVES: Tinnitus is a highly prevalent symptom with potential severe morbidity. Fortunately, only a small proportion of the population experience problems due to their tinnitus in such a degree that it adversely affects their quality of life (clinically significant tinnitus). It is not known why these individuals develop more burden from tinnitus. It seems likely that the severity of tinnitus can be influenced by different factors, such as socio-demographic or tinnitus characteristics or additional health complaints. It remains unclear from the current literature as to what are the main independent variables that have a bearing on tinnitus severity. This study addresses this problem by investigating variables previously described in the literature as well as additional variables. The aim of this study is to identify socio-demographic, health, and tinnitus variables that independently relate to tinnitus severity the most. DESIGN: This is a retrospective cohort study performed at the Tinnitus Care Group of the University Medical Center, Utrecht, in 309 consecutively seen chronic tinnitus patients. At this care group, patients are examined according to a structured diagnostic protocol, including history-taking by an otorhinolaryngologist and audiologist, physical examination, and audiometry. Based on results from previous research and theoretical considerations, a subset of data acquired through this diagnostic protocol were selected and used in this study. Univariate and multivariate correlations with tinnitus severity were investigated for 28 socio-demographic, health, and tinnitus variables. Tinnitus severity was measured with the Tinnitus Questionnaire (TQ) and the Tinnitus Handicap Inventory (THI). RESULTS: Eighteen variables related univariately with the TQ and 16 variables related univariately with the THI. Among these, 14 variables related univariately with both the TQ and the THI. Multivariate analyses showed three variables with an independent significant effect on both the TQ and the THI: percentage of tinnitus awareness during the day, self-reported depression and/or anxiety, and loudness on a Visual Analogue Scale. Three additional variables contributed independently significantly to the explained variance in either the TQ or the THI: level of education, somatic complaints, and tinnitus variability in loudness and/or pitch on a Visual Analogue Scale. These variables were among the first not to reach significance on the other questionnaire. CONCLUSIONS: Tinnitus severity is shown to be strongly related to percentage of tinnitus awareness during the day, self-reported depression and/or anxiety, subjectively experienced loudness, level of education, existence of additional somatic complaints, and subjectively experienced variability in loudness and/or pitch. Further research is needed to investigate the causal relationship between these variables and tinnitus severity. This knowledge may contribute to a better recognition, follow-up, and/or counseling of more vulnerable patients.

Bilateral low-frequency repetitive transcranial magnetic stimulation of the auditory cortex in tinnitus patients is not effective: a randomised controlled trial.

BACKGROUND: Although some therapies may be beneficial for some patients in reducing tinnitus, there is no curative therapy. Repetitive transcranial magnetic stimulation (rTMS) has been applied as a treatment for chronic tinnitus, but the effect remains controversial. MATERIAL AND METHODS: Fifty patients were treated with rTMS or placebo. Treatment consisted of 2,000 TMS pulses on each auditory cortex, at a rate of 1 Hz and an intensity of 110% of the individual motor threshold, on 5 consecutive days. rTMS and placebo effects were evaluated directly after treatment, after 1 week, and after 1, 3 and 6 months. Primary outcome was the Tinnitus Questionnaire (TQ). Secondary outcomes were the Tinnitus Handicap Inventory (THI) and a visual analogue scale. RESULTS: At none of the follow-up evaluation moments a significant difference between rTMS and placebo was observed with respect to changes in TQ or THI scores relative to pretreatment scores. Multilevel modelling (MLM) analyses did not show a global treatment effect either. Patients with a higher degree of burden showed slightly greater improvement after rTMS (only significant on the THI with MLM analyses). CONCLUSION: Bilateral low-frequency rTMS of the auditory cortex was not effective in treating tinnitus.

Cortical potentials evoked by tone frequency changes can predict speech perception in noise.

Accurate and objective assessment of higher order auditory processing is challenging and mainly relies on evaluations that require a subjects' active participation in tests such as frequency discrimination or speech perception in noise. This study investigates the value of cortical auditory evoked potentials (CAEPs) evoked in response to auditory change stimuli, known as acoustic change complexes (ACCs), as an objective measurement of auditory performance in hearing impairment. Secondary objectives were to assess the effect of hearing loss and non-professional musical experience on the ACC, and compare the ACC to the 'conventional' CAEP evoked in response to stimulus onset. In 24 normal-hearing subjects, consisting of 12 musicians and 12 non-musicians, and 13 age-matched hearing-impaired subjects ACCs were recorded in response to 12% frequency increases at four base frequencies (0.5, 1, 2 and 4 kHz). ACC amplitudes and latencies were compared to frequency discrimination thresholds at each base frequency, and to speech perception in noise. Frequency discrimination and speech perception in noise were significantly better for larger ACC N1-P2 amplitudes and shorter N1 latencies, whereas both frequency discrimination and speech perception did not correlate with onset CAEP amplitude or latency. Multiple regression analysis for prediction of speech perception in noise revealed that the strongest model was obtained by averaging over three frequencies (1, 2 and 4 kHz) with two significant predictors: hearing loss (R2 = 0.52) and ACC latency (R2 = 0.35). Thus, explaining 87% of the variance, this model indicates that subjects with longer ACC latencies have worse speech perception in noise than subjects with comparable hearing thresholds and shorter ACC latencies. If hearing loss was removed from this model, the combination of ACC amplitude and latency over those three frequencies explained 74% of the total variance in speech perception in noise. There were no differences in frequency discrimination, speech perception, CAEP, or ACC between recreational musicians and non-musicians. We conclude that the objective ACC N1 latency is a good predictor of speech perception in noise. When confirmed in validation studies with larger numbers of subjects, it can aid clinicians in their evaluation of auditory performance and higher order processing, in particular when behavioral testing is unreliable.

Anticonvulsants for tinnitus.

BACKGROUND: Tinnitus is the perception of sound or noise in the absence of an external or internal acoustic stimulation. It is a common and potentially distressing symptom for which no adequate therapy exists. OBJECTIVES: To assess the effectiveness of anticonvulsants in patients with chronic tinnitus. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Specialised Register, CENTRAL (2010, Issue 2), MEDLINE, EMBASE, bibliographies and additional sources for published and unpublished trials. The date of the most recent search was 26 May 2010. SELECTION CRITERIA: We selected randomised controlled trials in patients with chronic tinnitus comparing orally administered anticonvulsants with placebo. The primary outcome was improvement in tinnitus measured with validated questionnaires. Secondary outcomes were improvement in tinnitus measured with self-assessment scores, improvement in global well-being or accompanying symptoms, and adverse drug effects. DATA COLLECTION AND ANALYSIS: Three authors assessed risk of bias and extracted data independently. MAIN RESULTS: Seven trials (453 patients) were included in this review. These studies investigated four different anticonvulsants: gabapentin, carbamazepine, lamotrigine and flunarizine. The risk of bias of most studies was 'high' or 'unclear'. Three studies included a validated questionnaire (primary outcome). None of them showed a significant positive effect of anticonvulsants. One study showed a significant negative effect of gabapentin compared to placebo with an increase in Tinnitus Questionnaire (TQ) score of 18.4 points (standardised mean difference (SMD) 0.82, 95% confidence interval (CI) 0.07 to 1.58). A second study showed a positive, non-significant effect of gabapentin with a difference compared to placebo of 2.4 points on the Tinnitus Handicap Inventory (THI) (SMD -0.11, 95% CI -0.48 to 0.25). When the data from these two studies are pooled no effect of gabapentin is found (SMD 0.07, 95% CI -0.26 to 0.40). A third study reported no differences on the THI after treatment with gabapentin compared to placebo (exact numbers could not be extracted from the article).A meta-analysis of 'any positive effect' (yes versus no) based on a self-assessment score (secondary outcome) showed a small favourable effect of anticonvulsants (RD 14%, 95% CI 6% to 22%). A meta-analysis of 'near or total eradication of tinnitus annoyance' showed no effect of anticonvulsants (risk difference (RD) 4%, 95% CI -2% to 11%). Side effects of the anticonvulsants used were experienced by 18% of patients. AUTHORS' CONCLUSIONS: Current evidence regarding the effectiveness of anticonvulsants in patients with tinnitus has significant risk of bias. There is no evidence from studies performed so far to show that anticonvulsants have a large positive effect in the treatment of tinnitus but a small effect (of doubtful clinical significance) has been demonstrated.

Cortical potentials evoked by tone frequency changes compared to frequency discrimination and speech perception: Thresholds in normal-hearing and hearing-impaired subjects.

Frequency discrimination ability varies within the normal hearing population, partially explained by factors such as musical training and age, and it deteriorates with hearing loss. Frequency discrimination, while essential for several auditory tasks, is not routinely measured in clinical setting. This study investigates cortical auditory evoked potentials in response to frequency changes, known as acoustic change complexes (ACCs), and explores their value as a clinically applicable objective measurement of frequency discrimination. In 12 normal-hearing and 13 age-matched hearing-impaired subjects, ACC thresholds were recorded at 4 base frequencies (0.5, 1, 2, 4 kHz) and compared to psychophysically assessed frequency discrimination thresholds. ACC thresholds had a moderate to strong correlation to psychophysical frequency discrimination thresholds. In addition, ACC thresholds increased with hearing loss and higher ACC thresholds were associated with poorer speech perception in noise. The ACC threshold in response to a frequency change therefore holds promise as an objective clinical measurement in hearing impairment, indicative of frequency discrimination ability and related to speech perception. However, recordings as conducted in the current study are relatively time consuming. The current clinical application would be most relevant in cases where behavioral testing is unreliable.

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.

Cortical Auditory Evoked Potentials in Response to Frequency Changes with Varied Magnitude, Rate, and Direction.

Recent literature on cortical auditory evoked potentials has focused on correlations with hearing performance with the aim to develop an objective clinical tool. However, cortical responses depend on the type of stimulus and choice of stimulus parameters. This study investigates cortical auditory evoked potentials to sound changes, so-called acoustic change complexes (ACC), and the effects of varying three stimulus parameters. In twelve normal-hearing subjects, ACC waveforms were evoked by presenting frequency changes with varying magnitude, rate, and direction. The N1 amplitude and latency were strongly affected by magnitude, which is known from the literature. Importantly, both of these N1 variables were also significantly affected by both rate and direction of the frequency change. Larger and earlier N1 peaks were evoked by increasing the magnitude and rate of the frequency change and with downward rather than upward direction of the frequency change. The P2 amplitude increased with magnitude and depended, to a lesser extent, on rate of the frequency change while direction had no effect on this peak. The N1-P2 interval was not affected by any of the stimulus parameters. In conclusion, the ACC is most strongly affected by magnitude and also substantially by rate and direction of the change. These stimulus dependencies should be considered in choosing stimuli for ACCs as objective clinical measure of hearing performance.

Comparison Between Simulated and Actual Unilateral Hearing in Sequentially Implanted Cochlear Implant Users, a Cohort Study.

Introduction: Previous studies have proven the effectiveness of bilateral cochlear implantation compared to unilateral cochlear implantation. In many of these studies the unilateral hearing situation was simulated by switching off one of the cochlear implants in bilateral cochlear implant users. In the current study we assess the accuracy of this test method. Does simulated unilateral hearing (switching off one cochlear implant) result in the same outcomes as real life unilateral hearing with one cochlear implant and a non-implanted contralateral ear? Study design: We assessed the outcomes of one arm of a multicenter randomized controlled trial. Methods: In the original trial, 38 postlingually deafened adults were randomly allocated to either simultaneous bilateral cochlear implantation or sequential bilateral cochlear implantation. In the current study we used the data of the sequentially implanted group (n = 19). The primary outcome was speech perception-in-noise from straight ahead. Secondary outcomes were speech perception-in-silence, speech intelligibility-in-noise from spatially separated sources and localization capabilities. A within-subjects design was used to compare the results of hearing with one cochlear implant and a non-implanted contralateral ear (1- and 2-year follow-up) with the results of switching off one cochlear implant after sequential bilateral implantation (3-year follow-up). Results: We found no significant differences on any of the objective outcomes after 1-, 2-, or 3-year follow-up. Conclusion: This study shows that simulating unilateral hearing by switching off one cochlear implant seems a reliable method to compare unilateral and bilateral hearing in bilaterally implanted patients. Clinical Trial Registration: Dutch Trial Register NTR1722.

No Squelch Effect After Sequential Bilateral Cochlear Implantation in Postlingually Deafened Adults: Is There a First Ear Advantage?

OBJECTIVES: To investigate whether a squelch effect develops in postlingually deafened adults after sequential bilateral cochlear implantation. STUDY DESIGN: Prospective study as part of a randomized controlled trial on the difference between simultaneous versus sequential bilateral cochlear implantation. SETTING: Tertiary referral center. PARTICIPANTS: Sixteen postlingually deafened adults. INTERVENTION: Sequential bilateral cochlear implantation with a 2-year interimplant interval. MAIN OUTCOME MEASURE: A squelch effect was defined as a better bilateral score than unilateral score on a speech-intelligibility-in-noise test with spatially separated sources. The squelch effect was evaluated for the participants' best performing cochlear implant (CI) ear, the left CI in the condition with speech from -60 degrees azimuth and noise from +60 degrees azimuth (S-60 N+60), the right CI (N-60 S+60), CI1 and CI2. Evaluations took place 1, 2 and median 4 years after sequential implantation. RESULTS: No significant squelch effect was found, except for the right CI (N-60 S+60) after 2 years. No differences in speech perception-in-noise from straight ahead were seen between CI1 and CI2. Comparing performance of participants whose better or worse ear was implanted first did not reveal differences either. For the best performing situation, 7/16, 6/16, and 3/12 participants exhibited a squelch effect after 1, 2, and 4 years of follow-up. CONCLUSIONS: Participants who underwent sequential bilateral cochlear implantation with a 2-year interimplant interval did not develop an evident squelch effect on group level after a median follow-up of 4 years. Individual participants were able to make use of the squelch effect. The less evident squelch effect is at odds with our group of simultaneously implanted bilateral cochlear implant users. Neither a difference between CI1 and CI2, nor implanting the better or worse ear first could explain the less evident squelch effect in these patients. TRIAL REGISTRATION: Dutch Trial Register NTR1722.

Predicting Performance and Non-Use in Prelingually Deaf and Late-Implanted Cochlear Implant Users.

OBJECTIVE: To analyze postoperative hearing performance and independent predictors of speech perception and to assess cochlear implant nonuse in adults with prelingual deafness who received an implant during adulthood. DESIGN: Retrospective cohort study including all prelingually deaf adults who received a cochlear implant at the University Medical Center Utrecht between 2000 and 2013. SETTING: Tertiary referral center. PATIENTS: Included were a total of 48 prelingually deaf patients diagnosed with severe to profound sensorineural hearing loss before the age of 2 years who received their implants during adulthood. MAIN OUTCOME MEASURES: Postoperative monosyllabic word and sentence recognition scores. RESULTS: The average maximum postoperative monosyllabic word score for all subjects was 25% correct. Preoperative speech perception and the extent of preoperative residual hearing were both positive independent predictors of postoperative speech recognition, explaining 47% of the variance. Almost half of the population experienced only little (27%) or no benefit (21%) of their implants in daily communication. These patients were more likely to have either no or only low-frequency residual hearing. Eventually, all subjects without any benefit became non-user. CONCLUSIONS: Postoperative performance of adult, prelingually deaf cochlear implant candidates, with long-term deafness is dependent on their preoperative speech perception and residual hearing. Candidates who have negligible residual hearing are expected to have no or only limited postoperative benefit of their implants and are at risk of becoming nonusers.

Development and internal validation of a multivariable prediction model for tinnitus recovery following unilateral cochlear implantation: a cross-sectional retrospective study.

OBJECTIVE: To develop and internally validate a prediction model for tinnitus recovery following unilateral cochlear implantation. DESIGN: A cross-sectional retrospective study. SETTING: A questionnaire concerning tinnitus was sent to patients with bilateral severe to profound hearing loss, who underwent unilateral cochlear implantation at the University Medical Center Utrecht, the Netherlands, between 1 January 2006 and 31 December 2015. PARTICIPANTS: Of 137 included patients, 87 patients experienced tinnitus preoperatively. Data of these 87 patients were used to develop the prediction model. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome of the prediction model was tinnitus recovery. Investigated predictors were: age, gender, duration of deafness, preoperative hearing performance, tinnitus duration, severity and localisation, follow-up duration, localisation of cochlear implant (CI) compared with tinnitus side, surgical approach, insertion depth of the electrode, CI brand and difference in hearing threshold following cochlear implantation. Multivariable backward logistic regression was performed. Missing data were handled using multiple imputation. The performance of the model was assessed by the calibrative and discriminative ability of the model. The prediction model was internally validated using bootstrapping techniques. RESULTS: The tinnitus recovery rate was 40%. A lower preoperative Consonant-Vowel-Consonant (CVC) score, unilateral localisation of tinnitus and larger deterioration of residual hearing at 250 Hz revealed to be relevant predictors for tinnitus recovery. The area under the receiver operating characteristics curve (AUC) of the initial model was 0.722 (IQR: 0.703-0.729). After internal validation of this prediction model, the AUC decreased to 0.696 (IQR: 0.667-0.700). CONCLUSION AND RELEVANCE: Lower preoperative CVC score, unilateral localisation of tinnitus and larger deterioration of residual hearing at 250 Hz were significant predictors for tinnitus recovery following unilateral cochlear implantation. The performance of the model developed in this retrospective study is promising. However, before clinical use of the model, the conduction of a larger prospective study is recommended.

Hearing loss and speech perception in noise difficulties in Fanconi anemia.

OBJECTIVES/HYPOTHESIS: Fanconi anemia is a hereditary chromosomal instability disorder. Hearing loss and ear abnormalities are among the many manifestations reported in this disorder. In addition, Fanconi anemia patients often complain about hearing difficulties in situations with background noise (speech perception in noise difficulties). Our study aimed to describe the prevalence of hearing loss and speech perception in noise difficulties in Dutch Fanconi anemia patients. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective chart review was conducted at a Dutch tertiary care center. All patients with Fanconi anemia at clinical follow-up in our hospital were included. Medical files were reviewed to collect data on hearing loss and speech perception in noise difficulties. RESULTS: In total, 49 Fanconi anemia patients were included. Audiograms were available in 29 patients and showed hearing loss in 16 patients (55%). Conductive hearing loss was present in 24.1%, sensorineural in 20.7%, and mixed in 10.3%. A speech in noise test was performed in 17 patients; speech perception in noise was subnormal in nine patients (52.9%) and abnormal in two patients (11.7%). CONCLUSIONS: Hearing loss and speech perception in noise abnormalities are common in Fanconi anemia. Therefore, pure tone audiograms and speech in noise tests should be performed, preferably already at a young age, because hearing aids or assistive listening devices could be very valuable in developing language and communication skills. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2358-2361, 2017.

Tinnitus after Simultaneous and Sequential Bilateral Cochlear Implantation.

IMPORTANCE: There is an ongoing global discussion on whether or not bilateral cochlear implantation should be standard care for bilateral deafness. Contrary to unilateral cochlear implantation, however, little is known about the effect of bilateral cochlear implantation on tinnitus. OBJECTIVE: To investigate tinnitus outcomes 1 year after bilateral cochlear implantation. Secondarily, to compare tinnitus outcomes between simultaneous and sequential bilateral cochlear implantation and to investigate long-term follow-up (3 years). STUDY DESIGN: This study is a secondary analysis as part of a multicenter randomized controlled trial. METHODS: Thirty-eight postlingually deafened adults were included in the original trial, in which the presence of tinnitus was not an inclusion criterion. All participants received cochlear implants (CIs) because of profound hearing loss. Nineteen participants received bilateral CIs simultaneously and 19 participants received bilateral CIs sequentially with an inter-implant interval of 2 years. The prevalence and severity of tinnitus before and after simultaneous and sequential bilateral cochlear implantation were measured preoperatively and each year after implantation with the Tinnitus Handicap Inventory (THI) and Tinnitus Questionnaire (TQ). RESULTS: The prevalence of preoperative tinnitus was 42% (16/38). One year after bilateral implantation, there was a median difference of -8 (inter-quartile range (IQR): -28 to 4) in THI score and -9 (IQR: -17 to -9) in TQ score in the participants with preoperative tinnitus. Induction of tinnitus occurred in five participants, all in the simultaneous group, in the year after bilateral implantation. Although the preoperative and also the postoperative median THI and TQ scores were higher in the simultaneous group, the median difference scores were equal in both groups. In the simultaneous group, tinnitus scores fluctuated in the 3 years after implantation. In the sequential group, four patients had an additional benefit of the second CI: a total suppression of tinnitus compared with their unilateral situation. CONCLUSION: While bilateral cochlear implantation can have a positive effect on preoperative tinnitus complaints, the induction of (temporary or permanent) tinnitus was also reported. CLINICAL TRIAL REGISTRATION: Dutch Trial Register NTR1722.

Objective and Subjective Measures of Simultaneous vs Sequential Bilateral Cochlear Implants in Adults: A Randomized Clinical Trial.

Importance: To date, no randomized clinical trial on the comparison between simultaneous and sequential bilateral cochlear implants (BiCIs) has been performed. Objective: To investigate the hearing capabilities and the self-reported benefits of simultaneous BiCIs compared with those of sequential BiCIs. Design, Setting, and Participants: A multicenter randomized clinical trial was conducted between January 12, 2010, and September 2, 2012, at 5 tertiary referral centers among 40 participants eligible for BiCIs. Main inclusion criteria were postlingual severe to profound hearing loss, age 18 to 70 years, and a maximum duration of 10 years without hearing aid use in both ears. Data analysis was conducted from May 24 to June 12, 2016. Interventions: The simultaneous BiCI group received 2 cochlear implants during 1 surgical procedure. The sequential BiCI group received 2 cochlear implants with an interval of 2 years between implants. Main Outcomes and Measures: First, the results 1 year after receiving simultaneous BiCIs were compared with the results 1 year after receiving sequential BiCIs. Second, the results of 3 years of follow-up for both groups were compared separately. The primary outcome measure was speech intelligibility in noise from straight ahead. Secondary outcome measures were speech intelligibility in noise from spatially separated sources, speech intelligibility in silence, localization capabilities, and self-reported benefits assessed with various hearing and quality of life questionnaires. Results: Nineteen participants were randomized to receive simultaneous BiCIs (11 women and 8 men; median age, 52 years [interquartile range, 36-63 years]), and another 19 participants were randomized to undergo sequential BiCIs (8 women and 11 men; median age, 54 years [interquartile range, 43-64 years]). Three patients did not receive a second cochlear implant and were unavailable for follow-up. Comparable results were found 1 year after simultaneous or sequential BiCIs for speech intelligibility in noise from straight ahead (difference, 0.9 dB [95% CI, -3.1 to 4.4 dB]) and all secondary outcome measures except for localization with a 30° angle between loudspeakers (difference, -10% [95% CI, -20.1% to 0.0%]). In the sequential BiCI group, all participants performed significantly better after the BiCIs on speech intelligibility in noise from spatially separated sources and on all localization tests, which was consistent with most of the participants' self-reported hearing capabilities. Speech intelligibility-in-noise results improved in the simultaneous BiCI group up to 3 years following the BiCIs. Conclusions and Relevance: This study shows comparable objective and subjective hearing results 1 year after receiving simultaneous BiCIs and sequential BiCIs with an interval of 2 years between implants. It also shows a significant benefit of sequential BiCIs over a unilateral cochlear implant. Until 3 years after receiving simultaneous BiCIs, speech intelligibility in noise significantly improved compared with previous years. Trial Registration: trialregister.nl Identifier: NTR1722.