Protocol for the Brain Health Support Program Study of the Canadian Therapeutic Platform Trial for Multidomain Interventions to Prevent Dementia (CAN-THUMBS UP): A Prospective 12-Month Intervention Study.

BACKGROUND/OBJECTIVES: CAN-THUMBS UP is designed as a comprehensive and innovative fully remote program to 1) develop an interactive and compelling online Brain Health Support Program intervention, with potential to positively influence dementia literacy, self-efficacy and lifestyle risk factors; 2) enroll and retain a community-dwelling Platform Trial Cohort of individuals at risk of dementia who will participate in the intervention; 3) support an open platform trial to test a variety of multidomain interventions that might further benefit individuals at risk of dementia. This manuscript presents the Brain Health Support Program Study protocol. DESIGN/SETTING: Twelve-month prospective multi-center longitudinal study to evaluate a fully remote web-based educational intervention. Participants will subsequently be part of a Platform Trial Cohort and may be eligible to participate in further dementia prevention clinical trials. PARTICIPANTS: Three hundred fifty older adults who are cognitively unimpaired or have mild cognitive impairment, with at least 1 well established dementia risk factor. INTERVENTION: Participants engage in the Brain Health Support Program intervention for 45-weeks and complete pre/post intervention measures. This intervention is designed to convey best available evidence for dementia prevention, consists of 181 chapters within 8 modules that are progressively delivered, and is available online in English and French. The program has been developed as a collaborative effort by investigators with recognized expertise in the program's content areas, along with input from older-adult citizen advisors. MEASUREMENTS: This study utilizes adapted remote assessments with accessible technologies (e.g. videoconferencing, cognitive testing via computer and mobile phone, wearable devices to track physical activity and sleep, self-administered saliva sample collection). The primary outcome is change in dementia literacy, as measured by the Alzheimer's Disease Knowledge Scale. Secondary outcomes include change in self-efficacy; engagement using the online program; user satisfaction ratings; and evaluation of usability and acceptance. Exploratory outcomes include changes in attitudes toward dementia, modifiable risk factors, performance on the Neuropsychological Test Battery, performance on self-administered online cognitive assessments, and levels of physical activity and sleep; success of the national recruitment plan; and the distribution of age adjusted polygenic hazard scores. CONCLUSIONS: This fully remote study provides an accessible approach to research with all study activities being completed in the participants' home environment. This approach may reduce barriers to participation, provide an easier and less demanding participant experience, and reach a broader geography with recruitment from all regions of Canada. CAN-THUMBS UP represents a Canadian contribution to the global World-Wide FINGERS program (alz.org/wwfingers).

Evolution of the candidacy requirements and patient perioperative assessment protocols for cochlear implantation.

Cochlear implantation as an approved clinical therapy ushered in an exciting era of innovation for the treatment of hearing loss. The U.S. Food and Drug Administration approved the use of cochlear implants as a treatment option for adults with profound sensorineural hearing loss in 1985. The landscape for treating adults and children with significant hearing loss has changed dramatically over the last three decades. The purpose of this paper is to examine the evolving regulatory process and changes to clinical care. A significant emerging trend in cochlear implantation is the consideration of steroids to preserve hearing during and following surgery. This parallels the quest for hearing preservation in noise-induced hearing disorders, especially considering the current interest in biological drug therapies in this population. The future will likely usher in an era of combination therapeutics utilizing drugs and cochlear implantation. For over 30+ years and following regulatory compliance, the Rocky Mountain Ear Center has developed an extensive candidacy and outcome assessment protocol. This systematic approach evaluates both unaided and aided auditory performance during candidacy stages and post-implantation. Adjunctive measures of cognition and quality-of-life augment the auditory assessment in specific populations. Practical insights into lessons learned have directed further clinical research and have resulted in beneficial changes to clinical care.

Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers.

BACKGROUND AND PURPOSE: Pediatric CNS tumors commonly present challenges for radiographic interpretation on conventional MR imaging. This study sought to investigate the safety and tolerability of hyperpolarized carbon-13 (HP-13C) metabolic imaging in pediatric patients with brain tumors. MATERIALS AND METHODS: Pediatric patients 3 to 18 years of age who were previously diagnosed with a brain tumor and could undergo MR imaging without sedation were eligible to enroll in this safety study of HP [1-13C]pyruvate. Participants received a one-time injection of HP [1-13C]pyruvate and were imaged using dynamic HP-13C MR imaging. We assessed 2 dose levels: 0.34 mL/kg and the highest tolerated adult dose of 0.43 mL/kg. Participants were monitored throughout imaging and for 60 minutes postinjection, including pre- and postinjection electrocardiograms and vital sign measurements. RESULTS: Between February 2017 and July 2019, ten participants (9 males; median age, 14 years; range, 10-17 years) were enrolled, of whom 6 completed injection of HP [1-13C]pyruvate and dynamic HP-13C MR imaging. Four participants failed to undergo HP-13C MR imaging due to technical failures related to generating HP [1-13C]pyruvate or MR imaging operability. HP [1-13C]pyruvate was well-tolerated in all participants who completed the study, with no dose-limiting toxicities or adverse events observed at either 0.34 (n = 3) or 0.43 (n = 3) mL/kg. HP [1-13C]pyruvate demonstrated characteristic conversion to [1-13C]lactate and [13C]bicarbonate in the brain. Due to poor accrual, the study was closed after only 3 participants were enrolled at the highest dose level. CONCLUSIONS: Dynamic HP-13C MR imaging was safely performed in 6 pediatric patients with CNS tumors and demonstrated HP [1-13C]pyruvate brain metabolism.

Longitudinal outcomes of cochlear implantation and bimodal hearing in a large group of adults: A multicenter clinical study.

OBJECTIVE: To evaluate speech understanding outcomes in a large adult cohort who demonstrated poor hearing performance with well fit hearing aids in the unilateral and bilateral or bimodal listening conditions at preimplant, 3-, 6- and 12-months. SUBJECTS: Post-linguistically deafened adults (N = 100) with bilateral moderate-to-profound sensorineural hearing loss and limited functional benefit from well fit bilateral hearing aids. METHOD: A multicenter, prospective, repeated-measures, within-subject controlled study was conducted. All subjects were implanted with a Slim Modiolar cochlear implant and were required to use bimodal stimulation (cochlear implant and hearing aid in contralateral ear) for 6-months postimplant and optionally to 12-months. Evaluations included: speech recognition for monosyllabic consonant-nucleus-consonant (CNC) words in quiet; AzBio sentences in coincident noise (at +5 and +10 dB signal-to-noise ratio (SNR)), in implant ear and bimodal conditions. All speech tests were performed at preimplant and 6-months postimplant for primary endpoint outcomes, and a subset of speech tests at 3- and 12-months. RESULTS: In the implant ear only, at 3-, 6- and 12-months postimplant, 84%, 93% and 97% of subjects respectively, demonstrated significantly improved monosyllabic word scores in quiet compared to preimplant hearing aid scores (p < 0.05). At 12-months, a mean gain of 51% points, for monosyllabic words and 32% points for sentences in noise was observed (p < 0.001). In the bimodal condition, at 6-months postimplant, 87% of subjects demonstrated significantly improved monosyllabic word scores in quiet compared to preimplant bilateral hearing aid scores (p < 0.05). At 6-months, a mean gain of 40% points, for monosyllabic words was observed (p < 0.001). Speech scores for sentences in noise significantly improved for the bimodal condition at 6- and 12-months (p < 0.001). In addition to speech scores for the implanted ear, bimodal condition scores demonstrated further increments, especially for sentences in noise at 6- and 12-months (p < 0.001). CONCLUSION: Results support that bimodal hearing is superior to bilateral hearing aids in this cohort of bilateral moderate-to-profound adult hearing aid users. Our study cohort demonstrated significant improvements for speech scores for the cochlear implant (CI) ear only and bimodal conditions compared to the baseline preimplant unilateral and bilateral hearing aid conditions respectively. The greatest gain in performance was in the first three months of device use with incremental improvement through 12 months. These findings indicate that when hearing aids fit to National Acoustics Laboratory (NAL-1) targets do not provide the necessary audibility needed for speech recognition, referral for CI-candidacy evaluation is strongly recommended. TRIAL REGISTRATION: Clintrial.govNCT03007472. Registered 01/02/2017, https://clinicaltrials.gov/ct2/show/NCT03007472?term=clinical+evaluation+of+the+nucleus+CI532&draw=2&rank=2.

Centrally Reduced Diffusion Sign for Differentiation between Treatment-Related Lesions and Glioma Progression: A Validation Study.

BACKGROUND AND PURPOSE: Differentiating between treatment-related lesions and tumor progression remains one of the greatest dilemmas in neuro-oncology. Diffusion MR imaging characteristics may provide useful information to help make this distinction. The aim of the study was to assess the diagnostic accuracy of the centrally reduced diffusion sign for differentiation of treatment-related lesions and true tumor progression in patients with suspected glioma recurrence. MATERIALS AND METHODS: The images of 231 patients who underwent an operation for suspected glioma recurrence were reviewed. Patients with susceptibility artifacts or without central necrosis were excluded. The final diagnosis was established according to histopathology reports. Two neuroradiologists classified the diffusion patterns on preoperative MR imaging as the following: 1) reduced diffusion in the solid component only, 2) reduced diffusion mainly in the solid component, 3) no reduced diffusion, 4) reduced diffusion mainly in the central necrosis, and 5) reduced diffusion in the central necrosis only. Diagnostic accuracy metrics and the area under the receiver operating characteristic curve were estimated for the diffusion patterns. RESULTS: One hundred three patients were included (22 with treatment-related lesions and 81 with tumor progression). The diagnostic accuracy results for the centrally reduced diffusion pattern as a predictor of treatment-related lesions ("mainly central" and "exclusively central" patterns versus all other patterns) were as follows: 64% sensitivity (95% CI, 41%-83%), 84% specificity (95% CI, 74%-91%), 52% positive predictive value (95% CI, 37%-66%), and 89% negative predictive value (95% CI, 83%-94%). CONCLUSIONS: The centrally reduced diffusion sign is associated with the presence of treatment effect. The probability of a histologic diagnosis of a treatment-related lesion is low (11%) in the absence of centrally reduced diffusion.

Comprehensive hearing aid assessment in adults with bilateral severe-profound sensorineural hearing loss who present for Cochlear implant evaluation.

PURPOSE: To comprehensively assess and describe functional auditory performance in a group of adults with bilateral, moderate sloping to profound sensorineural hearing loss who were dissatisfied users of well-fit bilateral hearing aids and presented for Cochlear implant evaluation. Participants were evaluated with bilateral hearing aids and after six months of bimodal (Cochlear implant and a contralateral hearing aid) hearing experience with a Cochlear implant and contralateral hearing aid. METHODS: Study participants were assessed using pure tone audiometry, aided speech understanding in quiet (CNC words) and in noise (AzBio sentences at +10 and +5 dB SNR) in the sound field with unilateral and bilateral hearing aids fit to target. Participants completed subjective scales of quality of life, (Health Utilities Index Mark 3), hearing disability, (Speech, Spatial and Qualities of Hearing Scale) and a device use satisfaction scale. Participants ≥55 years were administered the Montreal Cognitive Assessment screening tool. One-hundred enrolled individuals completed baseline evaluations. RESULTS: Aided bilateral mean speech understanding scores were 28% for CNC words and 31%, and 17% for AzBio sentences at a +10 dB, and +5 dB SNR, respectively. Mean scale ratings were 0.46 for overall quality of life and 3.19 for functional hearing ability. Ninety percent of participants reported dissatisfaction with overall hearing performance. CONCLUSIONS: Evaluation results, including functional performance metrics quantifying the deleterious effects of hearing loss for overall wellbeing, underscore that bilateral hearing aids are not an effective treatment for individuals with bilateral, moderate sloping to profound sensorineural hearing loss. Individuals with this degree of hearing impairment, who demonstrate poor aided speech understanding and dissatisfaction with hearing abilities in everyday life, require timely referral to a Cochlear implant clinic for further evaluation.

Benefits of Cochlear Implantation for Single-Sided Deafness: Data From the House Clinic-University of Southern California-University of California, Los Angeles Clinical Trial.

OBJECTIVES: Cochlear implants (CIs) have been shown to benefit patients with single-sided deafness (SSD) in terms of tinnitus reduction, localization, speech understanding, and quality of life (QoL). While previous studies have shown cochlear implantation may benefit SSD patients, it is unclear which point of comparison is most relevant: baseline performance before implantation versus performance with normal-hearing (NH) ear after implantation. In this study, CI outcomes were assessed in SSD patients before and up to 6 mo postactivation. Benefits of cochlear implantation were assessed relative to binaural performance before implantation or relative to performance with the NH ear alone after implantation. DESIGN: Here, we report data for 10 patients who completed a longitudinal, prospective, Food and Drug Administration-approved study of cochlear implantation for SSD patients. All subjects had severe to profound unilateral hearing loss in one ear and normal hearing in the other ear. All patients were implanted with the MED-EL CONCERTO Flex 28 device. Speech understanding in quiet and in noise, localization, and tinnitus severity (with the CI on or off) were measured before implantation (baseline) and at 1, 3, 6 mo postactivation of the CI processor. Performance was measured with both ears (binaural), the CI ear alone, and the NH ear alone (the CI ear was plugged and muffed). Tinnitus severity, dizziness severity, and QoL were measured using questionnaires administered before implantation and 6 mo postactivation. RESULTS: Significant CI benefits were observed for tinnitus severity, localization, speech understanding, and QoL. The degree and time course of CI benefit depended on the outcome measure and the reference point. Relative to binaural baseline performance, significant and immediate (1 mo postactivation) CI benefits were observed for tinnitus severity and speech performance in noise, but localization did not significantly improve until 6 mo postactivation; questionnaire data showed significant improvement in QoL 6 mo postactivation. Relative to NH-only performance after implantation, significant and immediate benefits were observed for tinnitus severity and localization; binaural speech understanding in noise did not significantly improve during the 6-mo study period, due to variability in NH-only performance. There were no correlations between behavioral and questionnaire data, except between tinnitus visual analog scale scores at 6 mo postactivation and Tinnitus Functional Index scores at 6 mo postactivation. CONCLUSIONS: The present behavioral and subjective data suggest that SSD patients greatly benefit from cochlear implantation. However, to fully understand the degree and time course of CI benefit, the outcome measure and point of comparison should be considered. From a clinical perspective, binaural baseline performance is a relevant point of comparison. The lack of correlation between behavioral and questionnaire data suggest that represent independent measures of CI benefit for SSD patients.

Hearing Outcomes after Revision Stapedectomy Managed with Total Ossicular Prostheses.

OBJECTIVES: (1) To describe the use of total ossicular prostheses (TOPs) in the setting of stapedectomy requiring an incus bypass procedure. (2) To analyze the short- and long-term audiometric results of TOP utilization in the setting of stapedectomy for an incus bypass procedure. STUDY DESIGN: Case series with chart review. SETTING: Tertiary neurotologic referral center. SUBJECTS AND METHODS: Seventeen cases of TOP reconstruction after stapedectomy were performed due to advanced incus erosion. The cases were assessed for pre- and postoperative bone conduction and air conduction pure-tone averages (PTAs; 0.5, 1, 2, 3 kHz), including high-tone bone conduction (1, 2, 4 kHz), air-bone gap, and speech discrimination scores. Hearing outcomes were measured: short-term (3 weeks) and long-term (average, 22 months). RESULTS: Among 17 ears undergoing revision stapedectomy managed with TOP reconstruction, the average number of previous revision attempts was 1.0 (SD, 1; range, 1-5). The preoperative bone conduction PTA was 30.7 dB preoperatively, while the preoperative air conduction PTA was 64.3 dB. The mean postoperative air-bone gap significantly decreased to 18.9 dB (SD, 12.7; range, 5-46.25; P < .003) with a mean follow-up of 22.2 months (SD, 25.0; range, 0.75-78). No significant decrement in high-tone bone conduction PTA was observed (mean, 0 dB; SD, 12.8; range, -36.7 to 20; P = .427); however, 1 ear revealed a severe decrease in PTA and speech discrimination score postoperatively. No further revisions were noted in follow-up. CONCLUSION: TOP reconstruction in the setting of previous revision stapedectomy with limited incudovestibular reconstructive options may lead to favorable hearing outcomes, but it carries an increased risk of sensorineural hearing loss.

Symptomatic cytomegalovirus gastrointestinal infection with positive quantitative real-time PCR findings in apparently immunocompetent patients: a case series.

Cytomegalovirus (CMV) gastrointestinal disease rarely occurs in immunocompetent patients, and is mainly diagnosed on the basis of histopathological findings. Real-time PCR for CMV DNA quantification is considered to be a useful diagnostic tool, but its place in the diagnostic strategy is not clearly defined. The goal of the study was to describe the clinical and paraclinical features of apparently immunocompetent patients with CMV gastrointestinal disease diagnosed according to quantitative PCR results. In this retrospective study conducted in a 1500-bed tertiary-care centre, we reviewed the case records of apparently immunocompetent patients with positive findings of CMV DNA in gastrointestinal biopsies with compatible symptoms and endoscopic findings. A total of 13 patients were included between January 2007 and December 2010. The median age was 81 years, and 54% of patients had underlying immune-modulating conditions. Diarrhoea, haematochezia and dysphagia were the main reported symptoms, and ulcers were the main endoscopic findings. The mean value of CMV DNA load in gastrointestinal biopsies was 3845 copies/µg total DNA (range, 15-15 500 copies/µg total DNA). The highest values were found in two patients who were diagnosed with adenocarcinoma in the subsequent course of CMV infection. Clinical features were similar to those in previous series in which diagnosis was based on histopathological analysis. Elderly people are more commonly affected, and a link with immune senescence is possible. Quantification of CMV DNA seems to be a useful tool for diagnosis when combined with clinical and endoscopic findings, but further studies are necessary to interpret quantitative values.

Retained dental needle migration across the skull base to the cochlea presenting as hearing loss.

OBJECTIVES: Long-term retained foreign bodies in the human body have been reported across many specialties, but relatively few exist in the ENT literature. PATIENTS: We present a case report of a patient with a broken dental needle fragment in the posterior oral cavity with subsequent migration to the cochlea over the course of 4 years, eventually leading to hearing loss. CT scan and middle ear exploration demonstrated a 4-cm metallic fragment abutting the base of the cochlea, immediately adjacent to the internal carotid artery. INTERVENTIONS: The needle segment was removed through an endaural approach without complication. RESULTS: Postoperatively, the patient had improvements in PTA and speech discrimination, as well as the resolution of chronic otalgia and jaw pain. Imaging, audiologic results, and surgical details and pictures are presented herein. CONCLUSION: To our knowledge, based on a thorough PubMed and Google Scholar search, there are no reports of such a foreign body migration from the oral cavity to the skull base.

Management of incus necrosis in revision stapedectomy using hydroxyapatite bone cement.

OBJECTIVE: Review audiological outcomes after revision stapedectomy using hydroxyapatite cement. STUDY DESIGN: Retrospective case review. SETTING: Tertiary neurotological referral center. PATIENTS: Thirty-seven cases of previously treated otosclerosis where incus erosion was observed during revision stapedectomy. INTERVENTION(S): Hydroxyapatite cement was used to rebuild the eroded incus and stabilize the prosthesis during revision stapedectomy. MAIN OUTCOME MEASURE(S): Pre- and postoperative bone conduction (BC) and air conduction (AC) pure-tone averages (PTA) (0.5, 1, 2, 3 kHz) including high tone BC (1, 2, 4 kHz), air-bone gap (ABG), and speech discrimination scores were measured. Short-term (3 wk) and longer-term (average 12 mo) hearing outcomes were measured. Data are reported according to the most recent guidelines of the AAO-HNS Committee on Hearing and Equilibrium. RESULTS: Among 37 ears undergoing revision stapedectomy with hydroxyapatite cement, the AC PTA was 59.8 dB preoperatively and 34.6 dB postoperatively (p < 0.0001) at latest follow-up. The mean postoperative ABG was 8.8 dB (SD = 8.6, range -1.3-36.3 dB) while a mean improvement of 2.1 dB (SD = 6.5, range -8.33-15.0 dB) of the high tone BC PTA was observed. One revision case was noted during the follow-up period. CONCLUSION: Hydroxyapatite cement is useful to reconstruct and stabilize the prosthesis in revision stapedectomy when erosion of the long process is encountered. Short- and longer-term hearing results are favorable when compared to previously reported results of revision stapedectomy.

Quantitative 7T phase imaging in premanifest Huntington disease.

BACKGROUND AND PURPOSE: In vivo MR imaging and postmortem neuropathologic studies have demonstrated elevated iron concentration and atrophy within the striatum of patients with Huntington disease, implicating neuronal loss and iron accumulation in the pathogenesis of this neurodegenerative disorder. We used 7T MR imaging to determine whether quantitative phase, a measurement that reflects both iron content and tissue microstructure, is altered in subjects with premanifest Huntington disease. MATERIALS AND METHODS: Local field shift, calculated from 7T MR phase images, was quantified in 13 subjects with premanifest Huntington disease and 13 age- and sex-matched controls. All participants underwent 3T and 7T MR imaging, including volumetric T1 and 7T gradient recalled-echo sequences. Local field shift maps were created from 7T phase data and registered to caudate ROIs automatically parcellated from the 3T T1 images. Huntington disease-specific disease burden and neurocognitive and motor evaluations were also performed and compared with local field shift. RESULTS: Subjects with premanifest Huntington disease had smaller caudate volume and higher local field shift than controls. A significant correlation between these measurements was not detected, and prediction accuracy for disease state improved with inclusion of both variables. A positive correlation between local field shift and genetic disease burden was also found, and there was a trend toward significant correlations between local field shift and neurocognitive tests of working memory and executive function. CONCLUSIONS: Subjects with premanifest Huntington disease exhibit differences in 7T MR imaging phase within the caudate nuclei that correlate with genetic disease burden and trend with neurocognitive assessments. Ultra-high-field MR imaging of quantitative phase may be a useful approach for monitoring neurodegeneration in premanifest Huntington disease.

Success and failure of artesunate treatment in five transplant recipients with disease caused by drug-resistant cytomegalovirus.

Cytomegalovirus (CMV) strains resistant to ganciclovir, cidofovir and/or foscarnet were genotypically and phenotypically characterised in two haematopoietic stem cell transplant recipients and three solid-organ transplant recipients with CMV disease. The anti-malaria drug artesunate led to a favourable virological and clinical response in three cases with mild CMV diseases (fever and neutropaenia) but was ineffective in two fatal CMV diseases with lung involvement in spite of a decrease in the CMV DNA load in blood and bronchoalveolar fluid.

Vibromechanical assessment of active middle ear implant stimulation in simulated middle ear effusion: a temporal bone study.

HYPOTHESIS: Active middle ear implant (AMEI) generated vibromechanical stimulation of the ossicular chain (ossicular chain vibroplasty [OCV]) or the round window (round window vibroplasty [RWV]) is not significantly affected by simulated middle ear effusion in a human temporal bone model. BACKGROUND: OCV and RWV may be employed for sensorineural, mixed, and conductive hearing losses. Although middle ear effusions may be encountered across patient populations, little is known about how effusions may affect AMEI vibromechanical efficiency. METHODS: Laser Doppler vibrometry of stapes velocities (SVs) were performed in a human temporal bone model of simulated effusion (N = 5). Baseline measurements to acoustic sinusoidal stimuli, OCV, and RWV (0.25-8 kHz) were made without effusion. The measurements were repeated with simulated middle ear effusion and compared with baseline measurements. Data were analyzed across 3 frequency bands: low (0.25-1 kHz), medium (1-3 kHz), and high (3-8 kHz). RESULTS: Acoustic stimulation with simulated middle ear effusion resulted in a significant (p < 0.001) frequency-dependent attenuation of SVs of 4, 10, and 7 dB (low, medium, and high ranges, respectively). OCV in simulated effusion resulted in attenuated SVs of 1, 5, and 14 dB (low, medium, and high) compared to without effusion; however, this attenuation was not significant (p = 0.07). Interestingly, in the setting of RWV, simulated effusion resulted in significantly (p = 0.001) increased SVs of 16, 11, and 8 dB (low, medium, and high). A 3-dB variance in AMEI efficiency was observed in repeated measurements in a single temporal bone. CONCLUSION: The efficiency of OCV was not significantly affected by the presence of a middle ear effusion. Improved efficiency, however, was observed with RWV.

The conductive hearing loss due to an experimentally induced middle ear effusion alters the interaural level and time difference cues to sound location.

Otitis media with effusion (OME) is a pathologic condition of the middle ear that leads to a mild to moderate conductive hearing loss as a result of fluid in the middle ear. Recurring OME in children during the first few years of life has been shown to be associated with poor detection and recognition of sounds in noisy environments, hypothesized to result due to altered sound localization cues. To explore this hypothesis, we simulated a middle ear effusion by filling the middle ear space of chinchillas with different viscosities and volumes of silicone oil to simulate varying degrees of OME. While the effects of middle ear effusions on the interaural level difference (ILD) cue to location are known, little is known about whether and how middle ear effusions affect interaural time differences (ITDs). Cochlear microphonic amplitudes and phases were measured in response to sounds delivered from several locations in azimuth before and after filling the middle ear with fluid. Significant attenuations (20-40 dB) of sound were observed when the middle ear was filled with at least 1.0 ml of fluid with a viscosity of 3.5 Poise (P) or greater. As expected, ILDs were altered by ~30 dB. Additionally, ITDs were shifted by ~600 µs for low frequency stimuli (<4 kHz) due to a delay in the transmission of sound to the inner ear. The data show that in an experimental model of OME, ILDs and ITDs are shifted in the spatial direction of the ear without the experimental effusion.

Performance of two commercially available automated immunoassays for the determination of Epstein-Barr virus serological status.

This study evaluated the performance of two automated Vidas (V) and Liaison (L) immunoassays for Epstein-Barr virus (EBV) serology. The detection of the viral capsid antigen (VCA) IgM, the VCA/early antigen (VCA/EA) IgG, and the Epstein-Barr nuclear antigen (EBNA) IgG was assessed on 526 sera collected for routine EBV testing in immunocompetent subjects. The determination of expected EBV status (186 EBV primary infections, 183 past EBV infections, and 157 EBV-seronegative individuals) was based on results of routine laboratory enzyme immunoassays (EIAs) together with clinical data. The sensitivity and specificity of each individual marker were determined in comparison to the expected EBV status. The agreement between the V and L profiles and the expected EBV status was established through the interpretation of combinations of the different EBV markers. Statistically significant differences between the two tests were found for the specificity of the VCA IgM marker (96.2% for V versus 93.2% for L), the sensitivity of the VCA/EA IgG marker (89% for V versus 94% for L), and the specificity of the EBNA IgG marker (96.5% for V versus 74.2% for L). The results determined for the two assays with respect to overall agreement with the established expected EBV status were not significantly different (89.7% for V versus 88.2% for L), with discrepancies mainly observed in sera referenced as primary infections. These findings demonstrated the similar performances of the Vidas and the Liaison assays for the establishment of an EBV serological status using the VCA, EA, and EBNA markers.

Third-window vibroplasty with an active middle ear implant: assessment of physiologic responses in a model of stapes fixation in Chinchilla lanigera.

HYPOTHESIS: Mechanical stimulation through a cochlear third window into the scala tympani in a chinchilla model with normal and fixed stapes can generate cochlear responses equivalent to acoustic stimuli. BACKGROUND: Cochlear stimulation via the round window (RW) using active middle ear implants (AMEIs) can produce physiologic responses similar to acoustic stimulation including in a model of stapes fixation. However, pathologic conditions, such as advanced otosclerosis, can preclude delivery of sound energy to the cochlea through the oval window and/or the RW. METHODS: Cochlear microphonic (CM) and laser Doppler vibrometer measurements of stapes and RW velocities were performed in 6 ears of 4 chinchillas. Baseline measurements to acoustic sinusoidal stimuli (0.25-8 kHz) were made. Measurements were repeated with an AMEI driving the RW or a third window to the scala tympani before and after stapes fixation. RESULTS: AMEI stimulation of the third window produced CM waveforms with morphologies similar to acoustic stimuli. CM thresholds with RW and third-window stimulation were frequency dependent but ranged from 0.25 to 10 and 0.5 to 40 mV, respectively. Stapes fixation, confirmed by laser Doppler vibrometer measurements, resulted in a significant frequency dependent impairment in CM thresholds up to 13 dB (at <3 kHz) for RW stimulation and a nonsignificant frequency-dependent improvement of up to 10 dB (at >3 kHz) via third-window stimulation. CONCLUSION: AMEI mechanical stimulation through a third window into the scala tympani produces physiologic responses nearly identical to acoustic stimulation including in a model of stapes fixation with decreased efficiency.

Physiological assessment of active middle ear implant coupling to the round window in Chinchilla lanigera.

OBJECTIVE: To study the effects of various active middle ear implant loading parameters on round window stimulation in an animal model. STUDY DESIGN: Physiological measurements of the cochlear microphonic and stapes velocity were made from active middle ear implant-generated sinusoidal stimuli with controlled changes in loading parameters. SETTING: Prospective study at an academic research institution. SUBJECTS AND METHODS: Cochlear microphonic and stapes velocities (H(EV)) were measured in 6 study subjects (Chinchilla lanigera) in response to active middle ear implant (Otologics MET, Boulder, Colorado) round window stimulation with assessment of effects of varying parameters of loading pressure, interposed connective tissue, and angle of stimulation with respect to the round window membrane. RESULTS: The measured performance variabilities in repeated applications of the active middle ear implant to the round window were 2.5 dB and 5.0 dB for H(EV) and cochlear microphonic thresholds, respectively. Loading pressure applied to the round window (51-574 dynes) and angle of approach (±30° with respect to coronal plane) did not have a significant effect on cochlear microphonic thresholds or H(EV). Significant improvements in cochlear microphonic thresholds and H(EV) were observed for interposed connective tissue regardless of tissue type. CONCLUSION: Variability in performance due to repeated couplings of the active middle ear implant to the round window is small and reproducible. Interposition of connective tissue significantly improves vibration energy transfer to the cochlea. Neither changes in loading pressure nor angle of stimulation of the round window affected active middle ear implant performance.

Sound pressure transformations by the head and pinnae of the adult Chinchilla (Chinchilla lanigera).

There are three main cues to sound location: the interaural differences in time (ITD) and level (ILD) as well as the monaural spectral shape cues. These cues are generated by the spatial- and frequency-dependent filtering of propagating sound waves by the head and external ears. Although the chinchilla has been used for decades to study the anatomy, physiology, and psychophysics of audition, including binaural and spatial hearing, little is actually known about the sound pressure transformations by the head and pinnae and the resulting sound localization cues available to them. Here, we measured the directional transfer functions (DTFs), the directional components of the head-related transfer functions, for 9 adult chinchillas. The resulting localization cues were computed from the DTFs. In the frontal hemisphere, spectral notch cues were present for frequencies from ∼6-18 kHz. In general, the frequency corresponding to the notch increased with increases in source elevation as well as in azimuth towards the ipsilateral ear. The ILDs demonstrated a strong correlation with source azimuth and frequency. The maximum ILDs were <10 dB for frequencies <5 kHz, and ranged from 10-30 dB for the frequencies >5 kHz. The maximum ITDs were dependent on frequency, yielding 236 µs at 4 kHz and 336 µs at 250 Hz. Removal of the pinnae eliminated the spectral notch cues, reduced the acoustic gain and the ILDs, altered the acoustic axis, and reduced the ITDs.