Different bimodal neuromodulation settings reduce tinnitus symptoms in a large randomized trial.

More than 10% of the population suffers from tinnitus, which is a phantom auditory condition that is coded within the brain. A new neuromodulation approach to treat tinnitus has emerged that combines sound with electrical stimulation of somatosensory pathways, supported by multiple animal studies demonstrating that bimodal stimulation can elicit extensive neural plasticity within the auditory brain. More recently, in a large-scale clinical trial, bimodal neuromodulation combining sound and tongue stimulation drove significant reductions in tinnitus symptom severity during the first 6 weeks of treatment, followed by diminishing improvements during the second 6 weeks of treatment. The primary objective of the large-scale randomized and double-blinded study presented in this paper was to determine if background wideband noise as used in the previous clinical trial was necessary for bimodal treatment efficacy. An additional objective was to determine if adjusting the parameter settings after 6 weeks of treatment could overcome treatment habituation effects observed in the previous study. The primary endpoint at 6-weeks involved within-arm and between-arm comparisons for two treatment arms with different bimodal neuromodulation settings based on two widely used and validated outcome instruments, Tinnitus Handicap Inventory and Tinnitus Functional Index. Both treatment arms exhibited a statistically significant reduction in tinnitus symptoms during the first 6-weeks, which was further reduced significantly during the second 6-weeks by changing the parameter settings (Cohen's d effect size for full treatment period per arm and outcome measure ranged from - 0.7 to - 1.4). There were no significant differences between arms, in which tongue stimulation combined with only pure tones and without background wideband noise was sufficient to reduce tinnitus symptoms. These therapeutic effects were sustained up to 12 months after the treatment ended. The study included two additional exploratory arms, including one arm that presented only sound stimuli during the first 6 weeks of treatment and bimodal stimulation in the second 6 weeks of treatment. This arm revealed the criticality of combining tongue stimulation with sound for treatment efficacy. Overall, there were no treatment-related serious adverse events and a high compliance rate (83.8%) with 70.3% of participants indicating benefit. The discovery that adjusting stimulation parameters overcomes previously observed treatment habituation can be used to drive greater therapeutic effects and opens up new opportunities for optimizing stimuli and enhancing clinical outcomes for tinnitus patients with bimodal neuromodulation.

A national survey of workplace-related musculoskeletal disorder and ergonomic practices amongst Irish otolaryngologists.

BACKGROUND: Work-related musculoskeletal disorder (WRMD) is a rising concern for surgeons, particularly those involved in minimally invasive surgery (MIS). Severe WRMD can adversely affect surgeon's health and foreshorten their careers if not appropriately managed. AIMS: The aim of this study was to assess the prevalence of WRMD among Irish otolaryngologists and determine their knowledge of the best ergonomic principles. METHODS: A national survey was distributed electronically to all otolaryngology consultants and non-consultant hospital doctors (NCHDs) in Ireland. The survey assessed respondents' age, grade, history of WRMD, and treatments sought for WRMD and knowledge of best ergonomic practice. RESULTS: Forty-nine of one hundred and two respondents completed the survey. The lifetime prevalence of WRMD among this cohort was 75.5%. Pain was the most commonly experienced symptom at 71.4%. The neck was the most frequently affected location (59.2%). Treatment for WRMD was sought by 36.7% of participants. The majority of respondents (73.5%) were unaware of recommendations made in the field of surgical ergonomics, while 85.7% were interested in learning ergonomic principles. CONCLUSION: This study demonstrates a high prevalence of WRMD amongst otolaryngologists working in Ireland and demonstrates a need for ergonomic training for surgeons.

Bimodal neuromodulation combining sound and tongue stimulation reduces tinnitus symptoms in a large randomized clinical study.

Tinnitus is a phantom auditory perception coded in the brain that can be bothersome or debilitating, affecting 10 to 15% of the population. Currently, there is no clinically recommended drug or device treatment for this major health condition. Animal research has revealed that sound paired with electrical somatosensory stimulation can drive extensive plasticity within the brain for tinnitus treatment. To investigate this bimodal neuromodulation approach in humans, we evaluated a noninvasive device that delivers sound to the ears and electrical stimulation to the tongue in a randomized, double-blinded, exploratory study that enrolled 326 adults with chronic subjective tinnitus. Participants were randomized into three parallel arms with different stimulation settings. Clinical outcomes were evaluated over a 12-week treatment period and a 12-month posttreatment phase. For the primary endpoints, participants achieved a statistically significant reduction in tinnitus symptom severity at the end of treatment based on two commonly used outcome measures, Tinnitus Handicap Inventory (Cohen's d effect size: -0.87 to -0.92 across arms; P < 0.001) and Tinnitus Functional Index (-0.77 to -0.87; P < 0.001). Therapeutic improvements continued for 12 months after treatment for specific bimodal stimulation settings, which had not previously been demonstrated in a large cohort for a tinnitus intervention. The treatment also achieved high compliance and satisfaction rates with no treatment-related serious adverse events. These positive therapeutic and long-term results motivate further clinical trials toward establishing bimodal neuromodulation as a clinically recommended device treatment for tinnitus.

Noninvasive Bimodal Neuromodulation for the Treatment of Tinnitus: Protocol for a Second Large-Scale Double-Blind Randomized Clinical Trial to Optimize Stimulation Parameters.

BACKGROUND: There is increasing evidence from animal and human studies that bimodal neuromodulation combining sound and electrical somatosensory stimulation of the tongue can induce extensive brain changes and treat tinnitus. OBJECTIVE: The main objectives of the proposed clinical study are to confirm the efficacy, safety, and tolerability of treatment demonstrated in a previous large-scale study of bimodal auditory and trigeminal nerve (tongue) stimulation (Treatment Evaluation of Neuromodulation for Tinnitus - Stage A1); evaluate the therapeutic effects of adjusting stimulation parameters over time; and determine the contribution of different features of bimodal stimulation in improving tinnitus outcomes. METHODS: This study will be a prospective, randomized, double-blind, parallel-arm, comparative clinical trial of a 12-week treatment for tinnitus using a Conformité Européenne (CE)-marked device with a pre-post and 12-month follow-up design. Four treatment arms will be investigated, in which each arm consists of two different stimulation settings, with the first setting presented during the first 6 weeks and the second setting presented during the next 6 weeks of treatment. The study will enroll 192 participants, split in a ratio of 80:80:16:16 across the four arms. Participants will be randomized to one of four arms and stratified to minimize baseline variability in four categories: two separate strata for sound level tolerance (using loudness discomfort level as indicators for hyperacusis severity), high tinnitus symptom severity based on the Tinnitus Handicap Inventory (THI), and tinnitus laterality. The primary efficacy endpoints are within-arm changes in THI and Tinnitus Functional Index as well as between-arm changes in THI after 6 weeks of treatment for the full cohort and two subgroups of tinnitus participants (ie, one hyperacusis subgroup and a high tinnitus symptom severity subgroup). Additional efficacy endpoints include within-arm or between-arm changes in THI after 6 or 12 weeks of treatment and in different subgroups of tinnitus participants as well as at posttreatment assessments at 6 weeks, 6 months, and 12 months. Treatment safety, attrition rates, and compliance rates will also be assessed and reported. RESULTS: This study protocol was approved by the Tallaght University Hospital/St. James's Hospital Joint Research Ethics Committee in Dublin, Ireland. The first participant was enrolled on March 20, 2018. The data collection and database lock are expected to be completed by February 2020, and the data analysis and manuscript submission are expected to be conducted in autumn of 2020. CONCLUSIONS: The findings of this study will be disseminated to relevant research, clinical, and health services and patient communities through publications in peer-reviewed journals and presentations at scientific and clinical conferences. TRIAL REGISTRATION: ClinicalTrials.gov NCT03530306; https://clinicaltrials.gov/ct2/show/NCT03530306. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13176.

Bi-modal stimulation in the treatment of tinnitus: a study protocol for an exploratory trial to optimise stimulation parameters and patient subtyping.

INTRODUCTION: Tinnitus is the perception of sound in the absence of a corresponding external acoustic stimulus. Bimodal neuromodulation is emerging as a promising treatment for this condition. The main objectives of this study are to investigate the relevance of interstimulus timing and the choices of acoustic and tongue stimuli for a proprietary bimodal (auditory and somatosensory) neuromodulation device, as well as to explore whether specific subtypes of patients are differentially responsive to this novel intervention for reducing the symptoms of chronic tinnitus. METHODS AND ANALYSIS: This is a two-site, randomised, triple-blind, exploratory study of a proprietary neuromodulation device with a pre-post and 12-month follow-up design. Three different bimodal stimulation parameter sets will be examined. The study will enrol 342 patients, split 80:20 between two sites (Dublin, Ireland and Regensburg, Germany), to complete 12 weeks of treatment with the device. Patients will be allocated to one of three arms using a stepwise stratification according to four binary categories: tinnitus tonality, sound level tolerance (using loudness discomfort level of <60 dB SL as an indicator for hyperacusis), hearing thresholds and presence of a noise-induced audiometric profile. The main indicators of relative clinical efficacy for the three different parameter sets are two patient-reported outcomes measures, the Tinnitus Handicap Inventory and the Tinnitus Functional Index, after 12 weeks of intervention. Clinical efficacy will be further explored in a series of patient subtypes, split by the stratification variables and by presence of a somatic tinnitus. Evidence for sustained effects on the psychological and functional impact of tinnitus will be followed up for 12 months. Safety data will be collected and reported. A number of feasibility measures to inform future trial design include: reasons for exclusion, completeness of data collection, attrition rates, patient's adherence to the device usage as per manufacturer's instructions and evaluation of alternative methods for estimating tinnitus impact and tinnitus loudness. ETHICS AND DISSEMINATION: This study protocol is approved by the Tallaght Hospital/St. James's Hospital Joint Research Ethics Committee in Dublin, Ireland, and by the Ethics Committee of the University Clinic Regensburg, Germany. Findings will be disseminated to relevant research, clinical, health service and patient communities through publications in peer-reviewed and popular science journals and presentations at scientific and clinical conferences. TRIAL REGISTRATION NUMBER: The trial is registered on ClinicalTrials.gov (NCT02669069) Pre-results.

An Investigation of Feasibility and Safety of Bi-Modal Stimulation for the Treatment of Tinnitus: An Open-Label Pilot Study.

OBJECTIVES: Tinnitus is the perception of sound in the absence of an external auditory stimulus. It is widely believed that tinnitus, in patients with associated hearing loss, is a neurological phenomenon primarily affecting the central auditory structures. However, there is growing evidence for the involvement of the somatosensory system in this form of tinnitus. For this reason it has been suggested that the condition may be amenable to bi-modal stimulation of the auditory and somatosensory systems. We conducted a pilot study to investigate the feasibility and safety of a device that delivers simultaneous auditory and somatosensory stimulation to treat the symptoms of chronic tinnitus. METHODS: A cohort of 54 patients used the stimulation device for 10 weeks. Auditory stimulation was delivered via headphones and somatosensory stimulation was delivered via electrical stimulation of the tongue. Patient usage, logged by the device, was used to classify patients as compliant or noncompliant. Safety was assessed by reported adverse events and changes in tinnitus outcome measures. Response to treatment was assessed using tinnitus outcome measures: Minimum Masking Level (MML), Tinnitus Loudness Matching (TLM), and Tinnitus Handicap Inventory (THI). RESULTS: The device was well tolerated by patients and no adverse events or serious difficulties using the device were reported. Overall, 68% of patients met the defined compliance threshold. Compliant patients (N = 30) demonstrated statistically significant improvements in mean outcome measures after 10 weeks of treatment: THI (-11.7 pts, p < 0.001), TLM (-7.5dB, p < 0.001), and MML (-9.7dB, p < 0.001). The noncompliant group (N = 14) demonstrated no statistical improvements. CONCLUSION: This study demonstrates the feasibility and safety of a new bi-modal stimulation device and supports the potential efficacy of this new treatment for tinnitus.

Spontaneous retropharyngeal and cervical emphysema: a rare singer's injury.

Spontaneous retropharyngeal and cervical emphysema is rare. We describe a case that was unusual in its etiology: the result of singing. Although this condition is usually benign, hospital admission for close observation and supportive therapy is prudent.

Detection of bone marrow micrometastases in the rib marrow of head and neck cancer patients: a prospective pilot study.

Flow cytometry has been validated as an objective method of demonstrating and quantifying micrometastases. Micrometastases within bone marrow indicate a poor prognosis in patients with upper gastrointestinal, colorectal and breast epithelial tumours. We prospectively sought to assess the feasibility of testing rib marrow for bone marrow micrometastases in head and neck cancer and to report their frequency in a cohort of patients. Nine patients were enrolled in the study. Bone marrow was obtained before manipulation of the primary tumour. Micrometastatic cells were detected by staining contaminant cytokeratin-18 positive cells and using the twin techniques of immuncytochemistry and flow cytometry. Cellular marrow was retrieved in 100% of cases. Micrometastases were detected in one out of nine epithelial tumours on both flow cytometry and immunocytochemistry. The detection rate appeared to be independent of TN staging. We were unable to culture the cells. Preoperative detection of bone marrow micrometastases may reflect transient shedding of cells, metastatic potential or residual disease. This prospective study confirms the feasibility of using rib marrow in future studies investigating micrometastases in head and neck cancer.

Paratracheal lymph node involvement in advanced cancer of the larynx, hypopharynx, and cervical esophagus.

OBJECTIVES/HYPOTHESIS: The presence of nodal metastatic disease in head and neck cancer is the foremost prognostic factor. Although neck dissection is the surgical gold standard for the treatment of cervical lymphatic spread, the paratracheal nodal group is not routinely included in the dissection. The study determined the nodal yield, presence of metastases, and prognostic importance of paratracheal nodes in patients with advanced carcinoma of the upper aerodigestive tract. STUDY DESIGN: Prospective histological and survival analysis. METHODS: Over a 4-year period (October 1994-June 1998), consecutive patients undergoing laryngectomy with or without pharyngectomy or cervical esophagectomy underwent paratracheal node dissection on a prospective basis. Nodal tissue was examined for the presence of metastases. Statistical comparison of survival probability was determined by use of log-rank/chi2 test. RESULTS: Fifty patients have been included in the study to date, with a minimal follow-up of 3 years. The average number of paratracheal nodes dissected was three per side (range, 1-5). Thirteen (26%) patients demonstrated histological evidence of paratracheal nodal metastases (larynx, 20%; postcricoid/cervical esophageal region, 43%). Five patients (10%) had positive paratracheal nodes alone in a histologically negative cervical neck dissection. The majority of positive paratracheal nodes were less than 1 cm in diameter and appeared negative preoperatively. The absence of positive paratracheal nodes may have a survival benefit. CONCLUSION: The study highlighted the propensity of advanced carcinoma of the upper aerodigestive tract to involve the paratracheal nodes. This area should be routinely dissected in the surgical management of these tumors.