Good practice in clinical trials advocates common standards for assessing and reporting condition-specific complaints ("outcome domains"). For tinnitus, there is no common standard. The Core Outcome Measures in Tinnitus International Delphi (COMiT'ID) study created recommendations that are relevant to the most common intervention approaches for chronic subjective tinnitus in adults using consensus methods. Here, the objectives were to examine why it is important to tailor outcome domain selection to the tinnitus intervention that is being evaluated in the clinical trial and to demonstrate that the COMiT'ID recommendations are robust. The COMiT'ID study used an online three-round Delphi method with three separate surveys for sound-, psychology-, and pharmacology-based interventions. Survey data were analyzed to assess quality and confidence in the consensus achieved across surveys and stakeholder groups and between survey rounds. Results found participants were highly discriminatory in their decision-making. Of the 34 outcome domains reaching the prespecified consensus definition in the final round, 17 (50%) were unique to one intervention, while only 12 (35%) were common to all three. Robustness was demonstrated by an acceptable level of agreement across and within stakeholder groups, across survey rounds, across medical specialties (for the health-care practitioners), and across health-care users with varying tinnitus duration. There were few dissenting voices, and results showed no attrition bias. In conclusion, there is compelling evidence that one set of outcomes does not fit all therapeutic aims. Our analyses evidence robust decisions by the electronic Delphi process, leading to recommendations for three unique intervention-specific outcome domain sets. This provides an important starting point for standardization.
We report an extremely rare case of duplication of the internal auditory canal associated with dysfunction of both the facial and vestibulocochlear nerves. We also review the literature regarding the integrity of the facial and vestibulocochlear nerves in such cases.
Clinical presentation of Menière's disease in children is not as typical as in adults. The triad of vertigo, tinnitus and deafness are not usually elicited, diagnosis often being made after years of follow up and batteries of investigation. A case of Menière's disease in a 3-year-old boy is presented. The diagnosis was only obvious at the age of 8 when the triad of vertigo, deafness and tinnitus were present. His disease progressed despite a trial of intratympanic gentamicin injections and endolymphatic sac decompression. Vestibular nerve section was subsequently performed for his intractable disease. Following the procedure he was asymptomatic and able to attend school.
AUT00063 is an experimental new medicine that has been demonstrated to suppress spontaneous hyperactivity by modulating the action of voltage-gated potassium-channels in central auditory cortical neurons of a rodent model. This neurobiological property makes it a good candidate for treating the central component of subjective tinnitus but this has not yet been tested in humans. The main purpose of the QUIET-1 (QUest In Eliminating Tinnitus) trial was to examine the effect of AUT00063 on the severity of tinnitus symptoms in people with subjective tinnitus. The trial was a randomised, placebo-controlled, observer, physician and participant blinded multi-centre superiority trial with two parallel groups and a primary endpoint of functional impact on tinnitus 28 days after the first drug dosing day. The trial design overcame the scale and logistical challenges of delivering a scientifically robust, statistically powered multi-centre study for subjective tinnitus within the National Health Service in England. The trial was terminated early for futility. Overall, 212 participants consented across 18 sites with 91 participants randomised to groups using age, gender, tinnitus symptom severity and hearing status as minimisation factors. While the pharmacokinetic markers confirm the uptake of AUT00063 in the body, within the expected therapeutic range, with respect to clinical benefit findings indicated that AUT00063 was not effective in alleviating tinnitus symptoms (1.56 point change in Tinnitus Functional Index). In terms of clinical harms, results indicated that a daily dose of 800 mg capsules of AUT00063 taken for 28 days was safe and well tolerated. These findings provide significant advances in the drug development field for hearing sciences, but raise questions about the predictive validity of certain rodent models of noise-induced hearing loss and tinnitus, as least for the mechanism evaluated in the present study. Trial Registration: (EudraCT) 2014-002179-27; NCT02315508.