Development of ebselen for the treatment of sensorineural hearing loss and tinnitus.

The global impact of hearing loss and related auditory dysfunction including tinnitus and hyperacusis on human health is significant and growing. A substantial body of literature has found that these hearing diseases and disorders result from significant number of genetic variations and molecular mechanisms. Investigational new drugs have been tested and several approved drugs have been repurposed in clinical trials, but no therapeutics for any auditory related indication have been FDA approved. A unique investigational new drug called ebselen (SPI-1005), that is anti-inflammatory and neuroprotective, has been shown to reduce noise-induced and aminoglycoside-induced hearing loss in animals. Multiple phase 2 clinical trials have demonstrated the safety and efficacy of SPI-1005 treatment in Meniere's disease and acute noise-induced hearing loss. SPI-1005 is currently being tested to prevent and treat tobramycin-induced ototoxicity in cystic fibrosis patients with acute lung infections. This review summarizes the published and presented data involving SPI-1005 and other drugs being tested to prevent or treat sensorineural hearing loss. Additionally, recent clinical data showing the relationship between pure tone audiometry and words-in-noise test results in a Meniere's disease are presented, which may have larger implications for the field of hearing research.

Ototoxicity in cystic fibrosis patients receiving intravenous tobramycin for acute pulmonary exacerbation: Ototoxicity following tobramycin treatment.

Aminoglycosides are commonly used to treat infections in CF patients and are highly ototoxic. The incidence of tobramycin-induced hearing loss, tinnitus, vertigo or dizziness (ototoxicity) varies widely from 0 to 56% secondary to variation in patient enrollment, dosing, audiometry, and ototoxic criteria. The aim of this study is to determine the incidence of ototoxicity after one course of once-daily IV tobramycin in CF patients. Adult CF patients with acute pulmonary exacerbations were enrolled on IV tobramycin (10 mg/kg/d, ≥10 days). Pure-tone audiometry was performed for standard and extended high frequencies in the sensitive range for ototoxicity (SRO). American-Speech-Language-Hearing-Association cochleotoxicity criteria were applied. Distortion product otoacoustic emissions (DPOAE) and the words-in-noise-test (WINT) were assessed. Tinnitus Functional Index (TFI) and Vertigo Symptoms Scale (VSS) were used. Eighteen CF patients, mean age 31.1 (18-59), were enrolled. The incidence of cochleotoxic change from baseline at 2 and 4 weeks post-treatment was 89% and 93%. For DPOAE, a measure of outer hair-cell function, the incidence of ≥5 dB decrease was 82% and 80%. For WINT, a measure of word recognition, the incidence of ≥10% decrease was 17% and 40%. For TFI, the incidence of ≥10pt increase was 12% and 8%, and for VSS, the incidence of ≥6pt increase was 0% and 8%. One course of IV tobramycin was sufficient to cause hearing loss and other ototoxic symptoms four weeks after treatment ended. Audiometric measures were more sensitive to ototoxic change than TFI & VSS. Age and duration of tobramycin treatment were not obvious factors for predicting ototoxicity.

A Comparison of the NCDB and SEER Database for Research Involving Head and Neck Cancer.

OBJECTIVE: To determine whether structural differences in data sampling between the National Cancer Database (NCDB), a non-population-based cancer registry, and Surveillance, Epidemiology, and End Results (SEER), a population-based cancer registry, result in differences in patient characteristics or oncologic outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: NCDB and SEER database. SUBJECTS AND METHODS: Patients with head and neck cancer (HNC) were included from 2004 to 2014. The primary outcome, weighted differences in characteristics between the databases, was evaluated for each head and neck subsite (oral cavity [OC], oropharynx [OP], hypopharynx [HP], and larynx [LX]). The secondary outcome measure, overall survival (OS), was evaluated using Kaplan-Meier (KM) estimates of survival and Cox proportional hazards (PH) regression modeling. RESULTS: In total, 112,007 and 340,420 HNC cases were registered in SEER and the NCDB, respectively. The mean age at diagnosis for the 4 head and neck subsites differed by no more than 1.1 years between the 2 databases. The largest difference in patient or tumor characteristics was the frequency of OC subsite lip cancer (weighted proportional difference, 6.9%; 95% confidence interval, 6.5%-7.3%). Unadjusted KM estimates of 5-year OS differed by no more than 2% (OP, HP, and LX subsites). On Cox PH modeling, adjusted hazard ratios ranged from 0.89 to 0.91 for patients of different head and neck subsites in the NCDB relative to SEER. CONCLUSIONS: Patients with HNC in the SEER database and NCDB do not greatly differ in terms of demographics, treatment, and survival. Decisions to use either database should be driven by the data fields, which vary between the registries.

The prevalence of olfactory dysfunction in chronic rhinosinusitis.

OBJECTIVES: Many studies have reported that olfactory dysfunction frequently occurs in chronic rhinosinusitis (CRS) populations; however, the prevalence and degree of olfactory loss has not been systematically studied. The aims of this study were to use combined data to report the prevalence of olfactory dysfunction and to calculate weighted averages of olfactory test scores in CRS patients. DATA SOURCES: A search was conducted in PubMed and Scopus, following the methods of Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. REVIEW METHODS: Studies reporting the prevalence of olfactory dysfunction using objective measures or olfactory test scores using validated scales were included. RESULTS: A total of 47 articles were included in a systematic review and 35 in the pooled data analysis. The prevalence of olfactory dysfunction in chronic rhinosinusitis was found to be 30.0% using the Brief Smell Identification Test, 67.0% using the 40-item Smell Identification Test, and 78.2% using the total Sniffin' Sticks score. Weighted averages ± standard deviation of olfactory test scores were 25.96 ± 7.11 using the 40-item Smell Identification Test, 8.60 ± 2.81 using the Brief Smell Identification Test, 21.96 ± 8.88 using total Sniffin' Sticks score, 5.65 ± 1.51 using Sniffin' Sticks-Threshold, 9.21 ± 4.63 using Sniffin' Sticks-Discrimination, 9.47 ± 3.92 using Sniffin' Sticks-Identification, and 8.90 ± 5.14 using the Questionnaire for Olfactory Disorders-Negative Statements. CONCLUSIONS: In CRS populations, a significant percentage of patients experience olfactory dysfunction, and mean olfactory scores are within the dysosmic range. Laryngoscope, 2016 127:309-320, 2017.