Studying Life Effects & Effectiveness of Palatopharyngoplasty (SLEEP) study: subjective outcomes of isolated uvulopalatopharyngoplasty.

OBJECTIVE: To test the hypothesis that uvulopalatopharyngoplasty (UPPP) improves sleep apnea-related quality of life (measured on the Functional Outcomes of Sleep Questionnaire [FOSQ]) at 3-month follow-up. Secondary objectives were to test (1) the stability of the outcomes at 6 months, (2) the effect on global sleep apnea quality-of-life change, and (3) the effect on sleep apnea symptoms. STUDY DESIGN: Multicenter, prospective, longitudinal case series. SETTING: Diverse university- and community-based otolaryngology practices. SUBJECTS AND METHODS: The cohort included 68 patients from 17 practices, with a mean ± standard deviation age of 44 ± 12 years and mean apnea-hypopnea index of 35 ± 32 events/hour. All patients underwent UPPP, defined as an open procedure modifying the shape and size of the palate, pharynx, and uvula, with or without tonsillectomy. Baseline data were collected on site before surgery, and outcome data were collected by mail 3 and 6 months after surgery, with follow-up rates of 51% and 50%, respectively. RESULTS: FOSQ scores improved from 14.3 ± 3.4 (scale 5-20, normal ≥17.9) at baseline to 17.2 ± 2.7 at 3 months (mean improvement 2.9; 95% confidence interval, 1.8-4.0; P < .001) and 17.5 ± 2.5 at 6 months (mean improvement 3.1; 95% confidence interval, 2.0-4.2; P < .001). All quality-of-life and symptom measures improved significantly at 3 and 6 months (all P < .05). CONCLUSION: This prospective, multicenter, university- and community-based study provides evidence that UPPP significantly improves disease-specific quality of life and sleep apnea symptoms in patients with sleep apnea. Validity may be limited by significant loss to follow-up and absence of an unoperated control group.

Gamma knife surgery of vestibular schwannomas: volumetric dosimetry correlations to hearing loss suggest stria vascularis devascularization as the mechanism of early hearing loss.

OBJECTIVE: Determine which variables are correlated with early hearing changes after gamma knife surgery of vestibular schwannomas (VSs). STUDY DESIGN: Prospective clinical study of hearing outcomes, radiation dosimetry, conformity, and tumor size of all sporadic unilateral VS patients treated between June 2000 and July 2009. SETTING: Tertiary referral center. PATIENTS: : Fifty-nine VS patients with at least 6 months of follow-up data were studied. INTERVENTIONS: Audiometry and imaging were performed to determine auditory thresholds, speech discrimination, and tumor size. Radiation doses to 5 volumes were measured. MAIN OUTCOME MEASURES: Pretreatment and posttreatment comparisons were performed with regard to change in tumor size; radiation dose to specific volumes including the internal auditory canal, cochlea, basal turn of the cochlea, and modiolus; and conformity of the treatment. RESULTS: The mean follow-up was 63.76 months (standard deviation, ±29.02 mo; range, 9-109 mo). The median follow-up was 65.5 months. A statistically significant association between maximum radiation dose to the cochlea volume and 3-frequency pure-tone average in patients starting with 50 dB or lesser PTA3 was demonstrated using linear regression analysis. CONCLUSION: Longitudinal changes in hearing occur over time, with the largest changes seen in the first 12 months after treatment. With our study outcomes as basis, limiting the dose of radiation to the cochlea to no more than 4 Gy would likely reduce vascular injury to the stria vascularis and improve hearing outcomes. Shielding the cochlea during the treatment planning process would be one mechanism to accomplish this goal.

Safety of high-dose corticosteroids for the treatment of autoimmune inner ear disease.

OBJECTIVE: To report the adverse effects associated with prolonged high-dose prednisone for the treatment of autoimmune inner ear disease (AIED). STUDY DESIGN: Prospective data collected as part of a multicenter, randomized, controlled trial for the treatment of corticosteroid-responsive AIED with methotrexate. SETTING: Tertiary referral centers. PATIENTS: One hundred sixteen patients with rapidly progressive, bilateral sensorineural hearing loss. INTERVENTION: All patients completed a 1-month course of prednisone (60 mg/d). In Phase 2, 67 patients with improvement in hearing underwent a monitored 18-week prednisone taper, resulting in 22 weeks of prednisone therapy at an average dose of 30 mg per day. Thirty-three patients were randomized to receive methotrexate in Phase 2. Thirty-four patients received prednisone and placebo. MAIN OUTCOME MEASURE: Adverse events (AE) in patients treated with prednisone only. RESULTS: Of 116 patients, 7 had to stop prednisone therapy during the 1-month challenge phase due to AE. Of 34 patients, 5 were unable to complete the full 22-week course of prednisone due to AE. The most common AE was hyperglycemia, which occurred in 17.6% of patients participating in Phase 2. Weight gain was also common, with a mean increase in body mass index of 1.6 kg/m2 (95% confidence interval, 0.77-2.3) during the 22-week steroid course. Patients entering Phase 2 were followed for a mean of 66 weeks. No fractures or osteonecrosis were reported. CONCLUSION: Although high-dose corticosteroids are associated with known serious side effects, prospective data in the literature are limited. The present study suggests that with appropriate patient selection, monitoring, and patient education, high-dose corticosteroids are a safe and effective treatment of AIED.

Evidence supporting functional rhinoplasty or nasal valve repair: A 25-year systematic review.

OBJECTIVE: To systematically review the existing literature supporting the efficacy of modern-day rhinoplasty techniques for treatment of nasal obstruction due to nasal valve compromise. DATA SOURCES: PubMed search of the English-language literature from January 1982 to August 2007 combined with manual review of citations within article bibliographies. REVIEW METHODS: A systematic review of the literature for the targeted objective was conducted. Citations acquired from the targeted search were filtered and primary articles were reviewed to abstract information including interventions and outcome measures. Articles were then assigned level-of-evidence grades as defined by the Oxford Centre for Evidence-Based Medicine. RESULTS: A total of 861 citations were generated and 291 abstracts were identified as potentially relevant articles. Of these abstracts, 82 articles merited full-text review. A total of 44 articles met inclusion criteria. The majority of the studies were classified as level 4 evidence, and only two studies met level 2b criteria. There was considerable variation in the quality of the studies within the level 4 category. All articles generally supported the effectiveness of functional rhinoplasty techniques for treatment of nasal obstruction. CONCLUSIONS: There is substantial level 4 evidence to support the efficacy of modern-day rhinoplasty techniques for treatment of nasal obstruction due to nasal valve collapse. More recent studies have incorporated validated patient-reported outcome measures, with more rigorous statistical analysis. Future study design improvements include the use of comparison cohorts and incorporating standardized objective outcome measures.

Quality of life after tonsillectomy in adults with recurrent or chronic tonsillitis.

OBJECTIVE: To describe changes in disease-specific and global quality of life (QOL) for adults with recurrent or chronic tonsillitis at 6 months and 1 year after tonsillectomy using two instruments: the Tonsil and Adenoid Health Status Instrument (TAHSI) and the SF-12 Health Survey (12-item short form of SF-36 Health Survey). STUDY DESIGN AND SETTING: Multicenter, prospective observational outcomes study. RESULTS: Seventy-two adults, mean age 28.0 years (SD 7.2 years), were enrolled with follow-up available for 42 adults at 6 months and for 40 adults at 1 year. Patients showed significant improvements in all six subscales of the TAHSI: airway and breathing, infection, health care utilization, cost of care, eating and swallowing, and behavior (all P < 0.0001). Significant improvements were also found in the physical functioning subscale of the SF-12 at 1 year. CONCLUSION: After tonsillectomy for recurrent and chronic tonsillitis, we found large improvements in disease-specific and global QOL. SIGNIFICANCE: Most prior studies on tonsillectomy for recurrent tonsillitis have assessed only the frequency of infections as an outcome measure. This study describes the changes in QOL measured in our cohort of reporting adults after tonsillectomy for chronic or recurrent tonsillitis. This study provides prospective evidence of the effectiveness of tonsillectomy on adult QOL.

Quality of life after tonsillectomy in children with recurrent tonsillitis.

OBJECTIVE: To describe changes in disease-specific and global quality of life (QOL) for children with recurrent or chronic tonsillitis at 6 months and 1 year after tonsillectomy using two validated instruments, the Tonsil and Adenoid Health Status Instrument (TAHSI) and the Child Health Questionaire-PF28 (CHQ-PF28). STUDY DESIGN AND SETTING: A multicenter, prospective observational outcomes study. RESULTS: Ninety-two children, mean age (SD) 10.6 (3.4) years, enrolled with follow-up available for 58 children at 6 months and 38 children at 1 year. The children showed significant improvements in all subscales of the TAHSI including airway and breathing, infection, health care utilization, cost of care, eating and swallowing (all P < 0.001), and behavior (P = 0.01). Significant improvements were also found on several subscales of the CHQ-PF28, such as general health perceptions, physical functioning, parental impact, and family activities (all P < 0.001). CONCLUSION/SIGNIFICANCE: This uncontrolled study provides prospective evidence of improved disease-specific and global QOL in children after tonsillectomy.

Gamma Knife surgery of vestibular schwannomas: longitudinal changes in vestibular function and measurement of the Dizziness Handicap Inventory.

OBJECT: Gamma Knife surgery (GKS) is one of the methods available to treat vestibular schwannomas (VSs), in addition to microsurgical resection; however, clear information regarding balance function outcomes and the impact of treatment on patients' quality of life over time remains an important clinical need. The purpose of this study was to assess the longitudinal balance outcomes and Dizziness Handicap Inventory (DHI) following GKS for VSs. METHODS: This was a prospective clinical study of balance outcomes in all patients with VSs treated in the Acoustic Neuroma and Skull Base Surgery Program at a tertiary referral center by the senior author and the Gamma Knife team between June 2000 and May 2008. The main outcome measures included preoperative vestibular testing and postoperative caloric testing performed at 6-month intervals to determine vestibular function. The DHI questionnaires were administered retrospectively to assess the impact of GKS on self-perceived disability. RESULTS: Between June 2000 and May 2008, 55 sporadic VSs were treated. There was a >or= 60-month follow-up available in 27 of these patients, >or= 48 months in 32, >or= 36 months in 38, >or= 24 months in 43, >or= 12 months in 51, and >or= 6 months in 54 (1 patient was excluded from the analysis because the follow-up was < 6 months). Various patterns of changes in vestibular function were observed in either positive or negative directions. A significant difference in total DHI score was seen only in the elderly (> 65 years old) patients pre-GKS compared with post-GKS (t = 1.34, p = 0.05). CONCLUSIONS: Longitudinal changes in vestibular function occur over time, with the largest changes seen in the first 6 months after treatment. Potential for clinical intervention, such as vestibular rehabilitation therapy, exists during this interval; however, larger cohorts must be studied to determine the timing and efficacy of this intervention. The statistically significant improvement in the DHI score in the patient cohort > 65 years old treated with GKS suggests that this group may benefit from this option when considering the symptom of dizziness.

Real-time updates of meta-analyses of HIV treatments supported by a biomedical ontology.

Meta-analyses involve a systematic statistical explanation of available evidence and are a commonly used systematic reviewing strategy for addressing health related scientific research. Publication biases often delay reporting of meta-analyses and subsequent policy making. Ontologies have the capacity to provide real time meta-analyses that can reduce publication delay. The purpose of this study was to describe the meta-analytic process of a recently revised ontology. Three recently published meta-analyses were replicated using an ontology that extracts appropriate statistical "tags" from the originally reviewed published manuscripts. The ontology was able to closely represent the findings of the original meta-analysis including funnel, forest, and summary statistics. The use of an ontology could improve the speed in which meta-analytic publications occur as well as potentially standardizing the required elements within a randomized controlled trial. The findings in this study demonstrate similar ontological output as used in the Trial Bank Project with decreased time requirements of the manuscript author and the software programmers. The use of an ontology may improve the reporting of meta-analysis and, when combined with an open access website, should assist in timely policy-making decisions by healthcare providers.

Treatment of tinnitus with gabapentin: a pilot study.

OBJECTIVE: To evaluate the effectiveness of gabapentin (Neurontin) improve the disease-specific quality of life in patients with moderate tinnitus. STUDY DESIGN: Randomized, double blind, placebo-controlled clinical trial. SETTING: Single-center academic outpatient otolaryngology practice. INTERVENTION: Gabapentin 1800 mg daily versus placebo. MAIN OUTCOME MEASURES: The study design is a randomized, double blind placebo controlled single site trial conducted in an academic medical center. Inclusion criteria included patients between ages 18 and 70 with a complaint of nonpulsatile, subjective tinnitus, bilateral or unilateral, greater than 3 months in duration. The primary outcome measure is the Tinnitus Handicap Inventory; secondary measures include the Profile of Mood States (POMS) rating scale, subjective tinnitus severity. The null hypothesis addressed in this study is that the drug would not result in significant alleviation of the symptom of tinnitus. RESULTS: Seventy-six patients completed the trial; of these 52 received the drug. No significant differences were found between the two groups after 5 weeks of treatment with gabapentin. CONCLUSION: There is insufficient evidence to support the effectiveness of gabapentin in the treatment of tinnitus.

Quality of life of patients with otitis media and caregivers: a multicenter study.

OBJECTIVE: The objective of this study was to determine the quality of life of otitis media (OM) patients and their caregivers. STUDY DESIGN: A cross-sectional study was conducted at 11 otolaryngology and five pediatric clinics in the United States between July 1998 and August 1999. All patients, regardless of primary complaint, completed a demographic survey, OM-6 survey, and Child Health Questionaire-PF28 survey by proxy. Physicians completed an International Classification of Diseases, 9th Revision diagnosis sheet for each patient. METHODS: Analysis, including Spearman rank correlation, was restricted to study patients with active OM. RESULTS: A total of 1,001 patients with active OM were identified: 503 OM with effusion, 267 acute OM, and 258 recurrent acute OM. Median patient age was 2 years (interquartile range, 1-5). Mean caretaker age was 32.6 years (standard deviation, 7.4). There was moderate correlation between OM frequency and physical suffering (r = 0.50; P < .001) and caregiver concerns (r = 0.45; P < .001). Moderate correlation was found between percentage of time with fluid in the ears and caregiver concerns (r = 0.46; P < .001) and physical suffering (r = 0.43; P < .001). OM patients over 5 years of age scored significantly worse than healthy children ages 5 to 7 years in almost all areas of global health, including physical functioning and impact on caretaker's personal time and emotions. CONCLUSION: The global quality of life of patients with OM over 5 years of age is worse than that of healthy children of similar age. Physical suffering and caregiver concerns are associated with frequent OM or effusion duration. Hopefully, these results will direct the focus of future outcomes studies.

Clinical practice guideline: acute otitis externa.

OBJECTIVE: This guideline provides evidence-based recommendations to manage diffuse acute otitis externa (AOE), defined as generalized inflammation of the external ear canal, which may also involve the pinna or tympanic membrane. The primary purpose is to promote appropriate use of oral and topical antimicrobials and to highlight the need for adequate pain relief. STUDY DESIGN: In creating this guideline, the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) selected a development group representing the fields of otolaryngology-head and neck surgery, pediatrics, family medicine, infectious disease, internal medicine, emergency medicine, and medical informatics. The guideline was created with the use of an explicit, a priori, evidence-based protocol. RESULTS: The group made a strong recommendation that management of AOE should include an assessment of pain, and the clinician should recommend analgesic treatment based on the severity of pain. The group made recommendations that clinicians should: 1) distinguish diffuse AOE from other causes of otalgia, otorrhea, and inflammation of the ear canal; 2) assess the patient with diffuse AOE for factors that modify management (nonintact tympanic membrane, tympanostomy tube, diabetes, immunocompromised state, prior radiotherapy); and 3) use topical preparations for initial therapy of diffuse, uncomplicated AOE; systemic antimicrobial therapy should not be used unless there is extension outside of the ear canal or the presence of specific host factors that would indicate a need for systemic therapy. The group made additional recommendations that: 4) the choice of topical antimicrobial therapy of diffuse AOE should be based on efficacy, low incidence of adverse events, likelihood of adherence to therapy, and cost; 5) clinicians should inform patients how to administer topical drops, and when the ear canal is obstructed, delivery of topical preparations should be enhanced by aural toilet, placing a wick, or both; 6) when the patient has a tympanostomy tube or known perforation of the tympanic membrane, the clinician should prescribe a nonototoxic topical preparation; and 7) if the patient fails to respond to the initial therapeutic option within 48 to 72 hours, the clinician should reassess the patient to confirm the diagnosis of diffuse AOE and to exclude other causes of illness. And finally, the panel compiled a list of research needs based on limitations of the evidence reviewed. CONCLUSION: This clinical practice guideline is not intended as a sole source of guidance in evaluating patients with AOE. Rather, it is designed to assist clinicians by providing an evidence-based framework for decision-making strategies. It is not intended to replace clinical judgment or establish a protocol for all individuals with this condition and may not provide the only appropriate approach to the diagnosis and management of this problem. SIGNIFICANCE: This is the first, explicit, evidence-based clinical practice guideline on acute otitis externa, and the first clinical practice guideline produced independently by the AAO-HNSF.

Optimal duration of allergic rhinitis clinical trials.

OBJECTIVE: Guidelines have been published by the Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) for the conduct of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) studies. These guidelines have differences regarding the duration of such trials: the FDA suggests 2 weeks for SAR and 4 weeks for PAR but the EMEA suggests 2 to 4 weeks for SAR and 6 to 12 weeks for PAR trials. In the interest of global harmonization, it would be desirable to have a uniform duration of such trials so that investigators, internationally, would be able to readily compare results for various types of treatments based on a single standard. Therefore, we performed an evidence-based review to answer the clinical question, What is the optimal duration for SAR and PAR clinical trials? METHODS: We performed a MEDLINE search of the published literature from 1995 to the present. We used appropriate search terms, such as allergic rhinitis, seasonal allergic rhinitis, perennial allergic rhinitis, SAR, and PAR, to identify pertinent articles. These articles were reviewed and graded according to the evidence quality. RESULTS: After an initial screening of more than 300 articles, 138 articles were analyzed thoroughly. No study specifically addressed the question of the optimal duration of SAR or PAR clinical trials. CONCLUSIONS: We conclude that the current FDA (draft) guidelines calling for a study length of 2 weeks for the assessment of drug efficacy for SAR and 4 weeks for the study of drug efficacy in PAR are appropriate and that longer study periods are not likely to add meaningfully to the assessment of drug efficacy.

Serial audiometry in a clinical trial of AIED treatment.

OBJECTIVE: We analyzed pure-tone and speech audiometric results from a prospective trial of anti-inflammatory treatment of subjects with active autoimmune inner ear disease (AIED). We sought to characterize the pattern and size of the treatment effect as reflected in clinical audiometry and to identify audiometric predictors of response to steroid treatment of AIED. SUBJECTS: Adult participants demonstrated clinically established criteria for AIED (n = 116). Eligibility required audiometric evidence of active AIED as indicated by idiopathic sensorineural hearing loss with threshold elevations within 3 months of enrollment. METHODS: We evaluated audiometric changes after 4 weeks of treatment with pharmacologic doses (60 mg/day) of prednisone. We examined the relationship between audiometric pure-tone thresholds at baseline and changes in word intelligibility score (WIS) using parametric and nonparametric analyses. Magnitudes of change were assessed using independent or paired t-tests. Separate analyses were performed on subgroups that did or did not show improved WIS score with steroid treatment. RESULTS: Overall mean pure-tone averages improved from baseline to closeout of prednisone treatment in better hearing ears from 52.4 to 48.3 dB (p < .0001). Mean WIS improved in the better ear from 71.4% to 78.1% (p < .0001). Of pure-tone measures, only the six-tone average showed significant correlation with both the absolute improvements in WIS and with the percentage change in WIS after treatment. Individual frequencies at baseline showed no significant relationship with changes in WIS score after treatment. In 69 (59.5%) of 116 subjects, WIS improved (range, 2-80%) in the better ear. In these subjects, the baseline pure-tone thresholds and pure-tone averages correlated significantly and positively with improvement in WIS. CONCLUSIONS: Steroid treatment in AIED-mediated hearing loss produce variable but significant hearing gains. Neither a focal, cochleotopic region of greatest vulnerability to AIED nor frequency-specific amenability to treatment were evident. We did observe that analysis of predictors and the degree of treatment effect vary with different approaches to measuring change in the WIS. Depending on the approach adopted, the size of the treatment effect may be greatest across intermediate hearing levels at baseline. These observations offer an audiometric database that may enable greater precision in judging clinically meaningful parameters for future studies of AIED treatment and other interventions for sensorineural hearing loss.

The Cooperative Outcomes Group for ENT: a multicenter prospective cohort study on the effectiveness of medical and surgical treatment for patients with chronic rhinosinusitis.

OBJECTIVE: To assess outcomes for patients with chronic rhinosinusitis. STUDY DESIGN AND SETTING: Prospective, multicenter study; 31 otolaryngologists enrolled 276 adult patients with chronic rhinosinusitis; patients completed surveys at 3-month intervals, and physicians provided clinical and treatment data. The primary outcome measure was the Chronic Sinusitis Survey-Duration (CSS-D). RESULTS: One hundred seventeen adult patients completed 12-month follow-up. Most patients reported sinus symptoms lasting longer than 3 years (74%). Patients showed significant improvement (group P < 0.0001) in the CSS-D score at each follow-up interval. Baseline CSS-D ( P < 0.0001), surgical intervention ( P < 0.003), and Lund-McKay score ( P < 0.04) were predictive of clinical success in regression analysis. CONCLUSIONS: Patients referred to an otolaryngologist have a severe sinus illness. Treatment by an otolaryngologist was associated with significant improvement in sinus-related symptoms. SIGNIFICANCE: The study demonstrated the feasibility of multicenter outcome studies in chronic rhinosinusitis and generated testable hypotheses for future investigation. EBM RATING: C.

The Cooperative Outcomes Group for ENT: a multicenter prospective cohort study on the outcomes of tympanostomy tubes for children with otitis media.

OBJECTIVE: Outcomes for patients with otitis media were assessed in this prospective, multicenter study. STUDY DESIGN AND SETTING: Thirty-one otolaryngologists enrolled 272 pediatric patients with otitis media; caregivers completed surveys at 3-month intervals, and clinical and treatment data was also collected. The Otitis Media 6 (OM-6) was the primary outcome measure. RESULTS: One hundred seventy-seven patients (mean age 2.0 years) completed 3-month follow-up. One hundred thirty-seven patients underwent tympanostomy tube placement. Large improvements in disease-specific quality of life (QOL) were seen up to 9 months of follow-up. Baseline OM-6 score was the best predictor of clinical success in regression modeling. CONCLUSIONS: Patients referred to an otolaryngologist for treatment of otitis media see large improvements in disease-specific QOL regardless of treatment rendered. SIGNIFICANCE: The study demonstrates the feasibility of multicenter outcomes studies and confirms appropriate triage of patients with otitis media into surgical versus medical interventions. EBM RATING: C.

Evidence supporting endoscopic sinus surgery in the management of adult chronic rhinosinusitis: a systematic review.

BACKGROUND: Evidence-based medicine calls for a critical evaluation of the scientific evidence for treatments of disease. This report synthesizes the available evidence on the use of endoscopic sinus surgery (ESS) in the management of adult chronic rhinosinusitis (CRS) examining the clinical question: "In adults with CRS who have failed medical management, does ESS improve symptoms and/or quality of life (QOL)?" METHODS: The American Rhinologic Society and the American Academy of Otolaryngology-Head and Neck Surgery convened a steering committee composed of the authors. Primary research articles evaluated for this report were identified using appropriate search terms and a Medline search. Two authors independently reviewed each article. Articles were assigned an evidence level based on accepted guidelines (level 1 = randomized trials; level 2 = prospective cohort studies with comparison group; level 3 = case-control studies; level 4 = retrospective case series; level 5 = expert opinion). RESULTS: We identified 886 abstracts to review, retrieved 75 articles for full review, and included 45 articles in our report. The vast majority of articles represented level 4 evidence (n = 42) and two articles represented level 5 evidence. One article was identified that qualified for level 2 evidence. All of these articles generally supported the finding that ESS improves symptoms and/or QOL in adult patients with CRS. CONCLUSION: There is substantial level 4 evidence with supporting level 2 evidence that ESS is effective in improving symptoms and/or QOL in adult patients with CRS. Future research efforts should focus on prospective studies that include appropriate comparison groups in their design.

Animal ototoxicity of topical antibiotics and the relevance to clinical treatment of human subjects.

OBJECTIVE: The objective of this study was to systematically review the literature on animal ototoxicity from ototopical medications. A secondary objective was to assess the relevance of animal data to the use of ototopical drops in clinical situations involving humans. STUDY DESIGN: We performed a MEDLINE search of the published literature using appropriate search terms to identify pertinent articles, which were reviewed, summarized, and tabulated. RESULTS: One hundred seventy-three articles were reviewed; 61 articles were appropriate to the study question and were further analyzed. CONCLUSIONS: Virtually all studies demonstrate that aminoglycoside antibiotics, when applied topically into the middle ear space, are ototoxic in experimental animals.