Efficacy and Safety of Ciprofloxacin Plus Fluocinolone Acetonide Among Patients With Acute Otitis Externa: A Randomized Clinical Trial.

Importance: Ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution seems to be efficacious and safe in treating acute otitis externa (AOE) compared with ciprofloxacin, 0.3%, or fluocinolone acetonide, 0.025%, otic solution alone. Objective: To evaluate the superiority of ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution compared with ciprofloxacin, 0.3%, or fluocinolone acetonide, 0.025%, otic solution alone in treating AOE. Design, Setting, and Participants: A phase 3 randomized, double-blind, active-controlled clinical trial was conducted between August 1, 2017, and September 14, 2018, at 36 centers in the US. The study population comprised 493 patients aged 6 months or older with AOE of less than 21 days' duration with otorrhea, moderate or severe otalgia, and edema, as well as a Brighton grading of II or III (tympanic membrane obscure but without systemic illness). Statistical analysis was performed from November 14, 2018, to February 14, 2019. Interventions: Participants were randomly assigned to receive ciprofloxacin plus fluocinolone, ciprofloxacin, or fluocinolone twice daily for 7 days and were evaluated on day 1 (visit 1; baseline), days 3 to 4 (visit 2; conducted via telephone), days 8 to 10 (visit 3; end of treatment), and days 15 to 17 (visit 4; test of cure). Main Outcomes and Measures: The primary outcome was therapeutic cure (clinical and microbiological) at the end of the treatment period. The principal secondary end point was the time to end of ear pain. Efficacy analyses were conducted in the microbiological intent-to-treat population, clinical intent-to-treat population, and microbiological intent-to-treat population with Pseudomonas aeruginosa and Staphylococcus aureus. Results: A total of 493 patients (254 female patients [51.5%]; mean [SD] age, 38.2 [23.1] years) were randomized (197 to receive ciprofloxacin plus fluocinolone, 196 to receive ciprofloxacin, and 100 to receive fluocinolone). Therapeutic cure in the modified intent-to-treat population with ciprofloxacin plus fluocinolone (63 of 103 [61.2%]) was statistically comparable to that of ciprofloxacin (49 of 91 [53.8%]; difference in response rate, 7.3%; 95% CI, -6.6% to 21.2%; P = .30) and fluocinolone (20 of 45 [44.4%]; difference in response rate, 16.7%; 95% CI, -0.6% to 34.0%; P = .06) at visit 3 and significantly superior to ciprofloxacin at visit 4 (90 of 103 [87.4%] vs 69 of 91 [75.8%]; difference in response rate, 11.6%; 95% CI, 0.7%-22.4%; P = .04). A statistically faster resolution of otalgia was achieved among patients treated with ciprofloxacin plus fluocinolone (median, 5.0 days [range, 4.2-6.3 days]) vs ciprofloxacin (median, 5.9 days [range, 4.3-7.3 days]; 95% CI, 4.3-7.3 days; P = .002) or fluocinolone (median, 7.7 days [range, 6.7-9.0 days]; 95% CI, 6.7-9.0 days; P < .001). Ciprofloxacin plus fluocinolone demonstrated statistical superiority in sustained microbiological response vs ciprofloxacin (94 of 103 [91.3%] vs 74 of 91 [81.3%]; difference in response rate, 9.9%; 95% CI, 0.3%-19.6%; P = .04) and fluocinolone (34 of 45 [75.6%]; difference in response rate, 15.7%; 95% CI, 2.0%-29.4%; P = .01) and in the microbiological outcome vs fluocinolone by visit 3 (99 of 103 [96.1%] vs 37 of 45 [82.2%]; difference in response rate, 13.9%; 95% CI, 2.1%-25.7%; P = .01) and ciprofloxacin by visit 4 (97 of 103 [94.2%] vs 77 of 91 [84.6%]; difference in response rate, 9.6%; 95% CI, 0.9%-18.2%; P = .02). Fifteen adverse events related to study medications were registered, all of which were mild or moderate. Conclusions and Relevance: Ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution was efficacious and safe in treating AOE but did not demonstrate superiority vs ciprofloxacin, 0.3%, or fluocinolone acetonide, 0.025%, otic solutions alone in the main study end point of therapeutic cure. Trial Registration: ClinicalTrials.gov Identifier: NCT03196973.

Complications and prognosis associated with intra-tympanic steroid injection to treat sudden sensorineural hearing impairment.

PURPOSE: The purpose of this study was to measure the incidence of complications in sudden sensorineural hearing loss (SSNHL) patients treated with intra-tympanic steroid injection (ITSI) and compare hearing recovery rates. MATERIALS AND METHODS: 123 patients with unilateral SSNHL receiving ITSIs were included in this study. Post-ITSI complications were documented including otalgia, dysgeusia, vertigo (duration>1 h), and persistent eardrum perforation. The pain intensity was evaluated with visual analog scale (VAS). Hearing was measured before ITSI and at 1 month after the final ITSI. We compared our patients' hearing threshold between presence and absence of different complications. RESULTS: 47.2% patients experienced post-injection otalgia with the average VAS score 3.2 (range 2-6). Five (4.1%) and six (4.9%) patients exhibited vertigo and persistent eardrum perforations, respectively. The patients were divided into three groups based on the absence of complications and the presence of vertigo and eardrum perforation. The hearing threshold improvements did not differ significantly among the three groups (p = 0.366). Although the difference was not significant (p = 0.664), the proportion of patients experiencing post-ITSI vertigo who were on contemporaneous oral steroids was lower than the proportion of non-vertigo patients on such steroids. CONCLUSION: The incidences of otalgia, vertigo, and persistent eardrum perforation in SSNHL patients treated with ITSI were 47.2%, 4.1% and 4.9%, respectively. We found no association between concurrent oral steroid use and the incidence of post-ITSI eardrum perforation or vertigo. Although statistical significance was lacking, patients who did not take contemporaneous oral steroids may have a higher rate of prolonged post-ITSI vertigo.

A Comparison of Triamcinolone Acetonide Econazole Cream and Nystatin Suspension in Treatment of Otomycosis.

OBJECTIVES/HYPOTHESIS: To compare the efficacy and adverse effects of triamcinolone acetonide econazole cream and nystatin suspension in the treatment of otomycosis, and to determine the clinical features, predisposing factors, and etiology of otomycosis. STUDY DESIGN: A prospective study. METHODS: A prospective clinical trial was conducted on 786 patients diagnosed with otomycosis. The study population was randomly divided into two treatment groups of triamcinolone acetonide econazole cream (TAEC) and nystatin suspension in a 1:1 ratio. After clearing all fungal deposits in the external auditory canal, the antimycotic drugs were locally applied for at least 2 weeks. The efficacy and adverse effects were compared between the two antifungal reagents by statistical analysis. Meanwhile, patient clinical data were collected to find out the clinical features, predisposing factors, and etiology. RESULTS: Pruritis was the most common symptom and Aspergillus niger was the leading fungal pathogen. There was high association (44.5%) of otomycosis with a history of unclean ear picking. The cure rate was 97.6% in the TAEC group and 73.5% in the nystatin group (P < .01). Treatment with TAEC resulted in 2.4% of patients complaining of discomforts (irritant dermatitis, otalgia, or headache) versus 59.8% of patients complaining discomforts treated with nystatin (P < .01). The residue rate of antifungals was 1.9% in the TAEC group and 89.9% in the nystatin group (P < .01) at the end of treatment. CONCLUSIONS: Thoroughly cleaning of the external auditory canal followed by local use of TAEC under endotoscope is an effective, convenient, and well-tolerated treatment for otomycosis. LEVEL OF EVIDENCE: 1 Laryngoscope, 131:E1640-E1646, 2021.

The possible effect of human menopausal gonadotropin on the audio-vestibular system.

OBJECTIVE: Human menopausal gonadotropin (HMG) is one of the commonest drugs used for ovarian stimulation with no reports on the audio-vestibular system. This study aims to examine HMG on the hearing profile of patients planning intracytoplasmic sperm injection (ICSI). METHODS: This prospective study was conducted from June 2016 to June 2017 in a tertiary referral hospital. The audio-vestibular system of a total of 30 patients was evaluated using pure tone audiometry, distortion product otoacoustic emissions (DPOAEs in the form of a DP-gram) and Vestibular-evoked myogenic potential (VEMP) immediately before therapy and at the day 10 after therapy. Audio-vestibular adverse effects including hearing loss, tinnitus, vertigo, and otalgia were also considered. RESULTS: Significant elevations in hearing thresholds were found on comparing thresholds at the day 10 at the onset of the study. The elevations were mostly at frequencies (1000, 2000 and 8000Hz) and did not affect speech perception. For DPOAE, significant differences were observed at all F2 frequencies on comparing both amplitudes and signal to noise ratios. Otologic complaints were significant for tinnitus and hearing loss. CONCLUSION: Significant auditory and vestibular adverse effects may result from HMG therapy, indicating the importance of prompt monitoring of auditory functions in these patients.

[Ototoxicity in head and neck cancers after radiotherapy and chemoradiotherapy: From primary prevention to tertiary prevention]. / Ototoxicité radio-induite et chimio-induite dans les cancers ORL : de la prévention primaire à la prévention tertiaire.

Each year, 15,000 head and neck cancer are treated in France. Prognosis is steadily improving. Consequently, limitation of late toxicities becomes essential. Ototoxicity is common, disabling and undervalued. We aimed to inventory primary, secondary and tertiary prevention measures to reduce ototoxicity induced by radiotherapy and chemotherapy, as well as its impact on quality of life of patients treated for head and neck cancer. External radiation therapy induced 30 to 40% of ototoxicity, including irreversible sensorineural hearing loss. Primary prevention of this risk is based on limiting the dose to the cochlea: 40Gy in case of radiotherapy alone, 10Gy during concomitant chemoradiotherapy with cisplatin. Dose gradients allowed by intensity-modulated radiotherapy help respecting these limits. Concurrent chemotherapy with high dose cisplatin (100mg/m2) also causes hearing loss by cochlear damages. Prescription of carboplatin-5-fluorouracil combination or cetuximab should be preferred in case of high risk of ototoxicity. This risk must be precisely evaluated before treatment. Ototoxicity monitoring during treatment allows early management, and lower long-term impact. Radiosensitivity predictive tests and research of genetic factors predisposing to chemo-induced ototoxicity should enable optimization of therapeutic choices and monitoring.

The use of extemporaneously compounded 1% tetracaine to improve adherence with clotrimazole 1% topical solution in the treatment of ear infection: a case report.

For most medically amenable conditions, adherence to drug therapy is a necessary condition for a successful outcome. Drug side effects, especially pain, can interfere with the desired outcome. We report a case of non-adherence due to severe pain associated with the topical use of clotrimazole 1% solution in the ear. Instillation of tetracaine 1% solution prior to the administration of the clotrimazole blocked the pain sensation allowing the patient to successfully complete the antifungal therapy.

The effects of pegylated interferon/lamivudine therapy on auditory functions in patients with chronic hepatitis B.

OBJECTIVES: The aim of this study was to assess the effects of pegylated interferon monotherapy and pegylated interferon+lamivudine combination therapy on auditory functions in patients with chronic hepatitis B (CHB) infection. METHODS: A total of 54 patients with a diagnosis of CHB were grouped into four treatment groups: patients in Group 1 received pegylated interferon-alpha 2a; patients in Group 2 received pegylated interferon-alpha 2a+lamivudine; patients in Group 3 received pegylated interferon-alpha 2b, and patients in Group 4 received pegylated interferon-alpha 2b+lamivudine treatment. The auditory system (using standard and high frequency audiometry) and the vestibulocochlear adverse effects including otalgia, tinnitus, vertigo and imbalance were assessed immediately before the onset of the study, and at the 12th, 24th, and 48th weeks of the study. RESULTS: A mean elevation of auditory threshold of 1-10dB was found in all treatment groups when the thresholds at the onset of the study and the thresholds at the 12th, 24th, and 48th weeks were compared. However, the elevations were not significant. The elevations were mostly at high frequencies (10,000, 12,000 and 16,000Hz). The most common vestibulocochlear adverse effects related to treatment were tinnitus, vertigo, imbalance, and otalgia, respectively. Tinnitus was the most common adverse effect in Group 2, vertigo was the most common in Group 3, imbalance was at equal frequency in Group 2 and 3, and otalgia was the most common adverse effect in Group 2 (p>0.05). CONCLUSION: There were no significant auditory adverse effects in the treatment groups. We think that it may be beneficial to monitor the auditory functions in patients receiving PEG-IFN treatment because of the mild elevation in the auditory thresholds (although not significant).

Adverse effects of pediatric emergency sedation after discharge.

PURPOSE: Sedation is commonly performed in children in the emergency department. However, little is known about adverse events that may occur after discharge. This study was conducted to evaluate adverse effects occurring after discharge in children following sedation in the emergency department. METHODS: Parents of 547 children receiving sedation in the emergency department of a pediatric, academic hospital were called A approximately 24 hours af t er discharge a nd asked to complete a telephone questionnaire. Data were analyzed using descriptive statistics. RESULTS: At least one adverse effect was reported in 42% of participants after discharge. This included lethargy (12%), vomiting (7%), behavioral changes (7%), headache (6%), balance/gait disturbances (5%), nausea (4%), sleep disturbances (4%), nightmares (4%), hallucinations (2%), and ear pain (0.2%). CONCLUSIONS: Children experience minor adverse effects from sedation after discharge from the emergency department. Anticipatory guidance about these adverse effects should be given to parents and caregivers prior to discharge.

Symptoms of mothers and infants related to total volatile organic compounds in household products.

The authors sought to determine whether reported symptoms of mothers and infants were associated significantly with the use of household products that raised indoor levels of total volatile organic compounds (TVOCs). Data collected from 170 homes within the Avon Longitudinal Study of Parents and Children (ALSPAC: a large birth cohort of more than 10,000) had determined which household products were associated with the highest levels of TVOCs. The latter data were collected over a period that approximated 6 mo of pregnancy and the infants' first 6 mo of life. This paper presents (a) the mothers' self-reports of the use of these products in their homes and (b) self-reported medical symptoms of mothers and infants postnatally. Higher TVOC levels were associated with air freshener and aerosol use. Infant diarrhea and earache were statistically significantly associated with air freshener use, and diarrhea and vomiting were significantly associated with aerosol use. Headache experienced by mothers 8 mo after birth was significantly associated with the use of air fresheners and aerosols; maternal depression was significantly associated with the use of air fresheners. The results of the study suggest a link between the use of products that raise indoor levels of TVOCs and an increased risk of certain symptoms among infants and their mothers.

Drug induced otalgia due to mesalazine and sulphasalazine.

A case of left otalgia in a patient suffering from longstanding ulcerative colitis is reported. The patient was treated for an exacerbation of his disease with courses of mesalazine and sulphasalazine during which time he developed otalgia. The otalgia disappeared with cessation of the drugs. It is concluded that in the absence of any other head and neck cause that the otalgia was a complication of the drug therapy.