Multicenter US Clinical Trial With an Electric-Acoustic Stimulation (EAS) System in Adults: Final Outcomes.

OBJECTIVE: To demonstrate the safety and effectiveness of the MED-EL Electric-Acoustic Stimulation (EAS) System, for adults with residual low-frequency hearing and severe-to-profound hearing loss in the mid to high frequencies. STUDY DESIGN: Prospective, repeated measures. SETTING: Multicenter, hospital. PATIENTS: Seventy-three subjects implanted with PULSAR or SONATA cochlear implants with FLEX electrode arrays. INTERVENTION: Subjects were fit postoperatively with an audio processor, combining electric stimulation and acoustic amplification. MAIN OUTCOME MEASURES: Unaided thresholds were measured preoperatively and at 3, 6, and 12 months postactivation. Speech perception was assessed at these intervals using City University of New York sentences in noise and consonant-nucleus-consonant words in quiet. Subjective benefit was assessed at these intervals via the Abbreviated Profile of Hearing Aid Benefit and Hearing Device Satisfaction Scale questionnaires. RESULTS: Sixty-seven of 73 subjects (92%) completed outcome measures for all study intervals. Of those 67 subjects, 79% experienced less than a 30 dB HL low-frequency pure-tone average (250-1000 Hz) shift, and 97% were able to use the acoustic unit at 12 months postactivation. In the EAS condition, 94% of subjects performed similarly to or better than their preoperative performance on City University of New York sentences in noise at 12 months postactivation, with 85% demonstrating improvement. Ninety-seven percent of subjects performed similarly or better on consonant-nucleus-consonant words in quiet, with 84% demonstrating improvement. CONCLUSION: The MED-EL EAS System is a safe and effective treatment option for adults with normal hearing to moderate sensorineural hearing loss in the low frequencies and severe-to-profound sensorineural hearing loss in the high frequencies who do not benefit from traditional amplification.

Ciprofloxacin 0.3% + dexamethasone 0.1% for the treatment for otitis media.

INTRODUCTION: Ciprofloxacin 0.3% with dexamethasone 0.1% (ciprofloxacin/dexamethasone) is an ototopical preparation for acute otitis externa, otorrhea with tympanostomy tubes, and is frequently used to treat chronic suppurative otitis media (CSOM). The advantage of topical therapy is the ability to deliver higher concentration of antibiotics to the treatment site when compared with oral or parenteral antibiotics. The delivery of a high concentration of antibiotics significantly decreases treatment failure and makes the development of resistant organisms unlikely. Previous ototopical preparations contained antibiotics such as aminoglycosides that are known to be ototoxic making treatment of otic infections without an intact tympanic membrane difficulty. AREAS COVERED: A literature search of PubMed was performed as the basis for a literature-based discussion on the clinical efficacy of ciprofloxacin/dexamethasone compared to oral antibiotics and ototopical therapy without a steroid component. The potential ototoxicity of ototopical therapies is discussed, including evidence demonstrating the lack of ototoxicity of fluoroquinolone and dexamethasone containing drops. EXPERT OPINION: Because multiple studies have demonstrated that fluoroquinolones are not ototoxic, fluoroquinolone ototopical drops should be a first-line treatment for otorrhea without an intact membrane. The addition of dexamethasone 0.1% to ciprofloxacin 0.3% has been shown to decrease granulation tissue, improve clinical cure and achieve greater rates of bacterial eradication when compared to ciprofloxacin 0.3% alone.

Ciprofloxacin 0.3%/dexamethasone 0.1% sterile otic suspension for the topical treatment of ear infections: a review of the literature.

The objective of this article is to review the literature related to ciprofloxacin 0.3% and dexamethasone 0.1% sterile otic suspension. A systematic literature search utilizing Medline was conducted to identify peer-reviewed articles related to safety and efficacy. A total of 47 publications were identified and reviewed herein. The literature supports the use of antibiotic/antiiflammatory combination ear drops in the treatment of both acute otitis externa and acute otitis media in pediatric patients with tympanostomy tubes. Ciprofloxacin/dexamethasone has been demonstrated as safe and effective with regard to clinical cures and microbiological eradication of pathogens in either disease with low treatment failure rates. Additionally, the literature also provides clear evidence for the contribution of dexamethasone when added to ciprofloxacin for the topical treatment of ear infections.

Ciprofloxacin 0.3%/dexamethasone 0.1% topical drops for the management of otic infections.

The American Academy of Otolaryngology-Head and Neck Surgery has recommended that, where possible, infections of the external auditory canal and middle ear be treated with topical preparations. The advantages of topical therapy include i) excellent efficacy; ii) decreased risk of systemic side effects; iii) less likelihood of selecting for resistant strains of microorganisms; and iv) lack of potential for ototoxicity. One advantage of topical therapy arises as a consequence of a very high concentration of antibiotic in topical preparations reaching the site of infection. Ciprofloxacin 0.3%/dexamethasone 0.1% (Ciprodex) is the only ototopical drop approved for use in both the middle ear and external auditory canal that combines a fluoroquinolone with a steroid. At 0.3% (3000 mcg/ml), the ciprofloxacin concentration of Ciprodex exceeds the MIC of virtually all relevant organisms by a very considerable margin. The clinical efficacy of ciprofloxacin/dexamethasone suspension has been demonstrated in several large prospective clinical trials. It has been consistently equal to or superior to comparator drugs. The authors believe that the use of topical ciprofloxacin/dexamethasone will increase as the advantages of fluoroquinolone/steroid combination therapy become more widely recognized.

A single topical agent is clinically equivalent to the combination of topical and oral antibiotic treatment for otitis externa.

OBJECTIVE: To demonstrate clinical equivalence (statistical noninferiority) of topical ciprofloxacin and hydrocortisone (CHC, Cipro HC) and topical neomycin/polymyxin b/hydrocortisone (NPH, Cortisporin) with systemic amoxicillin (AMX, Amoxil), for treatment of acute otitis externa (AOE). DESIGN: Randomized, active-control, observer-blind, multicenter trial. PATIENTS: Altogether, 206 patients were enrolled (CHC, 106; NPH + AMX, 100). Patients were > or =1 year of age, had AOE >2 days with at least mild symptoms, and gave informed consent. All were evaluable for safety, and 151 were evaluable for efficacy. INTERVENTIONS: Ciprofloxacin and hydrocortisone 3 drops twice daily for 7 days (adults and children) or NPH 4 drops (adults) or 2 drops (children) with AMX 250 mg (adults and children) 3 times daily for 10 days, as directed in approved product labeling. MAIN OUTCOME MEASURES: The primary efficacy variable was response to therapy 7 days after treatment ended (test of cure). Secondary variables included time to end of pain, symptom scores (otalgia and tenderness) and microbiological eradication. Noninferiority was declared if the lower confidence limit around the measurement difference was above -10 (nearer zero). RESULTS: Response to therapy was higher for CHC (95.71% vs 89.83%) but was statistically noninferior (lower confidence limit, -4.98) to NPH + AMX. Median time to end of pain was 6 days for both groups. Noninferiority was declared for symptom scores at all measurement periods and for microbiological eradication. No serious adverse events related to treatment were reported. CONCLUSIONS: Ciprofloxacin and hydrocortisone is clinically equivalent to NPH + AMX for the treatment of AOE in adults and children. However, low systemic exposure, absence of ototoxicity, and less frequent dosing clearly favor Cipro HC.

An assessment of the onset and duration of action of olopatadine nasal spray.

OBJECTIVE: Seasonal allergic rhinitis (SAR) is a highly prevalent disease. This study was conducted to evaluate the onset and duration of action of three concentrations of olopatadine nasal spray. METHODS: This was a randomized, double-blind, single-dose, placebo-controlled study, conducted in an environmental exposure chamber in patients with SAR. A total of 320 patients were exposed to ragweed allergen in the chamber and randomized to olopatadine nasal spray 0.2%, 0.4%, 0.6%, or placebo nasal spray. Symptoms (sneezing, runny, itchy, and stuffy nose) were self-assessed during a 12-hour study period. RESULTS: All concentrations of olopatadine nasal spray provided clinically meaningful reductions in total nasal symptom scores at 30 minutes compared to the placebo. Olopatadine nasal spray 0.6% was significantly more effective (P < 0.05) than placebo nasal spray at all time-points starting at 90 minutes post-dose and continuing over 12 hours. CONCLUSIONS: Olopatadine nasal spray 0.6% demonstrated a fast onset of action and maintained an effect for at least 12 hours after dosing.

Safety and efficacy of olopatadine hydrochloride nasal spray for the treatment of seasonal allergic rhinitis to mountain cedar.

BACKGROUND: A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR) to mountain cedar. OBJECTIVE: To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo nasal spray in patients with SAR to mountain cedar. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 677 patients aged 12 to 81 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 sprays per nostril twice daily for 2 weeks. Patients evaluated morning and evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and ocular symptoms. RESULTS: Olopatadine spray (0.4% and 0.6%) was statistically significantly superior to placebo for percentage change from baseline in overall reflective and instantaneous TNSSs. Also, 0.6% olopatadine was statistically significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny nose, itchy nose, stuffy nose, itchy eyes, and watery eyes. Olopatadine spray exhibited a safety profile comparable with that of placebo. CONCLUSIONS: Olopatadine nasal spray (0.4% and 0.6%) provided statistically significant improvements in allergic rhinitis symptoms compared with placebo regarding TNSSs and individual symptoms, including congestion, itchy and runny nose, sneezing, and itchy and watery eyes, in patients with SAR to mountain cedar. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.

A cost threshold analysis of ciprofloxacin-dexamethasone versus ofloxacin for acute otitis media in pediatric patients with tympanostomy tubes.

OBJECTIVE: The aim of this study was to determine the cost-effectiveness hreshold of a ciprofloxacin 0.3% and dexamethasone 0.1% (CD) otic suspension relative to olfloxacin otic solution (OFX) for the treatment of acute otitis media in pediatric patients with tympanostomy tubes (AOMT). METHODS: This study used a decision-analytic model to simulate the costs and consequences of the ototopical treatment of AOMT. The AOMT model consisted of 3 tiers of antimicrobial therapy. Each successive tier represented the repeat treatment of clinical failures from the preceding tier. Patients were modeled for treatment until cured or until third-tier therapy was complete, at which time patients were considered cured. First-tier therapy modeled a comparison of CD and OFX using efficacy rates taken from a randomized clinical trial with a population of 599 patients. Second-tier therapy modeled the use of amoxicillin and clavulanic acid using an efficacy rate taken from the medical literature. Third-tier therapy was modeled as being pathogen specific and could follow 1 of 3 possible clinical pathways: (1) PO fluconazole, (2) IM ceftriaxone, or (3) IV antibiotics administered in a hospital setting. Third-tier therapeutic pathway probabilities were based on the microbiologic spectrum of the treatment failures from the clinical trial. Cost information (in year-2003 US dollars) was taken from accepted cost reference sources and presented from the perspective of a third-party payer. The economic outcome of interest was the cost-effectiveness threshold of CD relative to OFX. RESULTS: Given the model parameters, CD had a cost-effectiveness threshold value of 4.5 times the wholesale acquisition cost of OFX. Based on actual cost, first-tier CD therapy was more cost-effective than OFX up to a threshold price of US 152.64 dollars. CONCLUSION: In this decision-analytic model, CD was more cost-effective than OFX for AOMT therapy in pediatric patients up to a threshold price of 4.5 times the price of OFX.

Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of granulation tissue in children with acute otitis media with otorrhea through tympanostomy tubes.

OBJECTIVE: Comparison of topical ciprofloxacin/dexamethasone otic suspension (CIP/DEX) to ofloxacin otic solution (OFL) for treatment of granulation tissue in children with AOMT. STUDY DESIGN: 599 children aged >/=6 months to 12 years with AOMT of up to 3 weeks' duration were enrolled. Patients received either CIP/DEX 4 drops twice daily for 7 days or OFL 5 drops twice daily for 10 days. Granulation tissue severity was graded at clinic visits on days 1, 3, 11, and 18. RESULTS: Granulation tissue was present in 90 of 599 AOMT patients (15.0%) at baseline. CIP/DEX treatment was superior to OFL for reduction of granulation tissue at the day 11 visit (81.3% compared with 56.1%, P = 0.0067) and the day 18 visit (91.7% compared with 73.2%, P = 0.0223). Both topical otic preparations are safe and well tolerated in pediatric patients. CONCLUSION: CIP/DEX was superior to OFL in the treatment of granulation tissue in children with AOMT.

Functional magnetic resonance imaging of activation in subcortical auditory pathway.

OBJECTIVES: Functional magnetic resonance imaging (fMRI) has been used to investigate activation of the auditory cortex; however, assessment of activation in the subcortical auditory pathway has been challenging. The aim of this study was to examine neural correlates of cortical and subcortical auditory activation evoked by pure-tone stimulus using silent fMRI. STUDY DESIGN: Prospective analysis. METHODS: Seventeen normal-hearing volunteers (7 male, 10 female; age range, 14-37 yrs) underwent silent fMRI. An audiometer was used to deliver pure tones of 1000 Hz to the left ear. Pure tones were presented at hearing thresholds determined in the scanner. Brain regions showing increased activation during pure-tone stimulus presentation were mapped and auditory activations exceeding P <.001 were included in the analysis. RESULTS: Pure-tone stimuli evoked bilateral activation in cortical regions of the transverse and superior temporal gyri and the planum temporale. Activation in subcortical structures included the medial geniculate body, inferior colliculus, lateral lemniscus, superior olivary complex, and cochlear nucleus. CONCLUSIONS: Silent functional magnetic resonance imaging findings documented the feasibility of detecting activation elicited by pure tone along the cortical and subcortical auditory pathway. The use of this technique in the assessment of disorders with auditory dysfunction merits further investigation.

Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of children with acute otitis media with otorrhea through tympanostomy tubes.

OBJECTIVE: To determine the efficacy and safety of topical ciprofloxacin/dexamethasone otic suspension compared with ofloxacin otic solution in the treatment of acute otitis media with otorrhea through tympanostomy tubes (AOMT) in pediatric patients. METHODS: This multicenter, prospective, randomized, observer-masked, parallel-group study was conducted at 39 sites in 599 children aged >or=6 months to 12 years with an AOMT episode of

Evaluation of auditory cortex activation by using silent FMRI.

PURPOSE: To evaluate auditory cortex activation evoked by pure-tone stimulus using silent functional magnetic resonance imaging (FMRI). MATERIAL AND METHODS: Nine volunteers with normal hearing as determined with pure-tone audiometry were studied. Auditory cortex activation was evoked by pure-tone stimuli presented monaurally at 1,000, 2,000, and 4,000 Hz. Images of auditory cortex activation were obtained using silent and conventional FMRI techniques. Heschl's gyrus activation was evaluated by the number of voxels exceeding a predetermined significance level (P <.0001). RESULTS: In both techniques, all subjects showed activation in the Heschl's gyrus. Silent FMRI detected more activation in all studied frequencies compared with the conventional FMRI. The observed difference in the Heschl's gyrus activation between the techniques reached statistical significance for 1,000 Hz frequency (P <.05). CONCLUSIONS: The amount of Heschl's gyrus activation detected with silent FMRI is greater than that of conventional FMRI. Silent FMRI technique can be used to acquire functional images of the auditory cortex without the confounding effects of scanner noise.